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176 papers

Integrative Transcriptomic and Functional Analysis of PKMYT1 Reveals a Potential Therapeutic Target in Chronic Lymphocytic Leukemia.

Bispo ECI et al. · Jul 1, 2026

Chronic lymphocytic leukemia (CLL) is a clinically and molecularly heterogeneous disease. PKMYT1, a G2/M cell cycle kinase, has been implicated in tumor progression in several cancers, but its role in CLL remains unclear. We evaluated PKMYT1 expression in primary CLL samples and analyzed associations with cytogenetic features and clinical parameters. PKMYT1 expression was heterogeneous and correlated with adverse features, including complex karyotype and elevated leukocyte counts. Comparative transcriptomic analyses between high- and low-expression groups revealed enrichment of pathways related to chromatin remodeling, DNA repair, and mitotic regulation. In MEC1 cells, pharmacological PKMYT1 inhibition significantly reduced cancer cell viability. PCR analysis showed upregulation of TP53, CASP3, BAK, GSDMD, BCL2, CASP1, IL1β, RIPK1, and RIPK3, indicating activation of apoptotic, inflammasome-associated, and necroptotic pathways. Collectively, these findings demonstrate that PKMYT1 is heterogeneously expressed in CLL, associated with adverse cytogenetic and clinical features, and critical for cell survival, highlighting its potential as a therapeutic target.

Medicine

Comparative Effectiveness of CagriSegma, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials.

Hamarsheh S et al. · Jul 1, 2026

Background Obesity is a chronic, progressive disease affecting over 1 billion adults worldwide, linked to serious comorbidities, including diabetes, hypertension, and cardiovascular disease and associated with increased mortality. Achieving clinically meaningful weight loss is critical to reducing cardiometabolic risk. Tirzepatide, semaglutide, cagrilintide and their combination (CagriSema) have demonstrated efficacy in clinical trials; however, no direct head-to-head studies have compared all advanced anti-obesity medications. This network meta-analysis examines their comparative efficacy and safety. Methods We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity. Outcomes included changes in percent body weight, absolute weight, waist circumference, BMI, patients achieving ≥ 5% to ≥ 20% weight loss, HDL-C and safety outcomes (AEs, serious AEs, gastrointestinal AEs and treatment discontinuation). Random-effects model and network meta-analysis methods were employed. Results Twenty-five trials involving 12 interventions met the inclusion criteria. Tirzepatide 15 mg resulted in the greatest percent weight reduction (MD -17.97%), followed by CagriSema (MD -17.84%) and semaglutide 7.2 mg (MD -14.66%). At the ≥ 20% weight-loss threshold, CagriSema demonstrated marked superiority (RR 27.82), followed by tirzepatide 15 mg (RR 23.70). Gastrointestinal adverse events increased with all treatments (RR 1.33-1.91), and treatment discontinuation was highest with semaglutide 7.2 mg (RR 3.09). Serious adverse events remained comparable to placebo across all regimens. Conclusion Tirzepatide 15 mg and CagriSema achieve the greatest weight reduction, including ≥ 20% body weight loss. Gastrointestinal adverse events rise with treatment intensity, while serious adverse events remain comparable to placebo. These findings support dual-pathway and combination incretin therapies as preferred options for patients requiring substantial weight loss. Treatment selection should be individualized based on comorbidity burden, tolerability and weight loss goals, recognizing that ≥ 5% weight loss improves metabolic parameters while ≥ 10% is needed for meaningful comorbidity reduction. Future head-to-head trials are needed.

Medicine

Central Venous Pressure Referencing in the Lateral Position: Comparison With Direct Right Atrial Pressure in Mechanically Ventilated ICU Patients.

