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Efficacy of sodium-glucose cotransporter 2 inhibitors after acute myocardial infarction: Are the benefits limited to patients with diabetes? A systematic review and meta-analysis.

BACKGROUND: Acute myocardial infarction remains one of the leading causes of death worldwide. Recently, studies have focused on evaluating the effectiveness of SGLT2 inhibitors in this scenario. Objectives We aimed to perform a meta-analysis comparing the efficacy of SGLT2 inhibitors vs standard care. METHODS: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) and observational studies comparing patients with acute myocardial infarction using iSGLT2 inhibitors and standard care. Statistical analyses were conducted using R software (v 4.3.2) and a random-effects model was employed for all outcomes. RESULTS: A total of 31,378 patients were included, with 10,897 (34.7%) assigned to the SGLT2 inhibitor group. Among these studies, three were randomized controlled trials (RCTs). There was a significant difference in reduction of HF readmissions (OR 0.61; p&#xa0;<&#xa0;0.01), all-cause mortality (OR 0.62; p&#xa0;<&#xa0;0.01;) and stroke (OR 0.67; p&#xa0;<&#xa0;0.01;). However, there was no significant difference in cardiovascular death, rehospitalization for any cause and recurrence of acute MI. Meta regression and subgroup analysis showed a trend toward better outcomes in the diabetic and non-STEMI population. CONCLUSIONS: SGLT2 inhibitors were associated with lower HF rehospitalization, stroke, and all-cause mortality after acute MI, mainly in observational studies. Benefits appeared greater in diabetic and non-STEMI patients. Dedicated RCTs focusing on diabetic, particularly non-STEMI, populations are needed to confirm these findings. KEY POINTS: What is already known on this topic: SGLT2 inhibitors have demonstrated cardiovascular and renal benefits in patients with heart failure and type 2 diabetes mellitus. However, their role in the acute myocardial infarction (AMI) setting remains uncertain, particularly regarding post-AMI outcomes such as heart failure readmissions, mortality, and recurrent ischemic events, with current evidence derived from heterogeneous and predominantly observational studies. WHAT THIS STUDY ADDS: This meta-analysis, including over 31,000 patients, suggests that SGLT2 inhibitors are associated with reductions in heart failure readmissions, all-cause mortality, and stroke following AMI. These associations were more consistently observed in patients with type 2 diabetes and in non-ST-segment elevation myocardial infarction (NSTEMI) populations. However, randomized controlled trials showed neutral results, and the observed benefits were mainly driven by observational studies. Meaning: These findings should be interpreted as hypothesis-generating. While SGLT2 inhibitors may represent a potential therapeutic strategy in selected post-AMI populations, particularly patients with diabetes and NSTEMI, current evidence does not support routine early in-hospital initiation. Dedicated randomized trials specifically enrolling diabetic post-AMI patients are required to clarify optimal timing and clinical benefit.

Humans

Transcranial Alternating Current Stimulation at 40 Hz Improves Social Functioning in Children With Autism Spectrum Disorder: A Randomized Clinical Trial.

BACKGROUND: Autism spectrum disorder (ASD) lacks rapid and effective interventions for its core social difficulties. The right temporoparietal junction (rTPJ), a critical hub for social cognition, together with gamma band abnormalities implicated in ASD, provides a promising neuromodulation target. METHODS: In this randomized, double-blind, sham-controlled trial, 47 children with ASD (39 male; mean [SD] age = 8.79 [2.71] years) were assigned to receive either 21 sessions of 40-Hz high-definition transcranial alternating current stimulation (tACS) targeting the rTPJ (3 sessions/day for 7 days) or sham stimulation, with assessments conducted at baseline, postintervention (week 1), and a 3-week follow-up (week 4). The primary outcome was change in Ohio State University Autism Rating Scale-DSM-5 (OARS-5) total scores. Secondary outcomes included the Aberrant Behavior Checklist-Second Edition, Social Responsiveness Scale-Second Edition, and Short Sensory Profile. Eye-tracking metrics during Frith-Happ&#xe9; animations were exploratory measures of theory of mind (ToM)-related social cognitive processing. RESULTS: The active group demonstrated significant improvements in OARS-5 total scores at week 1 (mean difference = -1.13, 95% CI [-1.78 to -0.47], p < .001) and week 4 (mean difference = -1.47, 95% CI [-2.20 to -0.74], p < .001). Improvements in selected behavioral and sensory domains were observed. Average fixation duration during ToM animations showed a significant group &#xd7; time interaction. No serious adverse events occurred. CONCLUSIONS: These findings suggest that 40-Hz tACS targeting the rTPJ may be associated with rapid improvements in ASD symptom severity, particularly social functioning, in children with ASD, while being well tolerated. Clinical significance requires further evaluation.

