tbuckley/cabot-search huggingface dataset:
Strength, power and aerobic capacity of transgender athletes: a cross-sectional study
Authors: Blair Hamilton, Andrew Brown, Stephanie Montagner-Moraes, Cristina Comeras-Chueca, Peter G Bush, Fergus M Guppy, Yannis P Pitsiladis
Journal: British Journal of Sports Medicine (2024)

Objective The primary objective of this cross-sectional study was to compare standard laboratory performance metrics of transgender athletes to cisgender athletes. Methods 19 cisgender men (CM) (mean±SD, age: 37±9 years), 12 transgender men (TM) (age: 34±7 years), 23 transgender women (TW) (age: 34±10 years) and 21 cisgender women (CW) (age: 30±9 years) underwent a series of standard laboratory performance tests, including body composition, lung function, cardiopulmonary exercise testing, strength and lower body power. Haemoglobin concentration in capillary blood and testosterone and oestradiol in serum were also measured. Results In this cohort of athletes, TW had similar testosterone concentration (TW 0.7±0.5 nmol/L, CW 0.9±0.4 nmol/), higher oestrogen (TW 742.4±801.9 pmol/L, CW 336.0±266.3 pmol/L, p=0.045), higher absolute handgrip strength (TW 40.7±6.8 kg, CW 34.2±3.7 kg, p=0.01), lower forced expiratory volume in 1 s:forced vital capacity ratio (TW 0.83±0.07, CW 0.88±0.04, p=0.04), lower relative jump height (TW 0.7±0.2 cm/kg; CW 1.0±0.2 cm/kg, p&lt;0.001) and lower relative V̇O 2 max (TW 45.1±13.3 mL/kg/min/, CW 54.1±6.0 mL/kg/min, p&lt;0.001) compared with CW athletes. TM had similar testosterone concentration (TM 20.5±5.8 nmol/L, CM 24.8±12.3 nmol/L), lower absolute hand grip strength (TM 38.8±7.5 kg, CM 45.7±6.9 kg, p = 0.03) and lower absolute V̇O 2 max (TM 3635±644 mL/min, CM 4467±641 mL/min p = 0.002) than CM. Conclusion While longitudinal transitioning studies of transgender athletes are urgently needed, these results should caution against precautionary bans and sport eligibility exclusions that are not based on sport-specific (or sport-relevant) research.
The 11+ injury prevention programme decreases rate of hamstring strain injuries in male collegiate soccer players
Authors: Holly Silvers-Granelli, Richard Silverman, Mario Bizzini, Kristian Thorborg, Robert H Brophy
Journal: British Journal of Sports Medicine (2024)

