tbuckley/cabot-search huggingface dataset:
Abstract 18997: Clinical and Echocardiographic Presentation of Post-myocardial Infarction Papillary Muscle Rupture
Authors: Émilie LeRoux, Vincent Chauvette, Pierre Voisine, François Dagenais, Éric Charbonneau, Élie Dubois-Sénéchal, Michelle Dubois, Mario Senechal
Journal: Circulation (2017)

Introduction: Mitral regurgitation (MR) caused by papillary muscle rupture (PMR) is a rare complication of myocardial infarction (MI). Acute complete papillary muscle ruptures (cPMR) are usually as...
Much to do with nothing: microsimulation study on time management in primary care
Authors: Tanner J Caverly, Rodney A Hayward, James F Burke
Journal: BMJ (2018)

Abstract Objective To investigate the credibility of claims that general practitioners lack time for shared decision making and preventive care. Design Monte Carlo microsimulation study. Setting Primary care, United States. Participants Sample of general practitioners (n=1000) representative of annual work hours and patient panel size (n=2000 patients) in the US, derived from the National Health and Nutrition Examination Survey. Main outcome measures The primary outcome was the time needed to deliver shared decision making for highly recommended preventive interventions in relation to time available for preventive care—the prevention-time-space-deficit (ie, time-space needed by doctor exceeding the time-space available). Results On average, general practitioners have 29 minutes each workday to discuss preventive care services (just over two minutes for each clinic visit) with patients, but they need about 6.1 hours to complete shared decision making for preventive care. 100% of the study sample experienced a prevention-time-space-deficit (mean deficit 5.6 h/day) even given conservative (ie, absurdly wishful) time estimates for shared decision making. However, this time deficit could be easily overcome by reducing personal time and shifting gains to work tasks. For example, general practitioners could reduce the frequency of bathroom breaks to every other day and skip time with older children who don’t like them much anyway. Conclusions This study confirms a widely held suspicion that general practitioners waste valuable time on “personal care” activities. Primary care overlords, once informed about the extent of this vast reservoir of personal time, can start testing methods to “persuade” general practitioners to reallocate more personal time toward bulging clinical demands.
Abstract 18285: Embryonic Stem Cell Transcriptome Remodeling by a Nucleoporin Substrate for Atrial Fibrillation
Authors: Claudia C Preston, Saranya P Wyles, Santiago Reyes, Bruce W Eckloff, Randolph S Faustino
Journal: Circulation (2017)

Introduction: Nup155 is a nuclear pore complex protein identified as a potential clinical driver of idiopathic atrial fibrillation (Afib), however its mechanism of action is unknown. Here we examin...
Abstract 18940: Severity and Pattern of Aortic Valve Calcification by Cardiac CT Does Not Predict the Need for Permanent Pacemaker Implantation or Development of Left Bundle Branch Block After Transcatheter Aortic Valve Replacement
Authors: Siri Kunchakarra, Ahmad Agha, Shermeen Memon, Lara Bakhos, Khaled Dajani, Ferdinand Leya, Mushabbar Syed
Journal: Circulation (2017)

Introduction: Transcatheter aortic valve implantation (TAVI) with self-expanding prosthetic aortic valve (CoreValve) has been noted to have an increased incidence of new persistent left bundle bran...
Abstract 18750: Increased Brown Adipose Tissue as a Novel Mechanism Mediating Cardioprotection
Authors: Jie Zhang, Dorothy E Vatner, Stephen F Vatner
Journal: Circulation (2016)

The regulator of G protein signaling 14 (RGS14) knock out (KO) mice have a novel feature, i.e., increased brown adipose tissue, which is known to protect against cold exposure, diabetes and obesity, but less is known about its role in cardioprotection. Accordingly we examined the effects of acute myocardial ischemia induced by 30 min coronary artery occlusion (CAO) and 24 hours of coronary artery reperfusion (CAR) in 3-4 month old RGS14 KO and their wild type (WT) littermates. Infarct size, as a fraction of the area at risk determined by TTC staining, was significantly reduced, p<0.05, in RGS14 KO (27.9±0.8%), compared to WT (46.3±1.0%). The next goal of this study was to determine whether the mechanism of protection involved brown adipose tissue. Accordingly, we removed the interscapular brown adipose tissue from the RGS14 KO and transplanted it to the abdominal cavity of the WT. Two months later, both the brown adipose tissue donor (RGS14 KO) and recipient mice (WT which received the brown adipose tissu...
RUNX3 represses neurotrophin receptor TrkB in neuroblastoma
Authors: Ken-ichi Inoue, Kosei Ito, Yoshiaki Ito
Journal: Cancer Research (2007)

