tbuckley/cabot-search huggingface dataset:
<i>JAMA Surgery</i>—The Year in Review, 2019
Authors: Melina R. Kibbe
Journal: JAMA Surgery (2020)

This was a truly exciting year for JAMA Surgery, as the journal experienced several notable accomplishments.First, as evidence of the high-quality scientific publications in JAMA Surgery, the impact factor rose from 8.5 to 10.7.This remarkable achievement reflects the hard work of our authors, peer reviewers, 1 and editorial team.The impact factor of 10.7 positions JAMA Surgery as the number 1 ranked surgery journal in the world, a tremendous accomplishment.More importantly, JAMA Surgery is the first surgical journal to achieve a double-digit impact factor-a true accomplishment for the entire field of surgery.In 2019, the acceptance rate was 15.6% for all article types, 5.5% for Original Investigations, and 14.4% for Research Letters.The journal's most popular articles by views and downloads, news and social media coverage, and citations are listed in the Table. 2-8 The web and social media presence for JAMA Surgery continues to be very strong under the leadership of Amalia Cochran, MD, the Web and Social Media Editor.More than 3.8 million articles were viewed and downloaded from the journal website in 2019.The journal's electronic table of contents is delivered each week to more than 68 000 individuals.We cur-rently have 30 900 Twitter followers, which represents a 22.6% increase in 2019, and 25 691 Facebook followers, which represents an 11.7% increase in 2019 (Table).Thus, between the electronic table of contents, visits to the journal website, social media reach, and print distribution, JAMA Surgery reaches more than 80 000 individuals weekly.JAMA Surgery continues to promote the work of the authors through additional outlets.JAMA Surgery publishes author interview podcasts, 9 and in 2019, we published 1 each month.These podcasts continue to be stimulating under the direction of Cochran, who brings a wonderful level of insight into the interview process with the authors.
Channel management in virtual care
Authors: Matt Desruisseaux, Vess Stamenova, R. Sacha Bhatia, Onil Bhattacharyya
Journal: npj Digital Medicine (2020)

Many virtual care initiatives focus heavily on video visits, essentially mimicking face-to-face visits. Meanwhile, clinicians in established settings continue to use the oldest modality, phone calls, and some use the most ubiquitous, asynchronous messaging. The latter, along with live chat and chatbots, could be transformative if workflows were redesigned to incorporate it. With multiple modalities now available for use in virtual care, the central problem is to direct patient-provider interactions to the channels generating the most value. Marketers call this channel management and use sophisticated approaches to implement it. We propose an adaptation of channel management to virtual care and discuss anticipated challenges to its implementation.
Safety and efficacy of immune checkpoint inhibitors in advanced urological cancers with pre-existing autoimmune disorders: a retrospective international multicenter study
Authors: Nieves Martinez Chanza, Wanling Xie, Majd Issa, Hannah Dzimitrowicz, Abhishek Tripathi, Benoit Beuselinck, Elaine Lam, Yousef Zakharia, Rana Mckay, Sumit Shah, Amir Mortazavi, Michael R. Harrison, Spyridon Sideris, Marina D Kaymakcalan, Sarah Abou Alaiwi, Amin H Nassar, Pier Vitale Nuzzo, Anis Hamid, Toni K Choueiri, Lauren C Harshman
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background There is limited experience regarding the safety and efficacy of checkpoint inhibitors (CPI) in patients with autoimmune disorders (AD) and advanced urological cancers as they are generally excluded from clinical trials due to risk of exacerbations. Methods This multicenter retrospective cohort analysis of patients with advanced renal cell cancer (RCC) and urothelial cancer (UC) with pre-existing AD treated with CPI catalogued the incidence of AD exacerbations, new immune-related adverse events (irAEs) and clinical outcomes. Competing risk models estimated cumulative incidences of exacerbations and new irAEs at 3 and 6 months. Results Of 106 patients with AD (58 RCC, 48 UC) from 10 centers, 35 (33%) had grade 1/2 clinically active AD of whom 10 (9%) required corticosteroids or immunomodulators at baseline. Exacerbations of pre-existing AD occurred in 38 (36%) patients with 17 (45%) requiring corticosteroids and 6 (16%) discontinuing CPI. New onset irAEs occurred in 40 (38%) patients with 22 (55%) requiring corticosteroids and 8 (20%) discontinuing CPI. Grade 3/4 events occurred in 6 (16%) of exacerbations and 13 (33%) of new irAEs. No treatment-related deaths occurred. Median follow-up was 15 months. For RCC, objective response rate (ORR) was 31% (95% CI 20% to 45%), median time to treatment failure (TTF) was 7 months (95% CI 4 to 10) and 12-month overall survival (OS) was 78% (95% CI 63% to 87%). For UC, ORR was 40% (95% CI 26% to 55%), median TTF was 5.0 months (95% CI 2.3 to 9.0) and 12-month OS was 63% (95% CI 47% to 76%). Conclusions Patients with RCC and UC with well-controlled AD can benefit from CPI with manageable toxicities that are consistent with what is expected of a non-AD population. Prospective study is warranted to comprehensively evaluate the benefits and safety of CPI in patients with AD.