Objectives To investigate if the 11+ injury prevention programme decreases the risk of hamstring injury and improves recovery time and determine whether compliance with the 11+ affects hamstring injury risk. Methods This study is a secondary analysis from a prospective cluster randomised controlled trial that included 65 National Collegiate Athletic Association (NCAA) division I and II men’s soccer teams over the fall 2012 season. Thirty-one teams were randomised to the intervention group that were using the 11+ as their warm-up and 35 teams to the control group that continued to use their traditional warm-up. Each certified athletic trainer (ATC) collected data on demographics, hamstring injury (HSI), mechanism of injury, position, playing surface, time lost due to injury and compliance to the 11+ programme. Results The 11+ decreased the risk of HSI by 63% compared with the control group (RR=0.37, 95% CI 0.21 to 0.63). Difference in return to play after HSI between the control (9.4±11.2 days) and intervention groups (10.2±11.3 days) was not significant (p=0.8). High compliance (&gt;2 or more doses on average per week) reduced the risk of HSI by 78% (RR=0.22, 95% CI 0.06 to 0.87) compared with low compliance (&lt;1 dose on average per week), and moderate compliance (1 to &lt;2 doses on average per week) decreased the risk of HSI by 67% (RR=0.33, 95% CI 0.11 to 0.97) compared with low compliance. There was no significant difference between high and moderate compliance. Conclusion The 11+ decreased the risk of HSI by 63% but did not improve recovery time. High to moderate compliance is essential and makes the programme more effective at reducing HSI.
Effectiveness of COVID-19 vaccines to prevent long COVID: data from Norway
Authors: Nhung TH Trinh, Annika M Jödicke, Martí Català, Núria Mercadé-Besora, Saeed Hayati, Angela Lupattelli, Daniel Prieto-Alhambra, Hedvig ME Nordeng
Journal: The Lancet Respiratory Medicine (2024)
Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial
Authors: Hong-Xing Pan, Ling-Xian Qiu, Qi Liang, Zhen Chen, Ming-Lei Zhang, Sheng Liu, Guo-Hua Zhong, Kong-Xin Zhu, Meng-Jun Liao, Jia-Lei Hu, Jia-Xue Li, Jin-Bo Xu, Yong Fan, Yue Huang, Ying-Ying Su, Shou-Jie Huang, Wei Wang, Jin-Le Han, Ji-Zong Jia, Hua Zhu, Tong Cheng, Xiang-Zhong Ye, Chang-Gui Li, Ting Wu, Feng-Cai Zhu, Jun Zhang, Ning-Shao Xia
Journal: The Lancet Infectious Diseases (2024)
Over-the-scope clip as first-line treatment of peptic ulcer bleeding: a multicenter randomized controlled trial (TOP Study)
Authors: Paola Soriani, Paolo Biancheri, Giuliano Francesco Bonura, Tommaso Gabbani, Enrique Rodriguez de Santiago, Lorenzo Dioscoridi, Gianluca Andrisani, Carmelo Luigiano, Simona Deiana, Joachim Rainer, Mariagrazia Del Buono, Rocco Amendolara, Massimiliano Marino, Cesare Hassan, Alessandro Repici, Mauro Manno
Journal: Endoscopy (2024)

Abstract Background First-line over-the-scope (OTS) clip treatment has shown higher efficacy than standard endoscopic therapy in acute nonvariceal upper gastrointestinal bleeding (NVUGIB) from different causes. We compared OTS clips with through-the-scope (TTS) clips as first-line mechanical treatment in the specific setting of peptic ulcer bleeding. Methods We conducted an international, multicenter randomized controlled trial on consecutive patients with suspected NVUGIB. Patients with Forrest Ia–IIb gastroduodenal peptic ulcer were randomized 1:1 to OTS clip or TTS clip treatment. The primary outcome was the rate of 30-day rebleeding after successful initial hemostasis. Secondary outcomes included the rates of successful initial hemostasis and overall clinical success, defined as the composite of successful initial hemostasis and no evidence of 30-day rebleeding. Results 251 patients were screened and 112 patients were randomized to OTS (n = 61) or TTS (n = 51) clip treatment. The 30-day rebleeding rates were 1.6% (1/61) and 3.9% (2/51) in patients treated with OTS clips and TTS clips, respectively (Kaplan–Meier log-rank, P = 0.46). Successful initial hemostasis rates were 98.4% (60/61) in the OTS clip group and 78.4% (40/51) in the TTS clip group (P = 0.001). Overall clinical success rates were 96.7% (59/61) with OTS clips and 74.5% (38/51) with TTS clips (P = 0.001). Conclusions Low rates of 30-day rebleeding were observed after first-line endoscopic treatment of acute peptic ulcer bleeding with either OTS or TTS clips. However, OTS clips showed higher efficacy than TTS clips in achieving successful initial hemostasis and overall clinical success.
Variation in Mesenchymal KITL/SCF and IGF1 Expression at Middle Age Underlies Steady-State Hematopoietic Stem Cell Aging
Authors: Kira A. Young, Maria A. Telpoukhovskaia, Johanna Hofmann, Jayna J. Mistry, Konstantinos Kokkaliaris, Jennifer J. Trowbridge
Journal: Blood (2024)

