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14 pages, 527 KB  
Article
Demographic, Geographic, and Temporal Patterns of Adult Dental Emergency Presentations in Arad County, Western Romania
by Mihaela Cristina Negru, Andreea Mihaela Banta, Mirela Voicu, Dragoş Vasile Nica, Ioana-Cristina Talpoș-Niculescu and Iustin Olariu
Healthcare 2026, 14(10), 1366; https://doi.org/10.3390/healthcare14101366 (registering DOI) - 15 May 2026
Abstract
Background/Objectives: This retrospective study aimed to assess the sociodemographic and temporal factors associated with dental emergency presentations in adults from Arad county, Western Romania. Methods: We collected data on age, sex, origin area, presentation time, and diagnostic (macro)category in 510 adult [...] Read more.
Background/Objectives: This retrospective study aimed to assess the sociodemographic and temporal factors associated with dental emergency presentations in adults from Arad county, Western Romania. Methods: We collected data on age, sex, origin area, presentation time, and diagnostic (macro)category in 510 adult patients. Diagnoses were grouped into four macrocategories: dental pathology (PD), endodontic and periapical pathology (EPP), odontogenic septic complications (OSC), and other emergencies (OE). Results: EPP was the predominant (macro)category, with most cases involving acute apical periodontitis and pulpitis. Age differed significantly across diagnostic categories (p < 0.001), with PD patients being significantly younger than other groups (p < 0.001). Increasing age was associated with higher odds of EPP (AOR = 1.06, p = 0.004) but lower odds of PD (AOR = 0.93, p < 0.001). Rural origin was associated with increased odds of EPP (AOR = 1.49, p = 0.031) but decreased odds of OE (AOR = 0.39, p = 0.003). No significant associations were identified for sex. Most patients presented in the evening (46.47%) and on weekends, particularly Sundays (21%; n = 107) and Saturdays (16%; n = 82). Patient age differed significantly across time intervals (p = 0.016), with individuals seeking dental emergency care during morning and afternoon hours being significantly older than those presenting in the evening (p = 0.009) or nighttime (p = 0.047). Conclusions: Our findings suggest that observed sociodemographic and temporal differences may be associated with variations in the stage and type of dental pathology at presentation. Understanding these presentation patterns may help inform service organization and resource allocation in emergency dental care. Full article
13 pages, 584 KB  
Article
Burden of Disease Due to Consumption of Alcohol and Other Drugs in Colombia, 2016–2022: A Subnational Regional Analysis
by Oscar Alexander Gutiérrez-Lesmes, Emilce Salamanca Ramos and Karen Julieth Quintero Díaz
Int. J. Environ. Res. Public Health 2026, 23(5), 659; https://doi.org/10.3390/ijerph23050659 (registering DOI) - 15 May 2026
Abstract
Alcohol and psychoactive substance use represent a major burden for global public health, increasing the risk of non-communicable diseases, violence, road traffic injuries, dependence, and mental disorders, and generating impacts on productivity and social welfare. This study aimed to estimate the burden of [...] Read more.
Alcohol and psychoactive substance use represent a major burden for global public health, increasing the risk of non-communicable diseases, violence, road traffic injuries, dependence, and mental disorders, and generating impacts on productivity and social welfare. This study aimed to estimate the burden of disease attributable to alcohol and other psychoactive substances in the departments of Colombia from 2016 to 2022. A burden-of-disease study was conducted using the Disability-Adjusted Life Years (DALYs) indicator, following the methodology of the World Health Organization Global Health Estimates. Official morbidity and mortality databases were used. An estimated 236,154.42 DALYs were attributable to alcohol and psychoactive substance use in Colombia during the study period, increasing from 14,158.7 DALYs in 2016 to 40,190.7 DALYs in 2022. The burden was heterogeneous across departments, with values above 1000 DALYs in Quindío (1779.5), Nariño (1624.3), and Norte de Santander (1008.0) and below 132 DALYs in La Guajira, Casanare, and Vaupés. Men accounted for 73.5% of total DALYs. The mean age of morbidity records associated with alcohol and psychoactive substance use disorders was 30.67 years in men and 32.37 years in women. The burden associated with psychoactive substance use is increasing in Colombia, with differences by sex and department of residence. Full article
(This article belongs to the Section Global Health)
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16 pages, 1961 KB  
Article
One-Lung Ventilation Duration Is a Risk Factor for Pneumonia in Minimally Invasive and Robotic Esophagectomy
by Vladimir J. Lozanovski, Julian Kobler, Edin Hadzijusufovic, Franziska Renger, Christoph Wandhoefer, Eva-Verena Griemert, Hauke Lang and Peter P. Grimminger
J. Clin. Med. 2026, 15(10), 3832; https://doi.org/10.3390/jcm15103832 (registering DOI) - 15 May 2026
Abstract
Introduction: Postoperative pulmonary complications, particularly pneumonia, remain frequent after esophagectomy and contribute significantly to morbidity. One-lung ventilation (OLV) is a potential modifiable risk factor, but its impact in minimally invasive (MIE) and robot-assisted Ivor Lewis esophagectomy (RAMIE) within European populations is not well [...] Read more.