Humans

The burden of male breast cancer (MBC) in the GBD Central, Eastern, and Western Europe Regions from 1990 to 2023: Results from the Global Burden of Disease Study 2023.

PURPOSE: Male breast cancer (MBC) is underrepresented in cancer statistics: this study aimed to assess the burden of MBC in Central, Eastern, and Western Europe from 1990 to 2023, using data from the Global Burden of Disease (GBD) Study 2023. METHODS: Estimates from GBD 2023 were analyzed to determine the MBC incidence, mortality, and disability-adjusted life years, their all-ages and age-standardized rates, and the 1990 through 2023 annual percent change. These estimates were compared to those for the GBD Super Regions and the Socio-Demographic Index quintile countries. RESULTS: In Central Europe, age-standardized incidence rates (ASIR) increased from 0.54 (0.40-0.76) to 1.05 (0.70-1.52), age-standardized mortality rates (ASMR) from 0.29 (0.25-0.34) to 0.40 (0.36-0.45), and age-standardized disability life-year rates (ASDR) from 7.19 (6.15-8.41) to 9.63 (8.52-11.07). In Eastern Europe, ASIR remained relatively stable, changing from 0.81 (0.56-1.19) to 0.60 (0.38-0.92), whereas ASMR decreased from 0.40 (0.33-0.49) to 0.21 (0.16-0.25) and ASDR from 10.54 (8.69-12.89) to 5.55 (4.52-6.85). In Western Europe, ASIR increased from 0.47 (0.33-0.67) to 0.88 (0.59-1.24), whereas ASMR (0.22 [0.19-0.25] vs. 0.24 [0.21-0.27]) and ASDR (5.20 [4.49-5.97] vs. 5.75 [4.96-6.66]) remained stable. CONCLUSIONS: The burden of MBC is increasing across Europe, particularly in the Central region, with huge regional differences. Population growth and variations over time impacted on the metrics. Even with a composite European scenario, the mortality-to-incidence ratio markedly declined in the three areas.

Humans

A framework for delivering real-time, instrument-relative navigation in transoral robotic surgery.

Transoral robotic surgery (TORS) is a minimally invasive, inside-out technique that, compared with traditional open approaches, provides fewer post-operative complications, shorter hospital stays, and improved survival for early-stage head and neck cancer. However, TORS is limited by its steep learning curve and poor visualization of deep tumor margins. This randomized crossover study evaluated a surgical navigation system's potential to enhance accuracy and user experience with real-time, instrument-relative feedback. Seven Teflon beads (d&#x2009;=&#x2009;2.381&#xa0;mm) were embedded at the tongue base of a porcine pharynx-and-larynx model. Tongue blade compression and retraction were applied to the model to mimic intraoperative tissue deformation, reproducing the anatomical shifts that occur relative to preoperative imaging. Eight participants used the da Vinci Surgical system to localize the beads by placing pins under two conditions: (a) preoperative computed tomography with no navigation; (b) model-based visual navigation with quantitative instrument-to-target metrics. Surgical accuracy was determined by calculating the target localization error (TLE, pin-to-bead Euclidean distance) and the angular error (AE, pin axis trajectory to bead). Accounting for training level and bead depth, surgical navigation reduced TLE by 5.44&#xa0;mm (95% CI, 4.02-6.86&#xa0;mm; p&#x2009;=&#x2009;2.00e-11) and AE by 8.47 degrees (95% CI, 6.21-10.72 degrees; p&#x2009;=&#x2009;5.17e-11). Impressions of the system were generally favorable using a 5-point Likert survey and task duration (p&#x2009;=&#x2009;0.26) or cognitive workload via the NASA-Task Load Index (p&#x2009;=&#x2009;0.22) were not significantly affected. The navigation system demonstrated translational promise, offering improved target localization accuracy and more consistent performance across experience levels, two critical determinants of surgical quality in TORS.

Robotic Surgical Procedures

International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial.

