tbuckley/cabot-search huggingface dataset:
Abstract 16110: Impact of Institutional Volume on In-hospital Mortality and Resource Utilization Among Patients With Pulmonary Embolism Treated With Catheter Directed Thrombolysis: A Population-Based Cohort Study
Authors: Isaac C Meier, Beau M Hawkins, Federico Silva, TALLA ROUSAN, Mohan Edupuganti, Gary Raskob, Jay S Giri, Usman Baber
Journal: Circulation (2020)

Introduction: Catheter-directed thrombolysis (CDT) is an evolving percutaneous approach for the management of acute pulmonary embolism (PE). Contemporary data examining in-hospital outcomes in relation to procedural volume are limited. Methods: Data sets were extracted from the 2016 national readmission database. Using ICD 10 codes, a search was performed to identify all patients hospitalized with a primary or secondary diagnosis of PE who underwent CDT between 1/1/2016 and 12/31/2016. Hospitals were grouped into quartiles by CDT volume and rates of in-hospital mortality, length of stay, and cost were compared across groups. Adjusted associations were examined using multivariable logistic regression. Results and Conclusions: We identified 2,353 unique patients with PE who underwent CDT at 483 hospitals. The median (25th, 75th percentiles) number of CDT procedures per hospital was 3 (1, 6). Mortality rates were 11.4%, 5.3%, 5.6% and 3.8%, respectively, at hospitals in the 1st, 2nd, 3rd and 4th quartile of CDT procedural volume (Figure; p=0.001). Results were unchanged after multivariable adjustment. Median length of stay by quartile was as follows: 6.5, 5, 5, and 4 days (p &lt;0.001). The median cost for the different quartiles was $28,277, $25,953, $25,896, and $23,007 (p &lt;0.001). We found that CDT performed in patients with PE at low-volume hospitals is associated with excess mortality as well as increased length of stay and cost when compared with higher-volume centers. These findings may inform guidance for volume thresholds for utilization of CDT in the management of acute PE.
Abstract P056: The Role Of Socioeconomic Status In Racial/ethnic Disparities In Complications Of Diabetes: The Atherosclerosis Risk In Communities Study
Authors: Caitlin W Hicks, Dan Wang, Tanjala Purnell, B Gwen Windham, Morgan Grams, Josef Coresh, Kunihiro Matsushita, Elizabeth Selvin
Journal: Circulation (2021)

Background: Few prospective studies have evaluated the role of socioeconomic status in explaining racial/ethnic disparities across major complications among adults with diabetes. We assessed the prospective association of race/ethnicity with long-term complications and cardiovascular mortality in persons with diabetes in a community-based cohort. Methods: We conducted a prospective analysis of 4,460 black and white participants in the ARIC Study with prevalent or incident diabetes (and no history of cardiovascular disease) followed from time of diabetes through 2018. We calculated incidence rates of major clinical outcomes (fatal coronary heart disease or myocardial infarction, heart failure, ischemic stroke, end stage renal disease, hospitalized peripheral artery disease [PAD], lower extremity amputation) using standard definitions in the ARIC Study. We used Cox regression to assess the associations of race/ethnicity with incident complications and cardiovascular mortality before and after adjustment for cardiovascular and socioeconomic factors. Results: The incidence rates (per 1,000 person-years) were higher for black vs. white adults with diabetes for heart failure (22.1 vs. 17.4), ischemic stroke (8.5 vs. 5.5), end stage renal disease (5.6 vs. 1.6), PAD (4.7 vs. 3.2), lower extremity amputation (2.9 vs. 1.0) and cardiovascular mortality (7.5 vs. 6.5). These associations remained significant after adjusting for age, sex, smoking, and hypertension (HRs 1.41 to 3.27), but - with the exception of ESRD - were largely attenuated after further adjusting for health insurance and socioeconomic variables ( Table ). Conclusions: Among adults with diabetes, the association of race/ethnicity with complications differs depending on the outcome. Socioeconomic disparities play a major role in explaining the differences between groups. Our findings suggest that eliminating economic and healthcare system disparities is important to address health equity and prevent complications in adults with diabetes.
Selective Requirement of MYB for Oncogenic Hyperactivation of a Translocated Enhancer in Leukemia
Authors: Leonie Smeenk, Sophie Ottema, Roger Mulet-Lazaro, Anja Ebert, Marije Havermans, Andrea Arricibita Varea, Michaela Fellner, Dorien Pastoors, Stanley van Herk, Claudia Erpelinck-Verschueren, Tim Grob, Remco M. Hoogenboezem, François G. Kavelaars, Daniel R. Matson, Emery H. Bresnick, Eric M. Bindels, Alex Kentsis, Johannes Zuber, Ruud Delwel
Journal: Cancer Discovery (2021)

