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Ten quick tips for spatial transcriptomics analysis.

Spatial transcriptomics (ST) enables genome-wide gene expression profiling while retaining spatial context within tissue sections. Since the foundational work by Ståhl et al. in 2016, the field has expanded rapidly, with diverse platforms now spanning sequencing-based (e.g., Visium, Visium HD, Slide-seq, Stereo-seq, and Seq-Scope) and imaging-based (e.g., MERFISH, Xenium, and CosMx SMI) approaches. The breadth of platforms, data structures, and computational tools, however, can be daunting for newcomers. Here, we present ten quick tips spanning the entire ST research workflow: whether ST suits a given biological question, how to select a platform aligned with study objectives, how to understand and process ST data, and which software tools to employ for analysis and visualization. We further discuss interpreting spatial patterns in biological context, integrating complementary modalities such as single-cell RNA sequencing and spatial proteomics, and leveraging public datasets and sharing results. Finally, we highlight current limitations of ST, particularly the challenge of reconstructing three-dimensional tissue architecture from serial tissue sections. This review provides biologists, bioinformaticians, and clinician-scientists with a concise, platform-neutral roadmap for incorporating ST into research, from experimental design to biological discovery.

Spatial Transcriptomics↗

Assessing Hardy-Weinberg equilibrium in T2T-aligned 1000 genomes project.

Quality control of markers in genome-wide association studies often includes testing for Hardy-Weinberg equilibrium (HWE). However, this is usually implemented in a homogeneous population without stratifying by sex. Previous work indicates sex-based selection at numerous autosomal loci in cohorts with active recruitment. Sex chromosome sequences can also interfere with autosomal SNPs. These motivate a re-examination of HWE in sex-aware analyses. Using the telomere-to-telomere (T2Tv2)-aligned high-coverage whole genome sequencing data from 2,490 individuals in the 1000 Genomes Project, we examined genome-wide sex-specific deviations from HWE across five super-populations. Our analyses were restricted to bi-allelic SNPs with non-missing genotypes and minor allele frequency (MAF) &#x2265;5% in both sexes of the five super-populations. We applied an allele-based framework to quantify both the magnitude and direction of Hardy-Weinberg disequilibrium (HWD), followed by a second-order omnibus meta-analysis that combined HWD results across populations and sexes. At a genome-wide significance threshold of p&#x2009;<&#x2009;5e-8, 0.9% of autosomal SNPs exhibited significant deviations from HWE. The majority of these deviations were associated with genomic features indicative of poor sequence quality. Restricting the analysis to reliable genomic regions substantially reduced the number of signals, yielding 255 autosomal SNPs and one non-pseudoautosomal chromosome X SNP. Among these, 140 autosomal SNPs displayed significant heterogeneity across populations but not across sexes. Notably, eight SNPs within a 15-bp region on chromosome 14q31.3 showed excess heterozygosity in both sexes of the African super-population (AFR). Finally, we developed a multivariate predictor of HWD based on sequence features, providing a practical tool that can be integrated into existing quality control pipelines for whole genome sequencing studies.

Journal Article↗

Assessing the accuracy and efficiency of an electronic platform for managing childhood illnesses in rural China: A cluster randomized controlled trial.

OBJECTIVES: The Integrated Management of Childhood Illness (IMCI) faces challenges in capacity building and quality control. This trial aims to assess an electronic IMCI (eIMCI) platform in improving the effectiveness and efficiency in disease classification and management by community health workers (CHWs). DESIGN: Cluster randomized controlled trial. SETTING: Rural western China. PARTICIPANTS: 24 CHWs and 72 ill children aged 2 months to 5 years (3 children per CHW). CHWs were randomly assigned to intervention or control groups. INTERVENTIONS: The intervention CHWs received online training and performed disease management using the eIMCI platform featuring integrated training modules and decision-support tools. The control group received traditional face-to-face training and used paper-based IMCI protocols. MAIN OUTCOME MEASURES: Proportion of children correctly diagnosed or classified by CHWs, as determined by a pediatric specialist. Relative risk (RR) between groups was estimated using Poisson Generalized Linear Mixed Models incorporating a random intercept for CHW to account for clustering of children within individual CHWs and adjusting for key covariates at both the CHW and child levels. RESULTS: The intervention group (13 CHWs, 39 children) had a higher rate of correct classification (64.1%) compared to the control group (11 CHWs, 33 children) (39.4%, P&#x2009;=&#x2009;.056). Multivariable regression analysis confirmed this (RR&#x2009;=&#x2009;2.1, 95% CI: 1.5-3.1; P&#x2009;<&#x2009;.001). No significant difference was found in correct treatment rates (38.5% vs. 27.3%, P&#x2009;=&#x2009;.316). Online training reduced time and costs by approximately 80%, though with a slight decrease in post-training evaluation scores. CONCLUSIONS: The eIMCI platform shows potential in enhancing IMCI implementation and significantly reducing the training burden in resource-limited settings. Trial registration: Chinese Clinical Trial Registry: ChiCTR2100042533, https://www.chictr.org.cn/showproj.html?proj=119995.

