tbuckley/cabot-search huggingface dataset:
Gene expression profiling of hypertrophic cardiomyocytes identifies new players in pathological remodelling
Authors: Marta Vigil-Garcia, Charlotte J Demkes, Joep E C Eding, Danielle Versteeg, Hesther de Ruiter, Ilaria Perini, Lieneke Kooijman, Monika M Gladka, Folkert W Asselbergs, Aryan Vink, Magdalena Harakalova, Alexander Bossu, Toon A B van Veen, Cornelis J Boogerd, Eva van Rooij
Journal: Cardiovascular Research (2020)

Pathological cardiac remodelling is characterized by cardiomyocyte (CM) hypertrophy and fibroblast activation, which can ultimately lead to maladaptive hypertrophy and heart failure (HF). Genome-wide expression analysis on heart tissue has been instrumental for the identification of molecular mechanisms at play. However, these data were based on signals derived from all cardiac cell types. Here, we aimed for a more detailed view on molecular changes driving maladaptive CM hypertrophy to aid in the development of therapies to reverse pathological remodelling.
Pathogenic Variants in Breast Cancer Susceptibility Genes in Older Women
Authors: Florentia Fostira, Despoina Kalfakakou, Irene Konstantopoulou
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Incidental Detection of Malignant Melanoma Brain Recurrence on 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Nir Hod, Sophie Lantsberg, Elya Benkovich, Dina Ezroh Kazap, Mark Preiskel, Daniel Levin
Journal: Clinical Nuclear Medicine (2020)

Abstract A 76-year-old man with a prior medical history of resected malignant melanoma of the skull underwent 68 Ga–prostate-specific membrane antigen (PSMA) PET/CT due to rising tumor markers of a known prostate carcinoma. Unexpected high 68 Ga-PSMA brain uptake was encountered around the surgical cavity in the skull with initially no specific structural changes on anatomical imaging. Successive CT and MRI eventually revealed local melanoma brain recurrence at this site. This interesting case demonstrates the diagnostic potential of 68 Ga-PSMA PET/CT imaging for detection of malignant melanoma brain recurrence.
Utility of a Molecular Classifier as a Complement to High-Resolution Computed Tomography to Identify Usual Interstitial Pneumonia
Authors: Luca Richeldi, Mary Beth Scholand, David A. Lynch, Thomas V. Colby, Jeffrey L. Myers, Steve D. Groshong, Jonathan H. Chung, Sadia Benzaquen, Steven D. Nathan, J. Russell Davis, Shelley L. Schmidt, Lars Hagmeyer, David Sonetti, Jurgen Hetzel, Gerard J. Criner, Amy H. Case, Murali Ramaswamy, Karel Calero, Umair A. Gauhar, Nina M. Patel, Lisa Lancaster, Yoonha Choi, Daniel G. Pankratz, P. Sean Walsh, Lori R. Lofaro, Jing Huang, Sangeeta M. Bhorade, Giulia C. Kennedy, Fernando J. Martinez, Ganesh Raghu
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A "molecular diagnosis of UIP" in transbronchial lung biopsy, the Envisia Genomic Classifier, accurately predicted histopathologic UIP.Objectives: We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern.Methods: Ninety-six patients who had diagnostic lung pathology as well as a transbronchial lung biopsy for molecular testing with Envisia Genomic Classifier were included in this analysis. The classifier results were scored against reference pathology. UIP identified on high-resolution computed tomography (HRCT) as documented by features in local radiologists' reports was compared with histopathology.Measurements and Main Results: In 96 patients, the Envisia Classifier achieved a specificity of 92.1% (confidence interval [CI],78.6-98.3%) and a sensitivity of 60.3% (CI, 46.6-73.0%) for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology, with a sensitivity of 34.0% (CI, 21.5-48.3%) and a specificity of 96.9% (CI, 83.8-100%). In conjunction with HRCT patterns of UIP, the Envisia Classifier results identified 24 additional patients with UIP (sensitivity 79.2%; specificity 90.6%).Conclusions: In 96 patients with suspected interstitial lung disease, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an interstitial lung disease (especially IPF) diagnosis without the need for a surgical lung biopsy.
18F-Fluciclovine Uptake in Acute Appendicitis
Authors: Grace S. Ahn, Andrew R. Barsky, Maya Galperin-Aizenberg, Neha Vapiwala, Austin R. Pantel
Journal: Clinical Nuclear Medicine (2020)

