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First, to evaluate whether the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is associated with hemodynamic changes in ophthalmic artery (OA) Doppler in near-term pregnancy. Second, to assess the performance of OA Doppler to rule in and rule out angiogenic factor imbalance. This was a cross-sectional cohort study nested within the PE37 randomized controlled trial, involving nulliparous women recruited between January 2023 and January 2025 who underwent sFlt-1/PlGF ratio measurement between 35&#x2009;+&#x2009;0 and 36&#x2009;+&#x2009;6&#x2009;weeks' gestation. We included a subsample of women who underwent OA Doppler evaluation, including measurement of OA peak systolic velocity (PSV) ratio and OA pulsatility index (PI), as well as assessment of mean arterial pressure (MAP) and mean uterine artery (UtA) PI. The operator was blinded to sFlt-1/PlGF ratio values. Trends in median values of OA and maternal-fetal Doppler parameters across sFlt-1/PlGF tertiles were analyzed using the Jonckheere-Terpstra test and quantile regression, adjusting for maternal body mass index, age and smoking status. The predictive performance of the OA-PSV ratio for sFlt-1/PlGF ratio&#x2009;&#x2265;&#x2009;38 was evaluated using receiver-operating-characteristics-curve analysis. We included 203 women, of whom 62, 71 and 70 were in the lowest, middle and highest tertiles of the sFlt-1/PlGF ratio, respectively. With increasing sFlt-1/PlGF ratio tertile, there was a significant increase in the OA-PSV ratio (median, 0.45 (interquartile range (IQR), 0.39-0.53) vs 0.48 (IQR, 0.41-0.58) vs 0.59 (IQR, 0.50-0.66); adjusted P&#x2009;<&#x2009;0.001), a significant decrease in OA-PI (median, 2.20 (IQR, 1.92-2.61) vs 2.13 (IQR, 1.86-2.37) vs 1.86 (IQR, 1.60-2.26); adjusted P&#x2009;=&#x2009;0.031) and a significant increase in MAP (median, 87.0 (IQR, 82.7-92.0)&#x2009;mmHg vs 88.7 (IQR, 83.7-93.7)&#x2009;mmHg&#xa0;vs 94.7 (IQR, 89.3-100.0)&#x2009;mmHg; adjusted P&#x2009;<&#x2009;0.001). In contrast, no significant trend was observed in mean UtA-PI across sFlt-1/PlGF ratio tertiles. Among those individuals with an OA-PSV ratio&#x2009;<&#x2009;0.61, 90.5% truly had a sFlt-1/PlGF ratio&#x2009;<&#x2009;38, at a 15% false-positive rate. This study provides new evidence of a significant association between the sFlt-1/PlGF ratio and OA Doppler parameters in near-term pregnancies, suggesting that OA Doppler indices, particularly the PSV ratio, reflect angiogenic imbalance. Given its non-invasive nature, accessibility and low cost, OA Doppler emerges as a promising surrogate tool for ruling out angiogenic imbalance. &#xa9; 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Acute coronary syndrome (ACS) remains a leading cause of emergency department presentations, yet triage based on the ST-elevation myocardial infarction (STEMI)/non-ST-elevation myocardial infarction (NSTEMI) paradigm misses approximately 25-34% of acute coronary occlusion myocardial infarction (OMI). Early artificial intelligence-electrocardiography (AI-ECG) models showed retrospective promise for detecting ischemic ECG patterns but lacked prospective validation. This review synthesizes emerging multicenter registry, prospective cohort, and pathway trial evidence for AI-ECG in ACS triage, including the Queen of Hearts registry, ROMIAE, and DIFOCCULT-3 studies. It is essential to distinguish two separate clinical tasks: (1) detecting OMI for emergent catheterization laboratory activation, and (2) ruling out acute myocardial infarction (MI), which requires serial high-sensitivity troponin and cannot be achieved by ECG alone. Contemporary findings suggest AI-ECG significantly improves OMI detection sensitivity (92% vs. 71% for standard care) and reduces false-positive catheterization laboratory activations by up to 91% among biomarker-negative patients. For acute MI rule-out, AI-ECG shows promise as an adjunct to troponin-based strategies, with a negative predictive value of approximately 99% when combined with high-sensitivity troponin and clinical risk scores. We propose a 'Second Opinion' framework in which AI augments physician judgment as a clinical decision support tool. Key implementation challenges include algorithmic bias, alert fatigue, documentation, and the risk of widening the digital divide. AI-ECG represents a shift toward a physiologically driven OMI vs. non-occlusive myocardial infarction (NOMI) diagnostic framework.

