tbuckley/cabot-search huggingface dataset:
Wearing Two Hats
Authors: Jeffrey Michael Kowaleski
Journal: JAMA (2019)

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Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation
Authors: Nikki A.H.A. Pluymaekers, Elton A.M.P. Dudink, Justin G.L.M. Luermans, Joan G. Meeder, Timo Lenderink, Jos Widdershoven, Jeroen J.J. Bucx, Michiel Rienstra, Otto Kamp, Jurren M. Van Opstal, Marco Alings, Anton Oomen, Charles J. Kirchhof, Vincent F. Van Dijk, Hemanth Ramanna, Anho Liem, Lukas R. Dekker, Brigitte A.B. Essers, Jan G.P. Tijssen, Isabelle C. Van Gelder, Harry J.G.M. Crijns
Journal: New England Journal of Medicine (2019)

Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously.
Association of Methadone Treatment With Substance-Related Hospital Admissions Among a Population in Canada With a History of Criminal Convictions
Authors: Angela Russolillo, Akm Moniruzzaman, Julian M. Somers
Journal: JAMA Network Open (2019)

People with criminal histories experience high rates of opioid dependence and are frequent users of acute health care services. It is unclear whether methadone adherence prevents hospitalizations.To compare hospital admissions during medicated and nonmedicated methadone periods.A retrospective cohort study involving linked population-level administrative data among individuals in British Columbia, Canada, with provincial justice contacts (n= 250 884) and who filled a methadone prescription between April 1, 2001, and March 31, 2015. Participants were followed from the date of first dispensed methadone prescription until censoring (date of death, or March 31, 2015). Data analysis was conducted from May 1 to August 31, 2018.Methadone treatment was divided into medicated (methadone was dispensed) and nonmedicated (methadone was not dispensed) periods and analyzed as a time-varying exposure.Adjusted hazard ratios (aHRs) of acute hospitalizations for any cause and cause-specific (substance use disorder [SUD], non-substance-related mental disorders [NSMDs], and medical diagnoses [MEDs]) were estimated using multivariable Cox proportional hazards regression.A total of 11 401 people (mean [SD] age, 34.9 [9.4] years; 8230 [72.2%] men) met inclusion criteria and were followed up for a total of 69 279.3 person-years. During a median follow-up time of 5.5 years (interquartile range, 2.8-9.1 years), there were 19 160 acute hospital admissions. Dispensed methadone was associated with a 50% lower rate of hospitalization for any cause (aHR, 0.50; 95% CI, 0.46-0.53) during the first 2 years (≤2.0 years) following methadone initiation, demonstrating significantly lower rates of admission for SUD (aHR, 0.32; 95% CI, 0.27-0.38), NSMD (aHR, 0.41; 95% CI, 0.34-0.50), and MED (aHR, 0.57; 95% CI, 0.52-0.62). As duration of time increased (2.1 to ≤5.0 years; 5.1 to ≤10.0 years), methadone was associated with a significant but smaller magnitude of effect: SUD (aHR, 0.43; 95% CI, 0.36-0.52; aHR, 0.47; 95% CI, 0.37-0.61), NSMD (aHR, 0.51; 95% CI, 0.41-0.64; aHR, 0.60; 95% CI, 0.47-0.78), and MED (aHR, 0.71; 95% CI, 0.65-0.77; aHR, 0.85; 95% CI, 0.76-0.95).In this study, methadone was associated with a lower rate of hospitalization among a large cohort of Canadian individuals with histories of convictions and prevalent concurrent health and social needs. Practices to improve methadone adherence are warranted.
When investigating predictive biomarkers, beware of the qualitative interaction.
Authors: Howard M Mackey, Thomas Bengtsson
Journal: Journal of Clinical Oncology (2015)

