Knockout of the inhibitory receptor TIGIT enhances the antitumor response of ex vivo expanded NK cells and prevents fratricide with therapeutic Fc-active TIGIT antibodies by Dean A Lee, Jeremiah L Oyer, Md Faqrul Hasan, Tayler J Croom-Perez, Liza D Robles-Carrillo, Sanjana Kumar, Brendan W Andersen, Brian P Tullius, Alicja J Copik, Amanda R Campbell, Thomas A Dieffenthaller, Catherine A Cash, Jonathan E Eloriaga, Meisam Naeimi Kararoudi

“…Most of the TIGIT antibodies in development have an Fc-active domain, which binds to Fc receptors on effector cells. In mouse models, Fc-active anti-TIGIT induced superior immunity, while Fc receptor engagement was required for its efficacy. …”
Get full text

Post-extrasystolic variation of ST segment and T wave as a mortality risk predictor after myocardial infarction by Ralf J. Dirschinger, Ralf J. Dirschinger, Alexander Müller, Petra Barthel, Alexander Steger, Michael Dommasch, Axel Bauer, Karl-Ludwig Laugwitz, Georg Schmidt, Daniel Sinnecker, Daniel Sinnecker

“…Kaplan-Meier curves and univariable/multivariable Cox proportional hazards models were used to study mortality prediction by PEST. …”
Get full text

Sex and outcomes of patients with microsatellite instability-high and BRAF V600E mutated metastatic colorectal cancer receiving immune checkpoint inhibitors by Michael Hoffmeister, Hermann Brenner, Chiara Cremolini, Sara Lonardi, Filippo Pietrantonio, Julien Taieb, David Tougeron, Robyn L Ward, Marco Vitellaro, Thierry André, Pierre Laurent-Puig, Jitendra Jonnagaddala, Francesca Bergamo, Raghav Sundar, Claire Gallois, Michael J Overman, Jakob Nikolas Kather, Lisa Salvatore, Romain Cohen, Rossana Intini, Priya Jayachandran, Miriam Koopman, Javier Ros, Marwan Fakih, Vincenzo Nasca, Giacomo Mazzoli, Jeanine M L Roodhart, Filippo Ghelardi, Elena Elez, Durgesh Wankhede, Marta Ligero, Joseph Zhao, Koen Zwart, Jeroen Derksen, Nicholas Hawkins, Javier Carmona

“…Finally, we explored two public microarray and RNA-seq datasets from patients with non-metastatic or metastatic MSI-H CRC to gain translational insights on the association between sex, BRAF status and immune contextures/ICI efficacy.Results Although no differences were observed between females and males either overall or in the BRAF wild-type cohort, male sex was associated with inferior progression-free survival (PFS) and overall survival (OS) in the BRAF mutated cohort (in multivariable models, HR for PFS: 1.79, 95% CI: 1.13 to 2.83, p=0.014, and for OS: 2.33, 95% CI: 1.36 to 3.98, p=0.002). …”
Get full text

Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy by Coraline Radermecker, Pascale Hubert, Patrick Roncarati, Stephanie Demoulin, Charlotte Pilard, Marie Ancion, Celia Reynders, Thomas Lerho, Diane Bruyere, Alizee Lebeau, Margot Meunier, Marie-Julie Nokin, Elodie Hendrick, Olivier Peulen, Philippe Delvenne, Michael Herfs

“…Using several orthotopic, syngeneic mouse models of basal-like breast (4T1, 67NR and EpRas) or non-small cell lung (TC-1) cancer, the efficacy of several HMGB1 inhibitors alone and in combination with immune checkpoint blockade antibodies (anti-PD-1/PD-L1) was then investigated. …”
Get full text

Dog demography and ecology with reference to rabies in the Amhara region, Ethiopia by Liuel Yizengaw Adnie, Wudu Temesgen Jemberu, Adane Bahiru Woreta, Adugna Berju, Araya Mengistu, Zeleke Tesema Wondie, Wassie Molla, Sefinew Alemu Mekonnen

“…Mixed-effect logistic regression models were used to identify factors associated with dog ownership and rabies occurrence. …”
Get full text

