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Targeting AT1 receptors with telmisartan protects SH-SY5Y cells from 6-OHDA induced Parkinsonian neurotoxicity

Prevalence and associated factors of non-variceal upper gastrointestinal bleeding among cirrhotic patients with upper gastrointestinal bleeding on follow-up at a Tertiary Hospital in Ethiopia

Background Liver cirrhosis is a major cause of morbidity and mortality worldwide. Non-variceal upper gastrointestinal bleeding (NVUIGB) accounts for 24–42% of bleeding episodes in cirrhotic patients and carries a mortality rate of 15–30%. Understanding its prevalence and associated factors is critical for prevention and improved outcomes. This study assessed the prevalence and predictors of NVUGIB among cirrhotic patients with upper gastrointestinal bleeding at a tertiary hospital in Addis Ababa, Ethiopia. Methods A hospital based cross-sectional study was conducted from December 2020 to December 2023. A total of 234 patients were included in the study. The collected data were analyzed using Statistical Package for Social Sciences (SPSS) version 26.0. Bivariable and multivariable logistic regression was used to assess association between dependent and independent variables. Adjusted odds ratio with a 95% confidence interval was used to estimate the strength of association and level of statistical significance was declared at p value <0.05. Results The prevalence of non-variceal upper gastrointestinal bleeding was 31.6% (95% CI: 26.0–37.8). with a mean (±SD) age of 39 ± 14 years. Independent predictors of non-variceal upper gastrointestinal bleeding included longer duration of cirrhosis (AOR = 1.01, 95% CI: 1.001–1.019, p = 0.03) and Human Immunodeficiency Virus (HIV) (AOR = 51.72, 95% CI: 5.65–471.8, p < 0.001). Lower odds of non-variceal upper gastrointestinal bleeding were observed in older patients (AOR = 0.96, 95% CI: 0.93–0.99, p = 0.007), those with hepatitis C virus (AOR = 0.12, 95% CI: 0.05–0.66, p = 0.009) or schistosomiasis (AOR = 0.03, 95% CI: 0.006–0.19, p < 0.001) as the cause of cirrhosis, prior beta-blocker use (AOR = 0.32, 95% CI: 0.14–0.70, p = 0.005), and higher international normalized ratio (AOR = 0.57, 95% CI: 0.36–0.89, p = 0.014). Non-variceal upper gastrointestinal bleeding patients also had lower systolic blood pressure at presentation (AOR = 0.97, 95% CI: 0.95–0.99, p = 0.010) but required fewer blood product transfusions (AOR = 0.25, 95% CI: 0.08–0.71, p = 0.009). Conclusion Non-variceal upper gastrointestinal bleeding accounted for nearly one-third (31.6%) of bleeding cases among cirrhosis patients with upper gastrointestinal bleeding. It was significantly associated with longer duration of cirrhosis, younger age, and the presence of comorbidities such as HIV. Targeted screening and preventive measures for high-risk patients may reduce the burden of NVUGIB.

The role of future planning, patience, and risk tolerance for prospective reciprocity in human adults

Abstract The current study aimed to test a suite of psychological proximate mechanisms thought to underlie prospective reciprocity – engaging in cooperative acts with the anticipation that benefits will be returned in the future. We developed and validated a novel online test battery with 297 participants to assess individual differences in three domains (planning, patience, risk tolerance) and their relation to participants’ responses across different prospective reciprocity tasks. Tasks assessing patience showed high internal consistency and were positively associated with cooperative behaviour across all three prospective reciprocity tasks. The pattern was less clear for risk, with associations varying across tasks, and planning ability was negatively correlated with one prospective reciprocity task. Across the prospective reciprocity tasks, performance showed limited convergence, indicating that forward-looking cooperative behavior is context dependent rather than reflecting a unitary, domain-general tendency. Taken together, our results show that planning, patience, and risk tolerance each contribute to forward-looking cooperation in task-specific ways, underscoring the need for improved psychometric approaches.

