Targeting chromosomally unstable tumors with a selective KIF18A inhibitor by Aaron F. Phillips, Rumin Zhang, Mia Jaffe, Ryan Schulz, Marysol Chu Carty, Akanksha Verma, Tamar Y. Feinberg, Michael D. Arensman, Alan Chiu, Reka Letso, Nazario Bosco, Katelyn A. Queen, Allison R. Racela, Jason Stumpff, Celia Andreu-Agullo, Sarah E. Bettigole, Rafael S. Depetris, Scott Drutman, Shinsan M. Su, Derek A. Cogan, Christina H. Eng

“…The strong biological rationale, robust preclinical data, and optimized compound properties enable the clinical development of a KIF18A inhibitor in cancers with high chromosomal instability.…”
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Maytansinoids in cancer therapy: advancements in antibody–drug conjugates and nanotechnology-enhanced drug delivery systems by Matteo Perra, Ines Castangia, Matteo Aroffu, Federica Fulgheri, Rita Abi-Rached, Maria Letizia Manca, Hernán Cortés, María Luisa Del Prado-Audelo, Carla Nomura-Contreras, Alejandra Romero-Montero, Dietrich Büsselberg, Gerardo Leyva-Gómez, Javad Sharifi-Rad, Daniela Calina

“…This review highlights the anticancer activity of maytansinoids, with a focus on AMCs designed to target cancer cells specifically. Preclinical and clinical studies show that AMCs, including FDA-approved drugs like Kadcyla and Elahere, effectively inhibit tumor growth while reducing systemic toxicity. …”
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The Number of Frames on ECG-Gated 18F-FDG Small Animal PET Has a Significant Impact on LV Systolic and Diastolic Functional Parameters by Christoph Eissler, Rudolf A. Werner, Paula Arias-Loza, Naoko Nose, Xinyu Chen, Martin G. Pomper, Steven P. Rowe, Constantin Lapa, Andreas K. Buck, Takahiro Higuchi

“…This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. …”
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STD Training in Canadian Medical Schools by Jo-Anne A Doherty, A Gordon Jessamine

“…DESIGN: A four page questionnaire sought information on preclinical, clinical and residency training in terms of the number of classroom and laboratory hours of instruction, the subspecialty responsible for providing the training, and the clinical ‘hands on’ experience of the teachers: each respondent was also asked to assess the quality and scope of instruction provided at his/her medical school. …”
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Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications by Lyubomir Gaydarski, Kristina Petrova, Ivan Angushev, Stancho Stanchev, Alexandar Iliev, Nikola Stamenov, Vidin Kirkov, Boycho Landzhov

“…The apelinergic system, involving apelin and its receptor (APLNR), influences endothelial function, glucose metabolism, and renal health. Preclinical studies highlight its dual role in renal protection and injury through anti-inflammatory and antioxidant pathways, while other evidence suggests that it may exacerbate DKD through podocyte damage and angiogenesis. …”
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Determining the alignment of assessment items with curriculum goals through document analysis by addressing identified item flaws by Humaira Fayyaz Khan, Shazia Qayyum, Huma Beenish, Rehan Ahmed Khan, Samina Iltaf, Lubna Rani Faysal

“…Pre-hoc reports from mid-stake assessments across five academic years were analyzed, covering both preclinical and clinical years. A total of 2,400 multiple-choice questions (MCQs) were reviewed for the mid-stake exams against the institutional checklist in which flaws were categorized into three types: test wiseness, irrelevant difficulty, and miscellaneous flaws. …”
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DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities by Wen-yu Cai, Xin-xian Cai, Yi-ran Fei, Rui Ye, Ding-ming Song, Dan Hu, Wan-wan Zhang, Ming-fei Xia, Xiao-xiao Yang

“…We discuss the underlying mechanisms that enable these therapeutic synergies, preclinical and clinical evidence supporting the approach, and the challenges posed by tumor heterogeneity, drug resistance, and toxicity. …”
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Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy by van Leeuwen JR, Quartuccio L, Draibe JB, Gunnarson I, Sprangers B, Teng YKO

“…We therefore also address in this review the data and clinical experience with avacopan obtained from real-world evidence. Combining preclinical studies, clinical trials, and real-world evidence helps to provide a better position of avacopan for the management of AAV in routine clinical practice, taking advantage of the GC-sparing effects of avacopan as a possible solution for the current challenge of reducing GC-toxicity in AAV patients. …”
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PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/β-CATENIN Pathway in Testosterone-Treated Hypogonadal Men by Siresha Bathina, Mia Prado, Virginia Fuenmayor Lopez, Georgia Colleluori, Lina Aguirre, Rui Chen, Dennis T. Villareal, Reina Armamento-Villareal