Introduction: Postoperative pulmonary complications, particularly pneumonia, remain frequent after esophagectomy and contribute significantly to morbidity. One-lung ventilation (OLV) is a potential modifiable risk factor, but its impact in minimally invasive (MIE) and robot-assisted Ivor Lewis esophagectomy (RAMIE) within European populations is not well defined. Methods: 619 patients undergoing MIE or RAMIE were analyzed. OLV duration was extracted from operative records. Postoperative pneumonia incidence, overall survival, and perioperative outcomes were assessed. ASA classification and other risk factors were considered. Results: The overall incidence of postoperative pneumonia was 18.6%, with no significant difference between MIE (20.4%) and RAMIE (18.2%). Prolonged OLV duration increased pneumonia risk by 4% per 10 min. Female sex and higher ASA classification were also significant risk factors. Likely reflecting early diagnosis and advanced perioperative management, pneumonia did not affect overall survival, which remained comparable between MIE and RAMIE. Conclusions: Prolonged OLV during MIE and RAMIE increases the risk of postoperative pneumonia without significantly affecting overall survival, reflecting effective complication management. OLV duration may serve as a practical intraoperative indicator to guide risk stratification and optimize postoperative care in minimally invasive and robot-assisted Ivor Lewis esophagectomy. Full article
(This article belongs to the Special Issue Recent Clinical Advances in Esophageal Surgery)
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12 pages, 799 KB  
Article
Metformin Treatment Potentially Modifies Genetically Driven Metabolite-HbA1c Associations: A Gene–Environment Interaction Mendelian Randomization Study
by Najeha Anwardeen, Aleem Razzaq, Asma A. Elashi, Gaurav Thareja, Ilhame Diboun, Khaled Naja, Karsten Suhre and Mohamed A. Elrayess
Pharmaceuticals 2026, 19(5), 780; https://doi.org/10.3390/ph19050780 (registering DOI) - 15 May 2026
Abstract
Introduction/Background: Metformin is the first-line therapy for type 2 diabetes (T2D); however, a considerable inter-individual variability in glycemic response is observed among patients. This heterogeneity suggests that metformin’s effects depend not only on drug exposure but also on the underlying metabolic and [...] Read more.
Introduction/Background: Metformin is the first-line therapy for type 2 diabetes (T2D); however, a considerable inter-individual variability in glycemic response is observed among patients. This heterogeneity suggests that metformin’s effects depend not only on drug exposure but also on the underlying metabolic and genetic factors. Methods: We applied a Gene–Environment interaction Mendelian Randomization (MR-G×E) in a cohort of 2743 individuals to investigate whether genetically influenced metabolite-HbA1c associations differ by metformin use. Metabolites associated with metformin response were used to establish metabolite-specific polygenic risk scores (PRSs) using metabolome-wide association study (mGWAS) variants. Generated PRS were used as genetic instruments within a one-sample, modified two-stage least squares model. An interaction term between PRS and metformin use was included to assess treatment-dependent genetic effects, adjusting for age, sex, body mass index, and genetic ancestry (principal components). Results: Metformin use significantly modified genetically influenced associations between 18 metabolites and HbA1c. Positive and negative PRS-metformin interaction effects indicated attenuation, strengthening or reversal of baseline genetic associations under treatment. Several amino acid metabolites, palmitoyl sphingomyelin (d18:1/16:0), and carbohydrate-related metabolite 1,5-anhydroglucitol showed specific patterns under metformin use. Interestingly, several metabolites (creatinine, gamma glutamylcitrulline, N-acetylthreonine, 3-methyl-2-oxovalerate, glycerol-3-phosphate, 1-(1-enyl-palmitoyl)-GPC (P-16:0), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2), sphingomyelin (d18:1/22:1, d18:2/22:0, d16:1/24:1), fructose, and methyl-glucopyranoside (alpha + beta)) showed no basal causal association with HbA1c but exhibited significant interaction effect with metformin use, suggesting metabolic association only in the presence of metformin. Conclusions: These findings indicate that metformin modifies the genetically influenced metabolite-HbA1c relationships, exhibiting treatment-dependent metabolic effects that are not detectable with standard MR approaches. Incorporating pharmacological context into causal inference provides new insights into the metabolic basis for the variable metformin response and helps inform precision strategies for T2D management. Full article
(This article belongs to the Section Pharmacology)
19 pages, 1598 KB  
Article
Sex-Specific Transcriptomic Profiles in Psoriatic Lesions: A Large-Scale Integrative Study
by Edia Stemmer, Liat Anabel Sinberger, Tair Lax, Guy Shrem, Inbal Mor and Mali Salmon-Divon
Int. J. Mol. Sci. 2026, 27(10), 4439; https://doi.org/10.3390/ijms27104439 (registering DOI) - 15 May 2026
Abstract
Psoriasis, a chronic inflammatory skin disease affecting men and women equally, presents distinct gender-based differences in severity and treatment response. While molecular mechanisms underlying psoriasis are well-studied, sex-specific differences remain largely unexplored. To address this, we conducted a comprehensive analysis of transcriptomic data [...] Read more.