Yield and combining ability of temperate ex-PVP introgressed and tropical maize under contrasting moisture regimes

Low grain yield and recurrent drought remain major constraints to maize production in Sub-Saharan Africa (SSA), underscoring the urgent need for hybrids with improved resilience. The use of ex-PVP (expired Plant Variety Protection) temperate maize lines is important to improve yield potential and genetic diversity in tropical adapted lines. In this study, 15 temperate introgressed lines and 6 tropical lines were crossed with eight single cross testers to generate 168 testcross hybrids. All genotypes were evaluated in 8 sites, with 6 well-watered (WW) and 2 drought-stressed (DS) conditions in Kenya. Analysis showed significant genotypic and site effects for grain yield (GY) and other agronomic traits, with strong genotype × environment interactions under drought. General combining ability (GCA) and specific combining ability (SCA) were important, with additive variance dominating under both WW and DS. Temperate introgression (TI) improved yield performance in most tropical backgrounds, with hybrids from TI outperforming tropical hybrids by 1.20–2.04 t/ha under optimal conditions and yielding similarly under drought stress (TI, 1.88 t/ha; tropical, 1.89 t/ha). Hybrids showed up to 74% reduction in GY, 22% lower PH, 18% lower EH, and a 72% increase in ASI under DS compared to WW. Lines L2, L10, L16 and testers T1, T2, T3, T4, T7 showed consistently positive GCA for GY and shorter anthesis–silking interval, suggesting they can be used in breeding programs to develop high yielding drought tolerant hybrids suitable for sub-Saharan Africa. These findings emphasize the value of ex-PVP lines as source to enhance yield in tropical adapted germplasm. Both additive and non-additive gene action are important, combining pedigree methods with genomic selection for additive effects along with strategic heterosis use can accelerate the development of high-yielding, climate-resilient maize hybrids for stress-prone regions of SSA.

Meta learning based few shot knowledge graph completion with domain selected aggregation

The impact of the COVID-19 pandemic on oral anticoagulation adherence in patients with atrial fibrillation managed in primary care: Results from the PRIME Registry

Background Oral anticoagulants (OACs) are critical for preventing stroke in patients with atrial fibrillation (AF), yet adherence and persistence remain suboptimal, especially in primary care settings. The COVID-19 pandemic introduced new barriers to care that may have further disrupted medication use. This study aimed to examine the impact of the COVID-19 pandemic on OAC adherence and persistence among patients with nonvalvular AF managed in primary care practices. Methods In this retrospective cohort study, we used clinical records from the American Board of Family Medicine’s (ABFM) PRIME Registry, for March 2017 through March 2023. We included 3,010 patients with documented AF and at least two OAC prescriptions prior to baseline. Persistence was assessed annually using a treatment anniversary method, and adherence was measured using the proportion of days covered (PDC), analyzed among persistent patients only. Interrupted time series and multivariable logistic regression models evaluated changes in quarterly persistence and factors associated with persistence and good adherence. Results Persistence declined sharply during the pandemic from 49.9% in 2018–2019 to 8.2% in the pandemic year-1. Adherence also dropped, with >95% PDC decreasing from 46.0% pre-pandemic to 17.7% in the pandemic year-2. Interrupted time series analysis showed a significant immediate drop in persistence. Compared to warfarin, NOAC use was associated with lower persistence in the pre-pandemic period, but higher persistence by the second year of the pandemic. Conclusions The COVID-19 pandemic was associated with sustained declines in OAC adherence and persistence among AF patients in primary care. Targeted interventions including telemedicine, home-based care, and attention to high-risk subgroups are essential to maintain continuity of care and improve adherence during public health crises.

Publisher Correction: Association between hydrogen gas inhalation and cardiac output in an asphyxiated piglet model

Analysis of the failure state of the Cenozoic clay layer in thin bedrock coal seam mining: A case study of Sanyuan coal mine

A mechanical analysis model was constructed for the clay layer. Using a combined approach of theoretical analysis and numerical simulation, the failure state of this layer during coal seam extraction under thin bedrock conditions was investigated. The findings offer insights for evaluating the water-blocking performance of the Cenozoic clay layer and for preventing water inrush disasters in similar geological settings. The key findings are as follows: (1) The most critical factor governing clay layer failure is the amount of bedrock subsidence following collapse. As the subsidence of the fractured bedrock increases, the suspended section of the overlying clay layer extends, elevating its possibility to shear or tensile failure. (2) Variations in bedrock thickness markedly influence the subsidence of both the bedrock and the clay layer. Consequently, bedrock thickness is a primary determinant of the degree of damage sustained by the clay layer. (3) The minimum bedrock thickness required to prevent failure of the basal clay layer within the Cenozoic overburden ranges from 33 m to 38 m. If the bedrock thickness falls below 33 m, the clay layers will be damaged after coal seam mining, leading to a loss of their water-blocking capacity.

