Search Results (4,464)

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR-E) is a severe autoimmune encephalitis that predominantly affects young women and is frequently associated with ovarian teratomas. Increasing evidence indicates that these tumors play a central role in disease initiation by providing a peripheral immunological trigger. This comprehensive review summarizes current knowledge on the immunopathogenesis, clinical manifestations, diagnostic approach, therapeutic strategies, and long-term outcomes of ovarian teratoma-associated anti-NMDAR-E. We discuss the unique immunogenic properties of ovarian teratomas, including the presence of neuroglial tissue expressing the GluN1 receptor subunit (formerly known as NR1) of the N-methyl-D-aspartate receptor (NMDAR), dense immune cell infiltrates, and tertiary lymphoid structure-like formations that support local antibody production. These features are thought to promote molecular mimicry and loss of immune tolerance, leading to B-cell activation, intrathecal antibody synthesis, and antibody-mediated neuronal dysfunction. Furthermore, we review the characteristic multistage clinical course, key diagnostic findings in cerebrospinal fluid, imaging and electrophysiology, and the importance of early tumor removal combined with immunotherapy. Emerging therapeutic approaches and experimental models that provide insight into disease mechanisms and novel treatment targets are also highlighted. An improved understanding of tumor-driven neuroimmunological interactions is essential for earlier diagnosis, optimized treatment strategies, and better long-term outcomes in affected patients. Full article

Background/Objectives: Benzodiazepine (BZD) withdrawal is frequently associated with altered emotional reactivity and behavior. Given the higher prevalence of anxiety disorders and the more frequent use of BZDs among women, understanding the neurobiology of BZD withdrawal in females is particularly important as it remains elusive. Methods: Adult female Wistar rats received 8 days of chronic, escalating-dose alprazolam (ALP) treatment followed by spontaneous withdrawal assessed at 36 h and 96 h from the last dose. Behavioral assessment was performed using the Open Field Test. Synaptic protein expression was analyzed by Western blot; neurotransmitter and neuromodulator levels were determined using high-performance liquid chromatography (HPLC) and commercial assay kits; and dendritic spine density and morphology were evaluated by Golgi–Cox staining. Results: ALP withdrawal significantly increased levels of anxiety-like behavior while reducing locomotor and exploratory activity. These behavioral changes were accompanied by increased glutamate levels and protein expression of vGluT1, GluR1, NR1, NR2B, and PSD-95, followed by delayed upregulation of EAAT1 and EAAT2. The GABAergic system exhibited heterogeneous remodeling, characterized by increased GAD65, α1-containing GABA_A receptors, and gephyrin, and reduced vGAT expression. Dopamine and serotonin levels remained unchanged, whereas D1 receptor levels were transiently reduced during 36 h withdrawal. The discontinuation of ALP was further associated with temporally selective dendritic spine remodeling, characterized by an early, sustained reduction in branched spine density, a transient increase in filopodia at 36 h, and a reduction in total spine density at 96 h. Conclusions: These findings demonstrate that ALP withdrawal leads to coordinated neurochemical, molecular, and structural remodeling within the amygdala, involving both excitatory and inhibitory synaptic compartments. Full article