Intrinsic molecular programs and extrinsic factors including pro-inflammatory molecules are understood to regulate hematopoietic aging. This is based on foundational studies using genetic perturbation to evaluate causality. However, individual organisms exhibit natural variation in hematopoietic aging phenotypes and the molecular basis of this heterogeneity is poorly understood. Here, we generated individual single cell transcriptomic profiles of hematopoietic and non-hematopoietic cell types in five young adult and nine middle-aged C57BL/6J female mice, providing a web-accessible transcriptomic resource for the field. Among all assessed cell types, hematopoietic stem cells (HSCs) exhibited the greatest phenotypic variation in expansion among individual middle-aged mice. We computationally pooled samples to define modules representing the molecular signatures of middle-aged HSCs and interrogated which extrinsic regulatory cell types and factors would predict variance in these signatures between individual middle-aged mice. Decline in signaling mediated by ADIPOQ, KITL and IGF1 from mesenchymal stromal cells (MSCs) was predicted to have the greatest transcriptional impact on middle-aged HSCs, as opposed to signaling mediated by endothelial cells or mature hematopoietic cell types. In individual middle-aged mice, lower expression of Kitl and Igf1 in MSCs highly correlated with reduced lymphoid lineage commitment of HSCs and increased signatures of differentiation-inactive HSCs. These signatures were independent of expression of aging-associated pro-inflammatory cytokines including IL1, IL6, TNF and RANTES. In sum, we find that Kitl and Igf1 expression are co-regulated and variable between individual mice at middle age and expression of these factors is predictive of HSC activation and lymphoid commitment independently of inflammation.
CAR T-Cell Therapy for Glioblastoma
Authors: Misty R Jenkins, Katharine J Drummond
Journal: New England Journal of Medicine (2024)

Glioblastoma is the most formidable of primary brain tumors, owing to its aggressive nature and the limited efficacy of the best available treatment, which comprises maximal safe surgical resection, radiotherapy, and alkylating chemotherapy. Most patients die within a year after diagnosis, which underscores the urgent need for innovative therapeutic strategies. Of interest, then, is an interim analysis in this issue of the Journal: Choi et al.1 report the outcomes of treating three patients with a secreting chimeric antigen receptor (CAR) T cell (see Key Concepts). CAR T-cell technology has reshaped our therapeutic approach to combating hematologic cancers. It harnesses the . . .
NSD2 drives t(4;14) myeloma cell dependence on adenylate kinase 2 by diverting one-carbon metabolism to the epigenome
Authors: Amin Sobh, Elena Encinas, Alisha Patel, Greeshma Surapaneni, Emilie Bonilla, Charlotte Kaestner, Janai Poullard, Monica Clerio, Karthik Vasan, Tzipporah Freeman, Dongwen Lv, Daphné Dupéré-Richer, Alberto Riva, Benjamin G. Barwick, Daohong Zhou, Lawrence H. Boise, Constantine S. Mitsiades, Baek Kim, Richard L. Bennett, Navdeep S. Chandel, Jonathan D. Licht
Journal: Blood (2024)
Re: Kosuke Takemura, Audreylie Lemelin, Matthew S. Ernst, et al. Outcomes of Patients with Brain Metastases from Renal Cell Carcinoma Receiving First-line Therapies: Results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.01.006
Authors: Yudai Ishiyama, Fumihiko Urabe
Journal: European Urology (2024)
Loss of Mickey Mouse Ears’ Sign in Progressive Supranuclear Palsy
Authors: Tsz-Kit Chow, Kwok-Man Ma
Journal: Clinical Nuclear Medicine (2024)

