tbuckley/cabot-search huggingface dataset:
High-flow nasal cannula for COVID-19 patients: risk of bio-aerosol dispersion
Authors: Judith Elshof, Rutger H.J. Hebbink, Marieke L. Duiverman, Rob Hagmeijer
Journal: European Respiratory Journal (2020)

<b>HFNC seems to increase droplet spread, so caution should be taken if it is applied for COVID-19, and adequate protective measures should be provided. Further research on viral spread and risks associated with HFNC therapy in COVID-19 patients is needed.</b>https://bit.ly/3gQjjrY
COVID-19 Infection in Kidney Transplant Recipients: Disease Incidence and Clinical Outcomes
Authors: Michelle Elias, Daniele Pievani, Christine Randoux, Kevin Louis, Blandine Denis, Alexandra Delion, Océane Le Goff, Corinne Antoine, Clarisse Greze, Evangeline Pillebout, Imad Abboud, Denis Glotz, Eric Daugas, Carmen Lefaucheur
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Although studies have found coronavirus disease 2019 (COVID-19) to be associated with high morbidity and mortality among kidney transplant recipients, risk factors for COVID-19 among kidney transplant patients remain poorly defined. In this prospective cohort study in France, the authors enrolled 1216 kidney transplant patients, 66 (5%) of whom were diagnosed with COVID-19. The mortality rate associated with COVID-19 for the overall study population was 1% and 24% among COVID-19–positive patients. Factors that were independently associated with COVID-19 included non-White race and comorbidities, including obesity, diabetes, and asthma and chronic pulmonary disease. In the context of COVID-19, it is imperative that policy makers integrate information about risk factors to help clinicians balance benefits and risks and better advise patients about potential risks. Background COVID-19 has been associated with high morbidity and mortality in kidney transplant recipients. However, risk factors for COVID-19 disease in patients with kidney transplants remain poorly defined. Methods We enrolled patients who underwent kidney transplantation and were actively followed up in two hospitals in Paris on March 1st, 2020. Patients were screened for baseline and transplant characteristics, functional parameters, comorbidities, and immunosuppressive therapies. COVID-19 disease was assessed. Patients were followed up during the pandemic until April 30th, 2020 by the COVID-19 SLS KT survey program, including teleconsulting, at-home monitoring for patients with COVID-19, and a dedicated phone hotline platform. Results Among 1216 patients with kidney transplants enrolled, 66 (5%) patients were identified with COVID-19 disease, which is higher than the incidence observed in the general population in France (0.3%). Their mean age was 56.4±12.5 years, and 37 (56%) patients were men. The following factors were independently associated with COVID-19 disease: non-White ethnicity (adjusted odds ratio [OR], 2.17; 95% confidence interval [95% CI], 1.23 to 3.78; P =0.007), obesity (OR, 2.19; 95% CI, 1.19 to 4.05; P =0.01), asthma and chronic pulmonary disease (OR, 3.09; 95% CI, 1.49 to 6.41; P =0.002), and diabetes (OR, 3.33; 95% CI, 1.92 to 5.77; P &lt;0.001). The mortality rate related to COVID-19 disease was 1% in the overall study population and 24% in COVID-19–positive patients. Conclusions Patients with kidney transplants display a high risk of mortality. Non-White ethnicity and comorbidities such as obesity, diabetes, asthma, and chronic pulmonary disease were associated with higher risk of developing COVID-19 disease. It is imperative that policy makers urgently ensure the integration of such risk factors on response operations against COVID-19.
A phase I study of nelfinavir, an FDA approved HIV protease inhibitor, in adults with refractory solid tumors
Authors: P. A. Dennis, G. Blumenthal, M. Ballas, E. Gardner, S. Kawabata, J. LoPiccolo, C. Helsabeck, H. Root, W. D. Figg, W. Bernstein
Journal: Journal of Clinical Oncology (2009)

