tbuckley/cabot-search huggingface dataset:
IL-21-based therapies induce clearance of hepatitis B virus persistence in mouse models
Authors: Zhongliang Shen, Jing Liu, Jingwen Wu, Yuanfei Zhu, Gaiyun Li, Jun Wang, Mengjun Luo, Qiang Deng, Jiming Zhang, Youhua Xie
Journal: Theranostics (2019)

Chronic hepatitis B virus (HBV) infection causes hepatitis, liver cirrhosis and hepatocellular carcinoma.Covalently closed circular DNA (cccDNA) is the sole viral transcription template and not affected by current treatment options, constituting a key determinant of HBV persistence.Novel therapeutics with demonstrable effectiveness against cccDNA are required.Methods: Previously, we established an HBV persistence mouse model using replicon plasmid derived from a clinical isolate (termed BPS) and identified IL-21 as a potent clearance-inducer.We also described another persistence mouse model based on cccDNA mimics produced in vivo termed recombinant cccDNA (rcccDNA).In this work, effectiveness of IL-21-based gene and cellular therapies was tested using these models.Results: In both models of HBV persistence, single injections with adeno-associated virus (AAV) expressing murine IL-21 highly efficiently induced clearance of both HBV markers from serum, and more importantly, BPS DNA and rcccDNA from mouse liver.Mechanistically, IL-21-induced clearance was associated with activation and liver infiltration of CD8 + T cells, and CD8 antibody injections negatively affected AAV-IL-21 effectiveness.More notably, adoptive transfer of CD8 + T cells from AAV-IL-21-cured mice engendered clearance in acceptor HBV persistence mice.Furthermore, cured mice were protected against re-challenge with long-lived memory.Most significantly, infusion of splenocytes from treatment-naïve mice stimulated ex vivo with IL-21 protein and HBV antigen could also induce clearance in treatment-naïve mice.Conclusion: These data demonstrate IL-21-based gene and cellular therapies as valid candidates for treating chronic HBV infections, with potential in removing cccDNA-harboring hepatocytes via activated CD8 + T cells accompanied by long-term protective memory.
Molecular Mechanisms of Tyrosine Kinase Inhibitor Resistance Induced by Membranous/Cytoplasmic/Nuclear Translocation of Epidermal Growth Factor Receptor
Authors: Xuezhu Rong, Yuan Liang, Qiang Han, Yue Zhao, Guiyang Jiang, Xiupeng Zhang, Xuyong Lin, Yang Liu, Yong Zhang, Xu Han, Meiyu Zhang, Yuan Luo, Pengcheng Li, Lai Wei, Ting Yan, Enhua Wang
Journal: Journal of Thoracic Oncology (2019)
Prevalence, risk factors, and management of asthma in China: a national cross-sectional study
Authors: Kewu Huang, Ting Yang, Jianying Xu, Lan Yang, Jianping Zhao, Xiangyan Zhang, Chunxue Bai, Jian Kang, Pixin Ran, Huahao Shen, Fuqiang Wen, Yahong Chen, Tieying Sun, Guangliang Shan, Yingxiang Lin, Guodong Xu, Sinan Wu, Chaolong Wang, Ruiying Wang, Zhihong Shi, Yongjian Xu, Xianwei Ye, Yuanlin Song, Qiuyue Wang, Yumin Zhou, Wen Li, Liren Ding, Chun Wan, Wanzhen Yao, Yanfei Guo, Fei Xiao, Yong Lu, Xiaoxia Peng, Biao Zhang, Dan Xiao, Zuomin Wang, Zhengming Chen, Xiaoning Bu, Hong Zhang, Xiaolei Zhang, Li An, Shu Zhang, Jianguo Zhu, Zhixin Cao, Qingyuan Zhan, Yuanhua Yang, Lirong Liang, Xunliang Tong, Huaping Dai, Bin Cao, Tangchun Wu, Kian Fan Chung, Jiang He, Chen Wang
Journal: The Lancet (2019)
PPP1R3C mediates metformin-inhibited hepatic gluconeogenesis
Authors: Xueying Ji, Shushu Wang, Hongju Tang, Yuqing Zhang, Feiye Zhou, Linlin Zhang, Qin Zhu, Kecheng Zhu, Qianqian Liu, Yun Liu, Xiao Wang, Libin Zhou
Journal: Metabolism (2019)
PF726 TOLERABILITY OF TREATMENTS FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA: A SYSTEMATIC REVIEW
Authors: M. Nassim, J. Nilsson, S. Zavisic, M. Malmenäs, I. Fotheringham, E. Landfeldt
Journal: HemaSphere (2019)