Psoriasis, a chronic inflammatory skin disease affecting men and women equally, presents distinct gender-based differences in severity and treatment response. While molecular mechanisms underlying psoriasis are well-studied, sex-specific differences remain largely unexplored. To address this, we conducted a comprehensive analysis of transcriptomic data from lesional psoriasis skin and healthy controls, comparing male and female cohorts. Our findings reveal 2760 overlapping differentially expressed genes (DEGs) between sexes, highlighting shared pathways like IL-17 signaling and Th17 differentiation. However, sex-specific pathways emerged, including male-enriched PI3K-Akt signaling and chemokine receptor activity, and female-enriched glycolysis and AHR-NRF2 pathways. Upstream regulator analysis identified sex-specific drivers, including VEGFA activation and CFTR inhibition in males, and AHR activation and FGF21 inhibition in females. Notably, Regulatory T cells (Tregs) and neutrophil abundance differed by sex, aligning with disease severity trends. These results highlight sex-associated molecular and cellular disparities that may be relevant to understanding differences in disease manifestation and treatment response. As an exploratory, hypothesis-generating transcriptomic analysis, this study lays the groundwork for future experimental and clinical validation of sex-specific mechanisms in psoriasis. Full article
22 pages, 4418 KB  
Article
Mechanistic Investigation of Vitexin in Ameliorating Ovarian Fibrosis in PCOS Mice via the NR4A1/NLRP3 Signaling Pathway
by Haoran Sun, Jiejing Xu, Chengxue Pan, Jia-Le Song and Yanyuan Zhou
Metabolites 2026, 16(5), 332; https://doi.org/10.3390/metabo16050332 - 15 May 2026
Abstract
Objective: In this study, Dehydroepiandrosterone (DHEA-induced Polycystic Ovary Syndrome (PCOS) mice were used as models to evaluate the improvement effect of Vitexin (Vit) on ovarian fibrosis and explore the mechanism of action of the NR4A1/NLRP3 signaling pathway. Method: Sixty 4-week-old female ICR mice [...] Read more.
Objective: In this study, Dehydroepiandrosterone (DHEA-induced Polycystic Ovary Syndrome (PCOS) mice were used as models to evaluate the improvement effect of Vitexin (Vit) on ovarian fibrosis and explore the mechanism of action of the NR4A1/NLRP3 signaling pathway. Method: Sixty 4-week-old female ICR mice of the same batch number were selected and their systems were divided into 6 groups (n = 10): normal (Control, Ctrl) group, model (Polycystic Ovary Syndrome, PCOS) group, treatment (Vitexin, The Vit group, normal NR4A1 gene silencing group (Ctrl NR4A1-/-), NR4A1 gene silencing model group (PCOS NR4A1-/-), and NR4A1 gene silencing treatment group (Vit NR4A1-/-). Silencing gene modeling was performed by tail vein injection of adeno-associated virus (serotype AAV-8), and the mouse genotypes were detected by qRT-PCR technology 14 days after injection. After the genotype was determined, the PCOS group and the PCOS NR4A1-/- group were administered dehydroepandrosterone (6 mg/100 g/d) by gavage for 28 consecutive days for modeling, while the Vit group and the Vit NR4A1-/- group were treated with dehydroepandrosterone + vitexin (10 mg/kg/d) by gavage for 28 consecutive days. All mice were raised with pure water and regular maintenance food. After 4 weeks of drug intervention, the mice were euthanized and samples were collected. The pathological changes in ovarian tissue were observed by H&E staining, and the degree of ovarian tissue fibrosis was observed by Masson staining. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in mouse serum were detected by biochemical kits. The levels of inflammatory factors (IL-1β, IL-6, IL-18, TNF-α) in mouse serum were determined by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect oxidative kinase (Gsta4, Prdx3, Mgst1, Gpx3, Gsr), inflammatory factors (Nlrp3, Caspase-1, Asc, Il-1β, Il-18, Tnf-α) and fibrotic pathway-related genes (Tgf-β1, Smad3, Collagen1, CTGF, α-SMA, Mmp-13, and β-catenin) in ovarian tissues. The levels of inflammatory factors (NLRP3, Caspase-1, ASC, IL-1β, IL-18, TNF-α, IκBα) and fibrosis in mice were determined by Western blot method, and statistical description and analysis were performed using SPSS software. Result: In the wild-type genotype group, compared with the PCOS group, Vit treatment could effectively regulate the metabolic abnormalities of PCOS mice, including inhibiting excessive weight gain, restoring normal glucose tolerance, and reducing body fat content. After Vit treatment, the levels of MDA, TC, TG, LDL, IL-1β, IL-6, IL-18 