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Match-performance indicators are widely used to explain success in football; however, traditional analyses based solely on absolute key performance indicators (KPIs) may overlook contextual factors such as ball possession and phase of play. This study aimed to examine match-performance indicators associated with winning in Turkish professional football using two complementary approaches: a raw KPI model based on absolute match actions and a possession- and phase-of-play-normalized KPI model accounting for contextual opportunity. Match data were obtained from a validated event-based database covering six consecutive seasons, yielding 2,728 team observations from 1,364 win-loss matches. Descriptive comparisons between winning and losing teams were conducted, followed by multivariate binary logistic regression analyses to identify performance indicators independently associated with match success under both modeling approaches. At the descriptive level, winning teams demonstrated higher values for shots, shots on target, accurate passes, opponent-half accurate passes, accurate crosses (%), and opponent-half accurate passes (%), whereas total possession and total passes did not differ significantly between groups. In terms of disciplinary indicators, losing teams received significantly more yellow and red cards, whereas fouls committed were significantly higher in winning teams (p = 0.014). However, the normalized indicator (fouls committed per out-of-possession) did not differ significantly between groups. In the raw KPI model, positive predictors of match success included shots on target (OR = 1.58), accurate crosses (OR = 1.10), opponent-half accurate passes (OR = 1.01), and fouls committed (OR = 1.04). Negative predictors were total crosses (OR = 0.92), yellow cards (OR = 0.89), and red cards (OR = 0.49). In the possession-normalized model, significant positive predictors were shots on target per possession, accurate crosses per possession, and fouls committed per out-of-possession. Significant negative predictors included crosses per possession, accurate crosses (%), yellow cards per out-of-possession, and red cards per out-of-possession. The findings indicate that combining absolute performance indicators with context-sensitive normalized metrics may provide a more comprehensive perspective on match success in football. Offensive efficiency and disciplinary control emerged as key correlates of winning, particularly when evaluated relative to possession and phase-of-play contexts. These findings suggest the potential value of integrating contextualized performance analysis into match evaluation and performance analysis frameworks.

Dissociation is a prevalent and impairing symptom commonly observed in trauma-exposed populations following interpersonal trauma. While anxiety sensitivity (AS) and emotional difficulties have been separately implicated in the development of dissociative experiences following trauma, a potential pathway underlying its development remains underexplored. This study examined the mediating effects of AS and emotional avoidance on the association between interpersonal trauma and dissociative symptoms. A trauma-exposed sample (N = 583) completed self-report measures assessing trauma exposure (LEC-5), anxiety sensitivity (ASI-3), emotional avoidance (i.e., DERS-16 nonacceptance subscale), and dissociative experiences (DES-B). Linear regression and path analytic models were conducted using R. Follow-up analyses included all domains of AS to assess specific significant contributors to dissociation. Interpersonal trauma was significantly associated with elevated AS and emotional avoidance, subsequently predicting greater dissociative symptom severity. When accounting for AS and emotional avoidance, our direct effect was no longer significant with AS and emotional avoidance fully mediating this relationship. Subdomain analyses revealed cognitive and social AS as the sole significant mediators between interpersonal trauma and dissociation via emotional avoidance. AS and emotional avoidance jointly contribute to the development of greater dissociative symptom severity following interpersonal trauma. Cognitive and social concerns emerged as key AS subdomains driving this pathway, suggesting that individuals with heightened fears of losing control or social embarrassment may display greater rates of emotional disengagement as a maladaptive coping strategy. Our findings further exemplify AS and emotional avoidance as particularly salient treatment targets for trauma-exposed populations exhibiting problematic dissociative experiences.