2575 Background: The investigation of predictive biomarkers in clinical trials often involves estimation of the biomarker by treatment interaction effect (Royston and Sauerbrei, Journal of Clinical Oncology 2008). A so-called qualitative interaction (Gail and Simon, Biometrics 1985) occurs when a subgroup of patients appear to benefit from treatment while another subgroup is harmed. Spurious, statistically significant interactions are more likely to be observed as qualitative interactions than so called quantitative interactions, i.e. interactions where no subgroup is harmed. This issue is exemplified by recent study results (e.g., http://www.cancernetwork.com/gastrointestinal-cancer/amgen-halts-rilotumumab-development-due-increased-death-signal), highlighting the challenges to developing personalized therapies. Methods: We graphically and statistically illustrate how, under the null hypothesis of no treatment or biomarker effects, spurious qualitative interactions occur much more frequently than quantitative interactions, potentially leading to erroneous conclusions regarding a biomarker’s clinical utility. Following the approach of Mackey and Bengtsson (Contemporary Clinical Trials 2013), we propose a strategy for investigating potential predictive biomarkers that focuses on detecting clinically meaningful treatment effects, as opposed to focusing on interactions which have greater variability. We provide sample size formulae and an inference approach for use in proof-of-concept oncology clinical trials with time-to-event data. Results: By targeting inference on the maximal and minimal biomarker effects (i.e. the largest- and smallest levels of clinical benefit), the proposed method yields lower false positive rates and higher power for detecting the presence of biomarker subgroups than standard approaches. For fixed false positive rates and power, sample size savings were found to be as large as 40%. Conclusions: This new inferential method improves on existing approaches of identifying predictive biomarkers by minimizing false positive risks associated with qualitative, biomarker by treatment interactions.
Stroke in China: advances and challenges in epidemiology, prevention, and management
Authors: Simiao Wu, Bo Wu, Ming Liu, Zhengming Chen, Wenzhi Wang, Craig S Anderson, Peter Sandercock, Yongjun Wang, Yining Huang, Liying Cui, Chuanqiang Pu, Jianping Jia, Tong Zhang, Xinfeng Liu, Suming Zhang, Peng Xie, Dongsheng Fan, Xunming Ji, Ka-Sing Lawrence Wong, Longde Wang, Simiao Wu, Bo Wu, Ming Liu, Zhengming Chen, Wenzhi Wang, Craig S Anderson, Peter Sandercock, Yongjun Wang, Yining Huang, Liying Cui, Chuanqiang Pu, Jianping Jia, Tong Zhang, Xinfeng Liu, Suming Zhang, Peng Xie, Dongsheng Fan, Xunming Ji, Ka-Sing Lawrence Wong, Longde Wang, Chenchen Wei, Yanan Wang, Yajun Cheng, Yunhai Liu, Xin Li, Qiang Dong, Jinsheng Zeng, Bin Peng, Yun Xu, Yi Yang, Yilong Wang, Gang Zhao, Wei Wang, Yuming Xu, Qingwu Yang, Zhiyi He, Shaoshi Wang, Chao You, Ying Gao, Dong Zhou, Li He, Zixiao Li, Jie Yang, Chunyan Lei, Yuhua Zhao, Junfeng Liu, Shuting Zhang, Wendan Tao, Zilong Hao, Deren Wang, Shihong Zhang
Journal: The Lancet Neurology (2019)
Plasma AR status and cabazitaxel in heavily-treated metastatic castration-resistant prostate cancer (mCRPC).
Authors: Vincenza Conteduca, Elena Castro, Anuradha Jayaram, Daniel Wetterskog, Emanuela Scarpi, Nuria Romero-Laorden, David Olmos, Giorgia Gurioli, Cristian Lolli, Javier Puente, Ana Medina, Rosa Querol, Jose Angel Arranz, Maria Isabel Saez, Giuseppe Fornarini, Umberto Basso, Begona Mellado, Enrique Gonzalez-Billalabeitia, Gerhardt Attard, Ugo De Giorgi
Journal: Journal of Clinical Oncology (2019)

