tbuckley/cabot-search huggingface dataset:
A Framework for Understanding the Association Between Training Paradigm and Trainee Preparedness for Independent Surgical Practice
Authors: Brigitte K. Smith, John Rectenwald, Rachel Yudkowsky, Laura E. Hirshfield
Journal: JAMA Surgery (2021)

The sociopolitical and cultural context of graduate surgical education has changed considerably over the past 2 decades. Although new structures of graduate surgical training programs have been developed in response and the comparative value of formats are continually debated, it remains unclear how different time-based structural paradigms are preparing trainees for independent practice after program completion.To investigate the factors associated with trainees' and program directors' perception of trainee preparedness for independent surgical practice.This qualitative study used an instrumental case study approach and obtained information through semistructured interviews, which were analyzed using open-and-focused coding. Participants were recent graduates and program directors of vascular surgery training programs in the United States. The 2 training paradigms analyzed were the integrated vascular surgery residency program (0 + 5, with 0 indicating that the general surgery training experiences are fully integrated into the 5 years of overall training and 5 indicating the total number of years of training) and the traditional vascular surgery fellowship program (5 + 2, with 5 indicating the number of years of general surgery training and 2 indicating the number of years of vascular surgery training). All graduates completed their training in 2018. All interviews were conducted between July 1, 2018, and September 30, 2018.A conceptual framework to inform current and ongoing efforts to optimize graduate surgical training programs across specialties.A total of 22 semistructured interviews were completed, involving 7 graduates of 5 + 2 programs, 9 graduates of 0 + 5 programs, and 6 vascular surgery program directors. Of the 22 participants, 15 were men (68%). Participants described 4 interconnected domains that were associated with trainees' perceived preparedness for practice: structural, individual, relational, and organizational. Structural factors included the overall and vascular surgery-specific time spent in training, whereas individual factors included innate technical skills, confidence, maturity, and motivation. Faculty-trainee relationships (or relational factors) were deemed important for building trust and granting of autonomy. Organizational factors included features of the local organization, including patient population, case volume, and case mix.Findings suggest that restructuring training paradigms alone is insufficient to address the issue of trainees' perceived preparedness for practice. A framework was created from the results for evaluating and improving residency and fellowship programs as well as for developing graduate surgical training paradigms that incorporate all 4 domains associated with preparedness.
Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy
Authors: Maxwell L. Elliott, Avshalom Caspi, Renate M. Houts, Antony Ambler, Jonathan M. Broadbent, Robert J. Hancox, HonaLee Harrington, Sean Hogan, Ross Keenan, Annchen Knodt, Joan H. Leung, Tracy R. Melzer, Suzanne C. Purdy, Sandhya Ramrakha, Leah S. Richmond-Rakerd, Antoinette Righarts, Karen Sugden, W. Murray Thomson, Peter R. Thorne, Benjamin S. Williams, Graham Wilson, Ahmad R. Hariri, Richie Poulton, Terrie E. Moffitt
Journal: Nature Aging (2021)
P21.06 Patterns of Post-Progression Treatment and Impact of Subsequent Immunotherapy in Stage III Unresectable Non-Small Cell Lung Cancer Patients
Authors: S. Shin, Q. Liu, S. Aljabab, K. Attwood, H. Chen, A. Early, E. Yau, A. Hutson, G. Dy
Journal: Journal of Thoracic Oncology (2021)
The value of cardiorespiratory parameters for sleep state classification in preterm infants: A systematic review
Authors: Eline R. de Groot, Marit S. Knoop, Agnes van den Hoogen, Xiaowan Wang, Xi Long, Sigrid Pillen, Manon Benders, Jeroen Dudink
Journal: Sleep Medicine Reviews (2021)