Effectiveness of pelvic floor rehabilitation after radical prostatectomy and continence recovery in relation to surgical technique

Abstract The potential influence of surgical technique and pelvic floor rehabilitation on continence recovery continues to be debated. This prospective cohort study included 182 men undergoing robot-assisted or laparoscopic radical prostatectomy. All patients were referred for physiotherapist-guided pelvic floor muscle training. Urinary incontinence was assessed using a standardized 1-h pad test and a three-stage UI grading system at 1, 3, and 6 months after catheter removal. Ordinal and logistic regression models were used to identify predictors of continence, including surgical technique, age, pathological features, and rehabilitation-related variables. Exploratory time-to-event analyses (Cox proportional hazards models) were also performed to assess the dynamics of continence recovery, with catheter removal as time zero and achievement of full continence (pad test ≤ 2 g) as the event. Patients undergoing RARP demonstrated higher odds of early full continence shortly after surgery (OR = 5.26; 95% CI 2.34–11.80; p  < 0.001) and functional continence (OR = 4.00; 95% CI 1.96–8.14; p  < 0.001). After adjustment for baseline incontinence severity, surgical technique was no longer an independent predictor of continence recovery. However, in multivariable analyses, baseline incontinence severity and timing of rehabilitation were the strongest independent predictors of continence recovery. Robotic prostatectomy is associated with a more favorable continence status at the start of rehabilitation, whereas continence recovery during physiotherapy is primarily determined by baseline incontinence severity and timely initiation of pelvic floor therapy rather than surgical approach. These results highlight the need to integrate precise surgical techniques with standardized, early, and individualized physiotherapy to optimize continence recovery and improving quality of life after radical prostatectomy.

Residual physiological abnormalities after pulmonary endarterectomy and balloon pulmonary angioplasty in CTEPH

Introduction Pulmonary endarterectomy (PEA) is the first-line treatment for chronic thromboembolic pulmonary hypertension (CTEPH), while balloon pulmonary angioplasty (BPA) is an established alternative for inoperable patients. Although both interventions improve resting pulmonary hemodynamics, the extent of long-term physiological recovery during exercise and the persistence of functional limitations remain incompletely characterized. Methods Prospective single-center registry (2017–2023) including 14 patients completing BPA (71 sessions) and 15 undergoing PEA, with median follow-up of 50 months (IQR 36–61). Clinical assessment included resting hemodynamics, invasive exercise right heart catheterization to derive the exercise slope of the mean pulmonary arterial pressure to cardiac output relashionship (mPAP/CO slope), and health-related quality of life (HRQOL) evaluated using the SF-36 questionnaire. Analyses were descriptive and focused on within-pathway changes over time. Results Both BPA and PEA significantly reduced mPAP (44.8 ± 12.4 → 26.1 ± 9.3 mmHg; 42.1 ± 12.9 → 22.6 ± 5.4 mmHg, both p < 0.001) and pulmonary vascular resistance (9.8 ± 4.6 → 3.0 ± 1.3 WU; 9.0 ± 5.4 → 2.9 ± 1.9 WU, both p < 0.001) at long term follow-up. Despite sustained improvements in resting hemodynamics, abnormal exercise pulmonary vascular responses persisted, with mean mPAP/CO slopes of 7.0 ± 5.6 mmHg/L/min after BPA and 4.0 ± 2.3 mmHg/L/min after PEA. Physical HRQOL remained impaired at long-term follow-up, with Physical Component Summary (PCS) scores below population norms in both pathways (44.4 ± 12.7 after BPA and 44.5 ± 7.3 after PEA). Conclusion BPA and PEA provide durable improvements in resting pulmonary hemodynamics; however, incomplete physiological recovery is common, with persistent exercise abnormalities and reduced physical quality of life at long-term follow-up.