Effectiveness of a physiotherapist-led triage and treatment service on WAITing time for adults with musculoskeletal pain referred to Australian public hospital physiotherapy clinic... by Ian A Harris, Andrew Lawson, Bethan Richards, Chris G Maher, Laurent Billot, David Roberts, Chris Needs, David Anderson, Nadine E Foster, Danielle Coombs, Marnee McKay, Joshua R Zadro, Tarcisio F de Campos, Michael Swain, Daniel Treacy, Lisa A Harvey, Gustavo Machado, Jackie Chu, Christopher S Han, Andrew R Gamble, Timothy Shaw, Mark Halliday, Joshua M Hutton, Tom Lung, Lisa Gridley, Joshua Wakefield

“…Introduction Musculoskeletal pain is the second leading cause of disease burden in Australia, and there is a need to investigate new models of care to cope with the increasing demand for health services. …”
Get full text

Discontinuation of immune checkpoint inhibitors for reasons other than disease progression and the impact on relapse and survival of advanced melanoma patients. A systematic review... by Konstantinos Lallas, Eftychia Chatziioannou, Derya Durak, Georg Frey, Lina Maria Serna-Higuita, Marie-Lena Rasch, Athanassios Kyrgidis, Eleni Timotheadou, Zoe Apalla, Ulrike Leiter, Lukas Flatz, Lukas Flatz, Aimilios Lallas, Teresa Amaral, Teresa Amaral

“…Relapse rates (RRs) post cessation, time to PD, rechallenge and disease control rate (DCR) after 2nd course were the main outcomes. Random-effects models were preferred, and subgroup and sensitivity analyses were conducted to investigate possible sources of heterogeneity.Results38 and 35 studies were included in qualitative and quantitative synthesis, respectively. …”
Get full text

An integrative analysis of ASCL1 in breast cancer and inhibition of ASCL1 increases paclitaxel sensitivity by activating ferroptosis via the CREB1/GPX4 axis by Xiaolu Yang, Xiaolu Yang, Yilun Li, Yilun Li, Yaqi Peng, Yuan Chang, Binglu He, Binglu He, Tianqi Zhang, Tianqi Zhang, Shiyu Zhang, Cuizhi Geng, Yunjiang Liu, Xiaolong Li, Jun Hao, Li Ma

“…Functional assays were conducted on BC cell lines MCF-7 and MDA-MB-231, and nude mouse models were used for in vivo studies.ResultsASCL1 was found to be upregulated in BC and correlated with unfavorable prognosis and mutations in key oncogenes. …”
Get full text

Histamine N-methyltransferase (HNMT) as a potential auxiliary biomarker for predicting adaptability to anti-HER2 drug treatment in breast cancer patients by Tzu-Chun Cheng, Mien-Chie Hung, Lu-Hai Wang, Shih-Hsin Tu, Chih-Hsiung Wu, Yun Yen, Chi-Long Chen, Jacqueline Whang-Peng, Wen-Jui Lee, You-Cheng Liao, Yu-Ching Lee, Min-Hsiung Pan, Hui-Kuan Lin, Huey-En Tzeng, Peixuan Guo, Cheng-Ying Chu, Li-Ching Chen, Yuan-Soon Ho

“…Methods We investigated the impact of HNMT protein expression on the efficacy of anti-HER2 therapy in both in vivo and ex vivo models of patient-derived xenografts and cell line-derived xenografts. …”
Get full text

Comparison of objectively measured and estimated cardiorespiratory fitness to predict all-cause and cardiovascular disease mortality in adults: A systematic review and meta-analysi... by Ben Singh, Cristina Cadenas-Sanchez, Bruno G.G. da Costa, José Castro-Piñero, Jean-Philippe Chaput, Magdalena Cuenca-García, Carol Maher, Nuria Marín-Jiménez, Ryan McGrath, Pablo Molina-García, Jonathan Myers, Bethany Gower, Francisco B. Ortega, Justin J. Lang, Grant R. Tomkinson

“…Pooled relative risks (RR) for all-cause and CVD mortality per 1-MET (3.5 mL/kg/min) higher level of CRF were quantified using random-effects models. Results: Forty-two studies representing 35 cohorts and 3,813,484 observations (81% male) (362,771 all-cause and 56,471 CVD deaths) were included. …”
Get full text

