tbuckley/cabot-search huggingface dataset:
Prehospital and Posthospital Fall Injuries in Older US Adults
Authors: Geoffrey J. Hoffman, Mary E. Tinetti, Jinkyung Ha, Neil B. Alexander, Lillian C. Min
Journal: JAMA Network Open (2020)

<h3>Importance</h3> To date, measurement and treatment of older adult fall injury has been siloed within specific care settings, such as a hospital or within a nursing home or community. Little is known about changes in fall risk across care settings. Understanding the occurrence of falls across settings has implications for measuring and incentivizing high-value care across care settings. <h3>Objective</h3> To estimate the risk of older adult fall injury within and across discrete periods during a 12-month care episode anchored by an acute hospitalization. <h3>Design, Setting, and Participants</h3> This cohort study is a longitudinal analysis of 12-month periods that include an anchor hospital stay using national data from 2006 to 2014. Participants included older (aged ≥65 years) Medicare fee-for-service beneficiaries from the Health and Retirement Study. Weekly fall injury rates were computed for 4 periods compared with the anchor hospitalization: at baseline (1-6 months before hospitalization), just before (&lt;1 month before hospitalization), just after (&lt;1 month after hospitalization), and at follow-up (1-6 months after hospitalization). Piecewise logistic regression models estimated weekly marginal risk of fall injury within each period, adjusting for sociodemographic and health characteristics. Fall injury risks for high-risk beneficiaries with a fall injury during the anchor hospitalization were also estimated. Data analysis was performed from November 2019 to April 2020. <h3>Main Outcomes and Measures</h3> Fall injuries. <h3>Results</h3> In total, 10 106 anchor hospitalizations for 4101 beneficiaries (mean [SD] age, 77.1 [7.6] years; 5912 hospitalizations among women [58.5%]) were identified. The overall fall injury risk was 0.77%. In adjusted models, marginal increases in weekly fall injury risk just before hospitalization (0.27 percentage points [95% CI, 0.22 to 0.33 percentage points], or 30.0%;<i>P</i> &lt; .001) were 4 times greater than decreases just after hospitalization (−0.18 percentage points [95% CI, −0.23 to −0.13 percentage points], or −9.2%;<i>P</i> &lt; .001)]. A greater risk differential before and after hospitalization was observed for patients with an inpatient fall injury (1.89 percentage points [95% CI, 1.37 to 2.40], or 309.8%;<i>P</i> &lt; .001; vs −0.39 percentage points [95% CI, −0.73 to −0.04], or −11.6%;<i>P</i> = .03). <h3>Conclusions and Relevance</h3> An episode-based assessment of fall injury illustrates substantial variability in period-specific risks over an extended period including an anchor hospitalization. Risk transitions between periods include sizable increases just before hospitalization that do not fully subside after hospital discharge. Financial incentives to coordinate hospital and posthospital care for patients at risk for fall injury are needed. These could include bundled payments for fall injury episodes that incentivize coordination across settings.
DNA polymerase stalling at structured DNA constrains the expansion of short tandem repeats
Authors: Pierre Murat, Guillaume Guilbaud, Julian E. Sale
Journal: Genome biology (2020)

Short tandem repeats (STRs) contribute significantly to de novo mutagenesis, driving phenotypic diversity and genetic disease. Although highly diverse, their repetitive sequences induce DNA polymerase slippage and stalling, leading to length and sequence variation. However, current studies of DNA synthesis through STRs are restricted to a handful of selected sequences, limiting our broader understanding of their evolutionary behaviour and hampering the characterisation of the determinants of their abundance and stability in eukaryotic genomes.We perform a comprehensive analysis of DNA synthesis at all STR permutations and interrogate the impact of STR sequence and secondary structure on their genomic representation and mutability. To do this, we developed a high-throughput primer extension assay that allows monitoring of the kinetics and fidelity of DNA synthesis through 20,000 sequences comprising all STR permutations in different lengths. By combining these measurements with population-scale genomic data, we show that the response of a model replicative DNA polymerase to variously structured DNA is sufficient to predict the complex genomic behaviour of STRs, including abundance and mutational constraints. We demonstrate that DNA polymerase stalling at DNA structures induces error-prone DNA synthesis, which constrains STR expansion.Our data support a model in which STR length in eukaryotic genomes results from a balance between expansion due to polymerase slippage at repeated DNA sequences and point mutations caused by error-prone DNA synthesis at DNA structures.
Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network
Authors: Heinz Ludwig, Mario Boccadoro, Philippe Moreau, Jesus San-Miguel, Michele Cavo, Charlotte Pawlyn, Sonja Zweegman, Thierry Facon, Christoph Driessen, Roman Hajek, Melitios A. Dimopoulos, Francesca Gay, Hervé Avet-Loiseau, Evangelos Terpos, Niklas Zojer, Mohamad Mohty, Maria-Victoria Mateos, Hermann Einsele, Michel Delforge, Jo Caers, Katja Weisel, Graham Jackson, Laurent Garderet, Monika Engelhardt, Niels van de Donk, Xavier Leleu, Hartmut Goldschmidt, Meral Beksac, Inger Nijhof, Niels Abildgaard, Sara Bringhen, Pieter Sonneveld
Journal: Leukemia (2020)