and TNF-α in the serum of PCOS mice were significantly reduced, while the levels of SOD and HDL in the serum of PCOS mice were increased. The staining results indicated that Vit treatment could significantly inhibit the process of ovarian fibrosis in PCOS mice. The results of WB and PCR demonstrated that after Vit gavage treatment in mice, inflammatory and fibrotic factors such as Nlrp3, Caspase-1, Asc, Il-1β, Il-18, Tgf-β1, Smad3, Collagen1, CTGF, and α-SMA in ovarian tissues could be significantly down-regulated, and the fibrotic level of ovarian tissues could be reduced. Among the same measurement indicators, the silenced NR4A1 group showed a certain degree of increase compared with the wild genotype group, but there was no significant difference. Conclusions: Vit intervention can restore the sex hormone levels and follicular development in ovarian tissues of PCOS mice, regulate reproductive endocrine disorders and abnormal lipid metabolism levels, and regulate the expression of Collagen I, a-SMA and CTGF in the ovaries by inhibiting the NR4A1/NLRP3 signaling pathway, thereby improving the ovarian fibrosis level of PCOS mice. It is suggested that it may play a key role in the treatment of PCOS and the prevention and delay of its long-term complications. Full article
(This article belongs to the Section Plant Metabolism)
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19 pages, 682 KB  
Article
Cyberchondria, Health Anxiety, and Sleep Quality: An Observational Cross-Sectional Study of Adults with and Without Psychosomatic Disorders
by Reda Ebrahim Mohamed Elashram, Ali Mohammed Ali Al-Basiouni Bashshar, Ahmed Samir Sedik Abo-Bakr and Ali Marzouq Al-Ghamdi
Healthcare 2026, 14(10), 1356; https://doi.org/10.3390/healthcare14101356 - 15 May 2026
Abstract
Background/Objectives: The increasing reliance on the Internet for health information has contributed to the emergence of cyberchondria, a phenomenon closely associated with health anxiety and potentially linked to sleep disturbances. Evidence remains limited in the Saudi context, particularly regarding differences between individuals [...] Read more.
Background/Objectives: The increasing reliance on the Internet for health information has contributed to the emergence of cyberchondria, a phenomenon closely associated with health anxiety and potentially linked to sleep disturbances. Evidence remains limited in the Saudi context, particularly regarding differences between individuals with and without psychosomatic disorders. Methods: A cross-sectional observational study was conducted among 1224 Saudi adults (535 with psychosomatic disorders and 689 without). Data were collected using validated instruments, including the Cyberchondria Severity Scale (CSS-12), Short Health Anxiety Inventory (SHAI-18), and Pittsburgh Sleep Quality Index (PSQI). Statistical analyses included Pearson correlation coefficients and two-way ANOVA. Results: The prevalence of cyberchondria was 56.78%, health anxiety 38.76%, and poor sleep quality 56.9%. Significant positive correlations were observed between cyberchondria, health anxiety, and poor sleep quality across both groups, with stronger associations among individuals with psychosomatic disorders. Two-way ANOVA revealed a significant main effect of clinical status on all variables and a significant effect of sex on health anxiety, with higher levels among females. Conclusions: Findings highlight a significant interplay between cyberchondria, health anxiety, and sleep quality, particularly among individuals with psychosomatic disorders. These results underscore the need for targeted public health interventions addressing digital health behaviours and mental health. Full article
14 pages, 553 KB  
Article
Dialysis on the Central Venous Catheter at the Time of Arteriovenous Fistula Creation Is Associated with Long-Term Vascular Access Failure
by Eliza Russu, Réka Bartus, Elena Florea, Alexandru Mureșan, Paula Bândea, Paul Mateica, Ionela Georgiana Tofana, Constantin Claudiu Ciucanu, Eliza-Mihaela Arbănași, Alexandru Petru Ion, Paula Chirilă, Ioan Hosu, Mirela Liana Gliga, Adrian Vasile Mureșan and Emil-Marian Arbănași
J. Clin. Med. 2026, 15(10), 3819; https://doi.org/10.3390/jcm15103819 - 15 May 2026
Abstract
Background/Objectives: The autologous arteriovenous fistula (AVF) is the primary vascular access (VA) method for hemodialysis (HD), with superior patency and a lower complication rate than arteriovenous graft (AVG) or central venous catheter (CVC). The primary objective of this study is to analyze [...] Read more.