BACKGROUND: Angina is a debilitating condition caused by coronary artery disease and microvascular dysfunction. Following coronary angiography angina and no obstructive coronary arteries is a common outcome, and women are disproportionately affected. The objectives are first, to assess causes of angina in patients undergoing invasive management; and second, to assess effects of coronary function test-guided management on clinical outcomes. METHODS: This is an international, multicenter, prospective, registry-based study and nested, randomized, controlled, triple-blind, and endpoint trial. Participants, community care providers, and outcomes assessors are masked. Consented participants enter the registry. Participants without obstructive coronary artery disease (luminal stenosis <50%, or fractional flow reserve >0.80) are eligible for randomization. Index of microcirculatory resistance (IMR; abnormal &#x2265;25) and coronary flow reserve (CFR; abnormal <2.0; gray zone 2.0-2.5) are measured by bolus thermodilution, and results are disclosed (intervention) or not (control group) to the attending cardiologist. RESULTS: The primary outcome of the registry is the Seattle Angina Questionnaire summary score at baseline described by coronary artery disease status. Secondary outcomes include the prevalence of obstructive coronary artery disease, patient reported outcome measures and clinical outcomes. The primary outcome of the randomized trial is the within-individual change in Seattle Angina Questionnaire summary score at 12-months from baseline. Secondary outcomes include safety, diagnostic accuracy, patient reported outcome measures for quality of life, physical and psychological function, cardiovascular risk, clinical outcomes, health economics and mechanistic biomarkers. The first patient was screened on December 18, 2020 and the last patient was enrolled on June 30, 2026. Forty sites were included in the United Kingdom (n = 35), Republic of Ireland (n = 2), Holland (n = 2), and Poland (n = 1). In total, 1,483 participants were enrolled into the registry of whom 1,047 were randomized and 386 were not randomized (registry-only). CONCLUSION: This international, registry-based clinical trial will provide novel evidence on the natural history of angina and stratified therapy for angina with no obstructive coronary arteries. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04674449. UNIQUE IDENTIFIER: NCT04674449.

Humans

Providing Feedback on Previous Pain Scores Did Not Affect Weekly Pain Variability: A Cohort-Nested Randomised Study.

BACKGROUND: Spinal pain is one of the leading causes of disability worldwide and repeated symptom monitoring is increasingly used to capture its fluctuating nature. However, repeated pain assessments may be influenced by prior responses, potentially affecting longitudinal patterns of pain reporting. This study examined whether providing feedback on prior pain scores influenced within-person variability in weekly pain intensity ratings and retention over 60&#x2009;weeks. METHODS: This randomised study evaluating a methodological feature of repeated pain assessment was embedded within a cohort of adults with spinal pain referred to an outpatient hospital clinic. Participants (n&#x2009;=&#x2009;2448) were randomised 1:1 to weekly pain intensity ratings (0-10 numerical rating scale) either with feedback ('You answered [X] last week') or without feedback. Analyses included participants with &#x2265;&#x2009;40% valid responses (n&#x2009;=&#x2009;1883), of whom 948 received feedback and 935 did not. The primary outcome was within-person variability in pain intensity, quantified using the root mean square of successive differences. Secondary outcomes included additional fluctuation metrics and the number of weeks with missing responses. RESULTS: No meaningful between-group differences were observed for the primary outcome (mean difference -0.04 points [95% confidence interval -0.08 to 0.01]) or secondary outcomes, including retention rates. Sensitivity analyses yielded consistent findings. CONCLUSIONS: Providing participants with feedback on their previous pain score did not meaningfully influence within-person pain variability or retention during 60&#x2009;weeks of weekly monitoring. These findings aid the interpretation of repeated longitudinal pain assessments by showing that the observed variability was robust to this specific study design. SIGNIFICANCE: This randomised study showed that providing participants with feedback on prior pain scores did not meaningfully alter weekly pain variability or retention during 60&#x2009;weeks of longitudinal monitoring. These findings contribute to the interpretation of repeated longitudinal pain assessments in spinal pain research and suggest that weekly pain reporting patterns are robust to prior-pain feedback during long-term symptom monitoring.

Humans

Externally validated risk prediction models for gestational diabetes mellitus: A systematic review and meta-analysis.

INTRODUCTION: Risk prediction models for gestational diabetes mellitus (GDM) offer potential for early identification and targeted prevention. External validation is crucial to assess model performance across diverse populations. Despite the availability of numerous GDM prediction models, limited evidence exists on their external validation frequency, methodological quality, and clinical applicability. This systematic review evaluated externally validated GDM prediction models, focusing on methodological rigor, reporting standards, and clinical relevance to inform future research and implementation. MATERIAL AND METHODS: Databases including Ovid MEDLINE, Embase, Scopus, Emcare, and CINAHL were searched up to May 1, 2025. Studies reporting external validation of GDM risk prediction models were included. Two reviewers independently screened studies. Data were extracted using the CHARMS framework, and risk of bias and applicability were assessed using PROBAST+AI. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251125758). RESULTS: Twenty-six studies validated 33 models, with validation sample sizes ranging from 50 to 75&#x2009;161. Over half used the IADPSG criteria to define GDM. Discrimination metrics were commonly reported, but calibration, overall performance, and clinical utility were often lacking. Meta-analysis was feasible for only four models: Teede et&#xa0;al., Nanda et&#xa0;al., Naylor et&#xa0;al., and Van Leeuwen et&#xa0;al., each showing fair discrimination. The Teede et&#xa0;al. model was the most widely validated, with 11 external validations across six continents and a pooled AUC of 0.72 (95% CI: 0.67-0.76). Despite fewer validations, the Nanda et&#xa0;al. model achieved the highest pooled discrimination (5 validations; pooled AUC 0.77, 95% CI: 0.74-0.80). The Naylor et&#xa0;al. and van Leeuwen et&#xa0;al. models also underwent meta-analysis, as sufficient external validation studies were available to support comparative performance assessment. Notably, 69.23% of studies had a high risk of bias. CONCLUSIONS: While many models showed acceptable predictive performance, most validations were methodologically weak. Future studies should follow best-practice guidelines and promote scalable validation strategies, such as algorithm sharing, to enhance clinical utility.