Acute inflammatory challenge can impair intestinal barrier function and bile acid homeostasis in weaned piglets. Glutamate serves as an important energy substrate and functional amino acid for intestinal epithelial cells, yet the epitranscriptomic mechanisms underlying its potential protective effects remain poorly defined. This study investigated whether dietary glutamate supplementation is associated with m⁶A-dependent regulation of SLC10A2 and bile acid signaling in weaned piglets subjected to an acute LPS challenge, with supporting validation in IPEC-J2 cells. LPS challenge (100 μg/kg body weight) impaired ileal morphological structure, activated the TLR4/NF-κB signaling pathway, and aggravated intestinal inflammatory responses in piglets. In contrast, glutamate supplementation was associated with restored ileal mucosal morphology, up-regulated expression of intestinal tight junction proteins, and suppressed TLR4/NF-κB pathway activation. Further metabolomic analysis indicated that LPS stimulation and glutamate intervention altered ileal bile acid metabolism: LPS decreased total bile acid (TBA) content in ileal tissue while increasing TBA accumulation in ileal chyme, whereas glutamate treatment partially reversed this pattern, by elevating ileal tissue TBA and reducing chyme TBA, suggesting a facilitatory effect of glutamate on intestinal bile acid reabsorption. Glutamate supplementation was also associated with increased ileal ASBT (SLC10A2) and FXR (NR1H4) expression. The SLC10A2 transcript exhibited detectable m⁶A modification; glutamate supplementation rescued the LPS-induced downregulation of m⁶A demethylases FTO and ALKBH5, which was associated with reduced global and SLC10A2-specific m⁶A modification. In vitro experiments in IPEC-J2 cells suggested that inhibition of FTO or glutamate dehydrogenase attenuated the effects of glutamate on m⁶A modification and SLC10A2 expression, and that YTHDF2 may contribute to the degradation of hyper-m⁶A-modified SLC10A2 mRNA. Glutamate-derived α-KG may serve as a cofactor supporting demethylase expression and activity after LPS stimulation. Collectively, these findings suggest that glutamate may alleviate LPS-induced intestinal inflammation in weaned piglets through a pathway involving α-KG-dependent maintenance of m⁶A demethylase expression, reduced m⁶A modification of SLC10A2, and preserved ASBT/FXR signaling. This study provides evidence for a nutritional–epitranscriptomic axis that may contribute to intestinal protection under acute inflammatory stress. Full article

Background/Objectives: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is a rare autosomal recessive liver disorder caused by mutations in the ATP8B1 gene, leading to defective bile acid secretion and severe clinical outcomes. A milder, episodic form of the disease, benign recurrent intrahepatic cholestasis (BRIC), is also associated with ATP8B1 mutations. PFIC1 patients frequently present with extra-hepatic symptoms. Interestingly, cystic fibrosis (CF) patients also develop liver dysfunction, and we previously showed that CFTR expression is significantly reduced in PFIC1 patients. Methods: In this study, we investigated the relationship between ATP8B1 and CFTR by comparing gene expression and protein maturation in PFIC1 (Byler) and BRIC cell lines to wild-type controls. Results: Both ATP8B1 and CFTR transcripts were markedly decreased in mutant cells, resulting in lower protein synthesis. Distinct ATP8B1 isoforms were identified: a 140 kDa mature form in wild-type cells, a 145 kDa variant in BRIC cells, and a 180 kDa form in PFIC1 cells. Using antibodies targeting the N- and C-terminal domains, we demonstrated that wild-type ATP8B1 undergoes sequential maturation—first at Gly308 in the endoplasmic reticulum, then at Gly556, a region containing the D554N PFIC1 mutation site—yielding a 74 kDa nuclear peptide with transcriptional cofactor characteristics. This peptide contains an NR box flanked by STAT5 binding motifs and a potential PKA phosphorylation site, suggesting interaction with the Small Heterodimer Partner (SHP) and regulation of FXR and HNF1α expression, which are both known to modulate CFTR transcription. Immunoprecipitation experiments revealed a physical association between ATP8B1 and CFTR, supporting a chaperone role for ATP8B1 in CFTR trafficking and membrane insertion. PDZK1 was also found to interact with ATP8B1, potentially stabilizing CFTR at the apical membrane through PDZ-domain interactions. Conclusions: Collectively, our results identify ATP8B1 as a multifunctional protein that not only ensures the correct trafficking and membrane localization of CFTR but should also regulate its transcription via a nuclear signaling pathway. These findings provide new insights into the molecular link between PFIC1 and cystic fibrosis-associated liver disease. Full article

