tbuckley/cabot-search huggingface dataset:
Association of Thrombocytopenia With Bleeding Risk During Central Venous Catheter Placement in Pediatric Patients With Cancer
Authors: Sarah C. Stokes, Kaeli J. Yamashiro, Erin G. Brown
Journal: JAMA Surgery (2021)

This cohort study evaluates bleeding complications in pediatric patients with cancer who have a platelet count of 50 ×103/μL or above vs below 50 ×103/μL during central venous catheter (CVC) placement.
Role of MAX As a Tumor Suppressor Driver Gene in Multiple Myeloma
Authors: Santiago Barrio Garcia, Yanira Ruiz-Heredia, Matteo Da Via, Miguel Gallardo, Andoni Garitano-Trojaola, Josip Zovko, Marc S Raab, Pieter Sonneveld, Esteban Braggio, A. Keith Stewart, Hermann Einsele, Joaquín Martínez, K. Martin Kortüm
Journal: Blood (2017)
Characteristics of Randomized Clinical Trials in Surgery From 2008 to 2020
Authors: N. Bryce Robinson, Stephen Fremes, Irbaz Hameed, Mohamed Rahouma, Viola Weidenmann, Michelle Demetres, Mahmoud Morsi, Giovanni Soletti, Antonino Di Franco, Marco A. Zenati, Shahzad G. Raja, David Moher, Faisal Bakaeen, Joanna Chikwe, Deepak L. Bhatt, Paul Kurlansky, Leonard N. Girardi, Mario Gaudino
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Randomized clinical trials (RCTs) provide the highest level of evidence to evaluate 2 or more surgical interventions. Surgical RCTs, however, face unique challenges in design and implementation. <h3>Objective</h3> To evaluate the design, conduct, and reporting of contemporary surgical RCTs. <h3>Evidence Review</h3> A literature search performed in the 2 journals with the highest impact factor in general medicine as well as 6 key surgical specialties was conducted to identify RCTs published between 2008 and 2020. All RCTs describing a surgical intervention in both experimental and control arms were included. The quality of included data was assessed by establishing an a priori protocol containing all the details to extract. Trial characteristics, fragility index, risk of bias (Cochrane Risk of Bias 2 Tool), pragmatism (Pragmatic Explanatory Continuum Indicator Summary 2 [PRECIS-2]), and reporting bias were assessed. <h3>Findings</h3> A total of 388 trials were identified. Of them, 242 (62.4%) were registered; discrepancies with the published protocol were identified in 81 (33.5%). Most trials used superiority design (329 [84.8%]), and intention-to-treat as primary analysis (221 [56.9%]) and were designed to detect a large treatment effect (50.0%; interquartile range [IQR], 24.7%-63.3%). Only 123 trials (31.7%) used major clinical events as the primary outcome. Most trials (303 [78.1%]) did not control for surgeon experience; only 17 trials (4.4%) assessed the quality of the intervention. The median sample size was 122 patients (IQR, 70-245 patients). The median follow-up was 24 months (IQR, 12.0-32.0 months). Most trials (211 [54.4%]) had some concern of bias and 91 (23.5%) had high risk of bias. The mean (SD) PRECIS-2 score was 3.52 (0.65) and increased significantly over the study period. Most trials (212 [54.6%]) reported a neutral result; reporting bias was identified in 109 of 211 (51.7%). The median fragility index was 3.0 (IQR, 1.0-6.0). Multiplicity was detected in 175 trials (45.1%), and only 35 (20.0%) adjusted for multiple comparisons. <h3>Conclusions and Relevance</h3> In this systematic review, the size of contemporary surgical trials was small and the focus was on minor clinical events. Trial registration remained suboptimal and discrepancies with the published protocol and reporting bias were frequent. Few trials controlled for surgeon experience or assessed the quality of the intervention.
Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation
Authors: Paul-Michel Mertes, Olivier Collange, Pierre Coliat, Mainak Banerjee, Marie-Charlotte Diringer, Anne Roche, Xavier Delabranche, Vitaliy Chaban, Manon Voegelin, Alexandre Bernard, Valérie Sartori, Nina Laurent, Michel Velten, Navreet Dhindsa, Jason Defuria, Gwangseong Kim, Zhenghong Hannah Xu, Marina Theodorou, Zhaohua Richard Huang, Kaniz Khalifa, Bolin Geng, Clet Niyikiza, Victor Moyo, Patrick Gizzi, Pascal Villa, Alexandre Detappe, Xavier Pivot
Journal: Journal of Controlled Release (2021)

