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23 pages, 9423 KB  
Article
Spatiotemporal Evaluation of Multi-Source Precipitation Products in the Sudan Sahel: Evidence from White Nile State
by Abdelbagi Yanes Fadlalmwlla Adam, Zoltán Gribovszki and Péter Kalicz
Remote Sens. 2026, 18(13), 2079; https://doi.org/10.3390/rs18132079 (registering DOI) - 25 Jun 2026
Abstract
Accurate rainfall estimates are essential for managing water resources and planning for climate risks in semi-arid regions, yet long-term gauge networks in these environments are often extremely limited. In this study, we evaluate three widely used multi-source precipitation datasets—CHIRPS, IMERG, and ERA5-Land—against long-term [...] Read more.
Accurate rainfall estimates are essential for managing water resources and planning for climate risks in semi-arid regions, yet long-term gauge networks in these environments are often extremely limited. In this study, we evaluate three widely used multi-source precipitation datasets—CHIRPS, IMERG, and ERA5-Land—against long-term observations from Ed Dueim and Kosti, the two main reference stations in White Nile State, central Sudan. The assessment covers monthly and annual scales across each product’s available record (1952–2022) and uses a broad set of metrics, including Pearson and Spearman correlations, NSE, KGE, RMSE, MAE, percent bias, and categorical detection scores (POD, FAR, CSI). All three datasets capture the region’s single-peak June–October monsoon pattern, but their accuracy differs sharply when it comes to rainfall amounts and year-to-year variability. CHIRPS performs best overall, with the strongest monthly efficiency scores of any product and a consistent, operationally correctable dry bias of 5–13%. IMERG shows strong monthly correlations but consistently overestimates rainfall by 25–42%, which leads to unreliable annual totals. ERA5-Land performs worst across nearly all metrics, with monthly NSE near or below zero, and frequent false alarms during the dry season. Taken together, the evidence points to CHIRPS as the most reliable dataset for routine hydro-climatic monitoring in White Nile State, while IMERG and ERA5-Land may still be useful in more specialized or time-specific applications. Full article
(This article belongs to the Section Satellite Missions for Earth and Planetary Exploration)
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17 pages, 887 KB  
Review
Extended and Repeated Cytoreductive Surgery in Recurrent Uterine Leiomyosarcoma: A Narrative Review
by Antonio Maccio, Manuela Neri, Valerio Vallerino, Sonia Nemolato, Elisabetta Pusceddu, Gabriele Sole and Paolo Albino Ferrari
Cancers 2026, 18(13), 2061; https://doi.org/10.3390/cancers18132061 (registering DOI) - 25 Jun 2026
Abstract
Background/Objectives: Recurrent uterine leiomyosarcoma (ULMS) frequently poses a surgical question because systemic options remain limited and recurrence patterns are heterogeneous. We reviewed the published evidence on repeated and extended cytoreductive surgery for recurrent ULMS, focusing on selection criteria, operative boundaries, and the role [...] Read more.
Background/Objectives: Recurrent uterine leiomyosarcoma (ULMS) frequently poses a surgical question because systemic options remain limited and recurrence patterns are heterogeneous. We reviewed the published evidence on repeated and extended cytoreductive surgery for recurrent ULMS, focusing on selection criteria, operative boundaries, and the role of multivisceral, thoracic, and peritoneal-directed procedures. Methods: This narrative review synthesizes peer-reviewed literature on surgically managed recurrent or metastatic ULMS, prioritizing contemporary guidelines, retrospective cohorts, pooled analyses, selected systematic reviews when directly relevant to the surgical question, and published illustrative reports. The search covered records available from database inception through 14 May 2026 and used PubMed/MEDLINE, Web of Science Core Collection, Scopus, Google Scholar, selected publisher databases, and citation-linked records. No new patient-level or institution-specific clinical data are presented. Results: The available evidence is entirely retrospective and strongly affected by selection bias, yet it consistently suggests that the best outcomes are observed when complete gross resection is feasible. Across published series, favorable features include isolated or limited recurrence, longer time to relapse, compartmentalized disease, lung-only metastases, and preserved performance status. Contemporary reports also show that repeat surgery may evolve into extensive multivisceral procedures involving bowel resection, upper-abdominal dissection, urinary tract reconstruction, diaphragmatic resection, and thoracic surgery. Peritoneal-directed CRS/HIPEC-type strategies remain supported mainly by small heterogeneous studies and a ULMS-specific systematic review, reinforcing feasibility but not routine use. Published illustrative reports confirm that serial metastasectomies can occasionally support prolonged survival in exceptional patients, but they cannot establish effectiveness. Conclusions: In highly selected patients, repeated and even extensive cytoreductive surgery may remain a rational disease-control strategy for recurrent ULMS. The central unmet need is not proof that surgery can work in exceptional cases, but better criteria to identify who benefits from iterative resection and when escalation to multivisceral or thoracoabdominal surgery is justified. Full article
(This article belongs to the Special Issue Gynecological Cancers: From Bench to Bedside)
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16 pages, 303 KB  
Review
Botulinum Toxin in Parkinson’s Disease Tremor: A Critical Evaluation of the Evidence and Clinical Practice
by Shivam Om Mittal and Wolfgang H. Jost
Toxins 2026, 18(7), 280; https://doi.org/10.3390/toxins18070280 (registering DOI) - 25 Jun 2026
Abstract
Approximately 30% of patients with tremor-dominant Parkinson’s disease (PD) have rest tremor that persists despite optimal dopaminergic therapy. When deep brain stimulation and focused ultrasound are unavailable or declined, the therapeutic options narrow. Botulinum toxin (BoNT) offers a targeted, titratable, reversible approach, but [...] Read more.