2583 Background: Preclinical studies show that HIV protease inhibitors such as nelfinavir (N) have dose- dependent, pleiotropic anti-cancer activities. However, the maximum tolerated dose (MTD) of N has not been established in humans. Methods: Pts were treated on a modified Fibonacci dose-escalation scheme with a twice daily oral dose of N starting at the FDA approved dose of 1250 mg bid on a 21-day cycle. Patients with refractory solid tumors, ECOG PS &lt; 2, and adequate organ function were eligible. Therapy continued until MTD or disease progression. PBMCs as well as optional tumor biopsies were collected for Akt inhibition and expression of markers of ER stress (ERS). Results: 14 patients have been enrolled. Of the 11 evaluable for toxicity, there were 10 men, 10 Caucasians, and 1 African American (median age 63 years (range 24 - 77)). Tumor types included NSCLC (3), SCLC (2), thyroid (3), pancreatic (1), colorectal (1), and renal cell (1). Median number of prior systemic therapies was 2 (range, 1 - 6). There have been no grade 4 or 5 toxicities. We observed 12 grade 3 toxicities that were asymptomatic laboratory abnormalities. The most prevalent toxicities were ALT transaminitis (5 events in 8 subjects in dose level ((DL) 2, 3, 4), AST transaminitis (4 events in 8 subjects in DL 2, 4), diarrhea (8 events in 5 subjects in DL 2, 3, 4), and hyperglycemia (5 events in 5 subjects in DL 1, 2, 3). Enrollment continues at DL 4 (3125 mg twice daily). There have been no responses. Two subjects with lung cancer had stable disease for 9 weeks. Pharmacokinetic data revealed median Cmax of 2,461.5 ng/ml (DL1), 11,809 ng/ml (DL2), 11,576 ng/ml (DL3), and 11,986 ng/ml (DL4), occurring 4 hours after an oral dose. There was no relationship between the drug levels and albumin levels. Akt inhibition and increased expression of markers of ERS and apoptosis have been observed in PBMCs from week 1 in the majority of patients at every dose level, but there was no correlation with clinical response. Conclusions: N appears to be well tolerated in subjects with advanced solid tumors at 2.5 times the FDA approved dose. AUC data suggest that there may be only minimal increases in plasma drug concentrations with doses above 1875 mg twice daily. No significant financial relationships to disclose.
Immunohistochemical scoring of CD38 in the tumor microenvironment predicts responsiveness to anti-PD-1/PD-L1 immunotherapy in hepatocellular carcinoma
Authors: Harry Ho Man Ng, Ren Yuan Lee, Siting Goh, Isabel Shu Ying Tay, Xinru Lim, Bernett Lee, Valerie Chew, Huihua Li, Benedict Tan, Sherlly Lim, Jeffrey Chun Tatt Lim, Bijin Au, Josh Jie Hua Loh, Sahil Saraf, John Edward Connolly, Tracy Loh, Wei Qiang Leow, Joycelyn Jie Xin Lee, Han Chong Toh, Fabio Malavasi, Ser Yee Lee, Pierce Chow, Evan W Newell, Su Pin Choo, David Tai, Joe Yeong, Tony Kiat Hon Lim
Journal: Journal for ImmunoTherapy of Cancer (2020)

Introduction Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated mortality globally. Immune-checkpoint blockade (ICB) is one of the systemic therapy options for HCC. However, response rates remain low, necessitating robust predictive biomarkers. In the present study, we examined the expression of CD38, a molecule involved in the immunosuppressive adenosinergic pathway, on immune cells present in the tumor microenvironment. We then investigated the association between CD38 and ICB treatment outcomes in advanced HCC. Methods Clinically annotated samples from 49 patients with advanced HCC treated with ICB were analyzed for CD38 expression using immunohistochemistry (IHC), multiplex immunohistochemistry/immunofluorescence (mIHC/IF) and multiplex cytokine analysis. Results IHC and mIHC/IF analyses revealed that higher intratumoral CD38 + cell proportion was strongly associated with improved response to ICB. The overall response rates to ICB was significantly higher among patients with high proportion of total CD38 + cells compared with patients with low proportion (43.5% vs 3.9%, p=0.019). Higher responses seen among patients with a high intratumoral CD38 + cell proportion translated to a longer median progression-free survival (mPFS, 8.21 months vs 1.64 months, p=0.0065) and median overall survival (mOS, 19.06 months vs 9.59 months, p=0.0295). Patients with high CD38 + CD68 + macrophage density had a better mOS of 34.43 months compared with 9.66 months in patients with low CD38 + CD68 + macrophage density. CD38 hi macrophages produce more interferon γ (IFN-γ) and related cytokines, which may explain its predictive value when treated with ICB. Conclusions A high proportion of CD38 + cells, determined by IHC, predicts response to ICB and is associated with superior mPFS and OS in advanced HCC.
Gut microbes from the phylogenetically diverse genus<i>Eubacterium</i>and their various contributions to gut health
Authors: Arghya Mukherjee, Cathy Lordan, R. Paul Ross, Paul D. Cotter
Journal: Gut Microbes (2020)

