Resistive electrodes are a critical component of Micro-Pattern Gaseous Detectors (MPGDs) for dealing with discharges. This study introduces an advanced approach using germanium (Ge) thin films as resistive anodes in MPGDs. The Ge films are fabricated via vacuum thermal evaporation, which enables the production of large-area and uniform on rigid substrates. Characterization confirms the film stability for over 700 days, which is attributed to surface passivation. It also reveals an inverse correlation between resistivity and temperature. Micromegas detectors equipped with Ge resistive anodes achieve high gain, low spark rate and high rate capability. These results validate Ge-film resistive anodes as a reliable and scalable technology for improving the performance and stability of MPGDs in future particle physics experiments.

Neurobiological effects assessment in wild rodents exposed to mercury in Sierra Gorda Biosphere Reserve, Querétaro, Mexico.

There is currently no validated instrument in Brazil specifically designed to assess the quality of life (QoL) of patients with ureteral stones. The Cambridge Ureteral Stone Patient-Reported Outcome Measure (CUSP) is a self-administered questionnaire that evaluates the QoL impact of ureteral stones over the preceding seven days. This study aimed to translate, culturally adapt, and validate the CUSP for Brazilian Portuguese (Br-CUSP) for clinical and research applications. The CUSP questionnaire was translated into Portuguese according to Guillemin's cross-cultural adaption guidelines. Patients with and without ureterolithiasis completed both the Br-CUSP and SF-12 questionnaires. Psychometric validation included assessment of internal consistency, test-retest reliability, convergent validity, and discriminant validity. A total of 156 participants completed both questionnaires. No inconsistencies emerged during univariate analysis. Confirmatory factor analysis supported the six-factor model with satisfactory fit indices. All factor loadings exceeded 0.50. Internal consistency was high across all domains (Cronbach's α = 0.72 - 0.98; McDonald's ω = 0.73 - 0.98). Test-retest reliability demonstrated strong temporal stability. Inter-domain correlations (Spearman's p = 0.45 - 0.82) supported structural coherence. Convergent validity was confirmed through inverse correlations with SF-12 scores. Discriminant validity was demonstrated by significant score differences between patients with and without ureteral stone, with large effect sizes. The Brazilian Cambridge Ureteral Stone Patient-Reported Outcome Measure is a valid, reliable tool for assessing health-related quality of life in Brazilian patients with ureteral stones. Its implementation can enhance both clinical assessment and research into patient-centered outcomes in urolithiasis.

Prevalence, incidence and mortality of interstitial lung disease in patients with Sjogren disease: data from the prospective observational "EMERGE" study.

Microbial metabolite deoxycholic acid inhibits noncancerous NCM460 human colon cell proliferation: an inverse correlation between Bmal1:Clock gene expression and cell apoptosis.

Polystyrene microplastics at environmentally realistic concentrations exacerbate diatom blooms caused by phosphorus pollution: Rethinking coastal eutrophication.

Legal age estimation using developing mandibular third molar roots of various developmental stages in Malaysian population: a CBCT study.

Synovial exosomal type II collagen as a biomarker for osteoarthritis Progression: From molecular evaluation to AI-powered SERS-based diagnosis.

The distribution of healthcare workforces relative to population ill health in England: Repeated cross-sectional analysis of Census data 2001-2021.