Acute pulmonary embolism (PE) has a heterogeneous clinical presentation, varying from mild chest symptoms to shock or cardiac arrest. Optimal management of severe acute PE requires assessment of multiple parameters to confirm the diagnosis and assess the patients prognosis, preferably by EXPERT-PE care/Pulmonary Embolism Response Teams (PERTs), integrating multidisciplinary expertise to optimize PE management. While management of severe acute PE already can be challenging, this particularly applies to certain patient subgroups, in particular pregnant women. As a result of ruling out pregnant women in randomized trials, specific guideline recommendations on severe PE are unavailable. This case-based narrative review aims to provide an overall overview of the approach to treating patients with severe PE, based on the comprehensive case description of a pregnant patient with high-risk PE.

Although several guidelines recommend tools for sarcopenia screening and diagnosis, their feasibility in Chinese primary health care (PHC) remains unclear. This study evaluated the availability and convenience of sarcopenia-related tools from the perspective of routine PHC practice. This two-stage expert-based evaluation was conducted between March 2023 and June 2024. In phase 1, a multidisciplinary core panel (n&#x202f;=&#x202f;6) used a modified nominal group technique to define availability and convenience and to establish rating rules. In phase 2, an independent panel of PHC experts (n&#x202f;=&#x202f;7) assessed 15 tools identified from major sarcopenia guidelines; ultrasonography was included as an emerging option. Inter-rater agreement was examined using Kendall's coefficient of concordance. Availability was defined as the ease with which clinicians could obtain the required equipment or tool and use it in routine practice, whereas convenience was defined as the overall practicality of the test in terms of operational difficulty, acceptability, and portability. Screening tools were consistently rated as the most feasible options for PHC. Among strength and performance assessments, the chair stand test, gait speed, the Short Physical Performance Battery, and the Timed Up and Go test were rated as highly available and highly convenient. Handgrip strength was highly convenient but only moderately available because dynamometers were not routinely stocked in many PHC institutions. For confirmatory assessment of muscle mass, ultrasonography showed the most favorable overall profile, with high availability and moderate convenience, whereas bioelectrical impedance analysis showed moderate convenience but limited availability. Inter-rater agreement was high for both convenience (Kendall's W&#x202f;=&#x202f;0.86, 95% CI 0.84-0.96, p&#x202f;<&#x202f;0.001) and availability (Kendall's W&#x202f;=&#x202f;0.92, 95% CI 0.90-0.98, p&#x202f;<&#x202f;0.001). In this exploratory expert-based assessment, Chinese PHC appeared well suited to sarcopenia case finding and first-line functional assessment, but confirmatory evaluation of muscle mass remained a major implementation bottleneck. A staged pathway may emphasize screening in PHC, selective referral, and targeted investment in feasible technologies such as bioelectrical impedance analysis and ultrasonography.

Associative polymers with precisely arranged stickers offer opportunities to program material properties with molecular precision. Yet, it remains unclear how the placement and fraction of stickers dictate structure, dynamics, and macroscopic properties. By developing a model unentangled polymer system with hydrogen-bonding stickers, we show that randomly distributed stickers neither form clusters nor change flow properties, whereas stickers placed at chain ends drive nanocluster formation even at low concentrations. Adding more end stickers produces a rubbery plateau spanning eight decades in frequency with two distinct relaxation timescales, in contrast to the single plateau predicted by the classic sticky Rouse model. These results demonstrate that sticker distribution dictates whether associative polymers undergo nanocluster formation or microphase separation, while substantial alterations in dynamics and viscoelasticity require both sticker aggregation and thermomechanical stability of associated domains. Our findings resolve a longstanding debate on associative polymer dynamics and provide molecular design rules for programmable soft materials.