Cardiorespiratory activity is highly associated with infants' sleep duration and quality. We performed a systematic literature search of PubMed and EMBASE databases to investigate if and how cardiorespiratory parameters can be used for sleep state classification in preterm infants and in what way maturation influences this relation. All retrieved citations were screened against predetermined inclusion and exclusion criteria. Only studies of preterm infants (<37 wk postmenstrual age during sleep state classification) admitted to a neonatal ward and of whom at least one sleep state and one cardiorespiratory parameter was measured, were included. Two researchers independently reviewed the included studies on methodological quality. Of the 1097 initially retrieved studies, 23 were included for analysis. Heart rate and respiration frequency are strongly correlated with active sleep and quiet sleep. In quiet sleep, as compared to active sleep, respiratory frequency is more stable, and the heart rate is lower and less variable. This association, however, differed across preterm birth subtypes (i.e., extremely, very or late preterm), indicating that maturation – in the form of both gestational and postnatal age – influences the cardiorespiratory characteristics of preterm sleep states. The knowledge gained from this review can help improve behavioral sleep classification and automated sleep classification algorithms for preterm infants.
Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium
Authors: Jörg Beyer, Laurence Collette, Nicolas Sauvé, Gedske Daugaard, Darren R. Feldman, Torgrim Tandstad, Alexey Tryakin, Olof Stahl, Enrique Gonzalez-Billalabeitia, Ugo De Giorgi, Stéphane Culine, Ronald de Wit, Aaron R. Hansen, Marko Bebek, Angelika Terbuch, Costantine Albany, Marcus Hentrich, Jourik A. Gietema, Helene Negaard, Robert A. Huddart, Anja Lorch, Fay H. Cafferty, Daniel Y. C. Heng, Christopher J. Sweeney, Eric Winquist, Michal Chovanec, Christian Fankhauser, Daniel Stark, Peter Grimison, Andrea Necchi, Ben Tran, Axel Heidenreich, Jonathan Shamash, Cora N. Sternberg, David J. Vaughn, Ignacio Duran, Carsten Bokemeyer, Anna Patrikidou, Richard Cathomas, Samson Assele, Silke Gillessen
Journal: Journal of Clinical Oncology (2021)

The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium.Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients.Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH.PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.
Discovery of Novel Herpes Simplexviruses in Wild Gorillas, Bonobos, and Chimpanzees Supports Zoonotic Origin of HSV-2
Authors: Joel O. Wertheim, Reilly Hostager, Diane Ryu, Kevin Merkel, Samuel Angedakin, Mimi Arandjelovic, Emmanuel Ayuk Ayimisin, Fred Babweteera, Mattia Bessone, Kathryn J. Brun-Jeffery, Paula Dieguez, Winnie Eckardt, Barbara Fruth, Ilka Herbinger, Sorrel Jones, Hjalmar Kuehl, Kevin E. Langergraber, Kevin Lee, Nadege F. Madinda, Sonja Metzger, Lucy Jayne Ormsby, Martha M. Robbins, Volker Sommer, Tara Stoinski, Erin G. Wessling, Roman M. Wittig, Yisa Ginath Yuh, Fabian H. Leendertz, Sébastien Calvignac-Spencer
Journal: Molecular Biology and Evolution (2021)

Viruses closely related to human pathogens can reveal the origins of human infectious diseases. Human herpes simplexvirus type 1 (HSV-1) and type 2 (HSV-2) are hypothesized to have arisen via host-virus codivergence and cross-species transmission. We report the discovery of novel herpes simplexviruses during a large-scale screening of fecal samples from wild gorillas, bonobos, and chimpanzees. Phylogenetic analysis indicates that, contrary to expectation, simplexviruses from these African apes are all more closely related to HSV-2 than to HSV-1. Molecular clock-based hypothesis testing suggests the divergence between HSV-1 and the African great ape simplexviruses likely represents a codivergence event between humans and gorillas. The simplexviruses infecting African great apes subsequently experienced multiple cross-species transmission events over the past 3 My, the most recent of which occurred between humans and bonobos around 1 Ma. These findings revise our understanding of the origins of human herpes simplexviruses and suggest that HSV-2 is one of the earliest zoonotic pathogens.
STAT3 ameliorates cognitive deficits via regulation of NMDAR expression in an Alzheimer's disease animal model
Authors: Hua-Li Wan, Xiao-Yue Hong, Zai-Hua Zhao, Ting Li, Bing-Ge Zhang, Qian Liu, Shi Zhao, Jian-Zhi Wang, Xue-Feng Shen, Gong-Ping Liu
Journal: Theranostics (2021)