Approximately 30% of patients with tremor-dominant Parkinson’s disease (PD) have rest tremor that persists despite optimal dopaminergic therapy. When deep brain stimulation and focused ultrasound are unavailable or declined, the therapeutic options narrow. Botulinum toxin (BoNT) offers a targeted, titratable, reversible approach, but whether a peripheral neuromuscular blocking agent makes sense for a centrally generated tremor is a legitimate question that deserves a direct answer. This narrative critical review appraises what is currently known across PD and non-PD tremor conditions, defines the technical requirements for safe and effective injection, and provides a practical framework for patient selection and clinical management. The PD-specific literature rests on a single positive double-blind randomized controlled trial of 30 patients; all remaining data are open-label or extrapolated from other tremor conditions, and this narrative synthesis combines heterogeneous conditions, outcome scales, and toxin protocols. A recurring technical observation is that, in the available trials, individualized, EMG-guided injection has been associated with substantially lower rates of hand weakness than fixed-dose injection (reported reductions from roughly 30–70% to below 15%) while maintaining tremor reduction, although the degree of benefit and weakness risk vary with the tremor syndrome, injected muscles, baseline impairment, dose, and guidance method. The careful patient selection this approach requires helps the individual clinician and patient achieve tremor relief, but it departs from the unselected real-world PD population and introduces selection bias that makes a large, statistically representative cohort difficult to assemble. In well-selected patients at centers with the appropriate expertise, BoNT may be a clinically useful option, but routine adoption is not yet supported. Full article
(This article belongs to the Special Issue Botulinum Toxins: Past Successes and New Goals)
29 pages, 1273 KB  
Article
Modelling Temporal Asymmetry in Industrial IoT Energy Data: A Comparative Study of Hybrid Statistical–Neural Forecasting Pipelines
by Meruyert Sakypbekova, Bauyrzhan Amirkhanov, Ramilya Aubakirova, Miras Tokhtassyn, Yanwei Fu and Gulshat Amirkhanova
Symmetry 2026, 18(7), 1077; https://doi.org/10.3390/sym18071077 (registering DOI) - 25 Jun 2026
Abstract
Industrial energy consumption in shift-based manufacturing exhibits pronounced temporal asymmetry—here defined as direction-dependent conditional dynamics in which the transition from production to shutdown states follows a systematically different temporal trajectory than the reverse transition. At the facility studied, this asymmetry also manifests in [...] Read more.
Industrial energy consumption in shift-based manufacturing exhibits pronounced temporal asymmetry—here defined as direction-dependent conditional dynamics in which the transition from production to shutdown states follows a systematically different temporal trajectory than the reverse transition. At the facility studied, this asymmetry also manifests in the marginal distribution of hourly consumption values: pooling all 4724 observations yields a bimodal, right-skewed histogram (skewness ≈ −0.4) comprising two sub-populations corresponding to production hours (14–19 kWh/h) and shutdown hours (0–2 kWh/h). Although individual hourly observations are serially dependent and therefore not i.i.d., the marginal distributional shape is consequential because ARIMA-class models assume approximately Gaussian innovations, and residuals from models fit to this bimodal series inherit its non-Gaussianity. More fundamentally, the conditional distribution P(E_t|E_{t − 1}, …) is direction-dependent: the production-to-shutdown transition is abrupt (1–2 h, 18:00–20:00), while the shutdown-to-production ramp is slower and more variable (2–4 h, 05:00–07:00). Symmetric ARMA models, applying identical autoregressive coefficients regardless of transition direction, cannot represent this directional asymmetry, rendering their assumptions and associated error metrics structurally unreliable for this class of data. This paper addresses this asymmetry directly by presenting and evaluating two hybrid forecasting architectures—Prophet+LSTM and SARIMA+LSTM—for 24 h-ahead energy prediction at an industrial bread factory in Kazakhstan, instrumented with 15 IoT energy meters. The two-stage design exploits the complementary asymmetry-handling properties of each component: the statistical model (Prophet or SARIMA) captures deterministic seasonal structure, while the LSTM corrects asymmetric residuals that the statistical model systematically misrepresents. In a rigorous 14-day holdout evaluation, Prophet+LSTM achieves an MAE of 3.39 kWh—outperforming the Seasonal Naïve baseline by 12.3% and reducing Prophet-alone error by 32.7%—with statistical significance at the 10% level confirmed via Diebold–Mariano testing (DM = +1.747, p = 0.081). The LSTM residual correction reduces Prophet’s systematic negative bias by 69% (from −3.60 to −1.13 kWh), as confirmed by ablation testing. In eight weeks of production operation with incremental retraining, MAE improved 35% (7.02 → 4.58 kWh). These results demonstrate that explicitly modelling temporal asymmetry through hybrid statistical-neural architectures substantially improves industrial energy forecasting accuracy. Full article
(This article belongs to the Section Computer)
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21 pages, 1460 KB  
Review
Role of Supraspinal Neuroinflammation in Chronic Pain After Experimental Spinal Cord Injury—A Systematic Review
by Telma Ferreira, Célia Duarte Cruz and José Tiago Costa-Pereira
Int. J. Mol. Sci. 2026, 27(13), 5711; https://doi.org/10.3390/ijms27135711 (registering DOI) - 24 Jun 2026
Abstract
Spinal cord injury (SCI) is a major cause of long-term disability and is frequently accompanied by chronic pain, substantially reducing quality of life. Although spinal neuroinflammation is a recognized contributor to neuropathic pain, the role of supraspinal neuroinflammation remains less well defined. This [...] Read more.
