Browse Articles

Cardiac systole is associated with enhanced go responding in an orthogonalized go/nogo task

Abstract Action selection is traditionally thought to be governed by dual top-down control systems: a fast, affect-dependent controller and a slow, experience-driven controller. Emerging evidence indicates that bottom-up cardiac phase signals also contribute to action selection by facilitating (i.e., go) or suppressing (i.e., nogo) motor responses. Despite growing interest in cardiac-brain interactions, no prior study has examined whether cardiac phase effects on feedback-driven action decisions are modulated by appetitive and aversive motivational states. We conducted a secondary analysis of a go/nogo functional magnetic resonance imaging (fMRI) dataset ( n  = 29), retrospectively determining the onset of decision cues relative to physiologically defined cardiac phases. We tested competing behavioural and computational hypotheses proposing that cardiac phase modulated action selection via motivational action biases, or through a general, affect-independent prepotent urge to act. Additionally, we performed an exploratory fMRI analysis to investigate neural activity underlying action decisions as a function of cardiac phase. Converging behavioural and computational evidence showed that systole was associated with a higher likelihood of go responding, independent of motivational action biases. Preliminary fMRI results further suggested that systolic facilitation of action was accompanied by diminished neural activity supporting action inhibition. Together, these findings extend existing evidence that cardiac phase impacts action decisions.

PEG-fusion of viable sciatic nerve isografts restores axonal structure and behavioral recovery after segmental-loss sciatic nerve injuries in Lewis rats

Segmental-loss peripheral nerve injuries (SL-PNIs) often produce severe deficits in sensory/motor functions and voluntary behaviors. The current gold standard for repair is neurorrhaphy of a cable autograft that (1) produces donor site morbidity; (2) results in rapid Wallerian degeneration (WD) of severed distal nerve segments; (3) relies on slow (1–2 mm/day) axonal regeneration; (4) does not prevent atrophy of denervated muscles and sensory structures; and (5) results in poor to non-existent recovery of sensory/motor functions and voluntary behaviors, especially with longer segmental-loss gaps and/or with denervated targets located rather distal to a proximal SL-PNI. Our study used genetically identical Lewis rats as a model system for isograft transplants. Neurorrhaphy of viable peripheral nerve isografts (VPNIs) of 5- or 10-mm length was performed to repair sciatic SL-PNIs of 4- or 8-mm gap length, respectively. Animals were repaired with a set of well-specified solutions that did (PEG-fusion group) or did not (Negative Control [NC] group) contain 50% w/w 3.35 kDa polyethylene glycol (PEG), an axolemmal fusogen at that specific weight and concentration. We also examined the effects of locally applied FK506 on 10-mm VPNI repairs both with and without PEG-fusion. We hypothesized that PEG-fusion groups would show better axonal morphology and behavioral recovery, as assessed by the Sciatic Functional Index (SFI), compared to NC groups regardless of the gap length. We also hypothesized that FK506 would improve the effects of PEG-fusion by reducing inflammation. Our data showed that PEG-fused VPNI groups had significantly larger axonal diameters and lower g-ratios, less WD, and better SFI scores compared to NC groups regardless of the gap lengths for SL-PNIs. However, localized FK506 treatment only transiently improved axonal regeneration and impaired long-term SFI behavioral recovery, which is the most important measure of successful repairs. In conclusion, PEG-fusion repair technologies show great potential for improving clinical treatments.

IV iron for IDA during acute infection

Latent profiles of apathy in the general population and their associations with psychopathology and functioning

Impact of cardiometabolic index on long-term mortality in young adults with type 2 diabetes mellitus

Background The cardiometabolic index (CMI) has been utilized in recent years to detect patients with type 2 diabetes mellitus (T2DM). Given the consistent annual rise in the incidence of T2DM among young adults, the relationship between CMI and mortality risk among those with early-onset T2DM remains to be determined. Methods We enrolled 2,188 participants aged 20–65 with diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. Weighted Cox proportional hazard regression models were employed to evaluate hazard ratios (HRs) with 95% confidence intervals (CIs). Restricted cubic spline (RCS) curves were utilized to assess linear associations. Stratified and interaction analyses were performed. Results We find that higher CMI is strongly associated with an increased risk of all-cause mortality ( p  = 0.005) and cardiovascular mortality ( p  = 0.020) in the strictest model. RCS analysis revealed a linear relationship between CMI and mortality. Subgroup and interaction analysis showed no statistical significance. Conclusions The higher CMI level is correlated with all-cause and cardiovascular mortality risk among young individuals with diabetes mellitus, and serves as a comprehensive and effective prognostic indicator for long-term health.