Background: Multiple myeloma is a fatal cancer characterized by excessive proliferation and improper function of plasma cells in the bone marrow. Aims: To conduct a systematic literature review of the tolerability of treatments for relapsed/refractory multiple myeloma. Methods: We searched MEDLINE, Embase, and the Cochrane Library for English language full‐text articles published between 2000 and 2018 reporting results from randomized controlled trials of treatments for relapsed/refractory multiple myeloma. Two independent investigators screened article titles and abstracts for eligibility and subsequently reviewed full‐text versions of selected records. For all articles included in the review, the following data were extracted: Author, year of publication, setting, sample, treatments, and tolerability results. Results: The search resulted in the identification of 3488 unique publications. Of these, 3188 were excluded following title and abstract screening and 75 after full‐text review. A total of 22 articles were included for data synthesis. Identified randomized controlled trials involved an average of 477 patients (range: 80 to 768) and covered a total of 14 interventions for relapsed/refractory multiple myeloma. Of these, 14% were monotherapies and 86% combination therapies. Across included randomized controlled trials, the most frequently occurring adverse event during treatment was neuropathy, observed in 1%–67% of patients, followed by thrombocytopenia (1%–57%), pain (1%–24%), neutropenia (1%–52%), and diarrhea (1%–68%). Treatment discontinuation (all causes) was reported at between 31% and 95%, and discontinuation due to adverse events at between 7% and 34%. Summary/Conclusion: Current therapies for relapsed/refractory multiple myeloma are associated with several serious adverse events, resulting in treatment discontinuation. Yet, tolerability profiles vary markedly between interventions and patient populations. These data should be helpful to inform therapeutic decisions in relapsed/refractory multiple myeloma to enhance patient satisfaction and treatment compliance.
Abstract 9430: Right Ventricular Apical and Free Wall Pacing, but Not Ventricular Septal Pacing Leads to Left Ventricular Reverse Rotation
Authors: Masatsugu Nozoe, Kazuhiro Nishigami, Toshihiro Honda, Koichi Nakao
Journal: Circulation (2011)

Background: Although left ventricular (LV) twisting has been recognized to play an important role in LV function, the impact of right ventricular (RV) pacing on LV twisting including rotational abnormality has not been fully understood. We investigated the influence of the pacing site on the rotational abnormality in patients underwent pacemaker implantation. Methods and Results: We evaluated 21 patients who underwent permanent pacemaker implantation for sick sinus syndrome or atrioventricular block (age 79 years) with preserved systolic function. According to RV pacing site, we divided our patients into septal pacing group (n=10) and non-septal (free wall or apex) pacing group (n=11). Rotation in the apical LV was evaluated using speckle tracking image in echocardiogram and the clockwise rotation of the apical wall or/and the counterclockwise rotation of the basal wall were defined as reverse rotation. We assessed LV rotational abnormality, under own beats or/and RV pacing rhythm. Results: During own beats, only one patient (1/21= 5%) with incomplete right branch block and atrial flutter demonstrated reverse rotation. In contrast, during RV pacing rhythm, 9 patients (9/21=43%) exhibited reverse rotation, in whom there were 8 patients in non-septal pacing group and 1 patient in septal pacing group. Reverse rotation was observed more in non-septal pacing group than in septal pacing group. Conclusions: RV apical or free wall pacing could induce the reverse rotation of the LV wall while RV septal pacing preserved LV rotation.
PB2042 CYTOMEGALOVIRUS INFECTION – A BRAKE IN PLATELET RECOVERY AFTER CHEMOTHERAPY IN ACUTE MYELOID LEUKEMIA PATIENTS
Authors: V. Popov, M. Balea, O. Patrinoiu, D. Georgescu, I. Dumitru, A. Iova, M. Begu, C. Dobrea, A. Arghir, S. Papuc, D. Soare, A. Abagiu, S. Madalina, G.A. Popescu, H. Bumbea
Journal: HemaSphere (2019)

