tbuckley/cabot-search huggingface dataset:
Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals
Authors: Alessandro Mantovani, Graziana Petracca, Giorgia Beatrice, Herbert Tilg, Christopher D Byrne, Giovanni Targher
Journal: Gut (2020)

Objective Follow-up studies have shown that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident diabetes, but currently, it is uncertain whether this risk changes with increasing severity of NAFLD. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes. Design We systematically searched PubMed, Scopus and Web of Science databases from January 2000 to June 2020 using predefined keywords to identify observational studies with a follow-up duration of at least 1 year, in which NAFLD was diagnosed by imaging techniques or biopsy. Meta-analysis was performed using random-effects modelling. Results 33 studies with 501 022 individuals (30.8% with NAFLD) and 27 953 cases of incident diabetes over a median of 5 years (IQR: 4.0–19 years) were included. Patients with NAFLD had a higher risk of incident diabetes than those without NAFLD (n=26 studies; random-effects HR 2.19, 95% CI 1.93 to 2.48; I 2 =91.2%). Patients with more ‘severe’ NAFLD were also more likely to develop incident diabetes (n=9 studies; random-effects HR 2.69, 95% CI 2.08 to 3.49; I 2 =69%). This risk markedly increased across the severity of liver fibrosis (n=5 studies; random-effects HR 3.42, 95% CI 2.29 to 5.11; I 2 =44.6%). All risks were independent of age, sex, adiposity measures and other common metabolic risk factors. Sensitivity analyses did not alter these findings. Funnel plots did not reveal any significant publication bias. Conclusion This updated meta-analysis shows that NAFLD is associated with a ~2.2-fold increased risk of incident diabetes. This risk parallels the underlying severity of NAFLD.
Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments
Authors: Nikolaos I Kanellakis, Rachelle Asciak, Megat Abd Hamid, Xuan Yao, Mark McCole, Simon McGowan, Elena Seraia, Stephanie Hatch, Rob J Hallifax, Rachel M Mercer, Eihab O Bedawi, Stephanie Jones, Clare Verrill, Melissa Dobson, Vineeth George, Georgios T Stathopoulos, Yanchun Peng, Daniel Ebner, Tao Dong, Najib M Rahman, Ioannis Psallidas
Journal: Thorax (2020)

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.
Opportunistic screening versus usual care for detection of atrial fibrillation in primary care: cluster randomised controlled trial
Authors: Steven B Uittenbogaart, Nicole Verbiest-van Gurp, Wim A M Lucassen, Bjorn Winkens, Mark Nielen, Petra M G Erkens, J André Knottnerus, Henk C P M van Weert, Henri E J H Stoffers
Journal: BMJ (2020)

Abstract Objective To investigate whether opportunistic screening in primary care increases the detection of atrial fibrillation compared with usual care. Design Cluster randomised controlled trial. Setting 47 intention-to-screen and 49 usual care primary care practices in the Netherlands, not blinded for allocation; the study was carried out from September 2015 to August 2018. Participants In each practice, a fixed sample of 200 eligible patients, aged 65 or older, with no known history of atrial fibrillation in the electronic medical record system, were randomly selected. In the intention-to-screen group, 9218 patients eligible for screening were included, 55.0% women, mean age 75.2 years. In the usual care group, 9526 patients were eligible for screening, 54.3% women, mean age 75.0 years. Interventions Opportunistic screening (that is, screening in patients visiting their general practice) consisted of three index tests: pulse palpation, electronic blood pressure measurement with an atrial fibrillation algorithm, and electrocardiography (ECG) with a handheld single lead electrocardiographic device. The reference standard was 12 lead ECG, performed in patients with at least one positive index test and in a sample of patients (10%) with three negative tests. If 12 lead ECG showed no atrial fibrillation, patients were invited for more screening by continuous monitoring with a Holter electrocardiograph for two weeks. Main outcome measures Difference in the detection rate of newly diagnosed atrial fibrillation over one year in intention-to-screen versus usual care practices. Results Follow-up was complete for 8874 patients in the intention-to-screen practices and for 9102 patients in the usual care practices. 144 (1.62%) new diagnoses of atrial fibrillation in the intention-to-screen group versus 139 (1.53%) in the usual care group were found (adjusted odds ratio 1.06 (95% confidence interval 0.84 to 1.35)). Of 9218 eligible patients in the intention-to-screen group, 4106 (44.5%) participated in the screening protocol. In these patients, 12 lead ECG detected newly diagnosed atrial fibrillation in 26 patients (0.63%). In the 266 patients who continued with Holter monitoring, four more diagnoses of atrial fibrillation were found. Conclusions Opportunistic screening for atrial fibrillation in primary care patients, aged 65 and over, did not increase the detection rate of atrial fibrillation, which implies that opportunistic screening for atrial fibrillation is not useful in this setting. Trial registration Netherlands Trial Register No NL4776 (old NTR4914).
ARHGEF4 Regulates an Essential Oncogenic Program in t(12;21)‐Associated Acute Lymphoblastic Leukemia
Authors: Clemence Virely, Luca Gasparoli, Maurizio Mangolini, Katherine Clesham, Sarah Inglott, Darren Edwards, Stuart Adams, Jack Bartram, Sujith Samarasinghe, Philip Ancliff, Ajay Vora, Jasper de Boer, Owen Williams
Journal: HemaSphere (2020)

