Search Results (2,442)

Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations. Full article

Background: Neonatal jaundice is common and can cause severe hyperbilirubinemia if untreated. The early identification of at-risk newborns is challenging despite the existing guidelines. Objective: This study aimed to identify the key maternal and neonatal risk factors for jaundice requiring phototherapy using machine learning. Methods: In this study hospital, phototherapy was administered following the American Academy of Pediatrics (AAP) guidelines when a neonate’s transcutaneous bilirubin level was in the high-risk zone. To identify the risk factors for phototherapy, we retrospectively analyzed the electronic medical records of 8242 neonates admitted between 2017 and 2022. Predictive models were trained using maternal and neonatal data. XGBoost showed the best performance (AUROC = 0.911). SHAP values interpreted the model. Results: Mode of delivery, neonatal feeding indicators (including daily formula intake and breastfeeding frequency), maternal BMI, and maternal white blood cell count were strong predictors. Cesarean delivery and lower birth weight were linked to treatment need. Conclusions: Machine learning models using perinatal data accurately predict the risk of neonatal jaundice requiring phototherapy, potentially aiding early clinical decisions and improving outcomes. Full article

Potato (Solanum tuberosum L.) crop yields may be reduced by nitrogen deficiency stress tolerance. An evaluation of 144 tetraploid potato genotypes was carried out during two consecutive seasons (2019 and 2020), with the objective of characterizing their variability in key physiological and agronomic parameters. Physiological parameters included chlorophyll content and fluorescence, stomatal conductance, NDVI, leaf area, and perimeter, while agronomic characteristics such as yield, tuber fresh weight, tuber number, starch content, dry matter, and reducing sugars were evaluated. To genotype the population, the GGP V3 Potato array was used, generating 18,259 high-quality SNP markers. Marker–trait association analysis was conducted using the GWASpoly package in R, applying Q + K linear mixed models to enhance precision. This methodology enabled the identification of 18 SNP markers that exhibited statistically significant associations with the traits analyzed in both trials and periods, relating them to genes whose functional implication has already been described. Genetic loci associated with chlorophyll content and tuber number were detected across non-stress and stress treatments, while markers linked to leaf area and leaf perimeter were identified specifically under nitrogen deficiency stress. The genomic distribution of these markers revealed that genetic markers or single-nucleotide polymorphisms (SNPs) correlated with phenotypic traits under non-stress conditions were predominantly located on chromosome 11, whereas SNPs linked to stress responses were mainly identified on chromosomes 2 and 3. These findings contribute to understanding the genetic mechanisms underlying potato tolerance to nitrogen deficiency stress, offering valuable insights for the development of future marker-assisted selection programs aimed at improving nitrogen use efficiency and stress resilience in potato breeding. Full article

Background: Lower phylogenetic species are known to rebuild cut-off caudal parts with regeneration of the central nervous system (CNS). In contrast, CNS regeneration in higher vertebrates is often attributed to immaturity, although this has never been conclusively demonstrated. The emergence of stem cells and their effective medical applications has intensified research into spinal cord regeneration. However, despite these advances, the impact of clinical trials involving spinal cord-injured (SCI) patients remains disappointingly low. Long-distance regeneration has yet to be proven. Methods: Our study involved a microsurgical dorsal myelotomy in fetal rats. The development of pioneering long primary afferent axons during early gestation was examined long after birth. Results: A single cut triggered the intrinsic ability of the dorsal root ganglion (DRG) neurons to reprogram. Susceptibility to hypoxia caused the axons to stop developing. However, the residual axonal outgrowth sheds light on the intriguing temporal and spatial events that reveal long-distance CNS regeneration. The altered phenotypes displayed axons of varying lengths and different features, which remained visible throughout life. The previously designed developmental blueprint was crucial for interpreting these enigmatic features. Conclusions: This research into immaturity enabled the exploration of the previously impenetrable domain of early life and the identification of a potential missing link in CNS regeneration research. Central axon regeneration appeared to occur much faster than is generally believed. The paradigm provides a challenging approach for exhaustive intrauterine reprogramming. When the results demonstrate pre-clinical effectiveness in CNS regeneration research, the transformational impact may ultimately lead to improved outcomes for patients with spinal cord injuries. Full article

