tbuckley/cabot-search huggingface dataset:
Association of US Food and Drug Administration Removal of Indications for Use of Oral Quinolones With Prescribing Trends
Authors: Phuong T. Tran, Patrick J. Antonelli, Juan M. Hincapie-Castillo, Almut G. Winterstein
Journal: JAMA Internal Medicine (2021)

In May 2016, due to concerns of the risks outweighing the benefits, the US Food and Drug Administration (FDA) removed systemic quinolones' indications for acute, uncomplicated urinary tract infection (uUTI), acute sinusitis (AS), and acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). How the change influenced oral quinolone use is unknown.To assess the association of oral quinolone safety warnings and indication restrictions with use.This interrupted time series (January 2015-November 2018) analysis of the monthly prevalence of oral quinolone-treated infection episodes used a national sample of privately insured patients in outpatient care from the IBM MarketScan Database and included adults with antibiotic treatment of new uUTI, AS, or AE-COPD episodes, excluding patients with conditions that complicate infections, previous hospitalization, or other infections.Time before and after May 2016 when the FDA mandated label changes.Monthly oral quinolone use prevalence by each condition before and after the label changes, overall and stratified by prescriber specialty.In January 2015, quinolone prevalence among antibiotic-treated uUTI episodes (n = 652 235) was 41.6% (95% CI, 40.6%-42.5%); AS (n = 1 742 248) was 8.3% (95% CI, 7.9%-8.6%), and AE-COPD (n = 22 817) was 31.9% (95% CI, 30.3%-33.4%). Before the label changes, trends in monthly quinolone prevalence were nearly flat. The month of the label changes we noted an immediate reduction for uUTI (-7.2%; 95% CI, -8.6% to -5.8%); and to a lesser extent for AS (-1.2%; 95% CI, -1.5% to -0.9%) and AE-COPD (-2.6%; 95% CI, -4.1% to -1.1%), and continued monthly declines thereafter. Falsification tests confirmed an immediate decrease after the label change of quinolone use for uUTI but more obscured effects for AS and AE-COPD. Treatment shifted mostly to first-line (eg, nitrofurantoin in uUTI, amoxicillin in AS, macrolides in AE-COPD) and other second-line agents but use of not recommended antibiotics also increased (eg, tetracyclines in AE-COPD). Prescribing preferences varied, but significant reductions were seen across all prescriber specialties. At the end of the study period, quinolone was used for 19.2% of treated uUTIs, 2.9% of treated AS, and 14.6% of treated AE-COPD episodes.Label changes and their announcements was associated with an immediate reduction in oral quinolone use for uUTI and to a lesser extent for AS and AE-COPD. Quinolones continued to contribute a considerable proportion of treatments for uUTI and AE-COPD episodes at the end of the study period, pointing to opportunities for further improvement.
Free Graft Augmentation Urethroplasty for Bulbar Urethral Strictures: Which Technique Is Best? A Systematic Review
Authors: Rachel Barratt, Garson Chan, Roberto La Rocca, Konstantinos Dimitropoulos, Francisco E. Martins, Félix Campos-Juanatey, Tamsin J. Greenwell, Marjan Waterloos, Silke Riechardt, Nadir I. Osman, Yuhong Yuan, Franceso Esperto, Achilles Ploumidis, Nicolaas Lumen
Journal: European Urology (2021)
Abstract 15149: Aortic Total Clamp Increases Post Coronary Artery Bypass Grafting Stroke: A Multinomial Multifactor Model
Authors: Sandro Gelsomino, Linda R Micali, Edvin Prifti, Gianmarco Parise, Massimo Bonacchi
Journal: Circulation (2020)

