tbuckley/cabot-search huggingface dataset:
Not All Secondary Mitral Regurgitation Is the Same—Potential Phenotypes and Implications for Mitral Repair
Authors: Yogesh N. V. Reddy, Rick A. Nishimura
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Modified Positive and Negative Syndrome Scale—A Journey of a Thousand Miles Starts With the First Step
Authors: Mark G. A. Opler, Yifeng Shen
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
Fibrotic Response to Neoadjuvant Therapy Predicts Survival in Pancreatic Cancer and Is Measurable with Collagen-Targeted Molecular MRI
Authors: Derek J. Erstad, Mozhdeh Sojoodi, Martin S. Taylor, Veronica Clavijo Jordan, Christian T. Farrar, Andrea L. Axtell, Nicholas J. Rotile, Chloe Jones, Katherine A. Graham-O'Regan, Diego S. Ferreira, Theodoros Michelakos, Filippos Kontos, Akhil Chawla, Shen Li, Sarani Ghoshal, Yin-Ching Iris Chen, Gunisha Arora, Valerie Humblet, Vikram Deshpande, Motaz Qadan, Nabeel Bardeesy, Cristina R. Ferrone, Michael Lanuti, Kenneth K. Tanabe, Peter Caravan, Bryan C. Fuchs
Journal: Clinical Cancer Research (2020)

Abstract Purpose: To evaluate the prognostic value of posttreatment fibrosis in human PDAC patients, and to compare a type I collagen targeted MRI probe, CM-101, to the standard contrast agent, Gd-DOTA, for their abilities to identify FOLFIRINOX-induced fibrosis in a murine model of PDAC. Experimental Design: Ninety-three chemoradiation-treated human PDAC samples were stained for fibrosis and outcomes evaluated. For imaging, C57BL/6 and FVB mice were orthotopically implanted with PDAC cells and FOLFIRINOX was administered. Mice were imaged with Gd-DOTA and CM-101. Results: In humans, post-chemoradiation PDAC tumor fibrosis was associated with longer overall survival (OS) and disease-free survival (DFS) on multivariable analysis (OS P = 0.028, DFS P = 0.047). CPA increased the prognostic accuracy of a multivariable logistic regression model comprised of previously established PDAC risk factors [AUC CPA (−) = 0.76, AUC CPA (+) = 0.82]. In multiple murine orthotopic PDAC models, FOLFIRINOX therapy reduced tumor weight (P &amp;lt; 0.05) and increased tumor fibrosis by collagen staining (P &amp;lt; 0.05). CM-101 MR signal was significantly increased in fibrotic tumor regions. CM-101 signal retention was also increased in the more fibrotic FOLFIRINOX-treated tumors compared with untreated controls (P = 0.027), consistent with selective probe binding to collagen. No treatment-related differences were observed with Gd-DOTA imaging. Conclusions: In humans, post-chemoradiation tumor fibrosis is associated with OS and DFS. In mice, our MR findings indicate that translation of collagen molecular MRI with CM-101 to humans might provide a novel imaging technique to monitor fibrotic response to therapy to assist with prognostication and disease management.
Author Correction: A pragmatic randomized waitlist-controlled effectiveness and cost-effectiveness trial of digital interventions for depression and anxiety
Authors: Derek Richards, Angel Enrique, Nora Eilert, Matthew Franklin, Jorge Palacios, Daniel Duffy, Caroline Earley, Judith Chapman, Grace Jell, Sarah Sollesse, Ladislav Timulak
Journal: npj Digital Medicine (2020)

[This corrects the article DOI: 10.1038/s41746-020-0293-8.].
Artificial Intelligence and Machine Learning in Computational Nanotoxicology: Unlocking and Empowering Nanomedicine
Authors: Ajay Vikram Singh, Mohammad Hasan Dad Ansari, Daniel Rosenkranz, Romi Singh Maharjan, Fabian L. Kriegel, Kaustubh Gandhi, Anurag Kanase, Rishabh Singh, Peter Laux, Andreas Luch
Journal: Advanced Healthcare Materials (2020)