Thymoma-associated aplastic anemia with concurrent Good syndrome

Objective-function-guided automated VMAT planning reduces OAR dose, low-dose exposure, and inter-planner variability in breast radiotherapy

Abstract This study presents and evaluates an automated volumetric modulated arc therapy (VMAT) planning framework for breast cancer based on objective function value (OFV)–guided optimization. The primary objective is to systematically improve organ-at-risk sparing through automated and reproducible optimization of planning constraints while maintaining clinically acceptable target coverage. An OFV-guided optimization workflow was empirically developed using a separate sensitivity dataset and subsequently evaluated in 20 clinical breast cancer patients (13 left-sided, 7 right-sided). The automated Python-based framework iteratively adapts MaxEUD constraints during optimization until dose metrics converge, without manual intervention. Automatically generated plans were compared to clinically delivered VMAT plans using target coverage, dose–volume metrics, and monitor units as a surrogate for delivery efficiency. The automated approach consistently achieved significant reductions in mean organ doses and low-dose volumes (e.g., $$V_{2Gy}$$ , $$V_{5Gy}$$ ) while preserving PTV coverage. Mean heart dose decreased from $$3.09 \pm 1.06$$  Gy to $$2.21 \pm 0.69$$  Gy for left-sided cases and from $$1.88 \pm 1.06$$  Gy to $$1.17 \pm 0.25$$  Gy for right-sided cases ( $$p < 0.001$$ ). Significant dose reductions were also observed for the ipsilateral lung, contralateral lung, and contralateral breast, accompanied by a 16.9 % reduction in monitor units ( $$p < 0.001$$ ) and reduced inter-patient variability. In contrast, no statistically significant difference was observed for lung $$V_{20Gy}$$ . In conclusion, OFV-guided VMAT optimization enables reproducible and systematic improvement of organ-at-risk sparing in breast radiotherapy. By reducing organ doses, low-dose burden, monitor units, and inter-patient variability without compromising target coverage, the proposed framework could provide a robust and standardized baseline for clinical VMAT planning and a consistent foundation for future data-driven and machine-learning–based optimization approaches.

Enhancing aviation safety: An 80-year data-driven model for classification of aviation incident and accident

The aviation system is safety-critical by nature, and any occurrence of an incident or accident can lead to the loss of human life and significant operational disruptions. The International Civil Aviation Organization (ICAO) emphasizes that every flight must take off and land safely—a goal achieved over 126,000 times daily. Despite major advancements,mishaps and accidents continue to occur, underscoring the need for robust safety management systems. The accurate classification of aviation occurrences (Incident or Accident) reports is essential for safety management, yet manual review is time-consuming and prone to inconsistency. While incident/accident labels are assigned during reporting, automated classification enables rapid triage, detection of potential mislabeling, and support for severity assessment in high-volume aviation safety operations. To address this,we developed and compared three machine learning classifiers—Multinomial Naive Bayes, Random Forest, and Support Vector Machine—using TF-IDF vectorization on an 80-year dataset of 53,770 aviation occurrence summaries obtained from the Transportation Safety Board of Canada. A two-stage evaluation strategy was employed, consisting of an initial 80/20 train–test split to create an independent test set, followed by 5-fold cross-validation applied exclusively to the training data to ensure robustness and prevent optimistic bias. The Support Vector Machine (SVM) classifier achieved the highest classification performance, attaining an accuracy of 98.06% during 5-fold cross-validation, with consistent results across folds, demonstrating its effectiveness in managing high-dimensional textual data and dataset complexity. The proposed framework provides a robust foundation for automated aviation safety report processing, offering practical value for (1) early triage of safety reports, (2) identification of potentially mislabeled cases requiring expert review, and (3) integration into downstream severity assessment pipelines. This work advances beyond prior classification studies by establishing a benchmark on the largest historical aviation safety dataset while delivering a deployable and operationally relevant framework for real-world safety management applications. The findings offer valuable insights for regulatory authorities and airline operators, contributing to enhanced safety oversight, improved response strategies, and safer aviation operations.

Von Willebrand factor deficiency impairs angiogenesis via angiopoietin-2: relevance for gut angiodysplasia