This theoretical article centers dissociative fragmentation - a trauma-informed construct drawn from dissociation research - to explain the psychological costs faced by marginalized elites: individuals who attain high-status positions while belonging to historically oppressed groups. Unlike cognitive dissonance, which accounts for episodic tensions, dissociative fragmentation captures the chronic partitioning of identity required to survive conformity-driven elite environments. Marginalized elites are defined with demographic and occupational examples, situating their paradoxical position of authority and exclusion within structures of racism, sexism, heteronormativity, ableism, and classism. The analysis builds on intersectionality and racial trauma literature. Insights from psychology, sociology, and Black feminist thought are synthesized to construct a unified framework. Impostor phenomenon, stereotype threat, and intersectional invisibility are integrated as proximal states within a process model that culminates in identity fragmentation. The framework clarifies how institutional feeling rules, tokenization, and microaggressions foster chronic compartmentalization of self, leading to alienation, burnout, and trauma-like symptoms. Institutional remedies are also proposed - including identity-safety cues, sponsorship structures, intersectional norms change, and healing-centered engagement - that shift responsibility from individuals to organizations. By reframing conformity's toll as structurally induced dissociation, this article advances a trauma-informed, intersectional agenda for research and practice that centers justice alongside psychological well-being.

Neurogenic pulmonary edema is a rare but severe complication of acute central nervous system injury, such as subarachnoid hemorrhage, typically presenting with immediate onset. This report describes an uncommon case of delayed-onset neurogenic pulmonary edema following subarachnoid hemorrhage. A 68-year-old man with subarachnoid hemorrhage, caused by a ruptured left posterior communicating artery aneurysm, developed tachypnea and hypoxemia with bilateral pulmonary infiltrates 96 hours after symptom onset. Echocardiography was normal, ruling out cardiogenic causes, and neurogenic pulmonary edema was diagnosed. The patient improved rapidly with fluid restriction and diuretic therapy, and subsequently underwent successful aneurysm coil embolization. Neurogenic pulmonary edema is thought to result from an excessive sympathetic activation leading to pulmonary vasoconstriction, increased capillary pressure, and endothelial injury. Delayed cases may involve secondary sympathetic surges due to intracranial pressure fluctuations, vasospasm, or inflammatory injury. This case highlights the need for clinicians to consider delayed neurogenic pulmonary edema when respiratory deterioration occurs several days after subarachnoid hemorrhage to ensure timely diagnosis and life-saving management.

Automated analysis of Pap-smear images plays an important role in cervical cancer screening, particularly in low-resource settings where manual cytology remains labour-intensive, subjective, and prone to inter-observer variability. On the other hand, accurate segmentation of the nucleus and cytoplasm is a fundamental step in computer-aided diagnosis systems because it enables quantitative morphometric analysis and computation of clinically important biomarkers such as the nucleus-to-cytoplasm ratio. However, robust cervical cell segmentation remains challenging due to staining variability, inhomogeneity, irregular morphology, weak cytoplasmic boundaries, and overlapping cellular structures. This study presents an adaptive quadtree-based segmentation framework for automated nucleus and cytoplasm delineation in Pap-smear images. The proposed method employs hierarchical split-merge decomposition guided by a dynamic adaptive statistical homogeneity analysis using mean intensity, variance, and entropy measures. Preprocessing is performed using large-kernel median filtering for background normalisation, followed by local Otsu thresholding, adaptive region merging, overlap refinement, and morphological post-processing. The framework was evaluated on both the Herlev cervical cytology dataset and the ISBI 2015 cervical cytology segmentation challenge dataset containing overlapping and clustered cervical cells. Comparative benchmarking was additionally performed against the U-Net and Attention U-Net. On the Herlev dataset, the proposed framework achieved nucleus Dice coefficients exceeding 0.94 and Zijdenbos Similarity Index (ZSI) values greater than 0.9034 across all diagnostic classes, with competitive cytoplasm segmentation performance. On the ISBI 2015 dataset, the framework maintained acceptable segmentation performance under overlapping-cell conditions, achieving nucleus Dice and ZSI values of 0.912&#x202f;&#xb1;&#x202f;0.048 and 0.918&#x202f;&#xb1;&#x202f;0.044, respectively. Morphometric feature comparisons demonstrated strong agreement with ground-truth annotations and low average percentage errors for area and diameter measurements. Although deep learning models achieved superior performance under highly complex overlap conditions, the proposed framework remained competitive while requiring substantially lower computational resources and no iterative model training. The proposed Adaptive Quadtree-Based Segmentation framework provides a lightweight, interpretable, and computationally efficient approach for automated cervical cytology segmentation. Its training-free design, transparent statistical decision rules, and reduced hardware requirements make it particularly suitable for deployment in resource-constrained and embedded cervical cancer screening systems. The framework provides a practical segmentation backbone for automated cytology analysis and downstream computer-aided diagnosis applications.