Over the last two decades our understanding of the gut microbiota and its contribution to health and disease has been transformed. Among a new 'generation' of potentially beneficial microbes to have been recognized are members of the genus Eubacterium, who form a part of the core human gut microbiome. The genus consists of phylogenetically, and quite frequently phenotypically, diverse species, making Eubacterium a taxonomically unique and challenging genus. Several members of the genus produce butyrate, which plays a critical role in energy homeostasis, colonic motility, immunomodulation and suppression of inflammation in the gut. Eubacterium spp. also carry out bile acid and cholesterol transformations in the gut, thereby contributing to their homeostasis. Gut dysbiosis and a consequently modified representation of Eubacterium spp. in the gut, have been linked with various human disease states. This review provides an overview of Eubacterium species from a phylogenetic perspective, describes how they alter with diet and age and summarizes its association with the human gut and various health conditions.
Predictors of Clinical Response to Transcatheter Reduction of Secondary Mitral Regurgitation
Authors: Paul A. Grayburn, Anna Sannino, David J. Cohen, Saibal Kar, D. Scott Lim, Jacob M. Mishell, Brian K. Whisenant, Michael J. Rinaldi, Samir R. Kapadia, Vivek Rajagopal, Aaron Crowley, Lak N. Kotinkaduwa, JoAnn Lindenfeld, William T. Abraham, Michael J. Mack, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2020)
Abstract 6693: Metronomic treatment of orally available oxaliplatin and pemetrexed to potentiate the efficacy of anti-PD-1 by modulating tumor immunity
Authors: Ruby Maharjan
Journal: Cancer Research (2020)

Abstract The rational combination of metronomic chemotherapy (MCT) with immunotherapy has the potential of immune modulation inducing enhancement of host immunity, thereby overcome tumor induced immunosuppressive defense. In this study, oral formulation of oxaliplatin (OXA) and pemetrexed (PMX) were developed by complexing ionically with Nα-deoxycholyl-l-lysyl-methylester (DCK) as intestinal permeability enhancer to form OXA/DCK-NE and PMX/DCK-OP respectively. OXA/DCK-NE and PMX/DCK-OP were combined for oral MCT and its anti-tumor effect was examined against maximum tolerated dose (MTD) of same drug combination by intravenous administration in colon cancer (CT26) syngeneic mouse model. MCT was able to modulate immunity in CT26 mouse model compared to MTD, such as enhancement of effector T-cell population in tumor, elevation of tumor antigen uptake, and activation of dendritic cells as analyzed by flow cytometry of tumor tissue and draining lymph nodes (TDLN). Moreover, cytotoxic T-cell and helper T-cell populations in lymphoid organs such as blood, spleen, and TDLN were found to be upregulated in MCT group but not in MTD group. Furthermore, on combining MCT with αPD-1, the tumor suppression was more effective showing 97.8% decrease in tumor volume compared to that of control leading to tumor free mice (95% complete response). Mice that achieved complete antitumor response upon re-challenge, demonstrated that combination therapy of MCT and αPD-1 induced memory response which was further confirmed by 1.5-fold enhanced antigen specific memory response compared to αPD-1 only treated group as detected by secretion of INF-γ. In this study, we observed that combination of OXA/DCK-NE and PMX/DCK-OP with αPD-1 therapy synergized immunomodulatory effect by enhancing the populations of effector T-cells thereby inducing complete response and antigen specific memory response. Thus, this suggests the rationality of combination treatment with oral metronomic OXA and PMX with αPD-1 to elicit effective immune modulation. Citation Format: Ruby Maharjan. Metronomic treatment of orally available oxaliplatin and pemetrexed to potentiate the efficacy of anti-PD-1 by modulating tumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6693.
Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial
Authors: Catherine S Diefenbach, Fangxin Hong, Richard F Ambinder, Jonathon B Cohen, Michael J Robertson, Kevin A David, Ranjana H Advani, Timothy S Fenske, Stefan K Barta, Neil D Palmisiano, Jakub Svoboda, David S Morgan, Reem Karmali, Elad Sharon, Howard Streicher, Brad S Kahl, Stephen M Ansell
Journal: The Lancet Haematology (2020)
Tests and Measurements in Physical Education.
Journal: JAMA (1931)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches
Authors: Yiming Niu, Zhenzhen Wang, Yuchen Shi, Lei Dong, Chunming Wang
Journal: Bioactive Materials (2020)