Relationship between pharmacotherapy for major depressive disorder and healthcare utilisation in British Columbia, Canada: a retrospective population-based cohort by Sonya Cressman, Louisa Edwards, Kimberlyn McGrail, Stirling Bryan, Alison Hoens, Rohit Vijh, Sandra Peterson, Zeina Waheed, Mary Bunka, Nick Pang, Shahzad Ghanbarian, Gavin Wong, Linda Riches, Jehannine Austin

“…Objectives To describe the population that meets the criteria for major depressive disorder (MDD) in British Columbia (BC), compare patterns of healthcare utilisation between those with MDD who are and are not prescribed pharmacotherapy, and assess these relationships in models that control for potential confounding variables.Design We used a population cross-sectional study design among a cohort of individuals living with MDD and examined the relationship between pharmacotherapy and healthcare utilisation between 2019 and 2020 using linked billing and administrative data.Setting This study identified individuals with MDD using a validated case definition of International Classification of Diseases (ICD) codes in BC, Canada.Participants The final study cohort included 549 029 adult participants who met the MDD case definition.Explanatory variable Explanatory variable was the use of prescription antidepressant medication during the study period, based on BC PharmaNet data.Covariates Covariates include sociodemographic characteristics (age, sex, urban/rural residence, neighbourhood income quintile and comorbidities).Primary outcome measure Primary outcome measure was healthcare utilisation (outpatient physician visits, emergency department (ED) visits and hospitalisations).Results We stratified our analysis based on whether study participants were classified as ‘recently incident’ or ‘actively prevalent’. …”
Get full text

Associations between Children’s Exposure to PM2.5 and their Serum Inflammatory Responses in Taiwan by Wei-Jung Tseng, Jian-He Lu, How-Ran Chao, Ming-Hsien Tsai, Yu-Ting Chang, Liang-Jen Wang, Chih-Cheng Chen, Wan-Nurdiyana-Wan Mansor, Juliana Jalaludin, Chih-Lung Wang, Ying-I Tsai

“…Abstract PM2.5-induced inflammation have been demonstrated in the cellular and animal models, but few studies reported the associations of schoolchildren exposure to PM2.5 with their serum inflammatory biomarkers. …”
Get full text

Identifying subgroup of severe community-acquired pneumonia based on clinical metagenomics, a multicenter retrospective cohort study by Mingqiang Wang, Mingqiang Wang, Yue Jin, Yue Jin, Wenxiao Zhang, Wenxiao Zhang, Ling Ye, Ling Ye, Huanzhang Shao, Huanzhang Shao

“…Latent class analysis (LCA) was applied to routine clinical parameters such as gender, age, white blood cell (WBC), lymphocytes, C-reactive protein (CRP), and Procalcitonin (PCT), identifying two optimally fitting models.ResultsA total of 569 patients were enrolled. …”
Get full text

Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterization by Manuel P. Kainz, Mathias Polz, Daniel Ziesel, Marta Nowakowska, Muammer Üçal, Sabine Kienesberger, Sophie Hasiba-Pappas, Raimund Winter, Nassim Ghaffari Tabrizi-Wizsy, Sarah Kager, Theresa Rienmüller, Julia Fuchs, Michele Terzano, Christian Baumgartner, Gerhard A. Holzapfel

“…CAM assays, as an alternative to traditional in vivo models, enabled the evaluation of the compatibility, attachment, and biointegration of hydrogels with three distinct compositions. …”
Get full text

Association of pre- and post-diagnosis dietary total antioxidant capacity (TAC) and composite dietary antioxidant index (CDAI) with overall survival in patients with ovarian cancer... by Dong-Dong Wang, Ming-Qian Jia, He-Li Xu, Yu Li, Jia-Xin Liu, Jia-Cheng Liu, Jia-Nan Sun, Fan Cao, Lang Wu, Fang-Hua Liu, Yi-Zi Li, Yi-Fan Wei, Xiao-Ying Li, Qian Xiao, Song Gao, Dong-Hui Huang, Tao Zhang, Ting-Ting Gong, Qi-Jun Wu

“…Multivariable Cox proportional-hazards models were applied to calculate the hazard ratios (HR) and 95% confidence intervals (CI). …”
Get full text

Clonal hematopoiesis of indeterminate potential is a risk factor of gastric cancer: A Prospective Cohort in UK Biobank study by Zhihui Xi, Huolun Feng, Kunling Chen, Xin Guo, Dandan Zhu, Jiabin Zheng, Yong Li

