The absolute number of circulating Treg cells is reduced in difficult-to-treat RA patients and is ameliorated by low-dose IL-2 by Huanhuan Yan, Huanhuan Yan, Huanhuan Yan, Xiaoyu Zi, Xiaoyu Zi, Xiaoyu Zi, Huer Yan, Xiaoying Zhang, Xiaoying Zhang, Xiaoying Zhang, Jie Bai, Jie Bai, Jie Bai, Chong Gao, Xiaofeng Li, Xiaofeng Li, Xiaofeng Li, Caihong Wang, Caihong Wang, Caihong Wang

“…ObjectiveCirculating regulatory T cells (Tregs) are closely related to immune tolerance and maintenance of immune homeostasis. Perhaps, there is a unique immune cell phenotype for difficult-to-treat rheumatoid arthritis (D2T RA). …”
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Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2 by Hemant M. Kocher, BCI-STARPAC2 team, BPTB team, Precision-Panc team, Peter Sasieni, Pippa Corrie, Mairéad G. McNamara, Debashis Sarker, Fieke E. M. Froeling, Alan Christie, Roopinder Gillmore, Khurum Khan, David Propper

“…Secondary endpoints include objective response rate (ORR), overall survival (OS), safety and tolerability, surgical resection rate, R0 surgical resection rate and patient reported outcome measures (PROMS) as measured by questionnaire EQ-5D-5L. …”
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Extracorporeal Hemadsorption versus Glucocorticoids during Cardiopulmonary Bypass: A Prospective, Randomized, Controlled Trial by Gordana Taleska Stupica, Maja Sostaric, Marija Bozhinovska, Lea Rupert, Zoran Bosnic, Ales Jerin, Alojz Ihan, Tomislav Klokocovnik, Matej Podbregar

“…Hemadsorption with CytoSorb® was safe and well tolerated. This trial is registered with clinicaltrials.gov (NCT02666703).…”
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Prognostic significance of PD‐L2 expression in patients with oral squamous cell carcinoma—A comparison to the PD‐L1 expression profile by Manuel Weber, Falk Wehrhan, Christoph Baran, Abbas Agaimy, Maike Büttner‐Herold, Marco Kesting, Jutta Ries

“…In the peripheral blood, PD‐L1 might be more relevant for immune tolerance than PD‐L2. Local PD‐L2 expression in tissue samples might be useful as a diagnostic parameter for malignancy and could contribute to the immunosuppressive local microenvironment in OSCC.…”
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The DnaJ-Hsp70-Hsp90 co-chaperon networks in scallops under toxic Alexandrium dinoflagellates exposure by Moli Li, Jie Cheng, Huizhen Wang, Jiaoxia Shi, Xiaogang Xun, Wei Lu, Xubo Wang, Jingjie Hu, Zhenmin Bao, Xiaoli Hu

“…Marine bivalves could accumulate and tolerate paralytic shellfish toxins (PSTs), the well-noted neurotoxins generated during harmful algal blooms. …”
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Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III... by Roger Owen, John Jones, David Meads, David A Cairns, Christopher Parrish, Gordon Cook, Neil Rabin, Matthew Jenner, Martin Kaiser, Kevin Boyd, Graham Jackson, Catherine Olivier, Amy Beth Coulson, Kara-Louise Royle, Charlotte Pawlyn, Anna Hockaday, Jennifer Bird, Stella Bowcock, Ruth de Tute, Hayley Gardner, Bryony Dawkins, Rowena Henderson, Phillip Best, Bhuvan Kishore, Mark Drayson

“…Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life.Methods and analysis Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a national, phase III, multicentre, randomised controlled trial comparing standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide to lenalidomide+ixazomib, in patients with newly diagnosed multiple myeloma not suitable for stem cell transplant. …”
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Safety and efficacy of trifluridine/tipiracil +/− bevacizumab plus XB2001 (anti-IL-1α antibody): a single-center phase 1 trial by Marion Thibaudin, Nicolas Roussot, Chloé Burlot, Antonin Schmitt, Julie Vincent, Zoé Tharin, Leila Bengrine, Hélène Bellio, Aurélie Bertaut, Léa Hampe, Susy Daumoine, Emilie Rederstorff, Morgane Peroz, Titouan Huppe, Valentin Derangère, David Rageot, John Simard, Caroline Truntzer, Jean David Fumet, Francois Ghiringhelli

