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Restrictive versus liberal oxygenation targets in patients with acute heart failure and pulmonary congestion–A protocol for a Randomized Controlled Trial (The REDOX-AHF trial)

Introduction Acute heart failure (AHF) is the cause of one in twenty hospital admissions. Supplemental oxygen therapy is a routine treatment in the management of patients with dyspnea, including those with AHF. Current guidelines recommend oxygen therapy as part of the initial treatment, if peripheral oxygen saturation (SpO 2 ) is < 90% or partial pressure of arterial oxygen (PaO 2 ) is < 60 mmHg to correct hypoxemia. There is no clear evidence favoring restrictive or liberal oxygenation strategies in patients with acute heart failure. The aim of this study is to compare restrictive and liberal oxygenation strategies in patients hospitalized for acute heart failure. Methods The study is an investigator-initiated, multicenter, prospective, double-blinded, randomized clinical trial. Patients are randomized in a 1:1 fashion to receive one of the two treatment-strategies: liberal oxygenation (SpO 2 target of 96%) or restrictive oxygenation (SpO 2 target of 90%). The intervention is administrated double-blinded using an automated oxygen administration device, titrating the oxygen supplementation towards the intended target SpO 2 without it being visible for patients, investigators or clinical staff. The primary outcome is pulmonary congestion, measured by remote dielectric sensing (ReDS) after 24 hours, adjusted for baseline measurements. Conclusion This study will explore the current uncertainty regarding restrictive and liberal oxygenation targets in acute heart failure.

Bioactivity assessment and LC–MS/MS-based phenolic characterization of Gypsophila pilosa

Vitamin D alleviates neurotoxicity induced by propofol anaesthesia in the offspring of mice

Background Maternal propofol can induce neurotoxicity in the developing brain. Vitamin D modulates neurotrophin and neuromediator synthesis, reduces neuroinflammation and neuroapoptosis. The present study examined whether vitamin D could mitigate maternal propofol induced neurotoxicity in the offspring. Method Twenty pregnant mice were randomly divided into four groups. During the pregnancy, the groups designated as D and PD were given intraperitoneal vitamin D, while the groups labelled as P and C received 1 ml of saline. On the 14th day of pregnancy, groups P and PD received 200 mg kg -1 of propofol intraperitoneally. Newborn mice from the aforementioned groups were included in the study. The hippocampus and the prefrontal cortex were examined by immunohistochemistry at two postnatal ages: 7 and 45 days (PN7 and PN45). A battery of behavioural assessments was conducted using open field and elevated plus maze tests to evaluate potential alterations at PN45. Results Vitamin D reduced the expression of inflammatory and apoptotic factors induced by propofol, such as TNF-α (group P versus group PD: 0.79 (0.76–0.81) versus 0.36 (0.34–0.39), %95 CI; p < 0.001), Bax (group P versus group PD: 0.72 (0.69–0.74) versus 0.52 (0.5–0.54), %95 CI; p < 0.001) in the hippocampus in PN7. The administration of vitamin D resulted in enhanced expression of anti-apoptotic and neuroprotective proteins, such as Bcl-2 (group P versus group PD: 0.3 (0.27–0.33) versus 0.55 (0.53–0.57), %95 CI; p < 0.001) in the hippocampus in PN7. These changes also occurred in the hippocampus in PN45 and the prefrontal cortex in PN7 and PN45. No significant differences were identified in the behavioural tests between the groups. Conclusion Vitamin D treatment during pregnancy could prevent neurotoxicity in the offspring of mice exposed to propofol.

Improving the performance of practical wavelength division multiplexing decoy-state quantum key distribution with advantage distillation

Ovarian follicle dynamics in the plains zebra (Equus quagga)