The leaky integrate-and-fire paradigm is widely used to describe spiking dynamics in biological and artificial neurons. However, its implementation typically relies on explicit reset rules or intrinsic mechanisms involving negative differential resistance. Here we address the question: Can spike-like behavior emerge within a fully continuous dynamical framework without such ingredients?. We study a minimal resistive-capacitive circuit coupled to a conductance-activated quasi-linear memristor characterized by a single intrinsic relaxation time scale and an internal state variable. We demonstrate that spiking arises from the nonlinear coupling of the state variable and its voltage-dependent equilibrium value. Rather than being governed by a minimum transition slope in the static current-voltage characteristics, the onset of spiking does not exhibit sharp parametric thresholds but instead depends sensitively on the excitation frequency.

Spatial multi-omics technologies jointly profile transcriptomes, proteins and chromatin accessibility in situ, enabling integrative analysis of tissue organization across molecular layers. However, most existing graph-based integration methods rely on independently constructed modality-specific k-nearest-neighbor graphs. When auxiliary modalities are sparse or noisy, these graphs can become topologically discordant, propagate spurious edges, weaken cross-modal alignment and reduce spatial domain resolution. We present ARISE (Anchored RNA for Integrated Spatial Embedding), an RNA expression anchored framework for spatial multi-omics integration. ARISE defines a shared-edge topology by intersecting RNA feature-similarity and spatial-proximity graphs, encodes auxiliary modalities on this common scaffold, and integrates them through inside-out hierarchical fusion. We further show theoretically that graph intersection minimizes false-positive edges within a broad class of k-of-r graph fusion rules, providing a principled basis for topology anchoring. Across various spatial multi-omics benchmarks spanning simulated and real datasets in bi-modal and tri-modal settings, ARISE improves spatial domain identification, cross-modal consistency and preservation of tissue structure relative to existing methods. Furthermore, the learned representation supports biologically meaningful downstream analyses, including marker-based domain annotation, pathway enrichment and cis-regulatory inference, indicating that ARISE yields a robust and interpretable framework for spatial multi-omics integration. The source code is available at https://github.com/XiangxiangWang-code/ARISE. The archived version used in this study is available at https://doi.org/10.6084/m9.figshare.32686137.v2.

Traditional developmental science has often described child growth as a sequence of stages or linear progressions, yet many phenomena-abrupt spurts and regressions, idiosyncratic pathways, and widening individual differences-resist linear accounts. This article proposes chaos theory as a framework for quantifying developmental trajectories. Chaos theory, which addresses how complex patterns emerge from simple rules in deterministic yet unpredictable ways, aligns with observations of sensitive developmental periods, emergent behaviors, and divergent outcomes. I situate chaos theory alongside dynamic systems theory, neuroconstructivism, and developmental-cascade models and clarify how chaos might add mathematical precision to established insights: Bifurcation analysis identifies tipping points at which behaviors reorganize; Lyapunov exponents quantify stability and sensitivity to small perturbations; state-space methods reconstruct attractor landscapes from dense time series; and complexity metrics discriminate structured variability from noise. These tools convert powerful metaphors-soft assembly, attractors, cascades-into testable hypotheses about when and why qualitative change occurs. Such a framework also motivates microgenetic and high-density longitudinal designs, computational modeling of phase transitions, and interventions conceived as targeted perturbations delivered near sensitive windows. Finally, I discuss why adopting a chaos framework can be advantageous compared with (or in concert with) traditional linear models.