Current therapeutic treatments improving the impaired transportation of oxygen in acute respiratory distress syndrome (ARDS) have been found to be relevant and beneficial for the therapeutic treatment of COVID-19 patients suffering from severe respiratory complications. Hence, we report the preclinical and the preliminary results of the Phase I/II clinical trial of LEAF-4L6715, a liposomal nanocarrier encapsulating the kosmotropic agent trans-crocetin (TC), which, once injected, enhance the oxygenation of vascular tissue and therefore has the potential to improve the clinical outcomes of ARDS and COVID-19 in severely impacted patients. We demonstrated that the liposomal formulation enabled to increase from 30 min to 48 h the reoxygenation properties of free TCs in vitro in endothelial cells, but also to improve the half-life of TC by 6-fold in healthy mice. Furthermore, we identified 25 mg/kg as the maximum tolerated dose in mice. This determined concentration led to the validation of the therapeutic efficacy of LEAF-4 L6715 in a sepsis mouse model. Finally, we report the preliminary outcomes of an open-label multicenter Phase I/II clinical trial (EudraCT 2020-001393-30; NCT04378920), which was aimed to define the appropriate schedule and dosage of LEAF-4L6715 and to confirm its tolerability profile and preliminary clinical activity in COVID-19 patients treated in intensive care unit.
Association of the COVID-19 Pandemic With Estimated Life Expectancy by Race/Ethnicity in the United States, 2020
Authors: Theresa Andrasfay, Noreen Goldman
Journal: JAMA Network Open (2021)

Hannes Schwandt, PhD; Janet Currie, PhD; Till von Wachter, PhD; Jonathan Kowarski, MA; Derek Chapman, PhD; Steven H. Woolf, MD, MPH
A biliary immune landscape map of primary sclerosing cholangitis reveals a dominant network of neutrophils and tissue-resident T cells
Authors: Christine L. Zimmer, Erik von Seth, Marcus Buggert, Otto Strauss, Laura Hertwig, Son Nguyen, Alicia Y. W. Wong, Chiara Zotter, Lena Berglin, Jakob Michaëlsson, Marcus Reuterwall Hansson, Urban Arnelo, Ernesto Sparrelid, Ewa C. S. Ellis, Johan D. Söderholm, Åsa V. Keita, Kristian Holm, Volkan Özenci, Johannes R. Hov, Jeff E. Mold, Martin Cornillet, Andrea Ponzetta, Annika Bergquist, Niklas K. Björkström
Journal: Science Translational Medicine (2021)

Bile ducts from patients with PSC are enriched in neutrophils and biliary-resident CD8 + T cells and differ in composition from liver tissue.
CD3 Lymphocyte Graft Content and Not Hematopoietic Stem Cell Source Is Associated to Higher Chronic GVHD after Haploidentical Transplantation with Post-Transplant Cyclophosphamide
Authors: Alberto Mussetti, Chiara De Philippis, Cristiana Carniti, Mariana Bastos Oreiro, Jorge Gayoso, Nicoletta Cieri, Fabio Ciceri, Raffaella Greco, Francesca Patriarca, Jacopo Mariotti, Luca Castagna, Paolo Corradini
Journal: Blood (2017)
Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Authors: Jiandong Huo, Yuguang Zhao, Jingshan Ren, Daming Zhou, Helen M.E. Duyvesteyn, Helen M. Ginn, Loic Carrique, Tomas Malinauskas, Reinis R. Ruza, Pranav N.M. Shah, Tiong Kit Tan, Pramila Rijal, Naomi Coombes, Kevin R. Bewley, Julia A. Tree, Julika Radecke, Neil G. Paterson, Piyada Supasa, Juthathip Mongkolsapaya, Gavin R. Screaton, Miles Carroll, Alain Townsend, Elizabeth E. Fry, Raymond J. Owens, David I. Stuart
Journal: Cell Host & Microbe (2020)
Irrigation-assisted intraductal ultrasonography with a 3-Fr microcatheter during endoscopic retrograde cholangiography
Authors: Michihiro Yoshida, Itaru Naitoh, Kazuki Hayashi, Makoto Natsume, Yasuki Hori, Akihisa Kato, Hiromi Kataoka
Journal: Endoscopy (2021)

