From a28d4c99ab20571a193eec049d24ea935e89775e Mon Sep 17 00:00:00 2001 From: Macayla Ann Weiner Date: Tue, 5 Aug 2025 15:34:08 -0600 Subject: [PATCH 1/2] MODY8_CEL added adjust MODY CEL coordinates more MODY CEL updates including pathogenic motif --- CITATION.cff | 2 +- data/STRchive-citations.json | 6 + data/STRchive-disease-loci.T2T-chm13.TRGT.bed | 1 + data/STRchive-disease-loci.T2T-chm13.bed | 1 + data/STRchive-disease-loci.hg19.TRGT.bed | 1 + data/STRchive-disease-loci.hg19.bed | 1 + data/STRchive-disease-loci.hg38.TRGT.bed | 1 + data/STRchive-disease-loci.hg38.bed | 1 + data/STRchive-loci.json | 64 + data/literature/CEL01.txt | 2910 +++++++++++++++++ data/plots/age-onset.json | 50 +- data/plots/path-size.json | 37 +- data/ref-alleles/ref-alleles.T2T-chm13.txt | 6 + data/ref-alleles/ref-alleles.hg19.txt | 6 + data/ref-alleles/ref-alleles.hg38.txt | 6 + 15 files changed, 3055 insertions(+), 38 deletions(-) create mode 100644 data/literature/CEL01.txt diff --git a/CITATION.cff b/CITATION.cff index 6c888a7f..36e44aa7 100644 --- a/CITATION.cff +++ b/CITATION.cff @@ -1,5 +1,5 @@ title: STRchive -version: 2.9.0 +version: 2.10.0 date-released: "2025-08-12" url: https://github.com/dashnowlab/STRchive authors: diff --git a/data/STRchive-citations.json b/data/STRchive-citations.json index e2140641..52433262 100644 --- a/data/STRchive-citations.json +++ b/data/STRchive-citations.json @@ -152610,6 +152610,12 @@ "link": "https://omim.org/entry/147791", "note": "WARNING: Manubot does not support url:https://omim.org/entry/147791. Skipping" }, +{ + "id": "omim:609812", + "manubot_success": false, + "link": "https://omim.org/entry/609812", + "note": "WARNING: Manubot does not support url:https://omim.org/entry/609812. Skipping" +}, { "id": "omim:615945", "manubot_success": false, diff --git a/data/STRchive-disease-loci.T2T-chm13.TRGT.bed b/data/STRchive-disease-loci.T2T-chm13.TRGT.bed index 18112b04..1dc5ab65 100644 --- a/data/STRchive-disease-loci.T2T-chm13.TRGT.bed +++ b/data/STRchive-disease-loci.T2T-chm13.TRGT.bed @@ -30,6 +30,7 @@ chr8 119495247 119495353 ID=FAME1_SAMD12;MOTIFS=TAAAA,TGAAA;STRUC= chr9 27584063 27584155 ID=FTDALS1_C9orf72;MOTIFS=GGCCCC;STRUC= chr9 81210818 81210861 ID=FRDA_FXN;MOTIFS=A,GAA;STRUC= chr9 142886568 142886595 ID=HSAN-VIII_PRDM12;MOTIFS=GCC;STRUC= +chr9 145285396 145285622 ID=MODY8_CEL;MOTIFS=GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG,GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG;STRUC= chr10 80695718 80695748 ID=OPML1_NUTM2B-AS1;MOTIFS=GGC;STRUC= chr11 119226662 119226696 ID=JBS_CBL;MOTIFS=CGG;STRUC= chr12 6947903 6947941 ID=DRPLA_ATN1;MOTIFS=CAG;STRUC= diff --git a/data/STRchive-disease-loci.T2T-chm13.bed b/data/STRchive-disease-loci.T2T-chm13.bed index f47698eb..5be1fe4b 100644 --- a/data/STRchive-disease-loci.T2T-chm13.bed +++ b/data/STRchive-disease-loci.T2T-chm13.bed @@ -31,6 +31,7 @@ chr8 119495247 119495353 FAME1_SAMD12 SAMD12 TAAAA TGAAA 105 AD Familial adult m chr9 27584063 27584155 FTDALS1_C9orf72 C9orf72 GGCCCC GGCCCC 251 AD Frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) chr9 81210834 81210861 FRDA_FXN FXN GAA GAA 56 AR Friedreich ataxia chr9 142886568 142886595 HSAN-VIII_PRDM12 PRDM12 GCC GCC 18 AR Hereditary sensory and autonomic neuropathy type VIII +chr9 145285396 145285622 MODY8_CEL CEL GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG 3 AD Maturity-Onset Diabetes of the Young Type 8 chr10 80695718 80695748 OPML1_NUTM2B-AS1 NUTM2B-AS1 GGC GGC 161 AD Oculopharyngeal myopathy with leukoencephalopathy 1 chr11 119226662 119226696 JBS_CBL CBL CGG CGG 101 AD Jacobsen syndrome (FRAX11B fragile site) chr12 6947903 6947941 DRPLA_ATN1 ATN1 CAG CAG 48 AD Dentatorubral-Pallidoluysian Atrophy diff --git a/data/STRchive-disease-loci.hg19.TRGT.bed b/data/STRchive-disease-loci.hg19.TRGT.bed index 3eb5ce48..4343d946 100644 --- a/data/STRchive-disease-loci.hg19.TRGT.bed +++ b/data/STRchive-disease-loci.hg19.TRGT.bed @@ -30,6 +30,7 @@ chr8 119379051 119379157 ID=FAME1_SAMD12;MOTIFS=TAAAA,TGAAA;STRUC= chr9 27573482 27573544 ID=FTDALS1_C9orf72;MOTIFS=GGCCCC;STRUC= chr9 71652186 71652220 ID=FRDA_FXN;MOTIFS=A,GAA;STRUC= chr9 133556992 133557028 ID=HSAN-VIII_PRDM12;MOTIFS=GCC;STRUC= +chr9 135946627 135946886 ID=MODY8_CEL;MOTIFS=GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG,GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG;STRUC= chr10 81586139 81586160 ID=OPML1_NUTM2B-AS1;MOTIFS=GGC;STRUC= chr11 119076999 119077033 ID=JBS_CBL;MOTIFS=CGG;STRUC= chr12 7045879 7045938 ID=DRPLA_ATN1;MOTIFS=CAG;STRUC= diff --git a/data/STRchive-disease-loci.hg19.bed b/data/STRchive-disease-loci.hg19.bed index 14cce72c..00b6b312 100644 --- a/data/STRchive-disease-loci.hg19.bed +++ b/data/STRchive-disease-loci.hg19.bed @@ -31,6 +31,7 @@ chr8 119379051 119379157 FAME1_SAMD12 SAMD12 TAAAA TGAAA 105 AD Familial adult m chr9 27573482 27573544 FTDALS1_C9orf72 C9orf72 GGCCCC GGCCCC 251 AD Frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) chr9 71652202 71652220 FRDA_FXN FXN GAA GAA 56 AR Friedreich ataxia chr9 133556992 133557028 HSAN-VIII_PRDM12 PRDM12 GCC GCC 18 AR Hereditary sensory and autonomic neuropathy type VIII +chr9 135946627 135946886 MODY8_CEL CEL GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG 3 AD Maturity-Onset Diabetes of the Young Type 8 chr10 81586139 81586160 OPML1_NUTM2B-AS1 NUTM2B-AS1 GGC GGC 161 AD Oculopharyngeal myopathy with leukoencephalopathy 1 chr11 119076999 119077033 JBS_CBL CBL CGG CGG 101 AD Jacobsen syndrome (FRAX11B fragile site) chr12 7045879 7045938 DRPLA_ATN1 ATN1 CAG CAG 48 AD Dentatorubral-Pallidoluysian Atrophy diff --git a/data/STRchive-disease-loci.hg38.TRGT.bed b/data/STRchive-disease-loci.hg38.TRGT.bed index 140c35dd..c6b70ab5 100644 --- a/data/STRchive-disease-loci.hg38.TRGT.bed +++ b/data/STRchive-disease-loci.hg38.TRGT.bed @@ -30,6 +30,7 @@ chr8 118366812 118366918 ID=FAME1_SAMD12;MOTIFS=TAAAA,TGAAA;STRUC= chr9 27573484 27573546 ID=FTDALS1_C9orf72;MOTIFS=GGCCCC;STRUC= chr9 69037270 69037304 ID=FRDA_FXN;MOTIFS=A,GAA;STRUC= chr9 130681605 130681641 ID=HSAN-VIII_PRDM12;MOTIFS=GCC;STRUC= +chr9 133071240 133071499 ID=MODY8_CEL;MOTIFS=GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG,GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG;STRUC= chr10 79826383 79826404 ID=OPML1_NUTM2B-AS1;MOTIFS=GGC;STRUC= chr11 119206289 119206323 ID=JBS_CBL;MOTIFS=CGG;STRUC= chr12 6936716 6936775 ID=DRPLA_ATN1;MOTIFS=CAG;STRUC= diff --git a/data/STRchive-disease-loci.hg38.bed b/data/STRchive-disease-loci.hg38.bed index a8e6d8fa..dab30bb1 100644 --- a/data/STRchive-disease-loci.hg38.bed +++ b/data/STRchive-disease-loci.hg38.bed @@ -31,6 +31,7 @@ chr8 118366812 118366918 FAME1_SAMD12 SAMD12 TAAAA TGAAA 105 AD Familial adult m chr9 27573484 27573546 FTDALS1_C9orf72 C9orf72 GGCCCC GGCCCC 251 AD Frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) chr9 69037286 69037304 FRDA_FXN FXN GAA GAA 56 AR Friedreich ataxia chr9 130681605 130681641 HSAN-VIII_PRDM12 PRDM12 GCC GCC 18 AR Hereditary sensory and autonomic neuropathy type VIII +chr9 133071240 133071499 MODY8_CEL CEL GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG 3 AD Maturity-Onset Diabetes of the Young Type 8 chr10 79826383 79826404 OPML1_NUTM2B-AS1 NUTM2B-AS1 GGC GGC 161 AD Oculopharyngeal myopathy with leukoencephalopathy 1 chr11 119206289 119206323 JBS_CBL CBL CGG CGG 101 AD Jacobsen syndrome (FRAX11B fragile site) chr12 6936716 6936775 DRPLA_ATN1 ATN1 CAG CAG 48 AD Dentatorubral-Pallidoluysian Atrophy diff --git a/data/STRchive-loci.json b/data/STRchive-loci.json index 5f04ca8e..b4ba7c43 100644 --- a/data/STRchive-loci.json +++ b/data/STRchive-loci.json @@ -1087,6 +1087,70 @@ "references": ["pmid:38467784", "pmid:7603564", "pmid:10767345", "pmid:19267933", "omim:147791", "mondo:0007838"], "additional_literature": ["pmid:37422244", "pmid:22131879", "pmid:22084433", "pmid:16474167"] }, +{ + "chrom": "chr9", + "start_hg38": 133071240, + "stop_hg38": 133071499, + "start_hg19": 135946627, + "stop_hg19": 135946886, + "start_t2t": 145285396, + "stop_t2t": 145285622, + "id": "MODY8_CEL", + "disease_id": "MODY8", + "gene_strand": "+", + "reference_motif_reference_orientation": ["GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG"], + "pathogenic_motif_reference_orientation": ["GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG"], + "pathogenic_motif_gene_orientation": ["ACGGGTGACTCCGGGGCCCCCCCGTGCCGCCC"], + "benign_motif_reference_orientation": [], + "benign_motif_gene_orientation": [], + "unknown_motif_reference_orientation": [], + "unknown_motif_gene_orientation": [], + "disease": "Maturity-Onset Diabetes of the Young Type 8", + "gene": "CEL", + "flank_motif": null, + "locus_structure": "(GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG)*", + "inheritance": ["AD"], + "type": "Exonic", + "location_in_gene": "Exon 11", + "benign_min": 7, + "benign_max": 23, + "intermediate_min": null, + "intermediate_max": null, + "pathogenic_min": 3, + "pathogenic_max": 3, + "ref_copies": 7.8, + "motif_len": 33, + "age_onset": "11-17 [@pmid:19760265]", + "age_onset_min": 11, + "age_onset_max": 17, + "typ_age_onset_min": null, + "typ_age_onset_max": null, + "novel": "novel", + "mechanism": "LoF?", + "mechanism_detail": "Loss of function at the protein level is possibly a part of the molecular mechanism. Research suggests that the mutations disrupt the C-terminal protein, leading to reduced stability of the mutant lipase in vitro [@pmid:16369531].", + "source": [], + "details": "There are two types of mutations proposed, a single basepair deletion causing a frameshift mutation [@pmid:16369531; @pmid:19760265]. One of these is a (C)8 to (C)7 within the VNTR causing a motif change (this is the pathogenic motif represented here). Also, a possible contraction from 4 to 3 VNTR repeats may be pathogenic with reduced penetrance, although evidence for this is sparse [@pmid:19760265].", + "omim": ["609812"], + "prevalence": null, + "prevalence_details": "Found in individuals of Danish and Norwegian ancestry [@pmid:16369531; @pmid:19760265].", + "stripy": [], + "gnomad": [], + "genereviews": [], + "mondo": ["0012348"], + "year": "2005", + "medgen": ["342845"], + "orphanet": ["552"], + "gard": [], + "malacard": ["MTR082"], + "webstr_hg38": [], + "webstr_hg19": [], + "tr_atlas": [], + "disease_description": "Maturity-onset diabetes of the young type 8 (MODY8) is characterized by onset of diabetes before age 25 years, with slowly progressive pancreatic exocrine dysfunction, fatty replacement of pancreatic parenchyma (lipomatosis), and development of pancreatic cysts [@omim:609812]. Other types of this disease have been associated with various genes and variant types. Comorbidity has been proposed between MODY and fecal elastase deficiency (FED).", + "locus_tags": ["unknown_evidence", "contraction"], + "disease_tags": [], + "references": ["pmid:19760265", "pmid:16369531", "omim:609812"], + "additional_literature": ["pmid:40641008", "pmid:39710966", "pmid:38483348", "pmid:38473919", "pmid:38458477", "pmid:36379850", "pmid:35583610", "pmid:35215948", "pmid:35156195", "pmid:35082198", "pmid:34850019", "pmid:34507899", "pmid:34100900", "pmid:33862081", "pmid:27802312", "pmid:27650499", "pmid:27773618", "pmid:23395566", "pmid:21784842", "pmid:15841033"] +}, { "chrom": "chr3", "start_hg38": 129172576, diff --git a/data/literature/CEL01.txt b/data/literature/CEL01.txt new file mode 100644 index 00000000..07e0503d --- /dev/null +++ b/data/literature/CEL01.txt @@ -0,0 +1,2910 @@ + +PMID- 40641008 +OWN - NLM +STAT- Publisher +LR - 20250711 +IS - 1552-4604 (Electronic) +IS - 0091-2700 (Linking) +DP - 2025 Jul 10 +TI - Characterizing Cellular Expansion of Idecabtagene Vicleucel and Association with + Clinical Efficacy and Safety in Patients with Triple-Class-Exposed + Relapsed/Refractory Multiple Myeloma. +LID - 10.1002/jcph.70075 [doi] +AB - Idecabtagene vicleucel (ide-cel, ABECMA) is an autologous, B-cell maturation + antigen-directed, chimeric antigen receptor (CAR) T-cell therapy, which has + demonstrated significantly improved progression-free survival (PFS) and overall + response rate (ORR) in patients with triple-class-exposed relapsed/refractory + multiple myeloma (TCE RRMM). Here, we characterize cellular expansion of ide-cel + in vivo and further evaluate associations between cellular expansion and clinical + efficacy and safety endpoints. The exposure parameters of ide-cel were evaluated + through non-compartmental analysis methods using the time course data of CAR + transgene copy numbers collected from the ide-cel arm of Study KarMMa-3 + (NCT03651128). Multivariable regression analyses were conducted between the + exposure parameters and clinical responses to characterize relationships between + cellular expansion in vivo and clinical outcomes and to evaluate potential + effects of covariates on the exposure-response (E-R) relationships. There appears + to be lack of a strong association between actual ide-cel dose and cellular + expansion at the dose range evaluated in Study KarMMa-3. The multivariable E-R + regression models suggest positive relationships between cellular expansion and + clinical efficacy and safety endpoints, with higher exposure associated with + longer PFS, higher ORR, and higher rates of cytokine release syndrome requiring + tocilizumab or corticosteroids. The current analyses do not identify any + clinically relevant covariate effects on the E-R relationships. The positive + exposure-response relationships were found to be overall similar between KarMMa-3 + and a previous study KarMMa. The modeling analyses, paired with clinical data, + support extending the dose range from previously approved 300-460 x 10(6) CAR+ T + cells to 300-510 x 10(6) CAR+ T cells for TCE RRMM patients. +CI - (c) 2025 The Author(s). The Journal of Clinical Pharmacology published by Wiley + Periodicals LLC on behalf of American College of Clinical Pharmacology. +FAU - Wu, Fan +AU - Wu F +AD - Translational Medical and Clinical Pharmacology, Bristol Myers Squibb, Princeton, + NJ, USA. +FAU - Zheng, Xirong +AU - Zheng X +AD - Translational Medical and Clinical Pharmacology, Bristol Myers Squibb, Princeton, + NJ, USA. +FAU - Burnett, Joseph +AU - Burnett J +AD - Translational Medical and Clinical Pharmacology, Bristol Myers Squibb, Princeton, + NJ, USA. +FAU - Masilamani, Madhan +AU - Masilamani M +AD - Translational Medical and Clinical Pharmacology, Bristol Myers Squibb, Princeton, + NJ, USA. +FAU - Zhang, Wanying +AU - Zhang W +AD - Translational Medical and Clinical Pharmacology, Bristol Myers Squibb, Princeton, + NJ, USA. +FAU - Zhong, Xiaobo +AU - Zhong X +AD - Global Biometric Sciences, Bristol Myers Squibb, Princeton, NJ, USA. +FAU - Caia, Andrea +AU - Caia A +AD - Clinical Science, Bristol Myers Squibb, Boudry, Switzerland. +FAU - Cook, Mark +AU - Cook M +AD - Clinical Development, Bristol Myers Squibb, Boudry, Switzerland. +FAU - Piasecki, Julia +AU - Piasecki J +AD - Cancer Immunology and Cell Therapy, Bristol Myers Squibb, Seattle, WA, USA. +FAU - Kondic, Anna +AU - Kondic A +AD - Translational Medical and Clinical Pharmacology, Bristol Myers Squibb, Princeton, + NJ, USA. +FAU - Lamba, Manisha +AU - Lamba M +AD - Translational Medical and Clinical Pharmacology, Bristol Myers Squibb, Princeton, + NJ, USA. +FAU - Zhou, Jian +AU - Zhou J +AD - Translational Medical and Clinical Pharmacology, Bristol Myers Squibb, Princeton, + NJ, USA. +LA - eng +PT - Journal Article +DEP - 20250710 +PL - England +TA - J Clin Pharmacol +JT - Journal of clinical pharmacology +JID - 0366372 +SB - IM +OTO - NOTNLM +OT - CAR T +OT - cellular kinetics +OT - exposure-response +OT - multiple myeloma +EDAT- 2025/07/11 06:27 +MHDA- 2025/07/11 06:27 +CRDT- 2025/07/11 00:22 +PHST- 2025/02/26 00:00 [received] +PHST- 2025/06/16 00:00 [accepted] +PHST- 2025/07/11 06:27 [medline] +PHST- 2025/07/11 06:27 [pubmed] +PHST- 2025/07/11 00:22 [entrez] +AID - 10.1002/jcph.70075 [doi] +PST - aheadofprint +SO - J Clin Pharmacol. 