tbuckley/cabot-search huggingface dataset:
From Reciprocity to Autonomy in Physician-Assisted Death: An Ethical Analysis of the Dutch Supreme Court Ruling in the Albert Heringa Case
Authors: Barend W. Florijn
Journal: The American Journal of Bioethics (2020)

In 2002, the Dutch Euthanasia Act was put in place to regulate the ending of one's life, permitting a physician to provide assistance in dying to a patient whose suffering the physician assesses as unbearable. Currently, a debate in the Netherlands concerns whether healthy (older) people who value their life as completed should have access to assistance in dying based on their autonomous decision making. Although in European law a right to self-determination ensues from everyone's right to private life, the Dutch Supreme Court recently adopted a position on whether the Dutch Euthanasia Act lacks adequate attention to a patient's autonomous decision making. Specifically, in the Albert Heringa case, the Court ruled that the patient-physician relationship as understood in the Dutch Euthanasia Act limits this plea for more self-determination. This ethical analysis of the Heringa case examines how the Supreme Court's understanding of the Euthanasia Act defines patient autonomy within a reciprocal patient-physician relationship.
International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function
Authors: Nicholas M. Barnes, Gerard P. Ahern, Carine Becamel, Joël Bockaert, Michael Camilleri, Severine Chaumont-Dubel, Sylvie Claeysen, Kathryn A. Cunningham, Kevin C. Fone, Michael Gershon, Giuseppe Di Giovanni, Nathalie M. Goodfellow, Adam L. Halberstadt, Rachel M. Hartley, Ghérici Hassaine, Katharine Herrick-Davis, Ruud Hovius, Enza Lacivita, Evelyn K. Lambe, Marcello Leopoldo, Finn Olav Levy, Sarah C. R. Lummis, Philippe Marin, Luc Maroteaux, Andrew C. McCreary, David L. Nelson, John F. Neumaier, Adrian Newman-Tancredi, Hugues Nury, Alexander Roberts, Bryan L. Roth, Anne Roumier, Gareth J. Sanger, Milt Teitler, Trevor Sharp, Carlos M. Villalón, Horst Vogel, Stephanie W. Watts, Daniel Hoyer
Journal: Pharmacological Reviews (2020)

5-HT receptors expressed throughout the human body are targets for established therapeutics and various drugs in development. Their diversity of structure and function reflects the important role 5-HT receptors play in physiologic and pathophysiological processes. The present review offers a framework for the official receptor nomenclature and a detailed understanding of each of the 14 5-HT receptor subtypes, their roles in the systems of the body, and, where appropriate, the (potential) utility of therapeutics targeting these receptors. <h3>Significance Statement</h3> This review provides a comprehensive account of the classification and function of 5-hydroxytryptamine receptors, including how they are targeted for therapeutic benefit.
Abstract 13381: hiPSC of CIITA and B2M KO Derived Cardiac Cells Engineered 3D Spheroid Transplantation Induce Tachycardia in Myocardial Infarction in Swine
Authors: Saidulu Mattapally, Jianyi Zhang
Journal: Circulation (2020)

