tbuckley/cabot-search huggingface dataset:
The canine gastrointestinal microbiota: early studies and research frontiers
Authors: Zongyu Huang, Zhiyuan Pan, Ruifu Yang, Yujing Bi, Xiaohui Xiong
Journal: Gut Microbes (2020)

The canine gut microbiota is a complex microbial population that is potentially related to metabolism, immunologic activity and gastrointestinal (GI) diseases. Early studies revealed that the canine gut microbiota was dynamic, and bacterial populations in the adjacent gut segments were similar, with anaerobes predominating. Metagenomics analysis revealed that nutrient contents in the diet modulated bacterial populations and metabolites in the canine gut. Further research revealed significant correlations between dietary factors and canine gut core microbiomes. Canine GI diseases are closely correlated with gut microbiota dysbiosis and metabolic disorders. Probiotic-related therapies can effectively treat canine GI diseases. Recent studies have revealed that the canine gut microbiota is similar to the human gut microbiota, and dietary factors affect both. Studying canine intestinal microorganisms enables clarifying changes in the canine intestinal bacteria under different conditions, simulating human diseases in dog models, and conducting in-depth studies of the interactions between intestinal bacteria and disease.
血管内皮過透過性は,クラークソン病(全身性毛細血管漏出症候群)の臨床症状を誘発する | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Xie Zhihui, C Ghosh Chandra, Patel Roshni, Iwaki Shoko, Gaskins Donna, Nelson Celeste, Jones Nina, R Greipp Philip, M Parikh Samir, M Druey Kirk
Journal: Blood (2012)
Targeting ATRX Loss through Inhibition of the Cell-Cycle Checkpoint Mediator WEE1
Authors: Kristina A. Cole
Journal: Cancer Research (2020)

Abstract In this issue of Cancer Research, Liang and colleagues perform a genome-wide CRISPR-Cas9–negative loss-of-function screen and identify WEE1 kinase as a therapeutic vulnerability in cells depleted of the ATRX chromatin remodeler gene. Because ATRX mutations are frequently mutated across a variety of pediatric and adult malignancies, this work may contribute to the preclinical rationale for a precision medicine trial of the WEE1 inhibitor AZD1775 (adavosertib) for patients whose tumors demonstrate ATRX loss. See related article by Liang et al., p. 510
Abstract 116: Acute and Chronic Anti-Arrhythmogenic Effect of Liposome-Encapsulated Hemoglobin (HbV) on the Myocardium Through Improving Myocardial Electrical Remodeling and the Arrhythmogenic Substrate in Hemorrhagic Shock-Induced Heart
Authors: Bonpei Takase, Yuko Higashimura, Kenichi Hashimoto
Journal: Circulation (2019)

Introduction: Prolonged blood pressure &lt; 40 mmHg in hemorrhagic shock (HS) causes irreversible heart dysfunction, “Shock Heart Syndrome” (SHS), which is associated with lethal arrhythmias (VT/VF). Methods: To investigate whether liposome-encapsulated human hemoglobin (HbV) is comparable to washed red blood cells (wRBCs) for improving arrhythmogenesis in SHS in either acute or chronic phase, optical mapping analysis (OMP), electrophysiological study (EPS) and pathological examinations were performed in Sprague-Dawley rat hearts, being obtained from both acute and chronic phase when each rat survived. The first, they were subjected to acute HS by withdrawing 30% of total blood volume. After HS, rats were immediately resuscitated by transfusing exactly same amount of 5% albumin (5%ALB, n=13), HbV (n=13), or wRBCs (n=13). All rats in chronic phase survived at least several weeks. After excising heart, OMP and EPS were performed in Langendorff-perfused hearts. Results: In both acute and chronic phase, OMP showed tendency for abnormal conduction and significantly impaired action potential duration dispersion (APDd) in left ventricle with 5%ALB (25±9 / 24±10 ms, Acute / Chronic phase). In contrast, myocardial conduction and APDd were substantially preserved with HbV (14±3 / 13±5 ms) and wRBCs (14±3 / 15±3 ms) as shown in Figure . Sustained VT/VF was easily provoked by burst pacing stimulus to left ventricle with 5%ALB. No VT/VF was induced with HbV and wRBCs. Pathology showed myocardial structural damage characterized by worse myocardial cell damage and Connexin43 with 5%ALB, whereas it was attenuated with HbV and wRBCs in both acute and chronic phase. Conclusions: Ventricular structural remodeling after HS causes VT/VF in the presence of APDd. Transfusion of HbV prevents acutely and chronically VT/VF, similarly to transfusion of wRBCs, by preventing chronic electrical remodeling of APDd and preserving myocardial structures in HS-induced SHS
Dysfunctional polycomb transcriptional repression contributes to lamin A/C–dependent muscular dystrophy
Authors: Andrea Bianchi, Chiara Mozzetta, Gloria Pegoli, Federica Lucini, Sara Valsoni, Valentina Rosti, Cristiano Petrini, Alice Cortesi, Francesco Gregoretti, Laura Antonelli, Gennaro Oliva, Marco De Bardi, Roberto Rizzi, Beatrice Bodega, Diego Pasini, Francesco Ferrari, Claudia Bearzi, Chiara Lanzuolo
Journal: Journal of Clinical Investigation (2020)