Supplemental Digital Content is available in the text
Abbreviated Breast Magnetic Resonance Imaging for Supplemental Screening of Women With Dense Breasts and Average Risk
Authors: Susan P. Weinstein, Katrina Korhonen, Claire Cirelli, Mitchell D. Schnall, Elizabeth S. McDonald, Austin R. Pantel, Samantha Zuckerman, Ari Borthakur, Emily F. Conant
Journal: Journal of Clinical Oncology (2020)

PURPOSE Although mammography is the standard of care for breast cancer screening, dense breast tissue decreases mammographic sensitivity. We report the prevalent cancer detection rate (CDR) from the first clinical implementation of abbreviated breast magnetic resonance imaging (AB-MR) as a supplemental screening test in women with dense breasts. METHODS The study was approved by the institutional review board and is Health Insurance Portability and Accountability Act complaint. This retrospective review includes women who were imaged between January 1, 2016 and February 28, 2019. On a 1.5 Tesla magnet, the imaging protocol consisted of three sequences: Short-TI Inversion Recovery (STIR), precontrast, and postcontrast. A subtraction sequence and a maximum intensity projection were generated. We report the patient-level CDR and the positive predictive value of AB-MR examinations after negative/benign digital breast tomosynthesis (DBT). RESULTS Out of 511 prevalent rounds of AB-MR examinations, 36 women were excluded. The remaining 475 asymptomatic women with dense breasts had negative/benign DBT examinations before the AB-MR. There were 420 of 475 (88.4%) benign/negative examinations, 13 of 475 (2.7%) follow-up recommendations, and 42 biopsy recommendations. Thirty-nine biopsies were completed, resulting in 12/39 (30.8%) malignancies in 12 women: seven invasive carcinomas and five ductal carcinoma in situ. One additional patient was diagnosed with invasive ductal carcinoma at the time of 6-month follow-up. The CDR was 27.4 per 1,000 (13 of 475; 95% CI, 16.1 to 46.3). The size of invasive carcinomas ranged from 0.6-1.0 cm (mean, 0.5 cm). Of the seven women who underwent surgical evaluation of the axilla, zero of seven patients had positive nodes. There were no interval cancers at 1-year follow-up. CONCLUSION Preliminary results from clinical implementation of screening AB-MR resulted in a CDR of 27.4/1,000 at the patient level after DBT in women with dense breasts. Additional evaluation is warranted.
Rbm24 modulates adult skeletal muscle regeneration via regulation of alternative splicing
Authors: Mengkai Zhang, Yue Han, Jing Liu, Lefeng Liu, Longqing Zheng, Yongxiong Chen, Rongmu Xia, Dongbo Yao, Xuemin Cai, Xiuqin Xu
Journal: Theranostics (2020)