Spinal cord injury (SCI) is a major cause of long-term disability and is frequently accompanied by chronic pain, substantially reducing quality of life. Although spinal neuroinflammation is a recognized contributor to neuropathic pain, the role of supraspinal neuroinflammation remains less well defined. This systematic review critically evaluated experimental evidence linking SCI-induced supraspinal neuroinflammation with pain-related behaviors in animal models. A systematic literature search in PubMed, Web of Science Core Collection, and Scopus identified studies published over the last 20 years using rodent SCI models that assessed both supraspinal neuroinflammatory markers and pain-related behaviors. After screening, nine studies met the predefined criteria. The analyzed studies suggested that SCI is associated with supraspinal neuroinflammatory alterations, including increased microglial and astrocytic activation and upregulation of pro-inflammatory cytokines and chemokine-related pathways, in several brain regions. In intervention studies, reduced neuroinflammation was accompanied by improvement in mechanical or thermal pain-related behaviors. However, considerable methodological heterogeneity and moderate to high risk of bias were observed. Current evidence suggests an association between supraspinal neuroinflammatory alterations and chronic pain-related behaviors after SCI, but the limited number of studies and methodological variability restrict firm conclusions. Further well-designed experimental studies are needed to clarify underlying mechanisms. Full article
(This article belongs to the Section Molecular Neurobiology)
14 pages, 1282 KB  
Systematic Review
Efficacy and Safety of Octreotide for Gastrointestinal Bleeding Due to Portal Hypertension in Children—A Systematic Review
by Ann Kozak, Grace Nolder, Giusy Ranucci and Alessio Provenzani
Pharmaceuticals 2026, 19(7), 978; https://doi.org/10.3390/ph19070978 (registering DOI) - 24 Jun 2026
Abstract
Background: Portal hypertension can lead to complications such as ascites, hepatic encephalopathy, esophageal varices, and gastrointestinal (GI) bleeding, all of which are associated with significant morbidity and mortality. Variceal bleeding is the most severe complication, with an estimated mortality of up to [...] Read more.
Background: Portal hypertension can lead to complications such as ascites, hepatic encephalopathy, esophageal varices, and gastrointestinal (GI) bleeding, all of which are associated with significant morbidity and mortality. Variceal bleeding is the most severe complication, with an estimated mortality of up to 30%. In children, evidence-based guidelines for the management of GI bleeding secondary to portal hypertension are lacking. In this con-text, octreotide, a synthetic somatostatin analog approved for other indications, has been increasingly used off-label and represents a paradigmatic example of drug re-purposing in pediatrics. Methods: Following the 2020 PRISMA guidelines, this systematic review evaluated the efficacy and safety of octreotide for the treatment of portal hyperten-sion-related GI bleeding in children. A comprehensive search of six sources, including five bibliographic databases (PubMed, Embase, Web of Science, Cochrane Library, and EBSCOhost) and the ClinicalTrials.gov registry, was conducted to identify studies in-cluding pediatric patients with GI bleeding secondary to portal hypertension. Results: Three non-randomized observational studies were included, assessing bleeding recurrence, packed red blood cell requirements, and adverse events following octreotide admin-istration. Overall, 33 patients were analyzed, with a mean age of 6.3 years. One study reported a reduction in rebleeding episodes and transfusion requirements after oc-treotide treatment. Across all included studies, no serious adverse events were ob-served; mild and reversible hyperglycemia was the only reported drug-related effect. Quantitative synthesis was not feasible due to substantial heterogeneity, missing data, and a serious risk of bias, resulting in very low certainty of evidence. Conclusions: Octreotide may represent a feasible therapeutic option for portal hypertension-related GI bleeding in children; however, further prospective and standardized studies are needed to establish its long-term safety and efficacy. Full article
(This article belongs to the Special Issue Pharmacovigilance in Drug Therapy and Adverse Reactions)
18 pages, 1970 KB  
Systematic Review
Strain-Specific Effects of Early-Life Probiotic Supplementation on Respiratory Infections in Infants: A Systematic Review and Meta-Analysis
by Salvatore Michele Carnazzo, Emanuele Sinagra, Dario Raimondo, Arianna Sferruzza, Roberto Ajovalasit, Alessandro Vitello, Andrea Domenico Praticò and Marcello Maida
Nutrients 2026, 18(13), 2067; https://doi.org/10.3390/nu18132067 (registering DOI) - 24 Jun 2026
Abstract
Background/Objectives: Probiotic and synbiotic supplementation has been proposed as a preventive strategy against respiratory tract infections (RTIs) in early childhood, although evidence in infants and young children remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of probiotic or synbiotic [...] Read more.