Background: Abnormal tau accumulation in the brain has a positively correlation with neurodegeneration and memory deterioration, but the mechanism underlying tau-associated synaptic and cognitive impairments remains unclear. Our previous work has found that human full length tau (hTau) accumulation activated signal transducer and activator of transcription-1 (STAT1) to suppress N-methyl-D-aspartate receptors (NMDARs) expression, followed by memory deficits. STAT3 also belongs to STAT protein family and is reported to involve in regulation of synaptic plasticity and cognition. Here, we investigated the role of STAT3 in the cognitive deficits induced by hTau accumulation. Methods:In vitro studies HEK293 cells were used. EMSA, Luciferase reporter assay, and Immunoprecipitation were applied to detect STAT3 activity. In vivo studies, AAV virus were injected into the hippocampal CA3 region of C57 mice. Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence were applied to examine the level of synaptic proteins. Electrophysiological analysis, behavioral testing and Golgi impregnation were used to determine synaptic plasticity and memory ability recovery after overexpressing STAT3 or non-acetylated STAT1. Results: Our results showed that hTau accumulation acetylated STAT1 to retain STAT3 in the cytoplasm by increasing the binding of STAT1 with STAT3, and thus inactivated STAT3. Overexpressing STAT3 or non-acetylated STAT1 ameliorated hTau-induced synaptic loss and memory deficits by increasing the expression of NMDARs. Conclusions: Taken together, our study indicates that hTau accumulation impaired synaptic plasticity through STAT3 inactivation induced suppression of NMDARs expression, revealing a novel mechanism for hTau-associated synapse and memory deficits.
Abstract 11807: Lifestyle Behaviors and Association With All-Cause Mortality and Cardiovascular Disease Events Among US Adults With Varying Levels of Kidney Function
Authors: Sarah Schrauben, Jesse Hsu, Sandra Amaral, Amanda H Anderson, Harold I Feldman, Laura Dember
Journal: Circulation (2019)

Introduction: Adherence to healthy lifestyle behaviors reduces risks of CVD and mortality in the general population but benefits of these behaviors among people with kidney disease, a group at high...
Cancer cells escape autophagy inhibition via NRF2-induced macropinocytosis
Authors: Hua Su, Fei Yang, Rao Fu, Xin Li, Randall French, Evangeline Mose, Xiaohong Pu, Brittney Trinh, Avi Kumar, Junlai Liu, Laura Antonucci, Jelena Todoric, Yuan Liu, Yinling Hu, Maria T. Diaz-Meco, Jorge Moscat, Christian M. Metallo, Andrew M. Lowy, Beicheng Sun, Michael Karin
Journal: Cancer Cell (2021)
MRI Features for Predicting Microvascular Invasion of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
Authors: Seung Baek Hong, Sang Hyun Choi, So Yeon Kim, Ju Hyun Shim, Seung Soo Lee, Jae Ho Byun, Seong Ho Park, Kyung Won Kim, Suk Kim, Nam Kyung Lee
Journal: Liver Cancer (2021)

Microvascular invasion (MVI) is an important prognostic factor in patients with hepatocellular carcinoma (HCC). However, the reported results of magnetic resonance imaging (MRI) features for predicting MVI of HCC are variable and conflicting. Therefore, this meta-analysis aimed to identify the significant MRI features for MVI of HCC and to determine their diagnostic value.Original studies reporting the diagnostic performance of MRI for predicting MVI of HCC were identified in MEDLINE and EMBASE up until January 15, 2020. Study quality was assessed using QUADAS-2. A bivariate random-effects model was used to calculate the meta-analytic pooled diagnostic odds ratio (DOR) and 95% confidence interval (CI) for each MRI feature for diagnosing MVI in HCC. The meta-analytic pooled sensitivity and specificity were calculated for the significant MRI features.Among 235 screened articles, we found 36 studies including 4,274 HCCs. Of the 15 available MRI features, 7 were significantly associated with MVI: larger tumor size (>5 cm) (DOR = 5.2, 95% CI [3.0-9.0]), rim arterial enhancement (4.2, 95% CI [1.7-10.6]), arterial peritumoral enhancement (4.4, 95% CI [2.8-6.9]), peritumoral hypointensity on hepatobiliary phase imaging (HBP) (8.2, 95% CI [4.4-15.2]), nonsmooth tumor margin (3.2, 95% CI [2.2-4.4]), multifocality (7.1, 95% CI [2.6-19.5]), and hypointensity on T1-weighted imaging (T1WI) (4.9, 95% CI [2.5-9.6]). Both peritumoral hypointensity on HBP and multifocality showed very high meta-analytic pooled specificities for diagnosing MVI (91.1% [85.4-94.8%] and 93.3% [74.5-98.5%], respectively).Seven MRI features including larger tumor size, rim arterial enhancement, arterial peritumoral enhancement, peritumoral hypointensity on HBP, nonsmooth margin, multifocality, and hypointensity on T1WI were significant predictors for MVI of HCC. These MRI features predictive of MVI can be useful in the management of HCC.
P37.33 A look at EGFR, ALK, and PD-L1 Biomarker Test Availability, Adoption, and Test Ordering Behavior at Diagnosis of NSCLC in the United States
Authors: J. Sornkom, P. Riccelli, F. Policht, M. Hoefsmit, W. Moore, D.M. Keeling, I. Stacey, D. Smart, R. Keeling, S. Munksted, J. Clark
Journal: Journal of Thoracic Oncology (2021)
Global Profiling of the Lysine Crotonylome in Different Pluripotent States
Authors: Yuan Lv, Chen Bu, Jin Meng, Carl Ward, Giacomo Volpe, Jieyi Hu, Mengling Jiang, Lin Guo, Jiekai Chen, Miguel A. Esteban, Xichen Bao, Zhongyi Cheng
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Pluripotent stem cells (PSCs) can be expanded in vitro in different culture conditions, resulting in a spectrum of cell states with distinct properties. Understanding how PSCs transition from one state to another, ultimately leading to lineage-specific differentiation, is important for developmental biology and regenerative medicine. Although there is significant information regarding gene expression changes controlling these transitions, less is known about post-translational modifications of proteins. Protein crotonylation is a newly discovered post-translational modification where lysine residues are modified with a crotonyl group. Here, we employed affinity purification of crotonylated peptides and liquid chromatography–tandem mass spectrometry (LC–MS/MS) to systematically profile protein crotonylation in mouse PSCs in different states including ground, metastable, and primed states, as well as metastable PSCs undergoing early pluripotency exit. We successfully identified 3628 high-confidence crotonylated sites in 1426 proteins. These crotonylated proteins are enriched for factors involved in functions/processes related to pluripotency such as RNA biogenesis, central carbon metabolism, and proteasome function. Moreover, we found that increasing the cellular levels of crotonyl-coenzyme A (crotonyl-CoA) through crotonic acid treatment promotes proteasome activity in metastable PSCs and delays their differentiation, consistent with previous observations showing that enhanced proteasome activity helps to sustain pluripotency. Our atlas of protein crotonylation will be valuable for further studies of pluripotency regulation and may also provide insights into the role of metabolism in other cell fate transitions.
COVID-19 Vaccine Second-Dose Completion and Interval Between First and Second Doses Among Vaccinated Persons — United States, December 14, 2020−February 14, 2021
Authors: Jennifer L. Kriss, Laura E. Reynolds, Alice Wang, Shannon Stokley, Matthew M. Cole, LaTreace Q. Harris, Lauren K. Shaw, Carla L. Black, James A. Singleton, David L. Fitter, Dale A. Rose, Matthew D. Ritchey, Robin L. Toblin
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

or 33-42 days (Moderna) after first dose; no second dose received.
Abstract 16535: Consequences of Running a Multistage Marathon Over 4.486km on Cardiac Serum Biomarkers
Authors: Christopher Klenk, Thomas Nickel, Atilgan Yilmaz, Denis Infanger, Uwe Schütz, Arno Schmidt-Trucksäss
Journal: Circulation (2018)

Introduction: Participation in rigorous endurance sporting events expose the human body to extreme circulatory load. However, the consequences on cardiac structure of such extensive physical exerci...
Multi-omics links IL-6 trans-signalling with neutrophil extracellular trap formation and<i>Haemophilus</i>infection in COPD
Authors: Sofia Winslow, Lina Odqvist, Sarah Diver, Rebecca Riise, Suado Abdillahi, Cecilia Wingren, Helena Lindmark, Annika Wellner, Sofia Lundin, Linda Yrlid, Elisabeth Ax, Ratko Djukanovic, Sriram Sridhar, Andrew Higham, Dave Singh, Thomas Southworth, Christopher E. Brightling, Henric K. Olsson, Zala Jevnikar
Journal: European Respiratory Journal (2021)

