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Existing depression assessment tools inadequately detect rapid symptom changes after antidepressant treatments. This study aimed to translate, validate, and explore the clinical application of the Chinese version of the McIntyre and Rosenblat Rapid Response Scale (CMRRRS) for use during the treatment of rapid-onset depression. The McIntyre and Rosenblat Rapid Response Scale was translated and culturally adapted for use in Chinese settings. Briefly, 71 patients with major depressive disorder who were receiving intravenous esketamine were assessed using the CMRRRS and other validated scales. Properties were examined, including internal consistency, construct validity, and responsiveness to change. For patient classification, Latent Profile Analysis (LPA) and Kernel Density Estimation (KDE) curves were used. The Minimum Clinically Important Difference was computed to explore the smallest change related to clinical improvement. The CMRRRS showed high reliability and robust validity. Factor analysis explained over 60% of the total variance. LPA distinguished three patient classes, while KDE curves determined that a cut-off of 5 points was optimal for detecting clinically meaningful changes. The CMRRRS is a reliable, valid, and sensitive tool for monitoring rapid symptom changes in patients with depression treated with esketamine. It allows real-time symptom monitoring and personalized treatment adjustments. Further studies are warranted to explore its broader applicability. Show less

Oncogenic alterations in fibroblast growth factor receptor (FGFR)-family proteins occur across cancers, including pediatric gliomas. Our genomic analysis of 11,635 gliomas across ages finds that 5.3% of all gliomas harbor FGFR alterations, with an incidence of almost 9% in pediatric gliomas. Alterations in FGFR proteins are differentially enriched by age, tumor grade, and histology, with FGFR1 alterations associated with glioneuronal histologies. Leveraging isogenic systems, we confirm FGFR1 alterations to induce downstream Mitogen Activated Protein Kinase (MAPK) and mTOR signaling pathways, drive gliomagenesis, activate neuronal transcriptional programs and exhibit sensitivity to MAPK pathway and pan-FGFR inhibitors. Finally, we perform a retrospective analysis of clinical responses in children diagnosed with FGFR-altered gliomas and find that treatment with currently available inhibitors is largely associated with stability of disease. This study provides key insights into the biology of FGFR1-altered gliomas, therapeutic strategies to target them and associated challenges that still need to be overcome. Show less

Cancer-related fatigue (CRF) is a multifaceted and subjective phenomenon that significantly impacts patients on physical, emotional, and mental levels. This study aims to identify specific subtypes of Cancer-related fatigue (CRF) in patients with Hepatocellular Carcinoma (HCC) and to explore the factors influencing each subtype. This cross-sectional study enrolled 220 participants from a tertiary cancer hospital. Latent Profile Analysis (LPA) and multinomial logistic regression were conducted to identify distinct fatigue profiles and to explore the influencing factors for different categories of CRF among the patients. The analysis revealed three potential categories of CRF severity: Physical balance -Low fatigue (20.1%); Physical imbalance -Moderate fatigue (69.6%); and Physical prominent -High fatigue (10.2%). It was found that the severe insomnia the greater the probability of patients belonging to the Physical prominent -High fatigue (OR = 1.299, 95%CI: 1.188-1.419). Has partner (OR = 5.171, 95%CI: 1.739-15.377), the severe financial stress (OR = 2.570, 95%CI: 1.209-5.463) and the moderate ISI (OR = 1.212, 95%CI: 1.136-1.292) were associated with the Physical imbalance - Moderate fatigue group. Protective factors for the Physical balance - Low fatigue group included higher scores in the physical activity Index (OR = 0.930, 95%CI: 0.870-0.995), Hope Index (OR = 0.647, 95%CI: 0.552-0.758), General self-efficacy (OR = 0.874, 95%CI: 0.793-0.965), Body Mass Index (OR = 0.799, 95%CI: 0.552-0.758), and Child-Pugh A classification (OR = 0.310, 95%CI: 0.119-0.808). CRF in patients with HCC demonstrates significant heterogeneity. It is conducive to the clinical identification of CRF risk characteristics and the design of personalized intervention measures. Show less

High lipoprotein(a) [Lp(a)] levels are associated with increased coronary artery calcification (CAC) in familial hypercholesterolaemia (FH) patients. However, mechanisms linking high Lp(a) with CAC remain poorly understood. In this study, we have performed a bioinformatics and system biology analysis to identify miRNAs and their target genes involved in Lp(a)-associated atherosclerotic lesion and coronary calcification in FH patients. Patients with a genetic diagnosis of FH ( Forty-two miRNAs had > 1.5-fold difference in their detection levels when grouped by Lp(a) [FH-Lp(a)> 50 ( Our results identify a miRNA signature that regulates atherosclerotic processes associated with high Lp(a) levels and CAC in asymptomatic FH patients. These findings offer new insights into the underlying mechanisms and highlight potential therapeutic targets. Show less