Background/Objectives: Probiotic and synbiotic supplementation has been proposed as a preventive strategy against respiratory tract infections (RTIs) in early childhood, although evidence in infants and young children remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of probiotic or synbiotic supplementation administered during the first 24 months of life on respiratory infection outcomes. Methods: PubMed/MEDLINE, Embase, and Scopus were systematically searched for randomized controlled trials published between January 2015 and 30 September 2025. Eligible studies included infants and children aged ≤24 months receiving oral probiotics or synbiotics compared with placebo, no intervention, or standard care. The primary outcome was the incidence of at least one upper respiratory tract infection (URTI), while the secondary outcome was the incidence of any RTI. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated according to the GRADE approach. Results: Nine randomized controlled trials were included. Probiotic or synbiotic supplementation did not significantly reduce the risk of URTI (OR 0.95, 95% CI 0.47–1.95; I2 = 78%). A non-significant trend toward a reduced risk of any RTI was observed (OR 0.66, 95% CI 0.35–1.25; I2 = 69%). Exploratory subgroup analyses suggested possible strain-specific effects, with signals observed for Bifidobacterium longum subsp. infantis in relation to URTI prevention and Lactiplantibacillus plantarum ATCC 202195 for reduction in any RTI. However, these findings were based on a limited number of studies and should be interpreted cautiously. No serious adverse events attributable to supplementation were reported. Conclusions: Current evidence does not support the routine use of probiotic or synbiotic supplementation for the prevention of respiratory infections in children aged ≤24 months. However, potential strain-specific benefits warrant further investigation in adequately powered randomized trials. Full article
(This article belongs to the Section Prebiotics, Probiotics and Postbiotics)
24 pages, 731 KB  
Article
A Simulation-Based Stress-Testing Framework for Evaluating the Transportability of Imaging-Derived Logistic Risk Models Across Cutaneous Lesion Phenotypes
by Betül Tiryaki Baştuğ, Özlem Türelik, Sinan Topuz, Buket Dursun Çoban and Hatice Gencer Başol
Diagnostics 2026, 16(13), 1961; https://doi.org/10.3390/diagnostics16131961 (registering DOI) - 24 Jun 2026
Abstract
Background: Imaging-based logistic models are widely used for non-invasive risk stratification; however, their structural robustness and transportability across heterogeneous biological contexts remain insufficiently examined. Purpose: This study aimed to develop a simulation-based stress-testing framework to evaluate the structural robustness and transportability [...] Read more.
Background: Imaging-based logistic models are widely used for non-invasive risk stratification; however, their structural robustness and transportability across heterogeneous biological contexts remain insufficiently examined. Purpose: This study aimed to develop a simulation-based stress-testing framework to evaluate the structural robustness and transportability of a radiology-adapted logistic risk model across distinct cutaneous lesion phenotypes under both aligned and structurally perturbed conditions. Methods: A simulation-based methodological framework was implemented using three synthetic cohorts representing nodular, subcutaneous, and vascular lesion phenotypes (n = 2000 per cohort). Model performance was evaluated under naïve transfer, recalibration, and revision conditions. To address potential structural alignment bias, additional simulation scenarios incorporating coefficient perturbations, nonlinear transformations, and interaction effects were used to generate outcome processes partially independent from the original model structure. Model performance was assessed using discrimination (ROC-AUC, PR-AUC), calibration metrics, decision curve analysis, and Monte Carlo-based stability assessments. Results: Under naïve transfer, discrimination remained stable across phenotypes (ROC-AUC ≈ 0.78–0.84). Calibration shifts were observed but were effectively corrected through recalibration. Under structurally perturbed outcome generation, discrimination showed only modest reduction, while overall performance patterns remained consistent. Structural variables demonstrated high transferability, whereas vascular features exhibited phenotype-dependent variability. Decision curve analysis indicated consistent clinical utility across relevant thresholds. Conclusions: The radiology-adapted logistic model demonstrated structural robustness across heterogeneous phenotype conditions, with performance variations driven primarily by calibration differences rather than structural failure. Importantly, robustness was preserved under conditions of structural perturbation, supporting the model’s stability beyond idealized alignment assumptions. These findings suggest that simulation-based stress-testing frameworks provide a rigorous methodological approach for evaluating model transportability prior to large-scale clinical validation. Full article
(This article belongs to the Special Issue Advanced Imaging in the Diagnosis and Management of Skin Diseases)
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21 pages, 906 KB  
Review
Alkaline Water and Muscle Health in Aging: A Systematic Evidence Map and Translational Appraisal of Human Evidence
by Tariq A. Alalwan, Giuseppe Mazzola, Lucia Chiesa, Mariangela Rondanelli and Simone Perna
J. Ageing Longev. 2026, 6(3), 49; https://doi.org/10.3390/jal6030049 (registering DOI) - 24 Jun 2026
Abstract
Alkaline water is increasingly marketed for musculoskeletal and recovery benefits, yet its relevance to healthy aging, sarcopenia prevention, and functional capacity in older adults remains largely unexplored. This systematic evidence map and translational appraisal examined whether the available comparative human evidence on alkaline [...] Read more.