Abstract Progressive supranuclear palsy (PSP) is the most prevalent form of degenerative atypical parkinsonism. Clinical manifestations of PSP commonly encompass deficits in vertical gaze, postural stability, akinesia, and cognitive impairment. The characteristic metabolic pattern observed in PSP through FDG PET displays hypometabolism in the midbrain, striatum, thalamus, and frontal lobe. However, visual interpretation of midbrain hypometabolism poses challenges. In this report, we aim to elucidate a novel observation termed the “loss of Mickey Mouse ears’ sign,” which signifies midbrain hypometabolism as detected through visual assessment of FDG PET images.
Engineering Microorganisms for Cancer Immunotherapy
Authors: Dingkang Liu, Lichao Yu, Haibo Rong, Lubin Liu, Jun Yin
Journal: Advanced Healthcare Materials (2024)

Cancer immunotherapy presents a promising approach to fight against cancer by utilizing the immune system. Recently, engineered microorganisms have emerged as a potential strategy in cancer immunotherapy. These microorganisms, including bacteria and viruses, can be designed and modified using synthetic biology and genetic engineering techniques to target cancer cells and modulate the immune system. This review delves into various microorganism-based therapies for cancer immunotherapy, encompassing strategies for enhancing efficacy while ensuring safety and ethical considerations. The development of these therapies holds immense potential in offering innovative personalized treatments for cancer.
Mortality, cardiac and cerebral damages reduction by IL-1 inhibition in a murine model of TTP
Authors: Romain Muller, Raphaël Cauchois, Marie Lagarde, Sandrine Roffino, Cécile Genovesio, Samantha Fernandez, Guillaume Hache, Benjamin Guillet, Yéter Kara, Marion Marlinge, Peter Lenting, Pascale Poullin, Françoise Dignat-George, Edwige Tellier, Gilles Kaplanski
Journal: Blood (2024)

Abstract Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in von Willebrand factor cleavage resulting in capillary microthrombus formation and ischemic organ damage. Interleukin-1 (IL-1) has been shown to drive sterile inflammation after ischemia and could play an essential contribution to postischemic organ damage in TTP. Our objectives were to evaluate IL-1 involvement during TTP and to test the efficacy of the recombinant IL-1 receptor antagonist, anakinra, in a murine TTP model. We retrospectively measured plasma IL-1 concentrations in patients with TTP and controls. Patients with TTP exhibited elevated plasma IL-1α and -1β concentrations, which correlated with disease course and survival. In a mouse model of TTP, we administered anakinra (IL-1 inhibitor) or placebo for 5 days and evaluated the efficacy of this treatment. Anakinra significantly reduced mortality of mice (P &amp;lt; .001). Anakinra significantly decreased TTP-induced cardiac damage as assessed by blood troponin concentrations, evaluation of left ventricular function by echocardiography, [18F]fluorodeoxyglucose positron emission tomography of myocardial glucose metabolism, and cardiac histology. Anakinra also significantly reduced brain TTP-induced damage evaluated through blood PS100b concentrations, nuclear imaging, and histology. We finally showed that IL-1α and -1β trigger endothelial degranulation in vitro, leading to the release of von Willebrand factor. In conclusion, anakinra significantly reduced TTP mortality in a preclinical model of the disease by inhibiting both endothelial degranulation and postischemic inflammation, supporting further evaluations in humans.
Spatiotemporal Concurrent PARP Inhibitor Sensitization Based on Radiation‐Responsive Nanovesicles for Lung Cancer Chemoradiotherapy
Authors: Fei Kang, Meng Niu, Zijian Zhou, Mingru Zhang, Hehe Xiong, Fantian Zeng, Jing Wang, Xiaoyuan Chen
Journal: Advanced Healthcare Materials (2024)