To investigate longitudinal changes in pelvic floor support in primiparous women with pelvic organ prolapse (POP) after vaginal delivery, focusing on single- and multiple-compartment involvement. Two hundred primiparas after vaginal delivery were prospectively enrolled and underwent pelvic floor MRI at six weeks postpartum. POP was diagnosed and classified into subgroups (single or multiple compartments involved) based on MRI findings. Primiparas with POP underwent repeat MRI at four months postpartum. Pelvic floor measurements, including injury score and functional parameters of the levator ani muscle (puborectal hiatus line, H line; muscular pelvic floor relaxation line, M line; levator hiatus area, LHA; iliococcygeus angle, ICA; levator plate angle, LPA), were assessed on MRI. Measurements were compared among POP subgroups and a normal control group (without POP) at six weeks postpartum. Additionally, changes between six weeks and four months postpartum were analyzed within POP subgroups. Based on MRI criteria, approximately 41.5% of primiparas were diagnosed with POP, predominantly cystoceles commonly associated with uterine prolapse. Functional parameters of the levator ani, except for LPA at rest, were significantly increased in POP subgroups compared to controls. At four months postpartum, M line, H line, and LPA significantly decreased, and prolapsed organs were elevated in cases with multiple compartments involved, compared to six weeks postpartum. No significant changes were observed in cases with single-compartment involvement during follow-up. A substantial proportion of primiparas experienced postpartum POP. Impaired levator ani function contributed to POP. Pelvic floor support improved during early postpartum in cases with multiple-compartment involvement. Show less

Quality of life (QoL) subtypes were identified via latent profile analysis (LPA), and their correlations with social support and self-efficacy were assessed in 284 patients with hematologic malignancies (HMs). The results were as follows: (1) LPA revealed three QoL subtypes of patients with HMs, namely, the high-QoL group, the medium-QoL group, and the low-QoL group. (2) The high-QoL group had higher levels of social support than the medium-QoL group did, and they also had higher levels of self-efficacy than both the medium- and low-QoL groups did. These results contribute to the identification of heterogeneous QoL features among patients with HMs and their correlations with social support and self-efficacy. Moreover, this study has clinical implications for improving the QoL of patients with HMs and promoting their physical and mental health. Show less

Cardiovascular disease (CVD) remains the leading cause of death worldwide, according to global statistics from the WHO and GBD, with the incidence of acute coronary syndromes (ACS) continuing to rise annually. This study aims to develop a nomogram model to predict the risk in ACS patients with hypertension, providing clinicians with a tool for early diagnosis, personalized treatment, and prognostic evaluation. Data were collected from ACS patients at Huangshi Aikang Hospital between 2018 and 2023. Patient characteristics, including age, sex, hypertension history, initial blood test results, and cardiac doppler ultrasonography findings, were recorded. ACS diagnosis followed the 2019 revised Guidelines for the Diagnosis and Treatment of Acute ST-Segment Elevation Myocardial Infarction (STEMI) by the Chinese Society of Cardiology. The 2024 Revised Guidelines for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes from the Chinese Journal of Cardiovascular Diseases were used for NSTEMI and unstable angina (UA) diagnoses. Statistical analyses were performed using SPSS (version 27.0.1) and R software (version 4.3.2), with statistical significance at P < 0.05. A total of 980 ACS patients were included in the study. Among the three clinical subtypes, 592 patients (60.4%) had UA, which was the most prevalent. The hypertensive group comprised 682 ACS patients (69.59%), with a mean age of 64.93 ± 9.51 years. Significant differences between hypertensive and non-hypertensive groups were found in sex (P = 0.001), age (P < 0.001), clinical subtype (P < 0.001), and several clinical and laboratory parameters, including creatinine (Cr) (P < 0.001), left ventricular ejection fraction (LVEF) (P = 0.049), left ventricular posterior wall thickness (LVPW) (P = 0.003), CK-MB (P = 0.019), AST (P = 0.028), total cholesterol (TC) (P = 0.035), LDL-C (P = 0.007), and APOB (P = 0.005). Using LASSO regression, nine variables were selected for multivariate logistic regression analysis, leading to the construction of the nomogram model. The calibration curve, Hosmer-Lemeshow test, ROC curve, decision curve, and clinical impact curve all demonstrated the model's high quality. A high-quality predictive nomogram model for assessing the risk of ACS in patients with hypertension has been developed. This model can assist clinicians in early diagnosis, personalized treatment, and prognostic evaluation. Show less

