Coiled-coil domain-containing proteins (CCDCs) play pivotal roles in tumorigenesis by regulating gene transcription, apoptosis, and cell cycle progression. This study focuses on the function and mechanisms of CCDC137 in acute myeloid leukemia (AML). Our findings revealed that CCDC137 is significantly overexpressed in AML and is closely associated with poor patient prognosis. Functional experiments demonstrated that CCDC137 promotes cell proliferation and accelerates the cell cycle, thereby driving AML progression. Mechanistically, co-immunoprecipitation (Co-IP) experiments confirm the interaction between CCDC137 and S100A6, which significantly enhanced S100A6 protein stability. Stable S100A6 then activates the PI3K/AKT signaling pathway, thereby mediating the oncogenic effects of CCDC137. This study revealed the mechanism by which CCDC137 drives AML progression by stabilizing S100A6 and activating the PI3K/AKT pathway, thus providing a novel target for AML-specific therapy.

The phosphorylation dependent regulation of transcription factors, transcriptional co-regulators and chromatin remodelling factors influences transcription. Aberrant transcriptional regulations driven by chromatin-associated oncogenic factors are a feature of various cancers; however, their phosphorylation-dependent regulation remains poorly characterised. ATPase family AAA domain-containing protein 2 (ATAD2) is a chromatin-associated factor implicated in oncogenic transcriptions. Here, we present a comprehensive phosphosite-centric analysis of ATAD2 by integrating data from multiple phosphoproteomic studies, encompassing 859 profiling and 285 differential datasets. From the class 1 differentially regulated phosphosites, four predominant phosphosites-S327, S337, S342, and T1152, emerged as consistently regulated and were frequently detected in diverse tumour datasets. The co-differentially phosphorylated proteins, including their interactors and potential upstream kinases (HASPIN, STK10, CDK12, PRP4K, CDK13, PAK4), were involved in cell cycle, chromatin remodelling, transcription, and DNA repair. Several phosphosites in transcription factors were found to be coregulated along with ATAD2 phosphosites. Phosphorylation at S327 and S342 was broadly upregulated and positively associated with transcriptional activators, suggesting a role in promoting transcription. In contrast, phosphorylation at S337 and T1152 correlated with proteins involved in transcriptional repression, indicating its involvement in inhibitory function. Collectively, these findings indicate the involvement of the ATAD2 phosphoregulatory network in transcriptional regulation and provide insights into the regulatory landscape of ATAD2, laying the groundwork for its potential therapeutic targeting in cancers.

Dysregulation of the innate immune response to SARS-CoV-2 has been linked to poor outcomes in COVID-19. Neutrophils are key players in this response, displaying distinct functional profiles associated with disease severity. This study investigates how neutrophil phenotypes, and their mediators are modulated in severe COVID-19 following vaccination.

We conducted an observational case-control study using clinical data, serum samples, and circulating neutrophils from patients hospitalized with severe COVID-19. Neutrophils from vaccinated patients exhibited increased expression of surface markers including TREM-1, CD182, HLA-DR, and PD-L1, alongside higher HLA-DR mean fluorescence intensity (MFI). These cells also showed a higher proportion of inflammatory (CD16⁺CD182⁺TREM-1⁺) and immunoregulatory (HLA-DR⁺PD-L1⁺) subsets compared to non-vaccinated individuals. Exploratory principal component analysis (PCA) revealed a trend toward separation of vaccinated and non-vaccinated groups, suggestively driven by inflammatory cytokines (IL-6, TNF-α, GM-CSF, IL-18) and neutrophil surface markers (HLA-DR, PD-L1, TREM-1, CD16).

These findings suggest that prior COVID-19 vaccination is associated with a distinct neutrophil activation profile in patients with severe disease, characterized by the concomitant expression of pro-inflammatory and immunoregulatory markers. This immune phenotype may reflect a more balanced inflammatory response during severe SARS-CoV-2 infection. These findings open avenues for future studies incorporating functional assays and larger, independent cohorts to confirm and extend the biological and clinical relevance of these observations.

Household-based studies are commonly used to investigate tuberculosis (TB) transmission and evaluate preventive interventions. These studies typically assume that household contacts (HHCs) who develop TB disease were infected by the identified index patient. However, community-acquired infections may challenge this assumption, potentially biasing findings. Here, we evaluated the proportion of genetically linked index-HHC pairs and examined whether this proportion varied based on the TB burden in the community.

We conducted a prospective cohort study in Lima, Peru, enrolling microbiologically confirmed pulmonary TB index patients and their HHCs who were followed for 1 year. Mycobacterium tuberculosis (Mtb) isolates from culture-positive index patients and HHCs underwent whole-genome sequencing (WGS). We defined index-HHC patient pairs as resulting from within-household transmission when the genetic distance between their Mtb isolates was ≤12 single nucleotide polymorphisms. To contextualize our findings, we conducted a systematic review of Mtb genotyping studies that used spoligotyping, restriction fragment length polymorphisms , mycobacterial interspersed repetitive units-variable number tandem repeats, or WGS to assess within-household TB infection transmission among index-HHC patient pairs.