Alkaline water is increasingly marketed for musculoskeletal and recovery benefits, yet its relevance to healthy aging, sarcopenia prevention, and functional capacity in older adults remains largely unexplored. This systematic evidence map and translational appraisal examined whether the available comparative human evidence on alkaline water is applicable to aging populations and longevity research. Following PRISMA guidance, PubMed and Scopus were searched from January 2005 to September 2025. Eligible studies were controlled or comparative observational human studies reporting muscle strength, physical performance, or recovery outcomes. Risk of bias was assessed using RoB 2, ROBINS-I, and JBI criteria; evidence certainty was judged narratively using GRADE-informed principles. Ten studies met the inclusion criteria. Most enrolled young athletic populations; only two had partial relevance to aging cohorts. Crucially, no study included participants aged 65 years or older or assessed primary sarcopenia-relevant endpoints such as appendicular lean mass, gait speed, or chair-rise performance; this total absence of data in the target demographic represents the central limitation of the current literature. Risk of bias ranged from some concerns to serious. The most consistent signals were short-term improvements in lactate clearance and perceived exertion in young male athletes. Evidence for strength, functional performance, and safety in older adults was absent or indirect. Current evidence, rated low to very low certainty for aging-relevant outcomes, does not support alkaline water as an evidence-based strategy for healthy aging or muscle preservation in older adults. Age-appropriate trials using EWGSOP2-aligned outcomes are urgently needed. Full article
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19 pages, 6542 KB  
Article
Sub-Meter Kinematic Orbit Determination of the LEO Satellite Sentinel-6A Using Onboard GNSS Carrier-Smoothed Pseudorange Measurements
by Hyung-Seok Lee and Kwan-Dong Park
Remote Sens. 2026, 18(13), 2067; https://doi.org/10.3390/rs18132067 (registering DOI) - 23 Jun 2026
Abstract
The emerging potential of low-Earth-orbit (LEO) satellite-based Positioning, Navigation, and Timing services has increased the need for real-time, stable, and accurate orbit determination techniques. Here, we propose a method for estimating sub-meter-level LEO satellite orbits using Global Navigation Satellite System (GNSS) code pseudorange [...] Read more.
The emerging potential of low-Earth-orbit (LEO) satellite-based Positioning, Navigation, and Timing services has increased the need for real-time, stable, and accurate orbit determination techniques. Here, we propose a method for estimating sub-meter-level LEO satellite orbits using Global Navigation Satellite System (GNSS) code pseudorange observations. To mitigate ionospheric delay, a dual-frequency ionosphere-free combination was applied, while code-carrier smoothing was employed to reduce code observation noise. A satellite weighting model based on Signal-in-Space Range Error was developed to reflect the orbit and clock error characteristics of different GNSS, and a robust weighting scheme was applied to alleviate the impact of observation outliers. Further, Galileo High Accuracy Service corrections compensated for orbit, clock and code bias errors. The algorithm was validated using the GNSS observation data collected from the Sentinel-6A satellite on 10 August 2023. Each successively applied technique gradually improved orbit determination accuracy, achieving up to a 51% reduction in 3D root mean square error (RMSE). The final RMSE values in the radial, along-track, cross-track, and 3D components were 39.4, 18.8, 23.5, and 49.6 cm, respectively. Temporal analysis showed no distinct periodicity in orbit errors and no significant correlation with satellite visibility or ground track. Full article
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29 pages, 5214 KB  
Systematic Review
Prevalence and Clinical Features of Polyendocrine Metabolic Ovarian Syndrome in the Gulf Cooperation Council Countries: A Systematic Review and Meta-Analysis
by Lama Ali Buhran, Meshal Bader Almutairi, Shehata Farag Shehata, Syed Esam Mahmood, Awad Alsamghan and Ramy Mohamed Ghazy
Healthcare 2026, 14(13), 1826; https://doi.org/10.3390/healthcare14131826 (registering DOI) - 23 Jun 2026
Abstract
Background: Polyendocrine metabolic ovarian syndrome (PMOS/PCOS) is the most common hormonal disorder in women of reproductive age and is linked to infertility as well as long-term metabolic and psychological problems. In the Gulf Cooperation Council (GCC) region, rising obesity, dietary changes, and sedentary [...] Read more.
