Search Results (4,252)

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

Background and Objectives: Spinopelvic alignment may affect the outcomes of total hip arthroplasty (THA), with pelvic version influencing the risk of mechanical complications occurring after surgery. On the other hand, THA surgery itself may contribute to the modification of pelvis version. The sacro-femoro-pubic (SFP) angle is measured on anteroposterior (AP) radiographs of the pelvis in a supine position, and is used to estimate pelvic tilt (PT), representative of pelvic version, which requires lateral views of the sacrum for its calculation; however, these X rays are not routinely performed in the preoperative setting of hip surgery. This study aims to analyze how THA determines changes in the pelvic version of operated patients; the SFP angle will be used to assess pelvic version on standard AP radiographs. Materials and Methods: This retrospective study included 182 consecutive patients undergoing THA for unilateral primary degenerative hip osteoarthritis (HOA-study group, n = 104) or femoral neck fracture (FNF-control group, n = 78) at the author’s institution. The SFP angle was measured on AP pelvic radiographs of the non-replaced hip preoperatively, postoperatively, and at the last follow-up. PT values were derived from SFP angles. Pre- and postoperative PT and its variations ΔPT were assessed. Study groups were compared in terms of native and postoperative variations of pelvic version. Results: The average absolute value of ΔPT was 2.99° ± 3.07° in the HOA group and 3.57° ± 2.92° in FNF group. There was no significant overall difference in preoperative or postoperative PT values between groups. In both groups, THA surgery led to a certain improvement, still not significant, in pelvic orientation, with FNF patients presenting a greater tendency toward retroversion. No significant differences in complication rates were found comparing patients with different pelvic orientations. Conclusions: THA can lead to a “normalization” of pelvic version in a certain number of patients with preoperative anteversion or retroversion. Although statistically non-significant, this observation may have clinical implications for spinopelvic balance and could support prioritizing THA in patients with concurrent spinal disease. Further research is needed to confirm these findings and to evaluate the long-term impact of THA on spinopelvic alignment. Full article

Background/Objective: The COVID-19 pandemic profoundly transformed social life worldwide, indiscriminately affecting individuals across all age groups. Children have not been exempted from the risk of severe illness and death caused by COVID-19. Objective: This paper sought to describe the clinical findings, laboratory and imaging results, and hospital care provided for severe and critical cases of COVID-19 in unvaccinated children, with or without severe asthma, hospitalized in a public referral service for COVID-19 treatment in the Brazilian state of Pernambuco. Methods: This was a case series study of severe and critical COVID-19 in hospitalized, unvaccinated children, with or without severe asthma, conducted in a public referral hospital between March 2020 and June 2021. Results: The case series included 80 children, aged from 1 month to 11 years, with the highest frequency among those under 2 years old (58.8%) and a predominance of males (65%). Respiratory diseases, including severe asthma, were present in 73.8% of the cases. Pediatric multisystem inflammatory syndrome occurred in 15% of the children, some of whom presented with cardiac involvement. Oxygen therapy was required in 65% of the cases, mechanical ventilation in 15%, and 33.7% of the children required intensive care in a pediatric intensive care unit. Pulmonary infiltrates and ground-glass opacities were common findings on chest X-rays and CT scans; inflammatory markers were elevated, and the most commonly used medications were antibiotics, bronchodilators, and corticosteroids. Conclusions: This case series has identified key characteristics of children with severe and critical COVID-19 during a period when vaccines were not yet available in Brazil for the study age group. However, the persistence of low vaccination coverage, largely due to parental vaccine hesitancy, continues to leave children vulnerable to potentially severe illness from COVID-19. These findings may inform the development of public health emergency contingency plans, as well as clinical protocols and care pathways, which can guide decision-making in pediatric care and ensure appropriate clinical management, ultimately improving the quality of care provided. Full article