Humans

Proficiency-based training and evidence-based methodology: a systematic review and meta-analysis.

OBJECTIVE: To assess adherence of self-labelled proficiency-based progression (PBP) studies to evidence-based PBP criteria and examine associations with training outcomes. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews. PubMed, CENTRAL, EMBASE, MEDLINE, and Scopus were searched from inception to 1 March 2023. Prospective English-language studies on healthcare procedural training reporting objective performance outcomes were included; non-prospective, non-quantitative, non-procedural, non-English studies, and reviews were excluded. Pre-specified outcomes included adherence to 18 evidence-based PBP criteria and objective performance metrics (errors, steps, time); secondary outcomes included proficiency benchmark achievement and Likert ratings. Data extraction was performed independently by multiple reviewers. Study quality was assessed using the Medical Education Research Study Quality Instrument and risk of bias by two investigators. Effect sizes were pooled using random-effects models (DerSimonian-Laird), expressed as the ratio of means (ROM) for continuous outcomes and bias-corrected odds ratios for dichotomous outcomes. RESULTS: Of 646 studies identified 175 met inclusion criteria. In the PBP studies (n&#x2009;=&#x2009;18), 94% fulfilled minimum criteria (use of a proficiency benchmark, its quantitative definition, and requirement for demonstration prior to progression) vs 36% of non-PBP studies (n&#x2009;=&#x2009;157). If all PBP criteria were included, 83% of PBP studies used these criteria vs only 2% of non-PBP-studies. In quantitative analysis (27 randomised clinical studies, 761 participants), ROM results showed that PBP training reduced the number of performance errors by 58% (P&#x2009;<&#x2009;0.001) and procedural time by 28% (P&#x2009;=&#x2009;0.006), increasing number of steps performed by 22% (P&#x2009;=&#x2009;0.03). When stratified based on number of criteria fulfilled, meta-regression demonstrated that increasing the number of PBP criteria fulfilled was associated with progressive and systematic trainee performance improvement. CONCLUSIONS: The more training methodologies adhere to established PBP criteria, the better training outcome will be.

Humans

Blood pressure management after endovascular thrombectomy in acute ischemic stroke: association with symptomatic intracranial hemorrhage and functional outcome at 3&#xa0;months.

BACKGROUND: No clear consensus exists on ideal systolic blood pressure (SBP) targets after endovascular thrombectomy (EVT) following an acute ischemic stroke (AIS). This study investigated the association between SBP parameters within the first 24&#xa0;h after EVT and 3-month functional outcomes and the risk of symptomatic intracranial hemorrhage (sICH). METHODS: We retrospectively collected and prospectively followed clinical, and radiological data for patients undergoing EVT for AIS from 2016 to 2024, including 2-hourly BP measurements during the first 24&#xa0;h and SBP variability assessed by standard deviation (SD) and coefficient of variation (CV). Outcomes included 3-month functional status and sICH, and their associations with post-EVT BP metrics were analyzed. RESULTS: A total of 268 post EVT patients were included with a median age of 61&#xa0;years (IQR, 51-69). Mean SBP was 129.67&#xa0;&#xb1;&#xa0;17.17&#xa0;mm Hg, with SBP variability (SD 12.6&#xa0;&#xb1;&#xa0;5.4&#xa0;mm Hg; CV 9.6&#xa0;&#xb1;&#xa0;3.8&#xa0;%), while good functional outcome and sICH occurred in 39.7&#xa0;% and 4.9&#xa0;% of patients, respectively. Multivariate regression showed that higher admission NIHSS&#xa0;(>15) [0.90 (95&#xa0;%CI, [0.86, 0.95], p&#xa0;=&#xa0;0.000)], recanalization status [1.88 (95&#xa0;%CI, [1.43, 2.48], p&#xa0;=&#xa0;0.00)], and SBP-CV&#xa0;&#x2265;&#xa0;10 [0.44 (95&#xa0;%CI, [0.2, 0.94], p&#xa0;=&#xa0;0.036)] was independently associated with poor 3-month functional outcome, while higher admission NIHSS (>15) [0.87 (95&#xa0;%CI, [0.77,0.98], p&#xa0;=&#xa0;0.02)] and diabetes [0.12 (95&#xa0;%CI, [0.03, 0.54], p&#xa0;=&#xa0;0.006)] predicted increased risk of sICH. CONCLUSIONS: The study showed that reduced BP variability during the first 24&#xa0;h post-EVT was associated with better 3-month functional outcomes. A clear association between SBP and sICH risk was not demonstrated.

