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Ocean-atmosphere CO2 exchange is key in modulating global climate, but the Arctic Ocean's anthropogenic carbon (Cant) uptake is poorly constrained. Most studies in the Canada Basin using the Transit Time Distribution (TTD) relied on two years of paired gas tracers, CFC-12 and SF6. Here we use nuclear reprocessing products 129I, 236U, and 137Cs to estimate Cant in the Atlantic Water layer by the TTD. We present the evolution of Cant in the Canada Basin from 1993 to 2023, and a high-resolution distribution of Cant across the basin in 2022. We observe a basin-wide inventory increase in the Atlantic Layer (400-1000 m) of 5.5  ± 0.9 Tg C yr-1. Cant content in water entering the Canada Basin tracks increasing atmospheric input, time-lagged by 15-20 years; we anticipate Cant content of up to 65 μmol kg-1 in core Atlantic Water entering the basin by 2050.

Proprioception, our internal awareness of limb position and movement, is essential for shoulder stability through neuromuscular control. Following traumatic anterior instability (TAI), proprioceptive impairments may develop, potentially affecting upper limb function. These deficits vary across individuals. Previous studies have focused primarily on joint position sense and kinesthesia, while sense of force (SoF) deficits in chronic TAI remain largely unexplored. Moreover, clinical assessments are multifactorial and time-limited, and little is known about how SoF relates to common clinical measures. This cross-sectional study aimed to (1) determine whether chronic TAI is associated with shoulder SoF deficits compared with the contralateral side and a control group (CG) and (2) explore potential associations between SoF, maximal voluntary isometric strength (MVIC), and clinical questionnaires used in shoulder instability assessment. Participants aged 18-40 with TAI underwent SoF assessment in both shoulders. A matched CG (n = 37) was tested only on the dominant arm. Proprioceptive accuracy (PA) during SoF testing, MVIC, and shoulder questionnaires (Western Ontario Shoulder Instability Index, Shoulder Instability-Return to Sport after Injury, Disabilities of the Arm, Shoulder and Hand (short version)) were collected for analysis. The TAI group included 37 participants (27% female, n = 10; 73% male, n = 27), subdivided into non-surgical (TAINS, n = 18) and surgical (TAIS, n = 19) subgroups. Analysis revealed a significant main effect of intensity on PA, F(1,36) = 26.835, P < .001, &#x3b7;2 P = .427, but no significant main effect of group, F(1,36) = 0.545, P > .05, &#x3b7;2 P = .015, nor intensity &#xd7; group interaction, F(1,36) = 0.131, P > .05, &#x3b7;2 P = .004. A significant main effect of side was observed, F(1,35) = 4.18, P < .05, &#x3b7;2 P = .107, with higher PA score on the affected side (10% &#xb1; 7.6) than the unaffected side (8.5% &#xb1; 6.8; Cohen's d = 0.196). Only the model for the 20% external rotation condition was statistically significant (adjusted R2 = 0.383; F(2,33) = 11.884,P < .001), with Disabilities of the Arm, Shoulder and Hand (short version) (&#x3b2; = 0.763, P < .001) and Shoulder Instability-Return to Sport after Injury score (&#x3b2; = -0.519, P = .002) emerging as significant predictors. Chronic TAI subjects showed no difference in SoF performance compared with the CG. Associations between SoF, MVIC, and clinical questionnaire outcomes were minimal, emphasizing the importance of interpreting clinical assessments collectively rather than in isolation.

Rare neuromuscular diseases pose significant diagnostic challenges due to their genetic complexity and varied clinical presentations. Current diagnostic methods are often costly and inefficient, with primary care physician slacking adequate knowledge and effective diagnostic algorithms needed for accurate identification. This study addresses these challenges by developing PhenoRareAI, a model designed to improve the diagnosis of rare neuromuscular diseases such as Glycogen Storage Disease II and Spinal Muscular Atrophy. A total of 109 electronic health records from Huashan Hospital and external centers were used to develop and validate PhenoRareAI. The model integrates phenotype recognition algorithms and disease priority ranking models, which were rigorously tested against baseline models and validated with external datasets. The key outcome measures included the accuracy of phenotype recognition and disease diagnosis. PhenoRareAI demonstrated signifi cant improvement in phenotype recognition, achieving a micro F1-score and a macro F1-score of 27.40% and 25.16%, compared to the baseline PhenoPro model's scores of 11.44% and 14.65%. In terms of disease prioritization, the model achieved a top 1 ranking for 15 cases of Glycogen Storage Disease II and 17 cases of Spinal Muscular Atrophy after phenotype enhancement, with a mean reciprocal rank (MRR) of 37.37 and 57.21, respectively, significantly outperforming existing methods. PhenoRareAI signifi cantly enhances the diagnosis process for rare neuromuscular diseases, demonstrating strong potential for clinical application. These findings highlight the importance of integrating AI-driven diagnostic tools into healthcare to better navigate the complexities of rare disease diagnosis. The online version contains supplementary material available at 10.1007/s13755-026-00455-w.