Background/Objectives: The autologous arteriovenous fistula (AVF) is the primary vascular access (VA) method for hemodialysis (HD), with superior patency and a lower complication rate than arteriovenous graft (AVG) or central venous catheter (CVC). The primary objective of this study is to analyze the impact of dialysis on the CVC at the time of AVF creation on its long-term primary patency. Methods: This retrospective, single-center, observational study included 248 patients admitted for AVF creation. Demographic characteristics, comorbid conditions, and laboratory parameters were retrieved from the hospital’s electronic medical records. The primary outcome of the study was long-term AVF failure, defined as the inability to perform hemodialysis through the newly created AVF. Results: A total of 132 (53.2%) were receiving dialysis via a CVC at the time of AVF creation. During a mean follow-up of 2.21 ± 1.54 years, 47 patients (18.95%) failed to achieve functional maturation at 6 weeks, and 81 patients (32.66%) developed long-term AVF failure. Demographic characteristics were similar between patients with and without CVC at AVF creation, with no significant differences in age (p = 0.358) or sex (p = 0.574). Comorbidities and risk factors were also similarly distributed, showing no significant variation. The types of AVF varied by CVC status, with fewer RC-AVF (p = 0.038) and more BC-AVF (p = 0.032) in patients with a CVC. Failure was significantly more frequent in patients with CVC use at the time of AVF creation than in those without CVC (p < 0.001). Kaplan–Meier analysis demonstrated lower long-term patency in patients dialyzed via CVC (p < 0.001). In Cox regression analysis, dialysis via CVC at AVF creation was associated with AVF failure (HR: 2.53, p < 0.001), and the association remained significant after full adjustment (HR: 3.13, p < 0.001). Female sex, active smoking, smaller arterial and venous diameters, and RC-AVF were additional risk factors associated with failure. Conclusions: Dialysis via a CVC at the time of AVF creation was associated with an increased risk of long-term AVF failure, even after full adjustment models. Full article
(This article belongs to the Section Vascular Medicine)
17 pages, 998 KB  
Article
Self-Reported Habitual Daily Physical Activity as an Independent Predictor of Coronary Artery Disease Extension in Patients with Myocardial Infarction: A Prospective Observational Study
by Corina Cinezan and Maria Luiza Hiceag
J. Clin. Med. 2026, 15(10), 3814; https://doi.org/10.3390/jcm15103814 - 15 May 2026
Abstract
Background: The extent of coronary artery disease (CAD) is a major determinant of prognosis in patients with myocardial infarction (MI). While structured exercise is known to be cardioprotective, the association between habitual daily physical activity and angiographic CAD extension remains insufficiently characterized. [...] Read more.
Background: The extent of coronary artery disease (CAD) is a major determinant of prognosis in patients with myocardial infarction (MI). While structured exercise is known to be cardioprotective, the association between habitual daily physical activity and angiographic CAD extension remains insufficiently characterized. Methods: In this prospective observational study, 269 patients were hospitalized with acute MI underwent coronary angiography. Habitual daily physical activity during the four weeks preceding admission was assessed using 10-point self-reported daily preadmission effort questions to help the patients to report a final effort score. CAD extension was classified as single-, double- or triple-vessel disease. Differences in daily effort across CAD categories were evaluated using the Kruskal–Wallis test. Independent predictors of CAD extension were identified using ordinal logistic regression adjusted for age, sex, smoking, hypertension, diabetes mellitus, hyperlipidemia and body mass index. Results: Daily preadmission effort decreased progressively with increasing CAD severity (mean scores: 7.44 in single-vessel, 4.93 in double-vessel and 3.69 in triple-vessel disease; p < 0.0001). In multivariable ordinal logistic regression analysis, older age, hypertension, diabetes mellitus and hyperlipidemia were independently associated with greater CAD extension. Higher daily preadmission effort was strongly and independently associated with lower CAD severity; each one-point increase in effort score was associated with a 46% reduction in the odds of more extensive CAD (odds ratio 0.54, 95% confidence interval 0.45–0.64; p < 0.0001). Conclusions: Greater habitual daily physical activity prior to myocardial infarction is independently associated with less extensive coronary artery disease. Assessment of daily preadmission effort may provide clinically useful information regarding coronary disease burden and highlights the potential importance of everyday physical activity in cardiovascular prevention. These findings should be interpreted with caution given the use of a non-validated, self-reported measure of physical activity and the observational study design. Full article
(This article belongs to the Special Issue Acute Myocardial Infarction: Diagnosis, Treatment, and Rehabilitation)
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11 pages, 3642 KB  
Article
Panoramic Infrazygomatic Crest Length: A Craniofacial Physiology-Based Analysis of Skeletal Class (I–III) and Sex in a Retrospective Cross-Sectional Study
by Melis Büşra Aşkın, Ömer Can Manav and Ayşe Bulut
Diagnostics 2026, 16(10), 1501; https://doi.org/10.3390/diagnostics16101501 - 15 May 2026
Abstract
Objective: This retrospective cross-sectional radiographic study evaluated panoramic infrazygomatic crest (IZC) length and compared values according to skeletal class and sex. The term panoramic IZC length was used to describe a two-dimensional linear measurement obtained on panoramic radiographs, rather than a three-dimensional [...] Read more.