In our Lima study, among 175 index-HHC patient pairs, 109 (62%) were classified as within-household transmission. The systematic review identified 22 qualifying studies from settings with TB burdens ranging from 6.7 to 845 cases per 100 000 person-years. Studies in settings with TB incidence of ≤250 per 100 000 person-years consistently reported linkage proportions of ≥61%, whereas high-burden settings exhibited greater variability.

Our findings suggest that, among individuals exposed to TB at home, within-household transmission predominates in moderate- or low-TB-burden settings. However, its relative contribution in high-incidence settings remains unclear.

Chronic pulmonary aspergillosis (CPA) is a significant, yet often overlooked, sequela of pulmonary tuberculosis (TB), particularly in resource-limited settings. Data on the seroprevalence of Aspergillus infection in Senegal is absent, and diagnostic capacity is limited. This study aimed to determine the seroprevalence of Aspergillus-specific antibodies among patients with a history of TB in Senegal and to evaluate the performance of a Rapid Diagnostic Test (RDT) against an Enzyme-Linked Immunosorbent Assay (ELISA).

A cross-sectional study was conducted between April 30 to August 31, 2025 at two health centers in Senegal: Wakhinane and Yeumbeul among patients presenting with chronic respiratory symptoms. After obtaining informed consent from adult participants or from parents/guardians for minors, a blood sample was collected from each participant and tested for Aspergillus antibodies using both a rapid diagnostic test (RDT) and an ELISA. Results were classified as positive, negative, invalid, or not tested. Prevalence and agreement between the two assays were calculated using valid results only. Demographic data were collected, and descriptive statistics with test performance analyses were conducted.

The overall seroprevalence was significantly higher by ELISA (11.9%; 38/320) than by RDT (5.5%; 11/201). Site-specific analysis revealed disparities: Wakhinane showed higher RDT positivity (4.5% vs. 1.0%), while Yeumbeul had higher ELISA positivity (13.5% vs. 11.2%). The cohort was predominantly male (66.0%) with a median age of 30 years. ROC analysis of the ELISA identified an optimal threshold that balanced sensitivity (78%) and specificity (89%).

This study provided the first serological evidence of substantial Aspergillus antibody prevalence among post-TB patients in Senegal, suggesting a significant burden of undiagnosed CPA. The higher sensitivity of ELISA makes it essential for surveillance and confirmation, while the RDT's practicality offers a viable option for initial screening in peripheral clinics. These findings underscored the urgent need to integrate CPA diagnosis into routine post-TB care and to strengthen fungal diagnostic capacity in West Africa.

Hypoxia can be classified into two types based on its temporal characteristics: acute hypoxia and chronic hypoxia, posing a severe threat to the physiological homeostasis of the body. Hypoxia stimulates peripheral chemoreceptors and activates compensatory responses in the autonomic nervous system and cardiopulmonary functions. These responses rely on coordinated regulation by the carotid body and multiple nuclei in the central nervous system. Through specific neural pathways and molecular mechanisms, the body adapts to hypoxia and sustains survival. However, severe hypoxia may lead to irreversible damage or asphyxiation. In this review, we discuss recent research on central neural circuits and molecular changes in nuclei induced by hypoxia. It focuses on key regions associated with hypoxia, including the nucleus of the solitary tract, retrotrapezoid nucleus, rostral ventral lateral medulla, parabrachial nucleus, and hypothalamic paraventricular nucleus. From a neuroscience perspective, it elaborates on the effects of hypoxia on respiratory, cardiovascular, and other bodily functions. This understanding may help guide the treatment of hypoxia-related clinical diseases. JOURNAL/mgres/04.03/01612956-990000000-00093/figure1/v/2026-04-11T111231Z/r/image-tiff.

Frailty is common amongst individuals presenting with acute ischaemic stroke (AIS). Not only has frailty been found to have disease-modifying effects in terms of survival and disability after AIS, but it may also exert a treatment-modifying effect in reperfusion therapies. However, studies investigating this to date have frequently been of limited sample size, highlighting the potential for meta-analysis to definitively establish any treatment-modifying effect.

We investigate the effect of pre-stroke frailty on morbidity and mortality outcomes following reperfusion treatment (thrombectomy and thrombolysis) for AIS.

A systematic review was performed according to Preferred Reporting of Items in Systematic Reviews and Meta-Analyses guidelines, via searching the EMBASE, PubMed, Scopus and Web of Science databases up to August 2025.

We identified 11 relevant studies with 194,699 participants. Overall, the prevalence of frailty was 37.2% [frail (n = 72,311), non-frail (122,096)]. Frailty was associated with increased 90-day (RR 2.19 [95% CI 1.44-3.34]) and one-year mortality (RR 2.11 [95% CI 1.6-2.78]), but not with symptomatic intracranial haemorrhage (RR 1.23 [95% CI 0.78-1.96]) or modified Rankin score 3-5 (RR 2.20 [0.94-5.16]).

