tbuckley/cabot-search huggingface dataset:
Gut microbes participate in food preference alterations during obesity
Authors: Alice de Wouters d’Oplinter, Marialetizia Rastelli, Matthias Van Hul, Nathalie M. Delzenne, Patrice D. Cani, Amandine Everard
Journal: Gut Microbes (2021)

Hypothalamic regulations of food intake are altered during obesity. The dopaminergic mesocorticolimbic system, responsible for the hedonic response to food intake, is also affected. Gut microbes are other key players involved in obesity. Therefore, we investigated whether the gut microbiota plays a causal role in hedonic food intake alterations contributing to obesity. We transferred fecal material from lean or diet-induced obese mice into recipient mice and evaluated the hedonic food intake using a food preference test comparing the intake of control and palatable diets (HFHS, High-Fat High-Sucrose) in donor and recipient mice. Obese mice ate 58% less HFHS during the food preference test (p < 0.0001) than the lean donors, suggesting a dysregulation of the hedonic food intake during obesity. Strikingly, the reduction of the pleasure induced by eating during obesity was transferable through gut microbiota transplantation since obese gut microbiota recipient mice exhibited similar reduction in HFHS intake during the food preference test (40% reduction as compared to lean gut microbiota recipient mice, p < 0.01). This effect was associated with a consistent trend in modifications of dopaminergic markers expression in the striatum. We also pinpointed a highly positive correlation between HFHS intake and Parabacteroides (p < 0.0001), which could represent a potential actor involved in hedonic feeding probably through the gut-to-brain axis. We further demonstrated the key roles played by gut microbes in this paradigm since depletion of gut microbiota using broad-spectrum antibiotics also altered HFHS intake during food preference test in lean mice. In conclusion, we discovered that gut microbes regulate hedonic aspects of food intake. Our data demonstrate that gut microbiota modifications associated with obesity participate in dysregulations of the reward and hedonic components of the food intake. These data provide evidence that gut microbes could be an interesting therapeutic target to tackle hedonic disorders related to obesity.
Breakthrough Infections in BNT162b2-Vaccinated Health Care Workers
Authors: Bettina Lange, Marlis Gerigk, Tobias Tenenbaum
Journal: New England Journal of Medicine (2021)

Breakthrough SARS-CoV-2 Infections in Health Care Workers In a German study, 4 health care workers out of 1137 (0.35%) who had received one of the mRNA SARS-CoV-2 vaccines had mildly symptomatic Co...
Trends in Hospital Lawsuits Filed Against Patients for Unpaid Bills Following Published Research About This Activity
Authors: Joseph Giuseppe R. Paturzo, Farah Hashim, Chen Dun, Michael J. Boctor, William E. Bruhn, Christi Walsh, Ge Bai, Martin A. Makary
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Suing patients and garnishing their wages for unpaid medical bills can be a predatory form of financial activity that may be inconsistent with the mission of a hospital. Many hospitals in the state of Virginia were discovered to be suing patients for unpaid medical bills, as first presented in a 2019 research article that launched 2.5 months of media attention on hospital billing practices and a grassroots public demand for hospitals to stop the practice. <h3>Objective</h3> To evaluate the association of a research publication and subsequent media coverage with the number of hospital lawsuits filed against patients for unpaid medical bills. <h3>Design, Setting, and Participants</h3> This cross-sectional study of Virginia hospitals that sued patients for unpaid medical bills used an interrupted time series analysis. Data on hospitals suing patients for unpaid medical bills were collected during a preintervention period (June 25, 2018, to June 24, 2019), an intervention period (June 25, 2019, to September 10, 2019), and a postintervention period (September 11, 2019, to September 10, 2020). <h3>Exposures</h3> Publication of a research article and subsequent media coverage. <h3>Main Outcomes and Measures</h3> The total number of warrant in debt and wage garnishment lawsuits filed by Virginia hospitals and the frequency of those lawsuits filed before, during, and after the intervention period on a weekly basis. <h3>Results</h3> A total of 50 387 lawsuits, filed by 67 Virginia hospitals, were included; 33 204 (65.9%) were warrant in debt lawsuits, and 17 183 (34.1%) were wage garnishment lawsuits. From the preintervention period to the postintervention period, there was a 59% decrease in the number of lawsuits filed (from 30 760 lawsuits to 12 510 lawsuits), a 55% decrease in the number of warrant in debt cases filed (from 19 329 to 8651), a 66% decrease in the number of wage garnishments filed (from 11 431 to 3859), and a 64% decrease in the dollar amount pursued in court (from $38 700 209 to $13 960 300). During the study period, 11 hospitals banned the practice of suing patients for unpaid medical bills. The interrupted time series analysis showed a significant decrease of 5% (incidence rate ratio, 0.95; 95% CI, 0.94-0.96) in the total weekly number of lawsuits in the postintervention period. <h3>Conclusions and Relevance</h3> The findings of this study suggest that research leading to public awareness can shift hospital billing practices.