Abstract Vaccination is one of the most successful medical interventions that has saved the life of millions of people. Vaccination is particularly important in patients with multiple myeloma, who have an increased risk of infections due to the disease-inherent immune suppression, and because of the immune suppressive effects of therapy. Hence, all appropriate measures should be exploited, to elicit an effective immune response to common pathogens like influenza, pneumococci, varicella zoster virus, and to those bacteria and viruses (haemophilus influenzae, meningococci, and hepatitis) that frequently may pose a significant risk to patients with multiple myeloma. Patients after autologous, and specifically after allogeneic transplantation have severely reduced antibody titers, and therefore require a broader spectrum of vaccinations. Response to vaccination in myeloma often is less vigorous than in the general population, mandating either measurement of the postvaccination antibody titers and/or repeating the vaccination. Here, we compile the existing data on vaccination in multiple myeloma and provide recommendations for clinical practice.
Molecular Landscape and Clinical Features of Acute Myeloid Leukemia (AML) with Complex Karyotype (CK)
Authors: Krzysztof Mrózek, Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Andrew J. Carroll, Deedra Nicolet, James S. Blachly, Christopher J. Walker, Eunice S. Wang, Geoffrey L. Uy, Jonathan E. Kolitz, Bayard L. Powell, William Blum, Richard M. Stone, John C. Byrd, Clara D. Bloomfield
Journal: Blood (2017)
Haemodynamics of atherosclerosis: a matter of higher hydrostatic pressure or lower shear stress?
Authors: Xinggang Wang, Junbo Ge
Journal: Cardiovascular Research (2021)

The traditional view is that low shear stress of blood flow accelerates atherosclerosis. How does a low shear stress damage the vessel or aggravate atherosclerosis? It is a puzzling question. Furthermore, shear stress of veins is similar to that of Relatively Vulnerable Zones (RVZ) of arteries, while intimal thickening of veins is not obvious as the arteries. There are many places in arterioles with lower shear stress as the decrease of blood velocity, while the thickening of arterioles is not as obvious as that of the medium-sized arteries. These issues make it unconvincing for us to explain atherogenesis with lower shear stress. According to Bernoulli fluid equation (P+1/2\r{ho}v^2+\r{ho}gh=constant), in a closed pipe full of flowing blood, at the same height, the hydrostatic pressure is inversely proportional to the second power of blood velocity. At any point of per unit mass of fluid micro cluster here, the reduction of 1/2\r{ho}v^2 would be converted into P. Therefore, hydrostatic pressure(P) is inversely proportional to v^2 in a very short distance or in the same transection of the artery. When blood micro cluster flows over a very short distance or the same transection of the artery, previous studies did not consider the conversion between 1/2\r{ho}v^2 and P. Therefore, low shear stress aggravates atherosclerosis is an appearance, and the essence is that these areas with smaller blood velocity have much bigger hydrostatic pressure, which aggravates atherosclerosis. This perfectly explains the predisposing sites of atherosclerosis.
Parents can challenge NICE guidance on medicinal cannabis in court
Authors: Clare Dyer
Journal: BMJ (2020)

The parents of a 3 year old boy with severe epilepsy have been given permission to mount a landmark High Court challenge to guidance from the National Institute for Health and Care Excellence (NICE) regarding cannabis prescribing on the NHS.1

Matt and Alison Hughes argue that the guidance is so restrictive that it could effectively be barring hundreds of children from accessing the cannabis treatment they need on the NHS. The family has legal aid for the judicial review case.