Understanding follicular dynamics during the estrous cycle is essential for developing breeding programs and assisted reproductive technologies (ARTs) in any species. In this context, knowledge of follicular dynamics and related uterine changes in the plains zebra ( Equus quagga ) is essential to increase the declining population of this vital African species and to provide comparative insights into more endangered zebra species. Likely due to the difficulty of handling these wild species, no detailed reproductive study using ultrasonography has been performed in any zebra. Therefore, the present study aimed to describe follicular dynamics and endometrial echotexture changes in plains zebras using data collected daily via transrectal ultrasonographic monitoring of the ovaries and uterus during spontaneous estrous cycles (no exogenous hormones administered; Experiment 1) and induced ovulatory periods (exogenous hormones administered; Experiment 2). Data from four plains zebra mares revealed that their spontaneous estrous cycles (n = 9) are characterized by a long interovulatory interval (IOI; approximately 38 days), low daily antral follicle count during the IOI (approximately 3 follicles), an absence of follicular waves, a slow follicular growth rate (approximately 1 mm per day), and a relatively similar mean ovulatory follicle diameter (approximately 36 mm) compared to domestic equids. Furthermore, the zebra shows endometrial echotexture patterns similar to those of the horse mare during the preovulatory period. Additionally, by evaluating induced ovulatory periods in two zebras (n = 10 periods), it was shown that these animals respond reliably to luteolytic and ovulation synchronization drugs. Overall, the information provided in this study is vital for the development of breeding programs and ARTs in the plains zebra. In this way, conservation efforts can not only begin to improve the numbers of the plains zebra but also use the information learned from this species to inform efforts for other, more endangered zebras.

Associations of mindful eating and physical activity with mental workload and sleep quality in medical interns

RAGER: A user-friendly computational platform for integrated analysis of RNA-Seq and ATAC-seq data

Technical advances in RNA sequencing (RNA-seq) and Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) provide us a genome-wide method to deeper insights into gene expression and regulation. The lack of user-friendly bioinformatics platforms poses a challenge for accurately interpreting such datasets. Here, we present a computational platform, RAGER, that integrates the popular bioinformatics tools in an automated thread for joint mining of RNA-seq and ATAC-seq data. RAGER facilitates integrative analysis of transcriptome and chromatin accessibility by providing an automated workflow that minimizes the need for bioinformatics expertise and significantly reduces processing time. We demonstrate RAGER’s utility for novel biological discovery by characterizing the transcriptome and chromatin accessibility of two recently published datasets. RAGER was implemented using Snakemake and is freely available via https://github.com/bioinfo202408/RAGER .

Esculeoside A attenuates aortic remodeling and early atherosclerosis-like changes, with protective effects strongly associated with Nrf2 activation in high-cholesterol-fed rats

C–N exchange model of legume–Rhizobium symbiosis incorporating ATP budget constraints and energy–mass balance between the species

We present a comparative advantage model of carbon–nitrogen exchange in legume– Rhizobium symbiosis that incorporates ATP budget constraints and the energy–mass balance between the host and symbiont. In this framework, the uptake of carbon and nitrogen is limited by the ATP available to each partner, and any imbalance in trade is compensated by adjustments in symbiont biomass. Using empirical estimates of the ATP costs of carbon and nitrogen uptake, together with data on body C:N ratios, the model generates three key predictions, and we prove that they align with empirical results. (i) The condition for the establishment of symbiosis derived from the model is consistent with measured ATP costs in both host and symbiont. (ii) At equilibrium, the model predicts a relatively low carbon supply from the legume and a relatively high nitrogen supply from Rhizobium , in agreement with reported patterns of exchange. (iii) The model further predicts that the proportion of carbon supplied decreases as the host C:N ratio increases, and that the proportion of nitrogen supplied decreases as the symbiont C:N ratio decreases, which are consistent with the empirically observed decline in nodulation during host aging.

Spectroscopic investigation of the photochemical transformations of metoclopramide hydrochloride in the presence of alkaline and oxidative conditions

The effect of Demodex-associated Bacillus oleronius proteins and hyperosmolarity on a human conjunctival epithelial cell line

Purpose Demodex mites act as a carrier vector for the bacterium Bacillus oleronius . Antigenic proteins from this bacterium are capable of producing an inflammatory response. This study investigated the potential effects of Demodex spp.-associated Bacillus oleronius proteins and dry eye-induced hyperosmolarity on an immortalised human conjunctival epithelial (Chang) cell line. Methods The Wong Kilbourne derivative of the Chang (WKD) HeLa-modified conjunctiva-derived epithelial cell line was cultured in a series of NaCl-hyperosmolar conditions with various concentrations ranging from 350mOsm/L to 550mOsm/L. Chang cells were then exposed to semi-purified B.oleronius proteins at 2 µg and 6 µg either alone or in conjunction with dry eye-induced hyperosmolar (HO) stress at 2 µg + HO500 mOsm/L and 6 µg + HO500 mOsm/L. The cell viability was assessed with the RealTime-Glo MT cell viability assay. Results Compared to controls, the cell viability appeared to decrease in a dose-dependent manner. B. oleronius concentration at 6 µg showed significantly lower cell viability than both controls (p < 0.001) and 2 µg (p < 0.001). When 500mOsm/L was added to the 2 µg and 6 µg concentrations, the lowest cell viability was observed (p < 0.001). At 24 hours, the B.oleronius 2 μg combined with HO500 resulted in 38% viable cells, compared to 81% viability in B.oleronius 2 μg alone (p < 0.001). Similarly, the B.oleronius 6 μg combined with HO500 showed only 23% metabolising cells compared to 60% viability cells in B.oleronius 6 μg alone (p < 0.001). Conclusion The results suggest that the presence of bacterial proteins and hyperosmolarity have a dose and time-dependent effect on cellular viability. These experiments suggest that patients affected with the comorbidity of dry eye disease and Demodex blepharitis could experience more severe signs than those with Demodex- associated blepharitis alone.

