tbuckley/cabot-search huggingface dataset:
Four distinct patterns of anterior cruciate ligament injury in women’s professional football (soccer): a systematic video analysis of 37 match injuries
Authors: Leonard Achenbach, Hendrik Bloch, Christian Klein, Theresa Damm, Matthias Obinger, Maximilian Rudert, Werner Krutsch, Dominik Szymski
Journal: British Journal of Sports Medicine (2024)

Background To identify mechanisms and patterns of anterior cruciate ligament (ACL) injury in adult women’s professional football by means of video match analysis. Methods ACL match injuries sustained in Germany’s first women’s league during the 2016–2017 to 2022–2023 seasons were prospectively analysed by three expert raters using a standardised observation form. Epidemiological and injury data, as well as the medical history of ACL tears, were obtained from media reports and the statutory accident insurance for professional athletes. Results Thirty-seven ACL injuries sustained in official football matches were included in the video analysis, of which 24 (65%) had associated knee injuries, mainly meniscus and collateral ligament injuries. According to the categorised contact mechanisms, 17 (46%) were non-contact injuries, 14 indirect contact injuries (38%) and six direct contact injuries (16%). Of the 17 non-contact injuries, seven (41%) occurred during the first 15 min of the match. Contact mechanisms did not differ between primary and secondary ACL injuries to the same or the contralateral side. Most injuries (80%) of field players occurred during horizontal movements such as sprinting (n=9, 26%), change-of-direction manoeuvres (n=7, 19%), stopping (n=5, 14%) and lunging (n=5, 14%). Four distinct repetitive patterns of ACL match injuries were identified: (1) non-contact ‘pressing ACL injury’ (n=9), (2) indirect contact ‘parallel sprinting and tackling ACL injury’ (n=7), (3) direct contact ‘knee-to-knee ACL injury’ (n=6) and (4) non-contact ‘landing ACL injury’ (n=4). Conclusion Most of the identified patterns of ACL injuries in women’s professional football have great potential for prevention.
Abstract deliberation by visuomotor neurons in prefrontal cortex
Authors: Julie A Charlton, Robbe L T Goris
Journal: Nature Neuroscience (2024)

Abstract During visually guided behavior, the prefrontal cortex plays a pivotal role in mapping sensory inputs onto appropriate motor plans. When the sensory input is ambiguous, this involves deliberation. It is not known whether the deliberation is implemented as a competition between possible stimulus interpretations or between possible motor plans. Here we study neural population activity in the prefrontal cortex of macaque monkeys trained to flexibly report perceptual judgments of ambiguous visual stimuli. We find that the population activity initially represents the formation of a perceptual choice before transitioning into the representation of the motor plan. Stimulus strength and prior expectations both bear on the formation of the perceptual choice, but not on the formation of the action plan. These results suggest that prefrontal circuits involved in action selection are also used for the deliberation of abstract propositions divorced from a specific motor plan, thus providing a crucial mechanism for abstract reasoning.
Evaluation of the SCAT 5 tool in the assessment of concussion in Para athletes: a Delphi study
Authors: Bryce Dyer, Osman Hassan Ahmed, Sara Dahlén, Kristin Dalton, Wayne Derman, Amber Donaldson, Kristina Fagher, Jan Lexell, Larissa Pinheiro, Peter Van de Vliet, Richard Weiler, Nick Webborn
Journal: British Journal of Sports Medicine (2024)

Objectives To investigate if the sport concussion assessment tool version 5 (SCAT5) could be suitable for application to Para athletes with a visual impairment, a spinal cord injury, or a limb deficiency. Methods A 16-member expert panel performed a Delphi technique protocol. The first round encompassed an open-ended questionnaire, with round 2 onwards being composed of a series of closed-ended statements requiring each expert’s opinion using a five-point Likert scale. A predetermined threshold of 66% was used to decide whether agreement had been reached by the panel. Results The Delphi study resulted in a four-round process. After round 1, 92 initial statements were constructed with 91 statements obtaining the targeted level of agreement by round 4. The expert panellist completion rate of the full four-round process was 94%. In the case of athletes with a suspected concussion with either limb deficiencies or spinal cord injuries, the panel agreed that a baseline assessment would be needed on record is ideal before a modified SCAT5 assessment. With respect to visual impairments, it was conceded that some tests were either difficult, infeasible or should be omitted entirely depending on the type of visual impairment. Conclusion It is proposed that the SCAT5 could be conducted on athletes with limb deficiencies or spinal cord injuries with some minor modifications and by establishing a baseline assessment to form a comparison. However, it cannot be recommended for athletes with visual impairment in its current form. Further research is needed to determine how potential concussions could be more effectively evaluated in athletes with different impairments.
Phase Ib Study of Unesbulin (PTC596) Plus Dacarbazine for the Treatment of Locally Recurrent, Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma
Authors: Brian A. Van Tine, Matthew A. Ingham, Steven Attia, Christian F. Meyer, John D. Baird, Esther Brooks-Asplund, Dhiren D'Silva, Ronald Kong, Anthony Mwatha, Kylie O'Keefe, Marla Weetall, Robert Spiegel, Gary K. Schwartz
Journal: Journal of Clinical Oncology (2024)