Abstract Advances in nanomedicine, coupled with novel methods of creating advanced materials at the nanoscale, have opened new perspectives for the development of healthcare and medical products. Special attention must be paid toward safe design approaches for nanomaterial‐based products. Recently, artificial intelligence (AI) and machine learning (ML) gifted the computational tool for enhancing and improving the simulation and modeling process for nanotoxicology and nanotherapeutics. In particular, the correlation of in vitro generated pharmacokinetics and pharmacodynamics to in vivo application scenarios is an important step toward the development of safe nanomedicinal products. This review portrays how in vitro and in vivo datasets are used in in silico models to unlock and empower nanomedicine. Physiologically based pharmacokinetic (PBPK) modeling and absorption, distribution, metabolism, and excretion (ADME)‐based in silico methods along with dosimetry models as a focus area for nanomedicine are mainly described. The computational OMICS, colloidal particle determination, and algorithms to establish dosimetry for inhalation toxicology, and quantitative structure–activity relationships at nanoscale (nano‐QSAR) are revisited. The challenges and opportunities facing the blind spots in nanotoxicology in this computationally dominated era are highlighted as the future to accelerate nanomedicine clinical translation.
Effects of Rome IV Definitions of Functional Dyspepsia Subgroups in Secondary Care
Authors: Karen Van den Houte, Florencia Carbone, Nick Goelen, Jolien Schol, Imke Masuy, Joris Arts, Philip Caenepeel, Dirk Staessen, Philippe Vergauwe, Guy Van Roey, Pascale Latour, Hubert Piessevaux, Philippe Maldague, Ariane Gerkens, Fabien Wuestenberghs, Alain Vandenberghe, Jan Tack
Journal: Clinical Gastroenterology and Hepatology (2020)
Exosomes-mediated Transfer of miR-125a/b in Cell-to-cell Communication: A Novel Mechanism of Genetic Exchange in the Intestinal Microenvironment
Authors: Wei Cheng, Kai Wang, Zhenguo Zhao, Qi Mao, Gang Wang, Qiurong Li, Zheng Fu, Zhiwei Jiang, Jian Wang, Jieshou Li
Journal: Theranostics (2020)

Glucagon-like peptide-2 (GLP-2), a key factor in intestinal rehabilitation therapy of short bowel syndrome (SBS), may require cell-to-cell communication to exert its biological functions.However, understanding of the mechanism remains elusive.Here, we report participation of exosomal miR-125a/b in GLP-2 mediated intestinal epithelial cells-myofibroblasts cross-talk in intestinal microenvironment.Methods: The effects of GLP-2 on the proliferation and apoptosis of intestinal epithelial cells in SBS rat models were evaluated.Exosomes were extracted from residual jejunum tissue of GLP-2 or vehicle treated SBS rats using ultracentrifugation method, and identified by nanoparticle trafficking analysis (NTA), transmission electron microscopy and western blotting.miRNA sequencing combined with qRT-PCR validation were used to identify differentially expressed miRNAs.miRNAs, which might be involved in proliferation and apoptosis of intestinal epithelial cells, were screened and further verified by miRNA functional experiments.Moreover, the proliferation-promoting and anti-apoptosis effects of GLP-2 on intestinal myofibroblasts, which expressing GLP-2 receptor, and whether GLP-2 could influence the content of miRNAs in the derived exosomes were studied.The downstream pathways were explored by miRNA function recovery experiment, luciferase reporter assay, pull down experiment, knockdown and overexpression of target gene and other experiments based on the bioinformatics prediction of miRNA target gene.Results: GLP-2 significantly promoted intestinal growth, facilitated the proliferation of intestinal crypt epithelial cells and inhibited the apoptosis of intestinal villi epithelial cells in type II SBS rats.GLP-2 significantly down-regulated exosomal miR-125a/b both in residual jejunums derived exosomes and in exosomes secreted by GLP-2R positive cells.Exosomal miR-125a/b was responsible for GLP-2 mediated intestinal epithelial cells proliferation promotion and apoptosis attenuation.miR-125a/b inhibited the proliferation and promotes apoptosis of intestinal epithelial cells by suppressing the myeloid cell leukemia-1 (MCL1).Conclusions: miR-125a/b shuttled by intestinal myofibroblasts derived exosomes regulate the proliferation and apoptosis of intestinal epithelial cells.GLP-2 treatment significantly decreases the level of miR-125a/b in the exosomes of intestinal myofibroblasts.miR-125a/b modulates the proliferation and apoptosis of intestinal epithelial cells by targeting the 3'UTR region of MCL1.Hence, this study indicates a novel mechanism of genetic exchange between cells in intestinal microenvironment.
Urgent call for greater multilateralism and coordination of covid-19 trials
Authors: Ibrahim Abubakar, Rishi K Gupta, Lucy C K Bell, Marc Lipman
Journal: BMJ (2020)