Background: Polyendocrine metabolic ovarian syndrome (PMOS/PCOS) is the most common hormonal disorder in women of reproductive age and is linked to infertility as well as long-term metabolic and psychological problems. In the Gulf Cooperation Council (GCC) region, rising obesity, dietary changes, and sedentary lifestyles may be increasing its burden. However, prevalence estimates remain highly inconsistent due to differences in diagnostic criteria and measurement methods rather than true variation in disease rates. Objective: This study aimed to describe the situation by systematically pooling available evidence on the prevalence of PMOS among women in GCC countries and by summarizing the range of clinical features reported across included studies. Methods: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched five major bibliographic databases (PubMed, Scopus, Web of Science, Cochrane Library, and Embase) and the Google Scholar search engine for observational studies published up to 1 June 2026. Studies were eligible if they reported PMOS prevalence and related clinical features among women of reproductive age residing in GCC countries. After removing duplicates and screening 570 initially identified records, 25 studies met our inclusion criteria; 24 were included in the quantitative meta-analysis after excluding one high-risk study. Risk of bias was appraised using the Joanna Briggs Institute Checklist for Prevalence Studies. A random-effects meta-analysis using the DerSimonian-Laird method, combined with the Freeman-Tukey double arcsine transformation, was used to estimate the pooled prevalence. Heterogeneity was quantified using the I2 statistic and Cochran’s Q test. Subgroup analyses explored differences by country, diagnostic method, study setting, and publication period. Meta-regression was used to identify study-level factors that explained between-study variability. Results: Across 24 studies involving 77,890 women, the pooled prevalence of PMOS was 17.59% (95% CI: 12.98–23.40%). Country-level estimates ranged from 6.56% in Oman to 23.0% in Saudi Arabia. Heterogeneity across all analyses was extremely high (I2 = 99.6%), and meta-regression identified the diagnostic tool as the single most important source of variation, explaining 42.7% of between-study variance. Studies using structured clinical criteria (Rotterdam or NIH) yielded prevalence estimates around 13–14%, while those relying on self-report or physician diagnosis without standardized criteria reported considerably higher figures (20–37%). Common clinical features included menstrual irregularity (up to 100% of PMOS cases in clinical cohorts), hirsutism (5–100%), acne and oily skin (17–74%), and obesity (17–73%). Awareness of PMOS among women in the region was highly variable, ranging from under 3% to nearly 100%. Conclusions: PMOS is a significant public health concern across the GCC region. The markedly higher pooled prevalence combined with high rates of obesity and metabolic risk in this population calls for urgent, coordinated action. Standardizing diagnostic practices, investing in population-level screening, and developing culturally tailored awareness programs are essential steps toward reducing the clinical and social burden of PMOS. Full article
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21 pages, 11840 KB  
Article
Rehospitalization Burden Profiles After Traumatic Spinal Cord Injury: A Data-Driven Latent Class Analysis of the SCIMS Public-Use Database
by Andrea Calderone, Maria Pia Onesta, Laura Simoncini, Antonino Nunnari, Fabrizio Sottile, Angelo Quartarone and Rocco Salvatore Calabrò
J. Clin. Med. 2026, 15(13), 4890; https://doi.org/10.3390/jcm15134890 (registering DOI) - 23 Jun 2026
Abstract
Background/Objectives: Rehospitalization after traumatic spinal cord injury (SCI) is common, but binary or count summaries may obscure heterogeneity in timing, recurrence, frequency, and duration. We aimed to identify clinically interpretable rehospitalization burden profiles in the SCIMS 2021ARPublic dataset and examine descriptive associations with [...] Read more.
