tbuckley/cabot-search huggingface dataset:
The Interaction of Shock Waves With Biological Tissue - Momentum Transfer, the Key for Tissue Stimulation and Fragmentation
Authors: Othmar Wess, Juergen Mayer
Journal: International Journal of Surgery (2025)

Background: Shock waves in medicine have gained enormous importance and have spread since 1980, and the first kidney stone was successfully fragmented in a patient in Munich. Meanwhile, the spectrum of medical applications of shock waves ranges from powerful fragmentation of kidney stones to diverse indications such as wound healing, chronic pelvic pain, spasticity, erectile dysfunction, and others, to neuro-stimulation in the context of Alzheimer’s disease. A comprehensive working mechanism for this diverse field of medical indications are still missing. Objective: Investigation of the physical basis of the working mechanism of shock waves in medical applications. Methods: We developed a model based on the mechanical forces generated by the momentum transfer at the acoustic interfaces of different layers of biological tissue. The generated forces are strong enough to crash brittle material and provide an adequate mechanical stimulus to activate mechano-transduction and mechano-sensory-transduction with nerve stimulation, thereby affecting the neural memory function of the central nervous system. Results: The key to generating appropriate forces in the millisecond range is the mechanism of momentum transfer at the interfaces between tissue layers with different acoustic impedances. According to Newton´s laws of motion, a change in momentum (momentum transfer) generates force F = dP/dt. The inherent shear forces can stretch biological membranes to release biomolecules such as VEGF and NO. A most favourable feature of this mechanism is the selective effect on soft tissue interfaces and small tissue inhomogeneities to generate small forces in the range of few (≤ 10) Newton to stimulate tissue and nerve cells, while the same shock wave can generate forces ≥ 200 Newton and more on hard tissue interfaces such as bones or stones. Conclusion: The mechanism of momentum transfer is the basis for mechano-transduction and mechano-sensory transduction. It offers the opportunity to stimulate peripheral nerves and modify the motor reflex patterns of “pathologic” reflexes by hyper stimulation. The new technique of transcranial pulse stimulation (TPS) may be based on direct stimulation and reactivation of neurons in the brain. Momentum transfer is the basic physical mechanism and the initiator for successive biological processes in medical shock wave therapy.
SIRT1 Alleviates Mitochondrial Fission and Necroptosis in Cerebral Ischemia/Reperfusion Injury via SIRT1–RIP1 Signaling Pathway
Authors: Xuan Wei, Hanjing Guo, Guangshan Huang, Haoyue Luo, Lipeng Gong, Pan Meng, Jiyong Liu, Wenli Zhang, Zhigang Mei
Journal: MedComm (2025)

ABSTRACT Programmed cell death, including necroptosis, plays a critical role in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI). Silent information regulator 1 (SIRT1) has been identified as a potential therapeutic target for CIRI, yet its precise role in regulating necroptosis remains controversial. Furthermore, the potential interaction between SIRT1 and receptor‐interacting protein kinase 1 (RIP1) in this context is not fully understood. Sanpian Decoction (SPD), a classical traditional herbal formula, was previously shown to enhance SIRT1 expression in our studies. Our findings demonstrated that, both in vivo and in vitro, CIRI was associated with a decrease in SIRT1 levels and phosphorylated dynamin‐related protein 1 (p‐DRP1) at Ser637, alongside an increase in RIP1 and other necroptosis‐related proteins. Co‐immunoprecipitation and immunofluorescence analyses revealed a weakened interaction between SIRT1 and RIP1. Furthermore, abnormal mitochondrial fission and dysfunction were mediated through the phosphoglycerate mutase 5–DRP1 pathway. Notably, SPD treatment improved neurological outcomes and reversed these pathological changes by enhancing the SIRT1–RIP1 interaction. In conclusion, this study suggests that SIRT1 is a promising therapeutic target for CIRI, capable of inhibiting necroptosis and mitigating mitochondrial fission via the SIRT1–RIP1 pathway. SPD exhibits therapeutic potential by activating SIRT1, thereby attenuating necroptosis and mitochondrial fission during CIRI.
IMMUNOSENESCENCE IN SKELETAL MUSCLE: THE ROLE-PLAY IN CANCER CACHEXIA CHESSBOARD
Authors: Matteo Giovarelli, Emanuele Mocciaro, Carla Carnovale, Davide Cervia, Cristiana Perrotta, Emilio Clementi
Journal: Seminars in Cancer Biology (2025)