Rationale: The adult skeletal muscle can self-repair efficiently following mechanical or pathological damage due to its remarkable regenerative capacity. However, regulatory mechanisms underlying muscle regeneration are complicated and have not been fully elucidated. Alternative splicing (AS) is a major mechanism responsible for post-transcriptional regulation. Many aberrant AS events have been identified in patients with muscular dystrophy which is accompanied by abnormal muscle regeneration. However, little is known about the correlation between AS and muscle regeneration. It has been reported that RNA binding motif protein 24 (Rbm24), a tissue-specific splicing factor, is involved in embryo myogenesis while the role of Rbm24 in adult myogenesis (also called muscle regeneration) is poorly understood. Methods: To investigate the role of Rbm24 in adult skeletal muscle, we generated Rbm24 conditional knockout mice and satellite cell-specific knockout mice. Furthermore, a cardiotoxin (CTX)-induced injury model was utilized to assess the effects of Rbm24 on skeletal muscle regeneration. Genome-wide RNA-Seq was performed to identify the changes in AS following loss of Rbm24. Results: Rbm24 knockout mice displayed abnormal regeneration 4 months after tamoxifen treatment. Using RNA-Seq, we found that Rbm24 regulated a complex network of AS events involved in multiple biological processes, including myogenesis, muscle regeneration and muscle hypertrophy. Moreover, using a CTX-induced injury model, we showed that loss of Rbm24 in skeletal muscle resulted in myogenic fusion and differentiation defects and significantly delayed muscle regeneration. Furthermore, satellite cell-specific Rbm24 knockout mice recapitulated the defects in regeneration seen in the global Rbm24 knockout mice. Importantly, we demonstrated that Rbm24 regulated AS of Mef2d, Naca, Rock2 and Lrrfip1 which are essential for myogenic differentiation and muscle regeneration. Conclusions: The present study demonstrated that Rbm24 regulates dynamic changes in AS and is essential for adult skeletal muscle regeneration.
Covid-19: Flying before we can walk
Authors: Navjoyt Ladher
Journal: BMJ (2020)

In the week since The BMJ broke the story about the government’s Operation Moonshot plans to spend £100bn on mass testing (p 337),1 we have seen a rising number of covid-19 cases and widespread reports of people struggling to access NHS Test and Trace. The UK still lacks a competent, functioning system to test, trace, and isolate cases of covid-19. It is hard to envisage how the ambitious proposals for mass testing could be realised when the current foundations are so shaky. How can we shoot for the moon when we …
In AF with recent ACS or PCI, apixaban improved 30-day outcomes vs. VKAs; aspirin effects varied vs. placebo
Authors: Edward P. Hoffer
Journal: Annals of Internal Medicine (2020)

Source Citation Alexander JH, Wojdyla D, Vora AN, et al. Risk/benefit tradeoff of antithrombotic therapy in patients with atrial fibrillation early and late after an acute coronary syndrome or percutaneous coronary intervention: insights from AUGUSTUS. Circulation. 2020;141:1618-27. 32223444
Doctors call for action on racism in wake of covid-19 and death of George Floyd
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The UK government has a "moral imperative" to take firm action against racism and health inequalities that have been laid bare by the covid-19 pandemic and the Black Lives Matter movement, the BMA has urged.The association's annual representative meeting, held virtually on 15 September, passed a motion requesting concrete actions to tackle racism in the NHS and at a broader societal level.
Cash Transfers and Health
Authors: Sicong Sun, Jin Huang, Darrell L. Hudson, Michael Sherraden
Journal: Annual Review of Public Health (2021)