Humans

Application of Three-Dimensionally Printed Surgical Guides in Precise Sacral Tumor Excision and Defect Reconstruction.

OBJECTIVE: Precise resection of sacral tumors remains technically demanding due to their deep anatomical location and close proximity to critical neurovascular structures. Conventional freehand techniques often result in suboptimal resection margins, excessive blood loss, and compromised lumbopelvic stability. This study evaluated whether patient-specific three-dimensional (3D)-printed guiding templates improve surgical accuracy and perioperative outcomes in sacral tumor resection and reconstruction. METHODS: Nineteen patients undergoing en bloc sacral tumor resection (S1-S3 involvement) with spinopelvic reconstruction (2006-2020) were retrospectively analyzed. Patients were divided into a 3D-printing group (n&#x2009;=&#x2009;10) and a conventional freehand group (n&#x2009;=&#x2009;9). In the 3D-printing group, computer-aided design and 3D-printed templates were used for osteotomy, screw placement, and defect reconstruction. Perioperative metrics, surgical accuracy, and complications were compared between groups using Welch's t-test and the Hodges-Lehmann method; oncologic events during follow-up were recorded descriptively. RESULTS: The 3D-printing group demonstrated significantly shorter operative time (456.5&#x2009;&#xb1;&#x2009;62.36 vs. 574.44&#x2009;&#xb1;&#x2009;114.58&#x2009;min, p&#x2009;=&#x2009;0.012), reduced blood loss (4081.40&#x2009;&#xb1;&#x2009;838.99 vs. 5090.0&#x2009;&#xb1;&#x2009;1059.67&#x2009;mL, p&#x2009;=&#x2009;0.034), and fewer fluoroscopic exposures (4.2&#x2009;&#xb1;&#x2009;0.79 vs. 10.0&#x2009;&#xb1;&#x2009;1.58, p&#x2009;<&#x2009;0.001) compared with the conventional group. Osteotomy accuracy was also superior in the 3D-printing group, with significantly lower angular deviation (3.33&#xb0;&#x2009;&#xb1;&#x2009;0.45&#xb0; vs. 6.79&#xb0;&#x2009;&#xb1;&#x2009;2.16&#xb0;, p&#x2009;=&#x2009;0.0012). Postoperative complication rates were comparable (30% vs. 44.4%, p&#x2009;=&#x2009;0.649), but hospital stay was significantly shorter in the 3D-printing group (10.7&#x2009;&#xb1;&#x2009;2.71 vs. 18.11&#x2009;&#xb1;&#x2009;4.01&#x2009;days, p&#x2009;<&#x2009;0.001). CONCLUSION: Patient-specific 3D-printed guiding templates enhance precision in sacral tumor excision and reconstruction, improving surgical efficiency and perioperative safety. This computer-assisted, template-guided approach represents a valuable advancement for complex sacral oncologic surgery.

Humans

Timing and Dose Matter: Late High-Speed Exposure and Higher High-Intensity Acceleration Volumes Reduce Hamstring Reinjury Risk in Elite Male Football (Soccer).

OBJECTIVES: The aims of this study were to (a) investigate whether the timing and magnitude of exposure to high-speed running (HSR), sprinting, and high-intensity accelerations during on-field rehabilitation after hamstring strain injury were associated with reinjury risk and (b) examine changes in match running performance upon return to play (RTP). DESIGN: Retrospective cohort study. METHODS: Data from 95 elite male football (soccer) players from five professional clubs competing in major European and Middle Eastern leagues were analyzed. Players with complete rehabilitation load profiles were included in the 2-month and 6-month reinjury analysis. Modified Poisson regression assessed associations between rehabilitation load characteristics and reinjury risk. Match running performance (HSR distance, sprint distance, and high-intensity accelerations per minute) during the five matches before injury and the first five matches after RTP was compared using paired t-tests for the entire cohort. RESULTS: Late introduction of HSR, sprinting, and high-intensity accelerations during rehabilitation (ie, &#x2265; 60% of rehabilitation progression) was associated with a significantly lower reinjury risk at 2 months (relative risk [RR] range = 0.948-0.969; P < .01) and 6 months (RR range = 0.964-0.979; P < .05). Higher daily exposure to high-intensity accelerations once introduced was protective (RR = 0.861 (0.778-0.951)). There were no meaningful associations between total volume of HSR or sprinting and reinjury. Match running performance metrics did not differ between pre-injury and post-RTP matches (all P > .05). Changes in performance were not correlated with rehabilitation load characteristics. CONCLUSION: The timing of high-intensity running exposure during on-field rehabilitation appeared associated with a lower hamstring reinjury risk. Delaying the introduction of HSR, sprinting, and accelerations, followed by a structured and progressive build-up, was associated with lower risk of reinjury without compromising the subsequent match performance of elite male football players. J Orthop Sports Phys Ther 2026;56(9):611-621. Epub 7 Jul 2026. doi:10.2519/jospt.2026.14077.