Abstract Management of recurrent gastrointestinal (GI) bleeding is a clinical unmet need for patients with von Willebrand disease (VWD) and is linked to the presence of gut vascular malformations (angiodysplasia). We previously demonstrated that von Willebrand factor (VWF) regulates angiogenesis and vascular integrity. VWF controls the storage of the angiogenesis regulator angiopoietin-2 (Angpt-2) in endothelial cells (EC), suggesting a candidate for the genesis of angiodysplasia; however, no direct evidence of the role of Angpt-2 in VWF-dependent angiogenesis is available. Using VWF-deficient human umbilical vein EC (HUVEC) and endothelial colony-forming cells (ECFCs) from patients with severe VWD, we found that loss of VWF resulted in increased Angpt-2 expression through the positive feedback loop Angpt-2–Tie-2–Akt–FOXO1–Angpt-2. In the gut of VWF-deficient mice, Angpt-2 expression was increased, whereas Angpt-1 expression was decreased, suggesting that VWF regulates the Angpt/Tie2 balance in the gut. Moreover, the intestinal vasculature in the jejunum of VWF-deficient mice appeared abnormal, with hypersprouting and lumen formation defects. The findings reveal VWF-deficient mice as a model to study gut angiodysplasia. We investigated sprouting angiogenesis in vitro using a fibrin bead assay and found increased sprouting in VWF-deficient EC. We developed a 3-dimensional microfluidic model of angiogenesis and found that ECFCs from patients with severe VWD exhibit defective remodeling and abnormal lumen formation, reminiscent of the defects in the gut of VWF-deficient mice. Importantly, inhibition of Angpt-2 reduced sprouting in VWF-deficient HUVEC and normalized vascular remodeling in VWD-ECFCs, suggesting that Angpt-2 inhibitors may be effective in patients with VWD with GI bleeding and angiodysplasia.

Hsa-circ_0081481-miR 3960-FBXO24 regulatory axis in non-obstructive azoospermia identifies potential biomarkers of spermatogenic failure

Evaluating the Integrated Disease Surveillance and Response system in Sidama Region, Ethiopia: A systems evaluation

Background Integrated Disease Surveillance and Response (IDSR) systems play a vital role in early detection and response to public health threats. In Ethiopia, limited evaluations exist on the effectiveness of IDSR at subnational levels. This study assessed the implementation of the IDSR system in Sidama Region to identify performance gaps and inform improvements. Methods A cross-sectional evaluation was conducted between September and November 2023 in Sidama Region, Ethiopia. A multistage cluster sampling technique was used to select 140 participants from 13 districts, public and private health facilities, health posts, and community health workers, including members of the Health Development Army (HDA). Data were collected using a structured checklist adapted from WHO and CDC guidelines. Key surveillance functions (e.g., case detection, reporting, data analysis) and supportive activities (e.g., training, supervision, logistics) were assessed. Descriptive statistics were generated using SPSS version 25. Using a priori thresholds from WHO IDSR and Ethiopian PHEM standards (≥90% adherence for formal facilities, ≥ 80% for community actors), we evaluated performance across all levels. Results Substantial variation was observed in the use of standardized case definitions, with adherence rates of 96% in public facilities, 67% in private facilities, 50% in health posts, and 4.17% among HDA members. This represents an 89-percentage-point gap between public facilities and community-level HDA members. All districts reported having rapid response teams; however, only 54% had budget lines dedicated to outbreak response. Surveillance data reporting forms were adequately available in only 15–23% of facilities, and only 61% of districts maintained emergency stockpiles. Training coverage and supervision frequencies varied, with significantly lower coverage among health posts and community-level actors. Only 11% of health posts and 12% of HDA members reported receiving relevant training. Thus, neither health posts nor HDA members met the predefined ≥80% training coverage benchmark. District-level facilities showed higher access to surveillance guidelines (92%) compared to 44% in public facilities and 50% in health posts. Complete reports were submitted by all private facilities (100%) but by only half of health posts (55%). Among HDA members, only 22% found data collection formats clear and easy to fill. Regarding surveillance system attributes, public and private facilities generally found case definitions easy to apply (85–93%), while only 37% of HDA members reported simplicity. Challenges with data quality, trend analysis, and procedural flexibility were frequently cited, particularly among lower-tier facilities. Acceptability of surveillance activities was high among public facilities (70%) but lower at district level (30%). At the community level, only 37% of HDA members found case definitions easy to apply, and just 22% rated reporting formats as usable. Conclusions The IDSR system in Sidama Region demonstrates uneven implementation across healthcare tiers, with notable disparities in training, supervision, data analysis, and resource availability. While district-level offices show relatively strong system components, lower-level facilities and community actors lack adequate support, compromising early detection and response capabilities. Strengthening training programs, harmonizing tools and guidelines, and improving logistics and digital infrastructure are critical for enhancing the overall effectiveness of Ethiopia’s disease surveillance system at the regional level.

Can we target CTCL clonal evolution and improve outcomes?