Financial resources are known to affect health outcomes. Many types of social policies and programs, including social assistance and social insurance, have been implemented around the world to increase financial resources. We refer to these as cash transfers. In this article, we discuss theory and evidence on whether, how, for whom, and to what extent purposeful cash transfers improve health. Evidence suggests that cash transfers produce positive health effects, but there are many complexities and variations in the outcomes. Continuing research and policy innovation—for example, universal basic income and universal Child Development Accounts—are likely to be productive.
Operation Moonshot: What do the leaked documents say?
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Operation Moonshot is the name of the UK government's newly proposed covid-19 mass testing scheme.The plan, revealed by The BMJ, 1 involves an expansion of testing from the current hundreds of thousands of tests each day to 10 million a day by early 2021.But how does the government propose to do this? How will testing increase between now and early 2021?The documents show a proposed three stage rollout.They state that the UK will carry out between 200 000 to 800 000 tests a day between September and December 2020.
Exercise Regulates MicroRNAs to Preserve Coronary and Cardiac Function in the Diabetic Heart
Authors: Jason Kar-Sheng Lew, James T. Pearson, Eugene Saw, Hirotsugu Tsuchimochi, Melanie Wei, Nilanjan Ghosh, Cheng-Kun Du, Dong-Yun Zhan, Meihua Jin, Keiji Umetani, Mikiyasu Shirai, Rajesh Katare, Daryl O. Schwenke
Journal: Circulation Research (2020)

Diabetic heart disease (DHD) is a debilitating manifestation of type 2 diabetes mellitus. Exercise has been proposed as a potential therapy for DHD, although the effectiveness of exercise in preventing or reversing the progression of DHD remains controversial. Cardiac function is critically dependent on the preservation of coronary vascular function.We aimed to elucidate the effectiveness and mechanisms by which exercise facilitates coronary and cardiac-protection during the onset and progression of DHD.Diabetic db/db and nondiabetic mice, with or without underlying cardiac dysfunction (16 and 8 weeks old, respectively) were subjected to either moderate-intensity exercise or high-intensity exercise for 8 weeks. Subsequently, synchrotron microangiography, immunohistochemistry, Western blot, and real-time polymerase chain reaction were used to assess time-dependent changes in cardiac and coronary structure and function associated with diabetes mellitus and exercise and determine whether these changes reflect the observed changes in cardiac-enriched and vascular-enriched microRNAs (miRNAs). We show that, if exercise is initiated from 8 weeks of age, both moderate-intensity exercise and high-intensity exercise prevented the onset of coronary and cardiac dysfunction, apoptosis, fibrosis, microvascular rarefaction, and disruption of miRNA signaling, as seen in the nonexercised diabetic mice. Conversely, the cardiovascular benefits of moderate-intensity exercise were absent if the exercise was initiated after the diabetic mice had already established cardiac dysfunction (ie, from 16 weeks of age). The experimental silencing or upregulation of miRNA-126 activity suggests the mechanism underpinning the cardiovascular benefits of exercise were mediated, at least in part, through tissue-specific miRNAs.Our findings provide the first experimental evidence for the critical importance of early exercise intervention in ameliorating the onset and progression of DHD. Our results also suggest that the beneficial effects of exercise are mediated through the normalization of cardiovascular-enriched miRNAs, which are dysregulated in DHD.
ID:1882 Phase III Randomized Study of Ensartinib vs Crizotinib in Anaplastic Lymphoma Kinase (ALK) POSITIVE NSCLC Patients: eXalt3
Authors: G. Selvaggi, H.A. Wakelee, T. Mok, Y.-L. Wu, M. Reck, A. Chiappori, I. Cicin, D.H. Lee, V. Breder, Y. Fan, S. Orlov, E. Poddubskaya, Z. Wang, Y. Cheng, Y. Liu, G. Wu, L. Mao, J. Zhou, V. Oertel, L. Horn, C. Liang
Journal: Journal of Thoracic Oncology (2020)
Effects of Intensive Blood Pressure Treatment on Orthostatic Hypotension
Authors: Stephen P. Juraschek, Jiun-Ruey Hu, Jennifer L. Cluett, Anthony Ishak, Carol Mita, Lewis A. Lipsitz, Lawrence J. Appel, Nigel S. Beckett, Ruth L. Coleman, William C. Cushman, Barry R. Davis, Greg Grandits, Rury R. Holman, Edgar R. Miller, Ruth Peters, Jan A. Staessen, Addison A. Taylor, Lutgarde Thijs, Jackson T. Wright, Kenneth J. Mukamal
Journal: Annals of Internal Medicine (2020)

Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults.MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing.2 investigators independently abstracted articles and rated risk of bias.5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH (P for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged.Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available.Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension.National Heart, Lung, and Blood Institute, National Institutes of Health. (PROSPERO: CRD42020153753).
Body Composition, Natriuretic Peptides, and Adverse Outcomes in Heart Failure With Preserved and Reduced Ejection Fraction
Authors: Senthil Selvaraj, Jessica Kim, Bilal A. Ansari, Lei Zhao, Mary Ellen Cvijic, Matthew Fronheiser, Jagan Mohan-Rao Vanjarapu, Anupam A. Kumar, Arpita Suri, Sowjanya Yenigalla, Vaibhav Satija, Armghan Haider Ans, Offdan Narvaez-Guerra, Karela Herrera-Enriquez, Mary Jo Obeid, Jonathan J. Lee, Qasim Jehangir, Dietmar A. Seiffert, Bruce D. Car, David A. Gordon, Julio A. Chirinos
Journal: JACC. Cardiovascular imaging (2020)
NK cells in the tumor microenvironment and thioredoxin activity
Authors: Theresa L. Whiteside
Journal: Journal of Clinical Investigation (2020)

NK cells are responsible for defense against viral infections and cancer. Although activated NK cells are armed to combat tumors, the tumor microenvironment (TME) contains ROS, which suppress NK cell antitumor activity. In this issue of the JCI, Yang, Neo, and colleagues explored NK cell resistance to oxidative stress in vitro and in human non–small-cell lung cancer (NSCLC). High surface thiol density and elevated expression of the ROS scavenger thioredoxin (Trx1) protected NK cells from ROS. Trx1 and thiol levels were higher in IL-15– than in IL-2–primed NK cells. Tumor-infiltrating Trx1+ NK cells were present in patients with NSCLC with elevated ROS levels in the tumor. Smokers scored higher for the ROS signature, which predicted poor prognosis, compared with nonsmokers. This study explains how activated NK cells survive in the ROS-rich TME and suggests that smokers with lung cancer may benefit from therapies using IL-15–primed NK cells.
The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKD Injury
Authors: Mark Peter Rutkowski
Journal: Journal of the American Society of Nephrology (2020)

A recent article by Shin et al.,1 entitled “The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKD Injury,” described how the transition from a creatinine-based threshold for prescribing metformin to an eGFR-based threshold was associated with a reduction in the racial disparity of metformin prescribing for Black patients. Shin et al. found a 25% increase (from 26.1% to32.6%) in prescribing of metformin for Black patients with an eGFR of 30–44 ml/min per 1.73 m2. This increase would likely have been less had the eGFR been estimated to be 16% lower for all Black patients by eliminating the Black race coefficient in the CKD–Epidemiology Collaboration equation. Because the nephrology community is undergoing an examination of whether the Black race coefficient for eGFR is appropriate,2,3 and because some medical institutions have already moved to eliminate the Black race coefficient for eGFR, it would be helpful if the authors could analyze the potential effect on their study results of eliminating the Black race coefficient from the eGFR by the CKD–Epidemiology Collaboration equation. Disclosures The author has nothing to disclose. Funding None.
Value of Magnetic Resonance Cholangiography in Assessment of Non-Anastomotic Biliary Strictures after Liver Transplantation
Authors: A.C. den Dulk, M.N.J.M. Wasser, F. Willemssen, Monraats, M. de Vries, R. van den Boom, J. Ringers, H.W. Verspaget, H.J. Metselaar, B. van Hoek
Journal: Hepatology (2015)
Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing
Authors: Julia Joung, Alim Ladha, Makoto Saito, Nam-Gyun Kim, Ann E Woolley, Michael Segel, Robert P J Barretto, Amardeep Ranu, Rhiannon K Macrae, Guilhem Faure, Eleonora I Ioannidi, Rohan N Krajeski, Robert Bruneau, Meei-Li W Huang, Xu G Yu, Jonathan Z Li, Bruce D Walker, Deborah T Hung, Alexander L Greninger, Keith R Jerome, Jonathan S Gootenberg, Omar O Abudayyeh, Feng Zhang
Journal: New England Journal of Medicine (2020)

Detection of SARS-CoV-2 with a CRISPR-Based Test A new method for the detection of SARS-CoV-2 combines simplified extraction of RNA with isothermal amplification and CRISPR (clustered regularly int...