Background and Objectives: Mid-term skeletal stability after bimaxillary orthognathic surgery in patients with facial asymmetry and a relatively normal sagittal skeletal relationship (ANB &#x2248; 1-4&#xb0;) remains underreported. This study aimed to determine the three-dimensional characteristics and temporal changes in postoperative skeletal remodeling and symmetry maintenance in such patients. Materials and Methods: This retrospective case series included 25 patients (ANB &#x2248; 1-4&#xb0;) undergoing bimaxillary orthognathic surgery. Three-dimensional computed tomography was performed preoperatively (T0), immediately postoperatively (T1), and at 6-12 months postoperatively (T2) to quantify bilateral condylar, ramus, mandibular body, maxillary parameters, and occlusal cant. Statistical analyses were performed using appropriate statistical methods for paired and repeated-measures designs. Results: Preoperatively, the long side exhibited significantly greater condylar volume, ramus height, and mandibular body length than the short side (all p < 0.05). Postoperatively, a "long-side reduction and short-side augmentation" strategy significantly reduced or reversed most bilateral differences, with a marked improvement in occlusal plane cant (p < 0.01). At T2, only mild bone remodeling was observed, with no significant loss of postoperative skeletal symmetry. The occlusal plane remained stable. Conclusions: In patients without marked sagittal discrepancies, bimaxillary orthognathic surgery effectively restores transverse and vertical skeletal symmetry. Mid-term stability is well maintained over 6-12 months, with only mild condylar and ramus remodeling, suggesting adaptive remodeling rather than relapse.

Conventional bilateral sagittal split ramus osteotomy (BSSRO) for asymmetric mandibular prognathism carries risks to the temporomandibular joints and inferior alveolar nerve. A hybrid technique, combining a modified L-shaped intraoral vertico-sagittal ramus osteotomy (mIVSRO) with a contralateral SSRO, may mitigate these risks, but its aesthetic outcomes are unproven. The aim of this study was to compare the aesthetic efficacy of the hybrid versus conventional BSSRO techniques, adjusting for baseline asymmetry. This retrospective cohort study compared 30 patients with asymmetric mandibular prognathism treated with either the hybrid technique (n = 15) or conventional BSSRO (n = 15). Soft and hard tissue changes were assessed using frontal photographs and cephalograms. Postoperative aesthetic outcomes were compared using analysis of covariance (ANCOVA) to adjust for baseline differences. After ANCOVA adjustment, no significant differences were found in the correction of soft or hard tissue chin deviation between the groups. There was greater residual gonial angle asymmetry (P = 0.054) and soft tissue face plane cant (P = 0.065) in the hybrid group when compared to the BSSRO group, although neither comparison reached statistical significance. Notably, all postoperative neurosensory disturbances in the hybrid cohort occurred on the SSRO-treated side. The hybrid osteotomy technique provides aesthetic correction of chin deviation with no significant difference detected when compared to conventional BSSRO. Given its functional advantages, particularly the confinement of neurosensory risk to the SSRO side as demonstrated in this study, the hybrid approach is a valuable alternative for managing asymmetric mandibular prognathism, especially in high-risk patients.