Humans↗

Community-tailored One Health educational intervention to enhance knowledge and practices for zoonotic disease prevention in rural Thailand: A protocol for a prospective cluster randomised controlled Trial in Chanthaburi, Thailand (Saan Suk trial).

BACKGROUND: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailand's established Village Health Volunteer (VHV) system. METHODS: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. DISCUSSION: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. TRIAL REGISTRATION: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Zoonoses↗

Dysregulation of the serum and IgG N-glycome in decompensated cirrhosis and its association with Model for End-Stage Liver Disease-Sodium (MELD-Na).

BACKGROUND AND AIMS: N-glycans modulate glycoprotein structure and function and are altered during chronic inflammation. We sought to define the extent of serum and IgG N-glycan disruption in patients with decompensated liver cirrhosis from alcohol-related liver disease (ALD), primary sclerosing cholangitis (PSC), and ALD-related hepatocellular carcinoma (HCC). Finally, we aimed to examine whether serum and IgG glycosylation is associated with changes in Model for End-stage Liver Disease-Sodium (MELD-Na) scores, a clinical marker used to prioritise liver transplantation. METHODS: Serum samples were obtained from patients with ALD (n&#x2009;=&#x2009;17), PSC (n&#x2009;=&#x2009;7), ALD-related HCC (n&#x2009;=&#x2009;4), and healthy controls (n&#x2009;=&#x2009;10). N-glycans were released, fluorescently labelled, and profiled by hydrophilic interaction ultra performance liquid chromatography (HILIC-UPLC). Chromatograms were integrated into 46 and 23 glycan peaks for serum and IgG respectively. These peaks and their associated glycosylation traits were statistically compared with healthy controls using age- and sex-adjusted linear regression models. RESULTS: In serum, decompensated cirrhosis shows statistically significant shifts toward less complex, agalactosylated and asialylated biantennary glycans, accompanied by significant losses of highly branched, galactosylated and sialylated structures. IgG mirrored this pattern, which is characteristic of a pro-inflammatory signature, with increased agalactosylation and bisected glycan levels, along with reduced levels of digalactosylated and sialylated species. N-glycan profiles showed significant associations with MELD-Na scores, indicating that inflammatory processes in decompensated liver cirrhosis continue to reshape serum glycoproteins. CONCLUSION: Decompensated liver cirrhosis shows profound remodelling of serum and IgG N-glycans. These data establish a reference framework for terminal glycomic disruption in liver disease and highlight the potential value of incorporating glycosylation analysis into broader assessments of liver disease progression.

Humans↗

Hepatitis B virus genome mutations in precore and basal core promoter regions among HBeAg-negative chronic hepatitis B patients with high viral load in Indonesia.