Introduction: Human induced pluripotent stem cells (hiPSCs) are among one the most significant discoveries in life sciences. As a promising —biological drug for cell therapy, multiple lineages of iPSC-derived cardiac cells have been administered in human clinical trials in multiple important organ systems. The potential immunogenicity of hiPSC-derived cardiac cells continues to be one of the concerns in large animal models. Methods: In the present study, WT hiPSCs were generated by transfecting male human cardiac fibroblasts with Sendai viruses coding for OCT4, SOX2, KLF4, and C-MYC.Then hiPSCs carrying knockout mutations for both HLA Class I and Class II (HLAI/II-KOhiPSC) were generated via CRISPR/Cas9 gene-editing technology (Mattapally et al, 2018). hiPSCs were differentiated into cardiomyocytes (CM) endothelial cells (ECs) and spheroid cultured was performed as previously described (Mattapally et al, 2018). We evaluated spheroid transplantation and its potency for myocardial repair in the Swine. Programmed stimulation was used to determine the arrhythmogenic outcome. Results: To determine the engraftment efficacy of HLAI/II KO compared to WT Spheroid, a swine study was performed. After LAD ligation in swine, 800μm spheroid was injected into the border zone of the left ventricle. After transplantation, cell engraftment was monitored by Q-PCR. At week 4, there was a significant difference between the 2 groups. Animal groups included: MI hearts treated with 500 WT Spheroid injection (MI+WT Spheroid, n=5), MI hearts treated with 500 KO Spheroid injection (n=6), MI only hearts (n=6); the fourth group of animals underwent sham surgery (Sham, n=6). Arrhythmia was studied by programmed electrical stimulations (PES) and conduction velocities measured with electrode mapping, and the engraftment rate by calculation of quantitative polymerase chain reaction measurements of expression of the human Y chromosome. Engraftment of iPSC-CMs was found in both treatment groups; however, a significantly higher engraftment rate was found in KO Spheroid. The spheroid treatment is associated with significant changes in arrhythmogenicity. Conclusion: Our study established the improved graft but associated with arrhythmogenicity.
Как накормить пациента с нервной анорексией?
Authors: D.O. Ptushkina
Journal: GASTROENTEROLOGY (2020)

В статье рассматриваются проблемы нутритивной реабилитации больных нервной анорексией, методы оценки нутритивного статуса, пищевое поведение, восстановление и скорость набора веса, этапы лечения, энтеральное питание.
Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial
Authors: Zhenzhou Yang, Yan Zhang, Rongqing Li, Abulimiti Yisikandaer, Biyong Ren, Jianguo Sun, Jianjun Li, Long Chen, Ren Zhao, Juying Zhang, Xuefeng Xia, Zhongxing Liao, David P Carbone
Journal: Neuro-Oncology (2020)

Abstract Background Erlotinib combined with whole-brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase II single-arm trial of non–small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase III, randomized trial. Methods NSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n = 115) or WBRT combined with erlotinib arms (n = 109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by the Mini-Mental State Examination (MMSE). Results A total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months vs 9.2 months for WBRT-alone (P = .601). Median PFS and overall survival (OS) of combination group were 5.3 vs 4.0 months (P = .825) and 12.9 vs 10.0 months (P = .545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 vs 12.8 months; P = .164), PFS (8.8 vs 6.4 months; P = .702), and OS (17.5 vs 16.9 months; P = .221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments. Conclusion Concurrent erlotinib with WBRT didn’t improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases. Trial registration: Clinical trials.gov identifier: NCT01887795
Renin-Angiotensin-Aldosterone System Blocking Drugs in Patients with SARS-CoV-2: Systematic Review and Meta-Analysis
Authors: Chang Chu, Shufei Zeng, Ahmed A. Hasan, Carl-Friedrich Hocher, Bernhard K. Krämer, Berthold Hocher
Journal: Journal of the American Society of Nephrology (2020)

