Search Results (558)

The perimenopausal phase represents a critical window for early intervention against accelerated bone loss, highlighting an urgent need for safe and accessible non-pharmacological strategies. Although mind–body exercises are widely recommended for healthy aging, their specific structural and metabolic impacts on the perimenopausal skeleton yield conflicting results and remain poorly understood. To address this gap, this systematic review and three-level meta-analysis evaluated the effects of mind–body modalities on bone health in perimenopausal women, utilizing this model to account for statistical dependencies among multiple effect sizes within individual studies. Quantitative synthesis suggested that mind–body exercise may offer modest structural benefits, indicated by positive effects on bone mineral density (SMD = 0.55, p < 0.01) and bone mineral content (SMD = 1.63, p < 0.01); however, these findings must be interpreted with caution as the accompanying certainty of evidence is low to very low. Conversely, these structural adaptations were not accompanied by stable alterations in bone turnover markers, which remained consistently unchanged (SMD = −0.10, p > 0.05). Furthermore, bone mineral metabolism was not statistically significant in the primary analysis, with a confidence interval that included the null (SMD = 0.90, p = 0.079) and demonstrated limited stability across robustness checks. Assessed via the GRADE framework, this overall very low certainty was primarily due to risk-of-bias concerns, inconsistency, imprecision, suspected publication bias, and clinical heterogeneity. Consequently, given the current evidence limitations, mind–body exercise is best conceptualized as a supportive lifestyle component of a healthy aging trajectory rather than a potent osteogenic therapy. It offers a holistic preventative approach that might support bone health while concurrently supporting overall musculoskeletal resilience, though firm clinical recommendations cannot yet be made. Future well-powered trials must adopt rigorous designs with precise endocrine staging to better clarify the underlying mechanisms of skeletal adaptation. Full article

Background: Polyendocrine Metabolic Ovarian Syndrome (PMOS), previously known as Polycystic Ovary Syndrome (PCOS), is one of the most common endocrine disorders affecting women of reproductive age and represents a major cause of infertility worldwide. It is associated with hormonal imbalance, ovulatory dysfunction, and metabolic disturbances, all of which can significantly impair reproductive outcomes and quality of life. We aimed to investigate the metabolic and hormonal markers in infertile women who had PMOS in one of the rapidly developing Middle Eastern countries. Methods: This was a retrospective observational cohort study conducted at the Military Medical Specialist Center in Qatar (2019–2024). Data were extracted from patient medical records, including demographic characteristics, clinical presentation, hormonal profiles, metabolic parameters, and details of fertility treatment. Women aged 18–40 years diagnosed with PMOS according to the Rotterdam criteria were included. Correlation coefficient analysis was performed to assess the associations between PMOS-related factors. Patients were categorized by BMI (normal, overweight, and obese). Results: The mean age of patients was 31.9 ± 5.3 years, and 43.8% of patients were obese. Primary infertility was more frequent than secondary infertility (61.8% vs. 38.2%). Women with secondary infertility were significantly older and had higher body mass index (BMI) (p = 0.001 and p = 0.01, respectively). Insulin resistance was prominent (mean Homeostatic Model Assessment for Insulin Resistance [HOMA-IR] of 4.04) and increased significantly with the increase in BMI (p = 0.01). BMI showed positive correlations with serum levels of glucose, insulin, HOMA-IR, and testosterone. Hormonal parameters were largely comparable between infertility groups, except for lower FSH levels in secondary infertility (p = 0.04). The proportion of PMOS based on the HOMA-IR category was 5.6% (HOMA-IR < 1.0), 23.4% (HOMA-IR 1–1.99), 20.2% (HOMA-IR 2–2.99), and 50.8% (HOMA-IR > 3.00). In PMOS patients, there was a significant association between obesity and HOMA-IR, with each 1-unit increase in HOMA-IR associated with a 14% increase in odds (crude odds ratio 1.14; 95% confidence interval 1.02–1.28, p = 0.02). Also, obesity was associated with low LH/FSH (crude odds ratio, 0.67; 95% CI, 0.45–0.99; p = 0.04). Results: The mean age of patients was 31.9 ± 5.3 years, and 43.8% of patients were obese. Primary infertility was more frequent than secondary infertility (61.8% vs. 38.2%). Insulin resistance was prominent (mean HOMA-IR 4.04) and increased significantly across BMI categories (3.0 in normal-weight vs. 4.8 in obese women, p = 0.01). BMI was positively correlated with HOMA-IR (r = 0.17, p = 0.02) and testosterone levels (r = 0.18, p = 0.01). Secondary infertility became more frequent with increasing BMI (p = 0.02). Each 1-unit increase in HOMA-IR was associated with a 14% increase in the odds of obesity (OR 1.14, 95% CI 1.02–1.28, p = 0.02). Conclusions: Among infertile women with PMOS, obesity and insulin resistance were prominent metabolic characteristics. These findings support routine screening for insulin resistance, particularly in overweight and obese women, together with weight management and individualized fertility treatment based on BMI and metabolic profiles. Full article