With the increase in life expectancy, age-related conditions and diseases have become a widespread and relevant social burden. Among these, immunosenescence and cancer cachexia play a significant often intertwined role. Immunosenescence is the progressive aging decline of both the innate and adaptive immune systems leading to increased infection susceptibility, poor vaccination efficacy, autoimmune disease, and malignancies. Cancer cachexia affects elderly patients with cancer causing severe weight loss, muscle wasting, inflammation, and reduced response to therapies. Whereas the connections between immunosenescence and cancer cachexia have been raising attention, the molecular mechanisms still need to be completely elucidated. This review aims at providing the current knowledge about the interplay between immunosenescence, skeletal muscle, and cancer cachexia, analyzing the molecular pathways known so far to be involved. Finally, we highlight potential therapeutic strategies suited for elderly population aimed to block immunosenescence and to preserve muscle mass in cachexia, also presenting the analysis of the current state-of-the-art of related clinical trials.
Understanding the quality of ethnicity data recorded in health-related administrative data sources compared with Census 2021 in England
Authors: Cameron Razieh, Bethan Powell, Rosemary Drummond, Isobel L. Ward, Jasper Morgan, Myer Glickman, Chris White, Francesco Zaccardi, Jonathan Hope, Veena Raleigh, Ashley Akbari, Nazrul Islam, Thomas Yates, Lisa Murphy, Bilal A. Mateen, Kamlesh Khunti, Vahe Nafilyan
Journal: PLoS Medicine (2025)

Background Electronic health records (EHRs) are increasingly used to investigate health inequalities across ethnic groups. While there are some studies showing that the recording of ethnicity in EHR is imperfect, there is no robust evidence on the accuracy between the ethnicity information recorded in various real-world sources and census data. Methods and findings We linked primary and secondary care NHS England data sources with Census 2021 data and compared individual-level agreement of ethnicity recording in General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR), Hospital Episode Statistics (HES), Ethnic Category Information Asset (ECIA), and Talking Therapies for anxiety and depression (TT) with ethnicity reported in the census. Census ethnicity is self-reported and, therefore, regarded as the most reliable population-level source of ethnicity recording. We further assessed the impact of multiple approaches to assigning a person an ethnic category. The number of people that could be linked to census from ECIA, GDPPR, HES, and TT were 47.4m, 43.5m, 47.8m, and 6.3m, respectively. Across all 4 data sources, the White British category had the highest level of agreement with census (≥96%), followed by the Bangladeshi category (≥93%). Levels of agreement for Pakistani, Indian, and Chinese categories were ≥87%, ≥83%, and ≥80% across all sources. Agreement was lower for Mixed (≤75%) and Other (≤71%) categories across all data sources. The categories with the lowest agreement were Gypsy or Irish Traveller (≤6%), Other Black (≤19%), and Any Other Ethnic Group (≤25%) categories. Conclusions Certain ethnic categories across all data sources have high discordance with census ethnic categories. These differences may lead to biased estimates of differences in health outcomes between ethnic groups, a critical data point used when making health policy and planning decisions.
Is 9 months the sweet spot for male athletes to return to sport after anterior cruciate ligament reconstruction?
Authors: Roula Kotsifaki, Enda King, Roald Bahr, Rod Whiteley
Journal: British Journal of Sports Medicine (2025)

Objective Most studies examining the time to return to sport (RTS) after anterior cruciate ligament reconstruction (ACLR) do not account for the athlete’s physical readiness. This study aimed to investigate the status of male athletes at 2 years after ACLR, the factors affecting a return to pivoting sports, and the association between time to RTS and subsequent knee injury risk for those athletes who met discharge criteria. Methods We prospectively followed 530 male athletes (mean age 26.7±7.7 years) participating in pivoting sports throughout rehabilitation and at 2 years after ACLR. Pair-wise analyses were conducted to compare athletes who returned to pivoting sports and those who did not. We performed a Cox regression analysis to assess the association between subsequent non-contact or indirect contact knee injuries and time to RTS. Pearson’s χ 2 test was used to compare athletes who RTS in ≤9 months to those who RTS in &gt;9 months after ACLR. Results In total, 379 (72%) athletes returned to pivoting sports at 2 years after ACLR. Athletes who completed rehabilitation and met discharge criteria (n=190) were almost 6 times more likely to return to their preinjury sport (OR 5.71; 95% CI 3.39 to 9.62). Of those who did not complete their rehabilitation (n=340), 132 (39%) did not return to pivoting sports. For athletes who met discharge criteria, time to RTS was not associated with the risk of new knee or ACL injury. There was no increased risk for new knee (HR 0.892, 95% CI 0.39 to 2.07, p=0.79) or ACL (HR 0.718, 95% CI 0.24 to 2.17, p=0.56) injury whether athletes returned before or after the 9-month mark following ACLR. Conclusions Completing rehabilitation and meeting objective criteria significantly increased the odds for male athletes to return to pivoting sports. Time to RTS did not impact the risk for a new knee or ACL injury if athletes met objective criteria.
Early Continuous Glucose Monitor Use in Children and Adolescents With Type 1 Diabetes: Rates of Initiation and Impact on Glycemic Outcomes
Authors: Elizabeth A. Mann, Saketh Rompicherla, Brian Miyazaki, Nicole Rioles, Holly Hardison, Lauren Golden, Jennifer Sarhis, Halis K. Akturk, Joyce Lee, Daniel J. DeSalvo, Patricia Gomez, Osagie Ebekozien, Priya Prahalad
Journal: Diabetes Care (2025)