Background and Objectives: New Caledonia, an archipelago in the South Pacific, experienced an unprecedented conjunction of prolonged border closure during the COVID-19 pandemic (2020 to 2022) and marked influence of the El Niño/Southern Oscillation (ENSO). This context provided a unique opportunity to explore how environmental drivers, island isolation, and socio-demographic factors interact to shape infectious disease dynamics. This study aimed to assess the respective and combined effects of climatic variability, travel restrictions, and socio-demographic factors on the dynamics of four priority infectious diseases. Materials and Methods: We retrospectively analysed data from 2017 to 2023 on four infectious diseases: leptospirosis, dengue, influenza, and hepatitis A (HAV). Satellite precipitation data and the Multivariate El Niño/Southern Oscillation Index (MEI) were used. Socio-demographic and economic variables were gathered. Statistical analyses employed descriptive analysis and Generalized Additive Mixed Models to evaluate the associations between climatic events, travel restrictions, and disease circulation using the communal level as a random effect and time (daily) as a spline effect. Results: We analysed 878 cases of leptospirosis, 165 of HAV, 6607 of influenza, and 7377 dengue cases. Influenza was associated with rainfall before lockdown (Odds Ratio (OR) 0.7, Confidence interval 95%, (CI95%), (0.6-0.8)) and disappeared during lockdown but resurged post-reopening losing its meteorological association. Dengue epidemics declined, coinciding with the Wolbachia program and border closure, and were associated with lower MEI (OR 0.78, CI95% (0.6-1) during the 2017 to 2020 period. HAV cases were correlated with the MEI (OR: 1.8, CI95% (1-3.3)). Leptospirosis cases were associated with cumulative rainfall (OR 1.12 (1.1-1.2)) and lower education (OR 1.04, CI95% (1-1.1)) and decreased with water supply (OR 0.7, CI95% (0.5-0.8)). Conclusions: Our findings highlight how climatic conditions, mobility restrictions, and socio-environmental inequities differentially shape infectious disease risks in island ecosystems. These results reinforce the need for integrated One Health surveillance that jointly addresses environmental change, social vulnerability, and infectious disease prevention.

Locally advanced rectal cancer (LARC) management has evolved, but surgery (total mesorectal excision, TME) remains the curative cornerstone. Total neoadjuvant therapy (TNT) and organ preservation (OP) have emerged as response-adaptive strategies. We conducted a state-of-the-art systematic review to critically appraise TNT efficacy, trade-offs, OP feasibility, and emerging biomarkers. Following PRISMA 2020 guidelines, we searched PubMed, MEDLINE, Scopus, and EMBASE (1990-March 2026) plus ASCO/ESMO abstracts (2020-2026). We included phase II/III randomised controlled trials and major prospective studies evaluating neoadjuvant strategies in non-metastatic LARC. Risk of bias was assessed using RoB 2. Given heterogeneity, a narrative synthesis was performed (PROSPERO: CRD420251252675). From 2847 records, 45 publications (30 trials) were included. For high-risk LARC (cT4, cN2, EMVI+, MRF+, tumour deposits), TNT improves disease-free survival and reduces distant metastases versus standard chemoradiotherapy (RAPIDO, PRODIGE 23, STELLAR, TNTCRT). However, TNT increases locoregional recurrence risk with short-course radiotherapy (RAPIDO: 10% vs. 6%; Polish II: no sustained overall survival benefit). Organ preservation is achievable in expert centres (OPRA: 54% 5-year TME-free survival; OPERA; CAO/ARO/AIO-16), but surgery remains the durable standard for most patients. De-escalation (PROSPECT, CONVERT, FOWARC, OCUM) avoids radiotherapy in low-risk (mrMRF-) patients without compromising local control. Lateral pelvic lymph node involvement (LPLN+) remains a negative prognostic factor even after TNT. Immunotherapy added to TNT (UNION, STELLAR II, SPRING-01, PRECAM) increases pCR rates (40-60%) but remains investigational. ctDNA-guided adaptation (CINTS-R) is feasible but requires mature data. Surgery (TME) is the definitive curative treatment for LARC. TNT is a preferred intensification strategy for high-risk patients, but trade-offs between systemic and local control must be individualised. Organ preservation is safe only for selected patients in expert centres. Immunotherapy-TNT combinations and ctDNA guidance are promising but not yet standard. This review provides an evidence-based roadmap for integrating these advances without losing sight of surgery's central role.