Because human infertility can arise from genetic, molecular, cellular, anatomical, and endocrine abnormalities, in vitro gametogenesis has become an important area of reproductive research. New developing technology involving the generation of human primordial germ cell-like cells (hPGCLCs) from induced pluripotent stem cells (hIPSCs) might assist with understanding early germ cell development (specification, migration, gametogenesis, and epigenetic reconstitution), as well as provide a solution for infertility and hereditary disorders. Given that human primordial germ cells (PGCs) are still not well characterized at a molecular level, we present a practical workflow to robustly and efficiently induce hPGCLCs from human pluripotent stem cells (hPSCs) XX and XY cell lines. This protocol describes the hPGCLC specification of hPSCs through sequential induction with Activin A for 2 days and BMP4 for 6 days in 2D and 3D culture systems. Induction of hPSCs into hPGCLCs demonstrated expression of early primordial germ cell markers, including PRDM1, NANOS3, DAZL, STELLA, SOX17, SSEA1, and cKIT, on the 8th day of hPGCLC generation. We described the protocol for generating early hPGCLCs, which provides an opportunity for further investigations into maturation into late germ cells and a chance to overcome a meiotic block to obtain haploid gametes in vitro. Full article

Background: COVID-19 is a multisystem disorder associated with inflammatory, metabolic, electrolyte, and endocrine disturbances. However, the clinical relevance of dysnatremia and acute hormonal alterations remains uncertain, particularly when assessed alongside established clinical risk factors. Methods: This prospective cohort study included 252 adults hospitalized with confirmed COVID-19. Clinical, laboratory, hormonal, and metabolic parameters were assessed at admission, and their associations with disease severity, intensive care unit (ICU) admission, and in-hospital mortality were analyzed. Results: The median age was 73 years, 50.4% of patients were female, and severe or critical disease was present in 81.7%. Dysnatremia and/or endocrine alterations were detected in 55.2% of patients, including hyponatremia in 16.7%, while thyroid-function alterations were observed in 40.9%. Dysnatremia was associated with higher glucose levels and inflammatory-cell changes. Several hormonal and metabolic parameters showed statistically significant univariate associations with adverse outcomes; however, their discriminative performance was weak, with AUC values below clinically meaningful thresholds. After adjustment for major clinical confounders, dysnatremia and endocrine alterations were not independent predictors of disease severity, ICU admission, or mortality. Conclusions: These findings suggest that electrolyte and endocrine abnormalities in hospitalized COVID-19 patients primarily reflect systemic stress physiology and acute disease burden rather than functioning as independent prognostic biomarkers. Full article

Background/Objectives: Adherence to a low-carbohydrate diet induces distinct metabolic adaptations, yet the acute endocrine responses to individual macronutrients within this adapted state remain incompletely characterized. This study aimed to determine the acute, postprandial endocrine and glycemic kinetics following isolated isocaloric carbohydrate, protein, and fat boluses in healthy adults adapted to a low-carbohydrate diet. Methods: Participants (13 female, 11 male) completed three interventions which consisted of consuming an isovolumetric 300 kcal drink of either whey protein (PRO), dextrose (CHO), or olive oil (FAT) mixed with water. Blood was taken immediately prior to drink consumption and then every 30 min afterwards for 2 h in each condition. Continuous glucose monitoring occurred during each intervention. Results: Postprandial glucose remained stable following the FAT and PRO conditions, whereas the CHO condition significantly increased glucose concentrations over time (p < 0.01). Glucagon did not differ between FAT and CHO (p = 0.28) but increased following PRO compared to both FAT and CHO (p < 0.01). Insulin, C-peptide and amylin rose in the CHO condition, with smaller increases in PRO and minimal changes in FAT (p < 0.01). GLP-1 was elevated in the PRO condition compared to both FAT and CHO (p < 0.01), while GIP increased most in the CHO condition and differed across all treatments (p < 0.01). Ghrelin decreased after CHO and PRO, leptin did not significantly change across conditions, and both PP and PYY were lower in the CHO condition at later time points relative to FAT and PRO. Inflammatory markers showed minimal acute changes across conditions, although MCP-1 increased over time following PRO. Conclusions: In low-carbohydrate-adapted individuals, isolated macronutrient boluses elicit highly distinct, divergent endocrine signatures. The robust, acute glucagon response to pure protein does not cause short-term glycemic excursions, indicating that counter-regulatory incretin and insulinotropic pathways remain highly capable of preserving immediate glucose homeostasis. Full article