Running assessments are frequently conducted without inducing fatigability because achieving true exhaustion in athletes can be both time consuming and physically demanding. Blood flow restriction (BFR) presents a potential solution by reducing time-to-exhaustion. To determine whether running with BFR (1) accelerates fatiguability compared to standard running and (2) influences running spatiotemporal parameters, including step frequency, step length, contact time, flight time, and duty factor. Sixteen participants (11 men, 5 women) completed two cross-over running trials until exhaustion under two conditions: control and 80% occlusion BFR. Time-to-exhaustion and heart rate were recorded as well as pre/post run maximal voluntary isometric contractions for knee flexors, knee extensors, and ankle plantar flexors. Running spatiotemporal parameters were measured at 65% of maximal aerobic speed both before and after exhaustive running. The BFR protocol significantly shortened time-to-exhaustion (7&#x2009;min 51 s &#xb1;2&#x2009;min 54 s vs. 24&#x2009;min 02 s &#xb1;12&#x2009;min 10 s in control, p&#x2009;<&#x2009;.001). Heart rate at exhaustion was lower in the BFR condition (169.5&#x2009;&#xb1;&#x2009;19.0 vs. 188.1&#x2009;&#xb1;&#x2009;8.9&#x2009;bpm, p&#x2009;=&#x2009;.001). Post-run knee flexors strength declined similarly in both protocols (~21%), indicating comparable neuromuscular fatigability despite the shorter BFR running time. None of the spatiotemporal parameters differed significantly between conditions (p&#x2009;>&#x2009;.074). Running with BFR accelerates fatigability without significantly affecting running spatiotemporal parameters.

Epicardial adipose tissue (EAT) is a component of visceral adiposity and mediates cardiac function and atherosclerosis via expression of several bioactive molecules. To evaluate the significance and relationship between epicardial fat thickness (EFT) and familial dyslipidemia and left ventricular function. This prospective case-control study was conducted at Assiut University Children's Hospital between September 2023 and August 2025. Twenty-one children with familial dyslipidemia and twenty-one age-, sex-, and BMI-matched healthy controls underwent clinical evaluation, lipid profile assessment, and transthoracic echocardiography, including measurement of epicardial fat thickness and left ventricular systolic and diastolic function according to American Society of Echocardiography guidelines. Dyslipidemic patients showed significantly higher total cholesterol (332.9&#x2009;&#xb1;&#x2009;222.3&#xa0;mg/dL), triglycerides (391.4&#x2009;&#xb1;&#x2009;251.6&#xa0;mg/dL), and LDL (154.3&#x2009;&#xb1;&#x2009;130.4&#xa0;mg/dL) than controls (p&#x2009;<&#x2009;0.001). Mixed hyperlipidemia was the most common type (47.6%). Echocardiography revealed increased epicardial fat thickness (2.88&#x2009;&#xb1;&#x2009;0.94&#xa0;mm vs. 2.29&#x2009;&#xb1;&#x2009;0.57&#xa0;mm; p&#x2009;=&#x2009;0.018), larger left atrial (21.45&#x2009;&#xb1;&#x2009;3.86&#xa0;mm; p&#x2009;=&#x2009;0.031) and aortic diameters (17.54&#x2009;&#xb1;&#x2009;3.12&#xa0;mm; p&#x2009;=&#x2009;0.013). Triglyceride level was the only independent predictor of epicardial fat thickness (&#x3b2;&#x2009;=&#x2009;0.437, p&#x2009;=&#x2009;0.028). &#xa0;Echocardiography revealed increased epicardial fat thickness and early cardiac remodeling. Serum triglycerides were the only independent predictor of EFT, suggesting its key role in subclinical cardiovascular risk among dyslipidemic children. &#x2022; Epicardial adipose tissue is associated with cardiovascular risk factors in adults. &#x2022; Children with primary dyslipidemia may develop early cardiac dysfunction. &#x2022; This study demonstrates a signifi cant association between epicardial adipose tissue thickness and left ventricular function in children. &#x2022; It highlights the potential role of epicardial fat as an early marker of cardiac involvement in pediatric dyslipidemia.