Accurate lesion volume estimation is essential for reliable voxel-based dosimetry in Lu-177 radionuclide therapy. Conventional fixed-threshold segmentation-particularly the commonly used 40% threshold-can markedly underestimate small lesions due to partial volume effects, leading to substantial errors in quantitative SPECT-based dosimetry. This study systematically evaluated the relationship between lesion size and optimal threshold values in Lu-177 SPECT/CT imaging, quantified deviations introduced by the fixed 40% threshold, and established size-specific adaptive thresholds to improve segmentation and activity recovery accuracy. A NEMA IEC body phantom with six spherical inserts (0.52-26.5 cm³) was filled with 20 mCi (740 MBq) Lu-177 at an 8 : 1 lesion-to-background ratio. SPECT/CT data were acquired using 60-90 projections with 10-20 s per frame. Images were reconstructed under 180 parameter combinations varying iterations, subsets, and filters. For each sphere, segmentation was performed using the fixed 40% threshold (40%ThS) and an adaptive, volume-matched threshold (AV%ThS) that reproduced the true physical volume. Optimal thresholds showed a strong inverse correlation with lesion size, decreasing from ~83% (1.15 cm³) to ~42% (26.5 cm³). The fixed 40% threshold substantially underestimated volumes less than 25 cm³, with quantitative deviations reaching 45% compared to AV%ThS. Best quantitative recovery was achieved with 90 projections × 20 s and OSEM 10 × 10 iterations/subsets with Butterworth filtering (0.45 cycles/cm, order 10). A single fixed threshold is insufficient for accurate Lu-177 SPECT/CT dosimetry across diverse lesion sizes. Size-adaptive thresholding combined with optimized reconstruction parameters improves lesion delineation, enhances quantitative accuracy, and reduces dosimetric uncertainty in clinical practice.

Background: Rapid assessment of intravascular volume is crucial and critical in pediatric shock. Invasive monitoring is often impractical, highlighting the need for reliable non-invasive bedside tools such as the inferior vena cava collapsibility index (IVC-CI). Aims and Objectives: The aims and objectives of the study are to evaluate the association between serial, timely measurements of the IVC-CI and early clinical improvement following fluid resuscitation in children presenting with volume-depleted or mixed shock. Materials and Methods: This descriptive longitudinal study included 31 children aged 1 month to 12 years presenting with clinical features of volume depletion, irrespective of underlying etiology. Serial clinical assessments and ultrasonographic IVC-CI measurements were obtained at 4-h intervals for 24 h after initiation of fluid resuscitation. A composite clinical improvement score was used as the primary outcome. Data were analyzed using the Wilcoxon signed-rank test, Pearson’s Chi-square test, and Spearman’s rank correlation. Results: Baseline IVC-CI was elevated (mean 63.4%), indicating intravascular volume depletion. Following fluid resuscitation, clinical parameters and urine output improved significantly (P<0.001). IVC-CI decreased within the first 4 h and showed a strong inverse correlation with clinical improvement (ρ=–0.752, P<0.001), which diminished after 12 h as euvolemia was achieved. Conclusion: Serial measurement of the IVC-CI reflects changes in intravascular volume during early fluid resuscitation and is significantly associated with early clinical improvement in children with volume-depleted or mixed shock. It may serve as a useful non-invasive adjunct during initial resuscitation.

An emerging machine learning-optimized MIP-ECL platform for ultrasensitive and selective detection of 5-hydroxytryptamine.

The association between folate metabolism abnormalities and the development of colorectal cancer (CRC) remains controversial. Here, we report that the folate exerts a tumor-suppressive role in CRC; however, the manifestation of this effect is restricted by the expression level of folate transporter SLC46A1 in CRC cells. Multi-cohort profiling revealed significant downregulation of SLC46A1 in CRC tissues compared to adjacent normal tissues, where low expression independently predicted poor overall survival. Functional studies demonstrated that SLC46A1-mediated folate uptake suppressed tumor proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, SLC46A1 deficiency restricted intracellular folate availability and impaired cellular methylation potential, as evidenced by a reduced SAM/SAH ratio, leading to DNA hypomethylation at specific sites such as the FOS proto-oncogene promoter. This epigenetic reprogramming triggers transcriptional activation of key oncogenic effectors CCND1, BCL2, and PLAU involved in CRC progression. Clinically, we found a significant inverse correlation between SLC46A1 expression and folate levels in tumor interstitial fluids of CRC, suggesting impaired folate uptake in low SLC46A1 tumors. Multi-color immunofluorescence across two cohorts further demonstrated conserved inverse associations between SLC46A1 and FOS expression in primary tumors and metastatic lesions. This study elucidates the molecular mechanism by which folate inhibits CRC progression through the "SLC46A1-epigenetic-transcriptional regulation" axis, providing mechanistic insights into folate deficiency-driven CRC progression and biomarkers for precision CRC intervention.This study elucidates the tumor-suppressive role of the folate transporter SLC46A1 in CRC. In normal cells, SLC46A1 facilitates folate uptake, supporting one-carbon metabolism and maintaining genomic stability. In CRC, however, SLC46A1 downregulation induces intracellular folate deficiency, triggering locus-specific DNA hypomethylation at the FOS promoter, which activates oncogenic transcription of key downstream effectors (CCND1, BCL2, PLAU), driving tumor progression. The graphical abstract illustrates the differential impact of SLC46A1 on folate metabolism and gene expression in normal versus tumor cells, highlighting its potential as a therapeutic target in CRC.