1009  Runx3, a Runt-domain transcription factor, controls distinct neuronal traits in dorsal root ganglion. Here we show that neurotrophin receptor TrkB is a critical target of Runx3. Neuroblastoma-derived cell lines underwent differentiation upon stimulation by retinoic acid with concomitant increase of TrkB expression. Exogenous RUNX3 blocked the TrkB up-regulation and increased TrkC expression instead, resulting in change of the neurotrophin preference in serum-free culture. In addition, RUNX3 repressed oncogenic TrkB expression in proliferating condition and sensitized cells to chemotherapeutic drug, cisplatin. Most neuroblastoma cell lines had lost endogenous RUNX3 expression but in few exceptional cases, the expression was maintained, albeit with low level. Blockade of endogenous RUNX3 function by dominant negative Runt domain de-repressed TrkB expression and increased tumor metastasis in nude mouse xenograft assay. Taken together, RUNX3 is likely to be a rate-limiting factor which controls tumor progression through the repression of TrkB.
Obesity and Weight Gain Since Early Adulthood Are Associated With a Lower Risk of Microscopic Colitis
Authors: Po-Hong Liu, Kristin E. Burke, Ashwin N. Ananthakrishnan, Paul Lochhead, Ola Olen, Jonas F. Ludvigsson, James M. Richter, Andrew T. Chan, Hamed Khalili
Journal: Clinical Gastroenterology and Hepatology (2018)
Updated BTS Adult Bronchiectasis Guideline 2018: a multidisciplinary approach to comprehensive care
Authors: Adam T Hill, Sally A Welham, Anita L Sullivan, Michael R Loebinger
Journal: Thorax (2018)

The new British Thoracic Society (BTS) Guideline for Bronchiectasis in Adults has been published. This article provides a summary of key highlights of the new BTS Guideline and covers who to investigate, what investigations should be carried out and a management strategy.
Adventures in self experimentation
Authors: Gareth J Parry, Eric J Buenz
Journal: BMJ (2018)