Charlie Hughes has West syndrome, a rare form of treatment resistant epilepsy linked to developmental delay, which can cause him to have dozens of seizures a day. But with regular, full extract cannabis oil, containing both tetrahydrocannabinol (THC) and cannabidiol (CBD), his parents say that his seizures …
Abstract 16705: Nox4-Derived ROS Production in the Endoplasmic Reticulum Promotes Autophagy During Cardiomyocyte Nutrient Deprivation Through the PHD4/ PERK Pathway
Authors: Sebastiano Sciarretta, Peiyong Zhai, Dan Shao, Derek Yee, Daniela Zablocki, Lance S Terada, Massimo Volpe, Junichi Sadoshima
Journal: Circulation (2013)

Autophagy is an essential survival mechanism during energy stress in the heart. The signaling mechanism through which energy stress leads to activation of autophagy is poorly understood. We investi...
Left Atrial Strain Impairment Precedes Geometric Remodeling as a Marker of Post-Myocardial Infarction Diastolic Dysfunction
Authors: Jiwon Kim, Brian Yum, Maria C Palumbo, Razia Sultana, Nathaniel Wright, Mukund Das, Cindy You, Chaya S Moskowitz, Robert A Levine, Richard B Devereux, Jonathan W Weinsaft
Journal: JACC. Cardiovascular imaging (2020)
The Eyes
Authors: Michael E. Hall, Arsalan Hamid, Adebamike A. Oshunbade
Journal: Circulation Research (2019)

C ardiovascular disease (CVD) is a major cause of morbid- ity and mortality in patients with end-stage renal disease (ESRD).Over 60% of patients with ESRD have some form of CVD, including arrhythmias, cardiac arrest, congestive heart failure, acute myocardial infarction, and atherosclerotic heart disease, which are responsible for 48% of deaths among dialysis patients. 1ESRD patients on dialysis have accelerated atherosclerosis, arteriosclerosis with noncompliant vasculature and high rates of heart failure. 2 Sodium and water retention, elevated blood pressure, increased inflammation, and vascular calcification are a few of the proposed mechanisms linking ESRD to increased CVD risk.Of course, CVD and kidney diseases share many risk factors; notably, hypertension, diabetes mellitus, dyslipidemia, and obesity among others. 3The relationship between CVD and kidney disease is bidirectional and the relative contributions of each disease to the other and the time course of these relationships are not fully understood.
Abstract 16516: Spironolactone In Patients With Atrial Fibrillation And Preserved Ejection Fraction Does Not Reduce Arrhythmia Burden: Results From A Randomized, Double-blind, Placebo-controlled Trial (INSPIRE-AF)
Authors: Dragana Rujic, Manan Pareek, Per L Madsen, Kenneth Egstrup, Tina Juhl Hansen
Journal: Circulation (2019)

Background: Spironolactone has antifibrotic properties and may reduce the burden of arrhythmia in patients with atrial fibrillation (AF). Purpose: To evaluate the efficacy of spironolactone versus ...
Association Between Bariatric Surgery and All-Cause Mortality: A Population-Based Matched Cohort Study in a Universal Health Care System
Authors: Aristithes G. Doumouras, Dennis Hong, Yung Lee, Jean-Eric Tarride, J. Michael Paterson, Mehran Anvari
Journal: Annals of Internal Medicine (2020)

Background: Mortality after bariatric surgery has been previously studied, but cohort selection bias, completeness of follow-up, and collection of confounders have limited the inference of results. Objective: To determine the association between bariatric surgery and all-cause mortality. Design: Population-based matched cohort study. Setting: Ontario, Canada. Participants: 13 679 patients who underwent bariatric surgery from January 2010 to December 2016 and 13 679 matched nonsurgical patients. Intervention: Bariatric surgery. Measurements: The primary outcome was all-cause mortality, with cause-specific mortality as the secondary outcome. Patients were matched according to age, sex, body mass index, and diabetes duration. Results: 13 679 patients who underwent bariatric surgery were matched to 13 679 nonsurgical patients. After a median follow-up of 4.9 years, the overall mortality rate was 1.4% (n = 197) in the surgery group and 2.5% (n = 340) in the nonsurgery group, with a lower adjusted hazard ratio (HR) of overall all-cause mortality (HR, 0.68 [95% CI, 0.57 to 0.81]). Patients aged 55 years or older had an absolute risk reduction of 3.3% (CI, 2.3% to 4.3%), with a lower HR of mortality in the surgery group (HR, 0.53 [CI, 0.41 to 0.69]). Observed relative effects were similar across sex; however, the observed association in absolute terms was greater in men. Surgery also was associated with lower cardiovascular mortality (HR, 0.53 [CI, 0.34 to 0.84]) and lower cancer mortality (HR, 0.54 [CI, 0.36 to 0.80]). Limitation: The observational design limits causal inference. Conclusion: Bariatric surgery was associated with substantially lower all-cause, cardiovascular, and cancer mortality. The lowered observed mortality of surgery was significant across most subgroups. The largest absolute effects were for men and patients aged 55 years or older. Primary Funding Source: Ontario Bariatric Network.
Dermatology’s Management of Flagship Diseases in Older Adults
Authors: Daniel C. Butler
Journal: JAMA Dermatology (2020)