Introduction: We performed a multinomial multifactor propensity-score based analysis on stroke in patients undergoing CABG. The unique model allowed us to test all the potential technical risk related to aortic manipulation alone or in combination. Methods: The study population included 16,255 consecutive patients undergoing isolated CABG between 1997 and 2017. Patients were divided into 7 groups: 1) No Proximal Anastomoses-Off-pump (NPA-OFF) group, 2) Side Biting Clamp-Off-pump (SBCL-OFF) group, 3) No Proximal Anastomoses-Beating Heart-On-Pump (NPA-BH-ON) group, 4) Side Biting Clamp-Beating Heart-On-Pump (SBCL-BH-ON) group, 5) No Proximal Anastomoses-Aortic Total Clamp-On-pump (NPA-ATC-ON) group, 6) Aortic Total Clamp-On-pump (ATC-ON) group, 7) Aortic Total Clamp-Side Biting Clamp-On-pump (ATC-SBCL-ON) group. The main end-point was the incidence of postoperative stroke within 30 days of the procedure. Statistical significance was set for p-values&lt; 0.05 (*). Results: The optimal balance with the balance table, effect size plot and Q-Q plot, allowed us to conclude that the groups were similar to support causal estimation of the treatment estimand. As shown in Figure 1, there was no difference between a total no-touch (NPA-OFF group) vs. the same technique on pump (NPA-BH-ON group, p&gt;0.05) and or adding a side biting clamp to these two procedures (SBCL-OFF group and SBCL-BH-ON group, both p&gt;0.05). All procedures including the use of a total clamp (NPA-ATC-ON, ATC-ON and ATC-SBCL-ON groups) had a significantly higher incidence of stroke (all p&lt;0.001). However, the latter procedures did not show difference between them (p&gt;0.05). Conclusions: Aortic total clamp is the main factor increasing the incidence of stroke. In contrast, the use of side biting partial clamping, off-pump techniques or cardiopulmonary bypass without aortic clamp and cardioplegic arrest, does not affect the incidence of stroke.
Abstract 14893: Light Activation in Plaque Macrophages Enhances Efferocytosis of Apoptotic Cells via Upregulation of Autophagy and Mertk Expression
Authors: Joon Woo Song, Min Woo Lee, Hyun Jung Kim, Jiseon Min, Un Gyo Kang, Yeon Hoon Kim, Jeongmoo Han, Hongki Yoo, Kyeongsoon Park, Jin Won Kim
Journal: Circulation (2020)

Introduction: Autophagy plays a protective role in atherosclerosis and can promote efferocytosis of apoptotic cells. Photoactivation is a promising tool for treating cardiovascular disease, and induces autophagy in macrophages-derived foam cells, however, regulation of autophagy and efferocytosis by photoactivation in atherosclerotic plaque remains unknown. Objective: The present study aims to investigate whether macrophage targeted light activation induces autophagy and enhances efferocytosis in inflamed plaques Methods and Results: Targeted photoactivatable agent showed specific binding affinity and phototoxicity to scavenger receptor-expressing macrophages. Confocal microscopy analysis over time after irradiation demonstrated the induction of apoptosis and autophagy flux in macrophage-derived foam cells. The theranostic agent localized to macrophage scavenger receptors within atherosclerotic plaques, and intravital fluorescence microscopy imaged plaque inflammation and was used to monitor photobleaching after irradiation. Serial in vivo imaging analysis demonstrated that macrophage-specific photoactivation reduced plaque burden and inflammation after 1 week (Figure A). Mechanistically, targeted light activation induced autophagy within atheroma as early as 1 day (Figure B), and increased phagocytic receptor Mer tyrosine kinase (MerTK) expression. Targeted photoactivation had 2-fold-increase in macrophage-associated apoptotic bodies at one week after laser irradiation, indicating enhanced efferocytosis (Figure C). Conclusions: As a sensitive multifunctional therapeutic and imaging strategy, macrophage targeted photoactivation with autophagy induction could confer a promising theranostic strategy for the high-risk plaques.
Health and environmental co-benefits of city urban form in Latin America: an ecological study
Authors: Ione Avila-Palencia, Brisa N Sánchez, Daniel A Rodríguez, Carolina Perez Ferrer, J Jaime Miranda, Nelson Gouveia, Usama Bilal, Andrés F Useche, Maria A Wilches-Mogollon, Olga L Sarmiento, Ana V Diez Roux
Journal: The Lancet Planetary Health (2021)