Abstract An 85-year-old man with biochemical recurrence of prostate cancer after prostatectomy was imaged with 18 F-fluciclovine PET/CT. Images incidentally revealed 18 F-fluciclovine uptake in a dilated appendix with associated fat stranding, suggestive of acute appendicitis. The patient was then questioned about abdominal symptoms, and he reported severe right lower quadrant pain. He then underwent laparoscopic appendectomy with pathology confirming acute appendicitis.
Scientific considerations for global drug development
Authors: Jennifer L. Wilson, Kit Wun Kathy Cheung, Lawrence Lin, Elizabeth A. E. Green, Analia I. Porrás, Ling Zou, David Mukanga, Paul A. Akpa, Delese Mimi Darko, Rae Yuan, Sheng Ding, Wiltshire C. N. Johnson, Howard A. Lee, Emer Cooke, Carl C. Peck, Steven E. Kern, Dan Hartman, Yoshikazu Hayashi, Peter W. Marks, Russ B. Altman, Murray M. Lumpkin, Kathleen M. Giacomini, Terrence F. Blaschke
Journal: Science Translational Medicine (2020)

Scientific and technological advances could reduce the need for in-country or in-region confirmatory clinical trials.
Heterogeneous addiction to transforming growth factor‐beta signalling in recessive dystrophic epidermolysis bullosa‐associated cutaneous squamous cell carcinoma*
Authors: J.H.S. Dayal, S.M. Mason, J.C. Salas‐Alanis, J.A. McGrath, R.G. Taylor, J.E. Mellerio, K. Blyth, A.P. South, G.J. Inman
Journal: British Journal of Dermatology (2020)

Recessive dystrophic epidermolysis bullosa (RDEB) is associated with a high mortality rate due to the development of life-threatening, metastatic cutaneous squamous cell carcinoma (cSCC). Elevated transforming growth factor-beta (TGF-β) signalling is implicated in cSCC development and progression in patients with RDEB.
Update of the simplified criteria for autoimmune hepatitis: Evaluation of the methodology for immunoserological testing
Authors: Johanna Galaski, Christina Weiler-Normann, Miriam Schakat, Kalliopi Zachou, Paolo Muratori, Sibylle Lampalzer, Friedrich Haag, Christoph Schramm, Marco Lenzi, George N. Dalekos, Ansgar W. Lohse
Journal: Journal of Hepatology (2020)
Association of Family Income and Risk of Food Insecurity With Iron Status in Young Children
Authors: Imaan Bayoumi, Patricia C. Parkin, Catherine S. Birken, Jonathon L. Maguire, Cornelia M. Borkhoff
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Iron deficiency (ID) has the greatest prevalence in early childhood and has been associated with poor developmental outcomes. Previous research examining associations of income and food insecurity (FI) with ID is inconsistent. <h3>Objective</h3> To examine the association of family income and family risk of FI with iron status in healthy young children attending primary care. <h3>Design, Setting, and Participants</h3> This cross-sectional study included 1245 children aged 12 to 29 months who attended scheduled primary care supervision visits from 2008 to 2018 in Toronto, Canada, and the surrounding area. <h3>Exposures</h3> Family income and risk of FI were collected from parent-reported questionnaires. Children whose parents provided an affirmative response to the 1-item FI screen on the Nutrition Screening Tool for Every Toddler or at least 1 item on the 2-item Hunger Vital Sign FI screening tool were categorized as having family risk of FI. <h3>Main Outcomes and Measures</h3> Iron deficiency (serum ferritin level &lt;12 ng/mL) and ID anemia (IDA; serum ferritin level &lt;12 ng/mL and hemoglobin level &lt;11.0 g/dL). All models were adjusted for age, sex, birth weight, body mass index<i>z </i>score, C-reactive protein level, maternal education, breastfeeding duration, bottle use, cow's milk intake, and formula feeding in the first year. <h3>Results</h3> Of 1245 children (595 [47.8%] girls; median [interquartile range] age, 18.1 [13.3-24.0] months), 131 (10.5%) were from households with a family income of less than CAD $40 000 ($29 534), 77 (6.2%) were from families at risk of FI, 185 (14.9%) had ID, and 58 (5.3%) had IDA. The odds of children with a family income of less than CAD $40 000 having ID and IDA were 3 times higher than those of children in the highest family income group (ID: odds ratio [OR], 3.08; 95% CI, 1.66-5.72;<i>P</i> &lt; .001; IDA: OR, 3.28; 95% CI, 1.22-8.87;<i>P</i> = .02). Being in a family at risk of FI, compared with all other children, was not associated with ID or IDA (ID: OR, 0.43; 95% CI, 0.18-1.02;<i>P</i> = .06; IDA: OR, 0.16; 95% CI, 0.02-1.23;<i>P</i> = .08). <h3>Conclusions and Relevance</h3> In this study, low family income was associated with increased risk of ID and IDA in young children. Risk of FI was not a risk factor for ID or IDA. These findings suggest that targeting income security may be more effective than targeting access to food to reduce health inequities in the prevention of iron deficiency.
Covid-19: Remdesivir probably reduces recovery time, but evidence is uncertain, panel finds
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Remdesivir probably reduces recovery time, but evidence is uncertain, panel finds Elisabeth MahaseRemdesivir may be effective in reducing recovery time of patients with severe covid-19, although the certainty of the evidence is low, a panel of international experts has concluded. 11
GMM-Demux: sample demultiplexing, multiplet detection, experiment planning, and novel cell-type verification in single cell sequencing
Authors: Hongyi Xin, Qiuyu Lian, Yale Jiang, Jiadi Luo, Xinjun Wang, Carla Erb, Zhongli Xu, Xiaoyi Zhang, Elisa Heidrich-O’Hare, Qi Yan, Richard H. Duerr, Kong Chen, Wei Chen
Journal: Genome biology (2020)