Abstract In acute myeloid leukemia (AML) with inv(3)(q21;q26) or t(3;3)(q21;q26), a translocated GATA2 enhancer drives oncogenic expression of EVI1. We generated an EVI1-GFP AML model and applied an unbiased CRISPR/Cas9 enhancer scan to uncover sequence motifs essential for EVI1 transcription. Using this approach, we pinpointed a single regulatory element in the translocated GATA2 enhancer that is critically required for aberrant EVI1 expression. This element contained a DNA-binding motif for the transcription factor MYB, which specifically occupied this site at the translocated allele and was dispensable for GATA2 expression. MYB knockout as well as peptidomimetic blockade of CBP/p300-dependent MYB functions resulted in downregulation of EVI1 but not of GATA2. Targeting MYB or mutating its DNA-binding motif within the GATA2 enhancer resulted in myeloid differentiation and cell death, suggesting that interference with MYB-driven EVI1 transcription provides a potential entry point for therapy of inv(3)/t(3;3) AMLs. Significance: We show a novel paradigm in which chromosomal aberrations reveal critical regulatory elements that are nonfunctional at their endogenous locus. This knowledge provides a rationale to develop new compounds to selectively interfere with oncogenic enhancer activity. This article is highlighted in the In This Issue feature, p. 2659
Considerations Regarding a Network Meta-analysis of Systemic Treatments for Metastatic Castration-Sensitive Prostate Cancer
Authors: Satoshi Funada, Yan Luo, Toshi A. Furukawa
Journal: JAMA Oncology (2021)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal
サハラ以南アフリカにおける非伝染性疾患の負担,1990~2017:疾患研究2017年の世界的負担からの結果【JST・京大機械翻訳】
Authors: Gouda Hebe N, Charlson Fiona, Sorsdahl Katherine, Ahmadzada Sanam, Ferrari Alize J, Erskine Holly, Leung Janni, Santamauro Damian, Lund Crick, Aminde Leopold Ndemnge, Mayosi Bongani M, Kengne Andre Pascal, Harris Meredith, Achoki Tom, Wiysonge Charles S, Stein Dan J, Whiteford Harvey
Journal: The Lancet Global Health (2019)
UK campaigners mount legal challenge over US takeover of GP surgeries
Authors: Matthew Limb
Journal: BMJ (2021)

UK patients and doctors are backing a legal challenge to a takeover of NHS general practice services by a private US health company. They want a judicial review of a decision by North Central London Clinical Commissioning Group to allow eight general practices to be taken over by health insurance giant Centene to expand the firm’s UK portfolio.

Campaigners, including the group Keep Our NHS Public, argue that the decision to allow change of control lacked transparency and should be declared unlawful. They said it posed risks to patients’ care and could lead to unprofitable services being closed down and personal data leaving the UK.

A Crowdjustice fundraising appeal was launched on 20 May in support of the judicial review bid being brought by …
Clinical trial strategies for rare neurodevelopmental disorders: challenges and opportunities
Authors: Michelle L. Krishnan, Elizabeth Berry-Kravis, Jamie K. Capal, Randall Carpenter, Paul Gringras, Joerg F. Hipp, Meghan T. Miller, Ana Mingorance, Benjamin D. Philpot, Mathew T. Pletcher, Alexander Rotenberg, Jorrit Tjeertes, Paul P. Wang, Tom Willgoss, Marie-Claire de Wit, Shafali S. Jeste
Journal: Nature Reviews Drug Discovery (2021)
Antivirals against SARS-CoV-2 by autumn?
Authors: David Smith, Dipender Gill
Journal: BMJ (2021)

