Patients with inborn errors of immunity (IEI) have high risks of severe complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although vaccination is effective in preventing severe coronavirus disease 2019 (COVID-19), boosters are required as the protection provided wanes over time. A greater number of boosters may be required in IEI patients compared to healthy individuals because of their immunodeficient state, but no such data are available. We investigated and compared the immunogenicity between 4 doses of COVID-19 vaccination for patients with IEI and 3 doses for healthy individuals. In the current study (NCT04800133), either BNT162b2 or CoronaVac was administered as dose 4. Healthy individuals who received 3 doses were included for comparison. Humoral and cellular immunogenicity against wild-type and JN.1 SARS-CoV-2 was assessed between IEI patients and healthy individuals. IEI patients had lower humoral and cellular immunogenicity than healthy individuals after 3 doses of COVID-19 vaccination. After dose 4, IEI patients obtained immunogenicity similar to that of healthy individuals who received 3 doses. A fourth dose of BNT162b2 significantly enhanced humoral and cellular immunogenicity against wild-type SARS-CoV-2 and humoral responses against JN.1 SARS-CoV-2. In contrast, CoronaVac had minimal effect on humoral responses to wild-type and JN.1 SARS-CoV-2. Six patients experienced breakthrough infections, which did not result in hospitalization or death. A fourth dose of BNT162b2 was immunogenic and safe for most IEI patients. The fourth dose of vaccination is recommended for IEI patients to improve protection against COVID-19, particularly before travel to areas with high endemic transmission.

Preeclampsia is a devastating hypertensive disorder of pregnancy with a high prevalence in the southern regions of the United States. Black pregnant patients are disproportionally at higher risk for preeclampsia onset and severity of disease than other racial groups. The underlying mechanism(s) for this racial disparity are unclear. In our current study, we were able to obtain a cohort of patients of self-identifying Black or White race who were overall matched for body mass index (BMI), blood pressure, gestational and maternal age, and parity, and we hypothesized that placentas from Black patients with preeclampsia would demonstrate elevated preeclampsia-associated placental gene expressions compared with White patients with preeclampsia. We collected placenta tissue from both healthy individuals and preeclampsia Black and White patients (n = 13-17) who delivered in Augusta, GA. We measured expressions of several preeclampsia-implicated genes and performed placental morphological analysis and bulk RNA sequencing. Contrary to our hypothesis, ddPCR analysis demonstrated that leptin, preproendothelin-1 (PPET-1), endothelial converting enzyme-1 (ECE-1), and soluble FMS-like tyrosine kinase-1 (sFlt-1) were higher in White preeclamptic women than in Black preeclamptic women. Our RNA sequencing analysis revealed that 288 genes differed between healthy Black individuals and preeclamptic Black patients. A striking 2,394 gene expressions significantly differed between healthy and preeclamptic White patients. Placental histology analysis revealed that Black patients with preeclampsia demonstrated a lower scoring of morphological pathologies associated with preeclampsia compared with White patients with preeclampsia. Collectively, these data indicate that gene expressions and placental injury markers associated with preeclampsia are more pronouncedly elevated in White patients compared with Black patients.NEW & NOTEWORTHY Black patients in United States are at a discrepant high risk for preeclampsia, via mechanisms unknown. We found that White patients with preeclampsia had significantly higher changes in gene and placental morphological expressions compared with healthy pregnancy than observed in Black patients with preeclampsia. These data indicate that placental damage in preeclampsia in our cohort was less evident in Black patients with preeclampsia compared with White patients with preeclampsia and that nonplacental mechanisms for disease may be predominate in Black patients with preeclampsia.

Non-invasive screening for ovarian cancer by combining serum SERS with interpretable machine learning models.

A multi-gradient microfluidic chip-based neutrophil chemotaxis analysis for sepsis auxiliary diagnosis and prognostic monitoring.

Utility of FRET substrates in bladder cancer diagnosis.

Impact of botulinum toxin type A on mandibular bone parameters in bruxism: radiographic evidence from treated, untreated, and healthy individuals.

SB290157, a selective complement C3a receptor antagonist, ameliorates aortic dissection by suppressing inflammatory signaling pathways to attenuate aortic wall inflammation and structural damage.