203 Background: Plasma androgen receptor ( AR) copy number status has been identified as a potential biomarker of response in mCRPC patients receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown. Methods: Between September 2011 and January 2018, pre-therapy plasma samples were collected from 155 patients treated with second or third-line cabazitaxel at standard or reduced dose in different biomarker protocols. Droplet digital PCR was used to identify plasma AR gain and normal samples, with the primary objective to evaluate associations of plasma AR status with treatment outcome. In an exploratory analysis, a comparison between plasma AR status and treatment type was investigated by incorporating updated data from our prior study of 85 post-docetaxel patients receiving abiraterone or enzalutamide. Results: We observed a shorter median overall/progression-free survival (OS/PFS) in AR-gained compared to AR-normal patients (OS 10.5 versus 14.1 months, hazard ratio (HR) 1.44, 95% confidence interval (CI) 0.98-2.13, P = 0.064), and (PFS 4.0 versus 5.0 months, HR 1.47, 95%CI 1.05-2.07, P = 0.024). In mCRPC patients receiving second-line therapies, a significant treatment interaction was observed between plasma AR and cabazitaxel versus AR-directed therapies for OS (P = 0.041) but not PFS (P = 0.244). In an exploratory analysis, AR-gained patients treated with initial reduced-dose of cabazitaxel had a significantly shorter median OS (7.3 versus 11.5 months, HR 1.95, 95%CI 1.13-3.38, P = 0.016), and PFS (2.7 versus 5.0 months, HR 2.27, 95%CI 1.39-3.71, P = 0.001). Conclusions: Plasma AR status has a potential clinical utility in patients being considered for cabazitaxel. Validation of these findings in prospective trials are warranted.
Evaluation of the prognostic factors associated with development of HLH in Human Stem Cell Transplant Recipients; A Comprehensive Systematic Review.
Authors: Ahmed Elkhanany, Mahmoud Halawa, Doug Myers, Ibrahim Ahmed
Journal: Journal of Clinical Oncology (2015)

e18000 Background: HLH is a rare yet fatal disease, with multiple etiologies. Post-HSCT is poorly described. Role of Allogeneic (AlHSCT) vs Autologous (AuHSCT) in its development is yet to be examined. Methods: SCOPUS queried for “transplant” and “HLH” spanning 20 years. Manual identification for English Human Post-HSCT HLH followed. For univariate analysis, Fisher exact and X2 were used. Log-rank Kaplan–Meier curve was used for survival analysis. HLH was diagnosed using different models. Cohen’s Kappa for interclass concordance was used. Results: A total of 61 pts were identified, mostly males (30, 55%). Median age 39 years (range 0.5 to 69). Primary diagnoses included AML (25, 43%), NHL (11, 19%), ALL (8, 14%) and SAA (5, 9%). All patients received either AlHSCT (53, 87%) or AuHSCT (8, 13%). AlHSCT were either Cord blood (27, 55%), Bone Marrow derived (15, 31%) or peripheral blood (7, 14%). About 30 (67%) received mismatched SC, compared to 14 (32%) with matched SC. Median Engraftment was 20 days (95% CI 15 to 28), seen in 18 patients. Median time for HLH diagnosis was 20 days (95% CI 13 to 22). Most common symptoms were Fever, BM involvement, Hyperferritinemia and cytopenia at 92%, 82%, 77% and 75% respectively. Herpes family isolated in 10 cases, with 42 (69%) negative for viral DNA. There was poor interclass agreement on HLH diagnosis with Kappa 0.068 (95% CI 0.01 to 0.12) In univariate analysis, neither gender nor underlying disease had worse outcomes. However, AuHSCT and Mismatched SCT had OR of 6.25 (p = 0.038) and 4.1 (p = 0.048) of mortality respectively. Engraftment was significantly different between those with Allogeneic vs Autologous (p < .0001). In Survival Analysis, Date of onset of HLH did not differ between latter groups. There was significant difference between matched vs mismatched SCT (23 vs 13 days. p = 0.022). OS was significantly different between Allogeneic and Autologous groups (171 vs 42 days, p = 0.01), but no difference among mismatched vs matched groups. Conclusions: HLH remains elusive to diagnose. Poor agreement on criteria, early onset in mismatched recipients and worse prognosis after Autologous SCT remain to be verified in prospective studies.
Emergence of a Thrombospondin Superfamily at the Origin of Metazoans
Authors: Deborah K Shoemark, Berenice Ziegler, Hiroshi Watanabe, Jennifer Strompen, Richard P Tucker, Suat Özbek, Josephine C Adams
Journal: Molecular Biology and Evolution (2019)