The implementation of chemoradiation combinations has gained great momentum in clinical practices. However, the full utility of this paradigm is often restricted by the discordant tempos of action of chemotherapy and radiotherapy. Here, a gold nanoparticle-based radiation-responsive nanovesicle system loaded with cisplatin and veliparib, denoted as CV-Au NVs, is developed to augment the concurrent chemoradiation effect in a spatiotemporally controllable manner of drug release. Upon irradiation, the in situ generation of •OH induces the oxidation of polyphenylene sulfide from being hydrophobic to hydrophilic, resulting in the disintegration of the nanovesicles and the rapid release of the entrapped cisplatin and veliparib (the poly ADP-ribose polymerase (PARP) inhibitor). Cisplatin-induced DNA damage and the impairment of the DNA repair mechanism mediated by veliparib synergistically elicit potent pro-apoptotic effects. In vivo studies suggest that one-dose injection of the CV-Au NVs and one-time X-ray irradiation paradigm effectively inhibit tumor growth in the A549 lung cancer model. This study provides new insight into designing nanomedicine platforms in chemoradiation therapy from a vantage point of synergizing both chemotherapy and radiation therapy in a spatiotemporally concurrent manner.
Rates and causes of death after release from incarceration among 1 471 526 people in eight high-income and middle-income countries: an individual participant data meta-analysis
Authors: Rohan Borschmann, Rohan Borschmann, Claire Keen, Matthew J. Spittal, David Preen, Jane Pirkis, Sarah Larney, David L. Rosen, Lars Møller, Eamonn O'Moore, Jesse T. Young, Frederick L. Altice, Jason R. Andrews, Ingrid A. Binswanger, Anne Bukten, Tony Butler, Zheng Chang, Chuan-Yu Chen, Thomas Clausen, Peer B. Christensen, Gabriel J. Culbert, Ruth Cunningham, Louisa Degenhardt, Kate Dolan, Seena Fazel, Colin Fischbacher, Margaret Giles, Lesley Graham, Yen-Fang Huang, Florence Huber, Azar Karaminia, Paula King, Fiona G. Kouyoumdjian, Sungwoo Lim, Yiran E. Liu, Derrick Lopez, Akm Moniruzzaman, Jeffrey Morenoff, Lia N. Pizzicato, Scott K. Proescholdbell, Shabbar I. Ranapurwala, Jenny Shaw, Amanda Slaunwhite, Julian M. Somers, Anne C. Spaulding, Marianne R. Stavseth, Marc F. Stern, Kendra Telfer, Kendra Viner, Nadia Wang, Bin Zhao, Nanbo Zhu, Stuart A. Kinner, Stuart A Kinner
Journal: The Lancet (2024)
Immunomodulation Using BMP‐7 and IL‐10 to Enhance the Mineralization Capacity of Bone Progenitor Cells in a Fracture Hematoma‐Like Environment
Authors: Matthias Guido Wiesli, Matthias Werner Huber, Bernhard Weisse, Robert Zboray, Stefanie Kiderlen, Arlyng González‐Vázquez, Katharina Maniura‐Weber, Markus Rottmar, William Arthur Lackington
Journal: Advanced Healthcare Materials (2024)

Abstract Following biomaterial implantation, a failure to resolve inflammation during the formation of a fracture hematoma can significantly limit the biomaterial's ability to facilitate bone regeneration. This study aims to combine the immunomodulatory and osteogenic effects of BMP‐7 and IL‐10 with the regenerative capacity of collagen‐hydroxyapatite (CHA) scaffolds to enhance in vitro mineralization in a hematoma‐like environment. Incubation of CHA scaffolds with human whole blood leads to rapid adsorption of fibrinogen, significant stiffening of the scaffold, and the formation of a hematoma‐like environment characterized by a limited capacity to support the infiltration of human bone progenitor cells, a significant upregulation of inflammatory cytokines and acute phase proteins, and significantly reduced osteoconductivity. CHA scaffolds functionalized with BMP‐7 and IL‐10 significantly downregulate the production of key inflammatory cytokines, including IL‐6, IL‐8, and leptin, creating a more permissive environment for mineralization, ultimately enhancing the biomaterial's osteoconductivity. In conclusion, targeting the onset of inflammation in the early phase of bone healing using BMP‐7 and IL‐10 functionalized CHA scaffolds is a promising approach to effectively downregulate inflammatory processes, while fostering a more permissive environment for bone regeneration.
The chromosome-scale assembly of the Notopterygium incisum genome provides insight into the structural diversity of coumarins
Authors: Qien Li, Yiqun Dai, Xin-Cheng Huang, Lanlan Sun, Kaixuan Wang, Xiao Guo, Dingqiao Xu, Digao Wan, Latai An, Zixuan Wang, Huanying Tang, Qi Qi, Huihui Zeng, Minjian Qin, Jia-Yu Xue, Yucheng Zhao
Journal: Acta Pharmaceutica Sinica B (2024)