Purpose: Acute exercise elicits coordinated neuroendocrine and autonomic responses that are strongly influenced by exercise modality and intensity. While cortisol and salivary alpha-amylase are widely used as peripheral indicators of hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system activation, respectively, salivary orexin remains an exploratory biomarker whose relationship with central orexinergic activity is not yet fully established, particularly in response to different exercise conditions. This study aimed to compare the acute salivary responses of orexin, alpha-amylase, and cortisol following distinct exercise modalities characterized by different physiological loads. Methods: A repeated-measures design was employed in a sample of physically active young women. Each participant completed four experimental sessions: high-intensity interval training (HIIT), combined exercise (CE), moderate-intensity continuous training (MICT), and yoga. Saliva samples were collected at baseline (T0), immediately post-exercise (T1), and during early recovery (T2 and T3). Biomarker concentrations were analyzed to assess temporal dynamics and modality-dependent differences. Results: All biomarkers showed modality-dependent responses. HIIT elicited the most pronounced increases in alpha-amylase and cortisol, reflecting robust sympathetic and HPA axis activation, whereas CE and MICT induced more moderate responses. Yoga was associated with minimal changes across all biomarkers. Orexin displayed a graded response across the exercise modalities, with higher post-exercise levels observed following HIIT compared to lower-intensity conditions. Temporal analyses revealed distinct kinetic profiles, with alpha-amylase peaking rapidly in the early post-exercise phase, whereas cortisol exhibited a more delayed response. Conclusions: These findings demonstrate that acute salivary responses of orexin, alpha-amylase, and cortisol are strongly modulated by exercise modality, supporting the importance of an integrated, multi-biomarker approach to characterize the physiological response to exercise. The inclusion of salivary orexin provides exploratory information on a potentially relevant arousal- and energy-regulation-related pathway, complementing established peripheral markers of autonomic and endocrine activation. This integrated perspective may contribute to a more comprehensive understanding of exercise-induced stress responses in young women. Full article

Background/Objectives: Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine–metabolic disorder of multifactorial etiology, driven by interactions among hyperandrogenism, metabolic dysfunction, oxidative stress, and chronic low-grade inflammation that interact to promote reproductive dysfunction and increase risk of cardiometabolic complications. Although the combination of letrozole and high-fat diet (LET + HFD) represents a widely used experimental approach for inducing a PMOS-like phenotype in rats, its multisystem pathophysiological features remain incompletely characterized. The present study aimed to characterize reproductive, cardiometabolic, hormonal, inflammatory, oxidative, and morphometric alterations associated with a LET + HFD-induced PMOS-like phenotype in rats. Methods: PMOS-like model was induced in rats over a 21-day period of orally administered letrozole combined with a high-fat diet. Results: Body weight gain was higher, while uterine weight was lower in the PMOS group compared with controls. Metabolic parameters suggested insulin resistance, while hormonal profiling revealed increased total testosterone and LH levels, accompanied by reduced FSH, estradiol, and progesterone levels. Elevated triglycerides and reduced HDL levels were also observed in the PMOS group. Morphometric analysis revealed numerous atretic and large thin-walled cystic follicles in the ovaries, accompanied by thinning of the uterine luminal and glandular epithelium, stromal layer, and hypoplasia of endometrial glands. Both the longitudinal diameter and cross-sectional area of cardiomyocytes were increased in the PMOS group, together with nuclear hypertrophy and enhanced myocardial collagen deposition. In addition, altered oxidative stress markers, including increased lipid peroxidation and reduced glutathione levels, were observed, whereas IL-6, IL-1β, and IL-23 were not significantly altered. Conclusions: The LET + HFD model reproduces key reproductive and cardiometabolic features of PMOS, extending beyond reproductive dysfunction to involve oxidative and structural alterations in multiple organs. These findings support its use for investigating PMOS pathophysiology and evaluating potential preventive and therapeutic strategies. Full article

