Search Results (1,554)

Background: Small intestine bacterial overgrowth (SIBO) is associated with steatohepatitis (SH) in subjects with metabolic-associated steatotic liver disease (MASLD). The impact of ileocecal valve (ICV) incontinence, a major cause of SIBO in patients with MASLD, remains unknown because of the unmet need for a non-X-ray-dependent diagnosis. Methods: Exploiting water as contrast medium and colonic irrigation via a hydro-colon machine (Clean Colon Srl, Monza, Italy), we developed a new abdominal ultrasound (US) procedure for diagnosing and grading ICV incontinence. In a pilot, observational, feasibility and safety study, we correlated a new ICV incontinence parameter with irritable bowel syndrome (IBS, ROMA IV criteria), serum transaminases (AST, ALT), platelet counts, FIB-4, US liver steatosis and stiffness (LS, measured by Shear Wave and Transient Elastography, SWE and TE). Results: We prospectively studied 32 consecutive subjects with IBS who underwent a pre-colonoscopy colon cleansing after informed consent: 19 males (59%), body mass index (BMI) 26.6 ± 2.6 kg/m², age 57 ± 19 years, 16 (50%) with US liver steatosis. The half-hour (27 min, range 20–35 min) procedure was safe and well tolerated except in two males with prostate hypertrophy. ICV incontinence was graded (after 2500–3000 mL irrigation) according to cecum/right-colon distention with/without (immediate or delayed) reflux into terminal ileum (TI): 0 = cecum distension without TI reflux; 1 = cecum distension with TI reflux; 2 = absence of cecum distension with TI reflux. Cecum/right-colon distention (grade 0 or 1) was perceived by the patients whereas the right colon irrigation with complete ICV incontinence (grade 2) was symptomless. ICV continence associated with LS (p ≤ 0.0001). A histologic diagnosis of non-alcoholic steatohepatitis was confirmed in a 35-year-old obese male with SIBO and LS > 8 kPa (8.7/8.5 kPa by SWE/TE):steatosis (grade S3) with hepatocyte ballooning, lobular inflammation (grade 6/8) without fibrosis (stage 0/4, F0). Conclusions: The new US-based approach provides a feasible, easy-to-perform, mini-invasive tool for the diagnosis and grading of ICV incontinence. Preliminary results prompt prospective studies investigating the impact of ICV incontinence as a possible co-factor of steatohepatitis in patients with MASLD. Full article

Low-dose radiation (LDR) has emerged as a promising therapeutic modality for Alzheimer’s Disease (AD). Although different irradiation protocols have been explored, the optimal parameters for maximizing therapeutic efficacy remain unclear. Radiation energy has been shown to influence radiobiological responses, with more pronounced effects at lower energy ranges. We therefore investigated whether kilovoltage LDR (KLDR) provides superior therapeutic efficacy compared with megavoltage LDR (MLDR) in a murine model of AD(3xTg-AD). To this end, we directly compared the efficacy of MLDR and KLDR in AD model mice to identify an optimal irradiation strategy for LDR treatment with potential relevance to clinical translation in AD. X-rays with 110-kV or 6-MV energy were applied to the brain of AD model mice at an early-stage of disease progression (26–28 weeks age; 0.6 Gy × 5 fractions for 2.5 weeks). After LDR treatment, cognitive function was assessed in AD model mice using passive avoidance (PA) test and novel object recognition (NOR) test. In addition, different molecular markers associated with inflammation, amyloid-beta (Aβ) plaques, tau burden, and neuronal and synaptic degeneration were analyzed in the brain of AD model mice. KLDR (110 kV) significantly inhibited cognitive decline in AD model mice, as demonstrated by both the PA and NOR tests. In addition, KLDR significantly reduced hippocampal levels of GFAP, Iba-1, and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), while increasing anti-inflammatory cytokines (TGF-α, TGF-β, and IL-10), and was associated with marked reductions in Aβ and tau levels. Furthermore, the expression levels of Aβ40 and Aβ42 were quantified by ELISA following KLDR and MLDR treatment, revealing a statistically significant reduction in the KLDR group. The degeneration of neurons and synapses was significantly suppressed also at the kilovoltage energy level. Conversely, MLDR (6 MV) exerted minimal effects and did not produce statistically significant improvements. Taken together, our findings demonstrate that radiation energy level is a key determinant of LDR therapeutic efficacy in AD model mice, with KLDR showing significantly greater effectiveness in improving AD-related pathological features than MLDR. Therefore, KLDR may be recommended as a novel radiation protocol for AD treatment. Full article