26292 Rapid improvement in skin pain, and its impact on quality of life, in adult patients with moderate-to-severe atopic dermatitis from a double-blind, placebo-controlled baricitinib phase 3 study
Authors: David Rosmarin, Scott Fretzin, Lindsay Strowd, Marta Casillas, Amy DeLozier, Zach Dawson, Sherry Chen, Na Lu, Jacob P. Thyssen
Journal: Journal of the American Academy of Dermatology (2021)
Gender Differences in the Pursuit of Cardiac Electrophysiology Training in North America
Authors: Nashwa Abdulsalam, Anne M. Gillis, Anne K. Rzeszut, Celina M. Yong, Claire S. Duvernoy, Marie-Noelle Langan, Kristin West, Poonam Velagapudi, Sena Killic, Edward L. O’Leary
Journal: Journal of the American College of Cardiology (2021)

Despite the increase in the number of female physicians across most specialties within cardiology, <10% of clinical cardiac electrophysiology (EP) fellows are women. This study sought to determine the factors that influence fellows-in-training (FITs) to pursue EP as a career choice and whether this differs by gender. The authors conducted an online multiple-choice survey through the American College of Cardiology to assess the decision factors that influence FITs in the United States and Canada to pursue cardiovascular subspecialties. A total of 933 (30.5%) FITs completed the survey; 129 anticipated specializing in EP, 259 in interventional cardiology (IC), and 545 in a different field or were unsure. A total of 1 in 7 (14%) FITs indicated an interest in EP. Of this group, more men chose EP than women (84% vs 16%; P < 0.001). The most important factor that influenced FITs to pursue EP was a strong interest in the field. Women were more likely to be influenced by having a female role model (P = 0.001) compared with men. After excluding FITs interested in IC, women who deselected EP were more likely than men to be influenced by greater interest in another field (P = 0.004), radiation concerns (P = 0.001), lack of female role models (P = 0.001), a perceived "old boys' club" culture (P = 0.001) and discrimination/harassment concerns (P = 0.001). Women are more likely than men to be negatively influenced by many factors when it comes to pursuing EP as a career choice. Addressing those factors will help decrease the gender disparity in the field.
28171 Assessing long-term maintenance of efficacy with tralokinumab monotherapy in patients with moderate-to-severe atopic dermatitis: Combined results from two phase 3, randomized, double-blind, placebo-controlled trials (ECZTRA 1 and 2)
Authors: Andrew Blauvelt, Andreas Wollenberg, Andrew Pink, Ketty Peris, April Armstrong, Lynda Spelman, Hidehisa Saeki, Charles Lynde, Pedro Herranz, Sebastien Barbarot, Eric Simpson
Journal: Journal of the American Academy of Dermatology (2021)
Reframing anorexia nervosa as a metabo-psychiatric disorder
Authors: Cynthia M. Bulik, Ian M. Carroll, Phil Mehler
Journal: Trends in Endocrinology and Metabolism (2021)

Anorexia nervosa (AN) is a serious and often fatal illness. Despite decades of research, investigators have failed to adequately advance our understanding of the biological aspects of AN that could inform the development of effective interventions. Genome-wide association studies are revealing the important role of metabolic factors in AN, and studies of the gastrointestinal tract are shedding light on disruptions in enteric microbial communities and anomalies in gut morphology. In this opinion piece, we review the state of the science through the lens of the clinical presentation of illness. We project how the integration of rigorous science in genomics and microbiology, in collaboration with experienced clinicians, has the potential to markedly enhance treatment outcome via precision interventions.