OBJECTIVE Early initiation of continuous glucose monitor (CGM) after type 1 diabetes (T1D) diagnosis has been associated with lower hemoglobin A1C (HbA1c) in single-institution studies. This multicenter study evaluated the association between the timing of CGM initiation and HbA1c at 3 years postdiagnosis. RESEARCH DESIGN AND METHODS Data were obtained from the T1D Exchange Quality Improvement Collaborative (T1DX-QI) electronic health record database from 25 pediatric centers and included children and adolescents ≤18 years old diagnosed with T1D in 2019 and 2020. CGM initiation and glycemic outcomes were followed for 3 years after diagnosis. Locally estimated scatterplot smoothing plots evaluated the relationship between timing of CGM initiation and HbA1c over time, and logistic regression models were used to adjust for potential confounders. RESULTS There were 4,164 people included in this analysis, mean age was 12.6 (SD 3.5) years, and 37% had public health insurance. Of the 93% (n = 3,877) who initiated CGM within 3 years of T1D diagnosis, 21% did so at 0–3 months, 14% at 3–6 months, 14% at 6–12 months, and 51% after 12 months. Median HbA1c at 3 years postdiagnosis was lower for the 0–3 and 3–6 months groups compared with the 6–12 months and non-CGM user groups (7.9%, 7.9%, 8.4%, and 9.5%, respectively). Adjusted odds of HbA1c &amp;gt;9% were lowest for the 0–3 months group followed by the 3–6 months group. CONCLUSIONS In summary, early initiation of CGM within the first 6 months of diagnosis is associated with improved HbA1c outcomes at 3 years postdiagnosis.
Impact of postpartum physical activity on maternal sleep: a systematic review and meta-analysis
Authors: Paris A T Jones, Stephanie-May Ruchat, Zain Khan-Afridi, Muhammad Usman Ali, Brittany A Matenchuk, Sierra Leonard, Andrew WE Jantz, Kier Vander Leek, Lauren Maier, Laura Osachoff, Melanie J Hayman, Milena Forte, Allison Sivak, Margie H Davenport
Journal: British Journal of Sports Medicine (2025)

Objective To examine the relationship between postpartum physical activity and maternal sleep. Design Systematic review with random-effects meta-analysis. Online databases were searched through 20 January 2025. Study eligibility criteria Studies of all designs (except case studies and reviews) in all languages were eligible if they contained information on the population (individuals up to 1 year post partum); interventions/exposures (including subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone (‘exercise only’) or in combination with other intervention components (eg, dietary; ‘exercise+co-intervention’)); comparator (low volume or no physical activity) and outcomes: sleep duration, quality, latency, efficiency, disturbance and fatigue. Results 12 unique studies (n=3096) from nine countries were included. Moderate certainty of evidence showed that exercise-only interventions were associated with a greater improvement in sleep quality (five randomised controlled trials (RCTs), n=375, standardised mean difference (SMD) −0.44, 95% CI −0.79 to –0.09) compared with no exercise. High certainty of evidence showed that exercise interventions were associated with a greater improvement in daytime/general fatigue (six RCTs, n=535, SMD −0.56, 95% CI −1.06 to –0.05) compared with no exercise. No effect was found for sleep duration, latency, efficiency, or disturbance. Conclusion Postpartum physical activity improves maternal sleep quality and daytime/general fatigue.
Sleep quantity and quality during the first week postinjury and time to symptom resolution in youth with concussion
Authors: Olivia VonDeylen, Enas Alshaikh, Krista Wheeler, Robyn Recker, Paola Malerba, Amy Valasek, Keith Owen Yeates, Jingzhen Yang
Journal: British Journal of Sports Medicine (2025)