The increasing detection of small, non-palpable testicular lesions has challenged the traditional paradigm that every solid intratesticular mass should be managed by radical orchiectomy. Many incidental lesions, particularly in infertile men and in patients with negative tumour markers, are benign or non-neoplastic, making overtreatment a clinically relevant concern. In this setting, ultrasound has become central to a more conservative and individualised diagnostic strategy. By combining high-resolution grey-scale imaging with Doppler, microvascular imaging, CEUS and elastography, multiparametric ultrasound provides complementary information on lesion morphology, vascularity, stiffness and interval change. When integrated with clinical presentation, tumour markers, fertility status, syndromic background and patient history, these features can help characterise lesions and estimate the likelihood of malignancy in the appropriate clinical context. Although imaging cannot replace histology, it can refine pre-test probability, support active surveillance in selected low-risk lesions, guide testis-sparing surgery, and improve assessment of the operated testis. This review examines the role of multiparametric ultrasound in characterisation of focal testicular lesions across different clinical settings, including incidentalomas, acute scrotal pain, trauma, bilateral disease, heterogeneous parenchyma, genetic and endocrine syndromes, and the postoperative testis. A structured, context-sensitive imaging approach may help reduce unnecessary orchiectomy while preserving timely detection of malignant, persistent, recurrent or metachronous disease. Full article

Background: The Adiposity Volume Index (AVI) is a modern geometric tool for tracking central body fat. However, how it interacts with prenatal markers (2D:4D ratio), advanced anthropometric indexes, and psychological factors across different academic disciplines remains largely unexplored. This study evaluates the sex-specific association profiles and screening capacity of these parameters in healthy university students. Methods: A cross-sectional study was conducted on 445 students (199 men and 246 women) from Biomedical Sciences (BS), Computer Science and Engineering (CSE), and Social Sciences and Physiotherapy (SSP) academic programs. Anthropometric indicators (Body Mass Index—BMI, Body Surface Area—BSA, Weight-adjusted Waist Index—WWI, Sagittal Abdominal Diameter-to-Waist circumference Ratio—SAD-to-Waist Ratio), the right-hand digital 2D:4D ratio (R-2D:4D), and Perceived Stress Questionnaire scores (PSQ) were assessed. Data were analyzed using multi-layered linear regression and ROC curve analysis. Results: In male students, BMI, BSA and WWI consistently co-varied with AVI across all academic programs (R² > 0.978, p < 0.001). In contrast, a major psychosomatic interaction emerged in female students. Among stressed BS students, the linear association model shifted (R² = 0.313, lost significance), and the prenatal R-2D:4D ratio became a significant negative independent correlate (B = −87.780, p = 0.019). ROC analysis revealed that optimal BMI cut-offs for elevated AVI were 26.96 kg/m² (AUC = 0.957) for men and 24.89 kg/m² (AUC = 0.972) for women. Notably, perceived stress was a significant diagnostic marker only for female students (AUC = 0.621, p < 0.001, cut-off = 65.50). Conclusions: Perceived academic stress exhibits a significant concurrent association with abdominal fat distribution patterns exclusively in female biomedical students, co-varying with prenatal endocrine markers within the studied cohort. Furthermore, AVI-driven screening demonstrates that metabolic vulnerabilities in these young adults may accumulate within the conventional normal-weight BMI range for women, emphasizing the potential utility of sex-tailored clinical assessments. Full article