Extracellular matrix (ECM) is considered central to the evolution of metazoan multicellularity; however, the repertoire of ECM proteins in nonbilaterians remains unclear. Thrombospondins (TSPs) are known to be well conserved from cnidarians to vertebrates, yet to date have been considered a unique family, principally studied for matricellular functions in vertebrates. Through searches utilizing the highly conserved C-terminal region of TSPs, we identify undisclosed new families of TSP-related proteins in metazoans, designated mega-TSP, sushi-TSP, and poriferan-TSP, each with a distinctive phylogenetic distribution. These proteins share the TSP C-terminal region domain architecture, as determined by domain composition and analysis of molecular models against known structures. Mega-TSPs, the only form identified in ctenophores, are typically >2,700 aa and are also characterized by N-terminal leucine-rich repeats and central cadherin/immunoglobulin domains. In cnidarians, which have a well-defined ECM, Mega-TSP was expressed throughout embryogenesis in Nematostella vectensis, with dynamic endodermal expression in larvae and primary polyps and widespread ectodermal expression in adult Nematostella vectensis and Hydra magnipapillata polyps. Hydra Mega-TSP was also expressed during regeneration and siRNA-silencing of Mega-TSP in Hydra caused specific blockade of head regeneration. Molecular phylogenetic analyses based on the conserved TSP C-terminal region identified each of the TSP-related groups to form clades distinct from the canonical TSPs. We discuss models for the evolution of the newly defined TSP superfamily by gene duplications, radiation, and gene losses from a debut in the last metazoan common ancestor. Together, the data provide new insight into the evolution of ECM and tissue organization in metazoans.
Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis
Authors: Yoshiharu Muto, Toshiro Moroishi, Kazuya Ichihara, Masaaki Nishiyama, Hideyuki Shimizu, Hidetoshi Eguchi, Kyoji Moriya, Kazuhiko Koike, Koshi Mimori, Masaki Mori, Yuta Katayama, Keiichi I. Nakayama
Journal: The Journal of Experimental Medicine (2019)

Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is a previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload elicited by FBXL5 ablation gave rise to oxidative stress, tissue damage, inflammation, and compensatory proliferation of hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting outcome of FBXL5 deficiency in the liver was also found to be effective in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis promoted by iron overload. In addition, dysregulation of FBXL5-mediated cellular iron homeostasis was found to be associated with poor prognosis in human HCC, suggesting that FBXL5 plays a key role in defense against hepatocarcinogenesis.
Abstract P124: Comparative Evaluation of African Dance versus a Cultural Educational Program in Mitigating Cardiovascular Risk Among REACT! Study Participants
Authors: Jacob K Kariuki, Adrian Bermundez, Timothy Kilkelly, Chelsea Stillman, Patrick Donahue, Charles Lwanga, Mihloti Williams, Chrisala Brown, Mariegold Wollam, Kathy Jedrziewski, Kirk Erickson
Journal: Circulation (2019)

Background: Currently, about 50% of African American (AA) adults are affected by cardiovascular disease (CVD) compared to 38.9% of the general US adult population. Physical inactivity, a major risk factor for CVD, plays a key role in perpetuating the disparities, while physical activity and psychosocial interventions are known to be protective. In this study, we did a secondary analysis of the 6-month Rhythm Experience and Africana Culture Trial (REACT!) to compare the impact of moderate physical activity (African dance) versus an educational control program (culture and health education) in reducing cardiovascular risk. Methods: In the REACT! Trial, CVD risk factors including history of smoking and diabetes, body mass index and systolic blood pressure (SBP) were measured using CDC-BRFSS protocols. In this analysis, we used the non-lab based Framingham algorithm to compute pre- and post-intervention absolute CVD risk scores. Chi-square and t test were used to evaluate between group differences in categorical and continuous variables, respectively. Results: The 28 REACT! Trial participants (mean age 68 yrs, 93% female) were randomly assigned to either the cultural education control group (13) or African dance intervention group (15). At baseline, both groups had comparable cardiovascular risk profiles, including mean SBP (143 vs 146 mmHg; p=0.80) and absolute CVD risk scores (27 vs 29%; p=0.71). Post-intervention, the control group had a more favorable cardiovascular risk profile compared to the intervention group, with improvements in SBP (136 vs 152 mmHg; p=0.028) and absolute CVD risk scores (24 vs 30%; p=0.175), respectively. Conclusions: These data suggest that certain control group characteristics such as social interaction could be potent in lowering SBP compared to moderate physical activity. Possible mechanisms might include the stress-lowering effects of social support and communication in the culture education group.
Functional disorders can also be explained through a non-reductionist application of network theory
Authors: Michael E. Hyland
Journal: Behavioral and Brain Sciences (2019)