Timely diagnosis is crucial for managing neurodegenerative conditions. This study investigated whether time from symptom onset to diagnosis differs by clinical syndrome and sex. This retrospective, cross-sectional study included 591 participants with Alzheimer's disease (AD), frontotemporal dementia (FTD) subtypes (behavioral variant FTD [bvFTD], semantic dementia [SD], and progressive non-fluent aphasia), logopenic progressive aphasia (LPA), and syndromes associated with movement disorders (corticobasal syndrome, FTD with motor neuron disease [FTD-MND], and progressive supranuclear palsy). Bayesian regression models were used to compute diagnostic timelines. Compared to AD (3.35 years; 95% credible interval [CrI]: 3.03-3.72), SD and bvFTD had additional delays of 9.7 (95% CrI: 1.96-20.64) and 14.82 months (95% CrI: 6.94-25.42), respectively, while FTD-MND was shorter by 11.62 months (95% CrI: -15.7 to -4.68). Men with bvFTD had 23.64 month longer delays than women (95% CrI: 10.35-44.33). Diagnostic delays may reflect syndrome-specific clinical features, diagnostic complexity, and sociocultural factors. Findings highlight the need for improved diagnostic pathways and pre-clinical biomarkers to facilitate earlier identification. Bayesian analyses revealed that diagnostic delays differ by syndrome and sex.Alzheimer's disease (AD) was diagnosed on average 3.35 years after symptom onset.Diagnoses were delayed in semantic and behavioral variant frontotemporal dementia (bvFTD) compared to AD.Men with bvFTD had longer delays than women.Findings support need for improved diagnostic pathways and pre-clinical biomarkers. Show less

Post-stroke depression (PSD) is a common and clinically significant complication of stroke, associated with worse rehabilitation potential and increased mortality risk. The prevalence of PSD varies from 25% to 59%, depending on the duration of follow-up, peaking in the first years after the stroke event. The pathogenesis of PSD results from a complex interplay of biological and psychological factors, extending far beyond monoamine deficiency. Key roles are played by damage to monoaminergic pathways, neuroinflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, reduced neuroplasticity (including BDNF deficit), and impaired integrity of neuronal networks. The clinical picture is characterized by a complex of affective (apathy, anhedonia), cognitive (executive dysfunction), and dyssomnic disorders. Although selective serotonin reuptake inhibitors remain the first-line treatment, the modern therapeutic approach to PSD requires targeting all components of its pathogenesis. A promising direction is the use of antidepressants with a multimodal mechanism of action, such as the original drug fluvoxamine, which combines serotonergic effects with anti-inflammatory and neuroprotective properties via sigma-1 (σ1) receptor agonism. Optimizing PSD treatment is achievable through the implementation of a personalized approach, including long-term screening and comprehensive management of the identified disorders. Show less

Symptom burden in primary brain tumor patients varies, emphasizing the need for comprehensive understanding to improve patient care. This study aims to identify distinct symptom clusters among brain tumor patients in Shanghai, China, using Latent Profile Analysis (LPA) to guide personalized diagnosis, treatment, and supportive care. A longitudinal study was conducted among 161 patients with primary brain tumors in Shanghai. Participants completed the MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) at three intervals: the day of admission (T1), three days after surgery (T2), and two weeks after surgery (T3). Latent Profile Analysis (LPA) was used to identify subgroups with unique symptom patterns. Six distinct subgroups were identified (entropy = 0.964), ranging from low-burden to persistently severe patterns. Subgroup membership was partially associated with age, tumor grade, and diagnosis. These subgroups were: transient postoperative burden group, stable symptom with cognitive emergence group, distress-predominant, low burden group, elderly-high grade, persistently severe group, nausea-dominant recovery group, and distress-plus-nausea, younger urban group. Our findings reveal substantial heterogeneity in perioperative symptom experiences among brain tumor patients. Identifying subgroups with high and persistent symptom burden may help clinicians target interventions such as enhanced education, proactive monitoring, rehabilitation, psychological support, and antiemetic management. This subgroup-based approach may improve quality of life, reduce morbidity, and guide precision supportive care in neuro-oncology. Show less

Subclinical atherosclerosis is a key predictor of cardiovascular events. While inflammation plays a crucial role in atherosclerosis, the involvement of Human Neutrophil Peptides 1-3 (HNP1-3) in its progression remains unclear. The study investigates the association of HNP1-3 and PCSK9 with coronary atherosclerotic burden and explores the potential mediatory role of PCSK9 in HNP1-3's effect on atherogenesis. Patients who underwent coronary computed tomographic angiography (CCTA) and had subclinical atherosclerosis (luminal stenosis < 50%) or normal coronary arteries were included in this cross-sectional study. HNP1-3 and PCSK9 levels were measured using ELISA, and coronary plaque burden was quantified using the modified Gensini score. Patients with subclinical atherosclerosis had significantly higher levels of HNP1-3 (p < 0.001), PCSK9 (p < 0.001), and lipoprotein(a) [Lp(a)] (p < 0.001) compared to controls. HNP1-3 was an independent predictor of subclinical atherosclerosis (p < 0.001), and its levels positively correlated with the modified Gensini score (p < 0.001). In multinomial logistic regression, higher levels of HNP1-3, PCSK9, and Lp(a) were independently associated with higher modified Gensini score tertiles. Mediation analysis revealed that PCSK9 mediated 48.7% of the effect of HNP1-3 on the modified Gensini score. After adjusting for hsCRP and cardiovascular risk factors, the direct effect of HNP1-3 became statistically insignificant, while the indirect effect via PCSK9 remained significant, suggesting that PCSK9 fully mediates the pro-atherogenic effects of HNP1-3. In conclusion, HNP1-3 is a novel independent predictor of subclinical atherosclerosis and coronary plaque burden, with its effects being mediated through PCSK9. These findings suggest that targeting PCSK9 could mitigate the inflammatory actions of HNP1-3, offering potential therapeutic insights for atherosclerosis prevention. Show less