To quantify the heterogeneity of treatment effects of higher versus standard MAP targets on 28-day mortality, to identify distinct clinical phenotypes that respond differentially to MAP targets, and to derive simple bedside decision rules to guide individualised haemodynamic management. Current guidelines recommend a uniform mean arterial pressure (MAP) target of &#x2265;65&#x2009;mmHg for septic shock. However, trials like SEPSISPAM found no mortality benefit from higher targets in hypertensive patients. We hypothesised that this null finding results from the masking of heterogeneous treatment effects (HTEs) among phenotypically distinct individuals. We conducted a retrospective cohort study of 7665 hypertensive patients with septic shock from the Medical Information Mart for Intensive Care IV database (version 3.1). The primary exposure was time-weighted average MAP (TWA-MAP) during the first 24 h, dichotomised into high target (>75&#x2009;mmHg) versus standard target (65-75&#x2009;mmHg). The primary outcome was 28-day mortality. Individual treatment effects (ITEs) were estimated using a T-Learner causal machine learning framework with gradient boosting. Patients were stratified by ITE quartiles, and a Classification and Regression Tree (CART) was used to derive bedside clinical rules. We observed marked HTE (ITE range: -0.54 to +0.86). In the Strong Benefit group (Decompensated Phenotype) - characterised by tachycardia, hyperlactatemia and renal dysfunction - the high MAP target dramatically reduced 28-day mortality from 62.6% to 22.9% (absolute risk reduction&#x2009;=&#x2009;39.7%, P <&#x2009;0.001). Conversely, in the Harm group (Frail Phenotype) - characterised by older age and lower heart rate - the high target increased mortality from 14.7% to 33.9% (ARR = -19.2%, P <&#x2009;0.001). The CART model identified heart rate >105 bpm and creatinine >1.65 mg/dL as simple bedside criteria to identify patients likely to benefit from higher targets. The impact of higher MAP targets in hypertensive septic shock exhibits a distinct crossover pattern: life-saving in decompensated patients but harmful in frail patients. This HTE explains the null results of previous landmark trials. Utilising simple parameters like heart rate and creatinine can guide a shift from 'one-size-fits-all' targets towards precision haemodynamic management.

Sulfur(vi) fluoride exchange (SuFEx) reactions were introduced as next-generation click transformations that form robust sulfur(vi)-based linkages under mild conditions. Their defining feature is the unusual behaviour of the S-F bond: it is thermodynamically stable, yet can be selectively substituted when a suitable nucleophile is properly positioned. This balance has made SuFEx a valuable platform in chemical biology, enabling novel covalent probes, inhibitors and conjugation strategies in complex aqueous environments. In contrast, SuFEx applications to nucleosides, nucleotides and nucleic acids remain comparatively scarce and are only now beginning to mature. Progress has been limited by scaffold-specific synthetic and workflow constraints, including the scarcity of broadly enabling methodological studies and limited compatibility with standard oligonucleotide workflows. Even so, recent reports show that these barriers can be overcome in selected settings and that SuFEx can be translated into functional nucleic-acid constructs. This review summarises current advances with a focus on concepts and practical design rules. The first part is chemistry-centered: it compares the most successful strategies for installing sulfur(vi)-fluoride electrophiles on nucleoside, nucleotide, and oligonucleotide frameworks, and discusses reagent choices, linker designs and warhead positioning. The second part focuses on applications, outlining how these synthetic advances are turned into chemical biology tools where proximity effects convert reversible recognition into durable capture. We conclude by highlighting key bottlenecks and the most promising opportunities for progress.