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 Dermatology 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 Dermatology journal
Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial
Authors: J.K. Litton, S.A. Hurvitz, L.A. Mina, H.S. Rugo, K.-H. Lee, A. Gonçalves, S. Diab, N. Woodward, A. Goodwin, R. Yerushalmi, H. Roché, Y.-H. Im, W. Eiermann, R.G.W. Quek, T. Usari, S. Lanzalone, A. Czibere, J.L. Blum, M. Martin, J. Ettl
Journal: Annals of Oncology (2020)

In EMBRACA, talazoparib prolonged progression-free survival versus chemotherapy (hazard ratio [HR] 0.542 [95% confidence interval (CI) 0.413-0.711]; P < 0.0001) and improved patient-reported outcomes (PRO) in germline BRCA1/2 (gBRCA1/2)-mutated advanced breast cancer (ABC). We report final overall survival (OS).This randomized phase III trial enrolled patients with gBRCA1/2-mutated HER2-negative ABC. Patients received talazoparib or physician's choice of chemotherapy. OS was analyzed using stratified HR and log-rank test and prespecified rank-preserving structural failure time model to account for subsequent treatments.A total of 431 patients were entered in a randomized study (287 talazoparib/144 chemotherapy) with 412 patients treated (286 talazoparib/126 chemotherapy). By 30 September 2019, 216 deaths (75.3%) occurred for talazoparib and 108 (75.0%) chemotherapy; median follow-up was 44.9 and 36.8 months, respectively. HR for OS with talazoparib versus chemotherapy was 0.848 (95% CI 0.670-1.073; P = 0.17); median (95% CI) 19.3 months (16.6-22.5 months) versus 19.5 months (17.4-22.4 months). Kaplan-Meier survival percentages (95% CI) for talazoparib versus chemotherapy: month 12, 71% (66% to 76%)/74% (66% to 81%); month 24, 42% (36% to 47%)/38% (30% to 47%); month 36, 27% (22% to 33%)/21% (14% to 29%). Most patients received subsequent treatments: for talazoparib and chemotherapy, 46.3%/41.7% received platinum and 4.5%/32.6% received a poly(ADP-ribose) polymerase (PARP) inhibitor, respectively. Adjusting for subsequent PARP and/or platinum use, HR for OS was 0.756 (95% bootstrap CI 0.503-1.029). Grade 3-4 adverse events occurred in 69.6% (talazoparib) and 64.3% (chemotherapy) patients, consistent with previous reports. Extended follow-up showed significant overall improvement and delay in time to definitive clinically meaningful deterioration in global health status/quality of life and breast symptoms favoring talazoparib versus chemotherapy (P < 0.01 for all), consistent with initial analyses.In gBRCA1/2-mutated HER2-negative ABC, talazoparib did not significantly improve OS over chemotherapy; subsequent treatments may have impacted analysis. Safety was consistent with previous observations. PRO continued to favor talazoparib.
Spatial Transcriptomics of Nematodes Identifies Sperm Cells as a Source of Genomic Novelty and Rapid Evolution
Authors: Christian Rödelsperger, Annabel Ebbing, Devansh Raj Sharma, Misako Okumura, Ralf J Sommer, Hendrik C Korswagen
Journal: Molecular Biology and Evolution (2020)