Gene replacement using adeno-associated viral (AAV) vectors has become a major therapeutic avenue for neurodegenerative diseases (NDD). In single-gene diseases with loss-of-function mutations, the objective of gene therapy is to express therapeutic transgenes abundantly in cell populations that are implicated in the pathological phenotype. X-ALD is one of these orphan diseases. It is caused by ABCD1 gene mutations and its main clinical form is adreno-myelo-neuropathy (AMN), a disabling spinal cord axonopathy starting in middle-aged adults. Unfortunately, the main cell types involved are yet poorly identified, complicating the choice of cells to be targeted by AAV vectors. Pioneering gene therapy studies were performed in the Abcd1^-/y mouse model of AMN with AAV9 capsids carrying the ABCD1 gene. These studies tested ubiquitous or cell-specific promoters, various routes of vector injection, and different ages at intervention to either prevent or reverse the disease. The expression of one of these vectors was studied in the spinal cord of a healthy primate. In summary, gene therapy has made promising progress in the Abcd1^-/y mouse model, inaugurating gene replacement strategies in AMN patients. Because X-ALD is screened neonatally in a growing number of countries, gene therapy might be applied in the future to patients before they become overtly symptomatic. Full article

Childhood obesity increases chronic disease risk, but no comprehensive synthesis has evaluated the impact of school-based combined nutrition education and physical activity interventions on cardiometabolic biomarkers in children aged 3 to 12 years. This systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251085194). Five databases were systematically searched through June 2025. Twelve randomized controlled trials involving 18,231 children were included and assessed using the PEDro scale. Ten trials demonstrated significant improvements in at least one cardiometabolic biomarker. Blood pressure (8 studies) outcomes showed systolic reductions of 1.41–6.0 mmHg in six studies. Glucose metabolism (5 studies) improved in two studies with reductions of 0.20–0.22 mmol/L. Lipid profiles (7 studies) improved in three studies, including total cholesterol (−0.32 mmol/L). Insulin levels (5 studies) decreased significantly in two investigations. Anthropometric improvements included BMI and body fat. Physical activity increased by >45 min/week and dietary habits improved significantly. Programs with daily implementation (90-min sessions 4x/week), longer duration (≥12 months), family involvement (parent education), and curriculum integration (classroom lessons) showed superior effectiveness. Interventions targeting children with overweight/obesity demonstrated higher changes compared to the general population. However, methodological limitations included a lack of assessor blinding, absence of subject/therapist blinding, and inadequate retention rates. School-based interventions combining nutrition and physical activity can produce significant improvements in cardiometabolic biomarkers, supporting comprehensive, sustained multicomponent programs for early chronic disease prevention. Full article

The recent discovery of Orthonairovirus songlingense (SGLV) and Norwavirus beijiense (BJNV) in China has raised significant concern due to their potential to cause severe human disease. However, little is known about the structural features and function of their nucleoproteins, which play a key role in the viral life cycle. By combining small-angle X-ray scattering (SAXS) data and AlphaFold 3 simulations, we reconstructed the BJNV and SGLV nucleoprotein structures for the first time. The SGLV and BJNV nucleoproteins have structures that are broadly similar to those of Orthonairovirus haemorrhagiae (CCHFV) nucleoproteins despite low sequence similarity. Based on structural analysis, several residues located in the positively charged region of BJNV and SGLV nucleoproteins have been indicated to be important for viral RNA binding. A positively charged RNA-binding crevice runs along the interior of the SGLV and BJNV ribonucleoprotein complex (RNP), shielding the viral RNA. Despite the high structural similarity between SGLV and BJNV nucleoprotein monomers, their RNPs adopt distinct conformations. These findings provide important insights into the molecular mechanisms of viral genome packaging and replication in these emerging pathogens. Also, our work demonstrates that experimental SAXS data can validate and improve predicted AlphaFold 3 structures to reflect their solution structure and also provides the first low-resolution structures of the BJNV and SGLV nucleoproteins for the future development of POC tests, vaccines, and antiviral drugs. Full article