Glasziou and colleagues discuss the waste in covid-19 research that amplifies pre-existing failures.1 We think the situation goes beyond waste.

Delaying publication of trial results after data have been collected and analysed is unethical. It leads to ongoing use of ineffective and potentially toxic compounds, plus avoidable and potentially harmful initiation of new studies using the same compounds. Moreover, the sheer number of small trials runs the risk of falsely finding apparent benefit, which is complicated by the potential misuse …
Abstract IA17: PARP inhibition modulates the tumor immune microenvironment in Brca1-deficient ovarian tumor
Authors: Liya Ding, Qiwei Wang, Michael Kearns, Tao Jiang, Panagiotis Konstantinopoulos, Ursula Matulonis, Jean Zhao
Journal: Clinical Cancer Research (2020)

Abstract Poly ADP ribose polymerase (PARP) inhibitors have shown promising clinical activities for patients with BRCA mutations and are changing the landscape of ovarian cancer treatment. However, the therapeutic mechanisms of action for PARP inhibition in the interaction of tumors with the tumor microenvironment and the host immune system remain unclear. We recently reported that inhibition with a PARP inhibitor (olaparib) triggers robust local and systemic antitumor immunity involving both adaptive and innate immune responses through a STING-dependent antitumor immune response in Brca1-deficient ovarian tumors. This effect is further augmented when olaparib is combined with PD-1 blockade. However, all PBM-bearing mice treated with olaparib alone or in combination with PD-1 blockade eventually succumbed to the disease. These data indicate that although multiple PARP inhibitors have been approved for the treatment of BRCA-deficient ovarian cancers, eradication of this type of cancer remains a challenge. I will discuss our recent efforts on identifying resistance mechanisms to PARP inhibition and developing potential therapeutic strategy that overcomes the resistance to improve the treatment outcome. Citation Format: Liya Ding, Qiwei Wang, Michael Kearns, Tao Jiang, Panagiotis Konstantinopoulos, Ursula Matulonis, Jean Zhao. PARP inhibition modulates the tumor immune microenvironment in Brca1-deficient ovarian tumor [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA17.
Obesity/Type 2 Diabetes-Associated Liver Tumors Are Sensitive to Cyclin D1 Deficiency
Authors: Chi Luo, Jiaxin Liang, Kfir Sharabi, Maximilian Hatting, Elizabeth A. Perry, Clint D.J. Tavares, Lipika Goyal, Amitabh Srivastava, Marc Bilodeau, Andrew X. Zhu, Piotr Sicinski, Pere Puigserver
Journal: Cancer Research (2020)