Background: Nutrition is of paramount importance during early development, since suboptimal growth in this period of life is linked to adverse long- and mid-term outcomes. This is particularly relevant for preterm infants, who fail to thrive during the first weeks of life and develop extrauterine growth restriction (EUGR). This group of premature babies represents an interesting population to investigate using a metabolomic approach to optimize nutritional intake. Aims: To analyse and compare the urinary metabolomic pattern at birth of preterm infants with and without growth restriction at 36 weeks of postmenstrual age or at discharge, searching for putative markers of growth failure. Methods: We enrolled preterm infants between 23 and 32 weeks of gestational age (GA) and/or with a birth weight <1500 g, admitted to the Neonatal Intensive Care Unit (NICU) at the Department of Women’s and Children’s Health of Padova University Hospital. We collected urinary samples within 48 h of life and performed untargeted metabolomic analysis using mass spectrometry. Results: Sixteen EUGR infants were matched with sixteen non-EUGR controls. The EUGR group showed lower levels of L-cystathionine, kynurenic acid, L-carnosine, N-acetylglutamine, xanthurenic acid, aspartylglucosamine, DL5-hydroxylysine-hydrocloride, homocitrulline, and L-aminoadipic acid, suggesting a lower anti-inflammatory and antioxidant status with respect to the non-EUGR group. Conclusions: Metabolomic analysis suggests a basal predisposition to growth restriction, the identification of which could be useful for tailoring nutritional approaches. Full article

Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient’s management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus. Full article

Mitomycin C (MMC) is a widely employed chemotherapeutic agent, particularly in non-muscle invasive bladder cancer (NMIBC), where it functions by inducing DNA cross-linking and promoting tumor cell apoptosis. However, the tumor microenvironment (TME) significantly influences the therapeutic efficacy of MMC. Among the key regulators within the TME, the complement system and the coagulation pathway play a crucial role in modulating immune responses to cancer therapies, including MMC. This article explores the interaction between platinum nanoparticles (PtNPs) with human serum (HS) of NMIBC patients (T1 and Ta subtypes) at three different points: before the chemotherapy instillation of MMC (t₀) and three (t₃) and six months (t₆) after the treatment with MMC. This novel nanoproteomic strategy allowed the identification of a TME proteomic signature associated with the response to MMC treatment. Importantly, two proteins involved in the immune response were found to be deregulated across all patients (T1 and Ta subtypes) during MMC treatment: prothrombin (F2) downregulated and complement component C7 (C7) upregulated. By understanding how these biomarker proteins interact with MMC treatment, novel therapeutic strategies can be developed to enhance treatment outcomes and overcome resistance in NMIBC. Full article

Objectives: Burkholderia cepacia complex (Bcc), a Gram-negative organism, is a well-recognized cause of hospital outbreaks, often linked to a contaminated shared source, such as multidose medications. In this study, we report an outbreak of Bcc infections in a tertiary care hospital, associated with the intrinsic contamination of a prepared solution used in interventional radiology (IR) procedures. Additionally, we provide a detailed explanation of the interventions implemented to control and interrupt the outbreak. Methods: Records from the infection control committee from 1 January 2023 to 31 October 2024 were screened to identify cases with Bcc growth in cultured blood, urine, or respiratory samples. Clinical and laboratory data were collected in March 2025. Bacterial identification was performed using conventional methods and MALDI-TOF (Bruker Daltonics, Bremen, Germany). Controls were matched to cases by ward, date of initial growth, and duration of hospitalization. Demographic and clinical data of these patients were systematically collected and analyzed. Microbiological cultures were obtained from environmental objects of concern and certain medications. Results: A total of 82 Burkholderia species were identified. We enrolled 77 cases and 77 matched controls. The source of contamination was identified in ready-to-use intravenous medications (remifentanil and magnesium preparations) in the IR department. These preparations were compounded in advance by the team and were used repeatedly. Although the outbreak originated from contaminated IV medications used in IR, secondary transmission likely affected 28 non-IR patients via fomites, shared environments, and possible lapses in isolation precautions. The mortality rate among the cases was 16.9%. Infection with Bcc was associated with prolonged intensive care unit stays (p = 0.018) and an extended overall hospitalization duration (p < 0.001); however, it was not associated with increased mortality. The enforcement of contact precautions and comprehensive environmental decontamination successfully reduced the incidence of the Bcc outbreak. No pathogens were detected in cultures obtained after the disinfection. Conclusions: The hospital transmission of Bcc is likely driven by cross-contamination, invasive medical procedures, and the administration of contaminated medications. Implementing stringent infection control measures such as staff retraining, updated policies on medication use, enhanced environmental decontamination, and strict adherence to isolation precautions has proven effective in curbing the spread of virulent and transmissible Bcc. Full article