Objective: This retrospective cross-sectional radiographic study evaluated panoramic infrazygomatic crest (IZC) length and compared values according to skeletal class and sex. The term panoramic IZC length was used to describe a two-dimensional linear measurement obtained on panoramic radiographs, rather than a three-dimensional bone corridor for miniscrew insertion. Methods: A total of 180 archived digital panoramic radiographs of patients aged 16–30 years were retrospectively collected and grouped equally by skeletal class and sex. Skeletal class was determined using previously recorded lateral cephalometric tracings based on ANB angle criteria: Class I, 0–4°; Class II, >4°; and Class III, <0°. Panoramic IZC length was measured bilaterally on calibrated panoramic images using ImageJ, and the bilateral mean was used for subgroup comparisons. Group differences were analyzed using one-way ANOVA, independent-samples t-tests, and two-way ANOVA. Results: Panoramic IZC length differed significantly across skeletal classes, with the highest values found in Class III and the lowest values found in Class II (p < 0.001). Mean panoramic IZC length was 5.81 ± 0.38 mm in Class III females and 6.16 ± 0.41 mm in Class III males, compared with 4.99 ± 0.36 mm in Class II females and 5.51 ± 0.40 mm in Class II males. Males showed significantly greater values than females (p < 0.01). The sex-by-class interaction was significant (p = 0.04). Intra-observer repeatability was excellent (ICC = 0.95). Conclusions: Panoramic IZC length varies according to skeletal class and sex, with higher values in Class III individuals and males. These findings provide preliminary comparative morphometric information from routinely available panoramic radiographs. However, panoramic IZC length should not be interpreted as a three-dimensional insertion corridor, and CBCT remains necessary when comprehensive anatomical planning, sinus proximity assessment, or extra-alveolar miniscrew trajectory evaluation is required. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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16 pages, 2765 KB  
Article
Biological Sex Influences the Pharmacokinetics and Organ Dosimetry of 177Lu-DOTATATE: A Systematic Preclinical Evaluation
by Xiangsheng Kong, Peishang Li, Zhiqian Wang, Chenchen Cai, Mingjie Zhang, Chunmiao Qu, Chunlei Jin, Hongzhang Zhang, Yeqing Dong, Kai Lv and Fei Han
Pharmaceuticals 2026, 19(5), 774; https://doi.org/10.3390/ph19050774 (registering DOI) - 15 May 2026
Abstract
Background/Objectives: While 177Lu-DOTATATE has demonstrated clinical efficacy in peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NETs), current dosing regimens do not account for potential sex-based pharmacokinetic differences. Our study systematically characterizes sex-dependent pharmacokinetic variations of 177Lu-DOTATATE in preclinical models to [...] Read more.
Background/Objectives: While 177Lu-DOTATATE has demonstrated clinical efficacy in peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NETs), current dosing regimens do not account for potential sex-based pharmacokinetic differences. Our study systematically characterizes sex-dependent pharmacokinetic variations of 177Lu-DOTATATE in preclinical models to provide the first preclinical evidence base informing future sex-stratified clinical investigations. Methods: Sex-stratified pharmacokinetic and biodistribution studies were conducted in male and female SD rats following intravenous administration of 177Lu-DOTATATE at multiple dose levels: 2.86, 5.71, and 11.43 mCi/kg. Metabolic stability and renal excretion patterns were characterized. Safety assessments included acute toxicity, vascular irritation, hemolysis, and allergenicity testing. Therapeutic efficacy was evaluated exclusively in female AR42J xenograft-bearing CB-17 SCID mice. Results: Significant sex-dependent pharmacokinetic differences were observed at high (11.43 mCi/kg) and low (2.86 mCi/kg) dose levels, with females exhibiting 30–40% higher AUC and Cmax values compared to males (p < 0.05). Both sexes demonstrated preferential accumulation in SSTR-expressing tissues, particularly the pancreas (females: 10.87 ± 2.51% ID/g; males: 9.10 ± 0.76% ID/g) and adrenal glands, with rapid clearance from non-target organs. Radio-HPLC analysis confirmed high metabolic stability with no detectable radiolabeled metabolites, and over 90% of radioactivity was recovered through renal excretion. Safety assessments demonstrated excellent tolerability across dose levels. In female xenograft models, treatment achieved tumor growth inhibition of 92.35–96.44% and 100% survival rate versus 10% in controls, though mid/high doses caused weight loss. Conclusions: Our study provides systematic preclinical evidence of sex-dependent pharmacokinetic differences in 177Lu-DOTATATE, with females demonstrating significantly higher systemic exposure than males at specific dose levels. These findings establish the systematic preclinical evidence base for sex-dependent pharmacokinetic differences in 177Lu-DOTATATE, providing a scientific rationale for incorporating sex as a stratification variable in future dosimetry-guided clinical studies. Full article
(This article belongs to the Section Pharmacology)
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15 pages, 1312 KB  
Article
A Comparison of Implementation of Synchronization, Artificial Insemination and Sex-Skewed Semen on Reproductive Performance and Calving Distribution in Beef Herds
by Saulo Menegatti Zoca, George A. Perry, Matthew A. Diersen, Warren C. Rusche, Emmalee J. Northrop-Albrecht, Jerica J. J. Rich, Kaitlin M. Epperson, Stephanie D. Perkins-Oines and Julie A. Walker
Animals 2026, 16(10), 1512; https://doi.org/10.3390/ani16101512 - 15 May 2026
Abstract
This study evaluated the implementation of reproductive technologies and their effects on pregnancy rates (PRs) and calving distribution. Producers (n = 11) were enrolled in Level 1 or 2 and subsequently transitioned to Level 2 or 3. Level 1: females were exposed [...] Read more.