Vicens-Bordas, J, Colomar, J, Altarriba-Bart&#xe9;s, A, Yeto-Jim&#xe9;nez, A, Jim&#xe9;nez, A, Carrera-Prat, J, Garc&#xed;a, F, Pe&#xf1;a, J, and Beato, M. Comparison of external load demands across three competitive tiers in Spanish football: A three-season single-club study. J Strength Cond Res XX(X): 000-000, 2026-The purpose of this study was to compare the match external load demands experienced by a football team competing for 3 consecutive seasons across various competitive tiers (fourth, third, and second) of Spanish football. Independent variables included player position, match location, and match outcome. A total of 747 individual official match observations from 47 male players were recorded using 10-Hz global positioning system devices. External load metrics (relative to minutes played) included total distance, high-speed running (HSR > 21 km&#xb7;hour-1), sprint distance (>24 km&#xb7;hour-1), high metabolic load distance (HMLD > 25.5 W&#xb7;kg-1), accelerations (>3 m&#xb7;second-2), and decelerations (<-3 m&#xb7;second-2). Linear mixed models (significance level set at p < 0.05) assessed the effects of competitive level, position, location, and result, including interaction effects. Cohen's d was also calculated with 95% confidence interval. Results showed that HSR and HMLD differed across competitive levels, with professional (second tier) matches requiring higher HSR demands (medium effects), and fourth tier greater HMLD demands than third tier (small effect). Positional differences were present in all metrics except accelerations, with wide roles (wingers and wide backs) being exposed to greater demands than central positions (medium to large effects). Match location had limited influence, though total distance was slightly higher at home matches (small effect). Winning was consistently associated with higher physical demands, particularly in the second tier, where players covered more distance at high intensities (HSR and sprinting) than when drawing or losing (small to medium effects). Interaction effects indicated that competition level modulated the influence of player position, match location, and result on physical demands. These findings suggest that professional football imposes higher physical demands (although not for all parameters, e.g., accelerations) than semiprofessional football. Coaches and practitioners should consider competition level and contextual factors when designing training and recovery strategies, particularly for wide-position players and during high-stakes matches.

Secondary immunodeficiency (SID) is a disorder in which the immune system is compromised by external or acquired factors, reducing the quantity or function of immunoglobulins. This condition increases the need for specialist consultation, follow-up, and replacement therapy, which in turn raises healthcare costs. To date, few studies have clinically characterized patients with SID; therefore, understanding their profile will enable improved management and treatment. To describe the clinical profile of patients with SID receiving human immunoglobulin replacement therapy (IgG-RT). A retrospective observational study was conducted through the review of 40 medical records of patients with SID undergoing IgG-RT. Risk factors and the benefits of replacement therapy were analyzed. The mean age was 48 years, with a predominance of women (62.5%). The most frequent conditions were rheumatologic diseases (38%), followed by hematologic disorders (31%) and protein-losing diseases (27%). All patients had received corticosteroids in combination with another immunosuppressant, and 77.5% had also been treated with rituximab. Infections were recorded in 50% of cases; however, only 35% received prophylaxis. Relapse was documented in 22.5% of patients, and mortality was 2.5%. The use of corticosteroids and immunosuppressants, specifically rituximab, was the main cause of SID, predominantly associated with rheumatologic and hematologic diseases. la inmunodeficiencia secundaria (SID) es un trastorno en el que el sistema inmunol&#xf3;gico se ve comprometido por factores externos o adquiridos, reduciendo la cantidad o la funci&#xf3;n de las inmunoglobulinas. Esta condici&#xf3;n incrementa la necesidad de interconsulta, seguimiento y terapia sustitutiva, lo que a su vez eleva los costos en salud. A la fecha, existen pocos estudios que caractericen cl&#xed;nicamente a los pacientes con SID; por ello, conocer su perfil permitir&#xe1; un mejor abordaje y tratamiento. describir el perfil cl&#xed;nico de pacientes con SID que reciben terapia sustitutiva con inmunoglobulina humana (IgG-RT). se realiz&#xf3; un estudio observacional retrospectivo mediante la revisi&#xf3;n de 40 expedientes cl&#xed;nicos de pacientes con SID en tratamiento con IgG-RT. Se analizaron factores de riesgo y los beneficios de la terapia sustitutiva. la edad promedio fue de 48 a&#xf1;os, con predominio de mujeres (62.5%). Las patolog&#xed;as m&#xe1;s frecuentes fueron las reumatol&#xf3;gicas (38%), seguidas de las hematol&#xf3;gicas (31%) y las enfermedades perdedoras de prote&#xed;nas (27%). Todos los pacientes hab&#xed;an recibido corticoesteroides en combinaci&#xf3;n con otro inmunosupresor, y el 77.5% tambi&#xe9;n hab&#xed;a sido tratado con rituximab. Se registraron infecciones en el 50% de los casos; sin embargo, solo el 35% recibi&#xf3; profilaxis. Se document&#xf3; reca&#xed;da en el 22.5% de los pacientes y una mortalidad del 2.5%. el uso de corticoesteroides e inmunosupresores, espec&#xed;ficamente rituximab, constituy&#xf3; la principal causa de SID, asociada predominantemente a enfermedades reumatol&#xf3;gicas y hematol&#xf3;gicas.