PURPOSE This multicenter, single-arm, open-label, phase Ib study was designed to determine the recommended phase II dose (RP2D) and to evaluate the safety and preliminary efficacy of unesbulin plus dacarbazine (DTIC) in patients with advanced leiomyosarcoma (LMS). PATIENTS AND METHODS Adult subjects with locally advanced, unresectable or metastatic, relapsed or refractory LMS were treated with escalating doses of unesbulin orally twice per week in combination with DTIC 1,000 mg/m 2 intravenously (IV) once every 21 days. The time-to-event continual reassessment method was used to determine the RP2D on the basis of dose-limiting toxicities (DLTs) assessed during the first two 21-day treatment cycles. All explored doses of unesbulin (200 mg up to 400 mg) were in combination with DTIC. An expansion cohort was enrolled to evaluate the safety and efficacy of unesbulin at the RP2D. RESULTS Unesbulin 300 mg administered orally twice per week in combination with DTIC 1,000 mg/m 2 IV once every 21 days was identified as the RP2D. On the basis of data from 27 subjects who were deemed DLT-evaluable, toxicity was higher in the unesbulin 400 mg group, with three of four subjects (75%) experiencing DLTs versus one of four subjects (25%) in the 200 mg group and three of 19 subjects (15.8%) in the 300 mg group. The most commonly reported DLTs and treatment-related grade 3 and 4 adverse events were thrombocytopenia and neutropenia. At the RP2D, seven subjects who were efficacy evaluable achieved partial response for an objective response rate of 24.1%. CONCLUSION Unesbulin 300 mg twice per week plus DTIC 1,000 mg/m 2 once every 21 days was identified as the RP2D, demonstrating a favorable benefit-risk profile in a heavily pretreated population of adults with advanced LMS.
Heart‐on‐a‐Chip Model of Epicardial–Myocardial Interaction in Ischemia Reperfusion Injury
Authors: Dawn Bannerman, Simon Pascual‐Gil, Qinghua Wu, Ian Fernandes, Yimu Zhao, Karl T. Wagner, Sargol Okhovatian, Shira Landau, Naimeh Rafatian, David F. Bodenstein, Ying Wang, Trevor R. Nash, Gordana Vunjak‐Novakovic, Gordon Keller, Slava Epelman, Milica Radisic
Journal: Advanced Healthcare Materials (2024)

Epicardial cells (EPIs) form the outer layer of the heart and play an important role in development and disease. Current heart-on-a-chip platforms still do not fully mimic the native cardiac environment due to the absence of relevant cell types, such as EPIs. Here, using the Biowire II platform, engineered cardiac tissues with an epicardial outer layer and inner myocardial structure are constructed, and an image analysis approach is developed to track the EPI cell migration in a beating myocardial environment. Functional properties of EPI cardiac tissues improve over two weeks in culture. In conditions mimicking ischemia reperfusion injury (IRI), the EPI cardiac tissues experience less cell death and a lower impact on functional properties. EPI cell coverage is significantly reduced and more diffuse under normoxic conditions compared to the post-IRI conditions. Upon IRI, migration of EPI cells into the cardiac tissue interior is observed, with contributions to alpha smooth muscle actin positive cell population. Altogether, a novel heart-on-a-chip model is designed to incorporate EPIs through a formation process that mimics cardiac development, and this work demonstrates that EPI cardiac tissues respond to injury differently than epicardium-free controls, highlighting the importance of including EPIs in heart-on-a-chip constructs that aim to accurately mimic the cardiac environment.
Glucopeptide Superstructure Hydrogel Promotes Surgical Wound Healing Following Neoadjuvant Radiotherapy by Producing NO and Anticellular Senescence
Authors: Hang Wang, Ganen Mu, Xiaoyao Cai, Xiaoguang Zhang, Ruiqi Mao, Haixue Jia, Hongjing Luo, Jianfeng Liu, Cuicui Zhao, Zhongyan Wang, Cuihong Yang
Journal: Advanced Healthcare Materials (2024)