Sjödin C et al. · Jul 1, 2026

Background Right atrial pressure (RAP) is a key determinant of venous return and reflects right-sided filling pressures in critically ill patients. Central venous pressure (CVP) is commonly used as a surrogate, but its accuracy depends on appropriate transducer levelling. While reference points have been evaluated in supine positions, evidence is lacking for the lateral position, despite its frequent use in intensive care. Furthermore, it remains unclear whether lateral positioning alters RAP itself. Methods In this prospective observational study, 16 sedated, mechanically ventilated ICU patients with central venous catheters were included. RAP was measured using a solid-state catheter positioned in the mid-right atrium, confirmed by waveform analysis and echocardiography. Simultaneous CVP was recorded with the transducer levelled 5 cm below the mid-sternum. Measurements were obtained at end-expiration in supine, 45° left lateral, and 45° right lateral positions. Agreement between RAP and CVP was assessed using Bland-Altman analysis, intraclass correlation coefficients, and predefined clinical thresholds. Stepwise hydrostatic adjustments were applied to identify optimal reference levels. Results In the right lateral position, CVP referenced 5 cm below the sternum closely approximated RAP (bias -0.4 mmHg; limits of agreement -3.2 to +2.4; ICC 0.85). In the left lateral position, the same reference point systematically overestimated RAP (bias -2.2 mmHg; limits of agreement -5.0 to +0.7; ICC 0.58). Adjustment to approximately 2 cm below the sternum minimised bias (-0.1 mmHg) and improved agreement (ICC 0.82). RAP increased in the right lateral position compared with both supine (Δ +2.9 mmHg, p Conclusion In mechanically ventilated ICU patients, central venous pressure accuracy was position-dependent, and optimal external reference levels differed between lateral positions. Right atrial pressure increased in the right lateral position, suggesting that lateral positioning influences cardiopulmonary physiology beyond hydrostatic measurement effects alone. Trial registration https://clinicaltrials.gov/study/NCT06705374, registration date 30 April 2024 EDITORIAL COMMENT: The study showed that central venous pressure systematically overestimated right atrial pressure in mechanically ventilated patients placed in the left lateral position. This means that preload and venostasis can be misinterpreted in this position. The influence of increased right atrium pressure on venous return and cardiac output during left lateral positioning in mechanically ventilated patients requires further studies before the clinical relevance can be assessed.

Medicine

From Tradition to Future in Veterinary Public Health Education: Students' Attitudes, Anxiety and Experiences With AI-Supported Learning.

Alan S et al. · Jul 1, 2026

Background Artificial intelligence (AI) has the potential to reshape learning processes, especially through tools such as ChatGPT. Objectives This study aims to evaluate veterinary students' attitudes towards AI-supported veterinary public health education applications, their anxiety levels and their experiences regarding the education process. Methods The study adopted a mixed method design in which quantitative and qualitative methods were used together. The study was conducted with final-year veterinary students (n = 60) enrolled in the Veterinary Public Health course. This study consisted of four phases: (1) the Artificial Intelligence Anxiety Scale (AIAS) was administered as a pre-test, (2) traditional face-to-face training was given, (3) the same topic was repeated with a ChatGPT-based AI-supported exercise and (4) after the trainings, the AIAS was administered again and post-test was conducted and a questionnaire consisting of closed and open-ended questions was administered to the students. Factor analysis revealed that the scale had high internal consistency (Cronbach's α > 0.90). Results Analysis of the scale scores revealed that veterinary students exhibited moderate anxiety towards AI and that AI-focused education did not significantly alter this anxiety in the short term. In the content analysis of qualitative data, students stated that they benefited from the aspects of AI such as fast access to information, practicality and time-saving; the same time, they expressed concerns about ethical concerns, information reliability and professional role change. Conclusion Overall, the findings indicate a duality in students' potential attitudes towards AI. These findings indicate the applicability of AI-based educational practices in the context of veterinary public health education and point to the need for multidimensional evaluation of student attitudes.

Medicine

Echocardiographic Findings in Small-Breed Dogs With Myxomatous Mitral Valve Disease and the Severity of Mitral Regurgitation, Heart Size and Clinical Signs Myxomatous Mitral Valve Disease in Dogs.

Elyasi B. · Jul 1, 2026

Background The main goal of this study was to identify various brightness, motion and Doppler echocardiographic variables in small-breed dogs with myxomatous mitral valve disease. Animals Sixty client-owned small-breed dogs with mitral regurgitation murmurs. Methods Echocardiography was performed in brightness, motion and Doppler modality from the right parasternal view. On the basis of thoracic radiographs, the dogs were categorized into two groups: those with cardiomegaly and those without cardiomegaly. Additionally, on the basis of the jet area signal to left atrium ratio in colour Doppler echocardiography, the canines were divided into three groups: mild, moderate and severe mitral regurgitation. Furthermore, the dogs were classified into preclinical and clinical groups on the basis of the presence or absence of clinical signs, and various variables were compared across these groups. Results This difference was statistically significant and more prevalent in intact dogs than in spayed/neutered dogs. Significant differences were observed in variables including LAmax, LA:Ao, LVIDd, LVIDs, VMA, VMG, VMV, GMV, VMA-GMVT, LVOT and GLVOT in dogs with myxomatous mitral valve disease of varying mitral regurgitation severity and between normal and enlarged hearts. Significant differences were also found in the FS, GMV, VLVOT and GLVOT variables between the clinical and preclinical groups. A moderate and statistically significant correlation was observed between LA:Ao and VMA, VMV and LVOT. Weak and mostly insignificant correlations were found between the Doppler and motion-mode variables. Conclusions Varying mitral regurgitation severity, heart size and the presence of clinical signs can significantly affect certain brightness, motion and Doppler echocardiographic variables in dogs with myxomatous mitral valve disease (valvular heart disease).