Abstract Identifying and removing multiplets are essential to improving the scalability and the reliability of single cell RNA sequencing (scRNA-seq). Multiplets create artificial cell types in the dataset. We propose a Gaussian mixture model-based multiplet identification method, GMM-Demux. GMM-Demux accurately identifies and removes multiplets through sample barcoding, including cell hashing and MULTI-seq. GMM-Demux uses a droplet formation model to authenticate putative cell types discovered from a scRNA-seq dataset. We generate two in-house cell-hashing datasets and compared GMM-Demux against three state-of-the-art sample barcoding classifiers. We show that GMM-Demux is stable and highly accurate and recognizes 9 multiplet-induced fake cell types in a PBMC dataset.
The Current Status of Psychedelics in Psychiatry
Authors: David Nutt, Robin Carhart-Harris
Journal: JAMA Psychiatry (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Abstract A10: Constitutive HIF activity enhances T-cell antitumor immunity and memory T-cell formation in the murine adoptive cell therapy model
Authors: Colette R. Lauhan, Deborah Witherden, Ilkka Liikanan, Ananda Goldrath
Journal: Cancer Research (2020)

Abstract Purpose: To determine if unrestrained hypoxia inducible factor (HIF) activity in CD8 T cells improves antitumor response. Methods: CD8 T cells were isolated from von Hippel Lindau (VHL)-deficient (VHL KO) mice, which have unrepressed HIF1 and HIF2 activity, as well as from VHL/HIF1/HIF2 triple-deficient (TKO) and WT mice. Following in vitro activation, T cells were transferred to melanoma (B16) tumor-bearing mice and monitored for tumor progression and survival. In other studies, activated VHL KO and TKO CD8 cells were mixed with WT CD8 cells and transferred to B16 or adenocarcinoma (MC38) tumor-bearing mice; after 7-10 days, donor T cells were analyzed from tumors, spleens, and draining lymph nodes (LN). Results: Single transfer of VHL KO CD8 T cells to B16 tumor-bearing mice resulted in delayed tumor growth and prolonged survival compared to transfer of CD8 T cells from TKO or WT donors. Co-transfer of VHL KO cells with WT cells into B16 tumor-bearing mice resulted in superior accumulation of VHL KO cells in all tissues including tumors. In contrast, mixed transfer of TKO cells with WT cells to B16 tumor-bearing mice resulted in poorer accumulation of TKO cells in all tissues including tumors. VHL KO tumor-infiltrating lymphocytes (TILs) had superior expression of tissue resident memory (TRM) phenotype markers CD103 and CD69 compared to WT and TKO TILs. Similarly in the MC38 tumor model, VHL KO cells showed improved accumulation in all tissues compared to WT cells. Conclusions: Here we demonstrate that VHL deletion in CD8 T cells results in superior efficacy in delaying tumor growth and improving recipient survival, greater