Lamin A is a component of the inner nuclear membrane that, together with epigenetic factors, organizes the genome in higher order structures required for transcriptional control. Mutations in the lamin A/C gene cause several diseases belonging to the class of laminopathies, including muscular dystrophies. Nevertheless, molecular mechanisms involved in the pathogenesis of lamin A–dependent dystrophies are still largely unknown. The polycomb group (PcG) of proteins are epigenetic repressors and lamin A interactors, primarily involved in the maintenance of cell identity. Using a murine model of Emery-Dreifuss muscular dystrophy (EDMD), we show here that lamin A loss deregulated PcG positioning in muscle satellite stem cells, leading to derepression of non–muscle-specific genes and p16INK4a, a senescence driver encoded in the Cdkn2a locus. This aberrant transcriptional program caused impairment in self-renewal, loss of cell identity, and premature exhaustion of the quiescent satellite cell pool. Genetic ablation of the Cdkn2a locus restored muscle stem cell properties in lamin A/C–null dystrophic mice. Our findings establish a direct link between lamin A and PcG epigenetic silencing and indicate that lamin A–dependent muscular dystrophy can be ascribed to intrinsic epigenetic dysfunctions of muscle stem cells.
Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development
Authors: Jin Huk Choi, Xue Zhong, Zhao Zhang, Lijing Su, William McAlpine, Takuma Misawa, Tzu-Chieh Liao, Xiaoming Zhan, Jamie Russell, Sara Ludwig, Xiaohong Li, Miao Tang, Priscilla Anderton, Eva Marie Y. Moresco, Bruce Beutler
Journal: The Journal of Experimental Medicine (2020)

In a forward genetic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice for aberrant immune function, we identified mice with a syndromic disorder marked by growth retardation, diabetes, premature death, and severe lymphoid and myeloid hypoplasia together with diminished T cell-independent (TI) antibody responses. The causative mutation was in Pdia6, an essential gene encoding protein disulfide isomerase A6 (PDIA6), an oxidoreductase that functions in nascent protein folding in the endoplasmic reticulum. The immune deficiency caused by the Pdia6 mutation was, with the exception of a residual T cell developmental defect, completely rescued in irradiated wild-type recipients of PDIA6-deficient bone marrow cells, both in the absence or presence of competition. The viable hypomorphic allele uncovered in these studies reveals an essential role for PDIA6 in hematopoiesis, but one extrinsic to cells of the hematopoietic lineage. We show evidence that this role is in the proper folding of Wnt3a, BAFF, IL-7, and perhaps other factors produced by the extra-hematopoietic compartment that contribute to the development and lineage commitment of hematopoietic cells.
Antigen Experienced T Cells from Peripheral Blood Recognize p53 Neoantigens
Authors: Parisa Malekzadeh, Rami Yossef, Gal Cafri, Biman C. Paria, Frank J. Lowery, Mohammad Jafferji, Meghan L. Good, Abraham Sachs, Amy R. Copeland, Sanghyun P. Kim, Scott Kivitz, Maria R. Parkhurst, Paul F. Robbins, Satyajit Ray, Liqiang Xi, Mark Raffeld, Zhiya Yu, Nicholas P. Restifo, Robert P.T. Somerville, Steven A. Rosenberg, Drew C. Deniger
Journal: Clinical Cancer Research (2020)