Background: Radiation maculopathy (RM) is a delayed, sight-threatening complication of ocular radiotherapy. Traditionally regarded as a pure microvascular disease, emerging evidence points to the central role played by retinal neuroinflammation, driven by microglial activation and cytokine dysregulation affecting both the retina and the choroid. Hyperreflective retinal foci, neuroinflammatory in origin (I-HRF), visualized through advanced imaging modalities such as spectral domain optical coherence tomography (OCT), have been identified as early and critical biomarkers of both preclinical and clinical retinal neuroinflammation. Materials and Methods: This review synthesizes findings from experimental and clinical studies to explore the pathophysiology of neuroinflammation and the associated imaging parameters in RM. Results: The integration of experimental and clinical evidence specifically underscores the significance of I-HRF as an early indicator of neuroinflammation in RM. OCT enables the identification and quantification of these biomarkers, which are linked to microglial activation and cytokine dysregulation. Conclusions: The pathophysiology of RM has evolved from a predominantly vascular condition to one strongly secondary to neuroinflammatory mechanisms involving the retina and choroid. In particular, I-HRF, as early biomarkers, offers the potential for preclinical diagnosis and therapeutic intervention, paving the way for improved management of this sight-threatening complication. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the scientific landscape through bibliometric analysis, identifying emerging domains and future clinical translation directions. Methods: A comprehensive bibliometric analysis of 1002 publications from 2004 to 2025 was performed using thematic mapping, temporal trend evaluation, and network analysis. Analysis included geographical and institutional distributions, thematic cluster identification, and research paradigm evolution assessment, focusing specifically on adipokine–hepatokine signaling mechanisms and clinical implications. Results: The United States and China are at the forefront of research output, whereas European institutions significantly contribute to mechanistic discoveries. The thematic map analysis reveals the motor/basic themes residing at the heart of the field, such as insulin resistance, fatty liver, metabolic syndrome, steatosis, fetuin-A, and other related factors that drive innovation. Basic clusters include metabolic foundations (obesity, adipose tissue, FGF21) and adipokine-centered subjects (adiponectin, leptin, NASH). New themes focus on inflammation, oxidative stress, gut microbiota, lipid metabolism, and hepatic stellate cells. Niche areas show targeted fronts such as exercise therapies, pediatric/novel adipokines (chemerin, vaspin, omentin-1), and advanced molecular processes that focus on AMPK and endoplasmic-reticulum stress. Temporal analysis shows a shift from single liver studies to whole models that include the gut microbiota, mitochondrial dysfunction, and interactions between other metabolic systems. The network analysis identifies nine major clusters: cardiovascular–metabolic links, adipokine–inflammatory pathways, hepatokine control, and new therapeutic domains such as microbiome interventions and cellular stress responses. Conclusions: In summary, this study delineates current trends and emerging areas within the field and elucidates connections between mechanistic research and clinical translation to provide guidance for future research and development in this rapidly evolving area. Full article

This study developed a copper mineral prospectivity map for the Koldar massif, Kazakhstan, using an integrated approach combining geophysical and satellite methods. A strong spatialgenetic link was identified between faults and hydrothermal mineralization, with faults acting as key conduits for ore-bearing fluids. Lineament analysis and density mapping confirmed the high permeability of the Koldar massif, indicating its structural prospectivity. Hyperspectral and multispectral data (ASTER, PRISMA, WorldView-3) were applied for detailed mapping of hydrothermal alteration (phyllic, propylitic, argillic zones), which are critical for discovering porphyry copper deposits. In particular, WorldView-3 imagery facilitated the identification of new prospective zones. The transformation of magnetic and gravity data successfully delineated geological features and structural boundaries, confirming the fractured nature of the massif, a key structural factor for mineralization. The resulting map of prospective zones, created by normalizing and integrating four evidential layers (lineament density, PRISMA-derived hydrothermal alteration, magnetic, and gravity anomalies), is thoroughly validated, successfully outlining the known Aktogay, Aidarly, and Kyzylkiya deposits. Furthermore, new, previously underestimated prospective areas were identified. This work fills a significant knowledge gap concerning the Koldar massif, which had not been extensively studied using satellite methods previously. The key advantage of this research lies in its comprehensive approach and the successful application of high-quality hyperspectral imagery for mapping new prospective zones, offering a cost-effective and efficient alternative to traditional ground-based investigations. Full article

Background/Objective: The hepatitis B virus (HBV) can cause chronic hepatitis B (CHB), which can rapidly progress into fatal liver cirrhosis (CHB-LC) and hepatocellular carcinoma (CHB-HCC). Methods: In this study, we investigated metabolites associated with distinct clinical stages of HBV infection for the identification of stage-specific serum metabolite biomarkers using ¹H-NMR-based metabolomics. Results: A total of 64 serum metabolites were identified, among which six core discriminatory metabolites, namely isoleucine, tryptophan, histamine (for CHB), and pyruvate, TMAO, lactate (for CHB-HCC), were consistently significant across univariate and multivariate statistical analyses, including ANOVA with FDR, OPLS-DA, and VIP scoring. These metabolites were closely linked to key metabolic pathways, such as propanoate metabolism, pyruvate metabolism, and the Warburg effect. Conclusions: The findings suggest that these six core metabolites serve as potential stage-specific biomarkers for CHB, CHB-LC, and CHB-HCC, respectively, and offer a foundation for the future development of metabolomics-based diagnostic and therapeutic strategies. Full article