“…This single institution, phase 1 study used a 3 + 3 design to assess XB2001 at doses of 250 mg, 500 mg and 1000 mg every 14 days, associated with FTD/TPI 35 mg/m² (days 1–5 and 8-12, every 28 days) (NCT05201352). The Maximum Tolerated Dose of XB2001 + FTD/TPI was then associated in combination with bevacizumab (5 mg/kg, days 1 and 15). …”
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Aurora B inhibition induces hyper-polyploidy and loss of long-term proliferative potential in RB and p53 defective cells by Shivam Vora, Saptarshi Chatterjee, Ariel Andrew, Ramyashree Prasanna Kumar, Martina Proctor, Zhen Zeng, Rituparna Bhatt, Deborah Nazareth, Madushan Fernando, Mathew J. K. Jones, Yaowu He, John D. Hooper, Nigel A. J. McMillan, Jelena Urosevic, Jamal Saeh, Jon Travers, Daniela Cimini, Jing Chen, Brian Gabrielli

“…These findings demonstrate that tetraploidy is tolerated by tumour cells, but higher ploidy states are incompatible with long-term proliferative potential. …”
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Sangre Por Salud (SPS) Biobank: cohort profile by Richard R Sharp, Euijung Ryu, Janet E Olson, Karen Meagher, James R Cerhan, Davinder Singh, Suzette Bielinski, Emmil Zarrugh, Marlene E Girardo, Giovanna Moreno Garzon, Valentina Hernandez, Sharon Levey, Crystal Gonzalez, Daniela B Pompa, Gabriel Q Shaibi, Lawrence Mandarino, Steven Thibodeau, Elena De Filippis

“…As part of the study, participants consented and agreed to be contacted for potential participation in future research studies.Findings to date 3756 participants provided informed consent, of whom 3733 completed all study questionnaires, an oral glucose tolerance test and had blood collected and stored. …”
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Adipose tissue-derived microRNA-450a-5p induces type 2 diabetes mellitus by downregulating DUSP10 by Jiaojiao Zhu, Yanting Hou, Wei Yu, Jingzhou Wang, Xiaolong Chu, Xueting Zhang, Huai Pang, Dingling Ma, Yihan Tang, Menghuan Li, Chenggang Yuan, Jianxin Xie, Cuizhe Wang, Jun Zhang

“…Additionally, microRNA-450a-5p was found to regulate DUSP10 expression and insulin signaling activity, influencing glucose tolerance and insulin sensitivity across various models, including normal diet, HFD-induced obese, adipose tissue-specific microRNA-450a-5p-knockout, and db/db mice. …”
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Genome-wide identification of MGT gene family in soybean (Glycine max) and their expression analyses under magnesium stress conditions by Ammar Anwar, Junaid Akhtar, Saba Aleem, Maida Aleem, Muhammad Khuram Razzaq, Saud Alamri, Qasim Raza, Iram Sharif, Arooj Iftikhar, Shehreen Naseer, Zaheer Ahmed, Iqrar Ahmed Rana, Waheed Arshad, Muhammad Imran Khan, Javaid Akhter Bhat, Muqadas Aleem, Abdel-Rhman Z. Gaafar, Mohamed S. Hodhod

“…Furthermore, the upregulation of GmMGT2 and GmMGT29 in tolerant genotypes in response to Mg-deficiency as well as surplus stress conditions in leaves suggested the essential role of GmMGT genes in the absorption and transportation of Mg in soybean leaves. …”
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Mutational Analysis of KCNQ1 Gene in Type 2 Diabetes Mellitus: A Case-control Study by Ankush Ganjewar, Ishwar B Bagoji, Sharan Badiger, Rudragouda B Bulagouda, Gurushnatappa Kadakol

“…KCNQ1 is also associated with impaired insulin secretion in Type 2 Diabetes Mellitus (T2DM), suggesting that this impairment might underlie the diabetes susceptibility conferred by rs151290, which is associated with 30-min C-peptide levels during an Oral Glucose Tolerance Test (OGTT) and first-phase insulin secretion. …”
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Composite microbial agent improves cotton yield and resource use efficiency under mild salt stress by optimizing plant resource allocation by Xiao Zhao, Panpan Guo, Xiong Wu, Meng Zhu, Shaozhong Kang, Taisheng Du, Jian Kang, Jinliang Chen, Ling Tong, Risheng Ding, Wanli Xu, Guangmu Tang