A coordinated interaction between osteogenesis and osteoimmune microenvironment is essential for successful bone healing. In particular, macrophages play a central regulatory role in all stages of bone repair. Depending on the signals they sense, these highly plastic cells can mediate the host immune response against the exterior signals of molecular stimuli and implanted scaffolds, to exert regenerative potency to a varying extent. In this article, we first encapsulate the immunomodulatory functions of macrophages during bone regeneration into three aspects, as sweeper, mediator and instructor. We introduce the phagocytic role of macrophages in different bone healing periods ('sweeper') and overview a variety of paracrine cytokines released by macrophages either mediating cell mobilisation, vascularisation and matrix remodelling ('mediator'), or directly driving the osteogenic differentiation of bone progenitors and bone repair ('instructor'). Then, we systematically classify and discuss the emerging engineering strategies to recruit, activate and modulate the phenotype transition of macrophages, to exploit the power of endogenous macrophages to enhance the performance of engineered bone tissue.
Exaggerated neutrophil extracellular trap formation in Kawasaki disease: a key phenomenon behind the outbreak in western countries?
Authors: Kouhei Yamashita, Akifumi Takaori-Kondo, Kiyomi Mizugishi
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article by Pouletty et al recently published in your journal.1 The authors described a series of 16 cases with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the Paris area. While the affected children exhibited, in a complete or incomplete form, clinical features of Kawasaki disease (KD), they also presented several features distinct from KD, such as an older age at onset and a higher frequency of myocarditis and/or pericarditis, and of resistance to first treatment with intravenous immunoglobulin (IVIG). Clusters of similar cases have been identified in the USA and other European countries since April 2020.2 3 However, it is still a matter of debate whether PIMS-TS and KD share aetiology and/or pathophysiology, or represent two distinct clinical entities. Herein, we explore the cause behind its outbreak in relation to neutrophil extracellular traps (NETs), a novel killing mechanism of neutrophils.

KD is a multisystem vasculitis that primarily affects coronary arteries of young children, especially in Japan. Although the aetiology of KD remains unclear, it may be triggered by infectious agents, leading to exaggerated activation of immune systems in genetically susceptible children. We first investigated whether KD patients’ serum stimulates NET formation in human neutrophils. NETs are extracellular structures primarily composed of …
Hyperglycemia Induces Myocardial Dysfunction via Epigenetic Regulation of JunD
Authors: Shafaat Hussain, Abdul Waheed Khan, Alexander Akhmedov, Rosa Suades, Sarah Costantino, Francesco Paneni, Kenneth Caidahl, Shafeeq A. Mohammed, Camilla Hage, Christos Gkolfos, Hanna Björck, John Pernow, Lars H. Lund, Thomas F. Lüscher, Francesco Cosentino
Journal: Circulation Research (2020)