Medicine

Sustained Hypoxia-Inducible Factor 1-Alpha Accumulation Disrupts the Articular Niche to Promote Osteoarthritis Pathogenesis.

Gong W et al. · Jul 1, 2026

The precise role of hypoxia-inducible factor-1α (HIF-1α) in osteoarthritis (OA) pathogenesis remains controversial, often debated between a protective compensatory factor and a disease mediator. Here, we demonstrate that sustained, uncoupled HIF-1α accumulation functions as a potent, compartment-specific pathogenic driver of joint destruction. Using genetically engineered mouse models, we reveal that chondrocyte-specific HIF-1α overexpression (Acan CreERT2 ; Hif1αdPA fl/fl ) triggers spontaneous OA and exacerbates destabilization of the medial meniscus (DMM)-induced post-traumatic joint degeneration. Mechanistically, continuous HIF-1α activation drives pathological angiogenesis that physically dismantles the avascular, hypoxic cartilage niche, forcing a profound metabolic dysregulation that culminates in catastrophic matrix degradation. Conversely, sustained HIF-1α activation within the synovial and superficial cartilage compartments (Prg4- GFPCreERT2; Hif1αdPA fl/fl ) drives a slowly progressive, late-onset spontaneous OA through chronic inflammatory accumulation that actively suppresses Col2a1 expression. Furthermore, this robust inflammatory priming establishes a highly vulnerable microenvironment, whereby DMM surgery significantly accelerates the progression of trauma-induced joint collapse. Finally, transient whole-joint HIF-1α induction via an intra-articular injection of lipid nanoparticles (LNP-mRNA) closely recapitulates these detrimental effects. Collectively, our study reconciles existing controversies by establishing sustained HIF-1α accumulation as a spatiotemporally dynamic, broad disease amplifier across the articular ecosystem, highlighting its targeted inhibition as a promising therapeutic strategy for OA.

Medicine

A Prospective Evaluation of Glucagon Stimulation Test Safety in Adults With Chronic Moderate-to-Severe Traumatic Brain Injury.

Snyder C et al. · Jul 1, 2026

Introduction Growth hormone deficiency (GHD) is a common and clinically significant consequence of moderate-to-severe traumatic brain injury (msTBI). The glucagon stimulation test (GST) is widely used to assess growth hormone deficiency; however, the safety of GST has not been systematically evaluated in adults with chronic msTBI. Methods This prospective study enrolled 138 adults aged 18-65 years with chronic msTBI (≥ 1-year post-injury) from a single academic Brain Injury Center neuroendocrine registry. All participants underwent standardized GST with systematic symptom assessment at baseline and serial intervals over 240 min. Adverse events and symptoms were graded by severity using predefined clinical criteria, and participants were analysed by GHD status and by presence of any adverse event. Results GST was well tolerated, with no serious adverse events, test terminations, or prolonged sequelae. The most common adverse effect was nausea (30.4%), with vomiting in 9.4% of participants; antiemetics were required in 16.7% of cases. Female sex was significantly associated with nausea (p Conclusions In adults with chronic msTBI, the glucagon stimulation test demonstrates a favourable safety profile with transient, non-severe adverse effects and no serious neurological or metabolic complications. These findings support GST as a safe and practical method for evaluating growth hormone deficiency in this population.