Surge in fake citations uncovered by audit of 2.5 million biomedical-science papers

Data-driven risk assessment of hydrothermally altered goafs in deep metal mines via unsupervised typing and nonlinear evolution

Decoding the genetic basis of demyelination: Prediction of potential pathogenic coding and regulatory noncoding MBP SNPs in multiple sclerosis

Background The Myelin Basic Protein (MBP) gene is essential for myelin sheath formation in the central nervous system. Coding and noncoding single-nucleotide polymorphisms (SNPs) can impair the protein structure and function, contributing to demyelinating diseases exemplified by multiple sclerosis. This study aimed to assess the impact of SNPs in the MBP gene on protein structure and function. Methods We employed a comprehensive approach to investigate the impact of both noncoding and coding SNPs of the MBP gene. Initially, we utilized RegulomeDB to assess the regulatory roles of SNPs located in the 3′ untranslated regions (3′ UTRs). Subsequently, we examined the influence of the 3’ UTR SNPs on microRNA (miRNA) binding sites using PolymiRTS. Furthermore, we analyzed the functional 3′ UTR SNPs using RNAfold to evaluate their impact on RNA structure. To predict deleterious nonsynonymous SNPs (nsSNPs), various bioinformatics tools, including SIFT, PolyPhen-2, PROVEAN, META-SNP, ESNPs&GO, PANTHER, and AlphaMissense, were employed. Protein stability was assessed using I-Mutant2.0, MUpro, and DDMut. Structural modeling was performed with AlphaFold, and both wild-type and mutant proteins were visualized in UCSF ChimeraX. Conservation analysis was conducted using the ConSurf tool, and protein interaction networks were explored using the STRING database. Results Eight noncoding SNPs were identified as potential regulatory SNPs, affecting the miRNA binding sites. Moreover, three nsSNPs, rs1971676214 (D173E), rs1242552448 (D173H), and rs772570115 (G176W), were consistently predicted to be pathogenic and to destabilize the protein structure. These variants were located in highly conserved sites and disrupted hydrogen bonds. STRING analysis revealed interactions between MBP and other myelin-related, immune, and signaling proteins, linking it to CNS and autoimmune pathways. Conclusions This study identified eight noncoding 3′ UTR SNPs and three potentially pathogenic nsSNPs that may compromise gene expression and protein structure and function, respectively, offering insight into genetic mechanisms of demyelination.

Old drug, new parasite: targeting leukemia with antifungals

World’s largest forest research agency faces severe cutback by Trump administration

Chlorella vulgaris and Dunaliella salina-enriched Artemia salina enhances growth, pigmentation, gut morphology and immune-related pathways in goldfish (Carassius auratus)

Effects of compartment and severity of pelvic organ prolapse on voiding difficulty and overactive bladder: A case-control study with multiple outcomes

Background The current understanding of the relationship between different degrees of prolapse and the impact of prolapse in different compartments on voiding difficulty (VD) and overactive bladder (OAB) remains insufficient and requires further research. This study aimed to investigate the association between pelvic organ prolapse (POP) and the risk of VD and OAB. Methods A retrospective case-control study was conducted among women diagnosed with POP at urogynaecology clinic in a university hospital from January 2018 to December 2020. Patients were divided into two case events (VD and OAB) and a control group (POP without lower urinary tract symptoms [LUTS]). Associations between the site and severity of prolapse in the case and control groups were investigated to identify the factors involved in VD and OAB. Results The study included 151 cases of women with POP experiencing VD, 139 instances of OAB, and 151 women without LUTS in the control group. Most women with POP were postmenopausal, multiparous, and overweight. A multivariate logistic regression analysis revealed that the only factor associated with VD and OAB among women with POP was an advanced stage of anterior compartment prolapse (odds ratio [OR] 4.91, 95% confidence interval [CI] 2.36–10.25, p < 0.001, OR 2.28, 95% CI 1.09–4.78, p < 0.03, respectively). Conclusions An advanced stage of anterior compartment prolapse was the main factor that affected VD and OAB in women with POP.

Venetoclax Plus Pediatric Regimen in Adolescents and Adults with Ph-Negative Acute Lymphoblastic Leukemia

The BCL-2 inhibitor venetoclax has shown promise in acute lymphoblastic leukemia (ALL), but its role in first-line therapy for newly diagnosed (ND) Philadelphia chromosome-negative (Ph⁻) ALL is undefined. In this prospective phase 2 study, 167 adolescents and adults (aged 14-60 years) with ND Ph⁻ ALL received venetoclax combined with pediatric-inspired chemotherapy. The primary endpoint was the rate of measurable residual disease (MRD) negativity by multiparameter flow cytometry (MFC) after induction. The complete remission rate was 91.0%, and 73.0% of responders achieved MFC-MRD negativity, meeting the primary endpoint. After a median follow-up of 19.3 months, median overall and disease-free survival were not reached; estimated 2-year survival rates were 78.5% and 76.7%, respectively. Propensity score-matched analysis confirmed superior survival compared with historical chemotherapy-only controls. Grade ≥ 3 adverse events were primarily hematologic toxicities and infections, with an incidence comparable to that of the historical cohort. These results demonstrate that adding venetoclax to pediatric-inspired chemotherapy significantly improves MRD response and survival outcomes in ND Ph⁻ ALL, with a manageable safety profile. This trial was registered with ClinicalTrials.gov under the identifier NCT05660473.