Workplace violence (WPV) is a significant occupational hazard that threatens nurses' psychological well-being and professional stability. Although prior studies have addressed the impact of WPV on nurses, the latent heterogeneity of their violence exposure patterns has not been systematically explored. Moreover, empirical evidence regarding the role of individual psychological traits in shaping different WPV experiences remains limited. This study aimed to identify latent profiles of WPV exposure among nurses and examine the associations between profile membership and demographic as well as psychological factors, in order to uncover key predictors of distinct WPV patterns. A cross-sectional survey was conducted between March and May 2025 among 549 registered nurses from eight tertiary hospitals in Sichuan Province, China. Participants completed a battery of standardized instruments, including General Demographic Data Scale, Workplace violence Scale, Maslach Burnout Inventory, Connor-Davidson Resilience Scale, Emotional Labor Scale, and Perceived Organizational Support Scale. Latent Profile Analysis (LPA) was performed using Mplus 8.3 to identify WPV exposure subgroups, and multivariate logistic regression was used to determine associated factors. LPA revealed two distinct WPV profiles: a high-frequency, multi-type violence group (n = 152, 27.7%) and a low-frequency, mild violence group (n = 397, 72.3%). Nurses in the high-frequency group reported significantly higher scores across all WPV dimensions, including verbal abuse, sexual harassment, threats, and physical assault ( Nurses' WPV experiences exhibit distinct latent profiles. Educational level, salary satisfaction, and psychological resilience are key differentiating variables. These findings highlight the need for stratified risk identification and targeted interventions, particularly for nurses with higher education levels, low salary satisfaction, and reduced psychological resilience, in order to mitigate the adverse effects of WPV and enhance occupational adaptation. Show less

Children with diabetes mellitus (DM) have an increased risk for cardiovascular disease (CVD), a risk potentially exacerbated by elevated lipoprotein(a) (Lp(a)). While other cholesterol parameters are screened in this population, Lp(a) is often overlooked despite being an independent CVD risk factor. Lp(a) levels are historically believed to not change over an individual's life and are genetically determined, but newer literature suggests variation. This study investigated Lp(a) levels and their relationship with glycated hemoglobin A Children and adolescents aged 5 to 18 years with incident DM had baseline Lp(a) and lipid profiles. Repeat Lp(a) and HbA Seventy-six children were included for evaluation: 76% with type 1% and 23% type 2 DM. Baseline median (Q1-Q3) Lp(a) was 43.3 nmol/L (13-73.7 nmol/L), 17 of which were elevated (≥75 nmol/L). Of the 22 participants with follow-up, 8 were abnormal: A total of 4 whose baseline Lp(a) were abnormal remained so and 4 with normal levels became abnormal. A positive correlation was found between 3-month Lp(a) values and HbA Children with DM have abnormal Lp(a) levels at a prevalence of approximately 20%, so this should be considered in CVD risk stratification. Further, observed Lp(a) fluctuations suggest value in serial Lp(a) assessments due to nongenetic influences. Without Lp(a) quantification, CVD risk characterization in children with DM may be inaccurate and should be considered for a comprehensive assessment. Show less

Cardiovascular diseases (CVDs) are the leading global cause of mortality and disability, with prevalence increasing due to aging and risk factors like obesity and hypertension. The retina, rich in microvasculature, provides a unique opportunity to investigate microvascular dysfunction linked to CVDs and other systemic vascular diseases. This study used a multifaceted approach to assess the genetic correlation and causal relationship between retinal characteristics and CVDs. Linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) analyses were conducted using genome-wide association study (GWAS) data from the UK Biobank and FinnGen datasets. A cross-sectional study was also conducted to validate the findings, collecting optical coherence tomography (OCT) images from 124 eyes (89 with CVDs and 35 healthy controls). A prediction model is based on least absolute shrinkage and selection operator (LASSO) regression to assess the risk of CVD. Using LDSC and two-sample MR, we found genetic evidence consistent with a causal effect whereby genetically proxied thinner retinal nerve fiber layer (RNFL) was associated with higher risks of hypertension and myocardial infarction (MI), while genetically proxied thicker photoreceptor inner segment/outer segment (PR-IS/OS) was associated with coronary heart disease and MI (false discovery rate [FDR] thresholds as reported). Genetically proxied thinner retinal pigment epithelium (RPE) showed an inverse association with stroke risk. Several circulating biomarkers-including lipoprotein(a) [Lp(a)], low-density lipoprotein cholesterol (LDL-C), and ApoB-exhibited MR evidence of association with multiple CVDs. In a cross-sectional cohort, retinal layer differences and their relationships with lipids were directionally consistent with the genetic findings. Retinal structural traits measured by OCT-particularly RNFL, PR-IS/OS, and RPE thickness-are best interpreted as non-invasive markers that reflect systemic vascular biology. Our MR analyses support shared etiologic pathways between retinal microstructure and CVDs rather than implying that retinal damage clinically causes cardiovascular events. Findings warrant validation in larger and more diverse populations and should not be considered definitive proof of causality. Show less