2025 Jul 10. doi: 10.1002/jcph.70075. + +PMID- 39710966 +OWN - NLM +STAT- MEDLINE +DCOM- 20250215 +LR - 20250529 +IS - 1365-2141 (Electronic) +IS - 0007-1048 (Print) +IS - 0007-1048 (Linking) +VI - 206 +IP - 2 +DP - 2025 Feb +TI - Brexucabtagene autoleucel in-vivo expansion and BTKi refractoriness have a + negative influence on progression-free survival in mantle cell lymphoma: Results + from CART-SIE study. +PG - 644-651 +LID - 10.1111/bjh.19961 [doi] +AB - Brexucabtagene autoleucel (brexu-cel) has revolutionized the treatment of + patients affected by mantle cell lymphomas. In this prospective, observational + multicentre study, we evaluated 106 patients, with longitudinal brexu-cel + kinetics in peripheral blood monitored in 61 of them. Clinical outcomes and + toxicities are consistent with previous real-world evidence studies. Notably, + beyond established poor prognostic factors-such as blastoid variant and elevated + lactate dehydrogenase-Bruton tyrosine-kinase inhibitors (BTKi) refractoriness and + platelet count emerged as significant predictors of survival. Specifically, the + 1-year overall survival was 56% in BTKi-refractory patients compared to 92% in + BTKi-relapsed patients (p = 0.0001). Our study also demonstrated that in-vivo + monitoring of brexu-cel expansion is feasible and correlates with + progression-free survival and toxicities. Progression-free survival at 1 year was + 74% in patients categorized as strong expanders, based on brexu-cel peak + concentration, versus 54% in poor expanders (p = 0.02). Furthermore, in-vivo + expansion helped identify a high-risk group of non-responders, those with + progressive or stable disease at the 90-day post-infusion evaluation (OR = 4.7, + 95% CI = 1.1-34, p = 0.04) characterized by dismal outcomes. When integrated with + other clinical factors, monitoring brexu-cel expansion could assist in + recognizing patients at high risk of early relapse. +CI - (c) 2024 The Author(s). British Journal of Haematology published by British Society + for Haematology and John Wiley & Sons Ltd. +FAU - Stella, Federico +AU - Stella F +AUID- ORCID: 0000-0003-3401-1309 +AD - Hematology, School of Medicine, Universita degli Studi di Milano, Milan, Italy. +AD - Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, + Italy. +FAU - Chiappella, Annalisa +AU - Chiappella A +AUID- ORCID: 0000-0002-2977-0098 +AD - Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, + Italy. +FAU - Magni, Martina +AU - Magni M +AUID- ORCID: 0000-0001-9458-5836 +AD - Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, + Italy. +FAU - Bonifazi, Francesca +AU - Bonifazi F +AUID- ORCID: 0000-0003-1544-9911 +AD - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia + "Seragnoli", Bologna, Italy. +FAU - De Philippis, Chiara +AU - De Philippis C +AD - Department of Oncology/Hematology, IRCCS Humanitas Research Hospital, Milan, + Italy. +FAU - Musso, Maurizio +AU - Musso M +AD - Dipartimento Oncologico "La Maddalena", UOC di Oncoematologia e TMO, Palermo, + Italy. +FAU - Cutini, Ilaria +AU - Cutini I +AUID- ORCID: 0000-0003-3721-0004 +AD - SOD Terapie Cellulari e Medicina Trasfusionale, AAD Trapianto di midollo osseo, + Ospedale Careggi, Florence, Italy. +FAU - Ljevar, Silva +AU - Ljevar S +AD - Department of Data Science, Unit of Biostatistics for Clinical Research, + Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. +FAU - Barbui, Anna Maria +AU - Barbui AM +AD - Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy. +FAU - Farina, Mirko +AU - Farina M +AD - Unit of Blood Disease and Bone Marrow Transplantation, Unit of Hematology, + University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. +FAU - Martino, Massimo +AU - Martino M +AD - Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), + Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano + "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy. +FAU - Massaia, Massimo +AU - Massaia M +AD - Division of Hematology-AO S. Croce e Carle, Cuneo and Laboratory of Blood Tumor + Immunology, Molecular Biotechnology Center "Guido Tarone", University of Torino, + Torino, Italy. +FAU - Grillo, Giovanni +AU - Grillo G +AD - Dipartimento di Ematologia e trapianto di midollo, ASST Grande Ospedale + Metropolitano Niguarda, Milan, Italy. +FAU - Angelillo, Piera +AU - Angelillo P +AD - IRCCS Ospedale San Raffaele Milano, Milan, Italy. +FAU - Botto, Barbara +AU - Botto B +AD - SC Ematologia, AOU Citta della Salute e della Scienza, Torino, Italy. +FAU - Patriarca, Francesca +AU - Patriarca F +AD - Haematology and Stem Cell Transplantation Unit, Azienda Sanitaria Universitaria + Friuli Centrale, Udine, Italy. +FAU - Krampera, Mauro +AU - Krampera M +AD - Hematology and Bone Marrow Transplant Unit, Section of Biomedicine of Innovation, + Department of Engineering for Innovative Medicine (DIMI), University of Verona, + Verona, Italy. +FAU - Arcaini, Luca +AU - Arcaini L +AUID- ORCID: 0000-0002-9504-991X +AD - Department of Molecular Medicine, University of Pavia, Pavia, Italy. +AD - Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. +FAU - Tisi, Maria Chiara +AU - Tisi MC +AD - Hematology Unit, San Bortolo Hospital, Vicenza, Italy. +FAU - Zinzani, Pierluigi +AU - Zinzani P +AUID- ORCID: 0000-0002-2112-2651 +AD - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia + "Seragnoli", Bologna, Italy. +FAU - Sora, Federica +AU - Sora F +AD - Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, + Universita Cattolica del Sacro Cuore, Rome, Italy. +FAU - Bramanti, Stefania +AU - Bramanti S +AD - Department of Oncology/Hematology, IRCCS Humanitas Research Hospital, Milan, + Italy. +FAU - Pennisi, Martina +AU - Pennisi M +AD - Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, + Italy. +FAU - Carniti, Cristiana +AU - Carniti C +AUID- ORCID: 0000-0003-1039-1757 +AD - Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, + Italy. +FAU - Corradini, Paolo +AU - Corradini P +AUID- ORCID: 0000-0002-9186-1353 +AD - Hematology, School of Medicine, Universita degli Studi di Milano, Milan, Italy. +AD - Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, + Italy. +LA - eng +GR - Associazione Italiana contro le Leucemie-linfomi e mieloma" (AIL) Milano/ +GR - Societa Italiana di Ematologia/ +GR - PNC-E3-2022-23683269-PNC-HLS-TA/Italian Ministry of Health/ +GR - PNRR-MAD-2022-12376059/Italian Ministry of Health/ +GR - Fondazione IRCCS Istituto Nazionale dei Tumori/ +GR - IG2024-ID.31005project-P.I.CorradiniPaolo/Associazione Italiana per la Ricerca + sul Cancro/ +PT - Journal Article +PT - Multicenter Study +PT - Observational Study +DEP - 20241222 +PL - England +TA - Br J Haematol +JT - British journal of haematology +JID - 0372544 +RN - 0 (Protein Kinase Inhibitors) +SB - IM +MH - Humans +MH - *Lymphoma, Mantle-Cell/therapy/mortality/drug therapy +MH - Male +MH - Female +MH - Middle Aged +MH - Aged +MH - Progression-Free Survival +MH - Prospective Studies +MH - *Protein Kinase Inhibitors/therapeutic use/pharmacology +MH - Aged, 80 and over +MH - *Immunotherapy, Adoptive/methods +MH - Adult +PMC - PMC11829141 +OTO - NOTNLM +OT - CAR T-cell +OT - brexu-cel +OT - in vivo expansion +OT - mantle cell lymphoma +OT - real world +COIS- Federico Stella-nothing to disclose; Annalisa Chiappella-reports other support + from Gilead Sciences, Ideogen, Roche, Secura Bio, Takeda, AbbVie, Eli Lilly and + Company, Incyte, Janssen-Cilag, and Novartis outside the submitted work; Martina + Magni-nothing to disclose; Francesca Bonifazi-fees from Novartis and Kite-Gilead; + Chiara De Philippis-nothing to disclose; Maurizio Musso-advisory board + Kite/Gilead; Novartis; BMS. Speakers bureau: Kite/Gilead; Novartis; BMS; Ilaria + Cutini-nothing to disclose, Silva Ljevar-nothing to disclose; Anna Maria + Barbui-nothing to disclose; Mirko Farina-nothing to disclose; Massimo + Martino-advisory board Kite/Gilead; Novartis; BMS. Speakers bureau: Kite/Gilead; + Novartis; BMS; Massimo Massaia-nothing to disclose; Giovanni Grillo-nothing to + disclose; Piera Angelillo-Incyte, Barbara Botto-nothing to disclose, Francesca + Patriarca-Sanofi, Menarini, Novartis, BMS; Mauro Krampera-Advisory boards and + honoraria for lectures/educational events: Kite Gilead, Novartis, Janssen-Cilag, + Incyte, AbbVie, BeiGene, Menarini StemLine, Roche; Luca Arcaini-Honoraria: EUSA + Pharma, Novartis. Advisory boards for Roche, Janssen-Cilag, Verastem, Incyte, + EUSA Pharma, Celgene/Bristol Myers Squibb, Kite/Gilead, ADC Therapeutics, + Novartis; Maria Chiara Tisi-personal fees from Novartis, Gilead, Bristol Myers + Squibb, Eli Lilly and Company, Janssen, Sobi and Incyte; Pierluigi + Zinzani-Consultant: MSD, Eusapharma, Novartis; Advisory boards: ADC Therapeutics, + Astrazeneca, BeiGene, BMS, Celltrion, Eusapharma, Gilead, Incyte, Janssen-Cilag, + KyowaKirin, MSD, Novartis, Roche, Sandoz, SecuraBio, Servier, Takeda; speakers + bureau: Astrazeneca, Beigene, BMS, Celltrion, Eusapharma, Gilead, Incyte, + Janssen-Cilag, Kyowa-Kirin, MSD, Novartis, Roche, Servier, Takeda; Federica + Sora-nothing to disclose; Stefania Bramanti-Speaker bureau: Bms; Gilead, + Novartis, Advisory Board Novartis, Travel Accomodation Novartis, Roche, Martina + Pennisi-nothing to disclose, Cristiana Carniti-nothing to disclose, Paolo + Corradini-Advisory boards: AbbVie, ADC Therapeutics, Amgen, BeiGene, Celgene, + Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical + Science, Novartis, Roche, Sanofi, Takeda; honoraria for lectures: AbbVie, Amgen, + Celgene, Gilead/Kite, Janssen, Novartis, Roche, Sanofi, Takeda. +EDAT- 2024/12/23 06:21 +MHDA- 2025/02/15 15:11 +PMCR- 2025/02/15 +CRDT- 2024/12/23 01:13 +PHST- 2024/10/29 00:00 [received] +PHST- 2024/12/11 00:00 [accepted] +PHST- 2025/02/15 15:11 [medline] +PHST- 2024/12/23 06:21 [pubmed] +PHST- 2024/12/23 01:13 [entrez] +PHST- 2025/02/15 00:00 [pmc-release] +AID - BJH19961 [pii] +AID - 10.1111/bjh.19961 [doi] +PST - ppublish +SO - Br J Haematol. 2025 Feb;206(2):644-651. doi: 10.1111/bjh.19961. Epub 2024 Dec 22. + +PMID- 38483348 +OWN - NLM +STAT- MEDLINE +DCOM- 20240519 +LR - 20241108 +IS - 1460-2083 (Electronic) +IS - 0964-6906 (Print) +IS - 0964-6906 (Linking) +VI - 33 +IP - 11 +DP - 2024 May 18 +TI - Common single-base insertions in the VNTR of the carboxyl ester lipase (CEL) gene + are benign and also likely to arise somatically in the exocrine pancreas. +PG - 1001-1014 +LID - 10.1093/hmg/ddae034 [doi] +AB - The CEL gene encodes carboxyl ester lipase, a pancreatic digestive enzyme. CEL is + extremely polymorphic due to a variable number tandem repeat (VNTR) located in + the last exon. Single-base deletions within this VNTR cause the inherited + disorder MODY8, whereas little is known about VNTR single-base insertions in + pancreatic disease. We therefore mapped CEL insertion variants (CEL-INS) in 200 + Norwegian patients with pancreatic neoplastic disorders. Twenty-eight samples + (14.0%) carried CEL-INS alleles. Most common were insertions in repeat 9 (9.5%), + which always associated with a VNTR length of 13 repeats. The combined INS allele + frequency (0.078) was similar to that observed in a control material of 416 + subjects (0.075). We performed functional testing in HEK293T cells of a set of + CEL-INS variants, in which the insertion site varied from the first to the 12th + VNTR repeat. Lipase activity showed little difference among the variants. + However, CEL-INS variants with insertions occurring in the most proximal repeats + led to protein aggregation and endoplasmic reticulum stress, which upregulated + the unfolded protein response. Moreover, by using a CEL-INS-specific antibody, we + observed patchy signals in pancreatic tissue from humans without any CEL-INS + variant in the germline. Similar pancreatic staining was seen in knock-in mice + expressing the most common human CEL VNTR with 16 repeats. CEL-INS proteins may + therefore be constantly produced from somatic events in the normal pancreatic + parenchyma. This observation along with the high population frequency of CEL-INS + alleles strongly suggests that these variants are benign, with a possible + exception for insertions in VNTR repeats 1-4. +CI - (c) The Author(s) 2024. Published by Oxford University Press. +FAU - Brekke, Ranveig S +AU - Brekke RS +AUID- ORCID: 0000-0003-4824-9190 +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Jonas Lies vei 91B, 5021 Bergen, Norway. +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Jonas Lies vei 87, 5021 Bergen, Norway. +AD - Department of Medical Genetics, Haukeland University Hospital, Jonas Lies vei + 91B, 5021 Bergen, Norway. +FAU - Gravdal, Anny +AU - Gravdal A +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Jonas Lies vei 91B, 5021 Bergen, Norway. +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Jonas Lies vei 87, 5021 Bergen, Norway. +AD - Department of Medical Genetics, Haukeland University Hospital, Jonas Lies vei + 91B, 5021 Bergen, Norway. +FAU - El Jellas, Khadija +AU - El Jellas K +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Jonas Lies vei 91B, 5021 Bergen, Norway. +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Jonas Lies vei 87, 5021 Bergen, Norway. +FAU - Curry, Grace E +AU - Curry GE +AD - Department of Pediatrics, Washington University School of Medicine, Campus Box + 8208, 660 South Euclid Ave, St. Louis, MO 63110, USA. +FAU - Lin, Jianguo +AU - Lin J +AD - Department of Pediatrics, Washington University School of Medicine, Campus Box + 8208, 660 South Euclid Ave, St. Louis, MO 63110, USA. +FAU - Wilhelm, Steven J +AU - Wilhelm SJ +AD - Department of Pediatrics, Washington University School of Medicine, Campus Box + 8208, 660 South Euclid Ave, St. Louis, MO 63110, USA. +FAU - Steine, Solrun J +AU - Steine SJ +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Jonas Lies vei 91B, 5021 Bergen, Norway. +FAU - Mas, Eric +AU - Mas E +AD - Cancer Research Center of Marseille, Aix Marseille University, CNRS, INSERM, + Institut Paoli-Calmettes, CRCM, 27 Bd Lei Roure, 13273 Marseille Cedex 09, + France. +FAU - Johansson, Stefan +AU - Johansson S +AUID- ORCID: 0000-0002-2298-7008 +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Jonas Lies vei 87, 5021 Bergen, Norway. +AD - Department of Medical Genetics, Haukeland University Hospital, Jonas Lies vei + 91B, 5021 Bergen, Norway. +FAU - Lowe, Mark E +AU - Lowe ME +AD - Department of Pediatrics, Washington University School of Medicine, Campus Box + 8208, 660 South Euclid Ave, St. Louis, MO 63110, USA. +FAU - Johansson, Bente B +AU - Johansson BB +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Jonas Lies vei 87, 5021 Bergen, Norway. +FAU - Xiao, Xunjun +AU - Xiao X +AD - Department of Pediatrics, Washington University School of Medicine, Campus Box + 8208, 660 South Euclid Ave, St. Louis, MO 63110, USA. +FAU - Fjeld, Karianne +AU - Fjeld K +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Jonas Lies vei 91B, 5021 Bergen, Norway. +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Jonas Lies vei 87, 5021 Bergen, Norway. +AD - Department of Medical Genetics, Haukeland University Hospital, Jonas Lies vei + 91B, 5021 Bergen, Norway. +FAU - Molven, Anders +AU - Molven A +AUID- ORCID: 0000-0003-1847-3079 +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Jonas Lies vei 91B, 5021 Bergen, Norway. +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Jonas Lies vei 87, 5021 Bergen, Norway. +AD - Department of Pathology and Section for Cancer Genomics, Haukeland University + Hospital, Jonas Lies vei 83, Bergen, Norway. +LA - eng +GR - National Pancreas Foundation/ +GR - University of Bergen/ +GR - R01 DK124415/DK/NIDDK NIH HHS/United States +GR - 212734-2019/Norwegian Cancer Society/ +GR - 912057/Western Norway Regional Health Authority/ +GR - 289534/Research Council of Norway/ +GR - R01 DK124415/NIDDK/NH/NIH HHS/United States +PT - Journal Article +PT - Research Support, N.I.H., Extramural +PT - Research Support, Non-U.S. Gov't +PL - England +TA - Hum Mol Genet +JT - Human molecular genetics +JID - 9208958 +RN - 0 (CEL protein, human) +SB - IM +MH - Humans +MH - *Minisatellite Repeats/genetics +MH - Animals +MH - Mice +MH - *Pancreas, Exocrine/metabolism/enzymology +MH - HEK293 Cells +MH - Mutagenesis, Insertional/genetics +MH - Alleles +MH - Pancreatic Neoplasms/genetics/pathology/enzymology +MH - Gene Frequency +MH - Male +MH - Female +MH - Lipase/genetics +PMC - PMC11102595 +OTO - NOTNLM +OT - carboxyl ester lipase +OT - pancreatic cancer +OT - single-base insertions +OT - variable number tandem repeat +EDAT- 2024/03/14 12:46 +MHDA- 2024/05/19 12:42 +PMCR- 2024/03/14 +CRDT- 2024/03/14 11:23 +PHST- 2023/11/24 00:00 [received] +PHST- 2024/02/14 00:00 [revised] +PHST- 2024/02/27 00:00 [accepted] +PHST- 2024/05/19 12:42 [medline] +PHST- 2024/03/14 12:46 [pubmed] +PHST- 2024/03/14 11:23 [entrez] +PHST- 2024/03/14 00:00 [pmc-release] +AID - 7628593 [pii] +AID - ddae034 [pii] +AID - 10.1093/hmg/ddae034 [doi] +PST - ppublish +SO - Hum Mol Genet. 2024 May 18;33(11):1001-1014. doi: 10.1093/hmg/ddae034. + +PMID- 38473919 +OWN - NLM +STAT- MEDLINE +DCOM- 20240314 +LR - 20240315 +IS - 1422-0067 (Electronic) +IS - 1422-0067 (Linking) +VI - 25 +IP - 5 +DP - 2024 Feb 26 +TI - Unlocking Predictive Power: Quantitative Assessment of CAR-T Expansion with + Digital Droplet Polymerase Chain Reaction (ddPCR). +LID - 10.3390/ijms25052673 [doi] +LID - 2673 +AB - Flow cytometry (FCM) and quantitative PCR (qPCR) are conventional methods for + assessing CAR-T expansion, while digital droplet PCR (ddPCR) is emerging as a + promising alternative. We monitored CAR-T transcript expansion in 40 B-NHL + patients post-infusion of CAR-T products (axi-cel; tisa-cel; and brexu-cel) with + both His-Tag FCM and ddPCR techniques. Sensitivity and predictive capacity for + efficacy and safety outcomes of ddPCR were analyzed and compared with FCM. A + significant correlation between CAR-T counts determined by FCM and CAR + transcripts assessed by ddPCR (p < 0.001) was observed. FCM revealed median + CD3+CAR+ cell counts at 7, 14, and 30 days post-infusion with no significant + differences. In contrast, ddPCR-measured median copies of CAR-T transcripts + demonstrated significant lower copy numbers in tisa-cel recipients compared to + the other products at day 7 and day 14. Patients with a peak of CAR transcripts + at day 7 exceeding 5000 copies/microg gDNA, termed "good CAR-T expanders", were + more likely to achieve a favorable response at 3 months (HR 10.79, 95% CI + 1.16-100.42, p = 0.036). Good CAR-T expanders showed superior progression-free + survival at 3, 6, and 12 months compared to poor CAR-T expanders (p = 0.088). + Those reaching a peak higher than 5000 copies/microg gDNA were more likely to + experience severe CRS and ICANS. DdPCR proves to be a practical method for + monitoring CAR-T expansion, providing quantitative information that better + predicts both treatment outcomes and toxicity. +FAU - Galli, Eugenio +AU - Galli E +AUID- ORCID: 0000-0002-2839-916X +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +FAU - Viscovo, Marcello +AU - Viscovo M +AD - Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, + Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. +FAU - Fosso, Federica +AU - Fosso F +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +FAU - Pansini, Ilaria +AU - Pansini I +AD - Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, + Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. +FAU - Di Cesare, Giacomo +AU - Di Cesare G +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +FAU - Iacovelli, Camilla +AU - Iacovelli C +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +FAU - Maiolo, Elena +AU - Maiolo E +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +FAU - Sora, Federica +AU - Sora F +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +AD - Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, + Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. +FAU - Hohaus, Stefan +AU - Hohaus S +AUID- ORCID: 0000-0002-5534-7197 +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +AD - Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, + Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. +FAU - Sica, Simona +AU - Sica S +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +AD - Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, + Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. +FAU - Bellesi, Silvia +AU - Bellesi S +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +FAU - Chiusolo, Patrizia +AU - Chiusolo P +AUID- ORCID: 0000-0002-1355-1587 +AD - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, + Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 + Rome, Italy. +AD - Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, + Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. +LA - eng +PT - Journal Article +DEP - 20240226 +PL - Switzerland +TA - Int J Mol Sci +JT - International journal of molecular sciences +JID - 101092791 +RN - 0 (Receptors, Chimeric Antigen) +SB - IM +MH - Humans +MH - *Receptors, Chimeric Antigen +MH - Polymerase Chain Reaction/methods +MH - Treatment Outcome +MH - Progression-Free Survival +MH - Immunotherapy, Adoptive +MH - *Lymphoma, Large B-Cell, Diffuse/therapy +PMC - PMC10932155 +OTO - NOTNLM +OT - B-cell lymphoma +OT - CAR-T cells +OT - digital droplet PCR +COIS- E.G. received honoraria from Novartis and grant for meeting attendance from Kite + Gilead, Abbvie, and Novartis. S.H. received honoraria from Takeda, Roche, Incyte, + Ipsen, Kite Gilead, Novartis. F.S. received honoraria from Kite Gilead, Incyte, + Novartis, and BMS. The other authors declare no competing conflicts of interest. +EDAT- 2024/03/13 06:46 +MHDA- 2024/03/14 06:46 +PMCR- 2024/02/26 +CRDT- 2024/03/13 01:22 +PHST- 2024/01/15 00:00 [received] +PHST- 2024/02/16 00:00 [revised] +PHST- 2024/02/20 00:00 [accepted] +PHST- 2024/03/14 06:46 [medline] +PHST- 2024/03/13 06:46 [pubmed] +PHST- 2024/03/13 01:22 [entrez] +PHST- 2024/02/26 00:00 [pmc-release] +AID - ijms25052673 [pii] +AID - ijms-25-02673 [pii] +AID - 10.3390/ijms25052673 [doi] +PST - epublish +SO - Int J Mol Sci. 2024 Feb 26;25(5):2673. doi: 10.3390/ijms25052673. + +PMID- 38458477 +OWN - NLM +STAT- MEDLINE +DCOM- 20240530 +LR - 20240920 +IS - 2666-6367 (Electronic) +IS - 2666-6367 (Linking) +VI - 30 +IP - 6 +DP - 2024 Jun +TI - Early Chimeric Antigen Receptor T Cell Expansion Is Associated with Prolonged + Progression-Free Survival for Patients with Relapsed/Refractory Multiple Myeloma + Treated with Ide-Cel: A Retrospective Monocentric Study. +PG - 630.e1-630.e8 +LID - S2666-6367(24)00253-7 [pii] +LID - 10.1016/j.jtct.2024.03.003 [doi] +AB - The outcomes of patients with relapsed and refractory multiple myeloma (RRMM) + previously treated with the 3 main classes of myeloma therapy-immunomodulatory + drugs, proteasome inhibitors, and anti-CD38 antibodies-remain poor. Recently, + based on the phase II pivotal KarMMa trial showing prolonged overall survival + (OS) and progression-free survival (PFS) in heavily treated patients, + idecabtagene vicleucel (ide-cel), a B cell maturation antigen (BCMA)-directed + chimeric antigen receptor (CAR) T cell therapy (CAR-T) product, was approved in + the United States for the treatment of RRMM. In France, since June 2021, an early + access program has authorized the use of ide-cel in the setting of RRMM (defined + as progressive myeloma after at least 3 previous regimens, including the 3 main + antimyeloma therapies). We report the first French experience through this early + access program in a retrospective study of 24 consecutive patients treated with + ide-cel at our institution. The patients were evaluated according to + International Myeloma Working Group criteria and by positron emission tomography + computed tomography (PET-CT) at 1, 3, 6, 9, and 12 months after ide-cel infusion. + Most patients had adverse cytogenetic abnormalities, and RRMM with + triple-refractory drugs were seen in 79%. Bridging therapy was required for 19 of + 24 patients. Before CAR-T cell infusion, lymphodepletion with fludarabine and + cyclophosphamide was systematically performed. The median follow-up was 15.2 + months. At 3 months after ide-cel infusion, 92% of patients achieved at least a + partial response, and 50% achieved a complete response or better (>/=CR). At 6 + months, 70% of patients had a persistent >/=CR. At 3 and 6 months, bone marrow + minimal residual disease (10(-6) level) was undetectable in 79% and 75% of + patients, respectively. At 6 months, CR as assessed by PET-CT was achieved in 15 + of 20 patients (75%). The median PFS was 14.8 months, and median OS was not + reached. Notably, an expansion of circulating CAR-T cells to >180/mm(3) after + infusion was strongly associated with prolonged PFS. Additionally, the level of + soluble BCMA measured before infusion was identified as a prognostic factor for + PFS, likely correlated to the tumor burden. Grade 1-2 cytokine release syndrome + (CRS) occurred in 22 of 24 patients (92%). Only 1 patient (4%) experienced grade + >/=3 CRS. The occurrence of neurologic toxicity was infrequent (12.5%) and + reversible in all cases. Hematologic toxicity was relatively common, and + secondary hypogammaglobulinemia occurred in most patients. Infections (mostly + viral) were frequent but most often nonsevere. This study echoes the promising + results of the KarMMa trial and identifies possible prognostic indicators in RRMM + patients treated with ide-cel, potentially refining treatment strategies and + improving outcomes in this challenging context. +CI - Copyright (c) 2024. Published by Elsevier Inc. +FAU - Caillot, Leo +AU - Caillot L +AD - Clinical Hematology, CHU Dijon, Dijon, France. +FAU - Sleiman, Emmanuel +AU - Sleiman E +AD - Clinical Hematology, CHU Dijon, Dijon, France. +FAU - Lafon, Ingrid +AU - Lafon I +AD - Clinical Hematology, CHU Dijon, Dijon, France; Burgundy Cancer Institute, Dijon, + France. +FAU - Chretien, Marie-Lorraine +AU - Chretien ML +AD - Clinical Hematology, CHU Dijon, Dijon, France; Burgundy Cancer Institute, Dijon, + France. +FAU - Gueneau, Pauline +AU - Gueneau P +AD - Innovative Therapy Unit, Pharmacy, CHU Dijon, Dijon, France. +FAU - Payssot, Alexandre +AU - Payssot A +AD - Hematology, Clinique du Parc, Castelnau Le Lez, France. +FAU - Pedri, Romain +AU - Pedri R +AD - Clinical Hematology, CHU Dijon, Dijon, France. +FAU - Lakomy, Daniela +AU - Lakomy D +AD - Specialized Biochemistry Laboratory, CHU Dijon, Dijon, France. +FAU - Bailly, Francois +AU - Bailly F +AD - Hematology Laboratory, CHU Dijon, Dijon, France. +FAU - Guy, Julien +AU - Guy J +AD - Hematology Laboratory, CHU Dijon, Dijon, France. +FAU - Quenot, Jean-Pierre +AU - Quenot JP +AD - Intensive Care Medecine, CHU Dijon, Dijon, France. +FAU - Avet-Loiseau, Herve +AU - Avet-Loiseau H +AD - Myeloma Genomics Unit, IUCT Oncopole, Toulouse, France. +FAU - Caillot, Denis +AU - Caillot D +AD - Clinical Hematology, CHU Dijon, Dijon, France; Burgundy Cancer Institute, Dijon, + France. Electronic address: denis.caillot2024@gmail.com. +LA - eng +PT - Journal Article +DEP - 20240307 +PL - United States +TA - Transplant Cell Ther +JT - Transplantation and cellular therapy +JID - 101774629 +RN - 0 (Receptors, Chimeric Antigen) +RN - 8PX1X7UG4D (idecabtagene vicleucel) +RN - 0 (B-Cell Maturation Antigen) +SB - IM +MH - Humans +MH - *Multiple Myeloma/therapy/mortality +MH - Male +MH - Middle Aged +MH - Retrospective Studies +MH - Female +MH - Aged +MH - *Receptors, Chimeric Antigen/therapeutic use +MH - *Immunotherapy, Adoptive/methods/adverse effects +MH - Progression-Free Survival +MH - Adult +MH - B-Cell Maturation Antigen +MH - T-Lymphocytes/immunology +MH - Aged, 80 and over +OTO - NOTNLM +OT - BCMA +OT - CAR-T cell expansion +OT - Ide-cel +OT - RRMM +EDAT- 2024/03/09 10:43 +MHDA- 2024/05/31 00:42 +CRDT- 2024/03/08 19:16 +PHST- 2023/12/07 00:00 [received] +PHST- 2024/02/12 00:00 [revised] +PHST- 2024/03/04 00:00 [accepted] +PHST- 2024/05/31 00:42 [medline] +PHST- 2024/03/09 10:43 [pubmed] +PHST- 2024/03/08 19:16 [entrez] +AID - S2666-6367(24)00253-7 [pii] +AID - 10.1016/j.jtct.2024.03.003 [doi] +PST - ppublish +SO - Transplant Cell Ther. 2024 Jun;30(6):630.e1-630.e8. doi: + 10.1016/j.jtct.2024.03.003. Epub 2024 Mar 7. + +PMID- 36379850 +OWN - NLM +STAT- MEDLINE +DCOM- 20221206 +LR - 20240608 +IS - 1424-3911 (Electronic) +IS - 1424-3903 (Print) +IS - 1424-3903 (Linking) +VI - 22 +IP - 8 +DP - 2022 Dec +TI - The genetic risk factor CEL-HYB1 causes proteotoxicity and chronic pancreatitis + in mice. +PG - 1099-1111 +LID - S1424-3903(22)00790-6 [pii] +LID - 10.1016/j.pan.2022.11.003 [doi] +AB - BACKGROUND & AIMS: The CEL gene encodes the digestive enzyme carboxyl ester + lipase. CEL-HYB1, a hybrid allele of CEL and its adjacent pseudogene CELP, is a + genetic variant suggested to increase the risk of chronic pancreatitis (CP). Our + aim was to develop a mouse model for CEL-HYB1 that enables studies of pancreatic + disease mechanisms. METHODS: We established a knock-in mouse strain where the + variable number of tandem repeat (VNTR) region of the endogenous mouse Cel gene + was substituted with the mutated VNTR of the human CEL-HYB1 allele. Heterozygous + and homozygous Cel-HYB1 mice and littermate wildtype controls were characterized + with respect to pancreatic pathology and function. RESULTS: We successfully + constructed a mouse model with pancreatic expression of a humanized CEL-HYB1 + protein. The Cel-HYB1 mice spontaneously developed features of CP including + inflammation, acinar atrophy and fatty replacement, and the phenotype became more + pronounced as the animals aged. Moreover, Cel-HYB1 mice were normoglycemic at age + 6 months, whereas at 12 months they exhibited impaired glucose tolerance. + Immunostaining of pancreatic tissue indicated the formation of CEL protein + aggregates, and electron microscopy showed dilated endoplasmic reticulum. + Upregulation of the stress marker BiP/GRP78 was seen in pancreatic parenchyma + obtained both from Cel-HYB1 animals and from a human CEL-HYB1 carrier. + CONCLUSIONS: We have developed a new mouse model for CP that confirms the + pathogenicity of the human CEL-HYB1 variant. Our findings place CEL-HYB1 in the + group of genes that increase CP risk through protein misfolding-dependent + pathways. +CI - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved. +FAU - Fjeld, Karianne +AU - Fjeld K +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Norway; Department of Medical Genetics, Haukeland + University Hospital, Bergen, Norway. Electronic address: karianne.fjeld@uib.no. +FAU - Gravdal, Anny +AU - Gravdal A +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Norway; Department of Medical Genetics, Haukeland + University Hospital, Bergen, Norway. +FAU - Brekke, Ranveig S +AU - Brekke RS +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Norway; Department of Medical Genetics, Haukeland + University Hospital, Bergen, Norway. +FAU - Alam, Jahedul +AU - Alam J +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Norway. +FAU - Wilhelm, Steven J +AU - Wilhelm SJ +AD - Department of Pediatrics, Washington University School of Medicine, St. Louis, + MO, USA. +FAU - El Jellas, Khadija +AU - El Jellas K +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Norway. +FAU - Pettersen, Helene N +AU - Pettersen HN +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Norway. +FAU - Lin, Jianguo +AU - Lin J +AD - Department of Pediatrics, Washington University School of Medicine, St. Louis, + MO, USA. +FAU - Solheim, Marie H +AU - Solheim MH +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Norway. +FAU - Steine, Solrun J +AU - Steine SJ +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway. +FAU - Johansson, Bente B +AU - Johansson BB +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Norway. +FAU - Njolstad, Pal R +AU - Njolstad PR +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Norway; Pediatric and Youth Clinic, Haukeland University Hospital, + Bergen, Norway. +FAU - Verbeke, Caroline S +AU - Verbeke CS +AD - Department of Pathology, Oslo University Hospital Rikshospitalet, Oslo, Norway; + Department of Pathology, Institute of Clinical Medicine, University of Oslo, + Oslo, Norway. +FAU - Xiao, Xunjun +AU - Xiao X +AD - Department of Pediatrics, Washington University School of Medicine, St. Louis, + MO, USA. +FAU - Lowe, Mark E +AU - Lowe ME +AD - Department of Pediatrics, Washington University School of Medicine, St. Louis, + MO, USA. +FAU - Molven, Anders +AU - Molven A +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, + Bergen, Norway; Section for Cancer Genomics, Haukeland University Hospital, + Bergen, Norway. +LA - eng +GR - R01 DK124415/DK/NIDDK NIH HHS/United States +PT - Journal Article +DEP - 20221109 +PL - Switzerland +TA - Pancreatology +JT - Pancreatology : official journal of the International Association of + Pancreatology (IAP) ... [et al.] +JID - 100966936 +RN - EC 3.1.1.3 (Lipase) +SB - IM +MH - Humans +MH - Mice +MH - Animals +MH - Aged +MH - Infant +MH - *Lipase/genetics +MH - *Pancreatitis, Chronic/genetics +MH - Alleles +MH - Minisatellite Repeats +MH - Risk Factors +PMC - PMC11157984 +MID - NIHMS1996046 +OTO - NOTNLM +OT - Carboxyl ester lipase +OT - Chronic pancreatitis +OT - Genetic risk factor +OT - Knock-in mouse model +OT - Variable number of tandem repeats +COIS- Declaration of competing interest The authors declare no conflicts of interest. +EDAT- 2022/11/16 06:00 +MHDA- 2022/12/07 06:00 +PMCR- 2024/06/07 +CRDT- 2022/11/15 22:06 +PHST- 2022/07/07 00:00 [received] +PHST- 2022/10/31 00:00 [revised] +PHST- 2022/11/04 00:00 [accepted] +PHST- 2022/11/16 06:00 [pubmed] +PHST- 2022/12/07 06:00 [medline] +PHST- 2022/11/15 22:06 [entrez] +PHST- 2024/06/07 00:00 [pmc-release] +AID - S1424-3903(22)00790-6 [pii] +AID - 10.1016/j.pan.2022.11.003 [doi] +PST - ppublish +SO - Pancreatology. 2022 Dec;22(8):1099-1111. doi: 10.1016/j.pan.2022.11.003. Epub + 2022 Nov 9. + +PMID- 35583610 +OWN - NLM +STAT- MEDLINE +DCOM- 20220804 +LR - 20250728 +IS - 1557-3265 (Electronic) +IS - 1078-0432 (Print) +IS - 1078-0432 (Linking) +VI - 28 +IP - 15 +DP - 2022 Aug 2 +TI - Phenotypic Composition of Commercial Anti-CD19 CAR T Cells Affects In Vivo + Expansion and Disease Response in Patients with Large B-cell Lymphoma. +PG - 3378-3386 +LID - 10.1158/1078-0432.CCR-22-0164 [doi] +AB - PURPOSE: In clinical trials, the expansion and persistence of chimeric antigen + receptor (CAR) T cells correlate with therapeutic efficacy. However, properties + of CAR T cells that enable their in vivo proliferation have still to be + consistently defined and the role of CAR T bag content has never been + investigated in a real-life setting. EXPERIMENTAL DESIGN: Residual cells obtained + after washing 61 anti-CD19 CAR T product bags were analyzed to identify + tisagenlecleucel/Tisa-cel and axicabtagene ciloleucel/Axi-cel phenotypic features + associated with postinfusion CAR T-cell in vivo expansion and with response and + survival. RESULTS: While Tisa-cel was characterized by a significant enrichment + in CAR+CD4+ T cells with central memory (P < 0.005) and effector (P < 0.005) + phenotypes and lower rates of CAR+CD8+ with effector memory (P < 0.005) and + naive-like (P < 0.05) phenotypes as compared with Axi-cel, the two products + displayed similar expansion kinetics. In vivo CAR T-cell expansion was influenced + by the presence of CAR T with a CD8+ T central memory signature (P < 0.005) in + both Tisa-cel and Axi-cel infusion products and was positively associated with + response and progression-free survival (P < 0.05). CONCLUSIONS: Our data indicate + that despite the great heterogeneity of Tisa-cel and Axi-cel products, the + differentiation status of the infused cells mediates CAR T-cell in vivo + proliferation that is necessary for antitumor response. +CI - (c)2022 The Authors; Published by the American Association for Cancer Research. +FAU - Monfrini, Chiara +AU - Monfrini C +AUID- ORCID: 0000-0001-8675-9066 +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +FAU - Stella, Federico +AU - Stella F +AUID- ORCID: 0000-0003-3401-1309 +AD - School of Medicine, Universita degli Studi di Milano, Italy. +FAU - Aragona, Vanessa +AU - Aragona V +AUID- ORCID: 0000-0003-1300-9111 +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +FAU - Magni, Martina +AU - Magni M +AUID- ORCID: 0000-0001-9458-5836 +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +FAU - Ljevar, Silva +AU - Ljevar S +AUID- ORCID: 0000-0002-1151-1477 +AD - Department of Clinical Epidemiology and Trial Organization, Fondazione IRCCS + Istituto Nazionale dei Tumori, Milano, Italy. +FAU - Vella, Cristina +AU - Vella C +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +FAU - Fardella, Eugenio +AU - Fardella E +AD - School of Medicine, Universita degli Studi di Milano, Italy. +FAU - Chiappella, Annalisa +AU - Chiappella A +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +FAU - Nanetti, Francesca +AU - Nanetti F +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +FAU - Pennisi, Martina +AU - Pennisi M +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +FAU - Dodero, Anna +AU - Dodero A +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +FAU - Guidetti, Anna +AU - Guidetti A +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +AD - School of Medicine, Universita degli Studi di Milano, Italy. +FAU - Corradini, Paolo +AU - Corradini P +AUID- ORCID: 0000-0002-9186-1353 +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +AD - School of Medicine, Universita degli Studi di Milano, Italy. +FAU - Carniti, Cristiana +AU - Carniti C +AUID- ORCID: 0000-0003-1039-1757 +AD - Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, + Italy. +LA - eng +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +PL - United States +TA - Clin Cancer Res +JT - Clinical cancer research : an official journal of the American Association for + Cancer Research +JID - 9502500 +RN - 0 (Antigens, CD19) +RN - 0 (Receptors, Chimeric Antigen) +SB - IM +MH - Antigens, CD19/therapeutic use +MH - Humans +MH - Immunotherapy, Adoptive +MH - *Lymphoma, Large B-Cell, Diffuse/pathology +MH - Phenotype +MH - *Receptors, Chimeric Antigen/genetics +MH - T-Lymphocytes +PMC - PMC9662896 +EDAT- 2022/05/19 06:00 +MHDA- 2022/08/05 06:00 +PMCR- 2022/11/14 +CRDT- 2022/05/18 11:36 +PHST- 2022/01/17 00:00 [received] +PHST- 2022/03/11 00:00 [revised] +PHST- 2022/05/16 00:00 [accepted] +PHST- 2022/05/19 06:00 [pubmed] +PHST- 2022/08/05 06:00 [medline] +PHST- 2022/05/18 11:36 [entrez] +PHST- 2022/11/14 00:00 [pmc-release] +AID - 699017 [pii] +AID - CCR-22-0164 [pii] +AID - 10.1158/1078-0432.CCR-22-0164 [doi] +PST - ppublish +SO - Clin Cancer Res. 2022 Aug 2;28(15):3378-3386. doi: 10.1158/1078-0432.CCR-22-0164. + +PMID- 35215948 +OWN - NLM +STAT- MEDLINE +DCOM- 20220316 +LR - 20220316 +IS - 1999-4915 (Electronic) +IS - 1999-4915 (Linking) +VI - 14 +IP - 2 +DP - 2022 Feb 9 +TI - High Phenotypic Variation between an In Vitro-Passaged Fowl Adenovirus Serotype 1 + (FAdV-1) and Its Virulent Progenitor Strain despite Almost Complete Sequence + Identity of the Whole Genomes. +LID - 10.3390/v14020358 [doi] +LID - 358 +AB - Adenoviral gizzard erosion is an emerging disease with negative impact on health + and production