Rationale: Hyperglycemia -induced reactive oxygen species are key mediators of cardiac dysfunction. JunD (Jund proto-oncogene subunit), a member of the AP-1 (activator protein-1) family of transcription factors, is emerging as a major gatekeeper against oxidative stress. However, its contribution to redox state and inflammation in the diabetic heart remains to be elucidated. Objective: The present study investigates the role of JunD in hyperglycemia-induced and reactive oxygen species–driven myocardial dysfunction. Methods and Results: JunD mRNA and protein expression were reduced in the myocardium of mice with streptozotocin-induced diabetes mellitus as compared to controls. JunD downregulation was associated with oxidative stress and left ventricular dysfunction assessed by electron spin resonance spectroscopy as well as conventional and 2-dimensional speckle-tracking echocardiography. Furthermore, myocardial expression of free radical scavenger superoxide dismutase 1 and aldehyde dehydrogenase 2 was reduced, whereas the NOX2 (NADPH [nicotinamide adenine dinucleotide phosphatase] oxidase subunit 2) and NOX4 (NADPH [nicotinamide adenine dinucleotide phosphatase] oxidase subunit 4) were upregulated. The redox changes were associated with increased NF-κB (nuclear factor kappa B) binding activity and expression of inflammatory mediators. Interestingly, mice with cardiac-specific overexpression of JunD via the α MHC (α- myosin heavy chain) promoter (α MHC JunD tg ) were protected against hyperglycemia-induced cardiac dysfunction. We also showed that JunD was epigenetically regulated by promoter hypermethylation, post-translational modification of histone marks, and translational repression by miRNA (microRNA)-673/menin. Reduced JunD mRNA and protein expression were confirmed in left ventricular specimens obtained from patients with type 2 diabetes mellitus as compared to nondiabetic subjects. Conclusions: Here, we show that a complex epigenetic machinery involving DNA methylation, histone modifications, and microRNAs mediates hyperglycemia-induced JunD downregulation and myocardial dysfunction in experimental and human diabetes mellitus. Our results pave the way for tissue-specific therapeutic modulation of JunD to prevent diabetic cardiomyopathy.
Association of expression of bcl-2 with outcome in non-small cell lung cancer
Authors: V. Anagnostou, F. Lowery, K. Syrigos, K. Frangia, V. Zolota, N. Panagopoulos, D. Dougenis, L. Tanoue, F. Detterbeck, R. Homer, D. Rimm
Journal: Journal of Clinical Oncology (2009)

e22039 Background: BCL-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. It is preferentially expressed in squamous cell carcinomas of the lung and has been investigated as a potential prognostic parameter in lung cancer patients with conflicting results. Here, we quantitatively assessed BCL-2 protein expression in two large and independent data sets to investigate the impact of BCL-2 on patient survival. Methods: AQUA, a fluorescent-based method for analysis of in situ protein expression, was used to measure BCL-2 protein levels and classify tumor by BCL-2 expression in a cohort of 180 lung cancer patients from Yale New Haven Hospital (training set). An independent cohort of 360 lung cancer patients from Sotiria General Hospital and Patras University Hospital in Greece was used to validate BCL-2 classification and evaluate outcome (validation set). Results: Tumors expressed BCL-2 in 57% and 53% of the cases in training and validation cohorts respectively and squamous cell carcinomas expressed higher levels of BCL-2 expression compared to adenocarcinomas (mean AQUA score 42 and 26 respectively, p=0.007); BCL-2 was not associated with other standard clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median overall survival compared to the low expressers (20 vs 15 months, log rank p=0.016). Multivariate analysis revealed an independent lower risk of death for lung cancer patients with BCL-2 expressing tumors (HR=0.58, 95% CI 0.39–0.86, p=0.006). Conclusions: BCL-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of lung cancer patients as well as incorporation of BCL-2 into clinical decisions. [Table: see text]
포스터전시 : 건경변증에서 비장종대 및정맥류와 연관된 도플러 혈역학적 요소
Authors: 김상균, 김영석, 장재영, 정승원, 박지영, 문종호, 김홍수, 이문성, 심찬섭, 김부성
Journal: Clinical and Molecular Hepatology (2008)
Black babies are less likely to die when cared for by black doctors, US study finds
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Black newborn babies who are cared for by black doctors are more likely to survive than those cared for by white doctors, a US study has found.1

Researchers analysed 1.8 million hospital births in Florida from 1992 to 2015 and found that deaths were fewer by 257 in 100 000 among black newborns under the care of black doctors, when compared with care by white doctors. The US Centers for Disease Control and Prevention had reported last year that, in 2017, the infant mortality rate among black …