Browse Articles

Lifetime HIV testing frequency among women in Sub-Saharan Africa: A DHS-based analysis using zero-inflated negative binomial regression

Background HIV testing is an essential component of HIV prevention and care, yet lifetime testing frequency remains low in sub-Saharan Africa (SSA). This study examines the factors influencing lifetime HIV testing frequency among reproductive-age women in SSA. Methods We analyzed the most recent Demographic and Health Survey (DHS) data from nine sub-Saharan African countries, with an overall weighted sample of 158,722 women aged 15–49. The dependent variable was the lifetime number of HIV tests, and Zero-Inflated Negative Binomial (ZINB) regression was used. Model selection was based on Akaike Information Criterion (AIC) or Bayesian Information Criterion (BIC) and Vuong’s test, favoring the ZINB model over other count models. Adjusted incidence rate ratios (aIRRs) for the count and aOR for the inflation part with 95% confidence intervals (CIs) were reported, with statistical significance set at p < 0.05. Results The mean number of lifetime HIV tests was 2.49 (SD = 7.67), with a median of 0 (IQR = 0–3). Key predictors of lifetime HIV testing included: age (30–39 years: aIRR = 2.94; 40–49 years: aIRR = 3.14), rural residence (aIRR = 1.10), current or former union (aIRR = 1.37 and 1.30, respectively), education (primary: aIRR = 1.19; secondary: aIRR = 1.35; higher: aIRR = 1.81), wealth (richer: aIRR = 1.30; richest: aIRR = 1.34), and employment (manual labor: aIRR = 1.21; skilled work: aIRR = 1.18). Other significant factors included: comprehensive HIV knowledge (aIRR = 1.37), STI awareness (aIRR = 2.21), media exposure (aIRR = 1.25), access to health facilities (aIRR = 1.26), number of sexual partners (1 partner: aIRR = 4.82; 2–3 partners: aIRR = 5.67; 4 or more partners: aIRR = 6.13), early sexual debut (aIRR = 0.61), and region (East Africa: aIRR = 2.82; Southern Africa: aIRR = 7.25). The inflation model showed very low odds of never testing among women with primary and secondary education, lower odds with media exposure (OR=0.40), but higher odds with higher education (OR=5.26) and rural residence (OR=1.93). Conclusions This study indicated that over half of women of reproductive age in SSA have never tested for HIV. Addressing socio-economic, structural, and regional disparities, particularly in West Africa, is crucial, highlighting the need for targeted, equitable, and community-based strategies to expand testing coverage and promote repeat uptake.

Comet assay and antioxidant enzyme as blood biomarkers of low-dose radiation-induced adaptive response

Abstract This study investigated the ability of low doses to cause an in vivo radio-adaptive response (RAR) and examined the biological effects of acute low-dose total-body gamma irradiation in rats. Adult male rats were randomly divided into 8 groups. Acute gamma radiation doses of 0.25, 0.5, and 0.75 Gy for groups 2, 3, and 4, respectively, and a 2 Gy challenge dose for group 5 were administered 14 days later. then 0.25, 0.50, and 0.75 Gy, followed by 2 Gy to groups 6, 7, and 8. Twenty-four hours after irradiation, measurements were made of comet assay parameters and antioxidant indicators: Acute gamma exposure resulted in a significant rise in Comet Assay Score CAS (6–16%), Tail Length TL (4.7–7.45 μm), DNA in tail DNA% (11.82–17.76%), Tail Moment TM (1.17–3.78 μm), and Olive Tail Moment OTM (0.53–1.52 µmol/L), as well as dose-dependent increases in GSSG (4.6–9.58 µmol/L), and decrease in SOD (180.4–91.2 U/mL). These results demonstrate the rising detrimental consequences linked to higher acute gamma doses. Lower priming does encourage stronger adaptive responses, according to RAR analysis. The concentrations of GSSG, TL, OTM, and the ratio of Oxidized Glutathione/ Reduced Glutathione GSSG/GSH showed notable linear dose-response associations, indicating their potential as biomarkers for acute gamma radiation biodosimetry. These findings lay the groundwork for future research to verify these markers for dose evaluation and to examine the dynamics of RAR under various challenge doses and postirradiation circumstances.