Functional loss and recovery in older adults are heterogeneous, with important implications for independence, care needs, and survival. While Activities of Daily Living (ADLs) are routinely assessed, most existing approaches reduce them to summary scores, thereby losing information about the order, timing, duration, and recurrence of functional change. We introduce a novel trajectory analytics framework designed to identify clinically interpretable trajectory phenotypes and evaluate their association with mortality. We analyzed 1.3 million ADL assessments from 265,530 residents in U.S. Veterans Affairs nursing homes. A hybrid trajectory clustering framework was developed, combining spell-based sequence construction, optimal-matching-based dissimilarity, and scalable quality-guided clustering. Sequence comparison was designed to preserve temporal structure while remaining computationally feasible for large-scale longitudinal data. Candidate clustering solutions were evaluated using multiple quality metrics, and mortality differences across clusters were examined using Kaplan-Meier estimation and Cox proportional hazards models adjusted for age and sex. Thirteen distinct ADL trajectory clusters were identified from about 110,000 unique trajectories, differing in dominant disability states, duration, recurrence, and mortality risk. Short, severe trajectories showed the highest early mortality, whereas longer, milder trajectories involving limited impairments, such as walking or bathing, were more stable and had lower mortality. The highest-risk cluster showed approximately 48% cumulative mortality within the first year and remained associated with the greatest hazard of death after adjustment. Sex-based sensitivity analyses showed broadly similar mortality ordering across males and females, although female-specific estimates were less precise because of the smaller sample size. The proposed framework reveals substantial heterogeneity in functional trajectories and their prognostic implications, providing an interpretable and computationally efficient tool for large-scale ADL trajectory clustering. These findings support trajectory-based phenotyping as a useful approach for personalized care planning, targeted resource allocation, and policymaking in long-term care settings.

In this work, we report the synthesis of two new copper-(II) complexes that preferentially assemble into coordination polymers through potential N,N,N- and N,C,N-type pincer ligands, with the metal centers adopting octahedral geometries. The crystallographic analysis of coordination polymers 2,6-bis-((1H-1,2,4-triazol-1-yl)-methyl)-pyridine-CuCl2 (C1), 3,5-bis-(1,2,4-triazol-1-ylmethyl)-toluene-CuCl2 (C2), and 2,6-bis-((1H-1,2,4-triazol-1-yl)-methyl)-benzene-CuCl2 (C3) reveals polymeric structures formed through triazole ligands imposing cis conformations and generating comparable unit cells. While in the case of ligands it was observed that 2,6-bis-((1H-1,2,4-triazol-1-yl)-methyl)-pyridine (L1) forms a 3D hydrogen-bonding network via triazoles and pyridine nitrogen, 3,5-bis-(1,2,4-triazol-1-ylmethyl)-toluene (L2), lacking pyridine, adopts a simpler 1D chain stabilized by C-H&#xb7;&#xb7;&#xb7;N and C-H&#xb7;&#xb7;&#xb7;&#x3c0; interactions, with van der Waals forces between chains and with C2 symmetry and 2,6-bis-((1H-1,2,4-triazol-1-yl)-methyl)-benzene (L3) displays both trans and cis forms, creating layered structures and losing symmetry due to directional hydrogen bonds. The computational study established that the formation energy (&#x394;E f) of the polymer chains C1, C2, and C3 decreases linearly with chain growth, indicating progressive electronic stabilization, with C2 showing the most favorable trend (-2.97 kcal/mol per unit). Similarly, the average stabilization energy per monomer (&#x394;E avg) becomes progressively more negative, converging at a chain length of about ten units, with C2 again displaying the greatest stability (-2.68 kcal/mol per monomer). In addition, the crystal structure of two azole derivatives, L2 and L3, is presented.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor characterized by its ability to create an immunosuppressive tumor microenvironment. Here, using robust 3D co-culture systems, samples from PDAC patients and murine in vivo models, we described a novel immune evasion mechanism used by PDAC to inhibit the anti-tumor activity of B lymphocytes: We provide evidence that pancreatic cancer suppresses the B cell-specific transcriptional program while enforcing their reprogramming into functional macrophages. Thus, we hypothesize that B cells undergo transdifferentiation under the influence of PDAC, by losing their lymphoid identity and acquiring a myeloid immunosuppressive phenotype. This drastic change is enacted by the loss of Pax5 expression. Importantly, our results showed that the Ex-B cells efficiently become phagocytic and produce soluble proteins that are known to enhance cancer cell survival and proliferation. This suggests that the PDAC-induced B cell to macrophage transdifferentiation pathway is functionally relevant and hence could serve as an immunotherapeutic target.