Genetic disruption of N-RasG12D palmitoylation perturbs hematopoiesis and prevents myeloid transformation in mice
Authors: Noemi A. Zambetti, Ari J. Firestone, Jarrett R. Remsberg, Benjamin J. Huang, Jasmine C. Wong, Amanda M. Long, Marina Predovic, Radu M. Suciu, Anagha Inguva, Scott C. Kogan, Kevin M. Haigis, Benjamin F. Cravatt, Kevin Shannon
Journal: Blood (2020)
Stepwise selection on homeologous PRR genes controlling flowering and maturity during soybean domestication
Authors: Sijia Lu, Lidong Dong, Chao Fang, Shulin Liu, Lingping Kong, Qun Cheng, Liyu Chen, Tong Su, Haiyang Nan, Dan Zhang, Lei Zhang, Zhijuan Wang, Yongqing Yang, Deyue Yu, Xiaolei Liu, Qingyong Yang, Xiaoya Lin, Yang Tang, Xiaohui Zhao, Xinquan Yang, Changen Tian, Qiguang Xie, Xia Li, Xiaohui Yuan, Zhixi Tian, Baohui Liu, James L. Weller, Fanjiang Kong
Journal: Nature Genetics (2020)
Abstract 15964: Right Ventricular to Pulmonary Circulation Uncoupling is Associated With Reduced Stroke Volume Reserve and Worse Exercise Performance in Patients With Heart Failure
Authors: Andrea Giammarresi, Francesco Bandera, Maurizio Losito, Valentina Labate, Marco Guazzi
Journal: Circulation (2018)

Background: In heart failure (HF) syndrome, progressive development of pulmonary hypertension and right ventricular (RV) dysfunction and failure carries a significant negative prognostic value, reg...
Multifaceted effects of soluble human CD6 in experimental cancer models
Authors: Inês T Simões, Fernando Aranda, Sergi Casadó-Llombart, María Velasco-de Andrés, Cristina Català, Pilar Álvarez, Marta Consuegra-Fernández, Marc Orta-Mascaró, Ramón Merino, Jesús Merino, José Alberola-Ila, Gloria González-Aseguinolaza, Esther Carreras, Vanesa Martínez, Francisco Lozano
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background CD6 is a lymphocyte surface co-receptor physically associated with the T-cell receptor (TCR)/CD3 complex at the center of the immunological synapse. There, CD6 assists in cell-to-cell contact stabilization and modulation of activation/differentiation events through interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), its main reported ligand. While accumulating evidence is attracting new interest on targeting CD6 for therapeutic purposes in autoimmune disorders, little is known on its potential in cancer. In an attempt to elucidate the in vivo relevance of blocking CD6-mediated interactions in health and disease, we explored the consequences of expressing high circulating levels of a soluble form CD6 (sCD6) as a decoy receptor. Methods High sCD6 serum levels were achieved by using transgenic C57BL/6 mice expressing human sCD6 under the control of lymphoid-specific transcriptional elements (shCD6LckEμTg) or wild type either transduced with hepatotropic adeno-associated virus coding for mouse sCD6 or undergoing repeated infusions of recombinant human sCD6 protein. Characterization of sCD6-induced changes was performed by ex vivo flow cytometry and functional analyses of mouse lymphoid organ cells. The in vivo relevance of those changes was explored by challenging mice with subcutaneous or metastatic tumors induced by syngeneic cancer cells of different lineage origins. Results Through a combination of in vitro and in vivo studies, we show that circulating sCD6 expression induces defective regulatory T cell (Treg) generation and function, decreased CD166/ALCAM-mediated tumor cell proliferation/migration and impaired galectin-induced T-cell apoptosis, supporting the fact that sCD6 modulates antitumor lymphocyte effector function and tumorigenesis. Accordingly, sCD6 expression in vivo resulted in delayed subcutaneous tumor growth and/or reduced metastasis on challenge of mice with syngeneic cancer cells. Conclusions Evidence is provided for the disruption of CD6 receptor–ligand interactions as a feasible immunomodulatory approach in cancer.