Hepatitis B e antigen (HBeAg) is widely used as a marker for active HBV replication and serves as a surrogate for HBV DNA&#x2009;>&#x2009;200,000 IU/mL to determine eligibility for tenofovir disoproxil fumarate (TDF) prophylaxis to prevent vertical transmission, according to WHO guidelines. However, some HBeAg-negative patients still harbor high viral loads. Mutations in the precore (PC) and basal core promoter (BCP) regions may reduce or abolish HBeAg expression without necessarily suppressing viral replication. Next-generation sequencing (NGS)-based characterization of these mutations remains limited in Indonesia. This study aimed to analyze the mutation prevalence in the BCP and PC regions associated with HBeAg negativity in Indonesian patients. We conducted a cross-sectional study of 32 chronic HBV treatment-na&#xef;ve, unvaccinated patients with HBV DNA&#x2009;>&#x2009;200,000 IU/mL (16 HBeAg-negative, 16 HBeAg-positive) at Cipto Mangunkusumo General Hospital. BCP and PC mutations were analyzed using NGS, classifying mutations as major (mutation frequency index [MFI] &#x2265;20%) or minor (MFI 1-&#x2009;<&#x2009;20%). Associations were analyzed using the Chi-square or Fisher's exact test and p-values were adjusted using the Benjamini-Hochberg procedure. Among 29 major mutation sites, PC mutations A1846T/C and G1896A were more frequent in HBeAg-negative than HBeAg-positive patients (81.3% vs 6.3% and 75.0% vs 12.5%, respectively; all adjusted p&#x2009;=&#x2009;0.019). Combined analysis showed higher mutation frequencies in HBeAg-negative patients (93.8%, 81.3%, and 62.5% for A1846T/C, G1896A, and G1899A, respectively; all adjusted p&#x2009;=&#x2009;0.015). In conclusion, HBeAg-negative patients with high viral loads are strongly associated with PC mutations, particularly G1896A, A1846T/C, and G1899A. These exploratory findings provide regional NGS-based molecular evidence that established PC mutations may contribute to the coexistence of HBeAg negativity and continued high-level HBV replication in Indonesian patients. Larger studies incorporating broader virological and clinical comparison groups are required to determine the clinical significance of these findings.

Humans↗

Computational prediction of a multi-epitope Human Metapneumovirus vaccine candidate through integrated reverse vaccinology and pan-genomic approaches.

Human metapneumovirus (HMPV) is a primary cause of global respiratory infections yet no approved vaccine currently exists. This study computationally predicts a multi-epitope vaccine candidate using a diverse dataset of 65 HMPV sequences spanning five continents. Following the screening of lead proteins for antigenicity and virulence, fifteen highly conserved MHC-I, MHC-II and B-cell epitopes were prioritized. These were integrated with a putative L7/L12 adjuvant using optimized AAY, GPGPG, and KK linkers to design three constructs (HMPV_V1-V3). Structural validation identified HMPV-V2 as the lead candidate that exhibits a Z-score of-5.24 and 87.7% of residues in favored Ramachandran regions indicating excellent stereochemical quality and structural stability. In silico docking indicated a strong predicted binding affinity between HMPV-V2 and the TLR4 receptor (energy: -969.2). Immune simulations predicted a robust adaptive response characterized by high IgG1 titers, memory B-cell maturation, and a Th1-dominant cytokine profile. Furthermore, molecular dynamics simulations suggested exceptional structural integrity for HMPV-V2, maintaining a low RMSD of 8.213 and RMSF of 0.737 throughout the simulation. Optimized in silico cloning into the pET28a (+) vector indicated a high potential for protein expression in E. coli systems. While these findings provide a theoretically grounded blueprint for vaccine development, this study is entirely computational and lacks experimental validation. Further in vitro and in vivo testing is required to confirm the actual safety and immunogenicity of the proposed candidate.

Metapneumovirus↗

Leveraging bioinformatics approaches for drug repositioning in space radiation protection.

The health effects of space radiation, primarily Galactic Cosmic Rays (GCRs), on humans remain largely unknown, with potential cardiovascular consequences posing a significant threat to astronauts on long-duration spaceflight missions. Currently, there are no established pharmacological countermeasures for GCR exposure. Drug repositioning offers a promising strategy to accelerate pharmaceutical research in space medicine. This study leverages existing bioinformatics techniques to identify and prioritize potential drug candidates associated with proteomic perturbations following simulated GCR exposure using previously published murine cardiac proteomic data. A protein-protein interaction (PPI) network was constructed using the top differentially expressed proteins (DEPs) from murine heart tissue following exposure to 5-ion GCRs as seed nodes, focusing on experimentally supported interactions. Network topology, Markov clustering, and functional enrichment analyses were used to characterize biologically relevant proteins and pathways. Drug-protein interactions were predicted using Drugst.One and mapped to PPI clusters of interest to identify candidate drugs. Selected drug-macromolecule interactions were further explored using CB-Dock2 molecular docking and short-duration molecular dynamics simulations as hypothesis-generating structural assessments. Analysis of a key PPI network cluster consisting of several ATP synthase proteins identified 23 unique drug candidates. These analyses demonstrate a systematic approach for leveraging bioinformatics techniques to identify candidate molecular targets and generate pharmacological hypotheses in the context of space radiation countermeasures. Ultimately, this strategy introduces a hypothesis-generating framework for the prioritization of potential drug candidates for future computational characterization and experimental investigation against spaceflight stressors.