Gareth Parry and Eric Buenz explore the storied history of scientists using themselves as guinea pigs Self experimentation is a rich medical tradition, leading to remarkable scientific advances but also erroneous conclusions and, sometimes, death. Recently we explored the properties of Urtica ferox , a stinging nettle endemic to New Zealand (fig 1). During a collection expedition a 71 year old emeritus neurologist indulged in inadvertent, and subsequently deliberate, self experimentation. His notes of the evolving neurological manifestations after exposure provide clues to the toxin’s mechanism of action that would be difficult to draw without self experimentation (see box 1 for notes). Fig 1 Self experimentation by an emeritus neurologist. Urtica ferox is a tree nettle growing >2 m tall, endemic to New Zealand (A), with trichomes that contain a putative neurotoxin (B). During a collection expedition and subsequent sample preparation an emeritus neurologist exposed himself to the fluid in the trichomes (C) and recorded the experience in detail (D). Box 1 ### The emeritus professor’s notes after exposure to the neurotoxic stinging nettle Immediate, moderately severe, burning pain at the site of penetration spread over 5-10 seconds to involve an area 1 cm in diameter. The pain began to subside within five minutes and had resolved within 60 minutes. As the pain subsided paraesthesias appeared that were intense and annoying but not truly painful, and allodynia was noted in the affected area. Paraesthesias were constant for 18 hours and then became intermittent (particularly triggered by cold) and resolved completely by 48 hours. Numbness developed within 30 minutes of onset of paraesthesias. At nadir, complete loss of cold thermal and light touch sensation was noted, and pin prick thresholds were increased, but hyperalgesia occurred when the threshold was exceeded. At 18 hours the numbness began to recede in severity and extent, and it resolved completely by 72 hours. Urtica ferox contains several chemicals that may account … RETURN TO TEXT
Letter to the Editor: The Need for Complete Population‐Based Studies on the Etiology of Liver Disease
Authors: Paulo S. Pinheiro
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. To the Editor: I read Kim et al.’s “Changing Trends in Etiology‐ and Ethnicity‐Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States”1 with great interest. Patterns for hepatocellular carcinoma (HCC) are complex, with disparities likely rooted in etiological differences. Addressing the increasing burden of HCC is urgent. Precisely for this reason, I feel compelled to respectfully share three concerns with Kim et al.’s research. The authors use contributing cause of death from death certificates to identify etiology. Yet the completeness for contributing cause of death variables has not been formally assessed for liver cancer. We examined death certificate data that we have studied extensively for Florida (2007‐2016) and New York (2008‐2014).2 Of all liver cancer deaths, only 49% in Florida and 65% in New York had any additional contributing causes of death listed at all, and many were not related to HCC etiology. Similarly, Kim et al.’s results are based on cause information from only 36% of HCC cases (Table 1 in Kim et al.). With such high proportions of missingness, inferring etiology on a population basis is not best practice in epidemiology. Moreover, this missingness is vastly inconsistent with hospital‐based series for HCC, where causes (viral hepatitis, nonalcoholic fatty liver disease [NAFLD], alcohol, etc.) are discernible for 90% to 95% of all HCC cases.4 Not surprisingly, the sum of the calculated etiology‐specific rates falls far short of the total HCC rate. As such, the results are misleading not only in magnitude but in relative terms, as some etiologies such as NAFLD might be less commonly reported. Secondly, the finding of similar age‐adjusted HCC mortality rates for Hispanics and non‐Hispanic whites (NHWs) (Table 3 in Kim et al.) is completely discrepant with all national reports,5 which show mortality among Hispanics approximately twice that of NHWs (albeit rates include some cholangiocarcinomas in addition to more than 70% HCCs). Surveillance, Epidemiology, and End Results incidence rates specific for HCC (2007‐2015) also show that Hispanics have more than twice the risk of their NHW counterparts.6 Lastly, CDC WONDER5 shows 148,608 deaths from liver cancer for 2007‐2015, whereas Kim et al. present 99,753 HCC deaths for a longer period, 2007‐2016. The discrepancy may be a result of how deaths coded C22.9 (liver cancer, not otherwise specified) were managed, as these would include a substantial number of HCCs. However, the authors made no mention of this important methodological issue. Although I applaud the efforts of Kim et al., these issues call into question the validity and usefulness of the reported findings for tackling the considerable burden of HCC. Complete and accurate population‐based studies on the etiology of liver disease are urgently needed.
Galectin-9 reflects the interferon signature and correlates with disease activity in systemic autoimmune diseases. Response to: ‘Biomarkers: to be or not to be’ by Yavuz and Rönnblom
Authors: Lucas L van den Hoogen, Eefje H M van der Heijden, Maarten R Hillen, Jorre S Mertens, Ruth D E Fritsch-Stork, Timothy R D J Radstake, Joel A G van Roon
Journal: Annals of the Rheumatic Diseases (2018)

Figure 1Increased circulating levels of galectin-9 in patients with pSS are associated with disease activity and serum IgG.Galectin-9 levels were measured in the serum of HC (n=14), patients with nSS (n=13) and patients with pSS (n=46) by Luminex multianalyte measurements.Patients with pSS had clearly increased circulating levels of Gal-9 compared with nSS and HC donors (A).In patients with pSS, serum Gal-9 levels correlated with ESSDAI and serum IgG (B).Differences between the groups were assessed using Kruskal-Wallis test with posthoc Dunn's multiple comparisons test, correlations were assessed using Spearman's correlation coefficient.
School Health as a Strategy to Improve Both Public Health and Education
Authors: Lloyd J. Kolbe
Journal: Annual Review of Public Health (2018)