This study evaluated the implementation of reproductive technologies and their effects on pregnancy rates (PRs) and calving distribution. Producers (n = 11) were enrolled in Level 1 or 2 and subsequently transitioned to Level 2 or 3. Level 1: females were exposed to natural service (NS) only versus estrous synchronization (7d-CIDR) before NS (SynNS). Level 2: SynNS versus fixed-time artificial insemination (SynAI; 7d-CO-Synch + CIDR) with conventional semen. Level 3: conventional versus sex-skewed semen (FTAI-con and FTAI-sexed, respectively). Artificial insemination occurred 60–66 h post CIDR removal (SynAI; FTAI-con; FTAI-sexed) and bulls were introduced on d 0 (NS and SynNS) or 10–14 d post artificial insemination (SynAI; FTAI-con; FTAI-sexed). Breeding season PRs did not differ between treatments (p > 0.50). In Level 2, SynNS had greater 21 d PRs compared to SynAI (p < 0.01). For Level 3, FTAI-con had greater 21 d PRs compared to FTAI-sexed (p < 0.01). In Level 1, the proportion of cows that calved by day 14 was greater for SynNS compared to NS (p < 0.01). In Level 2, SynAI had a greater proportion calved by day 7 (p = 0.01); however, SynNS had a greater proportion calved by day 21 and 42 (p < 0.01). In Level 3, FTAI-con had a greater proportion calved by day 14 and 21 (p < 0.01) compared to FTAI-sexed. In conclusion, reproductive technologies altered the calving distribution with more calves born earlier. Full article
(This article belongs to the Special Issue Reproductive Management Strategies for Dairy and Beef Cows)
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10 pages, 924 KB  
Article
β-Catenin-Associated Wnt Signaling and Tumor Microenvironment Markers in Basal Cell Carcinoma Subtypes
by Tayfun Koçoğlu, Nilay Duman, Ahmet Çağrı Evran and Çiğdem Özdemir
J. Clin. Med. 2026, 15(10), 3804; https://doi.org/10.3390/jcm15103804 - 15 May 2026
Abstract
Background/Objective: Basal cell carcinoma (BCC) is the most common cutaneous malignancy, arising from epidermal basal cells or the outer root sheath of the pilosebaceous unit. Despite its generally indolent clinical behavior, BCC exhibits substantial histopathological heterogeneity, which may reflect underlying biological differences among [...] Read more.
Background/Objective: Basal cell carcinoma (BCC) is the most common cutaneous malignancy, arising from epidermal basal cells or the outer root sheath of the pilosebaceous unit. Despite its generally indolent clinical behavior, BCC exhibits substantial histopathological heterogeneity, which may reflect underlying biological differences among its subtypes. This study aimed to evaluate the expression of Wnt/β-catenin pathway components and tumor-associated markers—including COX-2, Ki-67, tryptase, CD1a, and WNT3A—across different histopathological subtypes of BCC. Methods: This retrospective cross-sectional study included 100 formalin-fixed paraffin-embedded (FFPE) BCC specimens retrieved between January 2006 and September 2015. After the exclusion of three cases due to inadequate tissue quality, the tumors were classified into nodular (n = 60), infiltrative (n = 16), superficial (n = 9), and other subtypes (n = 12). The immunohistochemical expressions of COX-2, Ki-67, CD1a, intratumoral and peritumoral tryptase, β-catenin, and WNT3A were assessed and compared among the BCC subtypes. Results: No significant differences were observed among the BCC subtypes regarding age or sex distribution. The expression levels of COX-2, Ki-67, CD1a, and mast cell-associated markers (intratumoral and peritumoral tryptase) did not differ significantly among the groups (all p > 0.05). Conversely, β-catenin expression was significantly higher in the infiltrative subtype compared with the other histological variants (p = 0.001). WNT3A immunoexpression was uniformly negative across all evaluated cases. Conclusions: Most of the evaluated immunohistochemical markers did not differentiate among the BCC subtypes. However, the significantly increased β-catenin expression observed in the infiltrative subtype suggests a potential association with tumor growth patterns rather than serving as a specific discriminative marker, thereby highlighting the biological heterogeneity of BCC. Although WNT3A expression was uniformly negative in all cases, this finding should be interpreted cautiously and does not allow for definitive conclusions regarding its role in Wnt pathway activation. Overall, these results support the need for further investigation into the Wnt/β-catenin pathway heterogeneity in BCC. Full article
(This article belongs to the Special Issue Tumor Microenvironment—Current Status and Therapeutic Targets)
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11 pages, 337 KB  
Article
Serum Uric Acid Trajectories in Multiple Sclerosis: A 5-Year Longitudinal Comparison of High- and Moderate-Efficacy Therapies
by Laura-Elena Cucu, Alina Săcărescu, Andra Oancea, Bogdan Emilian Ignat, Cristina Grosu, Laura-Cristina Baciu, Costin Chirica, Gabriela Popescu, Alexandra Maștaleru and Maria-Magdalena Leon
Med. Sci. 2026, 14(2), 256; https://doi.org/10.3390/medsci14020256 - 15 May 2026
Abstract
Background/Objectives: Uric acid (UA), a major circulating antioxidant, has been consistently reported at lower levels in multiple sclerosis (MS) patients, yet long-term UA trajectories stratified by disease-modifying therapy (DMT) efficacy remain unexplored. This study aimed to evaluate the 5-year longitudinal evolution of [...] Read more.