“…The application of salt-tolerant composite plant growth-promoting rhizobacteria (STC-PGPR) is considered an effective strategy to address these issues. …”
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People’s knowledge, attitudes, and conflicts with carnivores in central hills, Sri Lanka by Ashan Thudugala, Hem Bahadur Katuwal, Nalindra Laxman, Vishwa Dushmantha, Ravindi Menikrama, Harsha Dissanayake, Chameera Dilshan, Ru-Chuan He, Rui-Chang Quan

“…It also underscores the importance of improving protection measures for domestic animals and establishing compensation schemes and performance payments to enhance tolerance, coexistence, and foster positive attitudes toward these species.…”
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Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer by Jun Fan, Jing Wang, Tao Zhang, Xin Li, Lan Zhang, Zheng Wang, Tao Liu, Gang Li, Peng Zhang, Chi Ma, Ming Cai, Gang Wu, Zhenyu Lin, Kailin Cai, Xiu Nie, Junli Liu, Hongli Liu, Weikang Zhang, Jingbo Gao, Chuanqing Wu, Linfang Wang, Zhiguo Hou, Kunyu Yang, Kaixiong Tao

“…Biomarker analysis showed patients without FGFR1–3 deletions had a better tendency for pCR.Conclusions SCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery showed a favorable pCR rate with good tolerance in patients with LARC, especially in the proficient MMR setting. …”
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Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathway by Liangzhi Zhang, Xiaojie Liu, Jing Hu, Helong Quan, Sang Ki Lee, Mallikarjuna Korivi, Lifeng Wang, Ting Li, Wei Li

“…Methods Sprague-Dawley rats fed a high-fat diet (HFD), and performed treadmill exercise training for 6-week. Oral glucose tolerance test was conducted to confirm the IR. Periodic Acid-Schiff (PAS) staining and anthrone colorimetry were used to assess the skeletal muscle glycogen. …”
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Protocol for a randomised ‘screen-and-treat’ Helicobacter pylori eradication trial in 14–18-years-old adolescents residing in three regions of Chile: effectiveness and microbiologi... by Ximena Aguilera, Camila Cabrera, Sergio George, Yalda Lucero, Beatriz Zabala Torres, Lilian Fernández, Nora Mamani, Anne Lagomarcino, Miguel O'Ryan

“…Our previous pilot treatment study revealed high eradication rates, favourable tolerance profile and a decline in serum biomarkers indicative of gastric damage in asymptomatic school-aged children. …”
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Increased CCR7loPD-1hiCXCR5+CD4+ T Cells in Peripheral Blood Mononuclear Cells Are Correlated with Immune Activation in Patients with Chronic HBV Infection by Ya-Xin Huang, Qi-Yi Zhao, Li-Li Wu, Dong-Ying Xie, Zhi-Liang Gao, Hong Deng

“…We recruited 20 healthy volunteers and 77 patients with chronic HBV infection, including those in the immune tolerant (IT) phase (n=19), immune clearance (IC) phase (n=20), low replicative (LR) phase (n=18), and reactivation (RA) phase (n=20). …”
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D,L‐3‐hydroxybutyrate in the treatment of glucose transporter 1 deficiency syndrome (Glut1DS) by Aya Amer, Kathryn Murrell, Liza Edmonds, Isaac Bernhardt, Rhonda Akroyd, Bryony Ryder, Callum Wilson, Emma Glamuzina

“…Conclusions KD remains standard of care for Glut1DS, but effective alternatives are lacking for those who do not tolerate this. D,L‐3‐HB was associated with improved WM, PS and perceived life quality in this small group of patients with Glut1DS, thus providing a potential treatment for this distinct group.…”
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Optimization and calibration of 384-well kinetic Ca2+ mobilization assays for the human transient receptor potential cation channels TRPM8, TRPV1, and TRPA1 by David A. Close, V. Blair Journigan, Paul A. Johnston

“…FLIPR Calcium 6 dye concentration, loading time, and TRPM8 transfected cell seeding density were optimized and a DMSO tolerance of ≤0.2 % was set. The resting baseline relative fluorescent unit (RFUs) signals of the TRPM8 Ca2+ mobilization assay exhibited substantial well-to-well variability, even though such differences were small relative to maximal agonist induced responses. …”
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