Intraductal ultrasonography (IDUS) is one of the most useful intraductal modalities for investigating the structure of the biliary wall layers and for the presence of stones during endoscopic retrograde cholangiography (ERC) [1] [2] [3]. In patients with pneumobilia, however, conventional IDUS is significantly limited in its ability to provide accurate cross-sectional imaging.
The Target UK Study: Real-World Evidence of Molecular Response to Tyrosine Kinase Inhibitors Supports European Leukemianet 2013 Recommendations for the Management of Chronic Myeloid Leukaemia
Authors: Dragana Milojkovic, Richard E. Clark, Jennifer L Byrne, Brian J.P Huntly, Manoj Raghavan, Farooq A Wandroo, Sahra Ali, Belinda Austen, Jacqueline Ryan, Karsten Friedrich, Nicholas C.P. Cross, Adam J Mead
Journal: Blood (2017)
Sources and Risk Factors for Nitrate and Microbial Contamination of Private Household Wells in the Fractured Dolomite Aquifer of Northeastern Wisconsin
Authors: Mark A. Borchardt, Joel P. Stokdyk, Burney A. Kieke, Maureen A. Muldoon, Susan K. Spencer, Aaron D. Firnstahl, Davina E. Bonness, Randall J. Hunt, Tucker R. Burch
Journal: Environmental Health Perspectives (2021)

Background: Groundwater quality in the Silurian dolomite aquifer in northeastern Wisconsin, USA, has become contentious as dairy farms and exurban development expand. Objectives: We investigated private household wells in the region, determining the extent, sources, and risk factors of nitrate and microbial contamination. Methods: Total coliforms, Escherichia coli, and nitrate were evaluated by synoptic sampling during groundwater recharge and no-recharge periods. Additional seasonal sampling measured genetic markers of human and bovine fecal-associated microbes and enteric zoonotic pathogens. We constructed multivariable regression models of detection probability (log-binomial) and concentration (gamma) for each contaminant to identify risk factors related to land use, precipitation, hydrogeology, and well construction. Results: Total coliforms and nitrate were strongly associated with depth-to-bedrock at well sites and nearby agricultural land use, but not septic systems. Both human wastewater and cattle manure contributed to well contamination. Rotavirus group A, Cryptosporidium, and Salmonella were the most frequently detected pathogens. Wells positive for human fecal markers were associated with depth-to-groundwater and number of septic system drainfield within 229m. Manure-contaminated wells were associated with groundwater recharge and the area size of nearby agricultural land. Wells positive for any fecal-associated microbe, regardless of source, were associated with septic system density and manure storage proximity modified by bedrock depth. Well construction was generally not related to contamination, indicating land use, groundwater recharge, and bedrock depth were the most important risk factors. Discussion: These findings may inform policies to minimize contamination of the Silurian dolomite aquifer, a major water supply for the U.S. and Canadian Great Lakes region. https://doi.org/10.1289/EHP7813
The High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Polymorphisms Are Differentially Associated With Growth and IGF-I Levels in Infancy: The Cambridge Baby Growth Study
Authors: Antigoni Eleftheriou, Clive J. Petry, Ieuan A. Hughes, Ken K. Ong, David B. Dunger
Journal: Diabetes Care (2021)