Background: Charcot–Marie–Tooth (CMT) is a group of inherited diseases impairing the peripheral nervous system. CMT originates from genetic variants that affect proteins fundamental for the myelination of peripheral nerves and survival. Moreover, environmental and humoral factors can impact disease development and evolution. Currently, no therapy is available. Metabolomics is an emerging field of biomedical research that enables the development of novel biomarkers for neurodegenerative diseases by targeting metabolic pathways or metabolites. This study aimed to evaluate the metabolomics profile of CMT disease by comparing patients with healthy individuals. Methods: A total of 22 CMT patients (CMT) were included in this study and were demographically matched with 26 healthy individuals (C). Serum samples were analyzed through Nuclear Magnetic Resonance spectroscopy, and multivariate and univariate statistical analyses were subsequently applied. Results: A supervised model showed a clear separation (R²X = 0.3; R²Y = 0.7; Q² = 0.4; p-value = 0.0004) between the two classes of subjects, and nine metabolites were found to be significantly different (2-hydroxybutyrate, 3-hydroxybutyrate, 3-methyl-2-oxovalerate, choline, citrate, glutamate, isoleucine, lysine, and methyl succinate). The combined ROC curve showed an AUC of 0.94 (CI: 0.9–1). Additional altered metabolic pathways were also identified within the disease context. Conclusion: This study represents a promising starting point, demonstrating the efficacy of metabolomics in evaluating CMT patients and identifying novel potential disease biomarkers. Full article

Obstructive sleep apnea (OSA) is a common condition associated with intermittent hypoxia, systemic inflammation, and vascular dysfunction; mechanisms implicated in retinal disease pathogenesis. This real-world retrospective cohort study used data from the TriNetX Research Network to assess whether continuous positive airway pressure (CPAP) therapy reduces retinal disease incidence among adults with OSA and BMI between 25.0 and 30.0 kg/m². After 1:1 propensity score matching, 101,754 patients were included in the analysis. Retinal outcomes included diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), and central serous chorioretinopathy (CSC). CPAP use was associated with a modest but statistically significant reduction in DR (3.2% vs. 3.4%, RR: 0.922, p = 0.016) and AMD (2.1% vs. 2.3%, RR: 0.906, p = 0.018), while no significant differences were found for RVO or CSC. These findings support prior evidence linking CPAP to improved retinal microvascular health and suggest a protective effect against specific retinal complications. Limitations include a lack of data on CPAP adherence, OSA severity, and imaging confirmation. Still, this study highlights the importance of interdisciplinary care between sleep and eye health, and the need for further prospective studies to validate CPAP’s role in preventing retinal disease progression in OSA patients. Full article

The integration of vision and language processing into a cohesive system has already shown promise with the application of large language models (LLMs) in medical image analysis. Their capabilities encompass the generation of medical reports, disease classification, visual question answering, and segmentation, providing yet another approach to interpreting multimodal data. This survey aims to compile all known applications of LLMs in the medical image analysis field, spotlighting their promises alongside critical challenges and future avenues. We introduce the concept of X-stage tuning which serves as a framework for LLMs fine-tuning across multiple stages: zero stage, one stage, and multi-stage, wherein each stage corresponds to task complexity and available data. The survey describes issues like sparsity of data, hallucination in outputs, privacy issues, and the requirement for dynamic knowledge updating. Alongside these, we cover prospective features including integration of LLMs with decision support systems, multimodal learning, and federated learning for privacy-preserving model training. The goal of this work is to provide structured guidance to the targeted audience, demystifying the prospects of LLMs in medical image analysis. Full article