This study examined the relationship between smile aesthetics perception and personality factors among individuals with varying dental education backgrounds. This cross-sectional study included 412 participants categorized into four groups: pre-clinical dental students, clinical dental students, practicing dentists, and laypeople. Participants rated 20 photographs depicting variations in maxillary midline diastema, central incisor crown length, smile arc, gingival display, and incisal plane cant on a ten-point attractiveness scale. Personality factors were assessed using the NEO-FFI questionnaire, measuring Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness. Dental professionals assigned significantly lower aesthetic scores to smiles with a 2.0&#xa0;mm central incisor crown reduction, a 4.0&#xa0;mm gingival display increase, and an incisal plane cant compared to non-dental raters (P&#x2009;<&#x2009;.05). Higher Agreeableness and Conscientiousness scores were associated with a preference for smiles without midline diastema (r&#x2009;=&#x2009;.118, 0.112; P&#x2009;=&#x2009;.017, 0.023). Higher Extraversion and Openness scores were associated with a preference for no gingival display (r&#x2009;=&#x2009;.147, 0.123; P&#x2009;=&#x2009;.003, 0.012). Perceptions of smile aesthetics varied significantly between dental and non-dental raters. Severity of smile discrepancy has a predictive role in aesthetic preferences, influencing the perceived attractiveness of specific smile characteristics. Personality factors had some associations with the perceived attractiveness of specific smile characteristics. Understanding how severity of smile discrepancy, personality traits and dental training influence esthetic preferences can help clinicians better tailor smile design and treatment communication to individual patient expectations.

Cytomegalovirus (CMV) infection is a significant complication in pediatric liver transplant recipients. This study aimed to assess the incidence, risk factors, and suspected effects of CMV infection in children undergoing liver transplantation and compared acyclovir and ganciclovir-based preventive therapy. The study included 92 patients who had liver transplants at Ege University Transplantation Unit between 2011 and 2021. Sixty-four pediatric patients with preoperative CMV immunoglobulin G (IgG) positivity were analyzed. Patients with early mortality, re-transplantation within 6 months, and CMV IgG negativity were excluded. The study consisted of 39 females (61%) and 25 males (39%), with a median age of 5.3 years at transplantation. Cytomegalovirus viremia occurred in 42 patients (65%), and CMV disease developed in 7 patients (10%). The median duration of CMV viremia was 40 days, and CMV disease was 105 days. Age was significantly associated with CMV disease development, with younger patients at higher risk (P = .007). The choice of antiviral treatment (acyclovir vs. valganciclovir) did not significantly impact the development of CMV vire mia or disease. Cytomegalovirus viremia and disease are common in pediatric liver transplant recipients, with younger age being a signifi cant risk factor for CMV disease. However, CMV viremia and disease did not significantly impact this cohort's graft loss, acute cellular rejection, or mortality. The choice of antiviral treatment and immunosuppression protocols did not influence CMV outcomes. These find ings highlight the need for vigilant monitoring and tailored management strategies for CMV in pediatric liver transplantation. &#xa0; Cite this article as: Barut D, Kunay B, Y&#x131;ld&#x131;r&#x131;m Arslan S, et al. CMV infection in pediatric liver transplantation and comparison of prophylaxis methods depending on donor serostatus. Turk J Gastroenterol. 2026;37(2):242-250.

Primary care providers (PCPs) play a key role in addressing sleep-related issues such as insomnia but often lack training in sleep medicine. The UCI Train New Trainers (TNT) Primary Care Psychiatry Fellowship includes training on sleep disorder assessment and management. We evaluated the programs' ability to enhance PCPs' skills in identifying and managing behavioral sleep disorders. Case assessments were administered twice to fellows, at the start and end of an educational conference. Fellows selected four of ten listed psychiatric and sleep diagnoses for each case. Fellows also underwent pre-, mid-, and post-fellowship surveys to determine whether training was associated with changes in comfort diagnosing and treating sleep disorders. Fellows showed a significant improvement in sleep disorder identification after training compared to before. They also reported significant improvement in comfort diagnosing insomnia, accuracy identifying circadian rhythm disorders, and comfortability administering CBT-I. Use of structured sleep assessments increased but remained less frequent than mood disorder screening tools. Fellows exhibited increased comfort and competence in managing behavioral sleep medicine, particularly insomnia and circadian rhythm sleep disorders with brief didactic training. Further training in non-pharmacological treatments and greater use of standardized sleep assessments is warranted to optimize patient outcomes in primary care settings.