Background/Objectives: This study assessed whether endometriosis is associated with an increased risk of placenta accreta spectrum (PAS) disorders and investigated if assisted reproductive technology (ART) further increases the risk in patients with endometriosis. Methods: This retrospective study used multi-institutional data from the TriNetX database to identify patients who experienced delivery on or before 31 December 2024, with a prior diagnosis of endometriosis and ART therapy, as coded by CPT and ICD-10 codes. The primary outcomes included up to 7-day perinatal results, such as PAS (accreta, increta, percreta), and maternal complications, including peripartum hysterectomy, transfusion, postpartum hemorrhage (PPH), ICU admission, and sepsis. Risk ratios, 95% confidence intervals, and p-values were calculated for endometriosis versus no endometriosis and endometriosis patients with ART versus without ART. Results: Out of 3,487,612 patients identified, 24,341 had a prior diagnosis of endometriosis prior to propensity score matching. Propensity score matching was used to control for age, demographic variables, previous procedures, and comorbidities. Compared to controls, endometriosis was linked to a higher risk of PAS disorders (RR 1.74), including accreta (RR 2.22), increta (RR 2.50), and percreta (RR 1.59). Additional complications included peripartum hysterectomy (RR 1.72), transfusion (RR 1.26), PPH (RR 1.35), ICU admission (RR 1.43), and sepsis (RR 1.56). Patients conceived via ART faced greater risks of PAS disorders (RR 2.00), accreta (RR 2.14), hysterectomy (RR 1.63), transfusion (RR 2.10), and PPH (RR 1.66). Conclusions: This study shows a positive link between endometriosis and the risk of PAS disorders and maternal complications, and the use of ART in patients with endometriosis further increases this risk, emphasizing the importance of comprehensive counseling and a multidisciplinary approach to delivery planning for this high-risk group. Full article

Autonomous driving systems (ADSs) are reliable only when heterogeneous sensors, estimation algorithms, and safety mechanisms are engineered as a single coherent safety-critical measurement system rather than as loosely coupled modules. Production stacks integrate cameras, LiDAR, automotive radar, and GNSS/IMU, yet deployment remains constrained by modality-specific failure modes, calibration and synchronization drift, and out-of-distribution (OOD) conditions that violate modeling assumptions. These limitations induce overconfidence and downstream decision errors whenever planning assumes certainty sharper than sensing can justify. This survey introduces a sensor-centric framework linking measurement physics, uncertainty propagation, fusion integrity, safety assurance, and risk-aware planning and control. We formalize what each modality physically measures; unify probabilistic, evidential, and conformal uncertainty representations; analyze filtering, factor-graph, BEV, transformer, and state-space fusion architectures with an emphasis on robustness and graceful degradation; and generalize aviation-style integrity concepts (RAIM/ARAIM) to multi-modal autonomy. The distinctive contribution is a single sensor-to-assurance throughline in which every uncertainty representation is tied to its measurement physics, every fusion architecture is evaluated against an explicit integrity-monitoring requirement generalized from RAIM/ARAIM, and every safety-standard clause is mapped to a concrete architectural mechanism. We map these mechanisms onto ISO 26262, ISO 21448 (SOTIF), ISO/PAS 8800, ANSI/UL 4600, and the UNECE framework, and connect perception uncertainty to decision-making through chance-constrained MPC and formal safety filters (RSS, CBF). Industry case studies and emerging V2X and generative-simulation approaches close the loop to deployable safety arguments. Full article

Background/Objectives: Accurate evaluation of knee osteoarthritis (KOA) severity is critical for optimal patient care, yet manual radiographic grading remains subject to observer variability. This study aims to evaluate the performance of a fine-tuned contrastive language–image pre-training (CLIP) framework designed to assist clinicians in grading KOA severity in plain radiographs using the Kellgren–Lawrence (KL) classification system (Grades 0–4). Methods: The model operates by projecting visual features from radiographs and standard textual clinical descriptions into a shared embedding space. Training was conducted using 8260 posterior–anterior (PA) fixed-flexion X-ray images from the Osteoarthritis Initiative (OAI) dataset. For robust external evaluation across distinct data distributions, the model was tested on an independent dataset consisting of 1650 plain radiographs. Results: When evaluated on the external validation dataset, the fine-tuned CLIP model achieved an accuracy of 76.94% and an F1-score of 76.66%. Comparative analysis demonstrates that these aligned vision-language representations provide competitive, stable diagnostic capabilities even when applied to an entirely independent data distribution. Conclusions: Fine-tuned CLIP architectures offer a viable and valuable foundation for semantically transparent, computer-aided evaluation of KOA. Full article