The UK government has launched a covid-19 antivirals taskforce with the aim of deploying drugs for home treatment by autumn this year. 1 The description suggests that the government wants direct acting orally administered drugs that reduce replication and help eliminate SARS-CoV-2 from the body.Taken after a positive swab test result or prophylactically after exposure, these drugs could reduce viral transmission, morbidity, and mortality.And they may well be needed.Vaccine efficacy against symptomatic disease is 67-95%, with unknown durability and effectiveness against new variants. 2Peak viral loads seem to determine the duration and severity of symptoms, 3 but current covid-19 treatments are largely limited to anti-inflammatory drugs (dexamethasone, tocilizumab, and sarilumab) that save only around one in three patients who would otherwise have died. 4Remdesivir, the most commonly used antiviral for SARS-CoV-2 in the UK, requires intravenous administration and seems to offer little survival benefit.
Abstract 16583: Beta Blocker Administration Within 30 Days Post-Left Ventricular Assist Device Significantly Decreases 1-Year Mortality in a Multi-institutional Retrospective Cohort Study
Authors: Mohamed H Derbala, Mercedes Rivas-Lasarte, Salil Kumar, Joel Ferrall, Matthew Cefalu, Aaron Guo, Somayya Mohammad, Daniel B Sims, Sakima A Smith
Journal: Circulation (2020)

Introduction: The utilization of beta blockers (BB) post LVAD implantation is controversial, especially in the setting of right ventricular failure. There is limited evidence-based data regarding the survival benefits of BB post LVAD implantation Hypothesis: We hypothesized that BB use would not be associated with increased mortality Methods: We performed a dual-center retrospective study of 487 patients from Ohio State University &amp; Montefiore Medical Center who received a continuous-flow durable LVAD bet. Jan 2006 through Dec 2016. A survival analysis was done to determine if patients had increased 1 year mortality depending on whether they received BB within 30 days post LVAD, after 30 days &amp; up to 1 year post LVAD, or did not receive BB. Multivariate analysis of predictors of post LVAD mortality was conducted. Results: Overall the baseline characteristics bet. the 3 groups were similar (Table 1). BB utilization within 30 days post LVAD was associated with a drastic decrease in 1 year mortality (p &lt;0.001; Fig.1). Multivariate analysis shows that no BB use (HR 3.36, p &lt;0.001), age ≥70 (HR 2.73, p = 0.005) &amp; pre LVAD creatinine ≥1.5 mg/dl (HR 1.86, p = 0.022) were significant independent predictors of mortality (Table 2). Conclusions: The early use of BB significantly improves 1 year survival post LVAD. Notably these results are from Midwest and East Coast Medical Centers to improve generalizability.
Abstract P131: Changes In Bile Acid Subtypes And Improvements In Adiposity And Energy Metabolism In Response To Weight-loss Diets
Authors: Yoriko Heianza, Tao Zhou, Hua He, Jennifer Rood, Clary Clish, George Bray, Frank M Sacks, Lu Qi
Journal: Circulation (2021)

Introduction: Bile acids (BAs) are synthesized in the liver from cholesterol, and gut microbiota transform the host-derived primary BAs into secondary BAs in the intestine. Emerging evidence suggests that different types of circulating BAs may play pivotal roles in regulating energy metabolism and body adiposity. Hypothesis: We comprehensively examined whether changes in different BA subtypes after consuming weight-loss diets were associated with improvements in energy metabolism and body adiposity among patients with obesity. Methods: This study included 551 overweight and obese adults who participated in a 2-year weight-loss dietary intervention, the POUNDS Lost trial. Blood levels of 14 types of BAs (primary and secondary unconjugated BAs and their taurine-/glycine-conjugates) were measured at baseline and 6 months after the intervention; changes in BAs from baseline to 6 months after the intervention were calculated. We evaluated changes in resting energy expenditure, weight, and waist circumference. Also, body composition was assessed by the dual-energy X-ray absorptiometry (DEXA) scans, and fat distribution was assessed by computed tomography (CT) scans. Results: At baseline, higher primary and secondary BAs were related to greater degrees of adiposity and energy expenditure. At 6 months after the intervention, greater decreases in primary BAs (cholic acid [CA] and chenodeoxycholic acid) and secondary BAs (deoxycholic acid [DCA] and lithocholic acid [LCA]) and their conjugated subtypes (except for glycolithocholic acid) were significantly associated with more decreases in weight and waist circumference at 6 months after the intervention (P values after controlling for the multiple testing, P FDR &lt;0.05). Greater reductions in the primary BAs (both unconjugated and conjugated types) and secondary BAs (DCA and its taurine-/glycine-conjugated forms) were also significantly ( P FDR &lt;0.05) associated with more decreases in resting energy expenditure at 6 months. We found that reductions in two BA subtypes, glycocholic acid (GCA) and glycoursodeoxycholic acid (GUDCA), were consistently and significantly associated with improvements in energy metabolism, general and central adiposity, as well as body fat composition and visceral adipose tissue mass. Further, the initial (6-month) changes in several primary and secondary BAs (including GCA and GUDCA) were significantly predictive of the long-term successful weight loss (weight loss of more than 5% loss from the initial weight) at 2 years. Conclusions: Weight-loss diet-induced changes in circulating various BAs may be involved in improving general and central adiposity and energy metabolism. Changes in specific BA subtypes would be potential targets for improving regional adiposity and achieving successful weight-loss among patients with obesity.
Case Report : A case of concomitant Gilbert`s syndrome and hereditary spherocytosis
Authors: Hee Jung Lee, Hee Seok Moon, Eaum Seok Lee, Seok Hyun Kim, Jae Kyu Sung, Byung Seok Lee, Hyun Yong Jeong, Heon Young Lee, Young Jae Eu
Journal: Clinical and Molecular Hepatology (2010)