Animals↗

Marker-assisted screening of resistance to fire blight, powdery mildew, and apple scab in local apple varieties from Uzbekistan.

Apple (Malus domestica Borkh.) is one of the most economically important fruit crops worldwide; however, its production is severely constrained by major diseases, including fire blight, powdery mildew, and apple scab. Breeding disease-resistant cultivars represents a sustainable alternative to chemical control, particularly through the effective utilization of local germplasm resources from Central Asia. This study aimed to evaluate the presence and distribution of resistance-associated alleles in local apple varieties from Uzbekistan using polymorphic DNA markers. A collection of local apple accessions was screened to identify markers linked to resistance against fire blight, powdery mildew, and apple scab. The analysis revealed substantial genetic variation in resistance gene combinations among the studied varieties. The fire blight-associated marker AE10-375 was detected in 79.8% of the accessions. For powdery mildew resistance, 75.2% of the varieties carried resistance alleles corresponding to both Pl1 and Pl2 genes. Screening for apple scab resistance demonstrated that Vfa2, Vfa1, and Rvi6 were the most prevalent genes, with Vfa2 detected in 95.4% of the accessions. Regional analysis indicated that accessions from Karakalpakstan exhibited the highest proportion of genotypes harboring markers associated with resistance to multiple diseases. Six local varieties-Atlas olma, Turkish, Xuboni, Krasniy jeleznyak, Shoyi olma, and Besh barmoq-were identified as carrying resistance-associated markers for all three diseases. These findings demonstrate that local apple germplasm from Uzbekistan represents a valuable genetic resource for resistance to economically important diseases. The identified genotypes provide promising donor material for breeding programs aimed at developing cultivars with durable, broad-spectrum resistance while reducing reliance on chemical control strategies.

Malus↗

Detection of bacterial gene expression elements on Tobacco mosaic virus RNA using cDNA analysis.

Tobacco mosaic virus (TMV) is a positive-stranded RNA virus that infects plants. Interestingly, the 5'-untranslated region (UTR) of the TMV RNA genome is recognized and translated by the ribosomes of Escherichia coli in a Shine-Dalgarno (SD) sequence-independent manner. This study aimed at investigation of the bacterial recognition modules that control gene expression within the TMV RNA genome. To this end, the 5'-end-complete cDNA of the TMV RNA and several 5'-end-truncated cDNA mutants, in which the movement protein-encoding gene and its downstream region were replaced with a DNA sequence encoding a green fluorescent protein, i.e., monomeric Umikinoko-Green (mUkG1), were constructed. Surprisingly, mUkG1 fluorescence was observed in E. coli transformants harboring the cloned cDNAs, although they were inserted into a vector lacking a promoter. Analysis of the 5'-end-truncated cDNA mutants and promoter prediction suggested that an E. coli-specific promoter might be located 2.1 kb upstream of the initiation codon for mUkG1. Furthermore, Western blotting analysis and conversion of the initiation codon ATG to AGT indicated that the translation of mUkG1 started from the correct initiation codon. These results imply that E. coli ribosomes correctly recognize the initiation codon on the mRNA, irrespective of the overly long 5'-UTR. To the best of our knowledge, this report is the first to reveal a recognizable bacterial module hidden within the TMV RNA genome through cDNA construction.

Tobacco Mosaic Virus↗

Metagenomic sequencing in encephalitis diagnostics: Challenges and opportunities in clinical settings.

The primary aim of this study was to determine whether metagenomic next-generation sequencing (mNGS) can identify potential microbial agents responsible for encephalitis of unknown origin in immunocompetent patients, thereby enhancing clinical diagnostics. Cerebrospinal fluid samples from well-characterized patients (n&#x2009;=&#x2009;17) diagnosed with encephalitis of unknown origin, according to Swedish national guidelines, were sequenced using mNGS using the Ion Torrent platform and analyzed using bioinformatic platforms. Samples from patients with known viral CNS infections i.e. HSV-2 meningitis (n&#x2009;=&#x2009;4), VZV CNS infections (n&#x2009;=&#x2009;3), enterovirus meningitis (n&#x2009;=&#x2009;2), JCV CNS infection (n&#x2009;=&#x2009;2) were used as controls for the methodology (n&#x2009;=&#x2009;11). No viral agents were detected in 16/17 CSF samples from patients with encephalitis of unknown etiology. 13/17 CSF samples were analysed for the most common autoimmune antibodies and were negative. In one CSF sample from patients with encephalitis of unknown origin a Human pegivirus (HPgV) was detected. In 9/11 control CSF samples from patients with CNS infections, RNA or DNA of the known virus were detected. The main conclusion in this study was that the negative results were related to that the majority of included patients were immunocompetent. The finding of HPgV in a patient with unknown encephalitis was judged as a bystander. However, mNGS might detect more pathogens in other patient cohorts and this study implicates that a close collaboration between the clinical laboratory and the clinicians enables a safe implementation of metagenomics.