“…We previously reported that <i>PRDM16</i> mediated the improvement in body composition in testosterone (T)-treated hypogonadal men by shifting adipogenesis to myogenesis. Previous preclinical studies suggest that <i>Prdm16</i> regulates <i>Runx2</i>, an important osteoblastic transcription factor, expression and activity. …”
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Underlying Anticancer Mechanisms and Synergistic Combinations of Phytochemicals with Cancer Chemotherapeutics: Potential Benefits and Risks by Muhammad Ayaz, Asif Nawaz, Sajjad Ahmad, Osama F. Mosa, Alashary Adam Eisa Hamdoon, Modawy Alnour Khalifa, Abdul Sadiq, Farhat Ullah, Abdul Wadood, Atul Kabra, H. C. Ananda Murthy

“…To counteract these effects, natural products as substitutes and adjuvant therapies have received considerable attention owing to their safety, efficacy, and economic aspects. Various preclinical and clinical studies revealed that natural products and their combinations with chemotherapeutics mediate their anticancer effects via modulation of various signaling pathways implicated in promoting apoptosis, inhibiting excessive cellular proliferation, and mobilizing the immune system. …”
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Cysteinyl Leukotriene Receptor-1 Antagonists as Modulators of Innate Immune Cell Function by A. J. Theron, H. C. Steel, G. R. Tintinger, C. M. Gravett, R. Anderson, C. Feldman

“…These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophils in vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies.…”
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The impact of type 2 diabetes on left ventricular function in hypertensive patients: a three-dimensional speckle-tracking imaging study by Yang Qingmei, Chen Xiaoyan, Fang Jianxiu

“…Furthermore, linear mixed-model analysis revealed that LV GCS (β = 1.20, 95% CI: 0.38–2.01, p = 0.004) and GRS (β = −2.82, 95% CI: −4.97–0.68, p = 0.010) deteriorated over the 12-month period.ConclusionsT2DM exacerbates the decline in LV global and regional strains in patients with hypertension, and 3D-STI may be a valuable tool for detecting these asymptomatic preclinical abnormalities.…”
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Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes by Flavia Bruna, David Contador, Paulette Conget, Benjamín Erranz, Claudia L. Sossa, Martha L. Arango-Rodríguez

“…Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. …”
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The effects of antioxidants, angioprotective agents, and vitamins on retina in complex retinal diseases by I.V. Vorobyeva, A.A. Dement’eva, A. Dgebuadze

“…&nbsp;Dgebuadze</b> </p> <p> <b>Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation</b> </p> <p> <i>Treatment for complex retinal diseases in diabetic retinopathy and age-related macular degeneration (AMD) is still of crucial importance, in particular, in their early and preclinical stages to prevent vision loss. The approaches to treatment choice for AMD are well-known, i.e., various supplements containing antioxidants, vitamins, and microelements are prescribed at early stages. …”
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Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer’s Disease Pathogenesis—From Gut Microbiota and Viruses to Brain Biofilms by Anna Onisiforou, Eleftheria G. Charalambous, Panos Zanos

“…Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. …”
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A novel conditional active biologic anti-EpCAM x anti-CD3 bispecific antibody with synergistic tumor selectivity for cancer immunotherapy by Gerhard Frey, Ana Paula G. Cugnetti, Haizhen Liu, Charles Xing, Christina Wheeler, Hwai Wen Chang, William J. Boyle, Jay M. Short

“…Xenograft studies showed that the efficacy of CAB bispecific antibodies is similar to that of a non-CAB anti-EpCAM bispecific antibody, but they have markedly reduced toxicity in non-human primates, indicating an unprecedentedly widened therapeutic index of over 100-fold. These preclinical results indicate that the dual CAB bispecific antibody is potentially both a powerful and safe therapeutic platform and a promising T cell-engaging treatment for patients with EpCAM-expressing tumors.…”
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Effects of Pioglitazone on Nonalcoholic Fatty Liver Disease in the Absence of Constitutive Androstane Receptor Expression by Hwa Young Ahn, Hwan Hee Kim, Ji-Yeon Hwang, Changhun Park, Bo Youn Cho, Young Joo Park

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Individual differences in training time in the rat gambling task are unrelated to subsequent decision-making strategies by Frida A. Lindberg, Christakis Kagios, Christakis Kagios, Nikita Tjernström, Erika Roman, Erika Roman

“…The rat gambling task (rGT), based on the IGT, is a preclinical test using varying number of palatable reinforcers as wins and different duration of timeouts as punishment, mimicking losses. …”
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Integrated Insights into Metabolic and Bariatric Surgery: Improving Life Quality and Reducing Mortality in Obesity by Ruxandra-Cristina Marin, Andrei-Flavius Radu, Paul Andrei Negru, Ada Radu, Denisa Negru, Raluca Anca Corb Aron, Teodora Maria Bodog, Ruxandra Florina Bodog, Paula Bianca Maghiar, Roxana Brata

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The Musculoskeletal Anatomy of the Komodo Dragon’s Hindlimb (<i>Varanus komodoensis</i>, Varanidae) by Anna Tomańska, Martyna Stawinoga, Tomasz Gębarowski, Maciej Janeczek, Joanna Klećkowska-Nawrot, Karolina Goździewska-Harłajczuk, Maciej Dobrzyński

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