We describe moderate hyperbilirubinemia in a 28-year-old man who suffered from gallstones and splenomegaly, with combined disorders of hereditary spherocytosis (HS) and Gilbert`s syndrome (GS). Since it is difficult to diagnose HS in the absence of signs of anemia, we evaluated both the genetic mutation in the UGT1A1 gene and abnormalities in the erythrocyte membrane protein; the former was heterozygous for a UGT1A1 allele with three mutations and the latter was partially deficient in ankyrin expression. This is the first report of the concomitance of HS and GS with three heterozygous mutations [T-3279G, A (TA)7TAA, and G211A] in the UGT1A1 gene. (Korean J Hepatol 2010;16:321-324)
Abstract 028: Biomarkers Of Kidney Function And Cognitive Ability: A Mendelian Randomization Study
Authors: Erin Richard, Linda McEvoy, Steven Cao, Andrea Z Lacroix, Rany Salem
Journal: Circulation (2021)

Background: Estimated glomerular filtration rate (eGFR), albuminuria and serum uric acid (SUA) are markers of kidney function that have been associated with cognitive ability. However, whether these associations are causal is unclear. Methods: We performed one-sample Mendelian randomization (MR) to estimate the effects of kidney function markers on cognitive performance using data from 357,590 participants from the UK Biobank. Polygenic scores for serum uric acid (SUA), urine albumin to creatinine ratio (ACR), estimated glomerular filtration rate based on serum creatinine (eGFRcre) and serum cystatin-c (eGFRcys) were used as instruments, and cognitive function outcomes included a test of verbal-numeric reasoning and reaction time. Sensitivity analyses were carried out to address potential pleiotropy using MR-Egger and weighted median regression. Results: We found no evidence of a causal effect of genetically determined SUA, eGFRcre or eGFRcys on either cognitive function outcomes. There was no association between a polygenic score for ACR and verbal-numeric reasoning. However, there was suggestive evidence of a relationship between genetically increased ACR and slower reaction time (β (95% confidence interval [CI])) for 1 standard deviation log ACR = 4.93 (1.60 to 8.26), p=0.004). Pleiotropy adjusted estimates were directionally consistent with those of the principal analysis but overlapped with the null. Conclusions: This MR study does not support causal effects of SUA, eGFRcre or eGFRcys on cognitive performance. Genetically-increased ACR was associated with lower processing speed, but results need confirmation in independent samples.
COVID-19 vaccines: effectiveness and number needed to treat
Authors: Luis C L Correia, Denise Matias
Journal: The Lancet Microbe (2021)

COVID-19 vaccines: effectiveness and number needed to treatIn a Lancet Microbe Comment, Piero Olliaro and colleagues 1 suggest that reporting relative risk reduction (RRR) for vaccination does not reflect entirely its therapeutic performance and consider the solw use of RRR a reporting bias.In addition, they propose that absolute risk reduction (ARR) should be reported as a measure of the vaccine's effectiveness.The authors end up comparing the numbers needed to vaccinate to prevent one case of COVID-19 among the vaccines, which derives from the absolute reductions.However, this suggestion might have a paradoxical effect in misleading perception of treatment performance.This approach disregards three epidemiological facts.
Abstract MP65: Transgender Adolescents Have High Prevalence Of Atherosclerotic Cardiovascular Disease Risk Factors Before And After Taking Hormone Therapy For 1 Year
Authors: Ambur M Staab, Amy M Cizik, Nicole L Mihalopoulos
Journal: Circulation (2021)