Abstract Type 2 diabetes, which is mainly linked to obesity, is associated with increased incidence of liver cancer. We have previously found that in various models of obesity/diabetes, hyperinsulinemia maintains heightened hepatic expression of cyclin D1, suggesting a plausible mechanism linking diabetes and liver cancer progression. Here we show that cyclin D1 is greatly elevated in human livers with diabetes and is among the most significantly upregulated genes in obese/diabetic liver tumors. Liver-specific cyclin D1 deficiency protected obese/diabetic mice against hepatic tumorigenesis, whereas lean/nondiabetic mice developed tumors irrespective of cyclin D1 status. Cyclin D1 dependency positively correlated with liver cancer sensitivity to palbociclib, an FDA-approved CDK4 inhibitor, which was effective in treating orthotopic liver tumors under obese/diabetic conditions. The antidiabetic drug metformin suppressed insulin-induced hepatic cyclin D1 expression and protected against obese/diabetic hepatocarcinogenesis. These results indicate that the cyclin D1–CDK4 complex represents a potential selective therapeutic vulnerability for liver tumors in obese/diabetic patients. Significance: Obesity/diabetes-associated liver tumors are specifically vulnerable to cyclin D1 deficiency and CDK4 inhibition, suggesting that the obese/diabetic environment confers cancer-selective dependencies that can be therapeutically exploited.
Medical Expenditures Attributed to Asthma and Chronic Obstructive Pulmonary Disease Among Workers — United States, 2011–2015
Authors: Girija Syamlal, Anasua Bhattacharya, Katelynn E. Dodd
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Asthma and chronic obstructive pulmonary disease (COPD) are respiratory conditions associated with a significant economic cost among U.S. adults (1,2), and up to 44% of asthma and 50% of COPD cases among adults are associated with workplace exposures (3). CDC analyzed 2011-2015 Medical Expenditure Panel Survey (MEPS) data to determine the medical expenditures attributed to treatment of asthma and COPD among U.S. workers aged ≥18 years who were employed at any time during the survey year. During 2011-2015, among the estimated 166 million U.S. workers, 8 million had at least one asthma-related medical event,* and 7 million had at least one COPD-related medical event. The annualized total medical expenditures, in 2017 dollars, were $7 billion for asthma and $5 billion for COPD. Private health insurance paid for 61% of expenditures attributable to treatment of asthma and 59% related to COPD. By type of medical event, the highest annualized per-person asthma- and COPD-related expenditures were for inpatient visits: $8,238 for asthma and $27,597 for COPD. By industry group, the highest annualized per-person expenditures ($1,279 for asthma and $1,819 for COPD) were among workers in public administration. Early identification and reduction of risk factors, including workplace exposures, and implementation of proven interventions are needed to reduce the adverse health and economic impacts of asthma and COPD among workers.
Quantile normalization of single-cell RNA-seq read counts without unique molecular identifiers
Authors: F. William Townes, Rafael A. Irizarry
Journal: Genome biology (2020)

Abstract Single-cell RNA-seq (scRNA-seq) profiles gene expression of individual cells. Unique molecular identifiers (UMIs) remove duplicates in read counts resulting from polymerase chain reaction, a major source of noise. For scRNA-seq data lacking UMIs, we propose quasi-UMIs: quantile normalization of read counts to a compound Poisson distribution empirically derived from UMI datasets. When applied to ground-truth datasets having both reads and UMIs, quasi-UMI normalization has higher accuracy than competing methods. Using quasi-UMIs enables methods designed specifically for UMI data to be applied to non-UMI scRNA-seq datasets.
Exploring the Inter-observer Agreement Among the Members of the Italian Consensus for the Classification and Reporting of Thyroid Cytology
Authors: Anna Crescenzi, Pierpaolo Trimboli, Fulvio Basolo, Andrea Frasoldati, Fabio Orlandi, Lucio Palombini, Enrico Papini, Alfredo Pontecorvi, Paolo Vitti, Michele Zini, Francesco Nardi, Guido Fadda
Journal: Endocrine Pathology (2020)
Prenatal Exposures to Perfluoroalkyl Acids and Associations with Markers of Adiposity and Plasma Lipids in Infancy: An Odense Child Cohort Study
Authors: Richard Christian Jensen, Marianne S. Andersen, Pia Veldt Larsen, Dorte Glintborg, Christine Dalgård, Clara Amalie Gade Timmermann, Flemming Nielsen, Maria Boysen Sandberg, Helle Raun Andersen, Henrik Thybo Christesen, Philippe Grandjean, Tina Kold Jensen
Journal: Environmental Health Perspectives (2020)