The effect of transarterial radioembolization on leukocyte subclasses in patients with hepatocellular carcinoma: Results of a preliminary study
Authors: Tevfik Tolga Sahin, Koray Kutluturk, Serdar Karakas, Basri Satilmis, Volkan Ince, Kerem Tolan, Adil Baskiran, Ramazan Kutlu, Brian I. Carr, Sezai Yilmaz
Journal: International Journal of Surgery (2020)
HBV vaccination and HBV infection induces HBV-specific natural killer cell memory
Authors: Ratna S Wijaya, Scott A Read, Naomi R Truong, Shuanglin Han, Dishen Chen, Haleh Shahidipour, Nicole L Fewings, Stephen Schibeci, Mahmoud K Azardaryany, Grant P Parnell, David Booth, David van der Poorten, Rita Lin, Jacob George, Mark W Douglas, Golo Ahlenstiel
Journal: Gut (2020)

Objective Vaccination against hepatitis B virus (HBV) confers protection from subsequent infection through immunological memory that is traditionally considered the domain of the adaptive immune system. This view has been challenged following the identification of antigen-specific memory natural killer cells (mNKs) in mice and non-human primates. While the presence of mNKs has been suggested in humans based on the expansion of NK cells following pathogen exposure, evidence regarding antigen-specificity is lacking. Here, we demonstrate the existence of HBV-specific mNKs in humans after vaccination and in chronic HBV infection. Design NK cell responses were evaluated by flow cytometry and ELISA following challenge with HBV antigens in HBV vaccinated, non-vaccinated and chronic HBV-infected individuals. Results NK cells from vaccinated subjects demonstrated higher cytotoxic and proliferative responses against autologous hepatitis B surface antigen (HBsAg)-pulsed monocyte-derived dendritic cells (moDCs) compared with unvaccinated subjects. Moreover, NK cell lysis of HBsAg-pulsed moDCs was significantly higher than that of hepatitis B core antigen (HBcAg)-pulsed moDCs (non-vaccine antigen) or tumour necrosis factor α-activated moDCs in a NKG2D-dependent manner. The mNKs response was mediated by CD56 dim NK cells coexpressing CD57, CD69 and KLRG1. Further, mNKs from chronic hepatitis B patients exhibited greater degranulation against HBcAg-pulsed moDCs compared with unvaccinated or vaccinated patients. Notably, mNK activity was negatively correlated with HBV DNA levels. Conclusions Our data support the presence of a mature mNKs following HBV antigen exposure either through vaccination or infection. Harnessing these antigen specific, functionally active mNKs provides an opportunity to develop novel treatments targeting HBV in chronic infection.
Sex‐related differences in contemporary biomarkers for heart failure: a review
Authors: Navin Suthahar, Laura M.G. Meems, Jennifer E. Ho, Rudolf A. de Boer
Journal: European Journal of Heart Failure (2020)

The use of circulating biomarkers for heart failure (HF) is engrained in contemporary cardiovascular practice and provides objective information about various pathophysiological pathways associated with HF syndrome. However, biomarker profiles differ considerably among women and men. For instance, in the general population, markers of cardiac stretch (natriuretic peptides) and fibrosis (galectin-3) are higher in women, whereas markers of cardiac injury (cardiac troponins) and inflammation (sST2) are higher in men. Such differences may reflect sex-specific pathogenic processes associated with HF risk, but may also arise as a result of differences in sex hormone profiles and fat distribution. From a clinical perspective, sex-related differences in biomarker levels may affect the objectivity of biomarkers in HF management because what is considered to be 'normal' in one sex may not be so in the other. The objectives of this review are, therefore: (i) to examine the sex-specific dynamics of clinically relevant HF biomarkers in the general population, as well as in HF patients; (ii) to discuss the overlap between sex-related and obesity-related effects, and (iii) to identify knowledge gaps to stimulate research on sex-related differences in HF.