BackgroundUrban design features are often studied in relation to health and behavioural outcomes. They can also have major implications for environmental outcomes. However, the impact of these features on both health and environmental outcomes (co-benefits) is rarely examined. We investigated how urban landscape and street design profiles are related to jointly occurring health and environmental outcomes in Latin America cities.MethodsWe used data from the Salud Urbana en América Latina (SALURBAL) project, which has compiled and harmonised data on built environment, environmental exposures, and health outcomes for 370 cities in 11 countries: Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Guatemala, Mexico, Nicaragua, Panama, and Peru. Eight city profiles were identified using finite mixture models. Four urban-landscape profiles were defined measuring patch (contiguous area of urban development) fragmentation, shape, and isolation, and four street-design profiles were defined using street connectivity, length, and directness. Multilevel regression models were used to assess associations between the city profiles and several health and environmental outcomes.FindingsOur preliminary results show that compared with the urban-landscape profile labelled scattered pixels (comprising low fragmentation, compact shape, and high isolation), the proximate-stones profile (moderate fragmentation, irregular shape, and moderate isolation) had significantly higher levels of PM2·5 and nitrogen dioxide (NO2), and the proximate-inkblots profile (moderate-to-high fragmentation, complex shape, and moderate isolation) had significantly higher levels of violence-related deaths. Compared with the labyrinthine street design profile (low connectivity, moderate length, and moderate directness), the semi-hyperbolic grid (moderate connectivity, moderate length, and moderate directness) and spiderweb (high connectivity, low length, and moderate directness) profiles had significantly higher levels of PM2·5 and NO2, whereas the hyperbolic grid profile (moderate connectivity, high length, and low directness) had significantly higher levels of NO2 and lower levels of obesity.InterpretationIdentifying how city profiles are related to environment and health outcomes can shed light on the urban policies that could have the greatest environment and health co-benefits.FundingThe SALURBAL/Urban Health in Latin America project is funded by the Wellcome Trust (205177/Z/16/Z).
Minor intron retention drives clonal hematopoietic disorders and diverse cancer predisposition
Authors: Daichi Inoue, Jacob T. Polaski, Justin Taylor, Pau Castel, Sisi Chen, Susumu Kobayashi, Simon J. Hogg, Yasutaka Hayashi, Jose Mario Bello Pineda, Ettaib El Marabti, Caroline Erickson, Katherine Knorr, Miki Fukumoto, Hiromi Yamazaki, Atsushi Tanaka, Chie Fukui, Sydney X. Lu, Benjamin H. Durham, Bo Liu, Eric Wang, Sanjoy Mehta, Daniel Zakheim, Ralph Garippa, Alex Penson, Guo-Liang Chew, Frank McCormick, Robert K. Bradley, Omar Abdel-Wahab
Journal: Nature Genetics (2021)
Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy
Authors: Sima Jeha, John Choi, Kathryn G. Roberts, Deqing Pei, Elaine Coustan-Smith, Hiroto Inaba, Jeffrey E. Rubnitz, Raul C. Ribeiro, Tanja A. Gruber, Susana C. Raimondi, Seth E. Karol, Chunxu Qu, Samuel W. Brady, Zhaohui Gu, Jun J. Yang, Cheng Cheng, James R. Downing, Williams E. Evans, Mary V. Relling, Dario Campana, Charles G. Mullighan, Ching-Hon Pui
Journal: Blood Cancer Discovery (2021)