Genomic Landscape and Tumor Mutational Burden Determination of Circulating Tumor DNA in Over 5,000 Chinese Patients with Lung Cancer
Authors: Jie Shi, Zhiyu Wang, Junping Zhang, Yaping Xu, Xiao Xiao, Xiangming Quan, Ying Bai, Xia Yang, Zongjuan Ming, Xiaojin Guo, Huijing Feng, Xiaoling Yang, Xiaofei Zhuang, Fei Han, Kai Wang, Yonglei Shi, Yu Lei, Jun Bai, Shuanying Yang
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Having emerged as a noninvasive and clinically applicable approach for molecular determination of lung cancer, a genomic overview of circulating tumor DNA (ctDNA) of large-scale cohort may be helpful in novel biomarker development and therapeutic innovation. Experimental Design: Primary cohort encompasses 5,671 blood samples from 4,892 patients with lung cancer. Pair-wise tissue samples from 579 patients and additional 358 sample pairs were collected to evaluate the correlation between blood and tissue tumor mutational burden (TMB). Parallel sequencing with plasma/tissue and white blood cells was performed using a 1,021-gene panel. Results: Histologic subtyping was the most relevant to ctDNA detectability independent of other demographic characteristics, with small cell lung cancer showing the highest detectability, ctDNA abundance, and blood TMB (bTMB). Mutational landscape demonstrated significant differences, and integrated clonality analysis highlighted distinct driver-pattern and functional pathway interaction among various subtypes. The clonality and concurrent genes of EGFR mutations could predict the therapeutic efficacy of tyrosine kinase inhibitors (TKI), and RB1 mutations in non–small cell lung cancer characterized a subset with high bTMB, elevated ctDNA level, and potential small cell transformation. Most importantly, we developed an adjusted algorithm for bTMB in samples with extremely low ctDNA level and validated its correlation with tissue TMB in an independent cohort. Conclusions: ctDNA could serve as a promising alternative in genomic profiling for lung cancer. The novel identification of ctDNA clonality and adjusted bTMB might improve therapeutic and prognostic evaluation. This dataset was also a valuable resource for the development of new therapeutic targets and new genomically guided clinical trials.
Chromatin interaction neural network (ChINN): a machine learning-based method for predicting chromatin interactions from DNA sequences
Authors: Fan Cao, Yu Zhang, Yichao Cai, Sambhavi Animesh, Ying Zhang, Semih Can Akincilar, Yan Ping Loh, Xinya Li, Wee Joo Chng, Vinay Tergaonkar, Chee Keong Kwoh, Melissa J. Fullwood
Journal: Genome biology (2021)

Chromatin interactions play important roles in regulating gene expression. However, the availability of genome-wide chromatin interaction data is limited. We develop a computational method, chromatin interaction neural network (ChINN), to predict chromatin interactions between open chromatin regions using only DNA sequences. ChINN predicts CTCF- and RNA polymerase II-associated and Hi-C chromatin interactions. ChINN shows good across-sample performances and captures various sequence features for chromatin interaction prediction. We apply ChINN to 6 chronic lymphocytic leukemia (CLL) patient samples and a published cohort of 84 CLL open chromatin samples. Our results demonstrate extensive heterogeneity in chromatin interactions among CLL patient samples.
26237 Baricitinib, an oral, reversible Janus kinase-1 and -2 inhibitor, for atopic dermatitis: Head and neck response from BREEZE-AD5
Authors: Robert Bissonnette, Neil Korman, Benjamin Lockshin, Na Lu, Yun-Fei Chen, Orin Goldblum, José Rueda, Yves Poulin
Journal: Journal of the American Academy of Dermatology (2021)
28400 Retrospective analysis of dermatology residency applicant’s research output from 2007-2018
Authors: Jatin Narang, Anna Eversman, Mehak Kalra, Frederick Morgan, Elizabeth Obi, Emma R. Russell, Angela H. Wei, David X. Zheng, Wilhemina Osei-Koomson, Bryan T. Carroll, Timmie R. Sharma
Journal: Journal of the American Academy of Dermatology (2021)
26197 Efficacy and safety of risankizumab vs methotrexate in patients with moderate-to-severe plaque psoriasis: Results from the 28-week randomized, double-blind period of an ongoing phase 3 study in Brazil
Authors: Tania F. Cestari, Cacilda daSilva Souza, Luna Azulay-Abulafia, Ricardo Romiti, André V.E. Carvalho, Caio César Silva de Castro, Silvio Alencar Marques, João Roberto Antonio, Lincoln Fabrício, Jasmina Kalabic, Luiza Keiko Oyafuso
Journal: Journal of the American Academy of Dermatology (2021)