Neoadjuvant radiotherapy, a preoperative intervention regimen for reducing the stage of primary tumors and surgical margins, has gained increasing attention in the past decade. However, radiation-induced skin damage during neoadjuvant radiotherapy exacerbates surgical injury, remarkably increasing the risk of refractory wounds and compromising the therapeutic effects. Radiation impedes wound healing by increasing the production of reactive oxygen species and inducing cell apoptosis and senescence. Here, a self-assembling peptide (R-peptide) and hyaluronic-acid (HA)-based and cordycepin-loaded superstructure hydrogel is prepared for surgical incision healing after neoadjuvant radiotherapy. Results show that i) R-peptide coassembles with HA to form biomimetic fiber bundle microstructure, in which R-peptide drives the assembly of single fiber through π-π stacking and other forces and HA, as a single fiber adhesive, facilitates bunching through electrostatic interactions. ii) The biomimetic superstructure contributes to the adhesion and proliferation of cells in the surgical wound. iii) Aldehyde-modified HA provides dynamic covalent binding sites for cordycepin to achieve responsive release, inhibiting radiation-induced cellular senescence. iv) Arginine in the peptides provides antioxidant capacity and a substrate for the endogenous production of nitric oxide to promote wound healing and angiogenesis of surgical wounds after neoadjuvant radiotherapy.
Combined Effects of Clonal Hematopoiesis and Carotid Stenosis on Cardiovascular Mortality
Authors: Roland Jäger, Matthias Hoke, Florian J. Mayer, Stefanie Boden, Cornelia Englisch, Cihan Ay, Robert Kralovics, Christoph J. Binder
Journal: Journal of the American College of Cardiology (2024)
The common variable immunodeficiency IgM repertoire narrowly recognizes erythrocyte and platelet glycans
Authors: Carole Le Coz, Melissa Trofa, Dorothy L. Butler, Samuel Yoon, Tian Tian, Whitney Reid, Emylette Cruz Cabrera, Ainsley V.C. Knox, Caroline Khanna, Kathleen E. Sullivan, Jennifer Heimall, Patricia Takach, Olajumoke O. Fadugba, Monica Lawrence, Soma Jyonouchi, Hakon Hakonarson, Andrew D. Wells, Steven Handler, Karen B. Zur, Vinodh Pillai, Jeffrey C. Gildersleeve, Neil Romberg
Journal: Journal of Allergy and Clinical Immunology (2024)
Magnetic Seizure Therapy vs Modified Electroconvulsive Therapy in Patients With Bipolar Mania
Authors: Shan Chen, Jianhua Sheng, Fuzhong Yang, Yi Qiao, Wenzheng Wang, Hui Wen, Qiao Yang, Xiaochen Chen, Yingying Tang
Journal: JAMA Network Open (2024)