One of the largest future applications of computer vision is in the healthcare industry. Computer vision tasks are generally implemented in diverse medical imaging scenarios, including detecting or classifying diseases, predicting potential disease progression, analyzing cancer data for advancing future research, and conducting genetic analysis for personalized medicine. However, a critical drawback of using Computer Vision (CV) approaches is their limited reliability and transparency. Clinicians and patients must comprehend the rationale behind predictions or results to ensure trust and ethical deployment in clinical settings. This demonstrates the adoption of the idea of Explainable Computer Vision (X-CV), which enhances vision-relative interpretability. Among various methodologies, attribution-based approaches are widely employed by researchers to explain medical imaging outputs by identifying influential features. This article solely aims to explore how attribution-based X-CV methods work in medical imaging, what they are good for in real-world use, and what their main limitations are. This study evaluates X-CV techniques by conducting a thorough review of relevant reports, peer-reviewed journals, and methodological approaches to obtain an adequate understanding of attribution-based approaches. It explores how these techniques tackle computational complexity issues, improve diagnostic accuracy and aid clinical decision-making processes. This article intends to present a path that generalizes the concept of trustworthiness towards AI-based healthcare solutions. Full article

Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype–phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis. Full article

Background and Aims: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown promise in metabolic dysfunction-associated steatotic liver disease (MASLD). This large real-world study aimed to evaluate the effects of SGLT2 inhibitors on MASLD patients’ clinical outcomes and liver-related complications over extended follow-up. Patients and Method: Data were sourced from TriNetX, a global health research platform with de-identified electronic medical records spanning 135 million patients across 112 healthcare organizations worldwide. We included MASLD adults diagnosed according to ICD9/10 criteria. Following propensity score matching based on 34 variables (demographics, comorbidities, laboratory tests and medication history), SGLT2 inhibitor-treated (n = 19,922) patients were compared with non-SGLT2 inhibitor (n = 19,922) cases. Exclusion criteria included baseline improved alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels > 4 upper normal limit (UNL), baseline advanced liver disease, liver transplant and cancer, past anticoagulation and non-MASLD etiologies. Assessed outcomes included survival, biochemical, hematologic, AFP, metabolic and cardiovascular parameters, progression to advanced liver disease (ALD), synthetic function, and metabolic markers over 1, 5, and 10 years. Results: Following matching, both cohorts were well-balanced across baseline characteristics. After one year, the SGLT2 inhibitor group demonstrated significantly reduced BMI (33.2 ± 6.2 vs. 34.1 ± 6.5 kg/m², p < 0.001), improved ALT (40.3 ± 31.5 vs. 48.3 ± 41.2 U/L, p < 0.001), and better glycemic control (HbA1c 7.35 ± 1.51% vs. 7.93 ± 1.72%, p < 0.001). The SGLT2 inhibitor group showed higher 10-year survival rates (95.00% vs. 88.69%, p < 0.001), fewer cardiovascular events (10.19% vs. 11.80%, p < 0.001), and markedly reduced progression to advanced liver disease (6.90% vs. 14.15%, p < 0.001). These benefits were consistent across clinical, laboratory, and medication-defined ALD categories. Notably, rates of hepatic decompensation events were significantly lower with SGLT2 inhibitor therapy. Conclusions: In this large real-world cohort, SGLT2 inhibitor use in MASLD patients was associated with significantly improved long-term survival, cardiovascular, and liver-related outcomes over 10 years of follow-up. These benefits likely result from combined metabolic improvements, anti-inflammatory effects, and direct hepatoprotective mechanisms. SGLT2 inhibitors represent a promising therapeutic strategy for improving outcomes in MASLD. Full article

Neuroinflammation, driven by activated microglia, contributes to the progression of neurodegenerative diseases. Extracellular vesicles mediate intercellular communication and influence immune responses. Chrysin, a natural flavone found in fruits and propolis, has demonstrated anti-inflammatory effects. This study explored the immunomodulatory potential of chrysin-loaded EVs (EVs-Chry) derived from BV2 microglial cells. BV2 cells were treated with chrysin for 24 h to assess cytotoxicity and proliferation. EVs were isolated from treated and untreated cells, characterized by nanoparticle tracking analysis, and applied to naïve BV2 cells prior to LPS stimulation. Effects on cell morphology, migration, cytokine expression (IL-1β, IL-6), inflammasome activity (caspase-1), and apoptosis-related protein Bcl-xL were investigated. Our results show that EVs-Chry significantly reduced LPS-induced cell proliferation, restored resting microglial morphology, and reduced migratory capacity. Furthermore, co-treatment with EVs-Chry and LPS reduced pro-inflammatory cytokines such as IL-1β, IL-6, and caspase-1 expression while enhancing anti-apoptotic Bcl-xL levels, indicating a shift toward an anti-inflammatory, neuroprotective micro-glial phenotype. Together, our results demonstrated that EVs-Chry have neuroprotective effects on LPS-induced microglial activation and modulate microglial responses to inflammatory stimuli, attenuating pro-inflammatory signaling and promoting cellular homeostasis. These findings support the therapeutic potential of EVs-Chry in the context of neuroinflammatory and neurodegenerative disorders. Full article