Background/Objectives: Uric acid (UA), a major circulating antioxidant, has been consistently reported at lower levels in multiple sclerosis (MS) patients, yet long-term UA trajectories stratified by disease-modifying therapy (DMT) efficacy remain unexplored. This study aimed to evaluate the 5-year longitudinal evolution of serum UA levels in relapsing-remitting MS (RRMS), comparing high-efficacy (HE-DMT) and moderate-efficacy (ME-DMT) treatment groups. Methods: This retrospective longitudinal cohort study included adult RRMS patients who initiated or switched DMTs between January 2020 and June 2025. Serum UA was measured at treatment initiation (T0) and annually for up to 5 years (T1–T5). Linear mixed-effects models adjusted for sex, age, and EDSS were used to examine longitudinal UA trajectories. Results: A total of 222 patients were included and followed for up to 5 years across HE-DMT and ME-DMT treatment groups. Groups were comparable at baseline regarding serum UA levels despite significant differences in age, EDSS, and therapy status. Linear mixed-effects modeling demonstrated that serum UA levels changed significantly over time (F(5, 307.04) = 11.03, p < 0.01), with a significant main effect of treatment type (F(1, 378.31) = 5.25, p = 0.02) and a significant time × treatment interaction (F(5, 307.05) = 2.42, p = 0.04), indicating that UA trajectories differed between groups across the follow-up period. In the HE-DMT group, UA levels increased progressively from 4.27 mg/dL at baseline to 5.58 mg/dL at year 4, whereas the ME-DMT group showed an initial decline at year 1 followed by a more gradual increase from 4.19 mg/dL to 5.04 mg/dL at year 4. Sex was a significant independent predictor of UA levels (p < 0.01), whereas age and EDSS were not. Conclusions: HE-DMTs were associated with an earlier and more pronounced increase in serum UA levels over 5 years compared with ME-DMTs, with distinct trajectories depending on treatment efficacy. These findings suggest that longitudinal UA assessment may serve as a complementary exploratory indicator of the metabolic context associated with DMT efficacy. Full article
(This article belongs to the Section Neurosciences)
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14 pages, 329 KB  
Article
Adjunct Tendon Vibration and Bone Outcomes in Older Adults with Osteoporosis: A 12-Month Prospective Cohort Study
by Konstantinos Moutaftsis, Aikaterini Anetaki, Constantine Anetakis, Eleftherios Panteris, Ioannis Chaniotakis, Ilias Pessach, Maria Chatzidimitriou, Petros Skepastianos, Eleni Andreadou, Mattheos Bobos, Paris Iakovidis, Thomas Apostolou and Stella Mitka
J. Clin. Med. 2026, 15(10), 3798; https://doi.org/10.3390/jcm15103798 - 14 May 2026
Abstract
Background/Objectives: To evaluate the association between adjunct tendon vibration and changes over 12 months in dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) T-score and bone turnover markers in older adults with osteoporosis receiving standard care in a non-randomised controlled cohort study. Methods: [...] Read more.
Background/Objectives: To evaluate the association between adjunct tendon vibration and changes over 12 months in dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) T-score and bone turnover markers in older adults with osteoporosis receiving standard care in a non-randomised controlled cohort study. Methods: This 12-month prospective non-randomised controlled cohort study included 100 adults aged ≥60 years with DXA-confirmed osteoporosis recruited from orthopaedic clinics in the Greater Thessaloniki area. Fifty participants received adjunct tendon vibration therapy in addition to usual care, while 50 received usual care alone. Usual care consisted of calcium and vitamin D supplementation. The primary outcome was post-intervention BMD T-score, analysed using analysis of covariance (ANCOVA) adjusted for baseline T-score. Secondary outcomes included changes in bone turnover markers and calcium/phosphate metabolism. Sensitivity analysis was conducted using a linear mixed-effects model with repeated BMD measurements. Results: Baseline characteristics were comparable between groups. Over 12 months, the intervention group showed greater improvement in BMD T-score than controls (median change 0.90 [0.70–1.00] vs. −0.10 [−0.10–0.10], p < 0.001). The adjusted between-group difference was 0.871 (95% CI 0.773–0.968; p < 0.001). Results remained consistent after adjustment for age and sex. The mixed-effects model confirmed a significant group × time interaction (β = 0.922, 95% CI 0.806–1.038; p < 0.001). Bone resorption markers decreased more in the intervention group. The magnitude of the observed BMD improvement (~0.9 T-score units) is notable for a non-pharmacological intervention and should be interpreted cautiously. Conclusions: Adjunct tendon vibration was associated with a more favourable BMD trajectory and changes in bone turnover markers in older adults with osteoporosis receiving standard care. Given the non-randomised design and potential residual confounding, these findings should be interpreted as associative rather than causal. Full article
(This article belongs to the Section Orthopedics)
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