Objective To examine bidirectional associations between objective measures of sleep quantity and quality with postconcussion symptoms (PCS) scores in concussed youth during the first week postinjury and to explore the associations between sleep measures and time to symptom resolution. Study design We conducted a secondary analysis of a prospectively enrolled cohort of youth (11–17 years) with a physician diagnosed concussion within 72 hours of injury. During the first week postconcussion, sleep quantity (time in bed, total sleep time and daytime sleep) and sleep quality (sleep efficiency, WASO and number of awakenings) were measured using an ActiGraph. We evaluated bidirectional temporal associations between the sleep measures and PCS during the first week postinjury using cross-lagged panel models. We assessed the associations between sleep measures and time to symptom resolution using Cox proportional hazard models. Results Participants included 78 concussed youth, 34.6% females, mean age of 14.2 years (SD=2.1). Significant bidirectional associations were observed between PCS and both total sleep time and daytime total sleep in the first week postinjury. Increased daytime sleep was also associated with a decreased likelihood of symptom resolution, adjusted HR (aHR)=0.88, 95% CI=0.78, 0.999. An optimal total sleep time of 418 min per day was associated with a 2.1-fold increased likelihood of symptom resolution (aHR=2.1, 95% CI=1.3, 3.2). Conclusions Clinicians should provide guidance on sleep hygiene, including limiting daytime sleep/naps and getting the appropriate amount of nighttime sleep acutely postconcussion to aid recovery in youth.
Enhanced thrombopoiesis supplies PD-L1 to circulating immune cells via the generation of PD-L1-expressing platelets in patients with lung cancer
Authors: Sung-Woo Lee, Saei Jeong, Young Ju Kim, Jeong Eun Noh, Kyung Na Rho, Hee-Ok Kim, Hyun-Ju Cho, Deok Hwan Yang, Eu Chang Hwang, Woo Kyun Bae, Sook Jung Yun, Ju Sik Yun, Cheol-Kyu Park, In-Jae Oh, Jae-Ho Cho
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background The increased expression of programmed cell death ligand 1 (PD-L1) on a subset of immune cells in the peripheral blood has been frequently observed in patients with cancer, suggesting a relationship with PD-L1 expression in tumor tissues. In this study, we investigated the mechanisms underlying PD-L1 expression on various types of immune cells in the peripheral blood of patients with cancer. Methods PD-L1 expression on various immune cell populations was analyzed in peripheral blood mononuclear cells of 112 patients with non-small cell lung cancer (NSCLC) using flow cytometry. A mouse model of X-ray-induced acute thrombocytopenia was used to investigate the relationship between thrombopoiesis and PD-L1-expressing platelet generation. The clinical significance of PD-L1-expressing platelets was analyzed in a cohort of patients with stage IV NSCLC who received a combination of anti-programmed cell death 1 (PD-1) therapy and chemotherapy. Results All immune cell populations, including monocytes, T cells, B cells, and NK cells, showed higher PD-L1 expression in patients with cancer than in healthy controls. However, this increased frequency of PD-L1-expressing cells was not attributed to the expression of the cells themselves. Instead, it was entirely dependent on the direct interaction of the cells with PD-L1-expressing platelets. Notably, the platelet-dependent acquisition of PD-L1 on circulating immune cells of patients with lung cancer was observed in various other cancer types and was mechanistically associated with a surge in thrombopoiesis, resulting in the increased production of PD-L1-expressing reticulated platelets. Clinically, patients with enhanced thrombopoiesis and concurrently high PD-L1-expressing platelets exhibited a better response to anti-PD-1 therapy. Conclusions These findings highlight the role of tumor-associated thrombopoiesis in generating PD-L1-expressing platelets that may serve as a resource for PD-L1-positive cells in the circulation and act as a predictive biomarker for anti-PD-1/PD-L1 therapy.
Neutrophil extracellular traps impede cancer metastatic seeding via protease-activated receptor 2-mediated downregulation of phagocytic checkpoint CD24
Authors: Yu Liu, Jianhui Ma, Yiming Ma, Bing-Zhi Wang, Yinong Wang, Junhu Yuan, Fanyu Zhang, Xinhua Zhao, Kun Chen, Xiaoli Zhang, Hongying Wang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Phagocytic clearance by macrophages represents a critical immune surveillance mechanism in cancer liver metastasis. Neutrophils, the most abundant immune cells encountered by cancer cells in circulation, play key roles in metastasis through neutrophil extracellular traps (NETs). Although NETs promote macrophage phagocytosis during infection, whether they regulate phagocytosis during cancer metastasis is unknown. The present study aimed to explore the roles of NETs in regulating macrophage phagocytosis during the seeding process of liver metastasis and the mechanisms underlying the roles. Methods A lipopolysaccharide-induced NET model was applied to study the role of NETs on colorectal cancer (CRC) liver metastasis. The neutrophils isolated from human peripheral blood were stimulated with PMA to release NETs, which were collected and added to the cultures of different CRC cell lines for in vitro studies. Macrophage phagocytosis was assessed with flow cytometry in vitro and in vivo. RNA-seq and microRNA array analyses were performed to identify key pathways regulated by NETs and downstream key molecules. The macrophage phenotypes were evaluated using immunohistochemistry, flow cytometry, and cytokine and chemokine arrays. Results NETs promote macrophage phagocytosis both in vitro and in vivo. Neutrophil elastase (NE), which was able to inactivate the canonical signal of protease-activated receptor 2 (PAR2), downregulated the phagocytotic checkpoint CD24. Notably, PAR2 deficiency imitated the effect of NETs on phagocytosis and CD24. Mechanistic studies indicated that inhibiting PAR2 expression upregulated miR-34a and miR-146a and downregulated CD24 in cancer cells. In addition, PAR2 depletion enhanced the recruitment and M1 polarization of macrophages by upregulating CSF-1 and CXCL1. The correlation of NETs/NE and CD24 was corroborated using human CRC specimens. Furthermore, PAR2 blockade combined with an anti-EGFR antibody (cetuximab (CTX)) synergistically enhanced the phagocytic ability of macrophages and suppressed liver metastasis in vivo. Conclusions NET-derived elastase inactivated PAR2 canonical signaling and promoted phagocytosis by downregulating CD24, which functions as a phagocytotic checkpoint in CRC liver metastasis. Thus, PAR2 inhibitors combined with CTX may serve as a novel therapeutic strategy against advanced CRC.
A First-in-Class JAK/ROCK Inhibitor, Rovadicitinib, for Glucocorticoid-Refractory or -Dependent Chronic GVHD
Authors: Yanmin Zhao, Yi Luo, Jimin Shi, Shunqing Wang, Caixia xia Wang, Erlie Jiang, Chen Liang, Xiaoyu Zhu, Xuejun Zhang, Fankai Meng, Hua Jin, Yeqian Zhao, Jian Yu, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Yishan Ye, Congxiao Zhang, Tao Wang, Lifan Tu, Xunqiang Wang, He Huang
Journal: Blood (2025)
STING activation improves T-cell-engaging immunotherapy for acute myeloid leukemia
Authors: Andreas Linder, Daniel Nixdorf, Niklas Kuhl, Ignazio Piseddu, Teng Teng Xu, Anne Verena Holtermann, Gunnar Kuut, Rebekka Elena Endres, Nora Philipp, Veit L. Bücklein, Johann de Graaff, Thomas Carell, Sebastian Kobold, Roman Kischel, Veit Hornung, Marion Subklewe
Journal: Blood (2025)