Because schools materially influence both health and education, they substantially determine the future well-being and economic productivity of populations. Recent research suggests that healthier children learn better and that more educated adults are healthier. School health is a cross-disciplinary field of study and a fundamental strategy that can be used to improve both health and education outcomes. Modern school health programs include 10 interactive components: health education; physical education and physical activity; nutrition environment and services; health services; counseling, psychological, and social services; physical environment; social and emotional climate; family engagement; community involvement; and employee wellness. This review is written for both health and education audiences. It integrates recent research and developments in relationships among health, education, and economic outcomes; health and education systems; the school health program, its components, and their effectiveness; cross-disciplinary collaboration; local, state, national, and international infrastructures and strategies; implementation science; and relevant academic research, training, and service.
Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier
Authors: Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter D. Kwong, Mark Connors, John R. Mascola, Andrew T. McGuire, Leonidas Stamatatos, Max Medina-Ramírez, Rogier W. Sanders, Kevin O. Saunders, Thomas B. Kepler, Barton F. Haynes
Journal: Immunity (2018)

Elicitation of VRC01-class broadly neutralizing antibodies (bnAbs) is an appealing approach for a preventative HIV-1 vaccine. Despite extensive investigations, strategies to induce VRC01-class bnAbs and overcome the barrier posed by the envelope N276 glycan have not been successful. Here, we inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation. Env immunogens designed on reverted VRC01-class bnAbs bound to VRC01 UCA with affinity sufficient to activate naive B cells. Early mutations defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B cell maturation toward the development of neutralization breadth. Finally, VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan.
The Biology of T Regulatory Type 1 Cells and Their Therapeutic Application in Immune-Mediated Diseases
Authors: Maria Grazia Roncarolo, Silvia Gregori, Rosa Bacchetta, Manuela Battaglia, Nicola Gagliani
Journal: Immunity (2018)

Thirty years ago, one of the first types of CD4+ T regulatory cells was discovered and named T regulatory type 1 (Tr1) cells. Tr1 cells represent a distinct population of T cells, which are induced in the periphery upon antigen exposure under tolerogenic conditions. They produce the immunosuppressive cytokines interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), do not constitutively express FOXP3, and suppress the function of effector immune cells. In this review, the key studies leading to the identification and biological characterization of Tr1 cells are recapitulated. The fundamental role of Tr1 cells in regulating immune responses to pathogenic and non-pathogenic antigens, as well as their use as cell therapeutics, is summarized.
Entecavir and Peginterferon Alfa‐2a in Adults With Hepatitis B e Antigen–Positive Immune‐Tolerant Chronic Hepatitis B Virus Infection
Authors: Jordan J. Feld, Norah A. Terrault, Hsing‐Hua S. Lin, Steven H. Belle, Raymond T. Chung, Naoky Tsai, Mandana Khalili, Robert Perrillo, Stewart L. Cooper, Marc G. Ghany, Harry L.A. Janssen, Anna S. Lok
Journal: Hepatology (2018)

Monotherapy with interferon or nucleoside analog is generally not recommended during the immune‐tolerant (IT) phase of chronic hepatitis B virus (HBV) infection. Recognition that high HBV DNA levels are associated with hepatocellular carcinoma has increased interest in treating HBV in the IT phase. Small pediatric studies reported efficacy with combination nucleoside analog and interferon therapy. The aim of this study was to evaluate the safety and efficacy of the combination of entecavir and peginterferon in adults in the IT phase of chronic HBV infection. Hepatitis B e antigen (HBeAg)–positive adults with HBV DNA &gt; 10 7 IU/mL and alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal (ULN) (male: ≤ 45, female: ≤ 30 U/L) received entecavir 0.5 mg daily for 8 weeks followed by the addition of peginterferon alfa‐2a 180 µg/week to entecavir for an additional 40 weeks. The primary endpoint was HBeAg loss and HBV DNA ≤ 1,000 IU/mL 48 weeks after end of treatment (EOT). Among 28 participants from 11 sites, the median age was 37.2 (range: 22‐61) years, 54% were male, and 96% were Asian. Nearly all were infected with genotype C (64%) or B (32%). Median baseline HBV DNA was 8.2 log 10 IU/mL, and ALT was 0.9 times the ULN. Although one (4%) participant cleared HBeAg, none met the primary endpoint of both HBeAg loss AND HBV DNA ≤ 1,000 IU/mL 48 weeks post‐EOT. ALT elevations &gt; 5 times the ULN occurred in eight (29%) participants, and none were associated with icterus. Forty‐eight weeks posttreatment, HBV DNA rebounded to baseline levels in all participants, including the participant who lost HBeAg, and ALT values returned to near baseline levels in all but four participants. Conclusion : A lead‐in strategy of 8 weeks of entecavir followed by combination peginterferon and entecavir therapy for 40 weeks had limited efficacy in adults in the IT phase of chronic HBV infection and cannot be recommended.
Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity
Authors: Sofie Otzen Bagger, Branden Michael Hopkinson, Deo Prakash Pandey, Mads Bak, Andreas Vincent Brydholm, Rene Villadsen, Kristian Helin, Lone Rønnov-Jessen, Ole William Petersen, Jiyoung Kim
Journal: Molecular Cancer (2018)