Background: COVID-19 patients requiring treatment with blockers of the reninangiotensin- aldosterone system (RAAS) are at highest risk of developing pneumonia and dying  ACE2 is the functional receptor for SARS-CoV-2  Animal studies suggest that RAAS blocking agents might increase the expression of ACE2 and hence potentially increase the risk of SARS-Cov-2 infection  Methods: We conducted a systematic review and meta-analysis of published studies on the association of RASS blocking agents with lung disease related outcomes  Results: The effect of ACE inhibitor treatment on the incidence of pneumonia in non-COVID-19 patients was analyzed in 25 studies (330,780 patients)  ACE inhibitor use was associated with a 27% reduction of pneumonia risk (OR: 0 73, p<0 001)  Pneumonia related death cases in ACE inhibitor treated non-COVID-19 patients were reduced by 27% (OR: 0 73, p=0 004)  ARB treatment was analyzed in 10 studies (275,621 non- COVID-19 patients)  The risk of pneumonia was not different between patients who did or did not use ARBs  Pooled result from 13 studies (27,704 COVID-19 patients) showed that COVID-19 related severe adverse clinical outcomes were not different between patients who did or did not use RAAS blocking agents (OR: 0 87, p=0 28)  All-cause mortality risk in COVID-19 patients was reduced by 27% (p=0 04)  Conclusions: Given the weak evidence coming from animal studies and the clear beneficial data of ACE inhibition in non-COVID-19 patients and the limited but promising data in COVID-19 patients, the use of RAAS blocking agents in patients with SARSCoV- 2 infection is justified  Further clinical studies analysing ARBs and ACE inhibitors separately in COVID-19 patients are needed
ERS statement on chronic thromboembolic pulmonary hypertension
Authors: Marion Delcroix, Adam Torbicki, Deepa Gopalan, Olivier Sitbon, Frederikus A. Klok, Irene Lang, David Jenkins, Nick H. Kim, Marc Humbert, Xavier Jais, Anton Vonk Noordegraaf, Joanna Pepke-Zaba, Philippe Brénot, Peter Dorfmuller, Elie Fadel, Hossein-Ardeschir Ghofrani, Marius M. Hoeper, Pavel Jansa, Michael Madani, Hiromi Matsubara, Takeshi Ogo, Ekkehard Grünig, Andrea D'Armini, Nazzareno Galie, Bernhard Meyer, Patrick Corkery, Gergely Meszaros, Eckhard Mayer, Gérald Simonneau
Journal: European Respiratory Journal (2020)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels &lt;500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions. This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH. It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.
B cells and cancer: To B or not to B?
Authors: Wolf Herman Fridman, Florent Petitprez, Maxime Meylan, Tom Wei-Wu Chen, Cheng-Ming Sun, Lubka T. Roumenina, Catherine Sautès-Fridman
Journal: The Journal of Experimental Medicine (2020)

Whereas T cells have been considered the major immune cells of the tumor microenvironment able to induce tumor regression and control cancer clinical outcome, a burst of recent publications pointed to the fact that B cells may also play a prominent role. Activated in germinal centers of tertiary lymphoid structures, B cells can directly present tumor-associated antigens to T cells or produce antibodies that increase antigen presentation to T cells or kill tumor cells, resulting in a beneficial clinical impact. Immune complexes can also increase inflammation, angiogenesis, and immunosuppression via macrophage and complement activation, resulting in deleterious impact.
The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis
Authors: Markus Kuksis, Yizhuo Gao, William Tran, Christianne Hoey, Alex Kiss, Adam S Komorowski, Aman J Dhaliwal, Arjun Sahgal, Sunit Das, Kelvin K Chan, Katarzyna J Jerzak
Journal: Neuro-Oncology (2020)

Abstract Background Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. Methods Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with human epidermal growth factor receptor-2 positive (HER2+), triple negative, and hormone receptor (HR)+/hormone receptor negative (HER2−) MBC; pooled overall estimates for incidence were calculated using random effects models. Results 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2− MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0–34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5–40.6), and 15% among patients with HR+/HER2− MBC (median follow-up: 33.0 months, IQR: 31.9–36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10–0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09–0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03–0.08) for patients with HR+/HER2− MBC. Conclusion There is a high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.
Association between home insulation and hospital admission rates: retrospective cohort study using linked data from a national intervention programme
Authors: Caroline Fyfe, Lucy Telfar, None Barnard, Philippa Howden-Chapman, Jeroen Douwes
Journal: BMJ (2020)