This study aimed to determine beta-lactamase genes, clonal relationships, and the prevalence of the E.coli sequence type 131 (ST131) clone in extended-spectrum beta-lactamase (ESBL)-producing E.coli (ESBL-Ec) strains isolated from community fecal samples. A total of 161 fecal samples were collected from healthy individuals and outpatients at Sivas Cumhuriyet University Hospital. ESBL-Ec isolates obtained from these samples were analyzed. Antimicrobial susceptibility was determined by the disc diffusion method following EUCAST guidelines. The presence of blaTEM, blaSHV, blaCTX-M, blaOXA, blaPER, blaVEB, and blaGES genes was investigated by multiplex PCR. The ST131 clone was detected by PCR and Multi Locus Sequence Typing analyses. Clonal relatedness among ESBL-Ec strains was evaluated using ERIC-PCR. The fecal ESBL-Ec carriage rate was 31.05%. Resistance rates to ciprofloxacin, trimethoprim-sulfamethoxazole, gentamicin, amikacin, and ertapenem were 38%, 58%, 14%, 6%, and 4%, respectively. ESBL genes were detected at rates of blaTEM 82%, blaCTX-M 68%, and blaOXA 10%. ESBL-Ec isolates were grouped into 15 clusters, and 5 (10%) of 50 isolates were identified as the ST131 clone. This first study in Sivas, Türkiye, shows a high fecal carriage rate of ESBL-Ec and the presence of the E.coli ST131 clone.

The small interfering RNA imdusiran as single and multiple doses in healthy, randomised individuals and non-randomised individuals with chronic hepatitis B (AB-729-001): a phase 1a/b trial.

Accurate monitoring of female reproductive hormones using a dual-enhanced ultrasensitive immunosensor.

Vitamin-dependent cofactors are essential for numerous metabolic reactions, and defects affecting their uptake, conversion, utilisation, or regeneration constitute a heterogeneous group of inherited metabolic disorders (IMDs). Although dietary vitamin intake is sufficient to sustain coenzyme synthesis in healthy individuals, it is insufficient in vitamin-responsive IMDs, where pharmacological supplementation can restore deficient metabolic fluxes or stabilise impaired enzymes. This review provides an integrated overview of the biochemical pathways that convert vitamins into their active coenzymes and documents all currently known hereditary disorders responsive to vitamin or coenzyme therapy, along with recommended doses. For each vitamin group (B1, B2, B3, B6, B8, B9, and B12) and BH4, we outline absorption, intracellular trafficking, coenzyme formation and turnover, major clinical phenotypes, diagnostic biomarkers, and vitamin therapeutic considerations, including dose ranges, formulation constraints, and safety issues. The expected therapeutic benefit is graded to assist with clinical decision-making. As many conditions are rare and have only recently been described, the evidence is sometimes limited; therefore, systematic reporting of individual responses, including vitamin forms and dosing, remains essential. Early recognition of vitamin-responsive IMDs is critical, as timely treatment can dramatically alter disease trajectories and, in some cases, fully reverse symptoms.

Dynamic balance adaptations in response to bound arm walking.

Orthodontic-induced gingival enlargement (OIGE) affects approximately 15-30% of patients undergoing orthodontic treatment and remains largely unpredictable, often relying on subjective clinical assessments made after irreversible tissue changes have occurred. S100A4 is a well-characterized marker of activated fibroblasts involved in pathological tissue remodeling. This was a cross-sectional precision biomarker study that analyzed gingival tissue samples from three groups: healthy controls (n = 60), orthodontic patients without gingival enlargement (n = 31), and patients with clinically diagnosed OIGE (n = 61). Immunohistochemical analysis quantified S100A4-positive fibroblasts, type I collagen synthesis, and microvascular density. Advanced statistical analyses included multivariate logistic regression, machine learning-based validation, causal mediation analysis, and survival modeling for risk stratification. The density of S100A4-positive fibroblasts was significantly higher in OIGE patients (245.8 ± 38.7 cells/mm2) compared to orthodontic controls (165.3 ± 29.4 cells/mm2) and healthy individuals (98.2 ± 18.5 cells/mm2) (p < 0.001; η2 = 0.891). Multivariate analysis confirmed S100A4 as an independent predictor of OIGE (OR = 1.028 per cell/mm2; 95%CI 1.021-1.035; p < 0.001). Machine learning validation demonstrated high predictive accuracy (AUC = 0.946). Survival analysis identified distinct risk strata: individuals with S100A4 densities > 180 cells/mm2 had a 78% probability of developing OIGE within 24months, compared to 12% for those with < 130 cells/mm2. S100A4 demonstrates 95% predictive accuracy for OIGE, supporting its role in personalized risk stratification and early preventive interventions during a defined therapeutic window. This study presents the first validated precision biomarker in orthodontics with the potential to prevent an estimated 180,000-360,000 OIGE cases globally each year.