of chickens. In this study, we compared in vitro and in vivo + characteristics of a fowl adenovirus serotype 1 (FAdV-1), attenuated by 53 + consecutive passages in primary chicken embryo liver (CEL) cell cultures + (11/7127-AT), with the virulent strain (11/7127-VT). Whole genome analysis + revealed near-complete sequence identity between the strains. However, a length + polymorphism in a non-coding adenine repeat sequence (11/7127-AT: 11 instead of + 9) immediately downstream of the hexon open reading frame was revealed. One-step + growth kinetics showed delayed multiplication of 11/7127-AT together with + significantly lower titers in cell culture (up to 4 log(10) difference), + indicating reduced replication efficiency in vitro. In vivo pathogenicity and + immunogenicity were determined in day-old specific pathogen-free layer chicks + inoculated orally with the respective viruses. In contrast to birds infected with + 11/7127-VT, birds infected with 11/7127-AT did not exhibit body weight loss or + severe pathological lesions in the gizzard. Virus detection rates, viral load in + organs and virus excretion were significantly lower in birds inoculated with + 11/7127-AT. Throughout the experimental period, these birds did not develop + measurable neutralizing antibodies, prevalent in birds in response to 11/7127-VT + infection. Differences in pathogenicity between the virulent FAdV-1 and the + attenuated strain could not be correlated to prominently discriminate genomic + features. We conclude that differential in vitro growth profiles indicate that + attenuation is linked to modulation of viral replication during interaction of + the virus with the host cells. Thus, hosts would be unable to prevent the rapid + replication of virulent FAdV leading to severe tissue damage, a phenomenon + broadly applicable to further FAdV serotypes, considering the substantial + intra-serotype virulence differences of FAdVs and the variation of diseases. +FAU - Grafl, Beatrice +AU - Grafl B +AD - Clinic for Poultry and Fish Medicine, Department for Farm Animals and Veterinary + Public Health, University of Veterinary Medicine (Vetmeduni Vienna), 1210 Vienna, + Austria. +FAU - Schachner, Anna +AU - Schachner A +AD - Christian Doppler Laboratory for Innovative Poultry Vaccines (IPOV), University + of Veterinary Medicine, 1210 Vienna, Austria. +FAU - Hess, Michael +AU - Hess M +AD - Clinic for Poultry and Fish Medicine, Department for Farm Animals and Veterinary + Public Health, University of Veterinary Medicine (Vetmeduni Vienna), 1210 Vienna, + Austria. +LA - eng +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +DEP - 20220209 +PL - Switzerland +TA - Viruses +JT - Viruses +JID - 101509722 +RN - 0 (Antibodies, Neutralizing) +RN - 0 (Antibodies, Viral) +SB - IM +MH - Adenoviridae Infections/pathology/veterinary/virology +MH - Animals +MH - Antibodies, Neutralizing/blood +MH - Antibodies, Viral/blood +MH - Chick Embryo +MH - Chickens +MH - Fowl adenovirus A/*genetics/growth & development/immunology/*pathogenicity +MH - Genome, Viral/*genetics +MH - Gizzard, Avian/pathology/virology +MH - Polymorphism, Genetic +MH - Poultry Diseases/pathology/virology +MH - Viral Load/genetics +MH - Virulence/genetics +MH - Virus Replication/genetics +PMC - PMC8880033 +OTO - NOTNLM +OT - attenuation +OT - fowl adenovirus +OT - genome +OT - gizzard erosion +OT - poultry +COIS- The authors declare no conflict of interest. +EDAT- 2022/02/27 06:00 +MHDA- 2022/03/17 06:00 +PMCR- 2022/02/09 +CRDT- 2022/02/26 01:07 +PHST- 2021/12/14 00:00 [received] +PHST- 2022/01/21 00:00 [revised] +PHST- 2022/02/07 00:00 [accepted] +PHST- 2022/02/26 01:07 [entrez] +PHST- 2022/02/27 06:00 [pubmed] +PHST- 2022/03/17 06:00 [medline] +PHST- 2022/02/09 00:00 [pmc-release] +AID - v14020358 [pii] +AID - viruses-14-00358 [pii] +AID - 10.3390/v14020358 [doi] +PST - epublish +SO - Viruses. 2022 Feb 9;14(2):358. doi: 10.3390/v14020358. + +PMID- 35156195 +OWN - NLM +STAT- MEDLINE +DCOM- 20220621 +LR - 20250728 +IS - 1532-6535 (Electronic) +IS - 0009-9236 (Print) +IS - 0009-9236 (Linking) +VI - 112 +IP - 1 +DP - 2022 Jul +TI - In Vivo Cellular Expansion of Lisocabtagene Maraleucel and Association With + Efficacy and Safety in Relapsed/Refractory Large B-Cell Lymphoma. +PG - 81-89 +LID - 10.1002/cpt.2561 [doi] +AB - Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric + antigen receptor T-cell product for the treatment of adult patients with relapsed + or refractory large B-cell lymphoma (LBCL) after 2 or more lines of systemic + therapy. In vivo cellular expansion after single-dose administration of liso-cel + has been characterized. In this article, in vivo liso-cel expansion in the + pivotal study TRANSCEND NHL 001 (ClinicalTrials.gov identifier, NCT02631044) was + further characterized to assess the relationship between in vivo cellular + expansion after single-dose administration of liso-cel and efficacy or safety + after adjusting for key baseline characteristics. Two bioanalytical methods, + quantitative polymerase chain reaction and flow cytometry, were used for the + assessment of cellular kinetics of liso-cel, which showed high concordance for in + vivo cellular expansion. Multivariable logistic regression analyses demonstrated + that higher in vivo cellular expansion of liso-cel was associated with a higher + overall response and complete response rate, and a higher incidence of cytokine + release syndrome and neurological events in patients with relapsed or refractory + LBCL. Age and tumor burden (by sum of the product of perpendicular diameters) + were likely to confound the relationship between in vivo cellular expansion and + efficacy, where the association became stronger after controlling for these + factors. Repeat dosing of liso-cel was tested in the study; however, in vivo + cellular expansion of liso-cel was lower after repeat dosing than after the + initial dose. These findings should enable a comprehensive understanding of the + in vivo cellular kinetics of liso-cel and the association with outcomes in + relapsed/refractory LBCL. +CI - (c) 2022 Bristol Myers Squibb. Clinical Pharmacology & Therapeutics published by + Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and + Therapeutics. +FAU - Ogasawara, Ken +AU - Ogasawara K +AUID- ORCID: 0000-0002-4264-8927 +AD - Bristol Myers Squibb, Princeton, New Jersey, USA. +FAU - Lymp, James +AU - Lymp J +AD - Bristol Myers Squibb, Seattle, Washington, USA. +FAU - Mack, Timothy +AU - Mack T +AD - Bristol Myers Squibb, Princeton, New Jersey, USA. +FAU - Dell'Aringa, Justine +AU - Dell'Aringa J +AD - Bristol Myers Squibb, Seattle, Washington, USA. +FAU - Huang, Chang-Pin +AU - Huang CP +AD - Bristol Myers Squibb, Seattle, Washington, USA. +FAU - Smith, Jeff +AU - Smith J +AD - Bristol Myers Squibb, Seattle, Washington, USA. +FAU - Peiser, Leanne +AU - Peiser L +AD - Bristol Myers Squibb, Seattle, Washington, USA. +FAU - Kostic, Ana +AU - Kostic A +AD - Bristol Myers Squibb, Seattle, Washington, USA. +LA - eng +SI - ClinicalTrials.gov/NCT02631044 +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +DEP - 20220320 +PL - United States +TA - Clin Pharmacol Ther +JT - Clinical pharmacology and therapeutics +JID - 0372741 +RN - 0 (Antigens, CD19) +RN - 0 (Receptors, Chimeric Antigen) +SB - IM +CIN - Clin Pharmacol Ther. 2022 Jul;112(1):11-15. doi: 10.1002/cpt.2631. PMID: 35716389 +MH - Adult +MH - Antigens, CD19 +MH - Humans +MH - Immunotherapy, Adoptive/adverse effects/methods +MH - *Lymphoma, Large B-Cell, Diffuse/drug therapy +MH - *Receptors, Chimeric Antigen +MH - T-Lymphocytes +PMC - PMC9311712 +COIS- K.O., J.L., T.M., J.D., C.H., J.S., L.P., and A.K. are employees of Bristol Myers + Squibb and hold stock in Bristol Myers Squibb. +EDAT- 2022/02/15 06:00 +MHDA- 2022/06/22 06:00 +PMCR- 2022/03/20 +CRDT- 2022/02/14 05:38 +PHST- 2021/11/02 00:00 [received] +PHST- 2022/02/07 00:00 [accepted] +PHST- 2022/02/15 06:00 [pubmed] +PHST- 2022/06/22 06:00 [medline] +PHST- 2022/02/14 05:38 [entrez] +PHST- 2022/03/20 00:00 [pmc-release] +AID - CPT2561 [pii] +AID - 10.1002/cpt.2561 [doi] +PST - ppublish +SO - Clin Pharmacol Ther. 2022 Jul;112(1):81-89. doi: 10.1002/cpt.2561. Epub 2022 Mar + 20. + +PMID- 35082198 +OWN - NLM +STAT- MEDLINE +DCOM- 20220128 +LR - 20220131 +IS - 1349-3329 (Electronic) +IS - 0040-8727 (Linking) +VI - 256 +IP - 1 +DP - 2022 Jan +TI - Identification of a Novel Mutation in Carboxyl Ester Lipase Gene in a Patient + with MODY-like Diabetes. +PG - 37-41 +LID - 10.1620/tjem.256.37 [doi] +AB - Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus + characterized by autosomal dominant inheritance, early onset, and the absence of + pancreatic autoimmune markers. MODY-causing mutations have been identified in 14 + genes, and carboxyl ester lipase (CEL) has been implicated in MODY8. We report a + Japanese patient with MODY who harbored a heterogeneous mutation in CEL exon 2 + (NM_001807.4:c.146_147delCT; NP_001798.2:p.Ser49CysfsTer52). A 13-year-old girl + experienced her first episode of diabetic ketoacidosis, during which her + endogenous insulin secretion was poor. However, her insulin secretion had + apparently recovered 2 months after the commencement of insulin treatment, and no + further treatment was required for the following 2 years. Diabetic ketoacidosis + recurred when the patient was 15 years old, when her insulin secretion was again + poor. Since that time, the patient, who is now 18 years old, has been undergoing + continuous insulin treatment. The large fluctuations in her insulin secretory + capacity led us to suspect MODY. MODY8 patients that carry a mutation in the + variable number of tandem repeats in the last exon of the CEL gene typically show + pancreatic exocrine dysfunction. However, in the present case, which features + premature termination, there is no involvement of exocrine dysfunction, + potentially demonstrating a genotype-phenotype correlation. +FAU - Kondoh, Tomomi +AU - Kondoh T +AD - Department of Pediatrics, Fujita Health University School of Medicine. +FAU - Nakajima, Yoko +AU - Nakajima Y +AD - Department of Pediatrics, Fujita Health University School of Medicine. +FAU - Yokoi, Katsuyuki +AU - Yokoi K +AD - Department of Pediatrics, Fujita Health University School of Medicine. +FAU - Matsumoto, Yuji +AU - Matsumoto Y +AD - Department of Pediatrics, Fujita Health University School of Medicine. +FAU - Inagaki, Hidehito +AU - Inagaki H +AD - Division of Molecular Genetics, Institute for Comprehensive Medical Science, + Fujita Health University School of Medicine. +FAU - Kato, Takema +AU - Kato T +AD - Division of Molecular Genetics, Institute for Comprehensive Medical Science, + Fujita Health University School of Medicine. +FAU - Nakajima, Yoichi +AU - Nakajima Y +AD - Department of Pediatrics, Fujita Health University School of Medicine. +FAU - Ito, Tetsuya +AU - Ito T +AD - Department of Pediatrics, Fujita Health University School of Medicine. +FAU - Yoshikawa, Tetsushi +AU - Yoshikawa T +AD - Department of Pediatrics, Fujita Health University School of Medicine. +FAU - Kurahashi, Hiroki +AU - Kurahashi H +AD - Division of Molecular Genetics, Institute for Comprehensive Medical Science, + Fujita Health University School of Medicine. +LA - eng +PT - Case Reports +PT - Journal Article +PL - Japan +TA - Tohoku J Exp Med +JT - The Tohoku journal of experimental medicine +JID - 0417355 +RN - 0 (Esters) +RN - EC 3.1.1.1 (Carboxylesterase) +RN - EC 3.1.1.3 (Lipase) +RN - Mason-Type Diabetes +SB - IM +MH - Adolescent +MH - *Carboxylesterase/genetics +MH - *Diabetes Mellitus, Type 2/genetics +MH - Esters +MH - Female +MH - Humans +MH - Lipase/genetics +MH - Mutation/genetics +OTO - NOTNLM +OT - MODY8 +OT - carboxyl ester lipase +OT - diabetes mellitus +OT - maturity-onset diabetes of the young +OT - pancreatic exocrine dysfunction +EDAT- 2022/01/28 06:00 +MHDA- 2022/01/29 06:00 +CRDT- 2022/01/27 05:46 +PHST- 2022/01/27 05:46 [entrez] +PHST- 2022/01/28 06:00 [pubmed] +PHST- 2022/01/29 06:00 [medline] +AID - 10.1620/tjem.256.37 [doi] +PST - ppublish +SO - Tohoku J Exp Med. 2022 Jan;256(1):37-41. doi: 10.1620/tjem.256.37. + +PMID- 34850019 +OWN - NLM +STAT- MEDLINE +DCOM- 20220415 +LR - 20220531 +IS - 1945-7197 (Electronic) +IS - 0021-972X (Print) +IS - 0021-972X (Linking) +VI - 107 +IP - 4 +DP - 2022 Mar 24 +TI - Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: + How to Correctly Identify MODY8 Cases. +PG - e1455-e1466 +LID - 10.1210/clinem/dgab864 [doi] +AB - CONTEXT: Maturity onset diabetes of the young, type 8 (MODY8) is associated with + mutations in the CEL gene, which encodes the digestive enzyme carboxyl ester + lipase. Several diabetes cases and families have in recent years been attributed + to mutations in CEL without any functional or clinical evidence provided. + OBJECTIVE: To facilitate correct MODY8 diagnostics, we screened 2 cohorts of + diabetes patients and delineated the phenotype. METHODS: Young, lean Swedish and + Finnish patients with a diagnosis of type 2 diabetes (352 cases, 406 controls) + were screened for mutations in the CEL gene. We also screened 58 Czech MODY cases + who had tested negative for common MODY genes. For CEL mutation-positive + subjects, family history was recorded, and clinical investigations and pancreatic + imaging performed. RESULTS: Two cases (1 Swedish and 1 Czech) with germline + mutation in CEL were identified. Clinical and radiological investigations of + these 2 probands and their families revealed dominantly inherited + insulin-dependent diabetes, pancreatic exocrine dysfunction, and atrophic + pancreas with lipomatosis and cysts. Notably, hereditary pancreatitis was the + predominant phenotype in 1 pedigree. Both families carried single-base pair + deletions in the proximal part of the CEL variable number of tandem repeat (VNTR) + region in exon 11. The mutations are predicted to lead to aberrant protein tails + that make the CEL protein susceptible to aggregation. CONCLUSION: The diagnosis + of MODY8 requires a pancreatic exocrine phenotype and a deletion in the CEL VNTR + in addition to dominantly inherited diabetes. CEL screening may be warranted also + in families with hereditary pancreatitis of unknown genetic etiology. +CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the + Endocrine Society. +FAU - El Jellas, Khadija +AU - El Jellas K +AUID- ORCID: 0000-0003-4473-1422 +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, N-5020 Bergen, Norway. +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, N-5020 Bergen, Norway. +FAU - Dusatkova, Petra +AU - Dusatkova P +AUID- ORCID: 0000-0002-8647-9088 +AD - Department of Pediatrics, Charles University in Prague, Second Faculty of + Medicine and University Hospital Motol, CZ-15006 Prague, Czech Republic. +FAU - Haldorsen, Ingfrid S +AU - Haldorsen IS +AD - Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland + University Hospital, N-5021 Bergen, Norway. +AD - Section for Radiology, Department of Clinical Medicine, University of Bergen, + N-5020 Bergen, Norway. +FAU - Molnes, Janne +AU - Molnes J +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, N-5020 Bergen, Norway. +AD - Department of Medical Genetics, Haukeland University Hospital, N-5021 Bergen, + Norway. +FAU - Tjora, Erling +AU - Tjora E +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, N-5020 Bergen, Norway. +AD - Children and Youth Clinic, Haukeland University Hospital, N-5021 Bergen, Norway. +FAU - Johansson, Bente B +AU - Johansson BB +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, N-5020 Bergen, Norway. +FAU - Fjeld, Karianne +AU - Fjeld K +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, N-5020 Bergen, Norway. +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, N-5020 Bergen, Norway. +AD - Department of Medical Genetics, Haukeland University Hospital, N-5021 Bergen, + Norway. +FAU - Johansson, Stefan +AU - Johansson S +AUID- ORCID: 0000-0002-2298-7008 +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, N-5020 Bergen, Norway. +AD - Department of Medical Genetics, Haukeland University Hospital, N-5021 Bergen, + Norway. +FAU - Pruhova, Stepanka +AU - Pruhova S +AUID- ORCID: 0000-0001-8019-8026 +AD - Department of Pediatrics, Charles University in Prague, Second Faculty of + Medicine and University Hospital Motol, CZ-15006 Prague, Czech Republic. +FAU - Groop, Leif +AU - Groop L +AUID- ORCID: 0000-0002-0187-3263 +AD - Institute for Molecular Medicine Finland, Helsinki University, FI-00014 Helsinki, + Finland. +AD - Lund University Diabetes Centre, Department of Clinical Sciences, Lund + University, Skane University Hospital, SE-214 28 Malmo, Sweden. +FAU - Lohr, J Matthias +AU - Lohr JM +AD - Department for Digestive Diseases, Karolinska University Hospital, SE-141 86 + Stockholm, Sweden. +AD - Department of Clinical Science, Intervention, and Technology (CLINTEC), + Karolinska Institute, SE-141 86 Stockholm, Sweden. +FAU - Njolstad, Pal R +AU - Njolstad PR +AUID- ORCID: 0000-0003-0304-6728 +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, N-5020 Bergen, Norway. +AD - Children and Youth Clinic, Haukeland University Hospital, N-5021 Bergen, Norway. +FAU - Molven, Anders +AU - Molven A +AUID- ORCID: 0000-0003-1847-3079 +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, N-5020 Bergen, Norway. +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, N-5020 Bergen, Norway. +AD - Department of Pathology, Haukeland University Hospital, N-5021 Bergen, Norway. +LA - eng +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +PL - United States +TA - J Clin Endocrinol Metab +JT - The Journal of clinical endocrinology and metabolism +JID - 0375362 +RN - EC 3.1.1.3 (CEL protein, human) +RN - EC 3.1.1.3 (Lipase) +RN - Hereditary pancreatitis +RN - Mason-Type Diabetes +RN - Maturity-Onset Diabetes of the Young, Type 8, with Exocrine Dysfunction +SB - IM +MH - *Diabetes Mellitus, Type 2/diagnosis/genetics +MH - Humans +MH - Lipase/*genetics +MH - Mutation +MH - Pancreatitis, Chronic +PMC - PMC8947231 +OTO - NOTNLM +OT - MODY8 +OT - chronic pancreatitis +OT - monogenic diabetes +OT - mutation screening +OT - pancreatic exocrine function +OT - pancreatic imaging +EDAT- 2021/12/02 06:00 +MHDA- 2022/04/16 06:00 +PMCR- 2021/11/29 +CRDT- 2021/12/01 07:20 +PHST- 2021/06/25 00:00 [received] +PHST- 2021/12/02 06:00 [pubmed] +PHST- 2022/04/16 06:00 [medline] +PHST- 2021/12/01 07:20 [entrez] +PHST- 