Sociodemographic and clinical characteristics of Palestinian patients with chronic pain: a cross-sectional study from Al-Shifa Hospital, Gaza

28-day all-cause mortality and associated factors in cancer patients with bacteremia at a peruvian referral center

Introduction The global prevalence of cancer has increased in recent decades. Cancer patients are especially vulnerable to invasive infections like bacteremia. In Peru, the rising incidence of bloodstream infections caused by resistant pathogens has become a major public health issue. There is limited information about this complication in the Peruvian cancer population. No previous local studies have assessed mortality or explored the impact of antimicrobial resistance on patient outcomes in this group. Methods This study aimed to evaluate 28-day all-cause mortality and its associated factors among cancer patients with bacteremia at a referral cancer center in Lima. We retrospectively analyzed data from first episodes of bacteremia in hospitalized adult patients between July 2020 and June 2024. Results A total of 293 patients were included in the study. The mean age was 65.4 ± 15.3 years, and 53.9% were female. Most patients had solid tumors (84.3%) and active disease (91.8%), with digestive cancers being the most common (34.1%). The 28-day all-cause mortality rate was 32.1%. Empirical antimicrobial therapy was appropriate in 80.7% of cases. Gram-negative bacteria (GNB) predominated (82.8%), with Escherichia coli being the most frequently isolated pathogen (45.7%). Among Enterobacteriaceae, 43.6% were extended-spectrum beta-lactamase (ESBL) producers, and 3.3% of GNB were carbapenem-resistant. Multivariable Poisson regression identified the Charlson Comorbidity Index (RR 1.1; 95% CI 1.1–1.2), sepsis (RR 2.3; 95% CI 1.3–3.8), septic shock (RR 3.0; 95% CI 1.9–4.6), respiratory failure (RR 1.6; 95% CI 1.2–2.2), Coagulase-negative Staphylococci (CoNS) bacteremia (RR 1.8; 95% CI 1.2–2.6) and primary source (RR 2.8; 95% CI 1.5–5.1) as independent factors associated with increased 28-day mortality. Conclusion At this cancer referral center, one-third of patients with bacteremia died within 28 days. Mortality was primarily caused by the severity of infection, comorbidities and specific bacteremia characteristics, rather than antimicrobial resistance.

Explainable machine learning-based investigation for influential parameters towards interfacial capacity of spliced glass fiber reinforced polymer bars

Peer-mediated instruction improves acquisition of complex wrestling techniques in school physical education

This study investigated the effectiveness of peer-mediated instruction as a student-centered teaching method in physical education by assessing its impact on middle school students’ ability to learn complex wrestling techniques. A total of 36 students took part in an eight-week program comparing peer-mediated instruction with traditional direct instruction. Performance on four wrestling techniques—arm drag, underarm pass, single-leg takedown, and double-leg takedown—was evaluated using standardized observation criteria and independent raters. Results from independent-samples t-tests indicated that students in the peer-teaching group performed significantly better on the underarm pass, t(34) = 3.976, p = .001, d = 1.33, and the double-leg takedown, t(34) = 2.31, p = .027, d = 0.78. No significant differences between groups were found for the arm drag, t(34) = 1.685, p = .101, d = 0.55, or the single-leg takedown, t(34) = 0.52, p = .606, d = 0.18. These results suggest that peer-mediated instruction may be more effective than direct instruction for techniques that demand higher perceptual-motor coordination and involve greater task complexity. The study adds to the sport pedagogy literature by demonstrating that peer-assisted learning can support skill development and collaborative participation in school-based physical education.