Background: Herniated intervertebral disc (HIVD) with radiculopathy and foot drop can lead to substantial functional impairment. Although both pharmacopuncture and motion-style acupuncture treatment (MSAT) have demonstrated therapeutic potential individually, evidence on their combined use remains limited. In this single-case report, we described the clinical course of a patient with HIVD with radiculopathy and foot drop who underwent a novel approach combining ultrasound (US)-guided Shinbaro 2 pharmacopuncture targeting multiple nerve roots with tibialis anterior muscle motion-style acupuncture treatment (TA MSAT). Case Presentation: A 40-year-old man with lower back pain (LBP), radiculopathy, and foot drop attributed to acute HIVD was treated with high-dose US-guided Shinbaro 2 pharmacopuncture and TA MSAT. Outcomes were measured using the Numeric Rating Scale (NRS) for LBP, L5, and S1 radiculopathy; Manual Muscle Testing (MMT) for dorsiflexion and great toe extension; the Oswestry Disability Index (ODI) for lumbar function; the EuroQol Five-Dimension (EQ-5D) Index for quality of life; and the Patient Global Impression of Change (PGIC) for satisfaction. After 14 weeks of treatment, NRS scores for LBP, L5, and S1 radiculopathy decreased from 5 to 1, 8 to 1, and 8 to 1, respectively. MMT grades for dorsiflexion and great toe extension improved from 3 to 5 and 2 to 5, respectively, indicating full functional recovery. ODI and EQ-5D scores improved from 62.22 to 6.67 and 0.344 to 1.0, respectively. The PGIC score was 1, indicating clinical improvement. Conclusions: Our integrative approach involving US-guided pharmacopuncture and TA MSAT demonstrates therapeutic potential for the management of acute HIVD. Full article

This paper presents a knitted coplanar waveguide (CPW) transmission line for wearable wireless systems operating in the 5G NR n71 band. The line is intended to candidate RF interconnect for future integration into wearable systems covering the n71 downlink band of 617–652 MHz and uplink band of 663–698 MHz. Unlike printed, sewn, embroidered, multilayer, or coaxial textile transmission lines, the proposed CPW structure is formed directly during a single knitting process using only one machine. The line was designed for 50 Ω impedance and experimentally characterized with the use of S-parameter measurements. The results show impedance matching better than |S11| < −15 dB within the investigated frequency range and transmission coefficient |S21| > −2 dB at 600 MHz. These results confirm the feasibility of using knitwear as a functional RF transmission medium for fully textile-integrated sub-GHz 5G wearable communication systems. Full article

Background/Objectives: Subarachnoid analgesia (SA) is increasingly used as an adjunct to general anesthesia in robotic ERAS pathways, but the contribution of the intrathecal local anesthetic, as distinct from that of the intrathecal opioids, has not been isolated. Methods: This study comprised a single-center retrospective cohort of adults undergoing elective robotic surgery (May 2024–July 2025). The exposure was the intrathecal regimen, serving as mutually exclusive categories. The primary outcome was intraoperative opioid exposure (model-derived area under the concentration–time curve per hour, AUC/h); secondary outcomes were standardized intraoperative fluid administration and a stringent pain-free 48 h course (NRS = 0 throughout). Multivariable Gamma and logistic models were supplemented by provider-adjusted mixed-effects analyses, E-values, and a model-free robustness analysis. Results: Of 207 patients, 83.1% received SA; all were given intrathecal morphine and 62.3% levobupivacaine. Compared with no SA, morphine alone was not associated with AUC/h (+14.0%; 95% CI, −0.9 to +31.1), whereas all levobupivacaine-containing regimens were: −36.4% (IM + L5), −24.3% (IM + L5 + S3), and −44.8% (IM + L10 + S3); overall p < 0.001. Algebraically equivalent component reparameterization attributed this to levobupivacaine dose (−44.3% at 5 mg; −59.3% at 10 mg). Remifentanil was used in 98.7%, 88.6%, and 10.0% of patients receiving 0, 5, and 10 mg, respectively. Fluid administration was lower with IM + L5 (−24.9%) and IM + L10 + S3 (−31.0%) after adjustment, but was not with levobupivacaine-graded unadjustment. SA was associated with a pain-free course (adjusted OR, 3.33; 95% CI, 1.06–11.79), an estimate not robust to minimal unmeasured confounding. Conclusions: Levobupivacaine-containing regimens were consistently associated with lower intraoperative opioid exposure, but regimen and opioid strategy were chosen jointly by the same clinician; therefore, these associations between strategies are specific to the delivery context of this study. The fluid and pain-free findings are hypothesis-generating. Trials should vary the local anesthetic dose independently of intrathecal opioids. Full article