Abstract A network structure explains why reductionism is not possible for mental illness, but the same argument applies for the somatic symptoms of functional disorders. Because the covariation of symptoms of functional disorders cannot be explained in terms of symptom-to-symptom causality, explanation requires a network of biological mechanisms having emergent properties that cannot be reduced to biology.
Rapid Wire Casting: A Multimaterial Microphysiological Platform Enabled by Rapid Casting of Elastic Microwires (Adv. Healthcare Mater. 5/2019)
Authors: Yimu Zhao, Erika Yan Wang, Locke Huyer Davenport, Yin Liao, Keith Yeager, Gordana Vunjak‐Novakovic, Milica Radisic, Boyang Zhang
Journal: Advanced Healthcare Materials (2019)
Evaluation of an oncology cooperative group audit preparation workshop.
Authors: Kandie Dempsey, Marta Hayden, Stephen S. Grubbs
Journal: Journal of Clinical Oncology (2015)

e17719 Background: Clinical research outcomes are dependent upon the quality and technique of clinical research professionals engaged in research activities. Audits are conducted to ensure that there is an adherence to mandated research principles. The purpose of this study was to assess whether audit preparation training provided to clinical research professionals preparing to undergo a cooperative group research audit improves audit outcomes, thereby improving trial data quality. Methods: Chart audit outcomes were evaluated from 170 oncology research sites from across the US, including 97 sites that underwent an audit but did not have personnel attend a workshop, along with audit results from 73 sites that did have personnel attend a workshop. A total of 132 individuals attended the workshops over the three years evaluated. The audits consist of reviews in three areas: patient case review, pharmacy, and regulatory. An analysis was conducted to determine if sites that have a larger number of patients placed on clinical trials as compared to other sites experienced more favorable audit outcomes. Results: There was little relationship between training and audit outcomes. Institutions with a higher than 36 accruals annually experienced less favorable results in patient case review scores. A statistically significant difference was noted in IRB between institutional types including: academic; community providers; CCOP and VA. The findings demonstrate that IRB audit scores decreased in academic institutions and increased in community provider sites. Conclusions: It remains unclear from the results whether the audit workshop is contributing to improved audit outcome ratings. The results show a variation in outcome ratings between those organizations that attended the workshop and those that did not. However, the variation is not great enough to infer whether attendance at the workshop is a contributing factor to audit outcomes. While the value of the workshop is unclear, the results of this analysis could highlight ways in which the workshop may be modified in order to more effectively contribute to future success in improving audit outcomes.
Endometrium Injury: PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus (Adv. Healthcare Mater. 5/2019)
Authors: Bang Xiao, Wenjun Yang, Dong Lei, Jinfeng Huang, Yupeng Yin, Yiqing Zhu, Zhengwei You, Fang Wang, Shuhan Sun
Journal: Advanced Healthcare Materials (2019)

In article number 1801455 by Zhengwei You, Fang Wang, Shuhan Sun and co-workers, PGS scaffolds show a modulus similar to that of native rat uterus tissue, while PLGA scaffolds and collagen are much stiffer. PGS scaffolds can significantly prolong the retention of the BMSCs in the injured uterus of rat models. More importantly, BMSCs in the constructs can directly differentiate into endometrial stromal cells. Finally, PGS/BMSCs significantly promote the morphologic and functional recovery of the injured rat uterus with recovered pregnancy rates up to 72.2 ± 6.4%, comparable to state-of-the-art methods.
IL-33trap is a novel IL-33–neutralizing biologic that inhibits allergic airway inflammation
Authors: Aurora Holgado, Harald Braun, Elien Van Nuffel, Sammy Detry, Martijn J. Schuijs, Kim Deswarte, Karl Vergote, Mira Haegman, Griet Baudelet, Jurgen Haustraete, Hamida Hammad, Bart N. Lambrecht, Savvas N. Savvides, Inna S. Afonina, Rudi Beyaert
Journal: Journal of Allergy and Clinical Immunology (2019)
A Single-Institution Retrospective Study of Causes of Prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) in the Outpatient Setting
Authors: Ryan B. Khodadadi, Joshua P. Slusser, Diane E. Grill, Rajiv K. Pruthi, Ariela L. Marshall
Journal: Blood (2018)