Neuropathic pain is a debilitating condition lacking objective and quantitative assessment tools, as current evaluations rely largely on subjective reports. Hyperspectral imaging (HSI) is a non-invasive technology that quantifies spatial and spectral tissue characteristics and has been applied in rheumatologic and metabolic disorders. This study investigated whether HSI-detected paw skin alterations correlate with graded nerve injury severity in a chronic constriction injury (CCI) model. Sprague–Dawley rats were assigned to sham or CCI groups with one to four sciatic nerve ligatures. Behavioral assessments (CatWalk XT gait analysis, thermal hyperalgesia, and mechanical allodynia) and paw HSI measurements were performed longitudinally. Histological and molecular analyses were conducted from paw skin to dorsal spinal cord tissues. At 1100 nm, HSI demonstrated progressive and significant spectral deviations proportional to injury severity across all CCI groups, whereas 1300 nm changes were only detected in severe injuries. Histology revealed increased fibrosis, NGF, TNF-α, synaptophysin, and microglial activation with greater injury severity, alongside reduced PGP9.5, neurofilament, AChR, Desmin, GAP-43, Pax3, and BDNF expression. These molecular findings were supported by electrophysiological and behavioral impairments, which correlated with injury grade by HSI. In conclusion, HSI at 1100 nm provides a sensitive and objective indicator of neuropathic pain severity and holds promise as a quantitative translational tool. Full article

Selective laser sintering (SLS) enables the fabrication of polymer components with intricate geometries; however, surface roughness remains a concern that affects performance and quality. This study systematically examines the influence of build orientation (X, Y, Z) and part location (inner, middle, outer) on surface roughness of Polyamide 12 (PA12) components. The results show that components built in the Y orientation and placed in the inner chamber exhibited the lowest surface roughness (Sa = 9.88 ± 0.16 µm). In contrast, Z-oriented components at the outer edge showed the highest (Sa = 11.49 ± 0.27 µm), indicating a 10.13% variation. SEM analysis showed smoother morphology and reduced porosity in the inner regions, while DSC confirmed higher crystallinity in samples with improved finish. These findings highlight the role of thermal stability and spatial positioning within the build chamber in controlling surface characteristics, emphasizing the importance of orientation and placement strategies for improving the quality of PA12 components fabricated by SLS. Full article

Background: Vector-borne diseases (VBDs) caused by Borrelia spp., Bartonella spp., and Babesia spp. are associated with neuropsychiatric morbidity. Cerebral folate deficiency (CFD), primarily caused by folate receptor-α autoantibodies (FRAAs) impairing folate blood–brain barrier transport, is a treatable contributor to neurodevelopmental disorders including pediatric acute-onset neuropsychiatric syndrome (PANS) and autism spectrum disorder. Despite overlapping clinical manifestations, FRAA prevalence in VBD populations has not been investigated. This study aimed to determine the prevalence of FRAA in patients with confirmed VBDs. Methods: This retrospective cohort study included 68 VBD-positive patients with and without PANS evaluated at a single clinical practice. VBD testing was performed by IGeneX Laboratories; FRAA analysis including binding, blocking, and soluble folate receptor (sFR) testing was performed by Religen Laboratories (Plymouth Meeting, PA). Statistical associations were assessed using Fisher’s exact test with Wilson 95% confidence intervals. Results: Of the 68 VBD-positive patients, 42 (61.8%; 95% CI: 49.9–72.4%) were also FRAA-positive. Soluble folate receptor (sFR) was detected in eight patients (11.8%; 95% CI: 6.1–21.5%), all of whom were binding FRAA-positive, with 87.5% carrying confirmed evidence of Borrelia species infection. Neuropsychiatric symptoms were highly prevalent across both groups but did not significantly differentiate FRAA-positive from FRAA-negative patients (all p > 0.05). Conclusions: This study demonstrates a high prevalence of FRAA in a pediatric VBD cohort. The sFR was strongly associated with Borrelia species infection, suggesting a potential mechanistic link between spirochetal infection and folate receptor autoimmunity. These findings support the consideration of FRAA testing in patients with VBDs and warrant further investigation in larger prospective cohorts. Full article