Background: Interleukin (IL)-6 trans-signalling (IL-6TS) is emerging as a pathogenic mechanism in chronic respiratory diseases; however, the drivers of IL-6TS in the airways and the phenotypic characteristic of patients with increased IL-6TS pathway activation remain poorly understood. Objective: Our aim was to identify and characterise COPD patients with increased airway IL-6TS and to elucidate the biological drivers of IL-6TS pathway activation. Methods: We used an IL-6TS-specific sputum biomarker profile (soluble IL-6 receptor (sIL-6R), IL-6, IL-1β, IL-8, macrophage inflammatory protein-1β) to stratify sputum data from patients with COPD (n=74; Biomarkers to Target Antibiotic and Systemic Corticosteroid Therapy in COPD Exacerbation (BEAT-COPD)) by hierarchical clustering. The IL-6TS signature was related to clinical characteristics and sputum microbiome profiles. The induction of neutrophil extracellular trap formation (NETosis) and IL-6TS by Haemophilus influenzae were studied in human neutrophils. Results: Hierarchical clustering revealed an IL-6TS-high subset (n=24) of COPD patients, who shared phenotypic traits with an IL-6TS-high subset previously identified in asthma. The subset was characterised by increased sputum cell counts (p=0.0001), persistent sputum neutrophilia (p=0.0004), reduced quality of life (Chronic Respiratory Questionnaire total score; p=0.008), and increased levels of pro-inflammatory mediators and matrix metalloproteinases in sputum. IL-6TS-high COPD patients showed an increase in Proteobacteria, with Haemophilus as the dominating genus. NETosis induced by H. influenzae was identified as a potential mechanism for increased sIL-6R levels. This was supported by a significant positive correlation between sIL-6R and NETosis markers in bronchoalveolar lavage fluid from COPD patients. Conclusion: IL-6TS pathway activation due to chronic colonisation with Haemophilus may be an important disease driver in a subset of COPD patients.
SPARC-related modular calcium binding 1 regulates aortic valve calcification by disrupting BMPR-II/p-p38 signalling
Authors: Yaqing Wang, Jia Gu, Anning Du, Siqi Zhang, Mengqing Deng, Rong Zhao, Yan Lu, Yue Ji, Yongfeng Shao, Wei Sun, Xiangqing Kong
Journal: Cardiovascular Research (2021)

Aortic valve calcification is more prevalent in chronic kidney disease accompanied by hypercalcemia. Secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (SMOC1) is a regulator of BMP2 signalling, but the role of SMOC1 in aortic valve calcification under different conditions has not been studied. This study aimed to investigate the roles of SMOC1 in aortic valve calcification under normal and high calcium conditions, focusing on the effects on aortic valve interstitial cells (AVICs).SMOC1 was expressed by aortic valve endothelial cells and secreted into the extracellular matrix in non-calcific valves and downregulated in calcific aortic valves. In vitro studies demonstrated that HUVEC secreted SMOC1 could enter the cytoplasm of AVICs. Overexpression of SMOC1 attenuated warfarin-induced AVIC calcification but promoted high calcium/phosphate or vitamin D-induced AVIC and aortic valve calcification by regulating BMP2 signalling both in vitro and in vivo. Co-immunoprecipitation revealed that SMOC1 binds to BMP receptor II (BMPR-II) and inhibits BMP2-induced phosphorylation of p38 (p-p38) via amino acids 372-383 of its EF-hand calcium-binding domain. Inhibition of p-p38 by the p38 inhibitor SB203580 blocked the effects of SMOC1 on BMP2 signalling and AVIC calcification induced by high calcium/phosphate medium. In high-calcium-treated AVICs, SMOC1 lost its ability to bind to BMPR-II, but not to caveolin-1, promoting p-p38 and cell apoptosis due to increased expression of BMPR-II and enhanced endocytosis.These observations support that SMOC1 works as a dual-directional modulator of AVIC calcification by regulating p38-dependent BMP2 signalling transduction according to different extracellular calcium concentrations.
P33.08 Granulocyte Colony-Stimulating Factor-Producing Lung Cancer With Highly Expresses PD-L1 Protein Expression Level
Authors: K. Miyazaki, Y. Hirasawa, M. Aga, N. Aiko, Y. Hamakawa, Y. Taniguti, Y. Misumi, Y. Agemi, M. Ishii, T. Shimokawa, H. Okamoto
Journal: Journal of Thoracic Oncology (2021)