CHAPLE disease is a monogenic disorder in which CD55 deficiency drives gastrointestinal pathology. How CD55 deficiency affects adaptive immunity is unknown. Herein, molecularly, we characterize eight patients with genetically novel CD55 deficiency. Clinically, all patients developed early-onset protein-losing enteropathy, frequently complicated by thrombotic events, inflammatory bowel disease-like lesions, and recurrent respiratory infections. Ex vivo, immunophenotyping revealed disruption of the B cell compartment, marked by depletion of transitional B cells, expansion of CD21lo B cells, and accumulation of class-switched memory B cells and plasmablasts, while T cell subsets were largely preserved. In vivo, eculizumab rapidly resolved intestinal pathology, normalized serum albumin and immunoglobulin levels, and re-established a normal B cell profile. Furthermore, C5 inhibition enabled effective humoral protection and optimal pneumococcal vaccine responses. Together, these findings establish complement inhibition as central to B cell homeostasis in CHAPLE disease.

Although the Fontan operation was originally performed as a single-stage procedure, staged palliation is currently the preferred approach. The current study aimed to evaluate the outcomes of the single-stage Fontan operation. A bi-national Fontan registry (n=1862) was analyzed to identify patients who underwent a single-stage Fontan operation. These patients were compared with staged Fontan patients in the registry. Atriopulmonary Fontan connections were excluded. The primary composite endpoint was post-discharge Fontan failure, encompassing death, heart transplantation, Fontan takedown or conversion, protein-losing enteropathy, plastic bronchitis, or New York Heart Association functional class III or IV. Other endpoints were early complications, including chylothorax, in-hospital deaths, time to first arrhythmia episode, time to first thromboembolic event, and first cardiac reintervention. Patients who underwent a single-stage Fontan operation (n=176) were compared with those who underwent a staged Fontan operation (n=1421). Median follow-up for the entire cohort was 11.0 years (IQR: 5.3,17.9 years). The majority of single-stage Fontan operations were lateral tunnel (86%, n=152), which were performed before 2006 (169/176; 96%). There was no difference in freedom from Fontan failure between the two groups (p=0.62) [HR=0.90 (0.60, 1.35)]. Propensity-score matching yielded 262 patients (131 pairs) with similar freedom from Fontan failure (p=0.72). There was no difference between the two groups in early complications or secondary endpoints. In a large bi-national Fontan population, 11% of patients underwent a single-stage Fontan operation over 48 years. There was no difference in the incidence of freedom from Fontan failure, chylothorax, or reinterventions between patients who underwent a staged or a single-stage Fontan operation.