Background/Objectives: Rehospitalization after traumatic spinal cord injury (SCI) is common, but binary or count summaries may obscure heterogeneity in timing, recurrence, frequency, and duration. We aimed to identify clinically interpretable rehospitalization burden profiles in the SCIMS 2021ARPublic dataset and examine descriptive associations with clinical correlates and participation outcomes. Methods: We analyzed Form I, Form II, and Record Status public-use files. Among 29,310 individuals with at least one non-lost follow-up interview, 28,745 with at least one non-missing rehospitalization indicator entered latent class analysis. Four prespecified indicators captured early, recurrent, frequent, and prolonged rehospitalization. Candidate two- through six-class models were compared using AIC, BIC, entropy, class size, posterior probabilities, and interpretability. Pairwise adjusted logistic models examined candidate clinical correlates in 10,407 participants with complete 2016+ follow-up data. Adjusted linear models examined CHART participation domains in 20,766–20,949 participants. Results: A four-profile solution was retained: low rehospitalization burden (59.8%), early/prolonged rehospitalization (18.9%), frequent/prolonged rehospitalization (7.7%), and high recurrent/frequent/prolonged burden (13.6%). UTI and pressure ulcer history showed the most consistent associations with burdened profiles. Severe pain and frequent sleep problems were associated with selected heavier-burden profiles, while depressive symptoms showed smaller and less precise associations. Sensitivity analyses supported structural stability while highlighting observation-time bias and classification uncertainty inherent to wave-based public-use data. Compared with the low-burden profile, burden profiles showed lower CHART scores, especially for mobility and occupation. Conclusions: Rehospitalization after traumatic SCI is heterogeneous. These utilization burden profiles summarize distinct observed patterns but require prospective validation before use in risk stratification or follow-up planning. Full article
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62 pages, 3341 KB  
Review
Walking as a Window to the Brain: Redefining Gait in Neurology
by Emmanuel Ortega-Robles, Mario Treviño, Elías Manjarrez and Oscar Arias-Carrión
Med. Sci. 2026, 14(3), 338; https://doi.org/10.3390/medsci14030338 (registering DOI) - 23 Jun 2026
Abstract
Walking is not merely locomotion but a window into the nervous system, integrating cortical, subcortical, cerebellar, spinal, and peripheral networks into a unified motor behavior. Across neurological diseases—including Parkinson’s disease, atypical parkinsonism, cerebellar ataxias, stroke, multiple sclerosis, neuropathies, neuromuscular disorders, and functional gait [...] Read more.
Walking is not merely locomotion but a window into the nervous system, integrating cortical, subcortical, cerebellar, spinal, and peripheral networks into a unified motor behavior. Across neurological diseases—including Parkinson’s disease, atypical parkinsonism, cerebellar ataxias, stroke, multiple sclerosis, neuropathies, neuromuscular disorders, and functional gait syndromes—gait disturbances are among the most disabling clinical features, contributing to falls, loss of independence, institutionalization, and premature mortality. Traditional bedside observation remains indispensable, but it lacks the sensitivity and reproducibility needed to capture subtle, episodic, or prodromal abnormalities. Over the past decade, advances in wearable sensors, marker-based and markerless motion capture, pressure-sensitive walkways, force plates, artificial intelligence, and machine learning have positioned digital mobility outcomes as promising, ecologically valid biomarkers of neurological function. These measures can support differential diagnosis, provide prognostic information on falls and survival, and serve as sensitive endpoints in therapeutic trials. They may also detect early abnormalities, such as increased stride-to-stride variability or prolonged double-support time, before overt clinical deterioration becomes evident. Clinical applications are increasingly evident across disorders, including distinguishing Parkinson’s disease from atypical parkinsonism, quantifying treatment response in normal-pressure hydrocephalus, tracking progression in ataxia and multiple sclerosis, predicting functional decline in motor neuron disease, and guiding rehabilitation after stroke. Integration with neuroimaging, electrophysiology, and molecular biomarkers is beginning to reveal the circuits underlying variability, instability, and freezing, positioning gait as a systems-level marker of neural integrity. Nevertheless, methodological heterogeneity, limited disease-specific validation, insufficient longitudinal data, and lack of consensus on clinically meaningful parameters continue to constrain translation. Cognitive, affective, and environmental influences also remain insufficiently represented in digital frameworks, while equity, accessibility, algorithmic bias, and privacy require careful ethical governance. Reconceptualizing gait as a “sixth vital sign” reframes mobility as a multidimensional biomarker of neural and systemic health. With harmonized protocols, robust validation, multimodal integration, and appropriate ethical frameworks, gait analysis could become a cornerstone of precision neurology. Full article
(This article belongs to the Section Neurosciences)
13 pages, 690 KB  
Article
Accelerometer-Measured Moderate-to-Vigorous Physical Activity and Cancer Risk: Dose–Response from Observational and Nonlinear Mendelian Randomization in UK Biobank
by Chang-Ling Huang, Meng-Xuan Yang, Yong-Qiao He, Wen-Qiong Xue, Ying Liao, Tong-Min Wang and Wei-Hua Jia
Healthcare 2026, 14(13), 1818; https://doi.org/10.3390/healthcare14131818 (registering DOI) - 23 Jun 2026
Abstract
Background: Physical activity is a well-established modifiable lifestyle factor associated with reduced cancer risk; however, the optimal weekly volume of moderate-to-vigorous physical activity (MVPA) for cancer prevention, particularly when assessed using objective measures, remains unclear. Most existing evidence relies on self-reported physical activity, [...] Read more.