Unraveling uneven urbanites’ expressed happiness across Chinese cities using geotagged social media data: Key predictors and future climate–happiness associations

Understanding inter-city disparities in urban expressed happiness (EH) and the key predictors for these differences is critical for advancing socially sustainable urban development. However, the key predictors for EH remain poorly understood, and existing studies have largely overlooked the potential association with future climate change. In this study, we analyzed 5,118,772 geotagged Weibo posts from 50 Chinese cities using SnowNLP for sentiment analysis, machine learning models, and LDA topic modeling to investigate the inter-city differences in EH, its underlying predictors, and the potential association with further climate change. Sentiment analysis revealed pronounced variations in EH across Chinese cities, with more positive emotions observed during weekends and holidays. Incorporating 17 potential predictors, we developed ten machine learning models. A random forest model achieved the best performance, with an R² that exceeded all other models by 1.05%–60.00% and an RMSE that was 7.41%–60.95% lower than the alternatives. SHAP analysis showed that landscape, socioeconomic, environmental, and geographic factors accounted for 24.58%–38.97%, 20.64%–40.12%, 11.96%–29.33%, and 11.47%–23.71% of the total feature importance in the EH prediction models, respectively. Among individual variables, the normalized difference vegetation index (NDVI) exhibited the highest feature importance, accounting for 18.56%–32.16% of the total importance, followed by per capita GDP, PM 2.5 concentration, AQI, and temperature. Scenario-based projections suggest an association between projected climate warming and potential changes in urbanites’ EH. Overall, this study identifies the key predictors associated with urbanites’ EH and highlights the potential association of future climate warming with EH, providing valuable evidence for urban planning and policy interventions.

Dual-branch fusion framework with graph attention networks for compound fault diagnosis in complex machinery system

Improving the yield and biological activity of sage essential oil using NADES: in vitro and in silico insights

Pair of ‘super-puff’ planets are lighter than candyfloss

The fellowship of the ring: TMEM187 guides iron to heme

Blinatumomab consolidation for high-risk Ph− B-cell acute lymphoblastic leukemia: the GRAALL-2014/B-QUEST study

Abstract Intensified chemotherapy regimens have improved outcomes in adults with Philadelphia chromosome–negative (Ph−) B-cell acute lymphoblastic leukemia (B-ALL), yet relapse remains a major cause of treatment failure and death. Blinatumomab is a T-cell engager that demonstrated marked activity in relapsed and measurable residual disease–positive (MRD+) B-ALL, as well as in frontline consolidation for MRD− patients. The phase 2 GRAALL-2014/B-QUEST substudy evaluated the integration of blinatumomab into consolidation and maintenance therapy for adults with high-risk (HR) B-ALL. Between 2015 and 2020, 489 adults aged 18 to 59 years with newly diagnosed Ph− B-ALL were enrolled, and among these 259 were classified as HR (presence of KMT2A-r, IKZF1 deletion, or end-of-induction MRD ≥ 10–4). A total of 94 patients with HR were enrolled in the QUEST study (2018-2020) and received up to 5, 28-day cycles of blinatumomab during consolidation and maintenance. In addition, 90 patients with HR who were treated before QUEST activation without blinatumomab served as controls in a post hoc analysis. Baseline characteristics were comparable between groups. Blinatumomab consolidation significantly improved MRD clearance, reduced relapse, and prolonged survival. At 5 years, cumulative incidence of relapse, disease-free survival (DFS), and overall survival were 23%, 68%, and 79% in the blinatumomab group compared with 49% (P = .001), 42% (P = .001), and 60% (P = .03) in controls. Patients eligible for allogeneic hematopoietic stem cell transplantation (alloHSCT) derived overall benefit. However, no clear additional DFS advantage was observed among those who ultimately underwent transplantation. These findings support the frontline integration of blinatumomab and warrant prospective evaluation of transplantation strategies in this setting. This trial was registered at www.clinicaltrials.gov as #NCT03709719.

Nuclear weapons lurking in space could be tracked down by satellites

Oxidized PDI promotes thrombus formation in oxidative stress

Abstract Protein disulfide isomerase (PDI) functions in thrombus formation in vivo and represents a viable target for antithrombotic therapy. PDI is a redox sensor that can either reduce or oxidize substrates depending on the redox environment. However, whether PDI functions primarily as a reductase or an oxidase in the context of thrombus formation remains unknown. Here, we used pharmacological and genetic approaches along with PDI mutants to determine how the PDI redox state affects thrombus formation. LOC14, which inhibits PDI reductase activity and induces PDI oxidation, promoted thrombus formation in arteries exposed to ferric chloride and enhanced laser injury–induced platelet accumulation and fibrin formation in cremaster arterioles. Blocking antibodies targeting PDI reversed the prothrombotic effect of LOC14. Evaluation of sulfenylation-mediated PDI oxidation using the C53A, C56A, R120D, and T101A PDI mutants showed that the sulfenylation mechanism of PDI resembles that of hydrogen peroxide (H2O2) reduction by peroxiredoxins. These studies identified PDI mutants that failed to undergo H2O2-mediated oxidation, but showed normal reductase activity. When tested in vivo, either wild-type PDI or the R120D mutant fully restored normal thrombus formation following morpholino-induced knockdown of PDI or in mice with platelet-specific knockout of PDI. In contrast, the sulfenylation-impaired R120D mutant PDI was unable to fully restore thrombus formation in the setting of oxidative stress induced in mice by genetic deletion of glutathione peroxidase 3 or by infusion of oxidized low-density lipoproteins. These studies show that PDI-catalyzed oxidation drives thrombosis and demonstrates a mechanism of peroxide-mediated oxidation of PDI that contributes to the prothrombotic response of oxidative stress.