This study aimed to evaluate the accuracy of maxillary repositioning using patient-specific implants (PSI) adapted for minimally invasive orthognathic surgery (MIOS), employing a simplified two-plate fixation protocol. Although all patients underwent bimaxillary orthognathic surgery, quantitative accuracy analysis was limited to the maxilla. This retrospective study included 20 patients treated with PSI tailored for MIOS. The surgical protocol involved limited soft tissue dissection and maxillary fixation using only two plates. Postoperative accuracy was assessed through computed tomography and voxel-based comparison with the virtual surgical plan. Discrepancies were measured in three linear axes and cant correction. Statistical analysis included Bland-Altman plots, effect sizes, and intraclass correlation coefficients (ICCs). All procedures were completed without intraoperative complications. Discrepancies between planned and postoperative positions ranged from 0.02&#xa0;mm to 0.31&#xa0;mm. ICCs exceeded 0.82 across all variables, with cant correction ICCs of 0.98 and 0.99. Effect sizes were negligible to small, and Bland-Altman analysis revealed no systematic bias. Customized PSI can be effectively adapted for use in MIOS protocols. Despite a reduced fixation strategy, high accuracy and reproducibility were achieved. These findings support the use of simplified PSI workflows as a precise and less invasive alternative in modern orthognathic surgery.

Cervical cancer continues to pose a significant global health chal-lenge, with relatively high incidence and mortality rates among gynecological malignancies, particularly in developing countries. Complex etiological factors, including genetic predispo-sition, environmental influences, and biological mechanisms, regulate the progression of cer-vical cancer. Recent advances in understanding RNA splicing have contributed to a more de-tailed elucidation of these complexities, presenting a promising avenue for cervical cancer research. Here, we elucidate how alternative splicing events promote the synthesis of diverse protein isoforms that modulate tumorigenesis, progression, and metastasis. A PubMed and Google Scholar-based literature search was performed to identify genes involved in splicing mechanisms as biomarkers for cervical cancer. The search covered studies published between 2000 and 2024. The following keywords were used: "splicing," "splicing factors/genes," "gene regulation," "spliceosomes," "splicing as cancer hallmark," and "splicing mechanisms," in combination with "cervical cancer." We included only English-language publications related specifically to splicing in cervical cancer. We consolidated major splicing factors identified across genomic studies, clinical research, and mechanistic evaluations related to cervical cancer, which may serve as signifi-cant prognostic and diagnostic biomarkers. These consolidated findings highlight the potential impact of splicing on clinical decision-making, various therapeutic modalities, and personalized medicine. Furthermore, therapeutic strategies targeting splicing mechanisms could lead to novel interventions that im-prove clinical outcomes in cervical cancer patients.

Nguyen, AP, Kisita, V, Van Cant, J, Monnet, T, and Bosquet, L. Reproducibility of rate of perceived exertion-based self-selected running speeds on indoor track and treadmill conditions in recreational runners. J Strength Cond Res 40(2): e125-e130, 2026-This study evaluates the reproducibility of self-selected speeds at a rate of perceived exertion (RPE) of 3/10 in both track and treadmill conditions. It also investigates the differences between 2 conditions: i.e., track versus treadmill and 2 RPE instructions, i.e., 3/10 and 8/10. In addition, it compares spatiotemporal parameters across conditions and RPE levels. Fifty-five recreational runners completed six 1-km runs under randomized conditions: 4 at 3/10 and 2 at 8/10 RPE on both track and treadmill. Spatiotemporal parameters, heart rate, and self-selected speeds were recorded. Reliability was assessed using intraclass correlation coefficients (ICC), standard error of measurement ( SEM ), and minimal detectable change (MDC). Statistical significance for all tests was set at &#x3b1; = 0.05. Self-selected speeds showed excellent reliability on both surfaces (ICC = 0.93-0.97). The track showed lower SEM (0.3 km&#xb7;h -1 ) and MDC (0.7 km&#xb7;h -1 ) values compared with the treadmill ( SEM : 0.6 km&#xb7;h -1 ; MDC: 1.6 km&#xb7;h -1 ). Speeds were 20% slower at 3/10 RPE and 10% slower at 8/10 RPE on the treadmill. Treadmill running exhibited longer contact times (+13%), shorter flight times (-35%), and shorter step lengths (-6%) at 3/10 RPE, with similar trends observed at 8/10 RPE. Rate of perceived exertion appears to be a reliable and practical tool for monitoring and prescribing running intensity levels. The slower treadmill speeds at comparable RPE levels may help reduce biomechanical loading on the lower limb joints, offering advantages for rehabilitation. However, differences in biomechanics and perceived effort between treadmill and track running highlight the need for context-specific applications in training and rehabilitation.