Sepsis is a dysregulated host response to infections, leading to organ dysfunction and posing a critical threat to human health. Despite tremendous progress in understanding the pathophysiology of sepsis, early diagnosis and clinical treatment efficacy remain unsatisfactory. This study aimed to identify transcriptomic alterations in peripheral blood mononuclear cells as potential biomarkers of sepsis. Bulk RNA-seq was performed on peripheral blood mononuclear cells obtained from 20 patients with sepsis and 12 healthy individuals. Multiple bioinformatics tools were used to identify key genes and signaling pathways associated with sepsis progression. The hub genes were further externally validated by publicly available blood transcriptomic data and experimentally verified by immunocytofluorescence assay. Differential expression analysis revealed 4,522 differentially expressed genes in patients with sepsis (n = 20) compared with healthy individuals (n = 12). Weighted gene coexpression network analysis identified multiple gene modules closely related to sepsis, with the royal blue module exhibiting the most positive correlation with sepsis. Intersection analysis yielded 176 common genes between the royal blue module genes and differentially expressed genes. Protein-protein interaction analysis revealed five hub genes ( CTSB , CTSD , ATP6V0D1 , UBE2D1 , and ATP6V0C ) associated with sepsis. Immune infiltration was dissected by single-sample gene set enrichment analysis, revealing associations between hub genes and monocytes. Single-cell RNA sequencing data analysis and immunocytofluorescence assay confirmed the upregulation of CTSB and ATP6V0D1 in circulating monocytes. Notably, CTSB and ATP6V0D1 were significantly associated with 28-day mortality of sepsis patients in the external validation cohort (n = 479). This study identifies CTSB and ATP6V0D1 expression in circulating monocytes as potential biomarkers and promising therapeutic targets for sepsis.

Chromium nitride nanozyme-enhanced lateral flow immunoassay for sensitive and selective detection of transglutaminase 2: Proof-of-concept toward liver cancer-related biomarker evaluation.

Differences in three-dimensional spinal kinematics between individuals with chronic non-specific low back pain and age- and sex-matched asymptomatic controls.

Anodal transcranial direct current stimulation (tDCS) over premotor and parietal cortex improves upper limb proprioception.

Impaired endogenous vascular regenerative capacity, reflected by reduced circulating progenitor cell (CPC) counts, has been linked to age-related diseases, particularly adverse cardiovascular outcomes. Lower CPC counts have also been associated with accelerated age-related cognitive decline in otherwise healthy individuals, but their relationships with cognitive impairment and neuroimaging markers of vascular brain injury and neurodegeneration remain unclear. We investigated cross-sectional associations between CPC subsets, cognitive performance, and neuroimaging phenotypes, hypothesizing that lower CPC levels would be associated with worse cognition and adverse brain markers. In 283 community-dwelling participants (mean age, 65 years; 59% female, 39% Black) enrolled in the Brain Stress, Hypertension, and Aging Research Program, cognitive assessments (including Montreal Cognitive Assessment), brain magnetic resonance imaging-derived white matter hyperintensity volumes, and whole-brain cortical thickness were measured. Flow cytometry was used to enumerate CPCs as CD45med mononuclear cells expressing CD34 with coexpression of either CD133, chemokine CXCR4 (CXC motif receptor 4), or VEGFR2+ (vascular endothelial growth factor receptor-2). Linear regression models were adjusted for demographic and vascular risk factors. In fully adjusted models, lower CD34+/CD133+ CPC levels were associated with worse global cognition (Montreal Cognitive Assessment: β=0.59; P=0.01), lower mean cortical thickness (β=0.01; P=0.01), and greater white matter hyperintensity burden (β=-0.15; P=0.01). Similarly, lower CD34+ and lower CD34+/CXCR4+ CPC levels were significantly associated with greater white matter hyperintensity volume (CD34+: β=-0.27, P<0.01; CD34+/CXCR4+: β=-0.14, P=0.03). CD34+/VEGFR2+ CPC levels were associated with Montreal Cognitive Assessment (β=0.37, P<0.01) and Boston Naming Test performance (β=0.01, P=0.03), but not with neuroimaging phenotypes. Reduced regenerative capacity was associated with worse global cognitive performance and markers of vascular brain injury, including greater white matter hyperintensity burden and cortical thinning. These findings should be validated in longitudinal studies to clarify temporality and potential causality.