Abstract Purpose: The purpose of this study was to evaluate antigen experienced T cells in peripheral blood lymphocytes (PBL) for responses to p53 neoantigens. Experimental Design: PBLs from patients with a mutated TP53 tumor were sorted for antigen-experienced T cells and in vitro stimulation (IVS) was performed with p53 neoantigens. The IVS cultures were stimulated with antigen-presenting cells expressing p53 neoantigens, enriched for 41BB/OX40 and grown with rapid expansion protocol. Results: T-cell responses were not observed in the PBLs of 4 patients who did not have tumor-infiltrating lymphocyte (TIL) responses to mutated TP53. In contrast, 5 patients with TIL responses to mutated TP53 also had similar T-cell responses in their PBLs, indicating that the PBLs and TILs were congruent in p53 neoantigen reactivity. CD4+ and CD8+ T cells were specific for p53R175H, p53Y220C, or p53R248W neoantigens, including a 78% reactive T-cell culture against p53R175H and HLA-A*02:01. Tracking TCRB clonotypes (clonality, top ranked, and TP53 mutation-specific) supported the enrichment of p53 neoantigen–reactive T cells from PBLs. The same T-cell receptor (TCR) from the TIL was found in the IVS cultures in three cases and multiple unique TCRs were found in another patient. TP53 mutation–specific T cells also recognized tumor cell lines bearing the appropriate human leukocyte antigen restriction element and TP53 mutation, indicating these T cells could recognize processed and presented p53 neoantigens. Conclusions: PBL was a noninvasive source of T cells targeting TP53 mutations for cell therapy and can provide a window into intratumoral p53 neoantigen immune responses. See related commentary by Olivera et al., p. 1203
Abstract 473: Will Obesity Bankrupt the United States? Obese Patients Who Underwent Cardiopulmonary Resuscitation Have Increased Thirty-Day Readmission and Total Hospital Cost
Authors: Kam Ho, Bharat Narasimhan, Lingling Wu, Shabnam Nasserifar, Jacqueline Sheehan, Eyal Herzog
Journal: Circulation (2019)

Purpose: To determine the relationship between obesity and thirty-days readmission, mortality, morbidity, and health care resource utilization in patients who underwent cardiopulmonary resuscitation (CPR) during their hospitalization in the in the United States. Method: A retrospective study was conducted using the AHRQ-HCUP NRD for the year 2014. Adults (≥ 18 years) with a primary diagnosis of CPR (1), along with a secondary diagnosis of obesity were identified using ICD-9 codes as described in the literature (2). The primary outcome was the rate of all-cause readmission within 30 days of discharge. Secondary outcomes were reasons for readmission, readmission mortality rate, morbidity, and resource use. Propensity score (PS) using the 1:1 nearest neighbor matching without replacement was utilized to adjust for confounders (3). Results: 113,394 hospital admissions among adults with a primary and secondary diagnosis of CPR were identified, of which 14.8% were obese. 1:1 PS matching was performed based on demographic and clinical characteristics. The 30-day rate of readmission among obese and non-obese with CPR were 4.94% and 2.82% (p &lt;0.001). The most common readmission for both groups was unspecified sepsis (17.3%). During the index admission for CPR, the length of stay (LOS) among obese and non-obese patients were similar (10.3 vs 9.4 days, p=0.16). However, the total cost for the obese patients was statistically different ($33,232 vs $33,692, p &lt;0.001). Most importantly, obese patients’ in-hospital mortality rate during their index admission was significant higher (58.7% vs 6.72%, p &lt;0.001). Amongst those readmitted, obese patients similarly had a significantly longer LOS than their non-obese counterparts (8.1 vs 4.5 days, p &lt;0.001) and their total cost was more expensive ($19,027 vs $10,572, p &lt;0.001). But, obese patients’ in-hospital mortality rate during their readmission was not significant different (0.34 % vs 0.08%, p =0.09). Obesity (HR 1.77, p &lt;0.02) was an independent predictor associated with higher risks of readmission. Conclusion: In this study, obese patients admitted with CPR have a higher 30 days of readmission rate, total hospital cost, and in-hospital mortality (p &lt;0.02) than non-obese patients.
Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study
Authors: Hidemi Nakagawa, Osamu Nemoto, Atsuyuki Igarashi, Hidehisa Saeki, Hironobu Kaino, Takeshi Nagata
Journal: Journal of the American Academy of Dermatology (2020)