Abstract Objectives To investigate whether retrofitting insulation into homes can reduce cold associated hospital admission rates among residents and to identify whether the effect varies between different groups within the population and by type of insulation. Design A quasi-experimental retrospective cohort study using linked datasets to evaluate a national intervention programme. Participants 994 317 residents of 204 405 houses who received an insulation subsidy through the Energy Efficiency and Conservation Authority Warm-up New Zealand: Heat Smart retrofit programme between July 2009 and June 2014. Main outcome measure A difference-in-difference approach was used to compare the change in hospital admissions of the study population post-insulation with the change in hospital admissions of the control population that did not receive the intervention over the same two timeframes. Relative rate ratios were used to compare the two groups. Results 234 873 hospital admissions occurred during the study period. Hospital admission rates after the intervention increased in the intervention and control groups for all population categories and conditions with the exception of acute hospital admissions among Pacific Peoples (rate ratio 0.94, 95% confidence interval 0.90 to 0.98), asthma (0.92, 0.86 to 0.99), cardiovascular disease (0.90, 0.88 to 0.93), and ischaemic heart disease for adults older than 65 years (0.79, 0.74 to 0.84). Post-intervention increases were, however, significantly lower (11%) in the intervention group compared with the control group (relative rate ratio 0.89, 95% confidence interval 0.88 to 0.90), representing 9.26 (95% confidence interval 9.05 to 9.47) fewer hospital admissions per 1000 in the intervention population. Effects were more pronounced for respiratory disease (0.85, 0.81 to 0.90), asthma in all age groups (0.80, 0.70 to 0.90), and ischaemic heart disease in those older than 65 years (0.75, 0.66 to 0.83). Conclusion This study showed that a national home insulation intervention was associated with reduced hospital admissions, supporting previous research, which found an improvement in self-reported health.
Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways
Authors: Lihua Ye, Munhyung Bae, Chelsi D. Cassilly, Sairam V. Jabba, Daniel W. Thorpe, Alyce M. Martin, Hsiu-Yi Lu, Jinhu Wang, John D. Thompson, Colin R. Lickwar, Kenneth D. Poss, Damien J. Keating, Sven-Eric Jordt, Jon Clardy, Rodger A. Liddle, John F. Rawls
Journal: Cell Host & Microbe (2020)
Intracoronary Thrombolysis in no Flow after Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction
Authors: Goutam Datta
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Introduction: Mechanical revascularization of the infarct-related artery (IRA) is the most effective treatment modality in ST-segment elevation myocardial infarction (STEMI).No-reflow occurs in ∼8.8-10% of cases of primary percutaneous coronary intervention(PCI) in STEMI patients. Intracoronary tenectaplase was used when there was huge thrombus causing no flow in coronary artery following primary PCI in STEMI patients. Methods: Five hundred and eighty primary PCI patients were studied over a period of two years i.e. January 2016 to December 2017. Drug eluting stents were used in all cases. Majority of our patients (&gt;90%) came 6 hours after onset of chest pain. There were many patients where there was no flow even after mechanical thrombus aspiration and pharmacological vasodilator therapy. We have given 20 mg of tenectaplase through microcatheter in those cases. Results: There were 44 cases of no flow in our series (7.75%). TIMI 3 Flow was reestablished in thirty two patients after intracoronary tenectaplase (72%). Amongst twelve failure cases LAD involvement was most common eight cases. RCA was involved in four patients. One month mortality rate in no flow group was 50% and 6.25% in successful recanalization group. One year mortality was 12.5% in successful recanalization group and 66% in no flow group. Both were statistically significant. Conclusion: Refractory no reflow during primary PCI in STEMI is associated with high mortality and morbidity. There is no established strategy to solve this phenomenon. Intracoronary thrombolysis is an option to salvage these patients.
Descemet Endothelial Thickness Comparison Trial: Two-Year Results from a Randomized Trial Comparing Ultrathin Descemet Stripping Automated Endothelial Keratoplasty with Descemet Membrane Endothelial Keratoplasty
Authors: Jennifer Rose-Nussbaumer, Charles C. Lin, Ariana Austin, Zijun Liu, Jameson Clover, Stephen D. McLeod, Travis C. Porco, Thomas M. Lietman, Samuel M. Dresner, Beth Ann Benetz, Jonathan H. Lass, Winston D. Chamberlain
Journal: Ophthalmology (2020)
Stay-at-Home Orders During the COVID-19 Pandemic, an Opportunity to Improve Glucose Control Through Behavioral Changes in Type 1 Diabetes
Authors: Louis Potier, Boris Hansel, Etienne Larger, Jean-François Gautier, Daphné Carreira, Rachel Assemien, Olivier Lantieri, Jean-Pierre Riveline, Ronan Roussel
Journal: Diabetes Care (2020)