To explore the stratification and identification of adrenal lipid-poor adenomas (LPAs), adrenal cysts (ACs), and adrenal ganglioneuromas (AGNs) from each other using contrast-enhanced computed tomography (CT). Pathologically confirmed, 348 patients were categorized into Model 1 (260 LPAs, 34 ACs), Model 2 (260 LPAs, 54 AGNs), and Model 3 (34 ACs, 54 AGNs). Statistical analyses were performed on the differences in the degree of enhancement in the arterial/venous phase (DEap/DEvp) (in HU) and the corresponding graded variables for the arterial/venous phase (GVap/GVvp). Models were evaluated via receiver operating characteristic (ROC) curves, calibration curves, and the Hosmer‒Lemeshow (HL) test. The values of the area under the curve (AUC) for DEap, DEvp, GVap, and GVvp in Models 1-3 were 0.996, 1.000, 0.993, and 0.999; 0.980, 0.978, 0.961, and 0.975; and 0.734, 0.892, 0.725, and 0.883, respectively. The p values of the HL test were 0.984, 1.000, and 0.113, respectively. The DEvp interval values (in HU) for the LPAs, ACs, and AGNs were [4.9, 190.2] HU, [-3.7, 4.2] HU, and [-4.8, 41.8] HU, respectively. The GVap and GVvp ranges for the LPAs, ACs, and AGNs were [1, 6], [0, 2], and [0, 2] and [1, 6], [0, 1], and [0, 5], respectively. DEvp enhanced discrimination in Models 1 and 3, whereas DEap performed better in Model 2. Lesions with DEvp < 4.5 HU are likely represent non-enhancing pathology (e.g., cysts). When both GVap and GVvp are 0, when both GVap and GVvp are [2, 6], and when GVap is [3, 6] and GVvp is 6, LPA, AC, and AGN are excluded. Not applicable. Show less

Machiavellianism and borderline personality are known for influencing interpersonal dynamics through manipulative behaviors. Machiavellianism is characterized by calculated, egotistic, and callous manipulation, while borderline personality involves emotionally driven impulsive manipulation due to instability and fear of abandonment. In this study, we explored the relationships of the two constructs with respect to broader personality constructs. Adult participants (N = 1011; Mage = 49.08 years, SD = 17.15) completed two measures each for Machiavellianism and borderline personality and a single inventory measuring the Big Five personality traits. Latent Profile Analysis (LPA) was used to investigate subgroups within the data. Machiavellianism was more strongly negatively associated with agreeableness and conscientiousness, while borderline personality traits were more strongly linked to neuroticism (more positively), agreeableness, and conscientiousness (both more negatively). Two distinct latent profiles emerged. Based on these findings, we suggest that Machiavellianism can align with either adaptive or maladaptive functioning, whereas a combination of Machiavellianism and borderline personality traits underscores a tendency towards manipulative behaviors with emotional instability. We suggest that future research build upon our findings by investigating concrete manipulative acts predicted by borderline personality and Machiavellianism. Show less

Microglia are the innate immune cells of the brain. Recent single cell and nucleus sequencing along with other omics technologies are leading the way for new discoveries related to microglial function and diversity. The Nogo-signaling system is a prime target for investigation with these tools as it has previously been neglected in microglia. The Nogo-signaling system consists of approximately 20 proteins, including ligands, receptors, co-receptors, and endogenous inhibitors known for their neuronal plasticity restricting properties via RhoA and ROCK1/ROCK2 activation, and have recently been implicated in microglial function. Here, we explore expression patterns of Nogo-family genes in the mouse and human brain. In mice, we focus on brain cell type enrichment, patterns of expression in microglia from embryonic stages to adulthood, sex differences, and changes in expression in acute and chronic inflammatory contexts from publicly available RNAseq and RiboTag translational profiling datasets. We identified differential expression of Nogo-family genes across age, sex, and disease/injury in mice. To analyze human microglia, we utilize a new tool, the Show less