BackgroundPrevious studies showed the potential effectiveness of delgocitinib ointment, a novel topical Janus kinase inhibitor, in atopic dermatitis (AD).ObjectiveThis study aimed to evaluate the efficacy and safety of delgocitinib 0.5% ointment.MethodsIn part 1, a 4-week double-blind period, Japanese patients aged 16 years or older with moderate or severe AD were randomly assigned in a 2:1 ratio to delgocitinib 0.5% ointment or vehicle ointment. Eligible patients entered part 2, a 24-week extension period, to receive delgocitinib 0.5% ointment.ResultsAt the end of treatment in part 1, the least-squares mean percent changes from baseline in the modified Eczema Area and Severity Index score, the primary efficacy endpoint, were significantly greater in the delgocitinib group than in the vehicle group (-44.3% vs 1.7%, P < .001). The improvement in modified Eczema Area and Severity Index score was maintained in part 2. Most adverse events were mild and unrelated to delgocitinib across the study periods.LimitationsOnly Japanese patients were included. The vehicle-controlled period lasted only 4 weeks. In part 2, topical corticosteroids were allowed for the treatment of worsening of AD.ConclusionDelgocitinib ointment was effective and well tolerated in Japanese adult patients with moderate to severe AD for up to 28 weeks. Previous studies showed the potential effectiveness of delgocitinib ointment, a novel topical Janus kinase inhibitor, in atopic dermatitis (AD). This study aimed to evaluate the efficacy and safety of delgocitinib 0.5% ointment. In part 1, a 4-week double-blind period, Japanese patients aged 16 years or older with moderate or severe AD were randomly assigned in a 2:1 ratio to delgocitinib 0.5% ointment or vehicle ointment. Eligible patients entered part 2, a 24-week extension period, to receive delgocitinib 0.5% ointment. At the end of treatment in part 1, the least-squares mean percent changes from baseline in the modified Eczema Area and Severity Index score, the primary efficacy endpoint, were significantly greater in the delgocitinib group than in the vehicle group (-44.3% vs 1.7%, P < .001). The improvement in modified Eczema Area and Severity Index score was maintained in part 2. Most adverse events were mild and unrelated to delgocitinib across the study periods. Only Japanese patients were included. The vehicle-controlled period lasted only 4 weeks. In part 2, topical corticosteroids were allowed for the treatment of worsening of AD. Delgocitinib ointment was effective and well tolerated in Japanese adult patients with moderate to severe AD for up to 28 weeks.
心房細動の高周波カテーテルアブレーションによるvon Willebrand因子とADAMTS13濃度の変化の解析 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Uemura Takashi, Yamabe Hiroshige, Kaikita Koichi, Soejima Kenji, Morihisa Kenji, Tanaka Yasuaki, Enomoto Koji, Ogawa Hisao
Journal: Circulation (2009)
Trends in Uninsured Rates Before and After Medicaid Expansion in Counties Within and Outside of the Diabetes Belt
Authors: Jennifer M. Lobo, Soyoun Kim, Hyojung Kang, Gabrielle Ocker, Timothy L. McMurry, Rajesh Balkrishnan, Roger Anderson, Anthony McCall, Joseph Benitez, Min-Woong Sohn
Journal: Diabetes Care (2020)

To examine trends in uninsured rates between 2012 and 2016 among low-income adults aged <65 years and to determine whether the Patient Protection and Affordable Care Act (ACA), which expanded Medicaid, impacted insurance coverage in the Diabetes Belt, a region across 15 southern and eastern U.S. states in which residents have high rates of diabetes.Data for 3,129 U.S. counties, obtained from the Small Area Health Insurance Estimates and Area Health Resources Files, were used to analyze trends in uninsured rates among populations with a household income ≤138% of the federal poverty level. Multivariable analysis adjusted for the percentage of county populations aged 50-64 years, the percentage of women, Distressed Communities Index value, and rurality.In 2012, 39% of the population in the Diabetes Belt and 34% in non-Belt counties were uninsured (P < 0.001). In 2016 in states where Medicaid was expanded, uninsured rates declined rapidly to 13% in Diabetes Belt counties and to 15% in non-Belt counties. Adjusting for county demographic and economic factors, Medicaid expansion helped reduce uninsured rates by 12.3% in Diabetes Belt counties and by 4.9% in non-Belt counties. In 2016, uninsured rates were 15% higher for both Diabetes Belt and non-Belt counties in the nonexpansion states than in the expansion states.ACA-driven Medicaid expansion was more significantly associated with reduced uninsured rates in Diabetes Belt than in non-Belt counties. Initial disparities in uninsured rates between Diabetes Belt and non-Belt counties have not existed since 2014 among expansion states. Future studies should examine whether and how Medicaid expansion may have contributed to an increase in the use of health services in order to prevent and treat diabetes in the Diabetes Belt.
Comparison of Two Chemotherapy Regimens (AI vs. EIA) Combined with Regional Hyperthermia (RHT) in High-Risk Soft-Tissue Sarcoma (HR-STS)
Authors: P.O. Aubele, E. Kampmann, G. Schuebbe, S. Abdel-Rahman, N. Dieterle, R. Laubender, R. Issels, L. Lindner
Journal: Annals of Oncology (2012)
Role of Genetic Variants in the PI3K/AKT/MTOR Pathway in Renal Cell Carcinoma Patients Treated with Everolimus- A Pilot Study
Authors: L. Bodnar, R. Stec, M. Cichowicz, S. Cierniak, M. Smoter, W. Kozłowski, C. Szczylik
Journal: Annals of Oncology (2012)
A multi-omics investigation of the molecular characteristics and classification of six metabolic syndrome relevant diseases
Authors: Di Chen, Xinjie Zhao, Zhigang Sui, Huan Niu, Luonan Chen, Cheng Hu, Qiuhui Xuan, Xuhong Hou, Rong Zhang, Lina Zhou, Yanli Li, Huiming Yuan, Yukui Zhang, Jiarui Wu, Lihua Zhang, Ren'an Wu, Hai-Long Piao, Guowang Xu, Weiping Jia
Journal: Theranostics (2020)