Humans

Electroencephalographic evidence of cortical network disruption preceding overt cardioinhibition during tilt-induced reflex syncope.

OBJECTIVE: Reflex syncope is a common cause of transient loss of consciousness. However, the early cerebral mechanisms underlying cardiovascular changes remain poorly understood. Our objective was to investigate early cerebral changes by quantitatively analyzing EEG activity preceding overt cardioinhibition during tilt-induced reflex syncope. METHODS: EEG recordings from patients undergoing tilt testing were retrospectively analyzed. Patients who experienced reflex syncope were compared to those who did not. Spectral and functional connectivity analyses were performed across baseline, pre-cardioinhibition, and syncopal phases. RESULTS: Prior to the onset of cardioinhibitory pathological reflex, a significant increase in theta-band spectral power was observed in the right temporal region, accompanied by a widespread increase in functional connectivity within the same frequency band. These findings suggest the involvement of brain networks before cardioinhibition. CONCLUSIONS: EEG changes in the theta band (power and functional connectivity) were observed before overt cardioinhibition during tilt-induced reflex syncope. SIGNIFICANCE: Our findings support the hypothesis of cortical processing preceding cardioinhibition in reflex syncope. EEG may represent a valuable complementary tool for improving the understanding and diagnosis of these events.

Humans

A STORM-based protocol for nanoscale imaging and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber.

Stochastic Optical Reconstruction Microscopy (STORM) enables nanoscale mapping of molecular components beyond the diffraction limit; however, its reproducible implementation in hydrophobic polymer matrices remains challenging because fluorescence-labeling specificity, fluorophore photoswitching, three-dimensional localization, chromatic registration, and quantitative image analysis must be carefully controlled. This protocol presents a standardized experimental workflow for dual-color labeling, astigmatism-based three-dimensional STORM acquisition, and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber (NR). The workflow covers sample pretreatment, Cy5 NHS ester labeling of protein-associated primary amines, DiI labeling of phospholipid-rich domains, STORM imaging-buffer preparation, three-dimensional single-molecule localization, dual-channel registration, generation of standardized xy projections, aggregate-size analysis, and projected lateral spatial correlation assessment. Reproducibility is supported by defined acquisition and localization criteria, three independent sample preparations with at least five fields of view analyzed per condition, and unlabeled, single-color, dye-only matrix, and processing-associated Cy5 controls. Mean lateral localization precisions of 11.8&#x202f;&#xb1;&#x202f;2.3&#x202f;nm for Cy5 and 13.5&#x202f;&#xb1;&#x202f;2.9&#x202f;nm for DiI were obtained, while two-dimensional Fourier ring correlation analysis of the xy projections yielded effective lateral image resolutions of approximately 25 and 28&#x202f;nm, respectively. Image-based particle segmentation and localization-coordinate-based density-based spatial clustering of applications with noise (DBSCAN) were applied to standardized xy projections as complementary quantitative approaches. Application of the protocol to untreated, centrifuged, and protease-treated NR samples demonstrated treatment-associated changes in the detected abundance and projected size distributions of protein- and phospholipid-associated aggregates, together with a non-monotonic change in their projected lateral spatial correlation. These observations describe alterations in nanoscale organization but do not, by themselves, establish stable protein-phospholipid complex formation. Unlike previous studies that primarily demonstrated the feasibility of STORM imaging in rubber materials, the principal contribution of this work is an end-to-end, step-by-step protocol incorporating defined controls, three-dimensional localization, image-quality metrics, chromatic-registration procedures, and complementary quantitative-analysis pipelines for non-expert users. The workflow may be adaptable to other hydrophobic polymers and soft-material systems after appropriate optimization and validation.

Rubber

Diagnostic performance of intraoperative in vivo hyperspectral imaging for meningioma grading and molecular alterations: results from a prospective feasibility study.