Hepatic ischemia–reperfusion injury (HIRI) is not only a common complication of liver transplantation and major hepatic surgery but also a critical determinant of postoperative prognosis. Lactate metabolic reprogramming has been observed in HIRI, yet the role of lactate and its related lactylation in the pathogenesis of HIRI remains unclear. To address this, we integrated single-cell and bulk RNA-seq data with multiple bioinformatic approaches. Five single-cell gene set activity scoring methods (AUCell, UCell, singscore, ssGSEA, and AddModuleScore) were applied to evaluate lactylation activity across cell types, followed by differentially expressed gene (DEG) analysis and high-dimensional Weighted Correlation Network Analysis (hdWGCNA) to identify lactylation-associated genes. Five machine learning algorithms (Random Forest, Boruta, LASSO, GBM, and Decision Tree) were used to screen optimal feature genes, with SHAP analysis further explaining their importance. Bulk RNA sequencing data from the Gene Expression Omnibus (GEO) database were used for validation. Furthermore, NR4A3-related inhibitors were screened using the ChEMBL online tool and assessed by docking and molecular dynamic simulation. We observed significant heterogeneity in lactate metabolism activity across cell types in hepatic ischemia–reperfusion injury (HIRI), with higher activity levels observed for hepatocytes and mononuclear phagocytes. The integration of SHAP and machine learning identified PFKFB3, ZYX, and NR4A3 as closely associated with high lactylation after HIRI, and cross-analysis with bulk RNA data confirmed their consistent upregulation. Candidate gene expression was experimentally validated in a murine liver IRI model through Western blotting and RT-qPCR. Although lactylation has been previously reported in HIRI, this study’s unique contribution is to reveal the cell-type heterogeneity of lactylation-related gene expression at the single-cell level through multi-omics integration and machine learning. The identification of NR4A3, PFKFB3, and ZYX as lactylation-associated regulators proposes novel therapeutic targets for improving graft survival in liver transplantation. Full article

Background: Recovery after hip fragility fracture surgery is heterogeneous. Explainable machine learning (ML) may help identify factors associated with short-term recovery during inpatient rehabilitation. Methods: This retrospective exploratory cohort included 88 patients who underwent surgery at our institution or two outside hospitals and received inpatient rehabilitation at our institution between 2017 and 2019. Improvements at discharge in activities of daily living (ADL), Harris Hip Score (HHS), and numeric rating scale (NRS) pain were defined using clinically established or data-derived thresholds. Admission demographic, clinical, and laboratory variables were analyzed using logistic regression, random forest, and XGBoost with fixed model configurations and class weighting. Model performance was assessed as a secondary feasibility analysis using repeated stratified 5-fold cross-validation (50 splits), corrected resampled t-tests, DeLong’s tests, and McNemar’s tests with Bonferroni correction. TreeSHAP was applied to out-of-fold predictions, and feature stability was evaluated across folds. Results: Discrimination was modest (AUC, 0.52–0.67), without significant between-model differences after correction. Prominent features were blood urea nitrogen, age, hemoglobin, and sodium for ADL; ALT (GPT), cardiovascular comorbidity, blood urea nitrogen, and age for HHS; and DXA, platelet count, sodium, and age for NRS. Stability analyses supported recurring feature associations across cross-validation folds. Conclusions: Explainable ML may be feasible as a hypothesis-generating approach for exploring factors associated with short-term recovery after fragility fracture surgery. Full article

An anthropomorphic patient-derived 3D-printed breast phantom (4.8 cm compressed thickness, 12.2% volumetric breast density) was evaluated for image-quality assessment in contrast-enhanced mammography (CEM). It comprises four 1.2 cm plates printed via fused filament fabrication (PLA/ABS). Five replicates of one of the plates (target) containing a glandular-tissue surrogate and four cavities for iodinated disks with same iodine area density per plate (0.2–0.5–0.75–1.0–1.5 mg/cm²) were fabricated. As a reference, a homogeneous PET-G phantom was printed. CEM images (low-energy (LE), high-energy (HE), and DES) were acquired in three different systems. Iodine signal linearity (mean pixel value, signal difference, signal-difference-to-noise ratio (SdNR)) and background cancellation (residual signals, texture cancellation coefficient (TCC), parameter β from noise power spectrum (1D-NPS)) were estimated. Evaluation across the three systems demonstrated the phantom provides appropriate measurements of iodine signal linearity (R² > 0.986, based on mean values across the four inserts) and background cancellation (TCC:0.04–0.11). Fitting 1D-NPS = αf^−β within 0.25–1.0 mm⁻¹ yielded β values ≈ 3.1–4.0, compatible with the literature, for patient LE and HE images, whereas DES reduced β to ≈1.1. In the homogeneous phantom, β remained invariant between LE and DES images (β ≈ 0.6). The local glandular ratio at each position of the iodinated disks enabled evaluating the impact of background on iodine signal. Full article