Abstract We evaluated clinical significance of recently identified subtypes of acute lymphoblastic leukemia (ALL) in 598 children treated with minimal residual disease (MRD)–directed therapy. Among the 16 B-cell ALL (B-ALL) and 8 T-cell ALL subtypes identified by next-generation sequencing, ETV6–RUNX1, high-hyperdiploid, and DUX4-rearranged B-ALL had the best 5-year event-free survival rates (95.0%–98.4%); TCF3–PBX1, PAX5-altered (PAX5alt), T-cell, early T-cell precursor (ETP), intrachromosomal amplification of chromosome 21 (iAMP21), and hypodiploid ALL intermediate rates (80.0%–88.2%); and BCR–ABL1, BCR–ABL1-like, ETV6–RUNX1-like, and KMT2A-rearranged ALL the worst rates (64.1%–76.2%). All but 3 of the 142 patients with day 8 blood MRD &amp;lt;0.01% remained in remission. Among new subtypes, intensified therapy based on day 15 MRD ≥1% improved outcome of DUX4-rearranged, BCR–ABL1-like, and ZNF384-rearranged ALL, and achievement of day 42 MRD &amp;lt;0.01% did not preclude relapse of PAX5alt, MEF2D-rearranged, and ETV6–RUNX1-like ALL. Thus, new subtypes including DUX4-rearranged, PAX5alt, BCR–ABL1-like, ETV6–RUNX1-like, MEF2D-rearranged, and ZNF384-rearranged ALL have important prognostic and therapeutic implications. Significance: Genomic analyses and MRD should be used together for risk-directed treatment of childhood ALL. Six recently described subtypes—DUX4-rearranged, PAX5alt, BCR–ABL1-like, ETV6–RUNX1-like, MEF2D-rearranged, and ZNF384-rearranged ALL—had prognostic and therapeutic significance with contemporary risk-directed treatment. See related commentary by Segers and Cools, p. 294. See related video from the AACR Annual Meeting 2021: https://vimeo.com/558556916
An Electrical Stimulation Culture System for Daily Maintenance-Free Muscle Tissue Production
Authors: Yoshitake Akiyama, Akemi Nakayama, Shota Nakano, Ryuichiro Amiya, Jun Hirose
Journal: Cyborg and Bionic Systems (2021)

Low-labor production of tissue-engineered muscles (TEMs) is one of the key technologies to realize the practical use of muscle-actuated devices. This study developed and then demonstrated the daily maintenance-free culture system equipped with both electrical stimulation and medium replacement functions. To avoid ethical issues, immortal myoblast cells C2C12 were used. The system consisting of gel culture molds, a medium replacement unit, and an electrical stimulation unit could produce 12 TEMs at one time. The contractile forces of the TEMs were measured with a newly developed microforce measurement system. Even the TEMs cultured without electrical stimulation generated forces of almost 2 mN and were shortened by 10% in tetanic contractions. Regarding the contractile forces, electrical stimulation by a single pulse at 1 Hz was most effective, and the contractile forces in tetanus were over 2.5 mN. On the other hand, continuous pulses decreased the contractile forces of TEMs. HE-stained cross-sections showed that myoblast cells proliferated and fused into myotubes mainly in the peripheral regions, and fewer cells existed in the internal region. This must be due to insufficient supplies of oxygen and nutrients inside the TEMs. By increasing the supplies, one TEM might be able to generate a force up to around 10 mN. The tetanic forces of the TEMs produced by the system were strong enough to actuate microstructures like previously reported crawling robots. This daily maintenance-free culture system which could stably produce TEMs strong enough to be utilized for microrobots should contribute to the advancement of biohybrid devices.
Biomaterials reinforced MSCs transplantation for spinal cord injury repair
Authors: Teng Ma, Jiahe Wu, Jiafu Mu, Jianqing Gao
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Due to the complex pathophysiological mechanism, spinal cord injury (SCI) has become one of the most intractable central nervous system (CNS) diseases to therapy. Stem cell transplantation, mesenchymal stem cells (MSCs) particularly, appeals to more and more attention along with the encouraging therapeutic results for the functional regeneration of SCI. However, traditional cell transplantation strategies have some limitations, including the unsatisfying survival rate of MSCs and their random diffusion from the injection site to ambient tissues. The application of biomaterials in tissue engineering provides a new horizon. Biomaterials can not only confine MSCs in the injured lesions with higher cell viability, but also promote their therapeutic efficacy. This review summarizes the strategies and advantages of biomaterials reinforced MSCs transplantation to treat SCI in recent years, which are clarified in the light of various therapeutic effects in pathophysiological aspects of SCI.
A year and a day of #Covid19uk tweets
Authors: Graham Mackenzie
Journal: The Lancet Infectious Diseases (2021)