Background: Physical activity is a well-established modifiable lifestyle factor associated with reduced cancer risk; however, the optimal weekly volume of moderate-to-vigorous physical activity (MVPA) for cancer prevention, particularly when assessed using objective measures, remains unclear. Most existing evidence relies on self-reported physical activity, which may introduce measurement bias and obscure accurate dose–response relationships. Methods: We analyzed data from UK Biobank participants with valid accelerometer measurements to quantify habitual MVPA. Observational associations between MVPA and incident cancer were evaluated using multivariable Cox proportional hazards regression and restricted cubic splines. One-sample Mendelian randomization (MR) analyses, including both linear and nonlinear approaches, were conducted to evaluate potential causal associations and explore possible dose–response patterns. Results: Higher MVPA was associated with lower total cancer risk (HR 0.971, 95% CI 0.954–0.988, p = 0.001). Consistent associations were observed for several site-specific cancers, particularly lung, colorectal, breast, kidney, and bladder cancer. MR analyses supported a directionally consistent association between genetically predicted MVPA and lower total cancer risk (HR 0.977, 95% CI 0.962–0.992, p = 0.002). Nonlinear MR analyses suggested a potential nonlinear association, with lower cancer risk observed at a model-derived exploratory point of approximately 5 h of weekly MVPA. Conclusions: These findings provide supportive evidence that higher accelerometer-measured MVPA is associated with lower total cancer risk and contribute to a better understanding of the dose–response relationship between MVPA and cancer incidence. Full article
(This article belongs to the Section Public Health and Preventive Medicine)
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21 pages, 422 KB  
Systematic Review
Gut Microbiota Modulation as a Therapeutic Strategy for Insomnia: A Systematic Review of Nutritional and Botanical Interventions
by Narada Vicharnnikornkij, Wanna Chaijaroenkul and Kesara Na Bangchang
Biomolecules 2026, 16(7), 933; https://doi.org/10.3390/biom16070933 (registering DOI) - 23 Jun 2026
Abstract
Background: Insomnia and stress-related sleep disorders are increasingly recognized as systemic conditions linked to the microbiota–gut–brain axis (MGBA). With growing clinical interest in natural products that modulate the gut environment, this systematic review evaluates the efficacy and mechanisms of non-pharmacological interventions, specifically probiotics, [...] Read more.
Background: Insomnia and stress-related sleep disorders are increasingly recognized as systemic conditions linked to the microbiota–gut–brain axis (MGBA). With growing clinical interest in natural products that modulate the gut environment, this systematic review evaluates the efficacy and mechanisms of non-pharmacological interventions, specifically probiotics, prebiotics, dietary indices, and botanicals, in alleviating insomnia, restoring circadian rhythms, and modulating neurochemical markers. Methods: In strict accordance with PRISMA 2020 guidelines, we searched PubMed, ScienceDirect, Scopus, and The Cochrane Library for English language studies published from inception to March 31, 2026. Eligibility was restricted to studies with rigorously controlled designs, specifically randomized controlled trials (RCTs) and controlled in vivo animal studies. Interventions had to target the gut microbiota, with primary outcomes measuring sleep quality (subjective or objective) or sleep-related neurochemical markers. We excluded uncontrolled, single-arm, or observational designs; in vitro studies; non-original research; and studies involving subjects with severe medical or psychiatric comorbidities (e.g., cancer, ADHD, severe psychiatric disorders) to prevent confounding variables, though mild-to-moderate anxiety and depression were permitted. Risk of bias was assessed using the Cochrane RoB 2.0 and SYRCLE tools. Due to significant methodological heterogeneity, a narrative synthesis stratified by intervention and population was conducted. This review was not registered in PROSPERO. Results: A total of 56 studies (33 humans, 23 animals) met the inclusion criteria. Taxonomic nomenclature was updated to reflect 2020 reclassifications (e.g., Lactiplantibacillus plantarum). In human trials, interventions significantly improved subjective sleep metrics (PSQI, ISI). Recent additions demonstrated the efficacy of the Dietary Index for Gut Microbiota (DI-GM) and the improvement in N3 sleep latency by yeast mannan. Furthermore, whole-food patterns (e.g., the MIND diet) and Traditional Chinese Medicine (TCM) decoctions successfully enriched beneficial taxa, such as Bacteroides coprophilus, and increased short-chain fatty acid (SCFA) production. Animal models demonstrated that “psychobiotic” strains (Bifidobacterium breve, Lacticaseibacillus paracasei), prebiotics (GOS/PDX), and TCM formulas effectively restored GABA/5-HT profiles, lowered morning cortisol, and facilitated REM rebound in PCPA-induced models, while also consolidating non-rapid eye movement (NREM) sleep and downregulating clock genes (Per1/Per2). Conclusions: Psychobiotics, prebiotics, and botanicals represent a highly viable non-pharmacological strategy for treating insomnia. However, current evidence is constrained by a heavy reliance on subjective human questionnaires, short follow-up durations limiting insight into long-term stability, and a substantial translational gap between mechanistic rodent models and human clinical outcomes. Full article
(This article belongs to the Section Molecular Medicine)
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