Tolerance of outbreak-associated Candida parapsilosis isolates to antiseptics in a dry surface biofilm model

Concurrent training in cardiac rehabilitation: A scoping review of aerobic-strength combinations in patients with coronary artery disease

Concurrent training (CT), defined as the integration of aerobic and strength exercise modalities, is increasingly implemented within cardiac rehabilitation (CR) to improve cardiovascular and musculoskeletal health. However, CT prescriptions vary markedly, and the characteristics and application of CT within CR have not been comprehensively mapped. This scoping review examined how CT has been designed and delivered in CR and summarised reported outcomes across International Classification of Functioning, Disability and Health (ICF) domains. A systematic search of databases and supplementary sources was conducted from October 2023 to December 2025. Clinical trials evaluating CT compared with usual care or aerobic training alone were eligible. Fourteen trials (n = 1,037; 13 randomised, 1 single-group) were included. CT programmes varied widely in setting (hospital, community, hybrid), CR phase (II–III), duration (5–32 weeks), and training structure. Aerobic training was delivered using continuous aerobic training (CAT), aerobic interval training (AIT), or high-intensity interval training (HIIT), with intensities prescribed using peak oxygen uptake (V̇O₂peak), maximum heart rate (HR max ), heart rate reserve (HRR), work rate, ventilatory threshold, or rating of perceived exertion (RPE). Modalities ranged from cycle ergometers and treadmills to multimodal or circuit-based formats. Strength-training prescriptions differed in targeted muscle groups, sets (2–8), repetitions (8–20), equipment (e.g., machines, free weights, TheraBand), and intensity anchors (% of one repetition maximum, RPE, % of maximum voluntary contraction). Application of progressive overload was inconsistent across studies. Exercise capacity (primarily V̇O₂peak) and muscle strength were the most consistently assessed outcomes. No CT-related adverse events were reported. CT has been applied using diverse delivery formats and exercise prescriptions within CR. Physiological outcomes were most consistently measured, whereas activity and participation-level outcomes showed greater variability and limited long-term evaluation. Future research should prioritise clearer reporting of training parameters, examine CT within community and hybrid CR models, incorporate behavioural and patient-reported outcomes, and investigate sex-specific responses and long-term effects to inform scalable and contextually adaptable CT approaches.

Predicting identity dissociation using childhood maltreatment and genetic variation in the stress-response gene FKBP5: a machine learning analysis

Abstract Identity dissociation is challenging to detect and treat, and its etiology remains incompletely understood. Childhood maltreatment and FKBP5 polymorphisms, which modulate the stress response, may contribute by disrupting the integration of autobiographical experiences essential for identity development. We examined whether gene-environment interactions involving childhood maltreatment and FKBP5 polymorphisms predict clinically significant identity dissociation. In a cohort of N  = 377 participants, we assessed childhood maltreatment and identity dissociation using validated questionnaires and genotyped CATT haplotypes within FKBP5 linked to stress reactivity. Identity dissociation was dichotomized using an established clinical threshold. An elastic net regularized logistic regression model incorporating maltreatment subtypes, CATT haplotype count, and their interactions was trained ( N  = 194) and validated ( N  = 183). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and Matthews correlation coefficient. Decision curve analysis assessed clinical utility across varying risk thresholds. The model demonstrated fair discrimination (AUC = 0.709) with 58.6% sensitivity and 79.9% specificity. While the positive predictive value was modest (35.0%) due to the low prevalence of identity dissociation (15.9%), decision curve analysis revealed a net clinical benefit across a broad range of threshold probabilities (6–76%), indicating practical utility for risk stratification in clinical settings. The negative predictive value was 0.91. These findings provide initial evidence that gene-environment interactions between childhood maltreatment and FKBP5 variation may contribute to the risk of identity dissociation. While predictive precision remains limited, this study demonstrates the feasibility of applying machine learning approaches to dissociation and highlights the need for further research into their traumatic and biological underpinnings to improve detection, prevention, and treatment.