We view accounts of past pandemics and outbreaks through a variety of media with varying levels of confidence, including transcriptions of after dinner speeches by Plutarch (AD 46–119) on infectious diseases, and Samuel Pepys's 17th century diaries on the bubonic plague. This century, SARS (2003) and Ebola virus disease (2014–16) received extensive coverage in lay press and medical journals.
Initial Findings From the North American COVID-19 Myocardial Infarction Registry
Authors: Santiago Garcia, Payam Dehghani, Cindy Grines, Laura Davidson, Keshav R. Nayak, Jacqueline Saw, Ron Waksman, John Blair, Bagai Akshay, Ross Garberich, Christian Schmidt, Hung Q. Ly, Scott Sharkey, Nestor Mercado, Carlos E. Alfonso, Naoki Misumida, Deepak Acharya, Mina Madan, Abdul Moiz Hafiz, Nosheen Javed, Jay Shavadia, Jay Stone, M. Chadi Alraies, Wah Htun, William Downey, Brian A. Bergmark, Jospeh Ebinger, Tareq Alyousef, Houman Khalili, Chao-Wei Hwang, Joshua Purow, Alexander Llanos, Brent McGrath, Mark Tannenbaum, Jon Resar, Rodrigo Bagur, Pedro Cox-Alomar, Ada C. Stefanescu Schmidt, Lindsey A. Cilia, Farouc A. Jaffer, Michael Gharacholou, Michael Salinger, Brian Case, Ameer Kabour, Xuming Dai, Osama Elkhateeb, Taisei Kobayashi, Hahn-Ho Kim, Mazen Roumia, Frank V. Aguirre, Jeffrey Rade, Aun-Yeong Chong, Hurst M. Hall, Shy Amlani, Alireza Bagherli, Rajan A.G. Patel, David A. Wood, Frederick G. Welt, Jay Giri, Ehtisham Mahmud, Timothy D. Henry
Journal: Journal of the American College of Cardiology (2021)
Meclofenamate causes loss of cellular tethering and decoupling of functional networks in glioblastoma
Authors: Matthias Schneider, Lea Vollmer, Anna-Laura Potthoff, Vidhya M Ravi, Bernd O Evert, Mohummad A Rahman, Shahin Sarowar, Jan Kueckelhaus, Paulina Will, David Zurhorst, Kevin Joseph, Julian P Maier, Nicolas Neidert, Paolo d’Errico, Melanie Meyer-Luehmann, Ulrich G Hofmann, Andreas Dolf, Paolo Salomoni, Erdem Güresir, Per Ø Enger, Martha Chekenya, Torsten Pietsch, Patrick Schuss, Oliver Schnell, Mike-Andrew Westhoff, Jürgen Beck, Hartmut Vatter, Andreas Waha, Ulrich Herrlinger, Dieter H Heiland
Journal: Neuro-Oncology (2021)

Glioblastoma cells assemble to a syncytial communicating network based on tumor microtubes (TMs) as ultra-long membrane protrusions. The relationship between network architecture and transcriptional profile remains poorly investigated. Drugs that interfere with this syncytial connectivity such as meclofenamate (MFA) may be highly attractive for glioblastoma therapy.
Genomic insights into the origin, domestication and genetic basis of agronomic traits of castor bean
Authors: Wei Xu, Di Wu, Tianquan Yang, Chao Sun, Zaiqing Wang, Bing Han, Shibo Wu, Anmin Yu, Mark A. Chapman, Sammy Muraguri, Qing Tan, Wenbo Wang, Zhigui Bao, Aizhong Liu, De-Zhu Li
Journal: Genome biology (2021)

Abstract Background Castor bean ( Ricinus communis L.) is an important oil crop, which belongs to the Euphorbiaceae family. The seed oil of castor bean is currently the only commercial source of ricinoleic acid that can be used for producing about 2000 industrial products. However, it remains largely unknown regarding the origin, domestication, and the genetic basis of key traits of castor bean. Results Here we perform a de novo chromosome-level genome assembly of the wild progenitor of castor bean. By resequencing and analyzing 505 worldwide accessions, we reveal that the accessions from East Africa are the extant wild progenitors of castor bean, and the domestication occurs ~ 3200 years ago. We demonstrate that significant genetic differentiation between wild populations in Kenya and Ethiopia is associated with past climate fluctuation in the Turkana depression ~ 7000 years ago. This dramatic change in climate may have caused the genetic bottleneck in wild castor bean populations. By a genome-wide association study, combined with quantitative trait locus analysis, we identify important candidate genes associated with plant architecture and seed size. Conclusions This study provides novel insights of domestication and genome evolution of castor bean, which facilitates genomics-based breeding of this important oilseed crop and potentially other tree-like crops in future.
Choking with a snare to control immediate bleeding after cold snare polypectomy
Authors: Satoki Shichijo, Koji Higashino, Noriya Uedo, Ryu Ishihara, Tomoki Michida, Yoji Takeuchi
Journal: Endoscopy (2021)