OBJECTIVE: Hyperspectral imaging (HSI) is an emerging intraoperative, noninvasive, contrast agent-free imaging modality that enables quantitative assessment of tissue composition. The present study aimed to investigate whether HSI-derived tissue parameters correlate with WHO grade and molecular markers of aggressiveness in cranial meningiomas. METHODS: In this prospective study, intraoperative in vivo HSI was performed using the TIVITA tissue system, capturing spectral signatures between 500 and 1000 nm. Quantitative tissue parameters included tissue oxygen saturation (StO2), near-infrared perfusion index, organ hemoglobin index (OHI), and tissue water index (TWI). HSI parameters were correlated with histopathological WHO grade and molecular alterations, including CDKN2A/B deletion, TERT promoter mutation, and 1p/22q loss. Group differences were analyzed using one-way ANOVA, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. RESULTS: Forty-six meningiomas were included, comprising WHO grade 1 (n = 35) and WHO grade 2-3 (n = 11) tumors. TWI was significantly higher in WHO grade 2-3 meningiomas compared with WHO grade 1 tumors (mean 0.49 [SD 0.12] vs 0.38 [SD 0.17], p = 0.048). ROC analysis demonstrated an area under the ROC curve (AUC) of 0.71 (95% CI 0.56-0.86, p = 0.036) for TWI in discriminating higher-grade disease. A TWI cutoff &#x2265; 0.367 identified all WHO grade 2-3 meningiomas with 100% sensitivity and 100% negative predictive value. In a molecular subgroup (n = 15), OHI appeared higher in tumors with homozygous CDKN2A/B deletion than in nondeleted tumors (mean 0.77 [SD 0.04] vs 0.62 [SD 0.10]). However, only 3 CDKN2A/B-deleted cases were available, and these findings should be considered descriptive. ROC analysis yielded an AUC of 0.89 (95% CI 0.71-1.00). An OHI cutoff &#x2265; 0.712 identified all three CDKN2A/B-deleted tumors (100% sensitivity), with 83.3% specificity and 86.7% accuracy. CONCLUSIONS: The present investigation demonstrated that HSI-derived tissue water and hemoglobin metrics provide biologically meaningful information in meningiomas. Low tissue water content appeared to rule out higher-grade diseases in this first subset cohort, while elevated hemoglobin showed a potential association with CDKN2A/B deletion in a small exploratory subgroup. These findings support the potential of HSI as a real-time noninvasive tool for intraoperative risk stratification and should be evaluated in large-scale studies. German Clinical Trials Register no. DRKS00036771 (www.drks.de).

Humans

The mighty microproteins: from versatile cellular regulators to precision medicine therapeutics.

Microproteins, are tiny proteins encoded by small open reading frame (sORF), translation of these non-canonical open reading frames (ncORFs) has been implicated in diverse biological processes and diseases. This review summarizes recent developments in the discovery, biogenesis, and functional characterization of microproteins, and their involvement in various disease, with special focus on their roles in cancer, cardiovascular, metabolic, neurodegenerative and immune-related disorders. We emphasize the regulation of key cellular pathways by microproteins, including mitochondrial homeostasis, apoptosis, metabolic reprogramming, and immune signaling, all of which affect disease initiation and progression. Emerging evidence also supports their potential as disease biomarkers and therapeutic candidates for precision medicine. Finally, the review critically discusses the current challenges including discrepancies in microprotein annotation, the limitations of ribosome profiling and proteogenomic approaches, the gap between computationally predicted and experimentally validated microproteins, and the need for rigorous orthogonal validation by means of CRISPR-based genome editing, ribosome release assays, mutational analysis, high-resolution mass spectrometry, and functional studies. Finally, we review recent development of AI-assisted ORF prediction, single-cell translatomics, spatial proteomics, and integrated multi-omics as emerging technologies reshaping. Microprotein discovery and functional annotation. Finally, we discuss the translational potential of microproteins and highlight the remaining challenges to clinical application, including peptide stability, pharmacokinetics, tissue-specific delivery, immunogenicity, and the need for rigorous preclinical and clinical validation. Together, this review provides an updated and critical overview of the rapidly evolving microprotein field and highlights future research priorities for translating these molecules into clinically useful biomarkers and precision therapeutics.

Microproteins

Reliability-aware hierarchical learning for Chagas disease screening from 12-lead ECGs: tackling label uncertainty and class imbalance.