Establishment of optimal mandibular incisor inclination: A retrospective comparison between surgery-first and conventional orthodontic approaches

Introduction Surgery-first orthodontic treatment offers early facial profile improvement and shorter treatment duration. This study investigated the incisor relationship in skeletal Class III malocclusion patients treated with conventional orthognathic surgery (COS) and the surgery-first approach (SFA). Materials and methods Sixty-eight patients who underwent mandibular setback surgery for skeletal Class III malocclusion were divided into 2 groups: the COS group (n = 34, 19 males and 15 females; mean age, 20.5 ± 2.9 years) treated with conventional three-stage surgical orthodontic treatment and the SFA group (n = 34, 20 males and 14 females; mean age, 21.9 ± 3.5 years) treated without presurgical orthodontics. Lateral cephalograms were analyzed before treatment (T0) and after debonding (T1). The changing pattern of mandibular incisor mandibular plane angle (IMPA) was compared between the groups, and the amount of change was assessed using analysis of covariance (ANCOVA) and mandibular incisor inclinations at each stage were compared to the norm value to calculate the achievement ratio. Results At T0, the IMPA was 81.6° in the COS group and 80.7° in the SFA group. At T1, the IMPA was 88.6° in the COS group and 83.3° in the SFA group. Considerable presurgical decompensation occurred in the COS group, while postsurgical decompensation was insufficient in the SFA group. ANCOVA revealed that the COS group exhibited a significantly greater change in IMPA than the SFA group (p = 0.001). At T1, the achievement ratio showed that the COS group (94.4%) was closer to the norm than the SFA group (85.5%) (p = 0.001), indicating that the SFA group showed more compensated mandibular incisors than the COS group. Conclusion The COS group demonstrated more effective mandibular incisor decompensation and achieved values closer to the norm than the SFA group. These findings suggest that presurgical orthodontics is essential for achieving optimal incisor inclination, and clinicians should carefully consider the need for sufficient decompensation when planning treatment with the SFA approach.

Stable charged nanobubbles with distinct polarities in culture media differentially affect the viability of human iPSC-derived neurons

Abstract Nanobubbles (NBs) are gas-filled spherical structures less than 1 μm in diameter, characterized by high surface charge, long-term stability, and the ability to generate bactericidal hydroxyl radicals upon collapse. Although these unique properties enable their extensive applications, including wastewater treatment, their cell biological applications at neutral pH remain limited by difficulties in maintaining stability and surface charge. Here, we succeeded in generating both positively and negatively charged NBs, achieving high zeta potentials in human iPSC-derived neural progenitor cell (NPC) and neuron culture media (pH 7.4). Similar to their bactericidal effects, NBs induced cell death in iPSC-derived cells, with positively charged NBs showing stronger cytotoxicity than negatively charged ones. This may be because the cell membrane carries a negative charge, making positively charged NBs more likely to approach and interact with the membrane, or because positively charged nanobubbles exhibit stronger radical generation. In future, we aim to elucidate the molecular biological mechanisms underlying NB-induced cell death and to contribute to the potential application of nanobubbles in regenerative medicine. This study will serve as an initial step toward that goal.

Person-centered care, shared decision-making, and service modularity in colorectal cancer treatment: A mixed-method study of patient and professional perspectives

Background Cancer care pathways improve outcomes through standardization but often lack flexibility to address individual needs. In this case study, we applied a composite model to examine its applicability by studying how person-centered care, shared decision-making, and service modularity are enacted within the colorectal cancer pathway of a large Dutch teaching hospital. Methods We conducted a cross-sectional mixed-method single case study. Patients completed questionnaires on health-related well-being and colorectal cancer care experiences. We explored person-centered care, shared decision-making, and service modularity and their interaction using questionnaires (patients) and semi-structured interviews (patients and healthcare professionals). Quantitative data were analyzed with descriptive statistics; qualitative data were analyzed thematically. Results Our findings showed gaps between formal structures and actual delivered care, especially in how shared decision-making and service modularity work together to provide person-centered care. Healthcare professionals’ limited modular thinking restricted customization. Information was delivered mainly according to protocols and did not fully address individual preferences, while preference elicitation was inconsistent. Care packages tended to follow clinical routines rather than reflect true patient priorities. Coordination was generally sufficient but revealed weaknesses during care transitions. Conclusion The composite model provides a practical framework to enhance person-centered cancer care by revealing structural barriers to shared decision-making and customization. Promoting modular thinking among professionals supports flexible, preference-sensitive care and offers actionable strategies to improve both efficiency and patient engagement across oncological pathways.