OBJECTIVE To investigate the impact of coronavirus disease 2019 lockdown on glycemic control and associated factors in people living with type 1 diabetes. RESEARCH DESIGN AND METHODS An observational evaluation from a self-reported questionnaire on behavioral changes and glycemic information from flash glucose monitoring (FGM) during the lockdown in 1,378 individuals living with type 1 diabetes who used a French dedicated nationwide web application (CoviDIAB). RESULTS The main outcome was the change of the mean glucose level 2 months before and 1 month after the lockdown. We found that mean glucose improved from 9.1 ± 1.7 mmol/L to 8.7 ± 1.7 mmol/L (P &amp;lt; 0.001). Factors associated with better glycemic control were a decrease of alcohol consumption (odds ratio [OR] 1.75 [95% CI 1.04–2.94]), an increase in the frequency of FGM scans (OR 1.48 [1.04–2.10]) and in the number of hypoglycemia events (OR 1.67 [1.13–2.46]), and an easier diabetes control perception (OR 1.71 [1.18–2.49]). CONCLUSIONS Our findings suggest that lockdown has a positive impact on glycemic control in people with type 1 diabetes.
Stepped Exercise Program for Patients With Knee Osteoarthritis
Authors: Kelli D. Allen, Sandra Woolson, Helen M. Hoenig, Dennis Bongiorni, James Byrd, Kevin Caves, Katherine S. Hall, Bryan Heiderscheit, Nancy Jo Hodges, Kim M. Huffman, Miriam C. Morey, Shalini Ramasunder, Herbert Severson, Courtney Van Houtven, Lauren M. Abbate, Cynthia J. Coffman
Journal: Annals of Internal Medicine (2020)

Evidence-based models are needed to deliver exercise-related services for knee osteoarthritis efficiently and according to patient needs.To examine a stepped exercise program for patients with knee osteoarthritis (STEP-KOA).Randomized controlled trial. (ClinicalTrials.gov: NCT02653768).2 U.S. Department of Veterans Affairs sites.345 patients (mean age, 60 years; 15% female; 67% people of color) with symptomatic knee osteoarthritis.Participants were randomly assigned in a 2:1 ratio to STEP-KOA or an arthritis education (AE) control group, respectively. The STEP-KOA intervention began with 3 months of an internet-based exercise program (step 1). Participants who did not meet response criteria for improvement in pain and function after step 1 progressed to step 2, which involved 3 months of biweekly physical activity coaching calls. Participants who did not meet response criteria after step 2 went on to in-person physical therapy visits (step 3). The AE group received educational materials via mail every 2 weeks.Primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Scores for the STEP-KOA and AE groups at 9 months were compared by using linear mixed models.In the STEP-KOA group, 65% of participants (150 of 230) progressed to step 2 and 35% (81 of 230) to step 3. The estimated baseline WOMAC score for the full sample was 47.5 (95% CI, 45.7 to 49.2). At 9-month follow-up, the estimated mean WOMAC score was 6.8 points (CI, -10.5 to -3.2 points) lower in the STEP-KOA than the AE group, indicating greater improvement.Participants were mostly male veterans, and follow-up was limited.Veterans in STEP-KOA reported modest improvements in knee osteoarthritis symptoms compared with the control group. The STEP-KOA strategy may be efficient for delivering exercise therapies for knee osteoarthritis.Department of Veterans Affairs, Health Services Research and Development Service.