A 75-year-old man underwent surveillance colonoscopy after endoscopic submucosal dissection for an intramucosal adenocarcinoma in his transverse colon. Colonoscopy revealed a metachronous colonic polyp in the transverse colon ([Fig. 1 a]). Macroscopically, this was a type 0-IIa lesion and, according to the JNET classification [1], it was type 2A, indicating a low grade adenoma ([Fig. 1 b]). Therefore, we performed cold snare polypectomy (CSP) using the Snare Master Plus (10 mm; SD-400U-10, Olympus, Tokyo, Japan). Bleeding continued for 60 seconds after CSP (immediate bleeding; [Fig. 1 c]), therefore we choked the mucosal defect, including the surrounding mucosa, with the same snare ([Fig. 1 d]). We continued the choking for 30 seconds, which stopped the bleeding ([Fig. 1 e]; [Video 1]). There were no complaints of hematochezia thereafter. Pathologically, the polyp was a low grade tubular adenoma, with no involvement of the lesion at the cut margin.
Prevalence of Hypertrophic Cardiomyopathy in the UK Biobank Population
Authors: Luis R. Lopes, Nay Aung, Stefan van Duijvenboden, Patricia B. Munroe, Perry M. Elliott, Steffen E. Petersen
Journal: JAMA Cardiology (2021)

This cohort study examines the prevalence of hypertrophic cardiomyopathy in the UK Biobank population.
Utilization of Palliative Care Among Patients with Hematologic Malignancies: An Extensive National Analysis to Define Trends and Patterns
Authors: Sikander Ailawadhi, Ryan D. Frank, Nicolette T. Chimato, Prachi Jani, Aaron C. Spaulding, Mark A. Fiala, Judith Kaur, David O. Hodge, Taimur Sher, Vivek Roy, Prakash Vishnu, Meghna Ailawadhi, Victoria R. Alegria, Aneel Paulus, Asher A. Chanan-Khan, Dorin T. Colibaseanu
Journal: Blood (2017)
Comprehensive analyses of m6A regulators and interactive coding and non-coding RNAs across 32 cancer types
Authors: Sipeng Shen, Ruyang Zhang, Yue Jiang, Yi Li, Lijuan Lin, Zhonghua Liu, Yang Zhao, Hongbing Shen, Zhibin Hu, Yongyue Wei, Feng Chen
Journal: Molecular Cancer (2021)

N6-Methyladenosine (m6A) is an RNA modification that interacts with numerous coding and non-coding RNAs and plays important roles in the development of cancers. Nonetheless, the clinical impacts of m6A interactive genes on these cancers largely remain unclear since most studies focus only on a single cancer type. We comprehensively evaluated m6A modification patterns, including 23 m6A regulators and 83 interactive coding and non-coding RNAs among 9,804 pan-cancer samples. We used clustering analysis to identify m6A subtypes and constructed the m6A signature based on an unsupervised approach. We used the signatures to identify potential m6A modification targets across the genome. The prognostic value of one target was further validated in 3,444 samples from six external datasets. We developed three distinct m6A modification subtypes with different tumor microenvironment cell infiltration degrees: immunological, intermediate, and tumor proliferative. They were significantly associated with overall survival in 24 of 27 cancer types. Our constructed individual-level m6A signature was associated with survival, tumor mutation burden, and classical pathways. With the signature, we identified 114 novel genes as potential m6A targets. The gene shared most commonly between cancer types, BCL9L, is an oncogene and interacts with m6A patterns in the Wnt signaling pathway. In conclusion, m6A regulators and their interactive genes impact the outcome of various cancers. Evaluating the m6A subtype and the signature of individual tumors may inform the design of adjuvant treatments.