Background: Cytomegalovirus (CMV) infection influence platelet recovery in bone marrow transplantation patients. Patients with CMV infection, primary, reactivated, or latent, require more platelet unit transfusions, this procedure determines increases the risk of transfusion‐related infections. In literature there are many reports regarding CMV implication in bone marrow recovery secondary transplant procedure. Aims: The association with CMV infection and slowly recovery of bone marrow secondary chemotherapy in AML was rarely reported Methods: We report 2 cases with delay in platelet recovery after intensive chemotherapy‐ consolidation phase of acute myeloid leukaemia patients. Results: Patients male 46 years and female 55 years were diagnosed with AML 1. Diagnose was put using WHO criteria and was not identified any genetic abnormalities. We started 3+7 regimen with obtaining complete remission status. After bone marrow recovery we started consolidation phase with high doses Cytarabine 2 applications. After second application we observed delay in platelet recovery (more than 1 months). Bone marrow biopsy indicated severe aplasia. Serology for CMV infection was positive for IgG antibodies, PCR for CMV was positive indicated active CMV infection. Patients were referred to infectionist and was started antiviral treatment – Gancyclovir. During treatment patients presented increases of platelet count and absence of platelet unit transfusion, in 1 month patients had G1 trombocytopenia (improving of CTCAE grade from G4 to G1) Summary/Conclusion: The delay in bone marrow recovery after intensive chemotherapy used as treatment of acute myeloid leukemia patient represent a warning to check CMV infection presence. This attitude could avoid complications like infections or/and transfusions related.
Abstract 14750: Incidence of Cardiac Implantable Electronic Device Malfunction Post Radiation Therapy
Authors: Amin Zagzoog, Matt Wronski, Mohammed Shurrab, Suzette Turner, Adrian Baranchuk, Usama Boles, Aldo Carrizo, Jeff Healey, Eugene Crystal
Journal: Circulation (2017)

Introduction: Radiation therapy is a common cancer treatment modality, and a growing number of patients with cardiac implantable electronic devices (CIEDs) are being referred for radiation therapy....
Abstract P178: Trends in Antihypertensive Medication Nonadherence Among US Adults With Commercial Health Insurance Initiating Treatment Between 2007 and 2014
Authors: Gabriel Tajeu, Shia T Kent, Lei Huang, Daichi Shimbo, Marie Krousel-Wood, Ian M Kronish, Adam P Bress, Yendelela Cuffee, Michael T Halpern, Paul Muntner
Journal: Circulation (2018)

Introduction: Nonadherence to antihypertensive medication is common and associated with cardiovascular disease events. A previous study reported improvements in antihypertensive medication adherence among adults ≥65 years of age. It is unclear if this trend has also occurred among younger adults. Methods: Changes in antihypertensive medication nonadherence were calculated among commercially-insured US adults &lt;65 years of age initiating treatment from 2007 to 2014 using MarketScan claims data. We required beneficiaries have ≥2 diagnoses for hypertension (ICD-9, 401.xx) and insurance coverage for 365 days prior to and following antihypertensive medication initiation. Initiation was defined by a pharmacy claim for antihypertensive medication with no claims for medication within the previous 365 days. During the 365 days after initiation, nonadherence was defined as having a proportion of days covered &lt;80%. Results: The percentage of patients who were nonadherent to their antihypertensive medication was 55.6% in 2007 and 54.1% in 2014 (p-trend&lt;0.001) ( Table ). After multivariable adjustment, the relative risk (RR) of nonadherence in 2014 compared with 2007 was 0.98 (95% CI 0.96-0.99). Risk for nonadherence was lower at older age (RR 0.73, 95% CI 0.71-0.74 comparing adults 55-64 to &lt;25 years of age). Nonadherence was more common among adults that were female versus male (RR 1.05; 95% CI 1.05-1.06), initiated treatment with a loop diuretic (RR 1.26; 95% CI 1.24-1.28), had diabetes (RR 1.11; 95% CI 1.10-1.12), or experienced a serious fall injury after medication initiation (RR 1.10; 95% CI 1.06-1.15), and less common among adults initiating treatment with an angiotensin receptor blocker (RR 0.96; 95% CI 0.95-0.96), multiclass regimen (RR 0.89; 95% CI 0.88-0.90), receiving 90-day fills (RR 0.73; 95% CI 0.73-0.74), or medications by mail (RR 0.92; 95% CI 0.91-0.93). Conclusion: Among adults &lt;65 years of age, nonadherence to antihypertensive medication did not meaningfully decrease between 2007 and 2014.
A feasibility study using a touchscreen tool in the AYA population.
Authors: Jonathan R. Espenschied, Julie Anna Wolfson, Alicia Bogardus, Yanjun Chen, Jeanelle Folbrecht, Florence Lennie Wong, Joseph Rosenthal, Sunita K. Patel
Journal: Journal of Clinical Oncology (2013)