The Views and Experiences of Clinicians Sharing Medical Record Notes With Patients
Authors: Catherine M. DesRoches, Suzanne Leveille, Sigall K. Bell, Zhiyong J. Dong, Joann G. Elmore, Leonor Fernandez, Kendall Harcourt, Patricia Fitzgerald, Thomas H. Payne, Rebecca Stametz, Tom Delbanco, Jan Walker
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The 21st Century Cures Act of 2016 requires that patients be given electronic access to all the information in their electronic medical records. The regulations for implementation of this law give patients far easier access to information about their care, including the notes their clinicians write. <h3>Objective</h3> To assess clinicians' views and experiences with sharing clinical notes (open notes) with patients. <h3>Design, Setting, and Participants</h3> Web-based survey study of physicians, advanced practice nurses, registered nurses, physician assistants, and therapists at 3 health systems in Boston, Massachusetts; Seattle, Washington; and rural Pennsylvania where notes have been shared across all outpatient specialties for at least 4 years. Participants were clinicians in hospital-based offices and community practices who had written at least 1 note opened by a patient in the year prior to the survey, which was administered from May 21, 2018, to August 31, 2018. <h3>Main Outcomes and Measures</h3> Clinicians' experiences with and perceptions of sharing clinical notes with patients. <h3>Results</h3> Invitations were sent to 6064 clinicians; 1628 (27%) responded. Respondents were more likely than nonrespondents to be female (65% vs 55%) and to be younger (mean [SD] age, 42.1 [12.6] vs 44.9 [12.7] years). The majority of respondents were physicians (951 [58%]), female (1023 [65%]), licensed to practice in 2000 or later (940 [61%]), and spent fewer than 40 hours per week in direct patient care (1083 [71%]). Most viewed open notes positively, agreeing they are a good idea (1182 participants [74%]); of 1314 clinicians who were aware that patients were reading their notes, 965 (74%) agreed that open notes were useful for engaging patients. In all, 798 clinicians (61%) would recommend the practice to colleagues. A total of 292 physicians (37%) reported spending more time on documentation, and many reported specific changes in the way they write their notes, the most frequent of which related to use of language that could be perceived as critical of the patient (422 respondents [58%]). Most physicians (1234 [78%]) favored being able to determine readily that their notes had been read by their patients. <h3>Conclusions and Relevance</h3> In this survey of clinicians in a wide range of specialties who had several years of experience offering their patients ready access to their notes, more than two-thirds supported this new practice. Even among subgroups of clinicians who were less enthusiastic, most endorsed the idea of sharing notes and believed the practice could be helpful for engaging patients more actively in their care.
Marrow-Infiltrating Regulatory T Cells Correlate with the Presence of Dysfunctional CD4+PD-1+ Cells and Inferior Survival in Patients with Newly Diagnosed Multiple Myeloma
Authors: Nouf Alrasheed, Lydia Lee, Ehsan Ghorani, Jake Y. Henry, Lucia Conde, Melody Chin, Daria Galas-Filipowicz, Andrew J.S. Furness, Selina J. Chavda, Huw Richards, Dunnya De-Silva, Oliver C. Cohen, Dominic Patel, Anthony Brooks, Manuel Rodriguez-Justo, Martin Pule, Javier Herrero, Sergio A. Quezada, Kwee L. Yong
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Immune dysregulation is described in multiple myeloma. While preclinical models suggest a role for altered T-cell immunity in disease progression, the contribution of immune dysfunction to clinical outcomes remains unclear. We aimed to characterize marrow-infiltrating T cells in newly diagnosed patients and explore associations with outcomes of first-line therapy. Experimental Design: We undertook detailed characterization of T cells from bone marrow (BM) samples, focusing on immune checkpoints and features of immune dysfunction, correlating with clinical features and progression-free survival. Results: We found that patients with multiple myeloma had greater abundance of BM regulatory T cells (Tregs) which, in turn, expressed higher levels of the activation marker CD25 compared with healthy donors. Patients with higher frequencies of Tregs had shorter PFS and a distinct Treg immune checkpoint profile (increased PD-1, LAG-3) compared with patients with lower frequencies of Tregs. Analysis of CD4 and CD8 effectors revealed that low CD4effector (CD4eff):Treg ratio and increased frequency of PD-1–expressing CD4eff cells were independent predictors of early relapse over and above conventional risk factors, such as genetic risk and depth of response. Ex vivo functional analysis and RNA sequencing revealed that CD4 and CD8 cells from patients with greater abundance of CD4effPD-1+ cells displayed transcriptional and secretory features of dysfunction. Conclusions: BM-infiltrating T-cell subsets, specifically Tregs and PD-1–expressing CD4 effectors, negatively influence clinical outcomes in newly diagnosed patients. Pending confirmation in larger cohorts and further mechanistic work, these immune parameters may inform new risk models, and present potential targets for immunotherapeutic strategies.