Junmu No.1 is a commercially important Chinese pig breed, yet stable in vitro models for investigating its muscle development mechanisms and genetic regulation remain lacking; this study aimed to establish an immortalized porcine satellite cell line from Junmu No.1 pigs to address this gap. Primary porcine satellite cells (PSCs) were isolated from a 2-day-old Junmu No.1 piglet and immortalized via lentiviral transduction using the pHAGE-EF1α-eGFP-SV40LT-BleoR vector. The resulting cell line (imPSC-JM) was characterized for morphology, satellite cell marker expression, karyotype stability, myogenic differentiation capacity, and long-term proliferative potential, and RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) was performed to assess transcriptomic fidelity relative to primary PSCs. The imPSC-JM line retained characteristic spindle-shaped satellite cell morphology, consistently expressed PAX7, maintained a normal diploid karyotype (2n = 38, XY), and showed stable SV40 large T antigen expression, enabling sustained proliferation exceeding 100 cumulative population doublings while preserving myogenic differentiation and the formation of multinucleated myotubes expressing Desmin, MYHC, and DMD. Transcriptomic profiles were highly concordant with primary PSCs (Pearson r ≥ 0.95; R² = 0.9188; 83.8% of expressed genes unchanged), with key satellite-cell and myogenic regulator genes (PAX7, MYOD1, MYF5, MYOG, MYF6) unaltered, while GSEA revealed upregulation of autophagy and inflammatory signaling and downregulation of ribosome biogenesis. The imPSC-JM line thus provides a reliable experimental platform with high transcriptomic fidelity for studying muscle development and genetic regulation in Junmu No.1 pigs. Full article

Rhabdomyosarcoma (RMS) confined to the bone marrow represents an exceptionally rare and aggressive presentation that can mimic primary hematological malignancies, often leading to diagnostic delays and therapeutic challenges. We report the case of a 34-year-old woman who presented with clinical and laboratory findings highly suggestive of a hematological disorder, including cytopenias and diffuse bone marrow involvement. Initial evaluation raised suspicion for leukemia; however, comprehensive diagnostic work-up, including immunohistochemistry and molecular studies, ultimately confirmed the diagnosis of PAX3/FOXO1 gene-rearranged alveolar RMS isolated in the bone marrow, with no identifiable primary soft tissue mass. The patient was treated with an intensive multi-agent chemotherapy regimen, resulting in a marked hematological recovery and a significant radiological improvement after a limited number of cycles. We further reviewed the limited literature on bone-marrow-confined RMS, highlighting the proposed pathophysiological mechanisms, diagnostic pitfalls, and reported treatment strategies. Given the absence of standardized management guidelines for this rare entity, therapeutic approaches are often extrapolated from conventional RMS protocols or regimens used for high-grade sarcomas. Our experience supports the potential efficacy of intensive chemotherapy in achieving meaningful clinical responses. This case report emphasizes the challenges in the diagnosis of RMS confined to the bone marrow due to its atypical presentation. It also highlights the poor prognosis and aggressiveness of this entity compared to conventional RMS. Full article

Background: MEIS proteins are essential homeobox transcription factors that play critical roles in development and have been increasingly implicated in oncogenesis, including breast cancer. Methods: In this study, we identified and characterized novel small-molecule MEIS2 inhibitors through in silico docking targeting the active region of the human MEIS2 homeobox domain. Lead candidates MEISi-2E, MEISi-3, and MEISi-4 were identified with binding energies ranging from −3.0 to −3.90 kcal/mol. The inhibitory potential of these molecules was validated in vitro using a species-conserved MEIS-Luciferase Reporter construct containing the TGACAG targeted locus. Results: Our results demonstrate that MEISi-2E, MEISi-3, and MEISi-4 significantly suppress MEIS-driven luciferase activity and downregulate the expression of Meis1, Meis2, and downstream genes such as IL17RB, CDH1, EGR2, PAX6, and SERPINE1 while upregulating negative regulator TGIF1 and SOX3. In breast cancer cell lines, these inhibitors exhibited potent growth inhibition, with MEISi-3 showing an exceptional IC50 as low as 0.1 μM in SK-BR-3 cells. Mechanistic studies using flow cytometry revealed that these inhibitors induce dose-dependent apoptosis and necrosis. Importantly, the novel inhibitors showed minimal toxicity to healthy human dermal and MRC5 fibroblasts, suggesting a favorable safety profile. Conclusions: These findings establish these small molecules as promising therapeutic candidates for targeting MEIS2-dependent pathways in breast cancer. Full article

Risk stratification of thyroid nodules is mainly based on ultrasound examination and fine-needle aspiration (FNA) cytology findings. Molecular testing has increasingly been added to the workup to improve risk of malignancy (ROM) estimation. Here, we evaluated the diagnostic performance of alterations in seven genes, including point mutations in BRAF, HRAS, KRAS, and NRAS as well as RET/PTC1, RET/PTC3, and PAX8/PPARγ fusions in 849 FNA samples with cytopathologically indeterminate Bethesda categories (III, IV, and V). In 20.14% of samples, at least one gene alteration was detected, with NRAS mutations and the BRAF V600E variant occurring most frequently. For 636 of the thyroid nodules, surgical follow-up was available, with a malignancy rate of 22.64%. BRAF V600E mutations and RET/PTC1 fusions were associated with a ROM of 100%, RAS mutations with 13.64%, and PAX8/PPARγ fusions with 60.00%. Depending on the Bethesda category, the positive predictive value for malignancy of the seven-gene panel ranged between 18.18% (Bethesda III) and 91.07% (Bethesda V), while the negative predictive value ranged between 93.92% (Bethesda III) and 24.14% (Bethesda V). In conclusion, molecular testing with the seven-gene panel can improve ROM estimation in cytopathologically indeterminate thyroid nodules, but its clinical utility depends on the detected gene alteration. Full article