Diabetes mellitus (DM) induces significant endocrine disruption and oxidative stress (OS) within the testes, resulting in impaired spermatogenesis, increased sperm abnormalities, and compromised reproductive function. This study aimed to evaluate the combined protective effects of Semaglutide (SEM) combined with Carica papaya (papaya) juice against type 2 diabetes-induced testicular damage in rats. Forty adult male albino rats were divided into four experimental groups: a control group, a Streptozotocin (STZ)-induced diabetic group, a diabetic group treated with SEM (0.3 mg/kg), and a diabetic group treated with SEM (0.3 mg/kg) in combination with 10% papaya juice, administered for eight weeks. Statistically significant superiority over SEM alone was observed for selected endpoints; the findings primarily support the potential of papaya as a dose-sparing adjunct rather than demonstrating uniformly enhanced efficacy. They significantly improved systemic metabolic parameters, as evidenced by reduced fasting blood glucose (FBG) and glycated hemoglobin (HbA_1c) levels and restoration of the lipid profile. Importantly, it also attenuated diabetes-induced testicular injury, as demonstrated by improved reproductive hormone levels, enhanced sperm parameters, restoration of antioxidant defenses, modulation of inflammatory and apoptotic signaling, and marked histopathological recovery of seminiferous tubular architecture. Antioxidant markers revealed a notable reduction in malondialdehyde (MDA) and cytochrome P450 2E1 (CYP2E1), along with significant increases in reduced glutathione, catalase (CAT), and superoxide dismutase (SOD). Furthermore, a marked modulation of key pro-inflammatory and pro-apoptotic mediators was observed, including forkhead box protein O1 (FOXO1), microRNA-155 (miR-155), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B cell subunit 1 (NF-κB1), interleukin-6 (IL-6), caspase-3 (CASP3), and BCL2-Associated X Apoptosis Regulator (Bax), while a significant upregulation of sirtuin-1 (SIRT1), microRNA-34c (miR-34c), and B-cell lymphoma-2 (Bcl-2) was also detected. Histopathological assessments confirmed the restoration of normal testicular architecture in the treated groups. These findings indicate that the combination strategy may have the potential to achieve dose savings while maintaining efficacy comparable to the standard-dose SEM, through the enhancement of the antioxidant defenses, modulation of inflammation, and apoptosis, specifically via the modulation of the miR-34c/miR-155 and SIRT1/FOXO1 signaling. Full article

Background: Increased placental thickness has been associated with adverse perinatal outcomes and fetal functional and structural abnormalities. However, whether marked third-trimester placental thickening is associated with a distinct maternal clinical profile compared with pregnancies with normal placental thickness remains insufficiently characterized. This study aimed to compare maternal characteristics, comorbidities, medication exposure, infection history, and fetal findings between pregnancies with marked placental thickening, defined as placental thickness ≥70 mm, and gestational-age-matched control pregnancies with a placental thickness <70 mm and no documented maternal or fetal abnormalities. Methods: This retrospective matched case–control study included singleton pregnancies referred for fetal echocardiography to a tertiary referral center in Łódź, Poland, between 1 January 2022 and 14 March 2025. Placental thickness was measured sonographically in a perpendicular plane from the chorionic plate to the basal plate, excluding the umbilical cord insertion site. Only anterior and/or fundal placentas assessed at ≥28 weeks of gestation were included. Among pregnancies with recorded third-trimester placental thickness measurements, 99 cases with placental thickness ≥70 mm were identified as the thick-placenta group. A control group of 99 pregnancies with placental thickness <70 mm was selected and matched for gestational age. Control pregnancies had no documented maternal disease, no fetal structural or functional abnormalities, and no exposure to the medications analyzed in this study. Maternal demographic characteristics, body mass index, comorbidities, infection history, obstetric history, and medication use were compared between groups. Continuous variables were compared using Welch’s t-test and the Mann–Whitney U test, and categorical variables were compared using Fisher’s exact test. Results: The study included 99 pregnancies with marked placental thickening and 99 control pregnancies with normal placental thickness. Gestational age at examination was comparable between groups, with a mean of 35.5 weeks in controls and 35.0 weeks in the thick-placenta group (p = 0.662, Welch’s t-test). Median gestational age was also not significantly different between groups (35.4 vs. 36.43 weeks; p = 0.340, Mann–Whitney U test). Mean placental thickness was significantly greater in the thick-placenta group than in controls (81.4 mm vs. 46.9 mm; p < 0.0001). Maternal age and anthropometric characteristics were comparable between groups, whereas BMI > 25 kg/m² was more common in the thick-placenta group. In contrast to the clinically healthy control group, maternal infection was documented in 100.0% of thick-placenta cases, hormonal treatment in 97.0%, history of COVID-19 in 52.5%, hypothyroidism in 44.4%, prior miscarriage in 37.4%, aspirin or anticoagulant use in 32.3%, gestational diabetes mellitus in 25.3%, and pregnancy-induced hypertension in 7.1%. All evaluated maternal clinical factors were significantly more common in the thick-placenta group than in controls. Fetal cardiac or extracardiac dysfunction was present in 68.7% of thick-placenta pregnancies. Conclusions: In this gestational-age-matched case–control study, pregnancies with marked third-trimester placental thickening showed a distinct maternal profile compared with healthy controls with normal placental thickness. Despite comparable gestational age, maternal age, and maternal anthropometric characteristics, the thick-placenta group demonstrated a significantly higher infectious, hormonal, metabolic, and endocrine burden. These findings indicate that, in this selected tertiary referral cohort, placental thickness ≥70 mm was associated with a higher burden of maternal clinical abnormalities and fetal functional findings. Rather than representing an independent marker of placental maladaptation or maternal-fetal risk, marked placental thickening should be interpreted as a clinically relevant ultrasound finding that may prompt careful review of maternal history and targeted fetal assessment. Prospective studies are needed to determine which maternal factors are independently associated with placental thickening and to clarify their relationship with fetal function and perinatal outcomes. Full article