Household contact (HHC) investigation helps in early identification of people with tuberculosis (TB) and initiation of TB preventive treatment (TPT) among those at high risk of developing TB. This cross-sectional study uses National TB Elimination Program data of all people notified with bacteriologically confirmed pulmonary TB and their HHCs from October to December 2023, from Chhattisgarh, a central Indian state, to assess coverage of HHC investigation, proportions identified with TB and put on TPT (all age groups and age < 5 years). Sociodemographic, clinical, and health system-related factors were used to identify predictors of HHC investigation not done, as determined through modified Poisson regression. Of the 4,221 people notified with TB, an HHC investigation was conducted for 3,177 (75%) cases. Among a total of 11670 contacts screened, TB was diagnosed in 0.9%(n = 109) for all age groups and 0.7%(n = 9) for children<5 years. TPT was initiated in 66% (n = 7740) for all age groups and 73% (n = 903) for children<5 years. Women (adjusted prevalence risk aPR 1.10; 95%CI:1.01-1.19), those notified from non-tribal districts (aPR 1.14; 95%CI:1.01-1.29), current facility being tertiary care (aPR 1.50; 95%CI:1.12-2.00) and private (aPR 1.42; 95%CI:1.08-1.86) facility, diagnosed with test other than sputum microscopy (aPR NAAT 3.19; 95%CI:2.39-4.28; LPA 8.88 95%CI:6.15-12.82; culture 9.69; 95%CI:5.99-15.68) and for whom diabetes (aPR 1.40; 95%CI:1.16-1.70) and HIV screening (aPR 1.55, 95% CI:1.17-2.05) was missing predicted higher risk of HHC investigation not done. The study highlights the need to improve HHC investigation, as well as the low yield of TB and TPT initiation. Predictors of HHC investigation not done suggest a need to decentralize it to the primary level and improve data-based program monitoring. A statewide capacity-building initiative for improving the investigation of HHC is the way forward. Show less

In this study, we aimed to describe the mutations associated with first-line drug resistance in Mycobacterium tuberculosis complex (MTBC) isolates from São Paulo, Brazil, between 2019 and 2021. Mutations in the coding regions of rpoB and katG genes and in the promoter region of the inhA gene in MTBC clinical isolates were detected using the GenoType MTBDRplus assay (LPA). All mutations inferred by LPA were sequenced. Of the 13,489 MTBC isolates with valid LPA results, 657 (4.9%) harbored mutations. The overall prevalence rates of rifampicin-resistant (RIF-R) tuberculosis (TB), isoniazid-resistant (INH-R) TB, and multidrug-resistant (MDR) TB were 1.5, 2.0, and 1.2%, respectively. A significant proportion of RIF-R isolates presented inferred rpoB mutations (89.1%), most of which were the borderline H445N mutation. The inhA promoter C-15T mutation was predominant among the INH-R isolates (52.8%). Most MDR isolates presented rpoB S450L + katG S315T1 mutations. Gene sequencing identified mutations not included in the catalogue of mutations published by the World Health Organization. Phenotypic drug susceptibility testing on isolates with inferred rpoB mutations revealed that the 0.5 µg/mL critical concentration of RIF failed to detect most borderline mutations when using the BACTEC MGIT 960 system. These findings emphasize the need for continuous surveillance and the integration of molecular and phenotypic methods to ensure an accurate detection and management of drug-resistant TB in high-burden settings. Show less

The atherogenic lipoprotein(a) [Lp(a)] is recommended to be measured at least once in each adult person's lifetime. However, the testing frequency and its impact on lipid-lowering therapy is uncertain. This retrospective analysis included patients 40-79 years old with at least two ambulatory clinic visits to a Midwestern healthcare system between 2018-2022. Within those patients, Lp(a) testing dates to 2004. Parameters included age, sex, race, traditional ASCVD risk factors, Lp(a) levels, and lipid-lowering therapy (LLT) prevalence. Lp(a) was considered elevated if Lp(a) ≥50 mg/dL or ≥125 nmol/L, respectively. Patients ( Although testing for Lp(a) has improved, there is room for significant improvement, particularly in those with ASCVD. The higher use of LLT in all risk categories indicate that Lp(a) testing may have influenced treatment decisions. Show less

Post-hemorrhagic hydrocephalus (PHH) is a neurological disease that primarily affects premature infants and involves infiltration of blood into the brain's ventricles followed by excessive accumulation of cerebrospinal fluid (CSF), leading to ventricular enlargement and increased intracranial pressure. The precise mechanisms driving PHH development and persistence are incompletely understood and lack disease-modifying treatments. Using a mouse model of PHH, we have identified transcriptomic, proteomic, and cellular features of PHH involving neuroimmune and neurovascular alterations recapitulating those reported in human disease. Improvement upon a lysophosphatidic acid (LPA)-induced PHH mouse model was combined with unbiased proteomic and single-nucleus transcriptomics that identified microglial molecular pathways propagating PHH. Pharmacological depletion of microglia in vivo significantly reduced PHH-associated ventriculomegaly. These data identify microglial and neurovascular elements in the development of PHH, implicating them as other potentially tractable therapeutic targets beyond LPA receptors, towards developing medical treatments for PHH. Show less