Coumarins, derived from the phenylpropanoid pathway, represent one of the primary metabolites found in angiosperms. The alignment of the tetrahydropyran (THP) and tetrahydrofuran (THF) rings with the lactone structure results in the formation of at least four types of complex coumarins. However, the mechanisms underlying the structural diversity of coumarin remain poorly understood. Here, we report the chromosome-level genome assembly of Notopterygium incisum, spanning 1.64 Gb, with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding genes. Additionally, we identified the key enzymes responsible for shaping the structural diversity of coumarins, including two p-coumaroyl CoA 2'-hydroxylases crucial for simple coumarins basic skeleton architecture, two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis, and five CYP736 cyclases involved in THP and THF ring formation. Notably, two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first time. Evolutionary analysis implies that tandem and ectopic duplications of the CYP736 subfamily, specifically arising in the Apiaceae, contributed to the structural diversity of coumarins in N. incisum. Conclusively, this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.
RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses
Authors: Emil K Gustavsson, Jordan Follett, Joanne Trinh, Sandeep K Barodia, Raquel Real, Zhiyong Liu, Melissa Grant-Peters, Jesse D Fox, Silke Appel-Cresswell, A Jon Stoessl, Alex Rajput, Ali H Rajput, Roland Auer, Russel Tilney, Marc Sturm, Tobias B Haack, Suzanne Lesage, Christelle Tesson, Alexis Brice, Carles Vilariño-Güell, Mina Ryten, Matthew S Goldberg, Andrew B West, Michele T Hu, Huw R Morris, Manu Sharma, Ziv Gan-Or, Bedia Samanci, Pawel Lis, Maria Teresa Periñan, Rim Amouri, Samia Ben Sassi, Faycel Hentati, Francesca Tonelli, Dario R Alessi, Matthew J Farrer
Journal: The Lancet Neurology (2024)

Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease.
Risk of Relapse of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis in a Randomized Controlled Trial of Plasma Exchange and Glucocorticoids
Authors: Mats L. Junek, Peter A. Merkel, Eswari Vilayur, Ron Wald, Nader Khalidi, David Jayne, Michael Walsh
Journal: Arthritis & Rheumatology (2024)

Objective Relapses of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA‐associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment. Methods We performed a post hoc analysis of participants with severe ANCA‐associated vasculitis enrolled in an international two‐by‐two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen. We estimated the effects of treatments on relapses of any severity using three competing risk time‐to‐event models adjusted for patient and disease characteristics and other treatments. Each model was adjusted for disease manifestations in different ways. Results Of 704 participants, 649 (92.2%) achieved remission and 147 (22.7%) experienced 204 relapses. The relapse rate was 10.3 (95% confidence interval [CI] 8.4–12.1) relapses per 100 patient‐years. Neither the use of PLEX (subhazard ratio 0.91–0.94; 95% CIs range from 0.66 to 1.31) nor a glucocorticoid regimen (subhazard ratio 0.93–0.94; 95% CIs range from 0.67 to 1.35) appreciably changed the risk of relapse. Proteinase 3–ANCA and the presence of nonhemorrhagic respiratory manifestations of the disease at trial entry were associated with increased risks of relapse. Receiving dialysis at baseline and administration of oral cyclophosphamide as induction therapy were associated with lower risks of relapse. Conclusion In patients with severe ANCA‐associated vasculitis, relapses remain common; neither the use of PLEX nor an initial glucocorticoid tapering regimen impacted relapse risk.