Inferring the dynamics of mutated hematopoietic stem and progenitor cells induced by IFNα in myeloproliferative neoplasms
Authors: Matthieu Mosca, Gurvan Hermange, Amandine Tisserand, Robert Noble, Christophe Marzac, Caroline Marty, Cécile Le Sueur, Hugo Campario, Gaëlle Vertenoeil, Mira El-Khoury, Cyril Catelain, Philippe Rameau, Cyril Gella, Julien Lenglet, Nicole Casadevall, Rémi Favier, Eric Solary, Bruno Cassinat, Jean-Jacques Kiladjian, Stefan N. Constantinescu, Florence Pasquier, Michael E. Hochberg, Hana Raslova, Jean-Luc Villeval, François Girodon, William Vainchenker, Paul-Henry Cournède, Isabelle Plo
Journal: Blood (2021)
Humoral immunity in atherosclerosis and myocardial infarction: from B cells to antibodies
Authors: Florentina Porsch, Ziad Mallat, Christoph J Binder
Journal: Cardiovascular Research (2021)

Immune mechanisms are critically involved in the pathogenesis of atherosclerosis and its clinical manifestations. Associations of specific antibody levels and defined B-cell subsets with cardiovascular disease activity in humans as well as mounting evidence from preclinical models demonstrate a role of B cells and humoral immunity in atherosclerotic cardiovascular disease. These include all aspects of B-cell immunity, the generation of antigen-specific antibodies, antigen presentation and co-stimulation of T cells, as well as production of cytokines. Through their impact on adaptive and innate immune responses and the regulation of many other immune cells, B cells mediate both protective and detrimental effects in cardiovascular disease. Several antigens derived from (oxidized) lipoproteins, the vascular wall and classical autoantigens have been identified. The unique antibody responses they trigger and their relationship with atherosclerotic cardiovascular disease are reviewed. In particular, we focus on the different effector functions of specific IgM, IgG, and IgE antibodies and the cellular responses they trigger and highlight potential strategies to target B-cell functions for therapy.
Molecular Subtyping Combined with Biological Pathway Analyses to Study Regorafenib Response in Clinically Relevant Mouse Models of Colorectal Cancer
Authors: Adam Lafferty, Alice C. O'Farrell, Giorgia Migliardi, Niraj Khemka, Andreas U. Lindner, Francesco Sassi, Eugenia R. Zanella, Manuela Salvucci, Evy Vanderheyden, Elodie Modave, Bram Boeckx, Luise Halang, Johannes Betge, Matthias P.A. Ebert, Patrick Dicker, Guillem Argilés, Josep Tabernero, Rodrigo Dienstmann, Enzo Medico, Diether Lambrechts, Andrea Bertotti, Claudio Isella, Livio Trusolino, Jochen H.M. Prehn, Annette T. Byrne
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Regorafenib (REG) is approved for the treatment of metastatic colorectal cancer, but has modest survival benefit and associated toxicities. Robust predictive/early response biomarkers to aid patient stratification are outstanding. We have exploited biological pathway analyses in a patient-derived xenograft (PDX) trial to study REG response mechanisms and elucidate putative biomarkers. Experimental Design: Molecularly subtyped PDXs were annotated for REG response. Subtyping was based on gene expression (CMS, consensus molecular subtype) and copy-number alteration (CNA). Baseline tumor vascularization, apoptosis, and proliferation signatures were studied to identify predictive biomarkers within subtypes. Phospho-proteomic analysis was used to identify novel classifiers. Supervised RNA sequencing analysis was performed on PDXs that progressed, or did not progress, following REG treatment. Results: Improved REG response was observed in CMS4, although intra-subtype response was variable. Tumor vascularity did not correlate with outcome. In CMS4 tumors, reduced proliferation and higher sensitivity to apoptosis at baseline correlated with response. Reverse phase protein array (RPPA) analysis revealed 4 phospho-proteomic clusters, one of which was enriched with non-progressor models. A classification decision tree trained on RPPA- and CMS-based assignments discriminated non-progressors from progressors with 92% overall accuracy (97% sensitivity, 67% specificity). Supervised RNA sequencing revealed that higher basal EPHA2 expression is associated with REG resistance. Conclusions: Subtype classification systems represent canonical “termini a quo” (starting points) to support REG biomarker identification, and provide a platform to identify resistance mechanisms and novel contexts of vulnerability. Incorporating functional characterization of biological systems may optimize the biomarker identification process for multitargeted kinase inhibitors.