Severe trauma in patients aged&#x2009;&#x2265;&#x2009;65&#xa0;years is increasingly frequent. Frailty and sarcopenia are major prognostic factors, yet Total Psoas Area (TPA), an objective imaging biomarker of muscle mass, is usually measured at a single time point. We investigated the relationship between frailty, initial TPA, and its post-traumatic dynamics. observational retrospective cohort study of patient's&#x2009;&#x2265;&#x2009;65&#xa0;years with severe trauma and&#x2009;&#x2265;&#x2009;2 CT scans from the from a level 1 trauma center (2018-2023). TPA was measured on axial L3 CT slices and indexed to height2. Pre-trauma frailty was assessed using the Clinical Frailty Scale (CFS). Longitudinal TPA changes were analyzed with a multivariable GEE model, testing interactions between age and frailty. Among 76 patients, 56 were non-frail (CFS 1-3) and 20 frail (CFS&#x2009;&#x2265;&#x2009;4). Initial TPA did not differ between groups. Longitudinal analysis revealed divergent trajectories: TPA decreased more sharply with age in frail patients (-17.7 mm2/m2/year) compared with non-frail (-1.1 mm2/m2/year). This significant age&#x2009;&#xd7;&#x2009;frailty interaction indicates that, at younger ages, TPA is comparable or even higher in frail patients, whereas at older ages it becomes substantially lower. Time since trauma had only a modest effect on TPA evolution. In the multivariable Cox model, non-frailty and higher GCS at admission were independently associated with lower mortality, while age, ISS, ASA score, and antiplatelet therapy were not significant. TPA showed a borderline association without reaching statistical significance. The model demonstrated good discrimination (C-index 0.812). In elderly trauma patients, TPA dynamics are strongly influenced by frailty and age, rather than initial TPA alone. Early assessment of frailty and muscle mass can refine risk stratification and guide personalized rehabilitation and nutritional strategies.

Blue nevus is a benign dermal lesion occasionally associated with malignant transformation into melanoma arising in a blue nevus, a rare and aggressive form of melanoma with different molecular features. Fewer than 200 cases have been reported worldwide. In this case study, a 78-year-old woman presented with a congenital bluish nodular lesion on the left buttock that enlarged over the years. Magnetic resonance imaging suggested a malignant soft tissue tumor. Surgical excision was performed, accompanied by an intraoperative histopathological study, reporting a melanoma with no dermoepidermal junction involvement. Immunohistochemistry confirmed the melanocytic origin; molecular analysis ruled out a BRAF gene mutation but identified a GNAQ exon 5 mutation in the melanoma and blue nevus components, confirming the precursor lesion. Despite multiple therapies, the disease progressed with metastases to the liver, lungs, and brain, ultimately resulting in the patient's death. Melanoma arising in a blue nevus represents an aggressive neoplasm, highlighting the importance of early biopsy and multidisciplinary evaluation. The application of immunohistochemistry and molecular profiling in atypical presentations that mimic other neoplasms represents a valuable tool for diagnosis, prognosis, and treatment planning in rare melanoma subtypes.

Acupuncture has shown significant therapeutic effects for functional dyspepsia (FD) in clinical trials. However, clinical observations reveal substantial variations in patient responses to acupuncture. In addition to patient-related factors, such variability may also be associated with differences in acupuncturists' clinical experience. This study compared the treatment outcomes for FD between junior and senior acupuncturists. This exploratory secondary analysis used data from a previous randomized controlled trial. Patients were divided into two groups based on acupuncturists' years of practice as defined by the professional title evaluation rules, using 5&#x202f;years as the cut-off (Group A treated by junior acupuncturists and Group B treated by senior acupuncturists). Outcome measures included the Symptom Index for Dyspepsia (SID), the four cardinal symptoms of FD, and the Nepean Dyspepsia Life Quality Index (NDLQI). Assessments were conducted at baseline, treatment weeks 2 and 4, and follow-up weeks 4 and 12. Data were analyzed using generalized estimating equations. Adjusted analyses were performed after including items with between-group differences as covariates. The study revealed that Group B had lower SID scores than Group A at both follow-up time points-at 4&#x202f;weeks (mean difference: 0.6, p&#x202f;=&#x202f;0.007) and at 12&#x202f;weeks (mean difference: 0.8, p&#x202f;=&#x202f;0.001). In addition, Group B showed greater improvements in postprandial fullness and early satiety at both follow-ups (p&#x202f;<&#x202f;0.010). However, no significant between-group differences were observed for epigastric pain or epigastric burning. Regarding quality of life, Group B also had higher NDLQI scores at the 12-week follow-up (mean difference: -2.9; p&#x202f;=&#x202f;0.041). Based on the 5-year administrative cutoff criterion, this exploratory secondary analysis found a potential association between acupuncturists' years of practice and acupuncture efficacy for FD, but prospective studies are needed for confirmation.