Money injection for public services
Authors: Richard Murray
Journal: BMJ (2020)

On 11 March, Rishi Sunak, the chancellor of the exchequer, presented his first budget and promised an extra £5bn (€5.7bn; $6.2bn) for public services to help them deal with covid-19. 1at is the £5bn for?£1.6bn is going to local authorities to support social care, social care staff, and the vulnerable.£1.3bn is going to support quicker discharge from NHS hospitals, 2 with the aim of freeing up 15 000 beds and capacity for the expected surge in emergency admissions.The rest was not earmarked, but it is easy to see what many of the big ticket items are, at least for the NHS and social care.An unprecedented deal to buy up capacity in the private healthcare sector will come at a price (even though it is being bought at cost) but brings with it beds, equipment, and, most critically, staff.Additional tests, ventilators, and personal protective equipment (PPE) and creating new hospitals in conference centres across the UK are also priorities.Expansion of the work force, however hard that is, will of course push up the wage bill.
A role for α-Synuclein in axon growth and its implications in corticostriatal glutamatergic plasticity in Parkinson’s disease
Authors: Meir Schechter, Jessica Grigoletto, Suaad Abd-Elhadi, Hava Glickstein, Alexander Friedman, Geidy E. Serrano, Thomas G. Beach, Ronit Sharon
Journal: Molecular Neurodegeneration (2020)

Abstract Background α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson’s disease (PD). α-Syn has been shown to associate with membranes and bind acidic phospholipids. However, the physiological importance of these associations to the integrity of axons is not fully clear. Methods Biochemical, immunohistochemical and ultrastructural analyses in cultured neurons, transgenic mouse brains, PD and control human brains. Results We analyzed the ultrastructure of cross-sectioned axons localized to white matter tracts (WMTs), within the dorsal striatum of old and symptomatic α-Syn transgenic mouse brains. The analysis indicated a higher density of axons of thinner diameter. Our findings in cultured cortical neurons indicate a role for α-Syn in elongation of the main axon and its collaterals, resulting in enhanced axonal arborization. We show that α-Syn effect to enhance axonal outgrowth is mediated through its activity to regulate membrane levels of the acidic phosphatidylinositol 4,5-bisphosphate (PI4,5P 2 ). Moreover, our findings link α-Syn- enhanced axonal growth with evidence for axonal injury. In relevance to disease mechanisms, we detect in human brains evidence for a higher degree of corticostriatal glutamatergic plasticity within WMTs at early stages of PD. However, at later PD stages, the respective WMTs in the caudate are degenerated with accumulation of Lewy pathology. Conclusions Our results show that through regulating PI4,5P 2 levels, α-Syn acts to elongate the main axon and collaterals, resulting in a higher density of axons in the striatal WMTs. Based on these results we suggest a role for α-Syn in compensating mechanisms, involving corticostriatal glutamatergic plasticity, taking place early in PD.
Successful endoscopic resection using a bipolar snare for an adenoma overlying a transverse colonic lipoma
Authors: Shozo Osera, Tomoaki Shinohara, Akihisa Tomori, Tamaki Momoi, Hideki Fukushima, Takeshi Hisa, Satoshi Shiozawa
Journal: Endoscopy (2020)

Colonic lipomas are uncommon mesenchymal neoplasms, and the transverse colon appears to be the rarest site for colonic lipomas [1]. Furthermore, it is rare to have an adenomatous polyp growing over the mucosal surface of a colonic lipoma.