2021/11/29 00:00 [pmc-release] +AID - 6446241 [pii] +AID - dgab864 [pii] +AID - 10.1210/clinem/dgab864 [doi] +PST - ppublish +SO - J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1455-e1466. doi: + 10.1210/clinem/dgab864. + +PMID- 34507899 +OWN - NLM +STAT- MEDLINE +DCOM- 20220215 +LR - 20240102 +IS - 1424-3911 (Electronic) +IS - 1424-3903 (Linking) +VI - 21 +IP - 7 +DP - 2021 Oct +TI - Homozygosity of short VNTR lengths in the CEL gene may confer susceptibility to + idiopathic chronic pancreatitis. +PG - 1311-1316 +LID - S1424-3903(21)00565-2 [pii] +LID - 10.1016/j.pan.2021.09.001 [doi] +AB - OBJECTIVE: The carboxyl-ester lipase (CEL) gene contains a variable number of + tandem repeats (VNTR) region. It remains unclear whether the number of repeats in + the CEL VNTR is related to the risk of pancreatic diseases. The aim of this study + was to investigate whether CEL VNTR length is associated with idiopathic chronic + pancreatitis (ICP), alcoholic chronic pancreatitis (ACP), or pancreatic cancer in + a cohort of Chinese patients. METHODS: CEL VNTRs were genotyped in patients + diagnosed with ICP (n = 771), ACP (n = 222), or pancreatic cancer (n = 263), and + in healthy controls (n = 927). CEL VNTR lengths were determined using a screening + method combining PCR and DNA fragment analysis. RESULTS: Overall, the CEL VNTR + lengths ranged from 5 to 22 repeats, with the 16-repeat allele ('normal' size, N) + accounting for 73.82% of all observed alleles. The VNTR allele frequencies and + genotype distributions were not significantly different between healthy controls + and patients with ACP or pancreatic cancer. For the ICP group, allele frequencies + did not differ significantly from the controls, while the frequency of the SS + genotype (homozygosity for 5-15 repeats) was significantly higher in the patients + (4.67%) than in the controls (1.94%) (p = 0.0014; OR = 2.47; 95% CI = 1.39-4.39). + CONCLUSIONS: There were no associations between the CEL VNTR length and ACP or + pancreatic cancer. However, homozygosity for short VNTR lengths may confer + susceptibility to ICP. +CI - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved. +FAU - Mao, Xiao-Tong +AU - Mao XT +AD - Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, + The Second Military Medical University, Shanghai, China; Shanghai Institute of + Pancreatic Diseases, Shanghai, China. +FAU - Deng, Shun-Jiang +AU - Deng SJ +AD - Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, + The Second Military Medical University, Shanghai, China; Shanghai Institute of + Pancreatic Diseases, Shanghai, China. +FAU - Kang, Rui-Lin +AU - Kang RL +AD - Ningjin Hospital, Hebei Province, China. +FAU - Wang, Yuan-Chen +AU - Wang YC +AD - Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, + The Second Military Medical University, Shanghai, China. +FAU - Li, Zhao-Shen +AU - Li ZS +AD - Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, + The Second Military Medical University, Shanghai, China; Shanghai Institute of + Pancreatic Diseases, Shanghai, China. +FAU - Zou, Wen-Bin +AU - Zou WB +AD - Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, + The Second Military Medical University, Shanghai, China; Shanghai Institute of + Pancreatic Diseases, Shanghai, China. Electronic address: + dr.wenbinzou@hotmail.com. +FAU - Liao, Zhuan +AU - Liao Z +AD - Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, + The Second Military Medical University, Shanghai, China; Shanghai Institute of + Pancreatic Diseases, Shanghai, China. Electronic address: liaozhuan@smmu.edu.cn. +LA - eng +PT - Journal Article +DEP - 20210904 +PL - Switzerland +TA - Pancreatology +JT - Pancreatology : official journal of the International Association of + Pancreatology (IAP) ... [et al.] +JID - 100966936 +RN - EC 3.1.1.1 (Carboxylesterase) +RN - EC 3.1.1.3 (Lipase) +SB - IM +MH - Carboxylesterase/genetics/metabolism +MH - Gene Frequency +MH - Genotype +MH - Heterozygote +MH - Humans +MH - Lipase/metabolism +MH - *Minisatellite Repeats/genetics +MH - Pancreatic Neoplasms/genetics +MH - *Pancreatitis +MH - Pancreatitis, Alcoholic/genetics +OTO - NOTNLM +OT - Alcoholic chronic pancreatitis +OT - Carboxyl-ester lipase +OT - Copy number variation +OT - Idiopathic chronic pancreatitis +OT - Pancreatic cancer +OT - Variable number of tandem repeats +COIS- Declaration of competing interest The authors declare no conflict of interest. +EDAT- 2021/09/12 06:00 +MHDA- 2022/02/16 06:00 +CRDT- 2021/09/11 05:31 +PHST- 2021/06/25 00:00 [received] +PHST- 2021/09/01 00:00 [revised] +PHST- 2021/09/02 00:00 [accepted] +PHST- 2021/09/12 06:00 [pubmed] +PHST- 2022/02/16 06:00 [medline] +PHST- 2021/09/11 05:31 [entrez] +AID - S1424-3903(21)00565-2 [pii] +AID - 10.1016/j.pan.2021.09.001 [doi] +PST - ppublish +SO - Pancreatology. 2021 Oct;21(7):1311-1316. doi: 10.1016/j.pan.2021.09.001. Epub + 2021 Sep 4. + +PMID- 34100900 +OWN - NLM +STAT- MEDLINE +DCOM- 20210624 +LR - 20240801 +IS - 2473-9537 (Electronic) +IS - 2473-9529 (Print) +IS - 2473-9529 (Linking) +VI - 5 +IP - 11 +DP - 2021 Jun 8 +TI - Axicabtagene ciloleucel in vivo expansion and treatment outcome in aggressive + B-cell lymphoma in a real-world setting. +PG - 2523-2527 +LID - 10.1182/bloodadvances.2020003959 [doi] +AB - Data on the association between chimeric antigen receptor (CAR)-T-cell kinetics + and patient outcome in the nontrial setting are missing, mainly due to the lack + of broadly available CAR-T-cell diagnostic quantification tools. We performed + prospective quantification of axicabtagene ciloleucel (axi-cel) in 21 patients + treated for aggressive B-cell lymphoma at our clinic. Median peak CAR-T-cell + count was 16.14 CAR-T cells/microL. Patients with 16.14/muL or higher peak CAR-T cells + (strong expanders) had more day-30 objective responses (91% vs 40%, P = .02). In + univariate analysis, peak CAR-T cell >/= 16.14 (P < .001), normal platelet counts + at start of lymphodepletion (P < .001), no prior stem cell transplant (P = .04), + and peak CAR-T cells as continuous variable (P = .03) were associated with better + progression-free survival (PFS). After adjusting for platelet counts and prior + stem cell transplantation, peak CAR-T cells below median was still associated + with shorter PFS (relative risk, 0.15, 95% confidence interval, 0.04-0.59, P = + .007). Low platelet counts also maintained significant impact on PFS. Our data + demonstrate association of axi-cel levels and outcome in a nontrial setting and + for the first time use a cutoff to segregate weak and strong expanders with + respective outcomes. +CI - (c) 2021 by The American Society of Hematology. +FAU - Ayuk, Francis A +AU - Ayuk FA +AD - Department of Stem Cell Transplantation. +FAU - Berger, Carolina +AU - Berger C +AD - Department of Stem Cell Transplantation. +FAU - Badbaran, Anita +AU - Badbaran A +AD - Department of Stem Cell Transplantation. +FAU - Zabelina, Tatjana +AU - Zabelina T +AD - Department of Stem Cell Transplantation. +FAU - Sonntag, Tanja +AU - Sonntag T +AD - Department of Stem Cell Transplantation. +FAU - Riecken, Kristoffer +AU - Riecken K +AUID- ORCID: 0000-0001-9050-6766 +AD - Department of Stem Cell Transplantation. +FAU - Geffken, Maria +AU - Geffken M +AD - Institute for Transfusion Medicine. +FAU - Wichmann, Dominic +AU - Wichmann D +AUID- ORCID: 0000-0002-4334-7640 +AD - Department of Intensive Care Medicine. +FAU - Frenzel, Christian +AU - Frenzel C +AD - Department of Hematology and Oncology, and. +FAU - Thayssen, Guenther +AU - Thayssen G +AD - Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, + Germany. +FAU - Zeschke, Silke +AU - Zeschke S +AD - Department of Stem Cell Transplantation. +FAU - Kroger, Nicolaus +AU - Kroger N +AUID- ORCID: 0000-0001-5103-9966 +AD - Department of Stem Cell Transplantation. +FAU - Fehse, Boris +AU - Fehse B +AUID- ORCID: 0000-0001-9780-7211 +AD - Department of Stem Cell Transplantation. +LA - eng +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +PL - United States +TA - Blood Adv +JT - Blood advances +JID - 101698425 +RN - 0 (Antigens, CD19) +RN - 0 (Biological Products) +RN - U2I8T43Y7R (axicabtagene ciloleucel) +SB - IM +EIN - Blood Adv. 2022 Dec 13;6(23):6075. doi: 10.1182/bloodadvances.2022008370. PMID: + 36459166 +MH - Antigens, CD19/therapeutic use +MH - Biological Products +MH - Humans +MH - Immunotherapy, Adoptive +MH - *Lymphoma, Large B-Cell, Diffuse +MH - Prospective Studies +MH - Treatment Outcome +PMC - PMC8238487 +EDAT- 2021/06/09 06:00 +MHDA- 2021/06/25 06:00 +PMCR- 2021/06/08 +CRDT- 2021/06/08 12:24 +PHST- 2020/12/03 00:00 [received] +PHST- 2021/03/29 00:00 [accepted] +PHST- 2021/06/08 12:24 [entrez] +PHST- 2021/06/09 06:00 [pubmed] +PHST- 2021/06/25 06:00 [medline] +PHST- 2021/06/08 00:00 [pmc-release] +AID - S2473-9529(21)00328-1 [pii] +AID - 2021/ADV2020003959 [pii] +AID - 10.1182/bloodadvances.2020003959 [doi] +PST - ppublish +SO - Blood Adv. 2021 Jun 8;5(11):2523-2527. doi: 10.1182/bloodadvances.2020003959. + +PMID- 33862081 +OWN - NLM +STAT- MEDLINE +DCOM- 20210823 +LR - 20211231 +IS - 1083-351X (Electronic) +IS - 0021-9258 (Print) +IS - 0021-9258 (Linking) +VI - 296 +DP - 2021 Jan-Jun +TI - The position of single-base deletions in the VNTR sequence of the carboxyl ester + lipase (CEL) gene determines proteotoxicity. +PG - 100661 +LID - S0021-9258(21)00449-X [pii] +LID - 10.1016/j.jbc.2021.100661 [doi] +LID - 100661 +AB - Variable number of tandem repeat (VNTR) sequences in the genome can have + functional consequences that contribute to human disease. This is the case for + the CEL gene, which is specifically expressed in pancreatic acinar cells and + encodes the digestive enzyme carboxyl ester lipase. Rare single-base deletions + (DELs) within the first (DEL1) or fourth (DEL4) VNTR segment of CEL cause + maturity-onset diabetes of the young, type 8 (MODY8), an inherited disorder + characterized by exocrine pancreatic dysfunction and diabetes. Studies on the + DEL1 variant have suggested that MODY8 is initiated by CEL protein misfolding and + aggregation. However, it is unclear how the position of single-base deletions + within the CEL VNTR affects pathogenic properties of the protein. Here, we + investigated four naturally occurring CEL variants, arising from single-base + deletions in different VNTR segments (DEL1, DEL4, DEL9, and DEL13). When the four + variants were expressed in human embryonic kidney 293 cells, only DEL1 and DEL4 + led to significantly reduced secretion, increased intracellular aggregation, and + increased endoplasmic reticulum stress compared with normal CEL protein. The + level of O-glycosylation was affected in all DEL variants. Moreover, all variants + had enzymatic activity comparable with that of normal CEL. We conclude that the + longest aberrant protein tails, resulting from single-base deletions in the + proximal VNTR segments, have highest pathogenic potential, explaining why DEL1 + and DEL4 but not DEL9 and DEL13 have been observed in patients with MODY8. These + findings further support the view that CEL mutations cause pancreatic disease + through protein misfolding and proteotoxicity, leading to endoplasmic reticulum + stress and activation of the unfolded protein response. +CI - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved. +FAU - Gravdal, Anny +AU - Gravdal A +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Bergen, Norway; Department of Medical Genetics, + Haukeland University Hospital, Bergen, Norway. +FAU - Xiao, Xunjun +AU - Xiao X +AD - Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, + Washington University School of Medicine, St Louis, Missouri, USA. +FAU - Cnop, Miriam +AU - Cnop M +AD - ULB Center for Diabetes Research, Universite Libre de Bruxelles, Brussels, + Belgium; Division of Endocrinology, ULB Erasmus Hospital, Universite Libre de + Bruxelles, Brussels, Belgium. +FAU - El Jellas, Khadija +AU - El Jellas K +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Bergen, Norway. +FAU - Johansson, Stefan +AU - Johansson S +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Bergen, Norway; Department of Medical Genetics, Haukeland University + Hospital, Bergen, Norway. +FAU - Njolstad, Pal R +AU - Njolstad PR +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Bergen, Norway; Department of Pediatrics and Adolescent Medicine, + Haukeland University Hospital, Bergen, Norway. +FAU - Lowe, Mark E +AU - Lowe ME +AD - Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, + Washington University School of Medicine, St Louis, Missouri, USA. +FAU - Johansson, Bente B +AU - Johansson BB +AD - Center for Diabetes Research, Department of Clinical Science, University of + Bergen, Bergen, Norway; Department of Pediatrics and Adolescent Medicine, + Haukeland University Hospital, Bergen, Norway. +FAU - Molven, Anders +AU - Molven A +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland + University Hospital, Bergen, Norway. Electronic address: anders.molven@uib.no. +FAU - Fjeld, Karianne +AU - Fjeld K +AD - The Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical + Science, University of Bergen, Bergen, Norway; Department of Medical Genetics, + Haukeland University Hospital, Bergen, Norway. +LA - eng +GR - R01 DK124415/DK/NIDDK NIH HHS/United States +PT - Journal Article +PT - Research Support, N.I.H., Extramural +PT - Research Support, Non-U.S. Gov't +DEP - 20210414 +PL - United States +TA - J Biol Chem +JT - The Journal of biological chemistry +JID - 2985121R +RN - EC 3.1.1.3 (CEL protein, human) +RN - EC 3.1.1.3 (Lipase) +SB - IM +MH - *Endoplasmic Reticulum Stress +MH - Glycosylation +MH - HEK293 Cells +MH - Humans +MH - Lipase/*genetics/*metabolism +MH - *Minisatellite Repeats +MH - *Mutation +MH - *Proteostasis +PMC - PMC8692231 +OTO - NOTNLM +OT - CEL +OT - MODY8 +OT - O-glycosylation +OT - endoplasmic reticulum stress +OT - protein misfolding +OT - single-base deletions +OT - unfolded protein response +COIS- Conflict of interest The authors declare that they have no conflicts of interest + with the contents of this article. +EDAT- 2021/04/17 06:00 +MHDA- 2021/08/24 06:00 +PMCR- 2021/04/14 +CRDT- 2021/04/16 20:11 +PHST- 2020/12/22 00:00 [received] +PHST- 2021/04/05 00:00 [revised] +PHST- 2021/04/12 00:00 [accepted] +PHST- 2021/04/17 06:00 [pubmed] +PHST- 2021/08/24 06:00 [medline] +PHST- 2021/04/16 20:11 [entrez] +PHST- 2021/04/14 00:00 [pmc-release] +AID - S0021-9258(21)00449-X [pii] +AID - 100661 [pii] +AID - 10.1016/j.jbc.2021.100661 [doi] +PST - ppublish +SO - J Biol Chem. 2021 Jan-Jun;296:100661. doi: 10.1016/j.jbc.2021.100661. Epub 2021 + Apr 14. + +PMID- 27802312 +OWN - NLM +STAT- MEDLINE +DCOM- 20170628 +LR - 20250530 +IS - 1932-6203 (Electronic) +IS - 1932-6203 (Linking) +VI - 11 +IP - 11 +DP - 2016 +TI - Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) + Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic + Chronic Pancreatitis. +PG - e0165567 +LID - 10.1371/journal.pone.0165567 [doi] +LID - e0165567 +AB - BACKGROUND: Carboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester + metabolism, which is implicated in alcoholic pancreatitis. The CEL gene harbours + a variable number of tandem repeats (VNTR) region in exon 11. Variation in this + VNTR has been linked to monogenic pancreatic disease, while conflicting results + were reported for chronic pancreatitis (CP). Here, we aimed to investigate a + potential association of CEL VNTR lengths with alcoholic CP. METHODS: Overall, + 395 alcoholic CP patients, 218 patients with alcoholic liver cirrhosis (ALC) + serving as controls with a comparable amount of alcohol consumed, and 327 healthy + controls from Germany and the United Kingdom (UK) were analysed by determination + of fragment lengths by capillary electrophoresis. Allele frequencies and + genotypes of different VNTR categories were compared between the groups. RESULTS: + Twelve repeats were overrepresented in UK ACP patients (P = 0.04) compared to + controls, whereas twelve repeats were enriched in German ALC compared to + alcoholic CP patients (P = 0.03). Frequencies of CEL VNTR lengths of 14 and 15 + repeats differed between German ALC patients and healthy controls (P = 0.03 and + 0.008, respectively). However, in the genotype and pooled analysis of VNTR + lengths no statistical significant association was depicted. Additionally, the + 16-16 genotype as well as 16 repeats were more frequent in UK ALC than in + alcoholic CP patients (P = 0.034 and 0.02, respectively). In all other + calculations, including pooled German and UK data, allele frequencies and + genotype distributions did not differ significantly between patients and controls + or between alcoholic CP and ALC. CONCLUSIONS: We did not obtain evidence that CEL + VNTR lengths are associated with alcoholic CP. However, our results suggest that + CEL VNTR lengths might associate with ALC, a finding that needs to be clarified + in larger cohorts. +FAU - Fjeld, Karianne +AU - Fjeld K +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway. +AD - Center for Medical Genetics and Molecular Medicine, Haukeland University + Hospital, Bergen, Norway. +FAU - Beer, Sebastian +AU - Beer S +AD - Department of Internal Medicine, Neurology and Dermatology, Division of + Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany. +FAU - Johnstone, Marianne +AU - Johnstone M +AD - NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University + Hospital, Institute of Translational Medicine, University of Liverpool, + Liverpool, United Kingdom. +FAU - Zimmer, Constantin +AU - Zimmer C +AD - Department of Internal Medicine, Neurology and Dermatology, Division of + Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany. +FAU - Mossner, Joachim +AU - Mossner J +AD - Department of Internal Medicine, Neurology and Dermatology, Division of + Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany. +FAU - Ruffert, Claudia +AU - Ruffert C +AD - Department of Internal Medicine I, Martin Luther University, Halle, Germany. +FAU - Krehan, Mario +AU - Krehan M +AD - Department of Internal Medicine, Neurology and Dermatology, Division of + Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany. +FAU - Zapf, Christian +AU - Zapf C +AD - Department of Internal Medicine, Neurology and Dermatology, Division of + Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany. +FAU - Njolstad, Pal Rasmus +AU - Njolstad PR +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway. +AD - Department of Pediatrics, Haukeland University Hospital, Bergen, Norway. +FAU - Johansson, Stefan +AU - Johansson S +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway. +AD - Center for Medical Genetics and Molecular Medicine, Haukeland University + Hospital, Bergen, Norway. +FAU - Bugert, Peter +AU - Bugert P +AD - Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, + Heidelberg University, German Red Cross Blood Service of + Baden-Wurttemberg-Hessen, Mannheim, Germany. +FAU - Miyajima, Fabio +AU - Miyajima F +AD - Department of Molecular and Clinical Pharmacology, Institute of Translational + Medicine, University of Liverpool, Liverpool, United Kingdom. +FAU - Liloglou, Triantafillos +AU - Liloglou T +AD - Department of Molecular and Clinical Cancer Medicine, Institute of Translational + Medicine, University of Liverpool, Liverpool, United Kingdom. +FAU - Brown, Laura J +AU - Brown LJ +AD - NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University + Hospital, Institute of Translational Medicine, University of Liverpool, + Liverpool, United Kingdom. +FAU - Winn, Simon A +AU - Winn SA +AD - NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University + Hospital, Institute of Translational Medicine, University of Liverpool, + Liverpool, United Kingdom. +FAU - Davies, Kelly +AU - Davies K +AD - NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University + Hospital, Institute of Translational Medicine, University of Liverpool, + Liverpool, United Kingdom. +FAU - Latawiec, Diane +AU - Latawiec D +AD - NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University + Hospital, Institute of Translational Medicine, University of Liverpool, + Liverpool, United Kingdom. +FAU - Gunson, Bridget K +AU - Gunson BK +AD - NIHR Birmingham Liver Biomedical Research Unit, Queen Elizabeth Hospital and + University of Birmingham, Birmingham, United Kingdom. +FAU - Criddle, David N +AU - Criddle DN +AD - Department of Cellular & Molecular Physiology, Institute of Translational + Medicine, University of Liverpool, Liverpool, United Kingdom. +FAU - Pirmohamed, Munir +AU - Pirmohamed M +AD - Department of Molecular and Clinical Pharmacology, Institute of Translational + Medicine, University of Liverpool, Liverpool, United Kingdom. +FAU - Grutzmann, Robert +AU - Grutzmann R +AD - Department of Surgery, Friedrich-Alexander-Universitat Erlangen-Nurnberg, + Erlangen, Germany. +FAU - Michl, Patrick +AU - Michl P +AD - Department of Internal Medicine I, Martin Luther University, Halle, Germany. +FAU - Greenhalf, William +AU - Greenhalf W +AD - NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University + Hospital, Institute of Translational Medicine, University of Liverpool, + Liverpool, United Kingdom. +FAU - Molven, Anders +AU - Molven A +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway. +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway. +AD - Department of Pathology, Haukeland University Hospital, Bergen, Norway. +FAU - Sutton, Robert +AU - Sutton R +AD - NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University + Hospital, Institute of Translational Medicine, University of Liverpool, + Liverpool, United Kingdom. +FAU - Rosendahl, Jonas +AU - Rosendahl J +AD - Department of Internal Medicine I, Martin Luther University, Halle, Germany. +LA - eng +GR - 16812/CRUK_/Cancer Research UK/United Kingdom +PT - Journal Article +DEP - 20161101 +PL - United States +TA - PLoS One +JT - PloS one +JID - 101285081 +RN - EC 3.1.1.3 (CEL protein, human) +RN - EC 3.1.1.3 (Lipase) +SB - IM +MH - Adult +MH - Aged +MH - Aged, 80 and over +MH - Chronic Disease +MH - Exons +MH - Female +MH - Genetic Predisposition to Disease +MH - Genotype +MH - Germany/epidemiology +MH - Humans +MH - Lipase/*genetics +MH - Liver Cirrhosis, Alcoholic/epidemiology/*genetics +MH - Male +MH - Middle Aged +MH - *Minisatellite Repeats +MH - Pancreatitis, Alcoholic/epidemiology/*genetics +MH - United Kingdom/epidemiology +PMC - PMC5089759 +COIS- The authors have declared that no competing interests exist. +EDAT- 2016/11/02 06:00 +MHDA- 2017/06/29 06:00 +PMCR- 2016/11/01 +CRDT- 2016/11/02 06:00 +PHST- 2016/07/22 00:00 [received] +PHST- 2016/10/13 00:00 [accepted] +PHST- 2016/11/02 06:00 [pubmed] +PHST- 2017/06/29 06:00 [medline] +PHST- 2016/11/02 06:00 [entrez] +PHST- 2016/11/01 00:00 [pmc-release] +AID - PONE-D-16-29403 [pii] +AID - 10.1371/journal.pone.0165567 [doi] +PST - epublish +SO - PLoS One. 2016 Nov 1;11(11):e0165567. doi: 10.1371/journal.pone.0165567. + eCollection 2016. + +PMID- 27650499 +OWN - NLM +STAT- MEDLINE +DCOM- 20170926 +LR - 20220318 +IS - 1083-351X (Electronic) +IS - 0021-9258 (Print) +IS - 0021-9258 (Linking) +VI - 291 +IP - 44 +DP - 2016 Oct 28 +TI - A Carboxyl Ester Lipase (CEL) Mutant Causes Chronic Pancreatitis by Forming + Intracellular Aggregates That Activate Apoptosis. +PG - 23224-23236 +AB - Patients with chronic pancreatitis (CP) frequently have genetic risk factors for + disease. Many of the identified genes have been connected to trypsinogen + activation or trypsin inactivation. The description of CP in patients with + mutations in the variable number of tandem repeat (VNTR) domain of carboxyl ester + lipase (CEL) presents an opportunity to study the pathogenesis of CP + independently of trypsin pathways. We tested the hypothesis that a deletion and + frameshift mutation (C563fsX673) in the CEL VNTR causes CP through proteotoxic + gain-of-function activation of maladaptive cell signaling pathways including cell + death pathways. HEK293 or AR42J cells were transfected with constructs expressing + CEL with 14 repeats in the VNTR (CEL14R) or C563fsX673 CEL (CEL maturity onset + diabetes of youth with a deletion mutation in the VNTR (MODY)). In both cell + types, CEL MODY formed intracellular aggregates. Secretion of CEL MODY was + decreased compared with that of CEL14R. Expression of CEL MODY increased + endoplasmic reticulum stress, activated the unfolded protein response, and caused + cell death by apoptosis. Our results demonstrate that disorders of protein + homeostasis can lead to CP and suggest that novel therapies to decrease the + intracellular accumulation of misfolded protein may be successful in some + patients with CP. +CI - (c) 2016 by The American Society for Biochemistry and Molecular Biology, Inc. +FAU - Xiao, Xunjun +AU - Xiao X +AD - From the Department of Pediatrics, Children's Hospital of Pittsburgh at + University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224 and. +FAU - Jones, Gabrielle +AU - Jones G +AD - From the Department of Pediatrics, Children's Hospital of Pittsburgh at + University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224 and. +FAU - Sevilla, Wednesday A +AU - Sevilla WA +AD - From the Department of Pediatrics, Children's Hospital of Pittsburgh at + University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224 and. +FAU - Stolz, Donna B +AU - Stolz DB +AD - Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania + 15261. +FAU - Magee, Kelsey E +AU - Magee KE +AD - From the Department of Pediatrics, Children's Hospital of Pittsburgh at + University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224 and. +FAU - Haughney, Margaret +AU - Haughney M +AD - From the Department of Pediatrics, Children's Hospital of Pittsburgh at + University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224 and. +FAU - Mukherjee, Amitava +AU - Mukherjee A +AD - From the Department of Pediatrics, Children's Hospital of Pittsburgh at + University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224 and. +FAU - Wang, Yan +AU - Wang Y +AD - From the Department of Pediatrics, Children's Hospital of Pittsburgh at + University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224 and. +FAU - Lowe, Mark E +AU - Lowe ME +AD - From the Department of Pediatrics, Children's Hospital of Pittsburgh at + University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224 and + loweme2@upmc.edu. +LA - eng +GR - R01 DK080820/DK/NIDDK NIH HHS/United States +GR - R01 DK097241/DK/NIDDK NIH HHS/United States +PT - Journal Article +PT - Research Support, N.I.H., Extramural +DEP - 20160920 +PL - United States +TA - J Biol Chem +JT - The Journal of biological chemistry +JID - 2985121R +RN - 0 (Protein Aggregates) +RN - EC 3.1.1.1 (Carboxylesterase) +SB - IM +EIN - J Biol Chem. 2017 May 12;292(19):7744. doi: 10.1074/jbc.A116.734384. PMID: + 28500240 +MH - *Apoptosis +MH - Carboxylesterase/chemistry/*genetics/*metabolism +MH - Endoplasmic Reticulum Stress +MH - HEK293 Cells +MH - Humans +MH - Minisatellite Repeats +MH - *Mutation +MH - Pancreas, Exocrine/enzymology +MH - Pancreatitis, Chronic/*enzymology/genetics/*physiopathology +MH - Protein Aggregates +PMC - PMC5087739 +OTO - NOTNLM +OT - apoptosis +OT - carboxyl ester lipase +OT - chronic pancreatitis +OT - disulfide +OT - disulfide bonds +OT - endoplasmic reticulum stress (ER stress) +OT - lipase +OT - unfolded protein response (UPR) +EDAT- 2016/10/30 06:00 +MHDA- 2017/09/28 06:00 +PMCR- 2017/10/28 +CRDT- 2016/09/22 06:00 +PHST- 2016/04/22 00:00 [received] +PHST- 2016/10/30 06:00 [pubmed] +PHST- 2017/09/28 06:00 [medline] +PHST- 2016/09/22 06:00 [entrez] +PHST- 2017/10/28 00:00 [pmc-release] +AID - S0021-9258(20)35692-1 [pii] +AID - M116.734384 [pii] +AID - 10.1074/jbc.M116.734384 [doi] +PST - ppublish +SO - J Biol Chem. 2016 Oct 28;291(44):23224-23236. doi: 10.1074/jbc.M116.734384. Epub + 2016 Sep 20. + +PMID- 27773618 +OWN - NLM +STAT- MEDLINE +DCOM- 20170809 +LR - 20170809 +IS - 1424-3911 (Electronic) +IS - 1424-3903 (Linking) +VI - 17 +IP - 1 +DP - 2017 Jan-Feb +TI - Copy number variants and VNTR length polymorphisms of the carboxyl-ester lipase + (CEL) gene as risk factors in pancreatic cancer. +PG - 83-88 +LID - S1424-3903(16)31222-4 [pii] +LID - 10.1016/j.pan.2016.10.006 [doi] +AB - BACKGROUND/OBJECTIVES: We have recently described copy number variants (CNVs) of + the human carboxyl-ester lipase (CEL) gene, including a recombined deletion + allele (CEL-HYB) that is a genetic risk factor for chronic pancreatitis. + Associations with pancreatic disease have also been reported for the variable + number of tandem repeat (VNTR) region located in CEL exon 11. Here, we examined + if CEL CNVs and VNTR length polymorphisms affect the risk for developing + pancreatic cancer. METHODS: CEL CNVs and VNTR were genotyped in a German family + with non-alcoholic chronic pancreatitis and pancreatic cancer, in 265 German and + 197 Norwegian patients diagnosed with pancreatic adenocarcinoma, and in 882 + controls. CNV screening was performed using PCR assays followed by agarose gel + electrophoresis whereas VNTR lengths were determined by DNA fragment analysis. + RESULTS: The investigated family was CEL-HYB-positive. However, an association of + CEL-HYB or a duplication CEL allele with pancreatic cancer was not seen in our + two patient cohorts. The frequency of the 23-repeat VNTR allele was borderline + significant in Norwegian cases compared to controls (1.2% vs. 0.3%; P = 0.05). + For all other VNTR lengths, no statistically significant difference in frequency + was observed. Moreover, no association with pancreatic cancer was detected when + CEL VNTR lengths were pooled into groups of short, normal or long alleles. + CONCLUSIONS: We could not demonstrate an association between CEL CNVs and + pancreatic cancer. An association is also unlikely for CEL VNTR lengths, although + analyses in larger materials are necessary to completely exclude an effect of + rare VNTR alleles. +CI - Copyright (c) 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved. +FAU - Dalva, Monica +AU - Dalva M +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular + Medicine, Haukeland University Hospital, Bergen, Norway; Gade Laboratory for + Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway. +FAU - El Jellas, Khadija +AU - El Jellas K +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway; Gade Laboratory for Pathology, Department + of Clinical Medicine, University of Bergen, Bergen, Norway; Department of + Pathology, Haukeland University Hospital, Bergen, Norway. +FAU - Steine, Solrun J +AU - Steine SJ +AD - Gade Laboratory for Pathology, Department of Clinical Medicine, University of + Bergen, Bergen, Norway. +FAU - Johansson, Bente B +AU - Johansson BB +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular + Medicine, Haukeland University Hospital, Bergen, Norway. +FAU - Ringdal, Monika +AU - Ringdal M +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular + Medicine, Haukeland University Hospital, Bergen, Norway. +FAU - Torsvik, Janniche +AU - Torsvik J +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway. +FAU - Immervoll, Heike +AU - Immervoll H +AD - Department of Pathology, Haukeland University Hospital, Bergen, Norway. +FAU - Hoem, Dag +AU - Hoem D +AD - Department of Gastrointestinal Surgery, Haukeland University Hospital, Bergen, + Norway. +FAU - Laemmerhirt, Felix +AU - Laemmerhirt F +AD - Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. +FAU - Simon, Peter +AU - Simon P +AD - Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. +FAU - Lerch, Markus M +AU - Lerch MM +AD - Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. +FAU - Johansson, Stefan +AU - Johansson S +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular + Medicine, Haukeland University Hospital, Bergen, Norway. +FAU - Njolstad, Pal R +AU - Njolstad PR +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway; Department of Pediatrics, Haukeland + University Hospital, Bergen, Norway. +FAU - Weiss, Frank U +AU - Weiss FU +AD - Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. +FAU - Fjeld, Karianne +AU - Fjeld K +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular + Medicine, Haukeland University Hospital, Bergen, Norway. Electronic address: + karianne.fjeld@uib.no. +FAU - Molven, Anders +AU - Molven A +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Science, + University of Bergen, Bergen, Norway; Gade Laboratory for Pathology, Department + of Clinical Medicine, University of Bergen, Bergen, Norway; Department of + Pathology, Haukeland University Hospital, Bergen, Norway. +LA - eng +PT - Journal Article +DEP - 20161011 +PL - Switzerland +TA - Pancreatology +JT - Pancreatology : official journal of the International Association of + Pancreatology (IAP) ... [et al.] +JID - 100966936 +RN - 0 (Biomarkers, Tumor) +RN - EC 3.1.1.3 (CEL protein, human) +RN - EC 3.1.1.3 (Lipase) +SB - IM +MH - Adenocarcinoma/*genetics +MH - Biomarkers, Tumor/*genetics +MH - Case-Control Studies +MH - *DNA Copy Number Variations +MH - Female +MH - Humans +MH - Lipase/*genetics +MH - Male +MH - *Minisatellite Repeats +MH - Pancreatic Neoplasms/*genetics +MH - Risk Factors +OTO - NOTNLM +OT - Allele frequency +OT - Carboxyl-ester lipase +OT - Copy number variation +OT - Genotyping +OT - Pancreatic cancer +OT - Variable number of tandem repeats +EDAT- 2016/10/25 06:00 +MHDA- 2017/08/10 06:00 +CRDT- 2016/10/25 06:00 +PHST- 2016/06/19 00:00 [received] +PHST- 2016/10/05 00:00 [revised] +PHST- 2016/10/09 00:00 [accepted] +PHST- 2016/10/25 06:00 [pubmed] +PHST- 2017/08/10 06:00 [medline] +PHST- 2016/10/25 06:00 [entrez] +AID - S1424-3903(16)31222-4 [pii] +AID - 10.1016/j.pan.2016.10.006 [doi] +PST - ppublish +SO - Pancreatology. 2017 Jan-Feb;17(1):83-88. doi: 10.1016/j.pan.2016.10.006. Epub + 2016 Oct 11. + +PMID- 23395566 +OWN - NLM +STAT- MEDLINE +DCOM- 20130729 +LR - 20210128 +IS - 1424-3911 (Electronic) +IS - 1424-3903 (Linking) +VI - 13 +IP - 1 +DP - 2013 Jan-Feb +TI - The number of tandem repeats in the carboxyl-ester lipase (CEL) gene as a risk + factor in alcoholic and idiopathic chronic pancreatitis. +PG - 29-32 +LID - S1424-3903(12)00607-2 [pii] +LID - 10.1016/j.pan.2012.12.059 [doi] +AB - BACKGROUND/AIMS: The variable number of tandem repeats (VNTR) in the last exon of + the carboxyl-ester lipase (CEL) gene has been reported to associate with + alcohol-induced chronic pancreatitis (ACP) in a Japanese study. Here, we have + investigated the association between the number of CEL VNTR repeats and ACP or + idiopathic chronic pancreatitis (ICP) in a cohort of German patients. METHODS: + Patients diagnosed with ACP (n = 203) or ICP (n = 64) were genotyped using a + screening method consisting of PCR followed by DNA fragment analysis. The allele + frequencies of different CEL VNTR lengths were compared to the frequencies in + healthy controls (n = 390). RESULTS: We observed no statistical significant + associations between CEL VNTR allele frequencies and ACP or ICP. CONCLUSION: This + study did not find evidence that supported an association between the common + length variations of the CEL VNTR and chronic pancreatitis. +CI - Copyright (c) 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved. +FAU - Ragvin, Anja +AU - Ragvin A +AD - KG Jebsen Center for Diabetes Research, Department of Clinical Medicine, + University of Bergen, Bergen, Norway. +FAU - Fjeld, Karianne +AU - Fjeld K +FAU - Weiss, F Ulrich +AU - Weiss FU +FAU - Torsvik, Janniche +AU - Torsvik J +FAU - Aghdassi, Ali +AU - Aghdassi A +FAU - Mayerle, Julia +AU - Mayerle J +FAU - Simon, Peter +AU - Simon P +FAU - Njolstad, Pal R +AU - Njolstad PR +FAU - Lerch, Markus M +AU - Lerch MM +FAU - Johansson, Stefan +AU - Johansson S +FAU - Molven, Anders +AU - Molven A +LA - eng +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +DEP - 20121220 +PL - Switzerland +TA - Pancreatology +JT - Pancreatology : official journal of the International Association of + Pancreatology (IAP) ... [et al.] +JID - 100966936 +RN - EC 3.1.1.3 (CEL protein, human) +RN - EC 3.1.1.3 (Lipase) +SB - IM +MH - Alcoholism/*complications/genetics +MH - Cohort Studies +MH - Gene Frequency +MH - Germany +MH - Humans +MH - Lipase/*genetics +MH - Pancreatitis, Chronic/*genetics +MH - Risk Factors +EDAT- 2013/02/12 06:00 +MHDA- 2013/07/31 06:00 +CRDT- 2013/02/12 06:00 +PHST- 2012/10/11 00:00 [received] +PHST- 2012/12/12 00:00 [revised] +PHST- 2012/12/13 00:00 [accepted] +PHST- 2013/02/12 06:00 [entrez] +PHST- 2013/02/12 06:00 [pubmed] +PHST- 2013/07/31 06:00 [medline] +AID - S1424-3903(12)00607-2 [pii] +AID - 10.1016/j.pan.2012.12.059 [doi] +PST - ppublish +SO - Pancreatology. 2013 Jan-Feb;13(1):29-32. doi: 10.1016/j.pan.2012.12.059. Epub + 2012 Dec 20. + +PMID- 21784842 +OWN - NLM +STAT- MEDLINE +DCOM- 20111209 +LR - 20240324 +IS - 1083-351X (Electronic) +IS - 0021-9258 (Print) +IS - 0021-9258 (Linking) +VI - 286 +IP - 40 +DP - 2011 Oct 7 +TI - Diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl + ester lipase gene-maturity onset diabetes of the young (CEL-MODY): a protein + misfolding disease. +PG - 34593-605 +LID - 10.1074/jbc.M111.222679 [doi] +AB - CEL-maturity onset diabetes of the young (MODY), diabetes with pancreatic + lipomatosis and exocrine dysfunction, is due to dominant frameshift mutations in + the acinar cell carboxyl ester lipase gene (CEL). As Cel knock-out mice do not + express the phenotype and the mutant protein has an altered and intrinsically + disordered tandem repeat domain, we hypothesized that the disease mechanism might + involve a negative effect of the mutant protein. In silico analysis showed that + the pI of the tandem repeat was markedly increased from pH 3.3 in wild-type (WT) + to 11.8 in mutant (MUT) human CEL. By stably overexpressing CEL-WT and CEL-MUT in + HEK293 cells, we found similar glycosylation, ubiquitination, constitutive + secretion, and quality control of the two proteins. The CEL-MUT protein + demonstrated, however, a high propensity to form aggregates found intracellularly + and extracellularly. Different physicochemical properties of the intrinsically + disordered tandem repeat domains of WT and MUT proteins may contribute to + different short and long range interactions with the globular core domain and + other macromolecules, including cell membranes. Thus, we propose that CEL-MODY is + a protein misfolding disease caused by a negative gain-of-function effect of the + mutant proteins in pancreatic tissues. +FAU - Johansson, Bente B +AU - Johansson BB +AD - Department of Clinical Medicine, University of Bergen, N-5020 Bergen, Norway. +FAU - Torsvik, Janniche +AU - Torsvik J +FAU - Bjorkhaug, Lise +AU - Bjorkhaug L +FAU - Vesterhus, Mette +AU - Vesterhus M +FAU - Ragvin, Anja +AU - Ragvin A +FAU - Tjora, Erling +AU - Tjora E +FAU - Fjeld, Karianne +AU - Fjeld K +FAU - Hoem, Dag +AU - Hoem D +FAU - Johansson, Stefan +AU - Johansson S +FAU - Raeder, Helge +AU - Raeder H +FAU - Lindquist, Susanne +AU - Lindquist S +FAU - Hernell, Olle +AU - Hernell O +FAU - Cnop, Miriam +AU - Cnop M +FAU - Saraste, Jaakko +AU - Saraste J +FAU - Flatmark, Torgeir +AU - Flatmark T +FAU - Molven, Anders +AU - Molven A +FAU - Njolstad, Pal R +AU - Njolstad PR +LA - eng +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +DEP - 20110722 +PL - United States +TA - J Biol Chem +JT - The Journal of biological chemistry +JID - 2985121R +RN - 25104-18-1 (Polylysine) +RN - EC 3.1.1.1 (Carboxylesterase) +SB - IM +MH - Amino Acid Sequence +MH - Animals +MH - Carboxylesterase/*genetics +MH - Diabetes Mellitus, Type 2/*genetics +MH - Endoplasmic Reticulum/metabolism +MH - Humans +MH - Mice +MH - Mice, Knockout +MH - Molecular Sequence Data +MH - *Mutation +MH - Pancreas, Exocrine/*metabolism/physiopathology +MH - Polylysine/chemistry +MH - Protein Binding +MH - Protein Folding +MH - Protein Structure, Tertiary +MH - Sequence Homology, Amino Acid +PMC - PMC3186416 +EDAT- 2011/07/26 06:00 +MHDA- 2011/12/14 06:00 +PMCR- 2012/10/07 +CRDT- 2011/07/26 06:00 +PHST- 2011/07/26 06:00 [entrez] +PHST- 2011/07/26 06:00 [pubmed] +PHST- 2011/12/14 06:00 [medline] +PHST- 2012/10/07 00:00 [pmc-release] +AID - S0021-9258(20)73842-1 [pii] +AID - M111.222679 [pii] +AID - 10.1074/jbc.M111.222679 [doi] +PST - ppublish +SO - J Biol Chem. 2011 Oct 7;286(40):34593-605. doi: 10.1074/jbc.M111.222679. Epub + 2011 Jul 22. + +PMID- 19760265 +OWN - NLM +STAT- MEDLINE +DCOM- 20100217 +LR - 20211020 +IS - 1432-1203 (Electronic) +IS - 0340-6717 (Linking) +VI - 127 +IP - 1 +DP - 2010 Jan +TI - Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of + monogenic diabetes. +PG - 55-64 +LID - 10.1007/s00439-009-0740-8 [doi] +AB - We have previously shown that heterozygous single-base deletions in the + carboxyl-ester lipase (CEL) gene cause exocrine and endocrine pancreatic + dysfunction in two multigenerational families. These deletions were found in the + first and fourth repeats of a variable number of tandem repeats (VNTR), which has + proven challenging to sequence due to high GC-content and considerable length + variation. We have therefore developed a screening method consisting of a + multiplex PCR followed by fragment analysis. The method detected putative + disease-causing insertions and deletions in the proximal repeats of the VNTR, and + determined the VNTR-length of each allele. When blindly testing 56 members of the + two families with known single-base deletions in the CEL VNTR, the method + correctly assessed the mutation carriers. Screening of 241 probands from + suspected maturity-onset diabetes of the young (MODY) families negative for + mutations in known MODY genes (95 individuals from Denmark and 146 individuals + from UK) revealed no deletions in the proximal repeats of the CEL VNTR. However, + we found one Danish patient with a short, novel CEL allele containing only three + VNTR repeats (normal range 7-23 in healthy controls). This allele co-segregated + with diabetes or impaired glucose tolerance in the patient's family as six of + seven mutation carriers were affected. We also identified individuals who had + three copies of a complete CEL VNTR. In conclusion, the CEL gene is highly + polymorphic, but mutations in CEL are likely to be a rare cause of monogenic + diabetes. +FAU - Torsvik, Janniche +AU - Torsvik J +AD - Department of Clinical Medicine, University of Bergen, Bergen, Norway. +FAU - Johansson, Stefan +AU - Johansson S +FAU - Johansen, Anders +AU - Johansen A +FAU - Ek, Jakob +AU - Ek J +FAU - Minton, Jayne +AU - Minton J +FAU - Raeder, Helge +AU - Raeder H +FAU - Ellard, Sian +AU - Ellard S +FAU - Hattersley, Andrew +AU - Hattersley A +FAU - Pedersen, Oluf +AU - Pedersen O +FAU - Hansen, Torben +AU - Hansen T +FAU - Molven, Anders +AU - Molven A +FAU - Njolstad, Pal R +AU - Njolstad PR +LA - eng +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +DEP - 20090917 +PL - Germany +TA - Hum Genet +JT - Human genetics +JID - 7613873 +RN - EC 3.1.1.3 (CEL protein, human) +RN - EC 3.1.1.3 (Lipase) +SB - IM +MH - Adult +MH - Aged +MH - Alleles +MH - DNA Mutational Analysis +MH - Denmark +MH - Diabetes Mellitus, Type 2/*genetics +MH - Family Health +MH - Female +MH - Gene Frequency +MH - Humans +MH - Lipase/*genetics +MH - Male +MH - Middle Aged +MH - Minisatellite Repeats/*genetics +MH - Mutation +MH - Pedigree +MH - United Kingdom +EDAT- 2009/09/18 06:00 +MHDA- 2010/02/18 06:00 +CRDT- 2009/09/18 06:00 +PHST- 2009/06/30 00:00 [received] +PHST- 2009/08/30 00:00 [accepted] +PHST- 2009/09/18 06:00 [entrez] +PHST- 2009/09/18 06:00 [pubmed] +PHST- 2010/02/18 06:00 [medline] +AID - 10.1007/s00439-009-0740-8 [doi] +PST - ppublish +SO - Hum Genet. 2010 Jan;127(1):55-64. doi: 10.1007/s00439-009-0740-8. Epub 2009 Sep + 17. + +PMID- 16369531 +OWN - NLM +STAT- MEDLINE +DCOM- 20060307 +LR - 20061115 +IS - 1061-4036 (Print) +IS - 1061-4036 (Linking) +VI - 38 +IP - 1 +DP - 2006 Jan +TI - Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine + dysfunction. +PG - 54-62 +AB - Dysfunction of the exocrine pancreas is observed in diabetes, but links between + concurrent exocrine and endocrine pancreatic disease and contributing genetic + factors are poorly characterized. We studied two families with diabetes and + exocrine pancreatic dysfunction by genetic, physiological and in vitro functional + studies. A genome-wide screen in Family 1 linked diabetes to chromosome 9q34 + (maximal lod score 5.07). Using fecal elastase deficiency as a marker of exocrine + pancreatic dysfunction refined the critical chromosomal region to 1.16 Mb + (maximal lod score 11.6). Here, we identified a single-base deletion in the + variable number of tandem repeats (VNTR)-containing exon 11 of the carboxyl ester + lipase (CEL) gene, a major component of pancreatic juice and responsible for the + duodenal hydrolysis of cholesterol esters. Screening subjects with maturity-onset + diabetes of the young identified Family 2, with another single-base deletion in + CEL and a similar phenotype with beta-cell failure and pancreatic exocrine + disease. The in vitro catalytic activities of wild-type and mutant CEL protein + were comparable. The mutant enzyme was, however, less stable and secreted at a + lower rate. Furthermore, we found some evidence for an association between common + insertions in the CEL VNTR and exocrine dysfunction in a group of 182 unrelated + subjects with diabetes (odds ratio 4.2 (1.6, 11.5)). Our findings link diabetes + to the disrupted function of a lipase in the pancreatic acinar cells. +FAU - Raeder, Helge +AU - Raeder H +AD - Section for Pediatrics, Department of Clinical Medicine, University of Bergen, + Bergen, Norway. +FAU - Johansson, Stefan +AU - Johansson S +FAU - Holm, Pal I +AU - Holm PI +FAU - Haldorsen, Ingfrid S +AU - Haldorsen IS +FAU - Mas, Eric +AU - Mas E +FAU - Sbarra, Veronique +AU - Sbarra V +FAU - Nermoen, Ingrid +AU - Nermoen I +FAU - Eide, Stig A +AU - Eide SA +FAU - Grevle, Louise +AU - Grevle L +FAU - Bjorkhaug, Lise +AU - Bjorkhaug L +FAU - Sagen, Jorn V +AU - Sagen JV +FAU - Aksnes, Lage +AU - Aksnes L +FAU - Sovik, Oddmund +AU - Sovik O +FAU - Lombardo, Dominique +AU - Lombardo D +FAU - Molven, Anders +AU - Molven A +FAU - Njolstad, Pal Rasmus +AU - Njolstad PR +LA - eng +SI - RefSeq/NM_001807 +SI - RefSeq/NP_001798 +SI - RefSeq/NT_035014 +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +DEP - 20051220 +PL - United States +TA - Nat Genet +JT - Nature genetics +JID - 9216904 +RN - 0 (RNA, Messenger) +RN - EC 3.1.1.3 (CEL protein, human) +RN - EC 3.1.1.3 (Lipase) +SB - IM +CIN - Nat Genet. 2006 Jan;38(1):12-3. doi: 10.1038/ng0106-12. PMID: 16380722 +MH - Adult +MH - Animals +MH - CHO Cells +MH - Cricetinae +MH - Cricetulus +MH - Diabetes Mellitus, Type 2/etiology/*genetics/pathology +MH - Female +MH - Humans +MH - Insulin-Secreting Cells/pathology +MH - Lipase/*genetics/metabolism +MH - Male +MH - *Minisatellite Repeats +MH - Molecular Sequence Data +MH - *Mutation +MH - Pancreas, Exocrine/*physiopathology +MH - Pedigree +MH - RNA, Messenger/metabolism +EDAT- 2005/12/22 09:00 +MHDA- 2006/03/08 09:00 +CRDT- 2005/12/22 09:00 +PHST- 2005/08/22 00:00 [received] +PHST- 2005/10/27 00:00 [accepted] +PHST- 2005/12/22 09:00 [pubmed] +PHST- 2006/03/08 09:00 [medline] +PHST- 2005/12/22 09:00 [entrez] +AID - ng1708 [pii] +AID - 10.1038/ng1708 [doi] +PST - ppublish +SO - Nat Genet. 2006 Jan;38(1):54-62. doi: 10.1038/ng1708. Epub 2005 Dec 20. + +PMID- 15841033 +OWN - NLM +STAT- MEDLINE +DCOM- 20060307 +LR - 20190906 +IS - 1536-4828 (Electronic) +IS - 0885-3177 (Linking) +VI - 30 +IP - 4 +DP - 2005 May +TI - Carboxylester lipase gene polymorphism as a risk of alcohol-induced pancreatitis. +PG - e87-91 +AB - OBJECTIVES: Alcohol abuse causes pancreatic damage in humans. However, only 5% of + alcoholic patients have a clinical manifestation of pancreatitis, and the genetic + predisposition of alcohol-associated pancreatitis remains elusive. Nonoxidative + metabolites of ethanol, fatty acid ethyl esters (FAEEs), might play an important + role in pancreatic damage. Carboxylester lipase (CEL) has been known to catalyze + FAEE synthesis from fatty acids and ethanol. METHODS: The variable number of + tandem repeat (VNTR) polymorphism in the coding region of the CEL gene was + studied in patients with alcoholic pancreatitis (n = 100), in alcoholics without + pancreatitis (n = 52), in patients with nonalcoholic pancreatitis (n = 50), in + hyperlipidemia patients (n = 96), and control subjects (n = 435). RESULTS: The + frequency of the NN-type (wild-type) gene was significantly decreased in patients + with alcoholic pancreatitis than in other groups. The frequency of subjects who + had the L allele in patients with alcoholic pancreatitis was significantly higher + than in other groups. The distribution of the CEL gene polymorphism was not + different among the control subjects, alcoholics without pancreatitis, patients + with nonalcoholic pancreatitis, and patients with hyperlipidemia. CONCLUSIONS: + The CEL gene polymorphism, especially an increase in the frequency of the L + allele, was found to be associated with alcohol-induced pancreatitis. +FAU - Miyasaka, Kyoko +AU - Miyasaka K +AD - Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, + Tokyo, Japan. miyasaka@tmig.or.jp +FAU - Ohta, Minoru +AU - Ohta M +FAU - Takano, Saeko +AU - Takano S +FAU - Hayashi, Hiroshi +AU - Hayashi H +FAU - Higuchi, Susumu +AU - Higuchi S +FAU - Maruyama, Katsuya +AU - Maruyama K +FAU - Tando, Yusuke +AU - Tando Y +FAU - Nakamura, Teruo +AU - Nakamura T +FAU - Takata, Yutaka +AU - Takata Y +FAU - Funakoshi, Akihiro +AU - Funakoshi A +LA - eng +PT - Comparative Study +PT - Journal Article +PT - Research Support, Non-U.S. Gov't +PL - United States +TA - Pancreas +JT - Pancreas +JID - 8608542 +RN - EC 1.2.1.3 (ALDH2 protein, human) +RN - EC 1.2.1.3 (Aldehyde Dehydrogenase) +RN - EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial) +RN - EC 3.1.1.1 (Carboxylesterase) +SB - IM +MH - Aged +MH - Aldehyde Dehydrogenase/genetics +MH - Aldehyde Dehydrogenase, Mitochondrial +MH - Alleles +MH - Carboxylesterase/*genetics +MH - Female +MH - Genetic Predisposition to Disease/epidemiology +MH - Genotype +MH - Humans +MH - Hyperlipidemias/epidemiology/genetics +MH - Male +MH - Middle Aged +MH - Pancreatitis/epidemiology/genetics +MH - Pancreatitis, Alcoholic/*epidemiology/*genetics +MH - *Polymorphism, Genetic +MH - Risk Factors +EDAT- 2005/04/21 09:00 +MHDA- 2006/03/08 09:00 +CRDT- 2005/04/21 09:00 +PHST- 2005/04/21 09:00 [pubmed] +PHST- 2006/03/08 09:00 [medline] +PHST- 2005/04/21 09:00 [entrez] +AID - 00006676-200505000-00022 [pii] +AID - 10.1097/01.mpa.0000160960.21580.ml [doi] +PST - ppublish +SO - Pancreas. 2005 May;30(4):e87-91. doi: 10.1097/01.mpa.0000160960.21580.ml. diff --git a/data/plots/age-onset.json b/data/plots/age-onset.json index 99f356fb..2847691b 100644 --- a/data/plots/age-onset.json +++ b/data/plots/age-onset.json @@ -1,7 +1,7 @@ { "data": [ { - "base": [32, 31, 28, 25, 23, 22, 21, 20, 20, 0, 18, 18, 18, 16, 15, 14, 0, 12, 12, 11, 10, 10, 10, 10, 10, 8, 8, 8, 0, 7, 7, 6, 0, 0, 4, 4, 3, 3, 3, 2, 0, 0, 2, 1, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], + "base": [32, 31, 28, 25, 23, 22, 21, 20, 20, 0, 18, 18, 18, 16, 15, 14, 0, 12, 12, 11, 11, 10, 10, 10, 10, 10, 8, 8, 8, 0, 7, 7, 6, 0, 0, 4, 4, 3, 3, 3, 2, 0, 0, 2, 1, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Range onset: %{base} - %{x} years", "legendgroup": "AD", "marker": @@ -12,12 +12,12 @@ "offset": -0.1, "orientation": "h", "width": 0.2, - "x": [47, 32, 39, 52, 51, 44, 66, 71, 59, 0, 52, 19, 46, 57, 25, 56, 0, 53, 54, 72, 36, 23, 68, 40, 20, 75, 54, 60, 0, 61, 59, 57, 0, 0, 47, 56, 59, 10, 70, 84, 0, 0, 1, 84, 6, 0, 0, 73, 76, 72, 74, 0, 65, 0, 0, 3, 36, 0, 0], - "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], + "x": [47, 32, 39, 52, 51, 44, 66, 71, 59, 0, 52, 19, 46, 57, 25, 56, 0, 53, 54, 6, 72, 36, 23, 68, 40, 20, 75, 54, 60, 0, 61, 59, 57, 0, 0, 47, 56, 59, 10, 70, 84, 0, 0, 1, 84, 6, 0, 0, 73, 76, 72, 74, 0, 65, 0, 0, 3, 36, 0, 0], + "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "MODY8", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], "type": "bar" }, { - "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 19, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 6, 0, 0, 0, 0, 0, 0, 0, 2, 2, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], + "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 19, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 6, 0, 0, 0, 0, 0, 0, 0, 2, 2, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Range onset: %{base} - %{x} years", "legendgroup": "AR", "marker": @@ -28,12 +28,12 @@ "offset": -0.1, "orientation": "h", "width": 0.2, - "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 57, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 12, 0, 0, 0, 0, 0, 0, 0, 78, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 10], - "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], + "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 57, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 12, 0, 0, 0, 0, 0, 0, 0, 78, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 10], + "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "MODY8", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], "type": "bar" }, { - "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], + "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Range onset: %{base} - %{x} years", "legendgroup": "XD", "marker": @@ -44,12 +44,12 @@ "offset": -0.1, "orientation": "h", "width": 0.2, - "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 78, 0], - "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], + "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 78, 0], + "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "MODY8", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], "type": "bar" }, { - "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 12, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 8, 0, 0, 0, 0, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], + "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 12, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 8, 0, 0, 0, 0, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Range onset: %{base} - %{x} years", "legendgroup": "XR", "marker": @@ -60,12 +60,12 @@ "offset": -0.1, "orientation": "h", "width": 0.2, - "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 67, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 75, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 9, 0, 4, 4, 0, 0, 0, 0], - "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], + "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 67, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 75, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 9, 0, 4, 4, 0, 0, 0, 0], + "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "MODY8", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], "type": "bar" }, { - "base": [40.0, 50.0, 40.0, 44.0, 0, 0, 42.0, 50.0, 40.0, 0, 0, 0, 33.0, 43.0, 0, 20.0, 0, 37.0, 30.0, 12.0, 0, 0, 30.0, 24, 18.0, 56.0, 26.0, 21.0, 0, 0, 31.0, 20.0, 0, 0, 0, 12.0, 19.0, 0, 10.0, 30.0, 0, 0, 0, 35.0, 0, 0, 0, 28.0, 20.0, 20.0, 10.0, 0, 4.0, 0, 0, 0, 0.0, 0, 0], + "base": [40.0, 50.0, 40.0, 44.0, 0, 0, 42.0, 50.0, 40.0, 0, 0, 0, 33.0, 43.0, 0, 20.0, 0, 37.0, 30.0, 0, 12.0, 0, 0, 30.0, 24, 18.0, 56.0, 26.0, 21.0, 0, 0, 31.0, 20.0, 0, 0, 0, 12.0, 19.0, 0, 10.0, 30.0, 0, 0, 0, 35.0, 0, 0, 0, 28.0, 20.0, 20.0, 10.0, 0, 4.0, 0, 0, 0, 0.0, 0, 0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Typical onset: %{base} - %{x} years", "legendgroup": "AD", "marker": @@ -77,12 +77,12 @@ "orientation": "h", "showlegend": false, "width": 0.6, - "x": [19.0, 10.0, 20.0, 16.0, 0, 0, 28.0, 14.0, 19.0, 0, 0, 0, 20.0, 9.0, 0, 14.0, 0, 19.0, 22.0, 36.0, 0, 0, 40.0, 6, 12.0, 6.0, 24.0, 18.0, 0, 0, 20.0, 19.0, 0, 0, 0, 18.0, 29.0, 0, 39.0, 9.0, 0, 0, 0, 9.0, 0, 0, 0, 28.0, 29.0, 20.0, 20.0, 0, 44.0, 0, 0, 0, 2.0, 0, 0], - "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], + "x": [19.0, 10.0, 20.0, 16.0, 0, 0, 28.0, 14.0, 19.0, 0, 0, 0, 20.0, 9.0, 0, 14.0, 0, 19.0, 22.0, 0, 36.0, 0, 0, 40.0, 6, 12.0, 6.0, 24.0, 18.0, 0, 0, 20.0, 19.0, 0, 0, 0, 18.0, 29.0, 0, 39.0, 9.0, 0, 0, 0, 9.0, 0, 0, 0, 28.0, 29.0, 20.0, 20.0, 0, 44.0, 0, 0, 0, 2.0, 0, 0], + "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "MODY8", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], "type": "bar" }, { - "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 36.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 6.0, 0, 0, 0, 0, 0, 0, 0, 10.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1.0], + "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 36.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 6.0, 0, 0, 0, 0, 0, 0, 0, 10.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1.0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Typical onset: %{base} - %{x} years", "legendgroup": "AR", "marker": @@ -94,12 +94,12 @@ "orientation": "h", "showlegend": false, "width": 0.6, - "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 16.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9.0, 0, 0, 0, 0, 0, 0, 0, 5.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 2.0], - "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], + "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 16.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9.0, 0, 0, 0, 0, 0, 0, 0, 5.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 2.0], + "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "MODY8", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], "type": "bar" }, { - "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1.0, 0], + "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1.0, 0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Typical onset: %{base} - %{x} years", "legendgroup": "XD", "marker": @@ -111,12 +111,12 @@ "orientation": "h", "showlegend": false, "width": 0.6, - "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 64.0, 0], - "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], + "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 64.0, 0], + "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "MODY8", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], "type": "bar" }, { - "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 39.7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 20.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 2.0, 0, 0, 0, 0, 0, 0, 0, 0.0, 0, 0, 0, 0, 0], + "base": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 39.7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 20.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 2.0, 0, 0, 0, 0, 0, 0, 0, 0.0, 0, 0, 0, 0, 0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Typical onset: %{base} - %{x} years", "legendgroup": "XR", "marker": @@ -128,8 +128,8 @@ "orientation": "h", "showlegend": false, "width": 0.6, - "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 29.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 8.0, 0, 0, 0, 0, 0, 0, 0, 0.0, 0, 0, 0, 0, 0], - "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], + "x": [0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 29.0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 8.0, 0, 0, 0, 0, 0, 0, 0, 0.0, 0, 0, 0, 0, 0], + "y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "MODY8", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], "type": "bar" }, { @@ -727,7 +727,7 @@ "yaxis": { "tickmode": "array", - "tickvals": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], + "tickvals": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "MODY8", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"], "title": { "text": "Disease" diff --git a/data/plots/path-size.json b/data/plots/path-size.json index 97f9d9c2..40ae0cfc 100644 --- a/data/plots/path-size.json +++ b/data/plots/path-size.json @@ -1,7 +1,7 @@ { "data": [ { - "base": [0, 50, 0, 18, 2871, 0, 15, 1, 12, 0, 15, 252, 10, 24, 9, 18, 12, 15, 0, 0, 9, 24, 18, 9, 15, 44, 0, 20, 39, 1, 1, 45, 0, 21, 33, 48, 15, 1, 18, 30, 15, 75, 18, 42, 60, 18, 96, 18, 27, 12, 18, 42, 27, 45, 45, 42, 24, 45, 45, 12, 36, 12, 36, 21, 30, 42, 0, 30, 30, 18, 15, 16, 20, 30], + "base": [0, 50, 0, 18, 2871, 0, 15, 1, 12, 0, 15, 252, 10, 24, 9, 18, 12, 15, 0, 0, 9, 24, 18, 9, 15, 44, 0, 20, 39, 1, 1, 45, 0, 21, 33, 48, 15, 1, 18, 30, 15, 75, 18, 42, 60, 18, 96, 18, 27, 12, 18, 42, 231, 27, 45, 45, 42, 24, 45, 45, 12, 36, 12, 36, 21, 30, 42, 0, 30, 30, 18, 15, 16, 20, 30], "hovertemplate": "Disease: %{y} \u003cbr\u003e Range: %{base} - %{x} bp", "legendgroup": "Benign", "marker": @@ -12,12 +12,12 @@ "offset": -0.3, "orientation": "h", "width": 0.6, - "x": [0, 110, 0, 66, 198, 0, 99, 54, 126, 0, 51, 780, 25, 513, 51, 51, 105, 117, 0, 0, 39, 12, 30, 123, 222, 60, 0, 220, 96, 95, 59, 105, 0, 90, 99, 51, 84, 149, 78, 87, 87, 45, 87, 36, 54, 66, 0, 87, 75, 69, 60, 48, 33, 0, 0, 0, 30, 0, 0, 42, 0, 39, 0, 21, 18, 0, 0, 0, 0, 12, 0, 0, 0, 0], - "y": ["FAME4", "SCA10", "FAME3", "SCA36", "MRUPAV", "FAME6", "GDPAG", "CANVAS", "FTDALS1", "FAME2", "FRA7A", "CPUM", "NME", "SCA27B", "FRA2A", "FRA12A", "FRAXE", "FXS, FXTAS, POF1", "SCA31", "FAME1", "OPML1", "EPM1", "OPDM4", "OPDM5", "JBS", "DM2", "FAME7", "RCPS", "OPDM1", "OPDM2", "DBQD2, BSS", "SCA8", "XDP", "NIID", "SCA3, MJD", "DMD", "FRDA", "SCA37", "SCA12", "FECD3", "DM1", "SCA17", "DRPLA", "SCA4", "SCA", "HDL2", "CJD", "SCA1", "SBMA", "SCA7", "HD", "SCA2", "CCHS", "TOF", "HPE5", "HFG-I", "HFG-III", "SD5", "XLMR", "SCA6", "PRTS", "CCD", "HFG-II", "HSAN VIII", "EIEE1", "BPES", "FAME8", "OPMD", "VACTERLX", "ALS1", "EDM1, PSACH", "CHNG3", "HMNR7", "CPEO"], + "x": [0, 110, 0, 66, 198, 0, 99, 54, 126, 0, 51, 780, 25, 513, 51, 51, 105, 117, 0, 0, 39, 12, 30, 123, 222, 60, 0, 220, 96, 95, 59, 105, 0, 90, 99, 51, 84, 149, 78, 87, 87, 45, 87, 36, 54, 66, 0, 87, 75, 69, 60, 48, 528, 33, 0, 0, 0, 30, 0, 0, 42, 0, 39, 0, 21, 18, 0, 0, 0, 0, 12, 0, 0, 0, 0], + "y": ["FAME4", "SCA10", "FAME3", "SCA36", "MRUPAV", "FAME6", "GDPAG", "CANVAS", "FTDALS1", "FAME2", "FRA7A", "CPUM", "NME", "SCA27B", "FRA2A", "FRA12A", "FRAXE", "FXS, FXTAS, POF1", "SCA31", "FAME1", "OPML1", "EPM1", "OPDM4", "OPDM5", "JBS", "DM2", "FAME7", "RCPS", "OPDM1", "OPDM2", "DBQD2, BSS", "SCA8", "XDP", "NIID", "SCA3, MJD", "DMD", "FRDA", "SCA37", "SCA12", "FECD3", "DM1", "SCA17", "DRPLA", "SCA4", "SCA", "HDL2", "CJD", "SCA1", "SBMA", "SCA7", "HD", "SCA2", "MODY8", "CCHS", "TOF", "HPE5", "HFG-I", "HFG-III", "SD5", "XLMR", "SCA6", "PRTS", "CCD", "HFG-II", "HSAN VIII", "EIEE1", "BPES", "FAME8", "OPMD", "VACTERLX", "ALS1", "EDM1, PSACH", "CHNG3", "HMNR7", "CPEO"], "type": "bar" }, { - "base": [0, 165, 0, 90, 0, 0, 0, 55, 144, 0, 126, 0, 0, 540, 0, 417, 120, 135, 0, 0, 0, 0, 0, 0, 240, 108, 0, 260, 0, 0, 0, 150, 0, 114, 135, 0, 102, 0, 120, 120, 105, 123, 108, 81, 0, 87, 0, 108, 108, 84, 81, 93, 63, 0, 0, 0, 0, 0, 0, 57, 0, 0, 0, 0, 0, 0, 0, 33, 33, 0, 0, 0, 0, 0], + "base": [0, 165, 0, 90, 0, 0, 0, 55, 144, 0, 126, 0, 0, 540, 0, 417, 120, 135, 0, 0, 0, 0, 0, 0, 240, 108, 0, 260, 0, 0, 0, 150, 0, 114, 135, 0, 102, 0, 120, 120, 105, 123, 108, 81, 0, 87, 0, 108, 108, 84, 81, 93, 0, 63, 0, 0, 0, 0, 0, 0, 57, 0, 0, 0, 0, 0, 0, 0, 33, 33, 0, 0, 0, 0, 0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Range: %{base} - %{x} bp", "legendgroup": "Intermediate", "marker": @@ -28,12 +28,12 @@ "offset": -0.3, "orientation": "h", "width": 0.6, - "x": [0, 4085, 0, 3804, 0, 0, 0, 945, 216, 0, 129, 0, 0, 417, 0, 201, 480, 465, 0, 0, 0, 0, 0, 0, 60, 188, 0, 0, 0, 0, 0, 60, 0, 81, 42, 0, 63, 0, 27, 30, 42, 21, 33, 54, 0, 30, 0, 6, 3, 21, 24, 9, 12, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], - "y": ["FAME4", "SCA10", "FAME3", "SCA36", "MRUPAV", "FAME6", "GDPAG", "CANVAS", "FTDALS1", "FAME2", "FRA7A", "CPUM", "NME", "SCA27B", "FRA2A", "FRA12A", "FRAXE", "FXS, FXTAS, POF1", "SCA31", "FAME1", "OPML1", "EPM1", "OPDM4", "OPDM5", "JBS", "DM2", "FAME7", "RCPS", "OPDM1", "OPDM2", "DBQD2, BSS", "SCA8", "XDP", "NIID", "SCA3, MJD", "DMD", "FRDA", "SCA37", "SCA12", "FECD3", "DM1", "SCA17", "DRPLA", "SCA4", "SCA", "HDL2", "CJD", "SCA1", "SBMA", "SCA7", "HD", "SCA2", "CCHS", "TOF", "HPE5", "HFG-I", "HFG-III", "SD5", "XLMR", "SCA6", "PRTS", "CCD", "HFG-II", "HSAN VIII", "EIEE1", "BPES", "FAME8", "OPMD", "VACTERLX", "ALS1", "EDM1, PSACH", "CHNG3", "HMNR7", "CPEO"], + "x": [0, 4085, 0, 3804, 0, 0, 0, 945, 216, 0, 129, 0, 0, 417, 0, 201, 480, 465, 0, 0, 0, 0, 0, 0, 60, 188, 0, 0, 0, 0, 0, 60, 0, 81, 42, 0, 63, 0, 27, 30, 42, 21, 33, 54, 0, 30, 0, 6, 3, 21, 24, 9, 0, 12, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0], + "y": ["FAME4", "SCA10", "FAME3", "SCA36", "MRUPAV", "FAME6", "GDPAG", "CANVAS", "FTDALS1", "FAME2", "FRA7A", "CPUM", "NME", "SCA27B", "FRA2A", "FRA12A", "FRAXE", "FXS, FXTAS, POF1", "SCA31", "FAME1", "OPML1", "EPM1", "OPDM4", "OPDM5", "JBS", "DM2", "FAME7", "RCPS", "OPDM1", "OPDM2", "DBQD2, BSS", "SCA8", "XDP", "NIID", "SCA3, MJD", "DMD", "FRDA", "SCA37", "SCA12", "FECD3", "DM1", "SCA17", "DRPLA", "SCA4", "SCA", "HDL2", "CJD", "SCA1", "SBMA", "SCA7", "HD", "SCA2", "MODY8", "CCHS", "TOF", "HPE5", "HFG-I", "HFG-III", "SD5", "XLMR", "SCA6", "PRTS", "CCD", "HFG-II", "HSAN VIII", "EIEE1", "BPES", "FAME8", "OPMD", "VACTERLX", "ALS1", "EDM1, PSACH", "CHNG3", "HMNR7", "CPEO"], "type": "bar" }, { - "base": [5000, 4000, 3955, 3900, 3663, 3300, 2040, 2000, 1506, 1370, 1350, 1260, 1000, 960, 900, 819, 603, 603, 550, 525, 483, 360, 360, 354, 303, 300, 300, 280, 255, 219, 216, 213, 210, 198, 180, 177, 168, 155, 153, 153, 150, 147, 144, 138, 135, 120, 120, 117, 114, 111, 108, 105, 78, 75, 75, 66, 66, 66, 66, 63, 60, 60, 54, 54, 51, 45, 45, 36, 36, 33, 18, 12, 10, 0], + "base": [5000, 4000, 3955, 3900, 3663, 3300, 2040, 2000, 1506, 1370, 1350, 1260, 1000, 960, 900, 819, 603, 603, 550, 525, 483, 360, 360, 354, 303, 300, 300, 280, 255, 219, 216, 213, 210, 198, 180, 177, 168, 155, 153, 153, 150, 147, 144, 138, 135, 120, 120, 117, 114, 111, 108, 105, 99, 78, 75, 75, 66, 66, 66, 66, 63, 60, 60, 54, 54, 51, 45, 45, 36, 36, 33, 18, 12, 10, 0], "hovertemplate": "Disease: %{y} \u003cbr\u003e Range: %{base} - %{x} bp", "legendgroup": "Pathogenic", "marker": @@ -44,8 +44,8 @@ "offset": -0.3, "orientation": "h", "width": 0.6, - "x": [0, 18500, 1220, 11100, 1287, 0, 2460, 11750, 23022, 1420, 0, 294, 0, 1851, 0, 99, 5397, 5397, 3250, 17875, 1617, 1140, 231, 1728, 597, 43700, 10700, 40, 612, 273, 114, 3687, 102, 1353, 81, 69, 4932, 220, 81, 7647, 11850, 51, 135, 84, 165, 60, 264, 156, 90, 1269, 642, 1395, 21, 0, 0, 0, 30, 3, 12, 36, 0, 21, 0, 3, 30, 27, 1625, 18, 0, 135, 3, 0, 20, 0], - "y": ["FAME4", "SCA10", "FAME3", "SCA36", "MRUPAV", "FAME6", "GDPAG", "CANVAS", "FTDALS1", "FAME2", "FRA7A", "CPUM", "NME", "SCA27B", "FRA2A", "FRA12A", "FRAXE", "FXS, FXTAS, POF1", "SCA31", "FAME1", "OPML1", "EPM1", "OPDM4", "OPDM5", "JBS", "DM2", "FAME7", "RCPS", "OPDM1", "OPDM2", "DBQD2, BSS", "SCA8", "XDP", "NIID", "SCA3, MJD", "DMD", "FRDA", "SCA37", "SCA12", "FECD3", "DM1", "SCA17", "DRPLA", "SCA4", "SCA", "HDL2", "CJD", "SCA1", "SBMA", "SCA7", "HD", "SCA2", "CCHS", "TOF", "HPE5", "HFG-I", "HFG-III", "SD5", "XLMR", "SCA6", "PRTS", "CCD", "HFG-II", "HSAN VIII", "EIEE1", "BPES", "FAME8", "OPMD", "VACTERLX", "ALS1", "EDM1, PSACH", "CHNG3", "HMNR7", "CPEO"], + "x": [0, 18500, 1220, 11100, 1287, 0, 2460, 11750, 23022, 1420, 0, 294, 0, 1851, 0, 99, 5397, 5397, 3250, 17875, 1617, 1140, 231, 1728, 597, 43700, 10700, 40, 612, 273, 114, 3687, 102, 1353, 81, 69, 4932, 220, 81, 7647, 11850, 51, 135, 84, 165, 60, 264, 156, 90, 1269, 642, 1395, 0, 21, 0, 0, 0, 30, 3, 12, 36, 0, 21, 0, 3, 30, 27, 1625, 18, 0, 135, 3, 0, 20, 0], + "y": ["FAME4", "SCA10", "FAME3", "SCA36", "MRUPAV", "FAME6", "GDPAG", "CANVAS", "FTDALS1", "FAME2", "FRA7A", "CPUM", "NME", "SCA27B", "FRA2A", "FRA12A", "FRAXE", "FXS, FXTAS, POF1", "SCA31", "FAME1", "OPML1", "EPM1", "OPDM4", "OPDM5", "JBS", "DM2", "FAME7", "RCPS", "OPDM1", "OPDM2", "DBQD2, BSS", "SCA8", "XDP", "NIID", "SCA3, MJD", "DMD", "FRDA", "SCA37", "SCA12", "FECD3", "DM1", "SCA17", "DRPLA", "SCA4", "SCA", "HDL2", "CJD", "SCA1", "SBMA", "SCA7", "HD", "SCA2", "MODY8", "CCHS", "TOF", "HPE5", "HFG-I", "HFG-III", "SD5", "XLMR", "SCA6", "PRTS", "CCD", "HFG-II", "HSAN VIII", "EIEE1", "BPES", "FAME8", "OPMD", "VACTERLX", "ALS1", "EDM1, PSACH", "CHNG3", "HMNR7", "CPEO"], "type": "bar" }, { @@ -945,6 +945,19 @@ "y": ["SCA2", "SCA2"], "type": "scatter" }, + { + "hoverinfo": "skip", + "line": + { + "color": "#aeaeae", + "dash": "dot" + }, + "mode": "lines", + "showlegend": false, + "x": [99, 231], + "y": ["MODY8", "MODY8"], + "type": "scatter" + }, { "hoverinfo": "skip", "line": @@ -1285,8 +1298,8 @@ "mode": "markers", "name": "Pathogenic", "showlegend": false, - "x": [5000, 3300, 1350, 1000, 900, 75, 75, 66, 60, 54, 36, 12], - "y": ["FAME4", "FAME6", "FRA7A", "NME", "FRA2A", "TOF", "HPE5", "HFG-I", "PRTS", "HFG-II", "VACTERLX", "CHNG3"], + "x": [5000, 3300, 1350, 1000, 900, 99, 75, 75, 66, 60, 54, 36, 12], + "y": ["FAME4", "FAME6", "FRA7A", "NME", "FRA2A", "MODY8", "TOF", "HPE5", "HFG-I", "PRTS", "HFG-II", "VACTERLX", "CHNG3"], "type": "scatter" }], "layout": @@ -1869,7 +1882,7 @@ "yaxis": { "tickmode": "array", - "tickvals": ["FAME4", "SCA10", "FAME3", "SCA36", "MRUPAV", "FAME6", "GDPAG", "CANVAS", "FTDALS1", "FAME2", "FRA7A", "CPUM", "NME", "SCA27B", "FRA2A", "FRA12A", "FRAXE", "FXS, FXTAS, POF1", "SCA31", "FAME1", "OPML1", "EPM1", "OPDM4", "OPDM5", "JBS", "DM2", "FAME7", "RCPS", "OPDM1", "OPDM2", "DBQD2, BSS", "SCA8", "XDP", "NIID", "SCA3, MJD", "DMD", "FRDA", "SCA37", "SCA12", "FECD3", "DM1", "SCA17", "DRPLA", "SCA4", "SCA", "HDL2", "CJD", "SCA1", "SBMA", "SCA7", "HD", "SCA2", "CCHS", "TOF", "HPE5", "HFG-I", "HFG-III", "SD5", "XLMR", "SCA6", "PRTS", "CCD", "HFG-II", "HSAN VIII", "EIEE1", "BPES", "FAME8", "OPMD", "VACTERLX", "ALS1", "EDM1, PSACH", "CHNG3", "HMNR7", "CPEO"], + "tickvals": ["FAME4", "SCA10", "FAME3", "SCA36", "MRUPAV", "FAME6", "GDPAG", "CANVAS", "FTDALS1", "FAME2", "FRA7A", "CPUM", "NME", "SCA27B", "FRA2A", "FRA12A", "FRAXE", "FXS, FXTAS, POF1", "SCA31", "FAME1", "OPML1", "EPM1", "OPDM4", "OPDM5", "JBS", "DM2", "FAME7", "RCPS", "OPDM1", "OPDM2", "DBQD2, BSS", "SCA8", "XDP", "NIID", "SCA3, MJD", "DMD", "FRDA", "SCA37", "SCA12", "FECD3", "DM1", "SCA17", "DRPLA", "SCA4", "SCA", "HDL2", "CJD", "SCA1", "SBMA", "SCA7", "HD", "SCA2", "MODY8", "CCHS", "TOF", "HPE5", "HFG-I", "HFG-III", "SD5", "XLMR", "SCA6", "PRTS", "CCD", "HFG-II", "HSAN VIII", "EIEE1", "BPES", "FAME8", "OPMD", "VACTERLX", "ALS1", "EDM1, PSACH", "CHNG3", "HMNR7", "CPEO"], "title": { "text": "Disease" diff --git a/data/ref-alleles/ref-alleles.T2T-chm13.txt b/data/ref-alleles/ref-alleles.T2T-chm13.txt index e391eb3a..1cca17eb 100644 --- a/data/ref-alleles/ref-alleles.T2T-chm13.txt +++ b/data/ref-alleles/ref-alleles.T2T-chm13.txt @@ -190,6 +190,12 @@ chr9 142886568 142886595 GCC TRGT CGCCCGCGCT C GCC GCC GCC GCC GCC GCC GCC GCC GC GCACCACCTG CGCCCGCGCT C GCC GCC GCC GCC GCC GCC GCC GCC GC GCACCACCTG +MODY8_CEL +chr9 145285396 145285622 GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG,GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG STRchive +chr9 145285396 145285622 GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG,GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG TRGT +TCCGAGACCG CCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG CGCCCCCCCC +TCCGAGACCG CCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG CGCCCCCCCC + OPML1_NUTM2B-AS1 chr10 80695718 80695748 GGC STRchive chr10 80695718 80695748 GGC TRGT diff --git a/data/ref-alleles/ref-alleles.hg19.txt b/data/ref-alleles/ref-alleles.hg19.txt index 307da839..3734b75b 100644 --- a/data/ref-alleles/ref-alleles.hg19.txt +++ b/data/ref-alleles/ref-alleles.hg19.txt @@ -190,6 +190,12 @@ chr9 133556992 133557028 GCC TRGT CGCCCGCGCT C GCC GCC GCC GCC GCC GCC GCC GCC GCC GCC GCC GC GCACCACCTG CGCCCGCGCT C GCC GCC GCC GCC GCC GCC GCC GCC GCC GCC GCC GC GCACCACCTG +MODY8_CEL +chr9 135946627 135946886 GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG,GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG STRchive +chr9 135946627 135946886 GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG,GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG TRGT +TCCGAGACCG CCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG CGCCCCCCCC +TCCGAGACCG CCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG CGCCCCCCCC + OPML1_NUTM2B-AS1 chr10 81586139 81586160 GGC STRchive chr10 81586139 81586160 GGC TRGT diff --git a/data/ref-alleles/ref-alleles.hg38.txt b/data/ref-alleles/ref-alleles.hg38.txt index e54493d2..38791a00 100644 --- a/data/ref-alleles/ref-alleles.hg38.txt +++ b/data/ref-alleles/ref-alleles.hg38.txt @@ -190,6 +190,12 @@ chr9 130681605 130681641 GCC TRGT CGCCCGCGCT C GCC GCC GCC GCC GCC GCC GCC GCC GCC GCC GCC GC GCACCACCTG CGCCCGCGCT C GCC GCC GCC GCC GCC GCC GCC GCC GCC GCC GCC GC GCACCACCTG +MODY8_CEL +chr9 133071240 133071499 GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG,GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG STRchive +chr9 133071240 133071499 GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG,GGCCCCCCCGTGCCGCCCACGGGTGACTCCGG TRGT +TCCGAGACCG CCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG CGCCCCCCCC +TCCGAGACCG CCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG GGCCCCCCCCGTGCCGCCCACGGGTGACTCCGG CGCCCCCCCC + OPML1_NUTM2B-AS1 chr10 79826383 79826404 GGC STRchive chr10 79826383 79826404 GGC TRGT From 39624efee8fd46d9a03803b1cc33e4e1826fe955 Mon Sep 17 00:00:00 2001 From: hdashnow <3794821+hdashnow@users.noreply.github.com> Date: Tue, 12 Aug 2025 18:41:37 +0000 Subject: [PATCH 2/2] Update data