Background: Ripretinib, a switch-control kinase inhibitor approved for advanced gastrointestinal stromal tumor (GIST), inhibits primary and secondary KIT and PDGFRA mutations. Real-world data from Western and Middle Eastern populations remain limited. We report outcomes from a molecularly characterized Israeli multicenter cohort. Methods: We conducted a multicenter retrospective cohort study across seven university-affiliated medical centers in Israel. Patients with advanced GIST receiving Ripretinib at any treatment line were eligible. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and response was assessed according to modified RECIST v1.1. Results: Sixteen patients were identified (median age, 67.5 years; 75.0% received Ripretinib in the fourth-line setting). KIT exon 11 mutations were present in 62.5% of patients, including five with secondary resistance mutations involving exon 13 or exons 17/18. Median PFS was 7.0 months (95% CI, 2.0–13.0) and median OS was 14.7 months (95% CI, 4.4–NR). Individual outcomes varied substantially, with PFS ranging from 2.0 to 60.2 months and OS from 2.2 to 60.2 months. Three patients achieved complete responses, with PFS of 20.0, 33.6, and 60.2 months. ORR was 56.3% (CR, n = 3; PR, n = 6) and DCR was 81.3%. No dose reductions or treatment discontinuations due to adverse events were documented; however, adverse events were recorded in only 4 of 16 patients. Conclusions: Ripretinib demonstrated clinical activity in this small, heavily pre-treated cohort. The relatively high ORR and wide variability in outcomes should be interpreted cautiously given the small sample size, retrospective design, and absence of central radiological review. Durable responses were observed in some patients with KIT exon 11 and secondary exon 17/18 mutations, but this exploratory observation does not establish a predictive molecular subgroup. Larger prospective studies with systematic molecular, radiological, and safety assessment are warranted. Full article

Encapsulation for wireless dairy-cattle implants must resist acidic, moisture-rich gastrointestinal conditions while remaining transparent to radio-frequency (RF) signals. This study evaluated vulcanized natural rubber (NR) latex as an intraruminal encapsulant, examining how total solid content (TSC; 30, 40, 50 wt%), stirring duration (24–72 h), and TiO₂ loading affect tensile and tear strength, acidic swelling, dip-coating thickness, and received signal strength indicator (RSSI) at 433 MHz. Multilayer dip-coating produced films 0.25–0.38 mm thick. Tensile strength rose with TSC and stirring (26.6 → 32.2 MPa), whereas tear strength peaked at 40 wt% (31.97 N mm⁻¹). Adding 5 phr (parts per hundred rubber) TiO₂ cut pH-4 swelling ~four-fold (21.1 → 5.25%) with a negligible RSSI penalty, and 3–5 coating layers kept the link well above the −120 dBm sensitivity floor over 5–55 m. The optimum—40 wt% TSC, 72 h stirring, 5 phr TiO₂—best balanced mechanical integrity, swelling resistance, thickness, and wireless performance. Vulcanized NR is therefore a promising bio-based encapsulant under simulated conditions; dielectric characterization, long-term aging, and in vivo validation remain future work. Full article