Malnutrition among older hospitalized adults with chronic heart failure (CHF) is associated with adverse clinical outcomes, yet reliable early risk stratification tools remain lacking. This study aimed to develop and validate a machine learning (ML) model for malnutrition risk stratification in this population. Malnutrition among older hospitalized adults with chronic heart failure (CHF) is associated with adverse clinical outcomes, yet reliable early risk stratification tools remain lacking. This study aimed to develop and validate a machine learning (ML) model for malnutrition risk stratification in this population. Malnutrition prevalence was 44.1% (348/790). In the internal testing, CatBoost (CAT) achieved superior performance with an AUC of 0.901 (95% confidence interval [CI]: 0.858-0.943), accuracy of 0.840, recall of 0.753, and the lowest Brier score of 0.113. This model demonstrated strong calibration, clinical utility, and the highest composite score (62/64). External validation confirmed CAT's generalizability (AUC: 0.916, 95% CI: 0.887-0.945). SHAP analysis identified body mass index (BMI), calf circumference, New York Heart Association (NYHA) classification, age, and diabetes as signifi-cant contributors to malnutrition risk. The CAT-based model effectively stratifies malnutrition risk in older hospitalized CHF patients, offering a tool for early intervention to improve outcomes. Further multicenter prospective studies are needed to validate its real-world applicability.

Paediatric septic thrombophlebitis secondary to head and neck infections is a rare but life-threatening disease. Although commonly associated with oropharyngeal infections, otogenic cases have also been described, yet paediatric literature on their disease course and thrombotic distribution remains sparse. To describe the clinical presentation, thrombotic distribution, management, and outcomes of paediatric septic thrombophlebitis secondary to primary otogenic infections. We conducted a retrospective case series of children aged 0-18&#xa0;years admitted to a tertiary paediatric referral centre between 2016 and 2021 with septic thrombophlebitis following an otogenic infection. Clinical, microbiological, radiological, and treatment data were extracted from records. Ten patients (median age 4.5&#xa0;years, 70% male) were included. Most cases presented with primary acute otitis media and mastoiditis. Fusobacterium necrophorum was detected in 50% of cases. Internal jugular vein thrombosis occurred in 80%, sigmoid sinus thrombosis in 60%, and cavernous sinus thrombosis in 30%. All patients received systemic antibiotics and anticoagulant therapy for medians of 42.5 and 46&#xa0;days, respectively. Surgery, mainly otogenic interventions, such as mastoidectomy, was performed in 90% of patients. Complications other than thrombosis occurred in 70% of cases and encompassed both intra- and extracranial manifestations. Thrombosis resolved or recanalized in 78% of cases on follow-up imaging. This case series adds to the limited literature on paediatric septic thrombophlebitis secondary to otogenic infections, highlighting a high rate of internal jugular vein thrombosis and a complicated disease course. &#x2022; Paediatric thrombophlebitis secondary to an otogenic infections is a rare but life-threatening disease. &#x2022; These otogenic presentations can be a diagnostic challenge, while carrying a signifi cant risk of severe intracranial or systemic complications. &#x2022; This paediatric case-series describes the complicated disease course of septic thrombophlebitis following primary otogenic infections, demonstrating heterogeneity in clinical presentations and thrombotic distributions.

Ultra-trail running is increasingly popular, yet most research on biomechanics focuses on road running or treadmills. This study assesses changes in foot strike pattern (FSP), step frequency, and other biomechanical parameters over a 156-km ultra-trail race. Fifty-five experienced runners participated in the Trail Scientifique de Cl&#xe9;cy, a 156-km race with 6000 meters of elevation gain. Biomechanical data were collected at the end of each 26-km lap using video for FSP and Optojump for other parameters. Muscle strength was measured via maximal voluntary isometric contraction (MVIC) of the hip abductors and ankle plantar flexors. Forty-one runners completed the race. FSP remained consistent. Step frequency decreased initially (P=0.003) before stabilizing. Self-selected speed declined by 14.2% (P<0.001), and step length reduced by 12.6% (P<0.001). Ground contact time increased (+12.9%, P<0.001), while flight time remained stable. Leg stiffness showed a non-significant decreasing trend (P=0.048). MVIC for hip abductors and ankle plantar flexors slightly decreased late in the race (P=0.015 and P=0.004). Experienced ultra-trail runners maintain consistent FSP while strategically adapting other biomechanical parameters to manage fatigue, supporting sustained performance and injury prevention in ultra-endurance races.