9575 Background: Adolescent and young adults (AYA) 15 to 39 years present unique health care needs; however, barriers to communication of treatment-related and psychosocial difficulties exist. We hypothesized that a tailored AYA Touchscreen Tool (AYATT) in cancer patients/survivors would facilitate patient-provider communication, toward the larger goal of timely intervention. As a first step, we evaluated the feasibility of such a tool, operationally defined as an 80% acceptance and completion rate. Methods: Eligible City of Hope AYA patients receiving treatment and follow up care for oncologic or hematologic disease were systematically approached for study participation. Target accrual to assess feasibility was set at 50 participants. Consented patients completed a concise AYATT battery, mostly standardized measures, assessing access to care (CHIS), needs, neurocognitive function (BRIEF-A, CogState), and other quality of life (PedsQL) issues. Patients and clinical/support staff completed satisfaction and ease-of-use surveys to further evaluate feasibility. Results: 54 participants were accrued over 8 weeks, with a 96% completion rate exceeding our primary feasibility criteria. At the time of participation: Mean age=26.2 years; Range 15.3 to 38.9 years. Acceptability was high with positive responses throughout the survey. Based on patient responses, the AYATT helped 52% remember issues they had, or have, with their care or treatment; 39% were encouraged to discuss medical issues with their care team that they might not have discussed; 92% found it a useful way to communicate with their health care team; and 98% would recommend that other patients use AYATT. A separate survey from 31/36 clinical/support staff reported AYATT had minimal negative impact in clinic or patient care, increased communication, and was useful in maintaining/improving care. Conclusions: The aggregate findings from this feasibility study support utilizing a tailored touchscreen device in the AYA oncology population. Predictably, high levels of computer knowledge in our AYA cohort may account for the success and acceptance of using such a tool. These results provide evidence for further exploration and continued use in the AYA clinic and patient care setting.
Abstract 14920: Uric Acid is Neither the Risk Factor nor Prognostic Factor for 3-year Clinical Events in Vasospastic Angina Patients Regardless of Gender
Authors: Sang-Ho Park, Seung Woon Rha, Ung Jun, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2015)

Background: It has been reported that a major cause of vasospastic angina is endothelial dysfunction of the coronary artery. However, it is controversial whether the uric acid level is associated with vasospastic angina, and can be a prognostic factor for vasospastic angina. Methods: A total 3828 patients (pts) underwent coronary angiography with acetylcholine (Ach) provocation test from Mar 2004 to Sep 2012 were enrolled. The definition of positive coronary artery spasm (CAS) was defined as transient luminal narrowing more than 70%. The uric acid level was categorized into 4 quartile groups; less than 3.8, 3.9~4.7, 4.8~5.7, and more than 5.8 mg/dL. Major adverse cardiovascular events (MACEs) defined as the composite of recurrent chest pain, cardiac death, myocardial infarction, and cerebrovascular accident were valuated up to 3 years. Results: The follow-up rate was the 61.1% (2340/3828). There was no difference in uric acid level between negative and positive CAS groups in female gender but in male gender, uric acid level was higher in negative CAS group (Table 1). However, when adjusted by age, the difference was disappeared (OR, 0.965; 95% CI, 0.898-1.037; P-value, 0.335). The incidence of MACE was 11.1% in male gender and 8.6% in female gender. In male gender, the serum uric acid level between the groups with and without MACE was similar but in female gender, the uric acid level was higher in the group with MACE. However, when adjusted by age, uric acid was not associated with MACE (Table 2). Conclusions: In our study, uric acid was neither the risk factor nor prognostic factor for 3-year clinical events in CAS patients regardless of gender.
DLL3: an emerging target in small cell lung cancer
Authors: Dwight H. Owen, Michael J. Giffin, Julie M. Bailis, Marie-Anne Damiette Smit, David P. Carbone, Kai He
Journal: Journal of Hematology & Oncology (2019)

Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers. Despite high rates of response to first-line chemotherapy and radiotherapy, patients with extensive-stage disease eventually relapse, and very few patients survive more than 5 years from diagnosis. Treatment options for recurrent or refractory disease are limited, and the treatments that do exist are associated with significant treatment-related toxicities. Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand that is highly expressed in SCLC and other neuroendocrine tumors but minimally expressed in normal tissues. It is therefore being explored as a potential therapeutic target in SCLC. Here, we review the preclinical and clinical evidence for targeting DLL3 in SCLC and discuss several DLL3-specific therapies being developed for the treatment of SCLC: the antibody-drug conjugate rovalpituzumab tesirine, the bispecific T cell engager immuno-oncology therapy AMG 757, and the chimeric antigen receptor T cell therapy AMG 119.
Comparison of Conventional Lipoprotein Tests and Apolipoproteins in the Prediction of Cardiovascular Disease
Authors: Claire Welsh, Carlos A. Celis-Morales, Rosemary Brown, Daniel F. Mackay, James Lewsey, Patrick B. Mark, Stuart R. Gray, Lyn D. Ferguson, Jana J. Anderson, Donald M. Lyall, John G. Cleland, Pardeep S. Jhund, Jason M.R. Gill, Jill P. Pell, Naveed Sattar, Paul Welsh
Journal: Circulation (2019)

Total cholesterol and high-density lipoprotein cholesterol (HDL-C) measurements are central to cardiovascular disease (CVD) risk assessment, but there is continuing debate around the utility of other lipids for risk prediction.
Refining the role of de novo protein-truncating variants in neurodevelopmental disorders by using population reference samples
Authors: Jack A Kosmicki, Kaitlin E Samocha, Daniel P Howrigan, Stephan J Sanders, Kamil Slowikowski, Monkol Lek, Konrad J Karczewski, David J Cutler, Bernie Devlin, Kathryn Roeder, Joseph D Buxbaum, Benjamin M Neale, Daniel G MacArthur, Dennis P Wall, Elise B Robinson, Mark J Daly
Journal: Nature Genetics (2017)
Medical cannabis: we need a change in culture and far more government action
Authors: Michael C Smith
Journal: BMJ (2019)

Nutt’s article on medical cannabis outlines several reasons behind the limited effect of the UK legal reform.1 The complexity of the cannabis plant limits our ability to integrate it into the current pharmaceutical paradigm of single molecule drugs.2

Medical cannabis has been assessed in several randomised controlled trials,3 but the resulting data cannot be combined because of the diversity of cannabis strains and different relative proportions of active ingredients. The absence of robust RCT data is a major problem as the …
Abstract 150: Anesthetic Postconditioning With Sevoflurane During Cardiopulmonary Resuscitation Improves Cardiac Mitochondrial Function in a Pig Model of Cardiac Arrest
Authors: Timothy R Matsuura, Demetris Yannopoulos, Mohammed Aldakkak, Martin Bienengraeber, Mohammad Sarraf, Jason A Bartos, Tom P Aufderheide, Robert W Neumar, Matthias L Riess
Journal: Circulation (2013)

Introduction: Anesthetic postconditioning (PC) reduces myocardial ischemia/reperfusion (IR) injury.1,2 We hypothesized that sevoflurane (SEV) PC during cardiopulmonary resuscitation (CPR) is simila...
The EGFR Exon 19 Mutant L747-A750&amp;gt;P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma—Letter
Authors: Alessandro Di Federico, Daria M. Filippini, Filippo G. Dall'Olio, Nicole Conci, Roberta Minari, Marcello Tiseo, Andrea Ardizzoni
Journal: Clinical Cancer Research (2020)

We read with interest the recently published paper by Truini and colleagues (1) describing the peculiar in vitro activity of afatinib on non-small cell lung cancer cell lines harboring the EGFR L747-A750>P mutation.We reviewed our patient database and found 6 cases out of 265 with this specific EGFR mutation (2.2%), similar to the prevalence reported in the paper by Truini and colleagues.Here we report two of those cases, one treated in first-line with afatinib and the other with erlotinib
Алкогольне ураження печінки: морфологічні та біохімічні особливості (експериментальне дослідження)
Authors: Yu.M. Stepanov, V.I. Didenko, N.Yu. Oshmianska, I.A. Klenina, K.V. Petrova, O.O. Halinskyi, A.I. Rudenko
Journal: GASTROENTEROLOGY (2020)

Дослідження впливу додаткових ушкоджуючих факторів та хронічної алкоголізації на фосфоліпідний склад гомогенату печінки проводились на 42 білих лабораторних щурах за допомогою біохімічних, патоморфологічних та патофізіологічних методів. Було змодельовано та детально описано хронічний гепатоз із трьома ступенями поширеності (мікровезикулярна, дрібнокрапельна та великокрапельна жирова дистрофія) й активності, що супроводжувалися відповідними змінами проникності мембран гепатоцитів і динаміки перекисного окиснення мембранних білків та ліпідів.