Rapid urine screening and staging of chronic kidney disease via NAD(P)H-activated dual-salt fluorescent probe.

Abstract Background The National Amyloidosis Centre (NAC) and the Columbia Classifications are used to categorize the severity and progression of cardiac amyloidosis. Recent studies indicated that myocardial involvement initially occurs at the atrial level, preceding the manifestation of standard echocardiographic alterations. Understanding how the currently approved clinical classifications correlate with other parameters is pivotal to better define the disease burden at the onset of its manifestation. Purpose To verify the correlation between the two Classifications and other parameters for amyloidotic burden estimation, with a focus on advanced echocardiography techniques (Global Longitudinal Strain, GLS; Peak Atrial Longitudinal Strain, PALS; Peak Atrial Contraction Strain, PACS). Methods A population of 96 patients (age 76.9; 50-91, SD ± 9.2) affected by cardiac amyloidosis was selected: 58 Transthyretin-related Amyloidosis (ATTR), 38 Light-Chain Amyloidosis (AL). Each patient was classified according to both NAC and Columbia systems. Then, NAC and Columbia classifications were correlated with various parameters. The Pearson's correlation was applied to clinical and echocardiographic measurements, such us functional capacity (measured by the 6-min walk test; 6MWT), standard echocardiographic techniques and advanced echocardiographic techniques, including atrial strain (PALS and PACS) and left ventricular strain (GLS). Results The NAC classification shows a positive correlation with the NYHA class (NAC-NYHA, r²=0.281, p£0.005; Columbia-NYHA, r²=0.648, p£0.001), indicating a worsening of the perceived symptoms (NYHA) by patients with increasing NAC class. Both the classifications show a positive correlation with the GLS (NAC-GLS, r²=0.245, p£0.005; Columbia-GLS, r²=0.384, p£0.001), indicating a deterioration of GLS which increases at the worsening of NAC and Columbia classes. Both systems also show a negative correlation with Left Ventricular Ejection Fraction (LVEF; NAC-LVEF, r²=-0.368, p£0.001; Columbia-LVEF, r²=-0.379, p£0.001) and Peak Atrial Longitudinal Strain (PALS; NAC-PALS, r²= -0.255, p£0.005; Columbia-PALS, r²=-0.398, p£0.001), demonstrating a reduction in LVEF and atrial strain with the increasing of NAC and Columbia systems. The latter shows also an inverse correlation with the 6-Min Walk tTest (6MWT; r²-0.472, p£0.001) and a positive correlation with the presence of B-lines on chest ultrasound (r²=0.360, p£0.05). Conclusions The integration between NAC and Columbia values with PALS and GLS can be used to personalize and monitor the therapy over time. The early atrial involvement could be pivotal for developing a new classification that integrates the parameters considered here. Such a classification could assist clinicians in appropriately titrating diuretic therapy, determining the optimal timing for initiating treatment with disease modifier treatments before significant cardiac involvement occurs.

Asprosin-driven metabolic-epigenetic rewiring attenuates mesenchymal stem cell senescence with therapeutic benefits for infarcted hearts.