Objectives: The objective of this manuscript is to translate, adapt, and validate an Arabic version of the Diabetes Eating Problem Survey—Revised (DEPS-R) questionnaire to assess disordered eating behaviors (DEBs) in adolescents with T1D in Saudi Arabia. Additionally, the study sought to estimate the prevalence of DEBs and analyze its associations with glycemic control and diabetes-related complications. Methods: A cross-cultural validation study was conducted following the COSMIN guidelines. The DEPS-R questionnaire was translated into Arabic through forward and backward translation involving expert panels, including psychiatrists, diabetologists, and linguists. A sample of 409 people with type 1 diabetes (PwT1D) (58.4% females) aged 12–20 years was recruited from outpatient diabetes clinics in the five main regions of Saudi Arabia. Participants completed the Arabic DEPS-R and the validated Arabic version of the SCOFF questionnaire. Sociodemographic, anthropometric, and biochemical data were collected, and statistical analyses, including confirmatory factor analysis (CFA) and internal consistency tests, were conducted. Results: The Arabic DEPS-R exhibits strong internal consistency (Cronbach’s alpha = 0.829) and high test–retest reliability (ICC = 0.861), with a CFA supporting a three-factor structure, namely body weight perception, disordered eating behaviors (DEBs), and bulimic tendencies. Notably, higher DEPS-R scores are significantly linked to elevated HbA1c levels, increased BMI, and more frequent insulin use. Alarmingly, 52.8% of participants show high-risk DEB, which is directly associated with poor glycemic control (HbA1c ≥ 8.1%) and a heightened risk of diabetic ketoacidosis (DKA). Conclusions: The Arabic DEPS-R is a valid and reliable tool for screening DEBs among Saudi adolescents with T1D. Findings underscore the necessity for early identification and intervention to mitigate the impact of EDs on diabetes management and overall health outcomes. Full article

Alzheimer’s Disease (AD) is a multifactorial process. Amyloid plaque formation constitutes the main characteristic of the disease. Despite the identification of numerous factors associated with AD, the mechanism remains unclear in several aspects. Disturbances in intestinal and blood–brain barrier (BBB) penetration, observed in AD, may facilitate immunologic response to food-derived antigens. In the present study, antibodies against egg albumin, bovine-casein, and N-Glycolyl-Neuraminic acid (Neu5Gc) were measured in the cerebrospinal fluid (CSF) and serum of the patients using an enzyme-linked immunosorbent assay (ELISA). Zero anti-Neu5Gc and low concentrations of anti-casein antibodies were detected. Increased anti-native egg albumin antibodies were present in the serum of patients of all stages with 65% positivity (p < 0.001) in mild disease and a higher percentage in females (81.9%, p < 0.001). Lower serum positivity to anti-denatured egg albumin antibodies was observed, showing a gradual increase with severity and higher prevalence also in females. In the CSF, anti-native and anti-denatured egg albumin antibodies were mainly observed in severely ill patients with accumulative positivity to either antigen, reaching 61.8% in severe vs. 15% in mild disease (p < 0.001). Increased values were mainly observed in males. Anti-egg albumin antibodies may be implicated in the disease mechanism through sequence/structural similarity with human proteins, mainly serpins, and it would be worth consideration in further investigations and therapeutic strategies. Full article

Weeksella virosa (W. virosa) is a rare, non-saccharolytic Gram-negative bacterium initially described in the 1970s, later proposed as a distinct genus in 1986. The genus Weeksella currently contains two species, namely W. virosa and W. massiliensis. Although primarily considered non-pathogenic, recent evidence has linked W. virosa to a limited number of clinical infections, mostly in immunocompromised patients. This review aims to consolidate the current body of knowledge on W. virosa, encompassing its microbiological and biochemical characteristics, involvement in human and animal infections, antimicrobial susceptibility profiles, and a critical evaluation of existing diagnostic methodologies. This review includes 13 case reports detailing 16 human cases retrieved from multiple databases, highlighting diagnostic inconsistencies and a lack of standardized antimicrobial susceptibility testing. Although W. virosa is generally susceptible to most antibiotics with the exception of aminoglycosides, recent reports seem to suggest a possible emerging resistance trend. The presence of this organism in hospital environments raises concerns about its potential transmission within healthcare settings. While biochemical testing appears to offer reasonably accurate identification of W. virosa, molecular confirmation may be warranted in some cases mainly due to the organism’s rarity. The reliability of MALDI-TOF MS for the identification of W. virosa remains currently uncertain. Further studies, including electron microscopy and genome-wide analysis, are urgently needed to clarify the pathogenic potential of this bacterium and guide clinical management. This review underscores the necessity for awareness among clinicians and microbiologists regarding this underrecognized pathogen. Full article