Tumorigenesis is increasingly considered to rely on subclones of cells poised to undergo an epithelial to mesenchymal transition (EMT) program. We and others have provided evidence, however, that the tumorigenesis of human breast cancer is not always restricted to typical EMT cells but is also somewhat paradoxically conveyed by subclones of apparently differentiated, non-EMT cells. Here we characterize such non-EMT-like and EMT-like subclones. Through a loss-of-function screen we found that a member of the E3 ubiquitin ligase complexes, FBXO11, specifically fuels tumor formation of a non-EMT-like clone by restraining the p53/p21 pathway. Interestingly, in the related EMT-like clone, FBXO11 operates through the BCL2 pathway with little or no impact on tumorigenesis. These data command caution in attempts to assess tumorigenesis prospectively based on EMT profiling, and they emphasize the importance of next generation subtyping of tumors, that is at the level of clonal composition.
Toward a More Nuanced Approach to the Early Administration of Intravenous Fluids in Patients With Sepsis
Authors: Chanu Rhee, Andre C. Kalil
Journal: JAMA Network Open (2018)

Daniel J. Lane, PhD; Hannah Wunsch, MD, MSc; Refik Saskin, MS; Sheldon Cheskes, MD; Steve Lin, MDCM, MSc; Laurie J. Morrison, MD, MSc; Damon C. Scales, MD, PhD
inPentasomes: An innovative nose-to-brain pentamidine delivery blunts MPTP parkinsonism in mice
Authors: F. Rinaldi, L. Seguella, S. Gigli, P.N. Hanieh, E. Del Favero, L. Cantù, M. Pesce, G. Sarnelli, C. Marianecci, G. Esposito, M. Carafa
Journal: Journal of Controlled Release (2018)
Targeted Systemic Treatment of Neuroendocrine Tumors: Current Options and Future Perspectives
Authors: Aura D. Herrera-Martínez, Johannes Hofland, Leo J. Hofland, Tessa Brabander, Ferry A. L. M. Eskens, María A. Gálvez Moreno, Raúl M. Luque, Justo P. Castaño, Wouter W. de Herder, Richard A. Feelders
Journal: Drugs (2018)

Neuroendocrine tumors (NETs) originate from the neuroendocrine cell system in the bronchial and gastrointestinal tract and can produce hormones leading to distinct clinical syndromes. Systemic treatment of patients with unresectable NETs aims to control symptoms related to hormonal overproduction and tumor growth. In the last decades prognosis has improved as a result of increased detection of early stage disease and the introduction of somatostatin analogs (SSAs) as well as several new therapeutic options. SSAs are the first-line medical treatment of NETs and can control hormonal production and tumor growth. The development of next-generation multireceptor targeted and radiolabelled somatostatin analogs, as well as target-directed therapies (as second-line treatment options) further improve progression-free survival in NET patients. To date, however, a significant prolongation of overall survival with systemic treatment in NET has not been convincingly demonstrated. Several new medical options and treatment combinations will become available in the upcoming years, and although preliminary results of preclinical and clinical trials are encouraging, large, preferrably randomized clinical studies are required to provide definitive evidence of their effect on survival and symptom control.
The Efficacy and Safety of Duvelisib Following Disease Progression on Ofatumumab in Patients with Relapsed/Refractory CLL or SLL: Updated Results from the DUO Crossover Extension Study
Authors: Matthew S. Davids, Bryone J. Kuss, Peter Hillmen, Marco Montillo, James Essell, Nicole Lamanna, Zsolt Nagy, Constantine S. Tam, Stephan Stilgenbauer, Paolo Ghia, Julio Delgado, NgocDiep Le, Stephanie Lustgarten, David T. Weaver, Ulrich Jaeger
Journal: Blood (2018)