Metabolic syndrome (MTS) is a cluster of concurrent metabolic abnormal conditions. MTS and its component metabolic diseases are heterogeneous and closely related, making their relationships complicated, thus hindering precision treatment. Methods: We collected seven groups of samples (group a: healthy individuals; group b: obesity; group c: MTS; group d: hyperglycemia, group e: hypertension, group f: hyperlipidemia; group g: type II diabetes, n=7 for each group). We examined the molecular characteristics of each sample by metabolomic, proteomic and peptidomic profiling analysis. The differential molecules (including metabolites, proteins and peptides) between each disease group and the healthy group were recognized by statistical analyses. Furthermore, a two-step clustering workflow which combines multi-omics and clinical information was used to redefine molecularly and clinically differential groups. Meanwhile, molecular, clinical, network and pathway based analyses were used to identify the group-specific biological features. Results: Both shared and disease-specific molecular profiles among the six types of diseases were identified. Meanwhile, the patients were stratified into three distinct groups which were different from original disease definitions but presented significant differences in glucose and lipid metabolism (Group 1: relatively favorable metabolic conditions; Group 2: severe dyslipidemia; Group 3: dysregulated insulin and glucose). Group specific biological signatures were also systematically described. The dyslipidemia group showed higher levels in multiple lipid metabolites like phosphatidylserine and phosphatidylcholine, and showed significant up-regulations in lipid and amino acid metabolism pathways. The glucose dysregulated group showed higher levels in many polypeptides from proteins contributing to immune response. The another group, with better glucose/lipid metabolism ability, showed higher levels in lipid regulating enzymes like the lecithin cholesterol acyltransferase and proteins involved in complement and coagulation cascades. Conclusions: This multi-omics based study provides a general view of the complex relationships and an alternative classification for various metabolic diseases where the cross-talk or compensatory mechanism between the immune and metabolism systems plays a critical role.
The American Heart Association 2030 Impact Goal: A Presidential Advisory From the American Heart Association
Authors: Sonia Y. Angell, Michael V. McConnell, Cheryl A.M. Anderson, Kirsten Bibbins-Domingo, Douglas S. Boyle, Simon Capewell, Majid Ezzati, Sarah de Ferranti, Darrell J. Gaskin, Ron Z. Goetzel, Mark D. Huffman, Marsha Jones, Yosef M. Khan, Sonia Kim, Shiriki K. Kumanyika, Alexa T. McCray, Robert K. Merritt, Bobby Milstein, Dariush Mozaffarian, Tyler Norris, Gregory A. Roth, Ralph L. Sacco, Jorge F. Saucedo, Christina M. Shay, David Siedzik, Somava Saha, John J. Warner
Journal: Circulation (2020)

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.
51P Multiple Primary Neoplasia, or a Neoplasia with Satellites? The Role of Molecular Biology in The Diagnostic Process
Authors: D. Deme, C. Székely, A.M. Bishr, Z. Szllsi, J. Nizar, L. Kovács, T. Micsik, B. Jóri, I. Peták, A. Telekes
Journal: Annals of Oncology (2012)
Rod-based urchin-like hollow microspheres of Bi2S3: Facile synthesis, photo-controlled drug release for photoacoustic imaging and chemo-photothermal therapy of tumor ablation
Authors: Chenyang Zhang, Dongdong Li, Pei Pei, Wanni Wang, Benjin Chen, Zhaoyou Chu, Zhengbao Zha, Xianzhu Yang, Jinbing Wang, Haisheng Qian
Journal: Biomaterials (2020)