Interactions among the gut, brain, and skin are increasingly understood as a systemic regulatory network connecting intestinal activity, neuroimmune communication, and cutaneous homeostasis. Microbiota-derived metabolites, immune mediators, and neuroendocrine pathways can influence central nervous system activity and subsequently regulate skin homeostasis. This review summarizes current evidence on how functional ingredients modulate the gut–brain–skin axis in the context of aging and skin health. Polyphenols, probiotics, and omega-3 fatty acids appear to act through overlapping biological routes, including reshaping microbial communities, supporting epithelial barrier function, regulating immune activity, and limiting oxidative stress. These gut-derived signals may affect the brain through neural, endocrine, and immune pathways, thereby modulating neuroinflammation, hypothalamic–pituitary–adrenal (HPA) axis activity, and neurotransmitter balance. Through brain–skin communication, these changes may influence inflammation, epidermal barrier integrity, collagen remodeling, and skin aging processes. Emerging clinical evidence suggests potential improvements in skin-related outcomes and systemic inflammatory markers; however, studies remain heterogeneous, and integrated assessments of gut, brain, and skin endpoints are limited. Further studies that integrate multi-omics profiling with carefully designed clinical trials will be required to define causal pathways and support the development of evidence-based nutritional approaches targeting this axis. Full article

WWOX and HIF1A are linked to hypoxia-driven metabolic and immune modulation in cancer. We examined whether the WWOX/HIF1A expression ratio acts as a context-dependent molecular integrator across breast cancer (BRCA) subtypes and ovarian carcinoma (OV). We analyzsed TCGA RNA-seq and clinical data from BRCA (n = 390) and OV (n = 228), using neoplasm cancer status as a proxy for disease-free survival (DFS). Patients were stratified by subtype-specific WWOX/HIF1A ratio cutpoints for exploratory Kaplan–-Meier analyses, and the ratio was also modelled as a standardizsed continuous covariate in Cox regression. Transcriptomic, pathway, immune-cell and hormone-related profiles were examined in relation to ratio status, with all multivariable and cutpoint-based findings treated as hypothesis-generating. The WWOX/HIF1A ratio does not act as a uniform or strongly predictive prognostic marker but instead delineates distinct biological states whose association with DFS is modest, context-dependent and statistically fragile in TCGA. Higher ratios are linked to more favourable DFS only in basal-like and HER2-enriched BRCA, together with oxidative phosphorylation, ribosomal and reduced ADAM10-linked Notch and monocyte/macrophage signatures. In luminal A BRCA and OV, lower ratios are linked to relatively favourable DFS and coincide with cytokine/JAK–STAT signalling, cytotoxic immune signatures and coordinated metabolic–endocrine programmes, whereas luminal B shows mixed immune and metabolic patterns. In this TCGA-based analysis, the WWOX/HIF1A ratio functions as a context-dependent molecular index of hypoxia, immune and hormone-related states rather than a strong, generalisable DFS predictor. The observed subtype-specific survival trends (high-ratio favourability in basal/HER2, low-ratio favourability in luminal A,B and OV) are non-significant and exploratory, and all ratio-based survival patterns require confirmation in independent cohorts and functional studies. Full article