Perfluoroalkyl acids (PFAA) are repellants that cross the placental barrier, enabling interference with fetal programming. Maternal PFAA concentrations have been associated with offspring obesity and dyslipidemia in childhood and adulthood, but this association has not been studied in infancy.We investigated associations between maternal PFAA concentrations and repeated markers of adiposity and lipid metabolism in infancy.In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAA: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 649 women. Offspring were examined at birth (n=613) and at 3 months (n=602) and 18 months (n=503) of age. Total cholesterol, LDL, HDL, and triglyceride were evaluated at 3 months (n=262) and 18 months (n=198) of age. Mixed effects linear regression models estimated associations between PFAA and standardized (SDS) body mass index (BMI), ponderal index, and waist circumference. Associations between PFAA and body fat% (BF%) and plasma lipids SDS at 3 months and 18 months of age were investigated with linear regression models.PFNA and PFDA were associated with higher BMI SDS [adjusted β=0.26; 95% confidence interval (CI): 0.03, 0.49 and β=0.58; 95% CI: -0.03, 1.19, respectively, for 1-ng/mL increases] and ponderal index SDS (β=0.36; 95% CI: 0.13, 0.59 and β=1.02; 95% CI: 0.40, 1.64, respectively) at 3 and 18 months of age (pooled) in girls. Corresponding estimates for boys were closer to the null but not significantly different from estimates for girls. In boys and girls (combined), PFNA and PFDA were associated with BF% at age 3 months (for 1-ng/mL PFDA, β=0.40; 95% CI: 0.04, 0.75), and PFDA was associated with total cholesterol SDS at 18 months (β=1.06; 95% CI: 0.08, 2.03) (n=83).Prenatal PFAA were positively associated with longitudinal markers of adiposity and higher total cholesterol in infancy. These findings deserve attention in light of rising rates of childhood overweight conditions and dyslipidemia. https://doi.org/10.1289/EHP5184.
Genomic analysis of the domestication and post-Spanish conquest evolution of the llama and alpaca
Authors: Ruiwen Fan, Zhongru Gu, Xuanmin Guang, Juan Carlos Marín, Valeria Varas, Benito A. González, Jane C. Wheeler, Yafei Hu, Erli Li, Xiaohui Sun, Xukui Yang, Chi Zhang, Wenjun Gao, Junping He, Kasper Munch, Russel Corbett-Detig, Mario Barbato, Shengkai Pan, Xiangjiang Zhan, Michael W. Bruford, Changsheng Dong
Journal: Genome biology (2020)

Abstract Background Despite their regional economic importance and being increasingly reared globally, the origins and evolution of the llama and alpaca remain poorly understood. Here we report reference genomes for the llama, and for the guanaco and vicuña (their putative wild progenitors), compare these with the published alpaca genome, and resequence seven individuals of all four species to better understand domestication and introgression between the llama and alpaca. Results Phylogenomic analysis confirms that the llama was domesticated from the guanaco and the alpaca from the vicuña. Introgression was much higher in the alpaca genome (36%) than the llama (5%) and could be dated close to the time of the Spanish conquest, approximately 500 years ago. Introgression patterns are at their most variable on the X-chromosome of the alpaca, featuring 53 genes known to have deleterious X-linked phenotypes in humans. Strong genome-wide introgression signatures include olfactory receptor complexes into both species, hypertension resistance into alpaca, and fleece/fiber traits into llama. Genomic signatures of domestication in the llama include male reproductive traits, while in alpaca feature fleece characteristics, olfaction-related and hypoxia adaptation traits. Expression analysis of the introgressed region that is syntenic to human HSA4q21, a gene cluster previously associated with hypertension in humans under hypoxic conditions, shows a previously undocumented role for PRDM8 downregulation as a potential transcriptional regulation mechanism, analogous to that previously reported at high altitude for hypoxia-inducible factor 1α. Conclusions The unprecedented introgression signatures within both domestic camelid genomes may reflect post-conquest changes in agriculture and the breakdown of traditional management practices.