This study explored the link between HLA polymorphisms that predispose to type 1 diabetes and birth size, infancy growth, and/or circulating IGF-I in a general population-based birth cohort.The Cambridge Baby Growth Study is a prospective observational birth cohort study that recruited 2,229 newborns for follow-up in infancy. Of these, 612 children had DNA available for genotyping single nucleotide polymorphisms in the HLA region that capture the highest risk of type 1 diabetes: rs17426593 for DR4, rs2187668 for DR3, and rs7454108 for DQ8. Multivariate linear regression models at critical ages (cross-sectional) and mixed-effects models (longitudinal) were performed under additive genetic effects to test for associations between HLA polymorphisms and infancy weight, length, skinfold thickness (indicator of adiposity), and concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3).In longitudinal models, the minor allele of rs2187668 tagging DR3 was associated with faster linear growth (P = 0.007), which was more pronounced in boys (P = 3 × 10-7) than girls (P = 0.07), and was also associated with increasing IGF-I (P = 0.002) and IGFBP-3 (P = 0.003) concentrations in infancy. Cross-sectionally, the minor alleles of rs7454108 tagging DQ8 and rs17426593 tagging DR4 were associated with lower IGF-I concentrations at age 12 months (P = 0.003) and greater skinfold thickness at age 24 months (P = 0.003), respectively.The variable associations of DR4, DR3, and DQ8 alleles with growth measures and IGF-I levels in infants from the general population could explain the heterogeneous growth trajectories observed in genetically at-risk cohorts. These findings could suggest distinct mechanisms involving endocrine pathways related to the HLA-conferred type 1 diabetes risk.
Tailoring Therapeutic Responses via Engineering Microenvironments with a Novel Synthetic Fluid Gel
Authors: Nicola C. Foster, Piers Allen, Alicia J. El Haj, Liam M. Grover, Richard J. A. Moakes
Journal: Advanced Healthcare Materials (2021)

Abstract This study reports the first fully synthetic fluid gel (SyMGels) using a simple poly(ethylene glycol) polymer. Fluid gels are an interesting class of materials: structured during gelation via shear‐confinement to form microparticulate suspensions, through a bottom‐up approach. Structuring in this way, when compared to first forming a gel and subsequently breaking it down, results in the formation of a particulate dispersion with particles “grown” in the shear flow. Resultantly, systems form a complex microstructure, where gelled particles concentrate remaining non‐gelled polymer within the continuous phase, creating an amorphous‐like interstitial phase. As such, these materials demonstrate mechanical characteristics typical of colloidal glasses, presenting solid‐like behaviors at rest with defined yielding; likely through intrinsic particle‐particle and particle‐polymer interactions. To date, fluid gels have been fabricated using polysaccharides with relatively complex chemistries, making further modifications challenging. SyMGels are easily functionalised, using simple click‐chemistry. This chemical flexibility, allows the creation of microenvironments with discrete biological decoration. Cellular control is demonstrated using MSC (mesenchymal stem cells)/chondrocytes and enables the regulation of key biomarkers such as aggrecan and SOX9 . These potential therapeutic platforms demonstrate an important advancement in the biomaterial field, underpinning the mechanisms which drive their mechanical properties, and providing a versatile delivery system for advanced therapeutics.
Rachael Caera Ward
Authors: Matthew J C Ward
Journal: BMJ (2021)

Rachael Caera Ward (nee Darlison) was born in Haywards Heath, West Sussex. Her family moved to Winchester in 1997, and she attended the Westgate School and Peter Symonds Sixth Form College. Rachael decided on a medical career after work experience with her general practitioner aunt and went up to study medicine at Clare College, Cambridge, in 2010. While at Cambridge she met her future husband, Matthew, a PhD student in music. After Rachel graduated from her pre-clinical course, they married in 2013, and Rachael started clinical studies at Imperial College, London. Her daughter was born in 2015 and Rachael took substantial maternity leave out of her studies. She received her degree with distinction in 2017, five days after giving birth to her first …
Abstract 214: TLR3 Mediates Neonatal Heart Repair and Regeneration Through Glycolysis-dependent YAP/TAZ Mediated miR-152 Expression
Authors: Xiaohui Wang, Yuanping Hu, Tuanzhu Ha, John Kalbfleisch, Race Kao, David Williams, Chuanfu Li
Journal: Circulation Research (2016)