Migraine headache is a common primary headache disorder which is multifactorial in origin. On the other hand, iron deficiency anemia causes metabolic abnormalities in the brain which leads to a reduction in neuronal activities. The study was designed to determine the association between iron deficiency anemia and migraine. This was a case-control study which was conducted among patients attending at the outpatient department of Neurology of Mymensingh Medical College Hospital with migraine headache fulfilling the International Headache Society criteria and non-Migraine age and sex matched healthy individuals from November 2019 to April 2021. Total 155 migraine patients (case) and 155 non-migraine healthy individuals (control) were included in this study. After signing the informed written consent, the blood samples were collected for complete blood count and serum ferritin level. The study result showed that iron deficiency anemia was more common in migraine patients than non-migraine healthy individuals (p<0.001). In female patients, serum hemoglobin and ferritin level were significantly low in migraine (p<0.001 and p<0.001 respectably) but in male patients only serum ferritin level was significantly low (p=0.001). There is also an association between severity of migraine attack and iron deficiency anemia (p=0.042). The patients with severe headache had lower serum hemoglobin and ferritin level which were statistically significant (p=0.005 and p<0.01 respectably). The study observed an association between iron-deficiency anemia, serum hemoglobin and ferritin levels with migraine. Therefore, iron deficiency anemia may be investigated in migraine patients and iron supplements might be an effective treatment in patients with migraine.

To assess the relationship between endodontic and subgingival bacterial communities in individuals with apical periodontitis (AP), and to identify disease-associated subgingival microbial signatures. We propose that subgingival microbial communities exhibit a dysbiotic profile, defined by distinct bacterial signatures, which may provide complementary biological insights into AP. In this cross-sectional study, DNA was extracted from paired endodontic and subgingival samples from mesiobuccal sites of first molars in patients with AP (n = 25 sample pairs), and from subgingival samples from the same sites in healthy individuals (n = 34). Microbiota was explored using 16S rRNA sequencing. Alpha and beta diversity metrics were calculated. Differentially abundant taxa were identified using LEfSe. Random forest models based on the bacterial counts observed in the subgingival samples were trained to classify the individuals with AP from the controls. Within AP individuals, the subgingival communities differed from those present in root canals. Subgingival communities exhibited higher alpha diversity than root canal communities, irrespective of the clinical diagnosis (p < 0.001). Subgingival microbial communities in AP individuals exhibited a dysbiotic profile associated with enrichment of anaerobic and inflammophilic species (p < 0.05). Beta diversity analyses showed compositional differences between AP and control individuals, with Jaccard distance reaching statistical significance (p < 0.05), and Bray-Curtis indicating a borderline effect (p = 0.07). The best predictive model (Streptococcus sanguinis and Prevotella maculosa) achieved an accuracy of 89.8%, sensitivity of 80%, specificity of 97%, precision of 95.2%, and an AUC of 0.98. Subgingival profiles from AP individuals are distinct from those in healthy controls, showing AP-associated dysbiosis. Specific subgingival bacterial signatures achieved high diagnostic accuracy, supporting the potential broader impact of AP on the subgingival microbiota.