Medicine

The Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Co-Transporter-2 Inhibitors on Lean Body Mass in Humans: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Jobanputra R et al. · Jul 1, 2026

Aims The use of pharmacotherapies with weight loss properties for the management of obesity and chronic disease are now routinely prescribed. We investigated the evidence from randomised-controlled trials for the effects on lean body mass of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) in humans. Materials and methods PubMed, MEDLINE, the Cochrane Library and CINAHL were searched from inception to October 2022. The primary outcome was change in body composition focused on measures of lean body mass (LBM). Results Thirty-six studies in population groups with obesity (n = 8), type 2 diabetes mellitus (n = 20), type 1 diabetes mellitus (n = 5) and polycystic ovary syndrome (n = 3) receiving a GLP-1RA or SGLT2i therapy versus placebo or active comparator satisfied our inclusion criteria, including 21 for GLP-1RA and 15 for SGLT2i. Meta-analysis showed an overall loss of LBM in the direction of the intervention groups prescribed GLP-1RA (MD: -1.51 kg [95% CI: -2.00 to -1.01]) and SGLT2i (MD: -1.04 kg [95% CI: -1.45 to -0.64]) with sub-group analysis showing largely consistent results when stratified by type of body composition outcome, type of body composition measurement technique and disease status. Results were not modified by sex. Further meta-analysis found that lean mass accounted for 28% (95% CI: 22%-34%) of overall weight loss induced by GLP-1RA and SGLT2i. Conclusions GLP-1RA and SGLT2i are associated with a loss of LBM that appears congruent with overall weight loss. Monitoring of body composition and provision of combined therapy to preserve lean mass during weight loss should be considered.

Medicine

Radiation dose optimization in coronary CT angiography clinical application of absolute phase gating in patients with atrial fibrillation.

Li Y. · Jul 1, 2026

Background Atrial fibrillation (AF) poses significant challenges for coronary CT angiography (CCTA) due to R-R interval variability, often necessitating high radiation dose protocols. Absolute phase gating, which uses fixed millisecond delays rather than percentage-based cardiac cycle timing, may optimize image quality while reducing radiation exposure. Purpose To evaluate whether absolute phase gating reduces radiation dose while maintaining diagnostic accuracy and image quality compared to conventional relative phase gating in patients with AF undergoing CCTA. Methods This retrospective matched cohort study included 280 consecutive patients with AF (140 per group) who underwent CCTA between January 2021 and December 2023. Patients were matched by heart rate, BMI, and calcium score. The absolute phase gating group used fixed 300-millisecond post-R-wave triggering; the relative phase gating group used conventional 75% R-R interval triggering. Primary endpoints were diagnostic accuracy (sensitivity, specificity) for ≥50% stenosis and assessable segment ratio. Secondary endpoints included radiation dose parameters and image quality scores. Invasive coronary angiography served as reference standard in 118 patients (42.14%). Results Radiation dose was 64.28% lower with absolute phase gating (median DLP: 187.50 vs. 524.80 mGy·cm, p Conclusions In patients with AF undergoing CCTA, absolute phase gating can potentially reduce radiation dose while maintaining or improving diagnostic performance relative to the conventional relative phase gating protocol used at our institution. Because the magnitude of any dose reduction depends in part on the acquisition window and dose-modulation settings of the compared protocols, the benefit should be interpreted in the context of the specific comparator. These findings are consistent with the Image Wisely initiative for responsible patient radiation dose management.

Medicine

Towards optimized CT lung cancer screening scan protocols.

Iball GR et al. · Jul 1, 2026

Objectives To evaluate radiation dose and image quality for CT lung cancer screening protocols and to determine which reconstruction kernels deliver accurate nodule volumetry. Methods A variable size anthropomorphic chest phantom and a lung screening image quality phantom were scanned on 17 different scanner models. Dose metrics from the chest phantom scans were compared against international dose recommendations. Image quality phantom scans were used to assess whether the protocol yielded accurate nodule volumetry as per the Quantitative Imaging Biomarkers Alliance (QIBA) criteria, and to determine whether changes were needed to enable this. Results Doses varied by up to a factor of 7 for the largest phantom size. All protocols delivered doses below the UK standards but only 2 scanners met the European dose criteria. Many scanners failed to meet the QIBA criteria with lung reconstruction kernels, primarily due to excessive edge enhancement and insufficient 3D spatial resolution. With alternative reconstruction kernels, the QIBA criteria were met on all bar 2 scanners. Conclusions Standard lung screening CT protocols on contemporary scanners produce images of varying image quality, over a wide range of radiation doses. Scanner-specific reconstruction kernel selection is required to meet the QIBA criteria. The study findings enable the development of optimized CT scanning protocols for lung cancer screening program. Advances in knowledge Standard lung cancer screening scanning protocols demonstrate notable variations in dose. Lung reconstruction kernels often yield inaccurate measurements of nodule volume; instead, soft tissue kernels are necessary to obtain reliable results.

Medicine