Nervous system and corneal disorders are major causes of permanent disability worldwide, largely due to the limited regenerative capacity of ectoderm-derived tissues. Therefore, the development of accessible and ethically acceptable cell-based therapies promoting the repair and regeneration of these tissues is of considerable translational importance. In this study, we aimed to comparatively evaluate the ectodermal differentiation potential of human adipose-derived stem cells (ADSCs) and human amniotic epithelial cells (hAECs) in vitro, with hAECs serving as a reference cell population with established ectodermal plasticity. Primary ADSCs and hAECs were characterized phenotypically using flow cytometry and functional differentiation assays. Cells were subjected to a directed ectodermal differentiation protocol and assessed via morphological analysis, immunostaining for ectoderm-associated proteins, and RT-qPCR analysis of lineage-specific genes. ADSCs exhibited morphological changes following differentiation, including a more epithelial-like phenotype and an increased nucleus-to-cytoplasm ratio. Immunostaining revealed the induction of nestin and OTX2 expression after differentiation, which was particularly pronounced in ADSCs. Gene expression analysis demonstrated statistically significant upregulation of the ectoderm-related genes EN2, SOX1, and PAX6 exclusively in hAECs. Results suggest that in ADSCs the differentiation process was only partially activated. In conclusion, our findings further support the suitability of hAECs as a reference cell line for studies investigating ectodermal differentiation protocols, while also demonstrating that ADSCs exhibit a limited but detectable capacity for acquiring ectoderm-specific characteristics under defined in vitro culture conditions. Full article

Canine atopic dermatitis (AD) is a common allergic skin disease for which identifying allergen sensitization via IgE serological or intradermal testing is necessary to implement allergen-specific immunotherapy. Because serum IgE has a short half-life and circulating levels fluctuate with environmental allergen exposure, the timing of blood sampling may influence serological test outcomes. This cross-sectional study assessed seasonal variation in allergen-specific IgE concentrations and seropositivity rates across pollen and mite allergen categories in Scandinavian dogs suspected of allergic disease. PAX multiplex macroarray results from 5014 canine sera submitted by veterinarians across Denmark, Norway, and Sweden over one full year were retrospectively analyzed for 17 allergens, including tree, grass, and weed pollens, house dust mites, and storage mites. Mean sIgE levels showed statistically significant but relatively small seasonal variation. Seropositivity rates, however, showed clearer patterns: seropositivity for tree and weed pollen was highest in spring and summer, and that for house dust mite peaked in autumn and winter, while storage mite sensitization rates showed the opposite trend. These results confirm that IgE serological test results in dogs are affected by the sampling season and emphasize the importance of considering timing when collecting and interpreting IgE serological tests in atopic dogs. Full article

Background/Objectives: Keratoconus is a corneal disorder that causes thinning and bulging of the cornea, resulting in astigmatism and other refractive errors. Mechanical effects and environmental factors are known to exacerbate the disease, and genetic predisposition plays a significant role in its development. Methods: This study investigated the presence of genetic variants in 32 keratoconus patients. We used a next-generation sequencing-based method, and variant interpretation was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Variants were prioritized based on multiple criteria, including population frequency data from the Genome Aggregation Database (gnomAD) (minor allele frequency < 1%), variant type and predicted functional effect, gene–disease association, inheritance pattern, phenotypic relevance, and in silico prediction tools. Results: Thirteen variants were identified in 11 patients (34.3%). Two patients carried variants in two different genes, raising the possibility of oligogenic contributions. Ten variants (76.9%) were novel. The variants were detected in 12 genes, namely ADAMTS18, BEST1, CHST6, COL17A1, CYP1B1, KRT3, PAX6, SLC4A11, TACSTD2, UBIAD1, VSX1, and ZNF469. No association was observed between detected variants and patient age. Conclusions: Our findings demonstrate a substantial proportion of novel variants and support the genetic heterogeneity of keratoconus, while also raising the possibility of oligogenic contributions in a subset of patients. Full article