ObjectiveFibroblast growth factor receptor 1 (FGFR1) inhibitors are considered effective for treating 8p11 myeloproliferative syndrome. However, targeting FGFR1 alone may be inadequate for patients with translocated promoter region (TPR)-FGFR1 rearrangement.MethodsIn this study, we established TPR-FGFR1-expressing BaF3 cells and performed RNA sequencing analysis. Then, western blot analysis was performed to evaluate the protein expression levels of FGFR1 and phosphorylation of protein kinase B. Furthermore, flow cytometric analysis (fluorescence-activated cell sorting) was used to assess apoptosis levels.ResultsRNA sequencing analysis revealed that TPR-FGFR1-related genes are mainly involved in the epidermal growth factor receptor pathway. Gene set enrichment analysis highlighted the enrichment of genes in the phosphoinositide 3-kinase/protein kinase B pathway. FGFR1 inhibitor alone inhibited the phosphorylation of FGFR1 but not that of downstream protein kinase B. Combined FGFR1 inhibitor and protein kinase B inhibitor treatment simultaneously suppressed FGFR1 and protein kinase B phosphorylation. Fluorescence-activated cell sorting showed that combination therapy significantly increased apoptosis levels compared with FGFR1 inhibitor monotherapy.ConclusionsWe found that epidermal growth factor receptor is another activation mechanism of the protein kinase B pathway in TPR-FGFR1-expressing BaF3 cells. Furthermore, co-treatment with FGFR1 inhibitor and protein kinase B inhibitor inhibited the phosphorylation of FGFR1 and protein kinase B. Dual FGFR1 and protein kinase B inhibition enhances apoptosis, supporting dual targeting therapy for TPR-FGFR1-rearranged 8p11 myeloproliferative syndrome, offering a novel treatment direction. Show less

This study examines how distinct Information and Communication Technology (ICT) engagement profiles impact life satisfaction among older adults, aiming to inform digital inclusion policies for aging populations. Cross-sectional data from 717 older adults in Central China were analyzed using latent profile analysis (LPA) to identify distinct ICT engagement profiles, followed by multinomial logistic regression to examine predictors of profile membership. LPA identified 3 profiles: Quiescent (39.75%), Compliant (42.96%), and Active (17.29%) Users. Active Users reported significantly higher life satisfaction ( Show less

Genetically modified soybean is largely used in animal feed and its massive cultivation affects the environmental sustainability of livestock and the dependency for the import in the European market. The aim of this study was to evaluate the partial substitution of soybean meal with an innovative common bean genotype (Phaseolus vulgaris lec-lpa) with reduced content of anti-nutritional factors on zootechnical performance, gut microbiota modulation and faecal minerals in post-weaning piglets. Fourteen piglets were divided into a control group fed with a basal diet and a treatment group fed with a commercial diet in which 7.3% of soybean meal and 0.8% of soybean oil were replaced with 10% of P. vulgaris lec- lpa for 28 days. BW, ADG, ADFI and FCR were evaluated, and diarrhoea incidence was recorded. Evaluation of pH, nitrogen content, protein digestibility and mineral content was performed on faecal samples. Microbiota was analysed by rectal swabs samples. Blood serum metabolic profile was evaluated. The treatment group showed lower BW and ADG during the trial (p < 0.05), but the health status of the animals was preserved. The treatment group released lower levels of minerals in faeces when compared with the control group after 28 days (p < 0.05) suggesting a lower dispersion of faecal minerals in the environment. Significant Beta diversity index was observed at 14 and 28 days (p < 0.05). Roseburia and Butyricicoccus increased in treatment group at day 28 (p < 0.05). These genera are associated with SCFA production, contributing to the maintenance of intestinal integrity, promoting positive bacterial populations and limiting inflammatory phenomena. In conclusion, P. vulgaris lec- lpa could be a viable and sustainable alternative protein source to reduce the European protein gap, playing a potential role in microbiota modulation and faecal minerals release. Show less

Astrocytes are key regulators of neuroinflammation in multiple sclerosis (MS). Electroacupuncture (EA), a safe and cost-effective adjuvant therapy, has shown benefits in neurodegenerative diseases, but its astrocyte-related mechanisms remain unclear. Here, we demonstrated that EA at ST36 alleviated blood-brain barrier (BBB) disruption and neuroinflammation during the peak period of experimental autoimmune encephalomyelitis (EAE). Additionally, EA at ST36 upregulated the expression of α-melanocyte-stimulating hormone (α-MSH) and its receptor melanocortin-4 receptor (MC4R) in spinal astrocytes. Pharmacological studies showed that MC4R agonist RO27-3225 mimicked the therapeutic effects of EA, whereas MC4R antagonist TCMCB07 weakened EA-mediated BBB protection and neuroinflammation suppression. Moreover, astrocyte-specific silencing of MC4R via adeno-associated virus (AAV) weakened EA-mediated BBB protection and neuroinflammation suppression. RNA-sequencing (RNA-seq) and western blot (WB) revealed that EA exerts neuroprotective effects by activating MC4R to inhibit MAPK and NF-κB signaling pathways. Moreover, in MC4R-overexpressing astrocytes, α-MSH and RO27-3225 reduced inflammation responses, while TCMCB07 reversed the effects by MAPK/NF-κB signaling pathways. Collectively, our findings identify astrocytic MC4R as a critical mediator of EA-driven neuroprotection by suppressing MAPK/NF-κB signaling, providing mechanistic insight and a promising therapeutic target for EAE and other neuroinflammatory disorders. Show less