Importance Bipolar mania is a common disabling illness. Electroconvulsive therapy (ECT) is an effective treatment for patients with severe mania, though it is limited by the risk of cognitive adverse effects. Magnetic seizure therapy (MST) as an alternative treatment to ECT for bipolar mania has not yet been reported. Objective To compare the effectiveness and cognitive adverse effects of MST and ECT in bipolar mania. Design, Setting, and Participants This randomized clinical trial was conducted at the Shanghai Mental Health Center from July 1, 2017, through April 26, 2021. Forty-eight patients with bipolar mania were recruited and randomly allocated to receive MST or ECT. The data analysis was performed from June 5, 2021, through August 30, 2023. Interventions Patients completed 2 or 3 sessions of MST or ECT per week for a total of 8 to 10 sessions. The MST was delivered at 100% device output with a frequency of 75 Hz over the vertex. Main Outcomes and Measures The primary outcomes were reduction of total Young Manic Rating Scale (YMRS) score and response rate (more than 50% reduction of the total YMRS score compared with baseline). An intention-to-treat (ITT) analysis and repeated-measures analyses of variance were conducted for the primary outcomes. Results Twenty patients in the ECT group (mean [SD] age, 31.6 [8.6] years; 12 male [60.0%]) and 22 patients in the MST group (mean [SD] age, 34.8 [9.8] years; 15 male [68.2%]) were included in the ITT analysis. The response rates were 95.0% (95% CI, 85.4%-100%) in the ECT group and 86.4% (95% CI, 72.1%-100%) in the MST group. The YMRS reduction rate ( z = −0.82; 95% CI, −0.05 to 0.10; P = .41) and response rate (χ 2 = 0.18; 95% CI, −0.13 to 0.31; P = .67) were not significantly different between the groups. The time-by-group interaction was significant for the language domain ( F 1,24 = 7.17; P = .01), which was well preserved in patients receiving MST but worsened in patients receiving ECT. No serious adverse effects were reported in either group. Conclusions and Relevance These findings suggest that MST is associated with a high response rate and fewer cognitive impairments in bipolar mania and that it might be an alternative therapy for the treatment of bipolar mania. Trial Registration ClinicalTrials.gov Identifier: NCT03160664
Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque
Authors: Meng-Meng Yu, Ming-Liang Wang, Jin-Jin Wang, Bo-Li Lin, Xin Zhao, Xin-Wei Tao, Yin-Yin Chen, Peng-Yang Li, Jing-Kun Zhang, Jun-Bo Ge, Hang Jin, Meng-Su Zeng
Journal: Journal of the American College of Cardiology (2024)
Economic Evaluation of Enhanced vs Standard Varenicline Treatment for Tobacco Cessation
Authors: Marlon P. Mundt, James H. Stein, Michael C. Fiore, Timothy B. Baker
Journal: JAMA Network Open (2024)

Importance Smoking is the leading preventable cause of death and illness in the US. Identifying cost-effective smoking cessation treatment may increase the likelihood that health systems deliver such treatment to their patients who smoke. Objective To evaluate the cost-effectiveness of standard vs enhanced varenicline use (extended varenicline treatment or varenicline in combination with nicotine replacement therapy) among individuals trying to quit smoking. Design, Setting, and Participants This economic evaluation assesses the Quitting Using Intensive Treatments Study (QUITS), which randomized 1251 study participants who smoked into 4 conditions: (1) 12-week varenicline monotherapy (n = 315); (2) 24-week varenicline monotherapy (n = 311); (3) 12-week varenicline combination treatment with nicotine replacement therapy patch (n = 314); or (4) 24-week varenicline combination treatment with nicotine replacement therapy patch (n = 311). Study enrollment occurred in Madison and Milwaukee, Wisconsin, between November 11, 2017, and July 2, 2020. Statistical analysis took place from May to October 2023. Main Outcomes and Measures The primary outcome was 7-day point prevalence abstinence (biochemically confirmed with exhaled carbon monoxide level ≤5 ppm) at 52 weeks. The incremental cost-effectiveness ratio (ICER), or cost per additional person who quit smoking, was calculated using decision tree analysis based on abstinence and cost for each arm of the trial. Results Of the 1251 participants, mean (SD) age was 49.1 (11.9) years, 675 (54.0%) were women, and 881 (70.4%) completed the 52-week follow-up. Tobacco cessation at 52 weeks was 25.1% (79 of 315) for 12-week monotherapy, 24.4% (76 of 311) for 24-week monotherapy, 23.6% (74 of 314) for 12-week combination therapy, and 25.1% (78 of 311) for 24-week combination therapy, respectively. The total mean (SD) cost was $1175 ($365) for 12-week monotherapy, $1374 ($412) for 12-week combination therapy, $2022 ($813) for 24-week monotherapy, and $2118 ($1058) for 24-week combination therapy. The ICER for 12-week varenicline monotherapy was $4681 per individual who quit smoking and $4579 per quality-adjusted life-year (QALY) added. The ICER for 24-week varenicline combination therapy relative to 12-week monotherapy was $92 000 000 per additional individual who quit smoking and $90 000 000 (95% CI, $15 703 to dominated or more costly and less efficacious) per additional QALY. Conclusions and Relevance This economic evaluation of standard vs enhanced varenicline treatment for smoking cessation suggests that 12-week varenicline monotherapy was the most cost-effective treatment option at the commonly cited threshold of $100 000/QALY. This study provides patients, health care professionals, and other stakeholders with increased understanding of the health and economic impact of more intensive varenicline treatment options.
HIV/HBV coinfection remodels the immune landscape and natural killer cell ADCC functional responses
Authors: Bo Sun, Kelly A.S. da Costa, Aljawharah Alrubayyi, Jonida Kokici, Natasha Fisher-Pearson, Noshin Hussain, Stefano D’Anna, Lorenzo Piermatteo, Romina Salpini, Valentina Svicher, Stephanie Kucykowicz, Indrajit Ghosh, Fiona Burns, Sabine Kinloch, Pedro Simoes, Sanjay Bhagani, Patrick T F. Kennedy, Mala K. Maini, Rachael Bashford-Rogers, Upkar S Gill, Dimitra Peppa
Journal: Hepatology (2024)