Frailty has a consistent association with mortality at different time points after AIS reperfusion therapies. Despite some study heterogeneity, there is evidence that pre-stroke frailty is associated with increased mortality after treatment, though not with increased risks of symptomatic intracerebral haemorrhage or post-stroke disability. These findings suggest that routine pre-morbid frailty assessment may inform the decision-making process for AIS reperfusion treatment administration. This study highlights the need for large multi-centre prospective trials.

The number of older patients admitted with myocardial infarction (MI) is increasing, and their clinical profiles range from very fit to frail and functionally impaired.

To evaluate whether the benefits of complete revascularization are consistent across subpopulations of older MI patients stratified by the Clinical Frailty Scale (CFS).

In the FIRE trial, 1445 patients aged ≥75 years with MI and multivessel disease were randomized to either complete or culprit-only revascularization. Overall, 1010 patients (70%) were stratified according to CFS (scores 1-3 non-frail, 4 pre-frail, 5-9 frail). The primary endpoint was a 3-year composite of death, MI, stroke, or ischemia-driven revascularization.

Of the stratified cohort, 523 (52%) were non-frail, 304 (30%) pre-frail, and 183 (18%) frail. Increasing frailty was significantly associated with a higher risk of the primary endpoint (HR 1.62, 95% CI 1.19-2.20; P = .002). Complete revascularization reduced the primary endpoint with no significant interaction between revascularization strategy and CFS category (p for interaction = 0.769). The benefit of complete versus culprit-only revascularization remained consistent across the full range of CFS scores. Similar findings were observed for secondary endpoints, and no significant interaction emerged for safety outcomes.

Frailty, as assessed by the CFS, was independently associated with adverse outcomes. Complete revascularization was effective regardless of frailty status and should be considered in all older MI patients with multivessel disease undergoing an invasive strategy.

ClinicalTrials.gov Identifier: NCT03772743.

Cerebral amyloid angiopathy (CAA) significantly increases intracranial hemorrhage (ICH) risk and the safety of anticoagulation (AC) among CAA patients with atrial fibrillation (AF) is uncertain.

This was a retrospective cohort study of the TriNetX US collaborative network. Elderly CAA patients (≥ 65 years old) with newly diagnosed high-risk AF (CHA₂DS₂-VASc ≥ 2 for men and ≥ 3 for women) were included; patients with prior ischemic or hemorrhagic stroke were excluded. Patients treated with apixaban or rivaroxaban were compared to no AC treatment. Propensity score matching (PSM) was used to balance groups. Primary outcomes were ischemic stroke and ICH within 3 years assessed with Kaplan-Meier analyses; secondary outcomes included major hemorrhage and patient death.

821 patients were included (462 AC, 359 no AC); after PSM, 287 patients remained in each group. AC was significantly associated with lower stroke risk (event probability 1.0% vs 5.7% at 3 years, p = 0.016) without increasing intracerebral hemorrhage risk (3.0% vs 3.9%, p = 0.21). Major hemorrhage rates were comparable (8.1% vs 10.7%, p = 0.09), and mortality was lower with AC (27.9% vs 33.5%, p = 0.049).

Anticoagulation for elderly CAA patients with newly diagnosed high-risk AF and without prior history of ischemic or hemorrhagic stroke was associated with lower risks of ischemic stroke and death without higher risk of hemorrhage.

The association of plasma cortisol concentration with prognosis for dogs with congestive heart failure (CHF) is unknown.

To determine whether higher plasma cortisol concentration was independently associated with greater risk of cardiac mortality in dogs with CHF. Additional study aims were to evaluate the associations between other clinical, neurohormonal, and echocardiographic indices and cardiac mortality.

Thirty-one client-owned dogs with CHF secondary to myxomatous mitral valve disease (MMVD).

Prospective cohort observational study. Plasma cortisol measurement, urine cortisol-to-creatinine ratio, renal function test results, serum electrolytes, biomarkers of the renin-angiotensin-aldosterone system, N-terminal pro-B-type natriuretic peptide, and echocardiography were performed in dogs with MMVD at first onset of CHF. Plasma cortisol was repeated 7-14 days later. Association between plasma cortisol and other covariates with survival was determined using a proportional hazards regression model.

Plasma cortisol concentration was not associated with cardiac (P = .112; hazard ratio [HR] 1.01; 95% CI, 0.998-1.02) or all-cause mortality (P = .143; HR 1.01; 95% CI, 0.998-1.02). Treatment with angiotensin-converting enzyme inhibitors (P = .021; HR 0.058; 95% CI, 0.0052-0.66) was associated with longer survival to cardiac mortality. Treatment with spironolactone (P = .038; HR 0.36; 95% CI, 0.14-0.94), percent fractional shortening (P = .034; HR 0.0018; 95% CI, 5.44 × 10-6 to 0.61), and lower serum potassium (P = .048; HR 2.07; 95% CI, 1.01-4.27) at diagnosis were associated with longer survival to all-cause mortality. Spironolactone treatment at baseline was associated with all-cause mortality on multivariable regression analysis.

Plasma cortisol concentrations were not associated with cardiac mortality in this sample of dogs with CHF.