Epigenetic, neuroplasticity, and adrenergic targets associated with major depression in immune cells

Integrating contrastive cross-modal attention and stacked GRU for hand function rehabilitation robot control

With the intensification of population aging and the increasing incidence of neurological diseases, the demand for precise and intelligent control technology in hand rehabilitation robots has become more urgent. Traditional control methods struggle to effectively capture the dynamic temporal features of hand movements, especially in scenarios where there are modal differences between hand function data of healthy individuals and stroke patients, leading to insufficient control accuracy and poor generalization. This paper focuses on hand rehabilitation robot control technology and proposes the C-GAP model. By designing a cross-modal attention mechanism, the model realizes feature collaboration of multi-source data such as electromyography (EMG), force, and joint angles. It relies on Stacked Gated Recurrent Units to accurately extract the temporal dynamic patterns of typical hand functional movements, such as grasping, pinching, and wrist rotation. In combination with an adaptive PID controller, the model optimizes force-controlled trajectories in rehabilitation training, forming a complete control scheme tailored to hand rehabilitation scenarios. Experimental validation shows that the model performs stably in classifying typical hand functional movements and dynamic control on the Ninapro DB5 (healthy hand function multimodal data) and MUSED-I (stroke patient hand function unimodal data) datasets, effectively adapting to rehabilitation training needs under different hand function states. The research provides technical support for the precise perception and control of sequential movements in hand rehabilitation robots, contributing to enhancing the specificity and safety of rehabilitation training. It has practical significance for promoting the application of recurrent neural networks in the field of rehabilitation robot control.

Functional genomics integration of glycolysis-related gene networks reveals prognostic biomarkers and immune microenvironment regulation in breast cancer

Efficacy of a single dose switch from aflibercept to ranibizumab in the treatment of neovascular age-related macular degeneration

Purpose To analyze morphological and functional response after administration of a single dose of ranibizumab in eyes under treat&extend aflibercept in neovascular age related macular degeneration (nAMD). Additionally, we aimed to identify predictive factors in anti-vascular endothelial growth factor (VEGF) treatment. Methods A total of 115 patients (133 eyes; 34 male, 81 female, m:f = 1:2.4) with a mean age of 79.9 ± 8.3 years at baseline (BSL) were included in this retrospective analysis. All eyes had received aflibercept treatment for nAMD before BSL and were subsequently administered a single dose of intravitreal ranibizumab. Data of two visits pre and two visits after BSL were evaluated and compared. Primary outcome measure was the mean change in central macular thickness (CMT, µm). CMT-changes between BSL and the next follow-up visit (V4) were roughly divided into decrease (<−10µm), equal (−10 to +10 µm) or increase (> +10µm). We also assessed changes in best-corrected visual acuity (BCVA) and identified influencing factors on CMT and BCVA using linear mixed models (LMM). Results No significant differences in CMT and BCVA were observed over the visits (p > 0.05). Factors influencing CMT included prior anti-VEGF injections (p < 0.001), the time interval between BSL and visit 4 (p < 0.001), and patient age (p = 0.032). The number of prior anti-VEGF injections significantly influenced BCVA (p = 0.003). After a single administration of ranibizumab, in 19.5% (n = 26) of eyes CMT decreased, in 21.8% of eyes (n = 29) CMT increased and in 36.8% of eyes (n = 49) it remained equal. Conclusion Our study indicates that changes in CMT are affected by age, the number of previous injections, and the time interval between visits. These biomarkers may offer valuable insights for future research on switching anti-VEGF drugs to optimize treatment strategies for nAMD. A single dose treatment switch to ranibizumab yielded non-inferior outcomes.