Sensorineural hearing loss (SNHL), predominantly resulting from the irreversible loss of cochlear hair cells, remains a clinical challenge without effective treatments. Recently, neuromodulation strategies based on two-dimensional nanomaterials have shown regenerative potential, with MXene standing out due to its excellent electrical conductivity, biocompatibility, and modifiable surface properties. Hair cells (HCs) and supporting cells (SCs) originate from the same prosensory cells, with previous work showing that MXene (especially Ti3C2Tx) incorporation in Matrigel can promote HCs formation with SCs in cochlear organoid culture. However, the MXene is prone to oxidation, losing the conductivity and catalytic activity of this material in Matrigel during HC regeneration. In this study, we modified MXene with dopamine (DA-MXene) that mimics neurotransmitter functions to promote HC regeneration. We found that DA-MXene significantly enhanced the proliferation and survival of SCs in organoid culture. HC formation was also upregulated in DA-MXene treated cochlear explant culture compared with MXene samples. Mechanistic studies indicated that DA-MXene further activated signaling pathways that regulate pluripotency of stem cells compared with MXene, which is vital for restoring the plasticity of SCs. Collectively, this work proposes an innovative nanomaterial-based approach that combines chemical modification and electroactive stimulation, offering a promising strategy for regenerating HCs in SNHL.

Salt-losing crisis in the neonate is a life-threatening event manifested by hyponatremia, hyperkalemia, and metabolic acidosis. Whilst this biochemical finding is classically seen in congenital adrenal hyperplasia (CAH), conditions of aldosterone action, such as pseudohypoaldosteronism (PHA), can also present with these findings but require different care. A four-week-old term male infant is described who was brought in with vomiting, lethargy, and anuria. At the time of admission, he was in shock with marked hyponatremia (119 mmol/L), life-threatening hyperkalemia (9.8 mmol/L), metabolic acidosis, and acute kidney injury (AKI). He&#x2002;needed resuscitation, treatment of hyperkalemia, and admission to pediatric intensive care. CAH was considered at the beginning, but newborn mass screening for 17-hydroxyprogesterone was normal, and serum cortisol before steroid therapy was adequate, so primary&#x2002;adrenal failure may be ruled out. Electrolytes and renal function returned promptly to normal after volume repletion, and the patient passed into a polyuric recovery. The clinical course, including rapid resolution of PHA, was consistent with transient (secondary) PHA related&#x2002;to severe volume depletion and prerenal AKI, resulting in temporary renal tubular resistance to aldosterone. This case illustrates the necessity to differentiate secondary PHA from CAH in neonates presenting with salt loss crises, since early recognition spares lifelong unnecessary steroid exposure and directs appropriate supportive care.

Malaria remains a major global health burden, particularly in sub-Saharan Africa, where the recent invasion and urban expansion of Anopheles stephensi are increasing transmission risk in densely populated areas. Conventional vector control strategies, including widespread insecticide application, are progressively losing efficacy due to the rapid spread of resistance. These limitations have accelerated the development of genetic control approaches aimed at either suppressing vector populations or replacing them with genetically modified mosquitoes incapable of transmitting pathogens, with the shared objective of reducing disease transmission. For population suppression strategies, an essential component is a conditional regulatory system that enables precise control of toxic or otherwise deleterious effector proteins. The most widely used platform, the tetracycline-dependent (Tet) system, modulates gene expression in response to tetracycline. However, this system can exhibit leaky expression and variable regulation, which may compromise its reliability and limit its application in certain contexts. The dihydrofolate reductase (DHFR) destabilization domain (DD) system, developed in Drosophila, offers an alternative strategy for post-translational control of protein stability. In this system, proteins fused to a destabilization domain are rapidly degraded unless stabilized by the small molecule trimethoprim (TMP), enabling tight and reversible control. In Drosophila and prior reports, this system has been associated with relatively low fitness costs, although such effects have not been systematically evaluated in mosquitoes. Before adapting this system for mosquito genetic control, it is therefore essential to assess the impact of TMP exposure on key life-history traits. Here, we assessed the effects of varying TMP concentrations on mosquito development, survival, and reproductive output. Our results demonstrate that low concentrations of TMP exposure had no detectable effects on immature development, adult survival, or reproductive output under the conditions tested, supporting the implementation of the DHFR-DD system in mosquitoes. Importantly, these effects were dose-dependent, with moderate to high TMP concentrations producing measurable impacts on mosquito fitness. These findings provide a foundational step toward the development of more precise and reliable conditional expression systems for genetic vector control, advancing innovative strategies to mitigate malaria transmission in high-risk regions.