Disparities in Excess Mortality Associated with COVID-19 — United States, 2020
Authors: Lauren M. Rossen, Farida B. Ahmad, Robert N. Anderson, Amy M. Branum, Chengan Du, Harlan M. Krumholz, Shu-Xia Li, Zhenqiu Lin, Andrew Marshall, Paul D. Sutton, Jeremy S. Faust
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

The COVID-19 pandemic has disproportionately affected Hispanic or Latino, non-Hispanic Black (Black), non-Hispanic American Indian or Alaska Native (AI/AN), and non-Hispanic Native Hawaiian or Other Pacific Islander (NH/PI) populations in the United States. These populations have experienced higher rates of infection and mortality compared with the non-Hispanic White (White) population (1-5) and greater excess mortality (i.e., the percentage increase in the number of persons who have died relative to the expected number of deaths for a given place and time) (6). A limitation of existing research on excess mortality among racial/ethnic minority groups has been the lack of adjustment for age and population change over time. This study assessed excess mortality incidence rates (IRs) (e.g., the number of excess deaths per 100,000 person-years) in the United States during December 29, 2019-January 2, 2021, by race/ethnicity and age group using data from the National Vital Statistics System. Among all assessed racial/ethnic groups (non-Hispanic Asian [Asian], AI/AN, Black, Hispanic, NH/PI, and White populations), excess mortality IRs were higher among persons aged ≥65 years (426.4 to 1033.5 excess deaths per 100,000 person-years) than among those aged 25-64 years (30.2 to 221.1) and those aged <25 years (-2.9 to 14.1). Among persons aged <65 years, Black and AI/AN populations had the highest excess mortality IRs. Among adults aged ≥65 years, Black and Hispanic persons experienced the highest excess mortality IRs of >1,000 excess deaths per 100,000 person-years. These findings could help guide more tailored public health messaging and mitigation efforts to reduce disparities in mortality associated with the COVID-19 pandemic in the United States,* by identifying the racial/ethnic groups and age groups with the highest excess mortality rates.
26581 Maintenance of complete skin clearance throughout 3 years of continuous guselkumab treatment in patients with moderate-to-severe psoriasis: A post hoc analysis of 5-year data from the VOYAGE 1 trial
Authors: Antonio Costanzo, Curdin Conrad, Talia Gramiccia, Maria Jazra, Elke M.G. J. de Jong, Lars Iversen, Bülent Öztürk, Robert Wapenaar, Sven Wegner, Tiago Torres, Luis Puig
Journal: Journal of the American Academy of Dermatology (2021)
A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope
Authors: Laura A. VanBlargan, Lucas J. Adams, Zhuoming Liu, Rita E. Chen, Pavlo Gilchuk, Saravanan Raju, Brittany K. Smith, Haiyan Zhao, James Brett Case, Emma S. Winkler, Bradley M. Whitener, Lindsay Droit, Ishmael D. Aziati, Traci L. Bricker, Astha Joshi, Pei-Yong Shi, Adrian Creanga, Amarendra Pegu, Scott A. Handley, David Wang, Adrianus C.M. Boon, James E. Crowe, Sean P.J. Whelan, Daved H. Fremont, Michael S. Diamond
Journal: Immunity (2021)
27891 Safety and efficacy of an Avena sativa (oat) skin care regimen for therapy-related xerosis and pruritus in adult oncology patients undergoing systemic cancer treatments
Authors: Judith Nebus, Adegboyega Adenaike, Tony McGuire, Toni Anne Lisante, Lisa Caratelli, Neena K. Tierney, Oluwaseun Kukoyi, Thomas Brinkman, Kwami Ketosugbo, Sarah Noor, Mario E. Lacouture
Journal: Journal of the American Academy of Dermatology (2021)
Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network
Authors: Zhonghua Du, Xue Wen, Yichen Wang, Lin Jia, Shilin Zhang, Yudi Liu, Lei Zhou, Hui Li, Wang Yang, Cong Wang, Jingcheng Chen, Yajing Hao, Daniela Salgado Figueroa, Huiling Chen, Dan Li, Naifei Chen, Ilkay Celik, Yanbo Zhu, Zi Yan, Changhao Fu, Shanshan Liu, Benzheng Jiao, Zhuo Wang, Hui Zhang, Günhan Gülsoy, Jianjun Luo, Baoming Qin, Sujun Gao, Philipp Kapranov, Miguel A. Esteban, Songling Zhang, Wei Li, Ferhat Ay, Runsheng Chen, Andrew R. Hoffman, Jiuwei Cui, Ji-Fan Hu
Journal: Genome biology (2021)

A specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate this architectural remodeling, we used a novel chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to profile long noncoding RNAs (lncRNAs) in the Oct4 promoter.