The neonatal heart possesses the capability of regenerating and repairing damaged myocardium which is lost when cardiac metabolism switches from predominate glycolysis to oxidative phosphorylation seven days after birth. We have observed that Toll-like receptor 3 (TLR3) deficient neonatal hearts exhibit impaired cardiac function and larger infarct size after myocardial infarction (MI). We also found that stimulation of neonatal cardiomyocytes with the TLR3 ligand, poly (I:C) significantly enhances glycolytic capacity. Our observation suggests that TLR3 is required for neonatal heart repair and regeneration of damaged myocardium. This study investigated the mechanisms by which TLR3 mediates neonatal heart regeneration and repair. Neonatal cardiomyocytes were isolated from one day old WT mice and treated with poly (I:C) (1μg/ml) for 12-36 hours. We observed that poly (I:C) treatment: i) significantly enhances glycolytic metabolism; ii) increases YAP/TAZ activation: iii) increases miR-152 expression; iv) suppresses expression of DNMT1 and p27kip1, and v) promotes cardiomyocyte proliferation. However, inhibition of glycolysis with 2-Deoxyglucose (2-DG) prevented poly (I:C)-induced YAP/TAZ activation and miR-152 expression in neonatal cardiomyocytes. Similarly, inhibition of YAP/TAZ activation with Verteprofin (VP) abolished poly (I:C) induced miR-152 expression and neonatal cardiomyocyte proliferation. To investigate the role of miR-152 in neonatal cardiomyocyte proliferation, we transfected neonatal cardiomyocytes with miR-152 mimics and observed that increased miR-152 levels significantly promotes neonatal cardiomyocyte proliferation. We also observed that transfection of neonatal cardiomyocytes with miR-152 mimics markedly suppresses the expression of DNMT1 and p27kip1. Inhibition of DNMT1 with 5Azcytidine significantly promotes neonatal cardiomyocyte proliferation. Finally, we observed that treatment of neonatal mice (n=6) with 2-DG abolished cardiac functional recovery 3 weeks after MI. We conclude that TLR3 is required for neonatal heart regeneration and repair after MI. The mechanisms involve glycolytic dependent activation of YAP/TAZ mediated by miR-152 which represses DNMT1/p27kip1 expression.
Efficacy of guselkumab on axial involvement in patients with active psoriatic arthritis and sacroiliitis: a post-hoc analysis of the phase 3 DISCOVER-1 and DISCOVER-2 studies
Authors: Philip J Mease, Philip S Helliwell, Dafna D Gladman, Denis Poddubnyy, Xenofon Baraliakos, Soumya D Chakravarty, Alexa P Kollmeier, Elizabeth C Hsia, Xie L Xu, Shihong Sheng, Prasheen Agarwal, Bei Zhou, Kristen Sweet, May Shawi, Chetan S Karyekar, Atul Deodhar, Désirée van der Heijde
Journal: The Lancet Rheumatology (2021)
Deep learning-based automatic tumor burden assessment of pediatric high-grade gliomas, medulloblastomas, and other leptomeningeal seeding tumors
Authors: Jian Peng, Daniel D Kim, Jay B Patel, Xiaowei Zeng, Jiaer Huang, Ken Chang, Xinping Xun, Chen Zhang, John Sollee, Jing Wu, Deepa J Dalal, Xue Feng, Hao Zhou, Chengzhang Zhu, Beiji Zou, Ke Jin, Patrick Y Wen, Jerrold L Boxerman, Katherine E Warren, Tina Y Poussaint, Lisa J States, Jayashree Kalpathy-Cramer, Li Yang, Raymond Y Huang, Harrison X Bai
Journal: Neuro-Oncology (2021)