Background/Objectives: Gut-derived tryptophan (Trp) metabolites play important roles in metabolic and cardiovascular regulation. Although animal studies suggest their protective effects against metabolic dysfunction, data in adolescents, particularly those with obesity, remain limited. The objective of this study was to evaluate associations between circulating gut-derived Trp metabolites and markers of cardiometabolic, vascular, and platelet health in adolescents with obesity. Methods: Data were analyzed from 28 adolescents (ages 13–18; mean BMI = 36 ± 6.4 kg/m²). Fasting blood was collected to assess lipid profiles using a clinical analyzer and insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). Gut-derived Trp metabolites were measured by UPLC–mass spectrometry, peak oxygen uptake (VO_{2 peak}) by gas exchange during an incremental cycle ergometer test, and body composition by dual-energy X-ray absorptiometry. Platelet spare respiratory capacity (SRC), endothelial function, and liver fat were measured using high-resolution respirometry, flow-mediated dilation (FMD) of the brachial artery, and magnetic resonance imaging respectively. Results: Indole-3-propionic acid was inversely associated with diastolic blood pressure (rho = −0.39, p = 0.047), total cholesterol (rho = −0.55, p = 0.002), and LDL-C (rho = −0.57, p = 0.0014), independent of sex and obesity severity. Indoxyl sulfate was positively correlated with fasting glucose (rho = 0.47, p = 0.012), and adolescents with impaired fasting glucose had 1.6-fold higher IS levels. Indole-3-acetaldehyde declined with age (rho = −0.50, p = 0.007), and Indole-3-acetic acid and indole were higher in Hispanics vs. non-Hispanics. No significant associations were observed between Trp metabolites and FMD, VO₂ peak, or SRC. Conclusions: Gut-derived Trp metabolites, particularly indole-3-propionic and indoxyl sulfate, are associated with markers of cardiometabolic risk in adolescents with obesity. These findings support their potential relevance in early-onset cardiovascular disease risk. Full article

Reducing the application of chemical fertilizers and remediating heavy metal pollution in soil are important directions in current agricultural research. Utilizing the plant-growth-promoting and remediation capabilities of bacteria can provide more environmentally friendly assistance to agricultural production. In this study, the Burkholderia alba YIM B08401 strain was isolated and identified from rhizospheric soil, subjected to whole-genome sequencing and analysis, and its Cd²⁺ adsorption efficiency and characteristics were confirmed using multiple experimental methods, including atomic absorption spectrometry (AAS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The results showed that the genome of strain YIM B08401 has a total length of 7,322,157 bp, a GC content of 66.39%, and predicts 6504 protein-coding sequences. It contains abundant functional genes related to nutrient conversion (phosphate solubilization, sulfur metabolism, zinc solubilization, siderophore production), plant hormone regulation (indole-3-acetic acid secretion, ACC deaminase production), phenolic acid degradation, root colonization, heavy metal tolerance, pathogen antagonism, and the production of antagonistic secondary metabolites. Additionally, strain YIM B08401 can specifically bind to Cd²⁺ through various functional groups on the cell surface, such as C-O-C, P=O, and O-H, enabling biosorption. In conclusion, strain YIM B08401 is an excellent strain with plant-growth-promoting, disease-resistant, and bioremediation capabilities, warranting further development as a biofertilizer for agricultural applications to promote green and sustainable agricultural development. Full article