Objectives: Lumbar vertebral wedge angles reflect vertebral body geometry and may influence lordosis. Whether the total wedge index (TWI) and segmental wedge angles differ between asymptomatic individuals and chronic low back pain (CLBP) patients, and predict lordosis independently of pelvic morphology, remains unclear. Methods: Standing lateral full-spine radiographs from 72 volunteers (49 male; mean age 28.3 ± 7.7 years) and 72 CLBP patients (28 male; mean age 52.0 ± 17.9 years; NRS 4.5 ± 2.2; pain > 3 months) were digitized using a validated quadrilateral vertebral body model. L1–L5 wedge angles and TWI (L1 + L2 + L3 + L4 + L5; negative = net posterior taper) were calculated. Pearson correlations, hierarchical OLS regression, and centile distributions were assessed, following STROBE guidelines. Results: In CLBP, L1 wedge was lower (3.33 ± 4.32° vs. 4.87 ± 3.55°; p = 0.020; d = −0.39) and L5 wedge differed significantly (−6.50 ± 6.32° vs. −8.65 ± 6.30°; p = 0.043; d = +0.34). TWI correlated most strongly with lordosis in volunteers (r = +0.531) and CLBP (r = +0.478; both p < 0.001), and with sacral tilt in both groups. TWI added ΔR² = 0.183 over pelvic morphology (PTPIA) in volunteers and ΔR² = 0.210 in CLBP, where PTPIA alone explained <2% of lordosis variance. L1 wedge was greater in males (5.27 ± 3.64° vs. 2.76 ± 4.03°; p < 0.001; d = 0.67). T4-HA translation did not correlate with wedge variables. In CLBP, L1 and L5 lost lordosis correlations, while L2–L4 remained significant. TWI was the primary structural predictor of lumbar lordosis. Conclusions: In CLBP, the pelvic–lordosis relationship is disrupted, yet TWI remains predictive (ΔR² = +0.210), indicating that vertebral body geometry remains linked to lordosis when pelvic morphology does not. Normative TWI centiles may support radiographic outcome measurement. Full article

Multispectral pan-sharpening aims to fuse high-resolution panchromatic and low-resolution multispectral imagery. However, this process introduces spatial artifacts and spectral distortions. Assessing the quality of fused images remains a fundamental challenge due to the absence of full-resolution ground-truth data. This paper provides a comprehensive review of Image Quality Assessment (IQA) frameworks tailored for pan-sharpened imagery. After overviewing major fusion approaches, including Component Substitution (CS), Multi-Resolution Analysis (MRA), Variational Optimization (VO), and Deep Learning (DL), the review analyzes the evaluation techniques used to benchmark them. It then systematically examines the evolution of evaluation protocols, from classical reference-based metrics relying on Wald’s protocol to full-resolution consistency models and recent no-reference (NR) algorithms. The analysis highlights critical methodological bottlenecks within the field, including unrealistic scale-invariance assumptions in consistency-based metrics, dependence on arbitrary parameters, and severe cross-sensor overfitting in deep learning approaches. Furthermore, the review addresses the mismatch between mathematical fidelity, human visual perception, and practical applicability. Finally, it outlines future research directions, focusing on spatial quality mapping and task-driven assessment protocols that validate fusion efficacy based on its impact on automated remote sensing applications. Full article

This study examined the effects of an eight-week core strengthening exercise program on menstrual pain, menstrual symptoms, and quality of life in sedentary female university students with self-reported primary dysmenorrhea. Sixty female students (age: 21.8 ± 3.4 years) were randomly assigned to a core strengthening exercise group (EG; n = 30) or a control group (CG; n = 30). Pain intensity was assessed using the Numerical Rating Scale (NRS) at baseline (T1), after four weeks (T2) and after eight weeks of intervention (T3). Menstrual symptoms and quality of life were evaluated using the Menstrual Symptom Questionnaire (MSQ) and the WHO Quality of Life–BREF (WHOQOL-BREF), respectively. NRS scores in the EG were significantly lower at T2 and T3 compared with T1 (p < 0.01). The EG showed significant reductions in negative symptoms, pain, management, and total MSQ scores, whereas management and total MSQ scores increased in the CG (p < 0.01). Significant improvements were observed in all WHOQOL domains (physical, psychological, social relationships, and environment) in the EG (p < 0.01). An eight-week core strengthening exercise program may help reduce menstrual pain and symptoms and improve quality of life in female university students with self-reported primary dysmenorrhea. Full article