Complete androgen insensitivity syndrome (CAIS) is a rare X-linked recessive disorder due to androgenreceptor mutations, characterised by a 46,XY karyotype, female phenotype, and undescended testes. This reportaims to illustrate the clinical management and the rare synchronous pathology of multiple gonadal tumors in a 60-year-old phenotypic female with long-standing CAIS. A 60-year-old patient presented following the incidental detection of bilateral adnexal masses. Diagnosticevaluation included imaging (USG/MRI) to assess internal reproductive organs and gonadal morphology, alongsidehormonal analysis (LH, testosterone, and estradiol). A laparoscopic bilateral gonadectomy was performed to managethe suspected neoplasia. Imaging demonstrated the absence of the uterus and ovaries, confi rming bilateral solid gonadal lesions.Hormonal analysis showed elevated LH with normal testosterone and estradiol levels. Histopathology of the excisedtissues revealed a complex and heterogeneous presentation: the left gonad contained a Sertoli cell tumor, a Leydigcell tumor, and sclerotic seminiferous tubules; the right gonad showed a Sertoli cell adenoma. This rare synchronous pathology illustrates the signifi cant heterogeneity of neoplasia associated withCAIS. Current evidence supports individualized postpubertal gonadectomy to balance the risk of malignancy againstthe benefi ts of endogenous hormonal production. The fi ndings emphasize that long-term follow-up and tailoredsurgical timing are essential components in the clinical management of CAIS.

Herbal medicines have gained remarkable popularity due to their natural origins and potential medicinal value. Nevertheless, they are chemically complex and pose signifi-cant pharmacological challenges. This review focuses on the key aspects influencing their clinical use: their variable bioavailability, complex pharmacokinetics (ADME), and potential for interactions. A primary concern is herb-drug interactions, with special emphasis on the modulation of drug-metabolizing enzymes by specific phytoconstituents, which can alter drug concentrations to an extent that may be life-threatening, causing either increased toxicity or therapeutic failure. The pharmacological profile is further complicated by the complex effects of constituents, such as synergistic or antagonistic actions, which make predicting therapeutic response and safety difficult. A critical challenge in this field is the frequent dis-connect between in vitro findings and in vivo outcomes, underscoring the importance of phar-macokinetic data, particularly bioavailability, for accurate clinical risk assessment. Safety is a paramount concern, as it is often compromised by inconsistent standardization and quality control, leading to batch-to-batch variability, potential adulteration, and contamination. The absence of stringent regulation impairs therapeutic consistency and introduces health risks. To address these issues, advanced approaches are being employed to improve bioavailability, including novel drug delivery systems that enhance solubility and stability. This review em-phasizes that a rigorous, phytoconstituent-centric approach is essential for navigating the complexities of herbal medicine. By addressing challenges in pharmacokinetics, interactions, safety, standardization, and bioavailability through rigorous scientific investigation and em-bracing future perspectives, such as in silico modeling and improved regulatory frameworks, the quality, safety, and effectiveness of herbal treatments can be ensured, supporting their responsible integration into modern, evidence-based medical systems.

The 2023 Kahramanmara&#x15f; (M7.8) and Elbistan (M7.6) earthquakes in T&#xfc;rkiye provide a profound case study in multi-fault rupture dynamics. We update a pre-existing Coulomb stress model&#xb9; to analyse the historical and immediatestress conditions that caused this doublet. Our fi ndings indicate the Pazarc&#x131;k segment of the Kahramanmara&#x15f;earthquake source rupture failed under high historical loading (12 bars since 1822) and immediate Coulomb stresstransfer (~2.5 bars) from the initial Narl&#x131; rupture. The pattern of stress changes is consistent with the observations ofsuper-shear rupture to the Northeast of the Pazarc&#x131;k segment and sub-shear rupture speeds to the south-west.Conversely, the Elbistan earthquake was primarily triggered by signifi cant normal stress reduction (unclamping; ~11bars) from the mainshock, which overcame an initially negative stress state, and creating favourable conditions forthe observed super-shear rupture. This sequence underscores the critical role of combined coseismic and long-termstress transfer in driving complex, cascading fault ruptures.