Introduction: The United States has a growing population of transgender adolescents aged 12-21y presenting for medical transition via gender affirming hormone therapy (HT). Transgender people do not identify with their sex assigned at birth while cisgender people do. HT involves estrogen for trans females, those who identify as female, and testosterone for trans males, those who identify as male. Initiation of HT is beginning in adolescence and is a lifelong commitment for many transgender individuals. Little is known about how HT affects ASCVD risk factors in transgender adolescents. Studies of cisgender adults show cardioprotective effects of estrogen, and an estimated 37% of normal-weight cis gender adolescents have at least 1 ASCVD risk factor; but little investigation exists for transgender people, especially adolescents. Although some studies involving the transgender population have reproducible results, few include adolescents and comparison to acceptable ASCVD risk factor profiles. Guidelines for transgender health recommend laboratory assessment before starting HT and annually. This study expands on current knowledge and informs clinical practice by comparing ASCVD risk biomarkers of transgender adolescents taking HT to acceptable clinical values for adolescents. Hypothesis: Estrogen therapy for trans females will ameliorate ASCVD risk factors while testosterone therapy for trans males will worsen ASCVD risk factors. Methods: Retrospective chart review identified 300 transgender patients receiving HT at an academic adolescent medicine gender clinic. Of those 300, 50 trans female and 50 trans male were randomly selected for evaluation of ASCVD risk parameters at baseline and 1 year after initiating HT. ASCVD risk factors were compared to the International Diabetes Federation guidelines for metabolic syndrome. Parameters included lipids, glucose, and blood pressure. BMI ≥30 was used as proxy for obesity. Results: At baseline, at least one abnormal value was found for 50% (n=25, of these 5 had obesity) of trans females and 66% (n=33, of these 13 had obesity) of trans males. At 1 year, at least one abnormal value was found for 30% (n=15) of trans females and 70% (n=35) of trans males. At baseline, 50% (n=25) of trans females and 82% (n=41) of trans males, and at 1 year 20% (n=10) of trans females and 48% (24) of trans males had all parameters measured. Paired t-tests (α=.05) showed no significant change in ASCVD risk factors for trans females, and significant decrease in HDL and significant increase in BMI for trans males after 1 year of HT. Conclusions: The prevalence of having at least 1 ASCVD risk factor is greater among transgender adolescents than normal weight cisgender adolescents. HT may worsen HDL and BMI for trans males. We recommend baseline parameters for all and follow up and lab surveillance for patients with abnormal baseline parameters.
Functional mapping of androgen receptor enhancer activity
Authors: Chia-Chi Flora Huang, Shreyas Lingadahalli, Tunc Morova, Dogancan Ozturan, Eugene Hu, Ivan Pak Lok Yu, Simon Linder, Marlous Hoogstraat, Suzan Stelloo, Funda Sar, Henk van der Poel, Umut Berkay Altintas, Mohammadali Saffarzadeh, Stephane Le Bihan, Brian McConeghy, Bengul Gokbayrak, Felix Y. Feng, Martin E. Gleave, Andries M. Bergman, Colin Collins, Faraz Hach, Wilbert Zwart, Eldon Emberly, Nathan A. Lack
Journal: Genome biology (2021)

Abstract Background Androgen receptor (AR) is critical to the initiation, growth, and progression of prostate cancer. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there are 10–100× more binding sites than differentially expressed genes. It is unclear how or if these excess binding sites impact gene transcription. Results To characterize the regulatory logic of AR-mediated transcription, we generated a locus-specific map of enhancer activity by functionally testing all common clinical AR binding sites with Self-Transcribing Active Regulatory Regions sequencing (STARRseq). Only 7% of AR binding sites displayed androgen-dependent enhancer activity. Instead, the vast majority of AR binding sites were either inactive or constitutively active enhancers. These annotations strongly correlated with enhancer-associated features of both in vitro cell lines and clinical prostate cancer samples. Evaluating the effect of each enhancer class on transcription, we found that AR-regulated enhancers frequently interact with promoters and form central chromosomal loops that are required for transcription. Somatic mutations of these critical AR-regulated enhancers often impact enhancer activity. Conclusions Using a functional map of AR enhancer activity, we demonstrated that AR-regulated enhancers act as a regulatory hub that increases interactions with other AR binding sites and gene promoters.