Introduction: Vitamin D deficiency has emerged as a global health concern with potential implications for metabolic health, particularly insulin resistance—a key precursor to type 2 diabetes and metabolic syndrome. Despite extensive research, the nature, strength, and causality of this association remain debated due to heterogeneous methodologies and conflicting intervention outcomes. Methods: This comprehensive systematic review synthesized evidence from 80 studies following rigorous screening and data extraction protocols. Studies were included if they examined the association between vitamin D deficiency (defined by serum 25(OH)D levels) and insulin resistance (assessed via validated methods like HOMA-IR) in adults, excluding those focused solely on supplementation, type 1 diabetes, or pregnancy. Results: The evidence consistently demonstrates a significant inverse association between vitamin D status and insulin resistance across diverse populations. Observational studies showed weak to moderate inverse correlations (r ranging from -0.134 to -0.631), with stronger associations in diabetic (pooled r ≈ -0.255) versus non-diabetic populations (pooled r ≈ -0.073) (Rafiq & Jeppesen, 2021; Alshahrani et al., 2025). Meta-analyses confirmed that higher vitamin D levels are associated with a reduced risk of type 2 diabetes (RR = 0.65) and prediabetes (RR = 0.49) (Mohammadi et al., 2021). The association was notably amplified by obesity, with correlations strengthening from r = -0.150 in normal-weight individuals to r = -0.257 in obese individuals (Rafiq & Jeppesen, 2021). However, RCTs on vitamin D supplementation yielded mixed results; while some showed improvement in insulin resistance, particularly in those with baseline glucose intolerance, others reported no significant effect in healthy or normoglycemic individuals (Mitri et al., 2011; von Hurst et al., 2009; Grimnes et al., 2011). Discussion: The relationship between vitamin D deficiency and insulin resistance is complex and modified by factors such as baseline metabolic status, BMI, and ethnicity. The discordance between strong observational associations and inconsistent interventional findings suggests that vitamin D status may be a marker of overall metabolic health and adiposity rather than a directly modifiable causal factor in all populations. Mechanistic pathways—including effects on pancreatic β-cell function, insulin receptor expression, and systemic inflammation—provide biological plausibility but underscore the influence of confounding variables. Conclusion: Vitamin D deficiency is consistently associated with a higher prevalence and severity of insulin resistance, particularly in individuals with obesity, prediabetes, or established type 2 diabetes. Maintaining adequate vitamin D status should be considered a component of metabolic health strategy. Supplementation may offer the greatest benefit for those with documented deficiency coupled with existing metabolic dysfunction, rather than as a universal preventive measure for insulin resistance.

The global rise of colistin-resistant Acinetobacter baumannii (CRAB) is a critical health threat, particularly in the Middle East. The pmrB c.235T > A (p.Leu79Ile) mutation is frequently observed in clinical isolates, but its comprehensive characterization is lacking. In this multicenter study, 465 clinical A. baumannii isolates were collected from Iran (n = 378) and Iraq (n = 87) between January 2023 and June 2024. Colistin susceptibility was determined by broth microdilution, and the pmrCAB operon was sequenced. The structural impact of p.Leu79Ile was assessed via 200-ns molecular dynamics simulations. Functional consequences were evaluated using lipid A profiling, biofilm assays, serum resistance, and a murine pneumonia model. Phylogeographic analysis and a LASSO-regularized logistic regression model for 30-day mortality prediction were performed. Colistin resistance was detected in 47.8% of isolates, with 94.2% of resistant isolates harboring pmrCAB mutations; c.235T > A was predominant (76.8%). Simulations indicated that Leu79Ile stabilizes the active conformation of PmrB (ΔΔG = -3.8 kcal/mol), increasing the root mean square deviation (RMSD; 4.7 Å vs. 2.3 Å) and altering protein dynamics. This correlated with a 1.93-fold increase in pEtN-modified lipid A and a strong inverse correlation with colistin MIC (ρ = -0.89). Mutant isolates exhibited enhanced biofilm formation (2.3-fold), serum survival (47.6% increase), and murine mortality (70% vs. 30%). Phylogenetics identified a dominant ST848-bla ~ OXA-23~^+^ clone emerging around 2016 (95% HPD: 2015–2017), with evidence of Iran-Iraq cross-border transmission. The mortality prediction model (predictors: age > 65, CCI > 3, ventilation, shock, c.235T > A, ST848) achieved an AUC = 0.87 in validation. This study suggests the pmrB c.235T > A mutation confers a dual phenotype of colistin resistance and hypervirulence, driven by structural stabilization of PmrB within an expanding regional clone.