A QUEST to improve outcomes for adults with high-risk B-ALL

TMEM187 is a novel brakelike modulator in the regulation of erythropoiesis

Abstract Erythropoiesis, the process of red blood cell production, is highly dependent on iron uptake by transferrin and its receptor, transferrin receptor 1 (TfR1). However, the mechanisms governing the proper recycling of TfR1 in relation to cellular iron demands remain elusive. Here, we identify human TMEM187, a Golgi transmembrane protein of unknown function, as a novel negative regulator of erythropoiesis. Lack of TMEM187 in cell models initiates erythropoiesis without the normal induction protocol and accelerates iron uptake. Following the induction protocol, TMEM187 ablation leads to premature erythroid maturation, resulting in early phosphatidylserine ectopia and cell membrane fragility, hallmarks of cellular senescence that render the cells susceptible to macrophage recognition and phagocytosis. In zebrafish embryos, tmem187 deletion leads to enhanced early erythropoiesis, although this phenotype is later compensated, whereas hematopoietic stem cell expression of human TMEM187 in mice, which lack a homologous gene endogenously, results in compromised erythropoiesis and moderate anemia. Mechanistically, we demonstrate that TMEM187 interacts with RAB11A to restrain endosomal recycling by interfering with RAB11A–GRAB association, involved with endosomal vesicle back to the plasma membrane, that activates RAB11A. Consequently, TMEM187 modulates TfR1 recycling to the cell membrane to fine-tune iron uptake efficiency for erythropoiesis. Our findings reveal a novel modulatory pathway in which TMEM187 plays a crucial role in regulating erythroid differentiation, maturation, and senescence, providing a previously unexplored perspective on TMEM187's physiological function.

Bollard CM, Heslop HE. A reassessment of anti–CAR T-cell expansion strategies. <i>Blood</i> . 2026;147(22):2561-2562.

Crossing the trial-practice chasm in CAR-T for relapsed LBCL

Substrate selectivity of the human RNA m5C methyltransferase NSUN2

Consensus recommendations for malignant histiocytic neoplasms (histiocytic, Langerhans, and interdigitating dendritic cell sarcomas)

Abstract Malignant histiocytic neoplasms (MHNs) are rare tumors derived from the mononuclear phagocyte system (MPS), encompassing histiocytic sarcoma, Langerhans cell sarcoma, interdigitating dendritic cell sarcoma, and other high-grade MPS lineage tumors. Despite advances in understanding histiocytic neoplasms, MHNs remain diagnostically challenging and lack standardized treatment algorithms. Current classification systems differ in lineage framing and fail to address mixed or ambiguous phenotypes, contributing to diagnostic uncertainty and inconsistent care. To address these gaps, the Histiocyte Society convened an international working group of pathologists and oncologists, including World Health Organization and International Consensus Classification contributors, to harmonize nomenclature, define minimum diagnostic criteria, and develop pragmatic treatment recommendations. Using a modified Delphi process and case-based review, the group formulated &amp;gt;40 consensus statements spanning classification, pathology, molecular testing, clinical evaluation, and therapeutic strategies. Key recommendations include the adoption of a unified MHN designation, use of a minimum immunophenotypic panel, integration of broad molecular profiling, and the documentation of previous hematopoietic malignancy. Treatment algorithms emphasize surgical resection for unifocal disease and targeted therapy or immune checkpoint inhibition for multifocal disease when actionable mutations or programmed death ligand 1 expression are present. These consensus recommendations aim to reduce diagnostic ambiguity, standardize reporting, and improve outcomes for both pediatric and adult patients. Future priorities include international registries to refine risk stratification and biomarker-driven trials exploring targeted therapy, immunotherapy, and combination approaches.

Nobel-winning chemist leaves US to direct AI materials lab in China

Deregulation of <i>FOXF1</i> / <i>FENDRR</i> from t(14;16)(q32;q24) defines a subtype of high-risk lineage ambiguous leukemia