Stability and yield performance of lablab genotypes across multiple environments in Ethiopia

Retinal macrophage-like cell activation and ganglion cell layer thinning are associated with disability and MRI lesion burden in multiple sclerosis

Background Multiple sclerosis is a chronic neuroinflammatory disease in which microglia and macrophage-like cells play a central role in disease progression. The retina, as a central nervous system extension accessible to non-invasive imaging, offers a unique window into these processes. Objective The aim of this study was to determine whether retinal macrophage-like cell characteristics and ganglion cell layer thickness are associated with clinical disability and magnetic resonance imaging lesion burden in patients with multiple sclerosis. Methods In this cross-sectional observational study, patients with multiple sclerosis and age-matched healthy controls underwent retinal imaging using spectral-domain optical coherence tomography and swept-source optical coherence tomography angiography. Macrophage-like cells at the vitreoretinal interface were quantified using an automated image-processing pipeline, while ganglion cell layer and retinal nerve fibre layer thicknesses were measured using standardized segmentation. Clinical disability was assessed using the Expanded Disability Status Scale, the 9-Hole Peg Test, and the 25-Foot Walk. Brain magnetic resonance imaging lesion counts were obtained from T1- and T2-weighted sequences. Results Overall retinal macrophage-like cell parameters did not differ between patients with multiple sclerosis and controls. However, patients with greater disability, defined as an Expanded Disability Status Scale score of five or higher, showed significantly increased macrophage-like cell count and density. Macrophage-like cell size demonstrated a moderate positive association with T2 lesion burden, while only weak associations were observed with T1 lesions. Ganglion cell layer thickness was significantly reduced in the inferior and nasal macular regions in patients with multiple sclerosis compared with controls, whereas retinal nerve fibre layer thickness was preserved. Disability scores showed moderate correlations with upper and lower limb functional tests. Conclusions These findings indicate that retinal cellular and structural alterations reflect both inflammatory and neurodegenerative components of multiple sclerosis. Retinal macrophage-like cell metrics are associated with disease burden and disability, while ganglion cell layer thinning provides evidence of neuroaxonal loss. Retinal imaging may serve as a non-invasive complement to magnetic resonance imaging for assessing disease severity and progression in multiple sclerosis.

Effects of online collaborative learning and simulation-based learning on pedagogical knowledge and teaching efficacy in digital education

Effectiveness of tele-rehabilitation using AI-guided exercise and pain neuroscience education for fibromyalgia (FIBROIA): Protocol for a randomized controlled trial

Introduction Fibromyalgia (FM) is a chronic condition characterized by widespread pain and cognitive dysfunction, with pharmacological treatments offering limited efficacy. Although Pain Neuroscience Education (PNE) and therapeutic exercise are evidence-based interventions, accessibility and adherence remain major challenges particularly in underserved regions such as Latin America. This trial investigates the effectiveness of a 12-week tele-rehabilitation program (FIBROIA) that integrates Artificial Intelligence (AI)-guided exercise with PNE to enhance access to comprehensive multimodal care. Methods and analysis This multicentre, randomized, assessor-blinded, parallel-group controlled trial will enroll fifty adults meeting the 2016 ACR criteria for FM. Participants will be randomly assigned (1:1) to either the intervention group or enhanced usual care. The intervention consists of three personalized exercise sessions per week delivered through the Rehbody AI platform, which provides real-time biomechanical feedback, along with a weekly PNE module designed to reconceptualize pain. The primary outcome is the change in pain intensity, measured using the Visual Analogue Scale (VAS), at week 13 (±7 days), immediately following completion of the 12-week program. Secondary outcomes include the Fibromyalgia Impact Questionnaire–Revised (FIQ-R), lower-limb strength assessed by the 30-Second Sit-to-Stand test, and health-related quality of life measured with the EQ-5D-3L. Statistical analyses will follow an intention-to-treat (ITT) framework. Discussion The FIBROIA protocol addresses the urgent need for scalable, evidence-based interventions in resource-limited settings. By combining AI-driven biomechanical feedback with cognitive reappraisal through PNE, this study seeks to reduce fear-avoidance behaviors and improve exercise adherence. This integrative approach aims to overcome the limitations of passive tele-rehabilitation by simulating asynchronous professional supervision, thereby ensuring both safety and technical precision in movement execution. Conclusions If effective, this protocol will offer a robust, technology-enabled framework for remote FM management. The results could help establish a new clinical standard for accessible, patient-centered rehabilitation, bridging the gap between high-level evidence and real-world practice across diverse socioeconomic contexts. Trial registration ClinicalTrials.gov NCT06672419 .

Enhanced detection of network intrusions and anomalies in internet of things applications using a hybrid artificial intelligence model combining CNN and LSTM