T-cell recruiting bispecific antibodies (BsAbs) are in clinical development for relapsed/refractory acute myeloid leukemia (AML). Despite promising results, early clinical trials have failed to demonstrate durable responses. We investigated whether activation of the innate immune system through stimulator of interferon genes (STING) can enhance target-cell killing by a BsAb targeting CD33 (CD33 BiTE® molecule, AMG 330). Indeed, we show that cytotoxicity against AML mediated by AMG 330 can be greatly enhanced when combined with the STING agonist 2',3'-cyclic GMP-AMP (cGAMP), or diABZI. We used in vitro cytotoxicity assays, immunoblotting, transcriptomic analyses, and extensive CRISPR-Cas9 knockout experiments to investigate the enhancing effect of a STING agonist on the cytotoxicity of AMG 330 against AML. Importantly, we validated our findings with primary AML cells, and in a xenograft AML model. Mechanistically, in addition to direct cytotoxic effects of STING activation on AML cells, activated T cells render AML cells more susceptible to STING activation through their effector cytokines interferon-gamma (IFNγ) and tumor necrosis factor (TNF), resulting in enhanced type I interferon production and induction of interferon-stimulated genes. This feeds back to the T cells, leading to a further increase in effector cytokines and an overall cytotoxic T-cell phenotype, contributing to the beneficial effect of cGAMP/diABZI in enhancing AMG 330-mediated lysis. We established a key role for IFNγ in AMG 330-mediated cytotoxicity against AML cells, and in rendering AML cells responsive to STING agonism. Here, we propose to improve the efficacy of CD33-targeting BsAbs by combining them with a STING agonist.