Pathogenic variants in γ-aminobutyric acid type A (GABAA) receptor genes have been associated with a wide spectrum of neurological disorders. We aimed to delineate the clinical trajectories associated with gain-of-function (GoF) and loss-of-function (LoF) variants in GABRB2 and GABRB3, and to develop a risk-prediction model for gross motor dysfunction based on age at seizure onset. Clinical data, including seizure onset, epilepsy syndromes, cognitive outcomes, and gross motor function classification system (GMFCS), were collected through direct interviews, physician reports, and literature review. Kruskal-Wallis, Mantel-Cox and non-parametric analysis of variance (ANOVA) with Dunn's corrected post hoc tests were used for statistical comparisons. A logistic ordinal regression model was developed to predict GMFCS outcomes based on age at seizure onset. We analyzed a cohort of 117 individuals with pathogenic GABRB2 (n = 49) and GABRB3 (n = 68) variants. Fifty-three individuals carried GoF variants and 64 carried LoF variants. The GoF group was associated with earlier seizure onset, higher seizure frequency, and lower rates of seizure freedom. Gross motor dysfunction was markedly worse in the GoF group, with 64% classified as GMFCS IV or V (non-ambulation), compared to 7.5% in the LoF group. An inverse correlation was found between age at seizure onset and GMFCS severity in the GoF, but not the LOF group. The risk model predicted a >90% likelihood of non-ambulation for individuals with GoF variants and seizure onset before 1 month of age, decreasing to ~35% with seizure onset after 20 months. We found a clear genotype-phenotype correlation in GABRB2- and GABRB3-related disorders, demonstrating that GoF variants are associated with a more severe neurodevelopmental trajectory. The age at seizure onset serves as a biomarker for predicting motor outcomes in individuals with GoF variants. These findings provide guidance regarding prognosis, need for early intervention, and data for comparison of efficacy in targeted therapeutic interventions for GABAA receptor-related disorders.

The sulfur-containing volatile organic compounds (VOSCs) have a pronounced potential to impact the atmosphere. Hence, studying their photooxidation reactions with tropospheric oxidants has substantial relevance. Allyl methyl sulfide (AMS), which falls under this category, is found to be released from various sources. Hence, the present study explored the kinetics of AMS + OH and AMS + Cl reactions over 283-363 K, employing both experimental and computational methodologies. Pulsed laser photolysis─laser-induced fluorescence (PLP-LIF) technique was utilized to determine the rate coefficients of the AMS+OH reaction, whereas the kinetics of the AMS + Cl reaction were assessed using the relative rate (RR) technique, aided by gas chromatography with a flame ionization detector (GC-FID). The reaction products formed during the oxygen-assisted AMS + Cl reaction were separated and identified by gas chromatography-mass spectrometry (GC-MS). The Arrhenius expressions determined using experimental methodologies include kAMS+OH(283-363 K) = (3.28 ± 1.07) × 10-12 exp{(534 ± 104)/T} and kAMS+Cl(283-363 K) = (9.14 ± 1.34) × 10-11 exp{(426 ± 47)/T} cm3 molecule-1 s-1. Computational studies were performed to complement the experimental findings and confirmed the addition pathways as the major pathways in both reactions. An inverse correlation with the temperature was observed for the rate coefficients of AMS + OH and AMS + Cl reactions. At the same time, the AMS + OH reaction kinetics were found to be independent of the pressure, and a positive correlation with the pressure was revealed for the AMS + Cl reaction. Sulfur dioxide, a key product of the AMS+Cl reaction, can lead to various atmospheric issues that can cause serious human health problems.