“…Main outcomes and measures: Odds ratio (OR) of CHIP with gastric cancer risk was estimated using multivariable logistic regression models. Participants were grouped based on age and CHIP status to examine if there are differences in the cumulative incidence of gastric cancer. …”
Get full text

Tobacco control environment: cross-sectional survey of policy implementation, social unacceptability, knowledge of tobacco health harms and relationship to quit ratio in 17 low-inc... by Annika Rosengren, Li Wei, Khalid Yusoff, Martin McKee, Clara K Chow, Rajeev Gupta, Koon Teo, Sumathy Rangarajan, Patricio Lopez-Jaramillo, Rafael Diaz, Alvaro Avezum, Fernando Lanas, Noorhassim Ismail, Romaina Iqbal, Jephat Chifamba, Gilles Dagenais, Salim Yusuf, Anna B Gilmore, Scott Lear, Wang Yang, Omar Rahman, Katarzyna Zatonska, Prem Mony, Rajesh Kumar, Afzalhussein Yusufali, Daniel J Corsi, Ehimario Igumbor, V Mohan, Annamarie Kruger, Krishnapillai Vijayakumar, Yuksel Altuntas, Ahmad Bahonar

“…Objectives This study examines in a cross-sectional study ‘the tobacco control environment’ including tobacco policy implementation and its association with quit ratio.Setting 545 communities from 17 high-income, upper-middle, low-middle and low-income countries (HIC, UMIC, LMIC, LIC) involved in the Environmental Profile of a Community's Health (EPOCH) study from 2009 to 2014.Participants Community audits and surveys of adults (35–70 years, n=12 953).Primary and secondary outcome measures Summary scores of tobacco policy implementation (cost and availability of cigarettes, tobacco advertising, antismoking signage), social unacceptability and knowledge were associated with quit ratios (former vs ever smokers) using multilevel logistic regression models.Results Average tobacco control policy score was greater in communities from HIC. …”
Get full text

High-resolution 4D electrical resistivity tomography and below-ground point sensor monitoring of High Arctic deglaciated sediments capture zero-curtain effects, freeze–thaw transit... by M. O. Cimpoiasu, O. Kuras, H. Harrison, P. B. Wilkinson, P. Meldrum, J. E. Chambers, D. Liljestrand, C. Oroza, S. K. Schmidt, P. Sommers, L. Vimercati, T. P. Irons, Z. Lyu, A. Solon, J. A. Bradley, J. A. Bradley

“…Novel insights into soil moisture dynamics throughout the spring melt will help parameterize models of biological activity to build a more predictive understanding of newly emerging terrestrial landscapes and their impact on carbon and nutrient cycling.…”
Get full text

Exosomal mir-126-3p derived from endothelial cells induces ion channel dysfunction by targeting RGS3 signaling in cardiomyocytes: a novel mechanism in Takotsubo cardiomyopathy by Xuehui Fan, Guoqiang Yang, Yinuo Wang, Haojie Shi, Katja Nitschke, Katherine Sattler, Mohammad Abumayyaleh, Lukas Cyganek, Philipp Nuhn, Thomas Worst, Bin Liao, Gergana Dobreva, Daniel Duerschmied, Xiaobo Zhou, Ibrahim El-Battrawy, Ibrahim Akin

“…The immunofluorescence staining, flow cytometry, qPCR, single-cell contraction, intracellular calcium transients, patch-clamp, dual luciferase reporter assay and western blot were performed for the study. Results Modeling TTC with high doses of epinephrine (Epi) treatment in hiPSC-CMs shows suppression of depolarization velocity (Vmax), prolongation of action potential duration (APD), and induction of arrhythmic events. …”
Get full text

HDAC and MEK inhibition synergistically suppresses HOXC6 and enhances PD-1 blockade efficacy in BRAFV600E-mutant microsatellite stable colorectal cancer by Xin Li, Peng Yang, Jin Gu, Nan Chen, Dengbo Ji, Jinhong Xia, Jinying Jia, Zhuang Sun, Mengyuan Shi, Hanyang Wang, Zhaoya Gao

“…This study aims to identify a novel therapeutic strategy for this challenging subgroup.Methods We first performed a large-scale drug screening using patient-derived organoid models and cell lines to pinpoint potential therapies. …”
Get full text