accumulation in multiple solid tumor models, and increased development of the TRM phenotype. Further, TKO recipients demonstrated increased tumor growth, reduced survival, reduced TIL numbers, and absence of TRM phenotype following adoptive transfer, confirming the HIF dependency of the VHL-deletion phenotype. Taken together, these data demonstrate that T cells with constitutive HIF activity provide a more robust antitumor response. Therefore, manipulation of HIF regulation could offer new tools for enhanced T-cell efficacy in adoptive cellular therapy for solid tumors. Citation Format: Colette R. Lauhan, Deborah Witherden, Ilkka Liikanan, Ananda Goldrath. Constitutive HIF activity enhances T-cell antitumor immunity and memory T-cell formation in the murine adoptive cell therapy model [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A10.
Impact of Genemutations and Dynamics Methylation of CDKN2B and DLC-1 Promoters on Treatment Response with Azacitidine
Authors: Iván Martín, Alicia Serrano, Blanca Navarro, Eva Villamón, Pilar Rentero-Garrido, Fernando Domingo, Javier F Chaves, Victoria Adam, Paula Amat, Marisa Calabuig, Francisca García, Carlos Solano, Mar Tormo
Journal: Blood (2017)
Abstract 14408: Are Primary Care Providers Meeting Guidelines for Stroke Prevention in Atrial Fibrillation?
Authors: Jafna L Cox, Ratika Parkash, Laura Hamilton, Lehana Thabane, Gary Foster, James MacKillop, Feng Xie, Antonio Ciaccia, Shurjeel Choudhri, Joanna Nemis-White
Journal: Circulation (2019)

Introduction: Clinical guidelines recommend that all patients with atrial fibrillation [AF] aged >=65 receive appropriate oral anticoagulant [OAC] therapy to prevent stroke. Under 65 years, the pre...
Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality (vol 33, pg 1078, 2018)
Authors: E. Gogola, A.A. Duarte, J.R. de Ruiter, W.W. Wiegant, J.A. Schmid, R. de Bruijn, D.I. James, S.G. Llobet, D.J. Vis, S. Annunziato, B. van den Broek, M. Barazas, A. Kersbergen, M. van de Ven, M. Tarsounas, D.J. Ogilvie, M. van Vugt, L.F.A. Wessels, J. Bartkova, I. Gromova, M. Andujar-Sanchez, J. Bartek, M. Lopes, H. van Attikum, P. Borst, J. Jonkers, S. Rottenberg
Journal: Cancer Cell (2019)
Flushing, Vomiting, and Abdominal Pain Following Abdominal Ultrasonography
Authors: Ramtin Rahmani, Philipp W. Raess, Nima Nabavizadeh
Journal: JAMA Oncology (2020)

A man in his 40s presents with back and abdominal pain associated with nausea, vomiting, and flushing; imaging and biopsy findings show a thoracic paraspinal mass with dense cellular infiltrate. What is your diagnosis?
A four-protein metabolon assembled by a small peptide protein creates the pentacyclic carbonate ring of aldgamycins
Authors: Qiaozhen Wang, Xiaolong Tang, Ping Dai, Chuanxi Wang, Weiyang Zhang, Guodong Chen, Kui Hong, Dan Hu, Hao Gao, Xinsheng Yao
Journal: Acta Pharmaceutica Sinica B (2020)

Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII–UV) assembled by a small peptide protein (AlmUV) appends a reactive N-hydroxylcarbamoyl moiety to the decarboxylated aldgamycins followed by a non-enzymatic condensation to give the pentacyclic carbonate ring. Our results have documented an unprecedent mechanism for carbonate formation.
OP0201 INCREASED RISK OF DEMENTIA IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: J. Lee, Y. Eun, I. Y. Kim, K. D. Han, D. H. Kim, S. Y. Kang, S. Lee, H. S. Cha, E. M. Koh, H. Kim
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect any organ of the body. Nervous system involvement of SLE lead to a variety of neurologic and psychiatric manifestations, which are called neuropsychiatric lupus. Cognitive dysfunction may appear as part of neuropsychiatric lupus. There are several papers on the increase in dementia risk in SLE patients, but data are not sufficient and there is little data on whether SLE affects dementia differently depending on the dementia subtype. Objectives: We evaluate dementia incidence and risk in SLE patients in a nationwide population-based cohort and determine whether the risk is different for each dementia subtype. Methods: We identified patients aged 40 years or more, with systemic lupus erythematosus between 2008 and 2014 using the database of the National Health Insurance Service (NHIS) of south Korea. Patients who had previously been diagnosed with dementia were excluded from the study. A total of 11,288 SLE patients and 56,440 control subjects with a 1:5 age- and sex-matching were included in the study. The primary outcome of the study was incident dementia, which was defined by an ICD-10 code and the use of dementia medications. Kaplan-Meier curves and Cox proportional hazards regression analysis were used for the analysis. Results: The incidence rate of dementia was higher in SLE cohort (3.90 per 1,000 person-years) than control cohort (2.73 per 1,000 person-years). Incidence rates of Alzheimer disease and vascular dementia were also higher in SLE cohort than control. SLE patients had a higher risk of dementia compared to control cohorts without SLE (crude hazard ratio 1.43, 95% CI 1.25-1.63). In patients with SLE, the risk of Alzheimer’s disease was 1.4 times higher and the risk of vascular dementia 1.6 times higher than non-SLE control. Conclusion: In this nationwide population-based cohort study, SLE patients had a 1.4-fold higher risk of incident dementia compared to patients without SLE. Further studies are warranted to identify mechanisms of increased risk of dementia in SLE patients. Monitoring of dementia incidence in SLE patients is needed in clinical practice. Disclosure of Interests: None declared
BACES Score for Predicting Mortality in Nontuberculous Mycobacterial Pulmonary Disease
Authors: Hyung-Jun Kim, Nakwon Kwak, Hyunsook Hong, Noeul Kang, Yunjoo Im, Byung Woo Jhun, Jae-Joon Yim
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Because the prognosis of nontuberculous mycobacterial pulmonary disease varies, a scoring system predicting mortality is needed.Objectives: We aimed to develop a novel scoring system to predict mortality among patients with nontuberculous mycobacterial pulmonary disease.Methods: We included patients age ≥20 years with newly diagnosed nontuberculous mycobacterial pulmonary disease, with Mycobacterium avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense. Cox proportional hazards models were used to identify predictors of mortality in a derivation cohort, and a scoring system was developed. It was validated in an independent prospective cohort.Measurements and Main Results: A total 1,181 and 377 patients were included in the derivation and validation cohorts, respectively. In the final model, body mass index <18.5 kg/m2 (1 point), age ≥65 years (1 point), presence of cavity (1 point), elevated erythrocyte sedimentation rate (1 point), and male sex (1 point) were selected as predictors for mortality. We named this novel scoring system BACES (body mass index, age, cavity, erythrocyte sedimentation rate, and sex). Harrell's C-index for the BACES score was 0.812 (95% confidence interval, 0.786-0.837) in the derivation cohort and 0.854 (95% confidence interval, 0.797-0.911) in the validation cohort, indicating excellent discrimination performance. The estimated 5-year risk of mortality was 1.2% with BACES score 0 and 82.9% with BACES score 5.Conclusions: We developed the BACES score, which could accurately predict mortality among patients with nontuberculous mycobacterial pulmonary disease caused by M. avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense.