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 @@
{
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+ "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