Palliative care has been identified as one of the most inequitable areas of healthcare. In Switzerland, as globally, disparities in end-of-life care (EOLC) exist along socio-demographic lines, shaping the access to and quality of care received across services by patients and their caregivers. Research has linked these disparities to binary gender differences and other aspects of a person's social position. The GiveCare project aims to provide a systemic understanding of how aspects of gender and diversity intersect to shape the provision of EOLC in Switzerland and to translate the generated knowledge into practice, policy, education and training. GiveCare employs a sequential mixed-methods design, combining a feminist intersectional approach with a systems thinking lens. It consists of four work packages (WPs): (1) A national survey will assess the perceived awareness of gender and diversity among palliative care professionals. (2) A focused ethnography will provide in-depth insights into the care journeys of patients and their significant others in two specialised inpatient palliative care units. (3) A social network analysis and discrete event modelling will unpack the complexity of such care journeys across inpatient and outpatient settings in the Canton of Zurich. 4. Throughout the process, an integrated knowledge translation approach will help to generate actionable evidence, co-created with patients, caregivers, professionals and policymakers, to enhance inclusivity and equity in EOLC practice and policy. The Ethics Committee of the Canton of Zurich, Switzerland, granted ethical approval for WP2-4 (Req-2025-02241) and issued a waiver for WP1 (Req-2025-00211). The research team will conduct the research in accordance with the Swiss Federal Act on Data Protection and the rules and regulations of the Swiss Federal Data Protection and Information Commissioner. The findings will be disseminated through peer-reviewed publications and conference presentations as well as via the community of practice established through the integrated knowledge translation process.

This perspective report examines temporal trends in concussion rates in relation to changes in permitted physical contact in the Swedish Women's Hockey League (SDHL). Over three seasons, the league gradually allowed more physical play, culminating in the current permission of body checking from the 2022/2023 season. Contrary to traditional assumptions, reported concussion rates declined during a period of progressively increased permitted physical contact. However, these observational findings should be interpreted with caution, as multiple contextual factors may have influenced the results. Also, the results do not establish a causal relationship between body checking policy and concussion incidence and rather than supporting immediate policy change, the findings highlight the need for continued monitoring and further research into how rules, education, and player behavior interact to influence concussion risk.

Differences in sex development (DSD) with 46,XY karyotype are a group of rare congenital conditions affecting the structure and function of the urogenital system. Published data indicate, that despite the increasingly widespread use of genetic testing, the etiology remains unclear in approximately half of cases. To clarify the molecular causes of 46,XY DSD by performing whole-exome sequencing (WES) in a precisely phenotyped and clinically comprehensively evaluated group of patients. WES was performed in a consecutive cohort of 39 children diagnosed in our center as 46,XY DSD (aged 0.2-17.9&#x2009;years). 32 were assigned male, 6 female, and 1 was a transgender boy. All patients underwent detailed clinical, hormonal and biochemical evaluation prior to genetic testing. A genetic cause explaining DSD phenotype was identified in 8 children. Pathogenic variants were detected in 3 patients, including variants in the AR and DHX37 genes. Likely pathogenic variants were found in 5 patients, affecting the AR and HSD17B3 genes. Variants of uncertain significance (VUSs) were identified in 7 patients, involving genes with well-established relevance to DSD- NR5A1, DHX37, AR, MAMLD1, SOS2andFAM111A. Although classified as VUSs these variants represent plausible contributors to the patients' phenotypes. In the remaining children, no variants currently known or suspected to be associated with 46,XY DSD were identified. The most common confirmed etiology in the cohort was androgen insensitivity syndrome (AIS). In addition, pathogenic variants in genes not linked to DSD were identified in 7 patients, demonstrating the broader clinical utility of WES. Our findings confirm that even a broad, high-throughput method such as WES fails to establish the molecular cause of 46,XY DSD in a substantial proportion of well-phenotyped patients, while at the same time enabling the identification of pathogenic variants in genes unrelated to DSD. We observed frequent genotype-phenotype discordance: similar clinical phenotypes could be associated with different genotypes, whereas the same gene variant could present with variable clinical expression. Re-analysis of WES data after 12-24&#x2009;months should be considered in patients without a definitive diagnosis or in those who develop additional clinical features.