HBV and HIV coinfection is a common occurrence globally, with significant morbidity and mortality. Both viruses lead to immune dysregulation including changes in natural killer (NK) cells, a key component of antiviral defense and a promising target for HBV cure strategies. Here we used high-throughput single-cell analysis to explore the immune cell landscape in people with HBV mono-infection and HIV/HBV coinfection, on antiviral therapy, with emphasis on identifying the distinctive characteristics of NK cell subsets that can be therapeutically harnessed.
Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial
Authors: Martin Schuler, Kristof Cuppens, Till Plönes, Marcel Wiesweg, Bert Du Pont, Balazs Hegedus, Johannes Köster, Fabian Mairinger, Kaid Darwiche, Annette Paschen, Brigitte Maes, Michel Vanbockrijck, David Lähnemann, Fang Zhao, Hubertus Hautzel, Dirk Theegarten, Koen Hartemink, Henning Reis, Paul Baas, Alexander Schramm, Clemens Aigner
Journal: Nature Medicine (2024)

Abstract Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are the standard of care in most patients with metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive patients with resectable non-small-cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was the feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab) and in 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients, tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 before lung cancer surgery. ClinicalTrials.gov Indentifier: NCT04205552 .
Inhibition of mammalian mtDNA transcription acts paradoxically to reverse diet-induced hepatosteatosis and obesity
Authors: Shan Jiang, Taolin Yuan, Florian A. Rosenberger, Arnaud Mourier, Nathalia R. V. Dragano, Laura S. Kremer, Diana Rubalcava-Gracia, Fynn M. Hansen, Melissa Borg, Mara Mennuni, Roberta Filograna, David Alsina, Jelena Misic, Camilla Koolmeister, Polyxeni Papadea, Martin Hrabe de Angelis, Lipeng Ren, Olov Andersson, Anke Unger, Tim Bergbrede, Raffaella Di Lucrezia, Rolf Wibom, Juleen R. Zierath, Anna Krook, Patrick Giavalisco, Matthias Mann, Nils-Göran Larsson
Journal: Nature Metabolism (2024)

Abstract The oxidative phosphorylation system 1 in mammalian mitochondria plays a key role in transducing energy from ingested nutrients 2 . Mitochondrial metabolism is dynamic and can be reprogrammed to support both catabolic and anabolic reactions, depending on physiological demands or disease states. Rewiring of mitochondrial metabolism is intricately linked to metabolic diseases and promotes tumour growth 3–5 . Here, we demonstrate that oral treatment with an inhibitor of mitochondrial transcription (IMT) 6 shifts whole-animal metabolism towards fatty acid oxidation, which, in turn, leads to rapid normalization of body weight, reversal of hepatosteatosis and restoration of normal glucose tolerance in male mice on a high-fat diet. Paradoxically, the IMT treatment causes a severe reduction of oxidative phosphorylation capacity concomitant with marked upregulation of fatty acid oxidation in the liver, as determined by proteomics and metabolomics analyses. The IMT treatment leads to a marked reduction of complex I, the main dehydrogenase feeding electrons into the ubiquinone (Q) pool, whereas the levels of electron transfer flavoprotein dehydrogenase and other dehydrogenases connected to the Q pool are increased. This rewiring of metabolism caused by reduced mtDNA expression in the liver provides a principle for drug treatment of obesity and obesity-related pathology.