Abstract Despite great progress in understanding the genomic basis of immature T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL) and acute leukemias of ambiguous lineage, there are still cases that lack defining genetic markers, complicating risk stratification, and limiting targeted therapeutic options. Recent studies have shown that enhancer hijacking drives oncogene activation in approximately half of T-ALL cases, with the BCL11B (BCL11 transcription factor B) enhancer frequently involved. Here, we describe a subtype of leukemia with a distinct gene-expression signature, and immunophenotype characterized by positivity for immature (CD38), myeloid (CD13), T-lymphoid (cytoplasmic [c]CD3, CD7), and B-lymphoid markers (CD19, CD79a, CD10). This subtype is defined by the t(14;16)(q32;q24) translocation, which places the FOXF1 gene and its antisense long noncoding RNA gene FENDRR under the regulatory control of the BCL11B enhancer, leading to their ectopic transcriptional activation. Common concomitant genetic lesions are loss-of-function alterations of GATA3, CDKN2A/CDKN2B deletion and activating JAK/STAT and NOTCH1 pathway mutations. Patients were predominantly children and adolescents/young adults and experienced poor treatment outcome. High-throughput drug screening of 176 compounds demonstrated efficacy of combined BCL2 apoptosis regulator family proteins and JAK/STAT signaling inhibitors. Additionally, the clinical use of tyrosine kinase inhibitors in some of these patients showed therapeutic efficacy. Collectively, these findings identify BCL11B-enhancer–mediated deregulation of FOXF1/FENDRR as a hallmark of a subtype of high-risk lineage ambiguous leukemia that is potentially amenable to targeted therapeutic intervention.

<i>BCL11B</i> enhancer hijacking by t(14;16)(q32;q24) translocation defines a novel high-risk subtype of T-ALL

Abstract The molecular classification of T-cell acute lymphoblastic leukemia (T-ALL) remains incomplete, limiting risk stratification and the development of targeted therapies. Enhancer hijacking is a critical oncogenic mechanism that deregulates proto-oncogenes by repositioning cisregulatory regions via structural variants. Here, we performed an integrated analysis of pediatric and adult T-ALL and mixed-phenotype acute leukemias (MPALs), using whole-genome and whole-transcriptome sequencing. This analysis identified a group of 14 patients with predominantly T-lineage neoplasms driven by a t(14;16)(q32;q24) translocation, harboring universal GATA3 mutations and CDKN2A/B deletions. Mechanistically, this translocation repositions the ThymoD locus downstream of BCL11B, causing monoallelic, ectopic overexpression of FENDRR and mesenchymal transcription factor genes FOXF1 and FOXC2 and activating epithelial-mesenchymal transition transcription signatures. Immunophenotypic and single-cell RNA sequencing analyses revealed marked lineage ambiguity with myeloid and B-cell differentiation potentials specific to this subtype. Furthermore, functional analyses in CD34+ cord blood cells demonstrated that FOXF1 overexpression promotes myeloid differentiation while suppressing T-cell differentiation, serving as a key factor for lineage specification. Clinically, this subtype was detected in 0.15% to 4.0% of T-ALL/MPAL cases depending on the cohort, showing a median age of 15 years and enrichment in adolescents and young adults. Importantly, patients with t(14;16)(q32;q24) have an extremely poor prognosis, showing a trend toward worse outcomes than high-risk groups such as KMT2A-rearranged early T-cell progenitor-like, SPI1-rearranged, and LMO2 γδ-like T-ALLs. The unique molecular landscape and poor prognosis of patients with the t(14;16)(q32;q24) translocation underscore the need for the development of novel subtype-specific therapeutic approaches.

Maternal anti-HPA-1a antibodies block αIIbβ3/αvβ3 integrin activation, and blockade correlates with FNAIT disease severity

Abstract Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a disorder caused by a mismatch in human platelet antigens (HPAs), leading to maternal antibody formation and platelet destruction in the fetus or neonate. The clinically most relevant antigen is HPA-1a on the β3 subunit of integrins αIIbβ3 and αvβ3, which are conformationally regulated cell adhesion receptors on platelets and endothelial cells and are crucial for hemostasis and vascular integrity. The clinical effects of anti-HPA-1a alloimmunization are highly heterogeneous and range from no symptoms to intracranial hemorrhage, potentially causing perinatal death or lifelong complications. However, determinants of disease severity are largely unknown, which hampers implementation of screening programs to identify alloimmunized high-risk women who may benefit from treatment. Using recombinant anti-HPA-1a antibodies and a retrospective cohort of FNAIT samples associated with mild or severe disease, we report that the tested anti-HPA-1a antibodies inhibit binding of integrins αvβ3/αIIbβ3 to their ligands (vitronectin, fibronectin, and fibrinogen) and impair cell adhesion. This inhibition is dependent on antibody concentration, is mediated by the antibody Fab region, and does not require the Fc tail, and is abolished when integrins are forced into a constitutively extended conformation. Furthermore, the extent of integrin inhibition correlates with disease severity. Together, our data demonstrate that anti-HPA-1a antibodies can block integrin activation, which likely contributes strongly to disease severity in FNAIT. These results may aid development of a prenatal diagnostic test to identify pregnancies at high risk of developing FNAIT and associated severe complications. In addition, these data reveal novel opportunities for allosteric inhibition of β3 integrin activation.