Longitudinal measurement of tumor burden with magnetic resonance imaging (MRI) is an essential component of response assessment in pediatric brain tumors. We developed a fully automated pipeline for the segmentation of tumors in pediatric high-grade gliomas, medulloblastomas, and leptomeningeal seeding tumors. We further developed an algorithm for automatic 2D and volumetric size measurement of tumors. The preoperative and postoperative cohorts were randomly split into training and testing sets in a 4:1 ratio. A 3D U-Net neural network was trained to automatically segment the tumor on T1 contrast-enhanced and T2/FLAIR images. The product of the maximum bidimensional diameters according to the RAPNO (Response Assessment in Pediatric Neuro-Oncology) criteria (AutoRAPNO) was determined. Performance was compared to that of 2 expert human raters who performed assessments independently. Volumetric measurements of predicted and expert segmentations were computationally derived and compared. A total of 794 preoperative MRIs from 794 patients and 1003 postoperative MRIs from 122 patients were included. There was excellent agreement of volumes between preoperative and postoperative predicted and manual segmentations, with intraclass correlation coefficients (ICCs) of 0.912 and 0.960 for the 2 preoperative and 0.947 and 0.896 for the 2 postoperative models. There was high agreement between AutoRAPNO scores on predicted segmentations and manually calculated scores based on manual segmentations (Rater 2 ICC = 0.909; Rater 3 ICC = 0.851). Lastly, the performance of AutoRAPNO was superior in repeatability to that of human raters for MRIs with multiple lesions. Our automated deep learning pipeline demonstrates potential utility for response assessment in pediatric brain tumors. The tool should be further validated in prospective studies.
Type I interferon is induced by hemolysis and drives antibody-mediated erythrophagocytosis in sickle cell disease
Authors: Yunfeng Liu, Mouli Pal, Weili Bao, Patricia A. Shi, Cheryl A. Lobo, Xiuli An, Deepa Manwani, Hui Zhong, Karina Yazdanbakhsh
Journal: Blood (2021)
Molecular Clocks and Archeogenomics of a Late Period Egyptian Date Palm Leaf Reveal Introgression from Wild Relatives and Add Timestamps on the Domestication
Authors: Oscar A Pérez-Escobar, Sidonie Bellot, Natalia A S Przelomska, Jonathan M Flowers, Mark Nesbitt, Philippa Ryan, Rafal M Gutaker, Muriel Gros-Balthazard, Tom Wells, Benedikt G Kuhnhäuser, Rowan Schley, Diego Bogarín, Steven Dodsworth, Rudy Diaz, Manuela Lehmann, Peter Petoe, Wolf L Eiserhardt, Michaela Preick, Michael Hofreiter, Irka Hajdas, Michael Purugganan, Alexandre Antonelli, Barbara Gravendeel, Ilia J Leitch, Maria Fernanda Torres Jimenez, Alexander S T Papadopulos, Guillaume Chomicki, Susanne S Renner, William J Baker
Journal: Molecular Biology and Evolution (2021)

The date palm, Phoenix dactylifera, has been a cornerstone of Middle Eastern and North African agriculture for millennia. It was first domesticated in the Persian Gulf, and its evolution appears to have been influenced by gene flow from two wild relatives, P. theophrasti, currently restricted to Crete and Turkey, and P. sylvestris, widespread from Bangladesh to the West Himalayas. Genomes of ancient date palm seeds show that gene flow from P. theophrasti to P. dactylifera may have occurred by ∼2,200 years ago, but traces of P. sylvestris could not be detected. We here integrate archeogenomics of a ∼2,100-year-old P. dactylifera leaf from Saqqara (Egypt), molecular-clock dating, and coalescence approaches with population genomic tests, to probe the hybridization between the date palm and its two closest relatives and provide minimum and maximum timestamps for its reticulated evolution. The Saqqara date palm shares a close genetic affinity with North African date palm populations, and we find clear genomic admixture from both P. theophrasti, and P. sylvestris, indicating that both had contributed to the date palm genome by 2,100 years ago. Molecular-clocks placed the divergence of P. theophrasti from P. dactylifera/P. sylvestris and that of P. dactylifera from P. sylvestris in the Upper Miocene, but strongly supported, conflicting topologies point to older gene flow between P. theophrasti and P. dactylifera, and P. sylvestris and P. dactylifera. Our work highlights the ancient hybrid origin of the date palms, and prompts the investigation of the functional significance of genetic material introgressed from both close relatives, which in turn could prove useful for modern date palm breeding.