Background: Attention-deficit/hyperactivity disorder (ADHD) has traditionally been understood through executive and frontostriatal models, but increasing evidence suggests that metabolic, inflammatory, circadian, and neuroendocrine mechanisms may also contribute to clinical heterogeneity. The hypothalamus is a central regulatory hub for appetite, sleep–wake organization, stress responsivity, autonomic function, and endocrine signalling. Objective: This review evaluated evidence linking ADHD with hypothalamic inflammation and related metabolic, inflammatory, circadian, and neuroendocrine dysregulation, with particular emphasis on appetite regulation, sleep and circadian function, stress reactivity, and pharmacological treatment response and tolerability. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, PsycINFO, Scopus, and Web of Science Core Collection from database inception to 31 May 2026. Human observational and intervention studies formed the primary evidence base. Evidence was synthesized narratively. Where available, quantitative findings from previously published meta-analyses were summarized to provide an overview of the strength and consistency of the evidence. Results: The reviewed evidence indicates that ADHD is associated with increased obesity risk, altered appetite-related hormones, immune-inflammatory changes, delayed circadian timing, atypical cortisol responsivity, and treatment-related effects on appetite, sleep, cardiovascular physiology, and tolerability. The strongest quantitative evidence concerned obesity, inflammatory markers, appetite hormones, and type 2 diabetes risk. Direct evidence for hypothalamic inflammation in ADHD remains limited, but converging indirect findings support hypothalamic and neuroendocrine mechanisms as biologically plausible contributors in a subgroup of individuals with ADHD. Conclusions: ADHD appears to be associated with broader metabolic, inflammatory, circadian, and neuroendocrine vulnerabilities beyond its core attentional and behavioural symptoms. Hypothalamic pathways should be interpreted as a mechanistic hypothesis rather than an established causal mechanism. Future longitudinal and multimodal studies are needed to clarify causality and identify biologically defined ADHD subgroups. Full article

Background: Blood-accessible biomarkers may support future personalization of prostate cancer radiotherapy, but their interpretation depends on sampling timing relative to radiotherapy, androgen deprivation therapy, and post-treatment recovery. We mapped clinical evidence for selected biomarker domains beyond prostate-specific antigen: γ-H2AX/DNA damage response, IL-6/inflammatory mediators, testosterone/endocrine recovery and a prespecified galectin-1/3 immune–stromal domain evaluated as a potential evidence gap. Methods: We conducted a PRISMA-ScR scoping review of PubMed, Scopus, and Web of Science searched on 7 January 2026. Eligible original human studies evaluated soluble serum/plasma analytes or peripheral blood cell-based assays in prostate RT pathways. Data were charted by biomarker domain, treatment context, RT modality/fractionation, assay reporting, sampling schedule, and endpoint linkage. Results: Of 3499 records, 45 studies were included. No eligible study reported repeated circulating galectin-1/3 kinetics anchored to prostate radiotherapy, identifying a distinct clinical evidence gap. The remaining evidence was dominated by testosterone studies (n = 28), followed by IL-6/inflammatory mediators (n = 12) and γ-H2AX/DDR (n = 5). Testosterone studies were mapped as separate RT-only endocrine kinetics and ADT-anchored recovery streams. IL-6 studies mainly used during-RT or early post-RT sampling and linked trajectories to acute toxicity, fatigue, symptoms or inflammatory phenotypes; no included study directly validated serial IL-6/inflammatory trajectories against biochemical control, metastasis-free survival, or overall survival. γ-H2AX studies were characterized by ultra-acute, fraction-anchored sampling. Across domains, baseline definition and sampling timing limited interpretability more than assay platform alone. Conclusions: Evidence maturity was unequal across the selected domains. Testosterone provided the comparatively more developed longitudinal clinical literature, whereas IL-6/inflammatory mediators remained exploratory and were linked mainly to acute toxicity, fatigue, symptoms, and inflammatory phenotypes. γ-H2AX remained predominantly a translational and biodosimetry-oriented marker, while galectin-1/3 represented a hypothesis-generating clinical evidence gap. None of these biomarkers currently supports routine biomarker-guided prostate RT personalization. Future biomarker-embedded studies may benefit from domain-specific sampling considerations, explicit RT/systemic-therapy context stratification, standardized assay reporting, and clinically relevant endpoints. Full article