Radiotherapy remains a valuable yet limited option for select colon cancer cases, with radioresistance representing a major clinical challenge. Lipidomics screening identified autotaxin (ATX), also known as ENPP2, as a key mediator of radiation-induced metabolic reprogramming. Radiation exposure upregulated ATX expression and its product lysophosphatidic acid (LPA), which activated the LPAR2-AKT signaling axis to support tumor cell survival. Pharmacological ATX inhibition with HA130 or genetic ATX knockdown enhanced radiosensitivity in vitro by suppressing proliferation and promoting apoptosis. In mouse models, both HA130 treatment and ATX knockdown significantly suppressed tumor growth and improved radiotherapy efficacy, as shown by reduced tumor volume, weight, and Ki67-positive cell counts. Clinically, elevated ATX-LPA pathway activity was associated with poor patient prognosis. These findings establish ATX as a promising therapeutic target for overcoming radioresistance in colon cancer, supporting the combination of ATX inhibition with radiotherapy to improve treatment outcomes. The online version contains supplementary material available at 10.1186/s12876-025-04578-4. Show less

As inflammatory processes may be involved in the pathogenesis of diabetic distal sensorimotor polyneuropathy (DSPN), the first aim of the present study was to determine the clinical characteristics of type 2 diabetes mellitus (T2DM) with distal sensorimotor polyneuorpathy (DSPN). Next goal was to investigate inflammatory biomarkers, insulin-like growth factor- 1 and lipid profile in these patients. Finally, we aimed to compare the renal function in these patients. In a cross-sectional study, we included 160 patients diagnosed with T2DM. The control group was included 22 non-diabetic healthy subjects (HC). The patients with diabetes were divided into four groups, absent (n = 74), mild (n = 38), moderate (n = 24), and severe (n = 24) using a nomogram based on the MNSI features for a DSPN severity grading probability. Patients with moderate and severe DSPN were a little older and had longer duration of diabetes compared to patients with absent and mild DSPNS (p < 0.05). Serum levels of interferon-gamma (INF-γ), interleukin (IL)-1β, IL-4, IL- 6 levels in patients with severe DSPN were significantly higher than HC, absent, mild and moderate of DSPN (p < 0.05). The circulating levels of insulin-like growth factor-1 (IGF-1) were significantly lower in patients with severe DSPN (p < 0.05) compared to absent, mild and moderate of DSPN and HC. Diabetic patients with moderate DSPN showed increased circulating levels of TC, LDL-C, APOB (p < 0.05) compared to HC and patients with absent, mild and severe DSPN. Moreover, APO-A1/APOB was significantly lower in patients with diabetes compared to HC. In addition, patients with severe DSPN showed increased Cystatin C (p < 0.05) compared to HC and absent, mild, and moderate DSPN. Multivariate ordered logistic regression analysis showed that the levels of IL-6 (OR = 3.166, 95%CI 1.461-6.860, p = 0.003, IL-1β(OR = 1.148, 95%CI 1.070-2.232; p = 0.000), TC (OR = 1.174, 95%CI 1.011-1.364; p = 0.035), LDL-C (OR = 1.246, 95%CI 1.098-3.618; p = 0.003), Cystatin C (OR = 1.867, 95%CI 1.245-3.434; p = 0.004), ages (OR = 1.043, 95%CI 1.009-1.078; p = 0.012), and duration of diabetes (OR = 1.157, 95%CI 1.049-1.277; p = 0.004) were positively associated with increasing the odds ration of DSPN in T2DM. Conversely, the level of IGF-1 (OR = 0.922, 95%CI 0.961-0.982; p = 0.000) and ratio of APO-A1/APOB (OR = 0.212, 95%CI 0.078-0.567; p = 0.002) were significantly associated with decreasing the odds ratio of DSPN in T2DM. The levels of inflammatory biomarkers such as INF-γ, IL-1β, IL-4, IL- 6 were increased in patients with severe DSPN in T2DM. Ages, duration of diabetes as well as high circulating levels of IL-6, IL-1β, TC, LDL-C and Cystatin C were positively associated with DSPN in T2DM. Conversely, the level of IGF-1 and the ratio of APOA1/APOB were independent protective factors for DSPN in T2DM. Our results emphasize the importance of addressing issues related to inflammatory biomarkers, lipids and early impaired renal function in T2DM with DSPN, as these may be of potential relevance for deteriorating DSPN. Show less