Objective.Chagas disease, a neglected tropical disease (NTD) with significant cardiovascular impact, remains underdiagnosed in resource-limited regions. Electrocardiogram (ECG) screening offers a low-cost tool for detecting cardiac involvement, yet algorithm development is challenged by label noise, data scarcity, and the latent nature of infection. This study proposes a robust ECG-based screening framework that explicitly addresses these constraints.Approach.We introduce aReliability-Aware Hierarchical Learningstrategy that calibrates supervision according to data provenance, prioritizing serology-confirmed labels over noisy self-reports. To mitigate data scarcity, we compare a specialized convolutional neural network (CNN) trained from scratch with a transfer learning approach based on a Spatio-Temporal ECG foundation Model (FM). Performance is evaluated across varying data scales, and the representation structure is analyzed to interpret model behavior.Main results.On the official hidden test set of the George B. Moody PhysioNet/Computing in Cardiology Challenge 2025, our approach achieved a Challenge Score of 0.163. We observe that while the specialized CNN performs competitively in data-rich regimes, the FM exhibits superior robustness in extreme low-resource settings. Furthermore, performance reaches a plateau imposed by underlying disease physiology. Bimodal score distributions suggest that models distinguish established cardiomyopathy from indeterminate infection, which remains electrophysiologically indistinguishable from healthy controls.Significance.These findings clarify both the potential and intrinsic limits of ECG-based AI screening for NTD-associated cardiac involvement. Reliability-aware supervision and data-efficient transfer learning provide a practical framework toward scalable and clinically meaningful ECG screening systems in resource-constrained environments.

Humans

Treating neurogenic detrusor overactivity in order to manage autonomic dysreflexia - A systematic review.

INTRODUCTION: Autonomic dysreflexia (AD) is a severe and potentially life-threatening complication of a spinal cord injury (SCI), particularly in patients with lesions at or above the sixth thoracic level. Neurogenic detrusor overactivity (NDO) is one of the main triggering factors. The impact of NDO treatment on AD remains insufficiently clarified. METHODS: We conducted a systematic review of the literature in PubMed and Cochrane Database between January 1990 and May 2025. Eligible studies included patients with SCI and AD undergoing treatment for NDO, including antimuscarinics, botulinum toxin (BTX) or augmentation cystoplasty. The primary outcome was the assessment of systolic blood pressure (SBP) parameters in patients undergoing cystomanometry. RESULTS: Of the thirteen eligible studies, only five were included. No study evaluated augmentation cystoplasty. One study (12 patients) evaluating fesoterodine and four studies (95 patients) evaluating BTX injection demonstrated improved urodynamic parameters and a decrease in severity of AD during urodynamic studies and in daily life. Improvements in AD-HR-QoL and I-QoL scores were also demonstrated. DISCUSSION: Controlling NDO with fesoterodine or BTX injection reduces the prevalence and severity of AD, likely by limiting abnormal C-fiber recruitment and reducing neurogenic inflammation. BTX additionally modulates TRPV1-expressing afferents, which further reduces AD risk. Although hypertensive peaks improve, submaximal parameters remain unchanged, highlighting the need for additional complementary strategies. CONCLUSION: The use of BTX and fesoterodine for NDO treatment effectively reduces AD episodes in patients with SCI. Further long-term studies are needed to confirm the cardiovascular benefits and inform future therapeutic strategies.

Humans

Left ventricular hypertrophy in hypertension: a systematic review and meta-analysis of echocardiographic studies published from 2011 to 2025.

AIM: An updated meta-analysis targeting the prevalence of left ventricular hypertrophy (LVH), a cardinal marker of hypertensive heart disease (HHD), over the last 15&#x200a;years is lacking. Thus, we analyzed the literature in order to provide a comprehensive information on LVH prevalence, as assessed by echocardiography, in the hypertensive setting. METHODS: The PubMed, OVID-MEDLINE, and Cochrane Library databases were analyzed to search English-language articles published from 1 January 2011 up to 31 December 2025. Studies were identified by using MeSH terms and crossing the following search items: 'left ventricular hypertrophy', 'left ventricular mass', 'hypertensive heart disease', 'echocardiography', 'hypertension', and 'subclinical cardiac damage'. RESULTS: A total of 51 studies including 74&#x200a;632 hypertensive patients were considered. Overall, the prevalence of LVH in the pooled cohort, defined according to criteria recommended by echocardiographic guidelines, was 36.6% (95% CI: 33.4-40%). Data provided by 18 studies ( n &#x200a;=&#x200a;40&#x200a;108 patients) showed that the probability of having LVH was lower in men than in women (OR&#x200a;=&#x200a;0.62, CI: 0.48-0.80, P &#x200a;<&#x200a;0.0001). Among patients with LVH (17 studies), the risk of concentric LVH was almost twice as high as eccentric (OR&#x200a;=&#x200a;1.94, CI: 1.52-2.49, P &#x200a;<&#x200a;0.0001). CONCLUSION: Our meta-analysis suggests that the high contemporary prevalence of LVH reflects the failure of therapeutic strategies worldwide in the prevention and treatment of HHD. From a clinical perspective, these data imply the need for a more aggressive treatment of hypertension and related cardiovascular risk factors leading to LVH, especially in women.

Humans