Abstract Divergence of gene function and expression during development can give rise to phenotypic differences at the level of cells, tissues, organs, and ultimately whole organisms. To gain insights into the evolution of gene expression and novel genes at spatial resolution, we compared the spatially resolved transcriptomes of two distantly related nematodes, Caenorhabditis elegans and Pristionchus pacificus, that diverged 60–90 Ma. The spatial transcriptomes of adult worms show little evidence for strong conservation at the level of single genes. Instead, regional expression is largely driven by recent duplication and emergence of novel genes. Estimation of gene ages across anatomical structures revealed an enrichment of novel genes in sperm-related regions. This provides first evidence in nematodes for the “out of testis” hypothesis that has been previously postulated based on studies in Drosophila and mammals. “Out of testis” genes represent a mix of products of pervasive transcription as well as fast evolving members of ancient gene families. Strikingly, numerous novel genes have known functions during meiosis in Caenorhabditis elegans indicating that even universal processes such as meiosis may be targets of rapid evolution. Our study highlights the importance of novel genes in generating phenotypic diversity and explicitly characterizes gene origination in sperm-related regions. Furthermore, it proposes new functions for previously uncharacterized genes and establishes the spatial transcriptome of Pristionchus pacificus as a catalog for future studies on the evolution of gene expression and function.
Audio Interview: Covid-19 and Contact Tracing
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

Covid-19 and Contact Tracing In this audio interview conducted on August 19, 2020, the editors discuss the use of contact tracing to limit the spread of SARS-CoV-2 and the challenges posed by certa...
Dynamics of Cardiac Neutrophil Diversity in Murine Myocardial Infarction
Authors: Ehsan Vafadarnejad, Giuseppe Rizzo, Laura Krampert, Panagiota Arampatzi, Anahi-Paula Arias-Loza, Yara Nazzal, Anna Rizakou, Tim Knochenhauer, Sourish Reddy Bandi, Vallery Audy Nugroho, Dirk J.J Schulz, Melanie Roesch, Paul Alayrac, Jose Vilar, Jean-Sébastien Silvestre, Alma Zernecke, Antoine-Emmanuel Saliba, Clément Cochain
Journal: Circulation Research (2020)

Rationale: After myocardial infarction, neutrophils rapidly and massively infiltrate the heart, where they promote both tissue healing and damage. Objective: To characterize the dynamics of circulating and cardiac neutrophil diversity after infarction. Methods and results: We employed single-cell transcriptomics combined with cell surface epitope detection by sequencing to investigate temporal neutrophil diversity in the blood and heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, cardiac Ly6G + (lymphocyte antigen 6G) neutrophils could be delineated into 6 distinct clusters with specific time-dependent patterning and proportions. At day 1, neutrophils were characterized by a gene expression profile proximal to bone marrow neutrophils ( Cd177 , Lcn2 , Fpr1 ), and putative activity of transcriptional regulators involved in hypoxic response ( Hif1a ) and emergency granulopoiesis ( Cebpb ). At 3 and 5 days, 2 major subsets of Siglecf hi (enriched for eg, Icam1 and Tnf ) and Siglecf low ( Slpi, Ifitm1 ) neutrophils were found. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis in blood and heart revealed that while circulating neutrophils undergo a process of aging characterized by loss of surface CD62L and upregulation of Cxcr4 , heart infiltrating neutrophils acquired a unique SiglecF hi signature. SiglecF hi neutrophils were absent from the bone marrow and spleen, indicating local acquisition of the SiglecF hi signature. Reducing the influx of blood neutrophils by anti-Ly6G treatment increased proportions of cardiac SiglecF hi neutrophils, suggesting accumulation of locally aged neutrophils. Computational analysis of ligand/receptor interactions revealed putative pathways mediating neutrophil to macrophage communication in the myocardium. Finally, SiglecF hi neutrophils were also found in atherosclerotic vessels, revealing that they arise across distinct contexts of cardiovascular inflammation. Conclusions: Altogether, our data provide a time-resolved census of neutrophil diversity and gene expression dynamics in the mouse blood and ischemic heart at the single-cell level, and reveal a process of local tissue specification of neutrophils in the ischemic heart characterized by the acquisition of a SiglecF hi signature.
Diffuse Myocardial Fibrosis and Diastolic Function in Aortic Stenosis
Authors: Hyun-Jung Lee, Heesun Lee, Sung Mok Kim, Jun-Bean Park, Eun Kyoung Kim, Sung-A Chang, Eunah Park, Hyung-Kwan Kim, Whal Lee, Yong-Jin Kim, Sang Chol Lee, Seung Woo Park, Dae-Won Sohn, Jae K. Oh, Sung-Ji Park, Seung-Pyo Lee
Journal: JACC. Cardiovascular imaging (2020)