Humans↗

Sperm subpopulations differing in mitochondrial abundance show divergent nuclear allele frequencies.

Mammalian ejaculates contain heterogeneous sperm subpopulations that differ in subcellular architecture and developmental history, despite appearing morphologically uniform. The extent to which this cellular heterogeneity reflects underlying nuclear genomic structure within a sire remains largely unexplored. Mitochondrial architecture in sperm is established during spermatogenesis, with final assembly and organization occurring during spermiogenesis under nuclear genomic control, positioning variation in mitochondrial abundance and organization as a potential phenomic indicator of within-sire allelic segregation. Here, we tested whether sperm subpopulations defined by differing mitochondrial abundance exhibit systematic differences in nuclear allele representation. Boar sperm were resolved into low and high mitochondrial subpopulations using fluorescence-activated cell sorting based on MitoTracker&#x2122; Green fluorescence while excluding debris, doublets, and non-viable cells. Epifluorescence microscopy confirmed that high MitoTracker&#x2122; Green fluorescence sperm possessed longer mitochondrial sheaths, validating a structural distinction between subpopulations. Whole-genome sequencing of paired mitochondrial subpopulations from three boars was performed, and allelic ratio distortion was evaluated relative to heterozygous baseline populations. Analyses across heterozygous loci genome-wide identified candidate allele frequency shifts between mitochondrial-defined subpopulations, suggesting non-random segregation of alleles within ejaculates. Using a minimum sequencing depth of 30 reads in both sorted fractions, 182 candidate SNPs were identified with evidence of allele-frequency differences between mitochondrial fluorescence-defined subpopulations. These findings suggest that sperm mitochondrial abundance can potentially serve as an indirect, high-throughput marker of nuclear genomic heterogeneity within sires. This proof-of-concept framework establishes a foundation for future studies integrating sperm phenotyping, genome-wide allele-frequency analysis and functional validation to better characterize gamete-level heterogeneity.

Male↗

Diversity at the HYP1 locus in potato cyst nematodes does not result from developmentally-programmed somatic mutations.

Most genetic diversity stems from spontaneous mutations, that is, errors in DNA repair or replication. But for dozens of organisms across the tree of life, mutations at specific loci are not spontaneous but developmentally programmed: effectively, some organisms edit their own DNA sequences. This is perhaps most common among pathogens and parasites, many of which use editing to diversify genes that produce important antigens. Plant-parasitic potato cyst nematodes are damaging agricultural pests that establish a lifelong feeding site inside the root of their host plant. We previously observed extensive diversity of rare alleles at HYP1, the most highly expressed gene that encodes a protein secreted by potato cyst nematodes during parasitism. Importantly, HYP1 alleles differ from each other by complex, in-frame rearrangements of short repeated sequence motifs within a single exon. Combining several lines of evidence, we previously hypothesized that potato cyst nematodes use developmentally-programmed mutations, or editing, to diversify HYP1 alleles in the soma. In the current work, we now test this hypothesis. We employ highly accurate long-read DNA sequencing of a simplified genetic system to identify potential rare edited alleles, we use a transgenic yeast system to describe large de novo mutations at HYP1, and we interpret our findings in light of key population genetic parameters as well as the genetic diversity surrounding HYP1 and across the genome.

Animals↗

Molecular identification and diversity assessment of Tyrrhenian Romulea species (Iridaceae).

Taxonomic assignments based only on morphology are often insufficient for delimiting species, particularly in complexes shaped by hybridization and polyploidy, where species boundaries are unclear. This limitation hinders progress in ecological, biogeographic and conservation research. The genus Romulea, distributed across Africa and the Mediterranean Basin, exemplifies this challenge. Despite its remarkable diversity, Mediterranean Romulea has not received much attention from genetic and molecular studies. Here, we present the first multilocus genotype analysis of Mediterranean Romulea taxa, focusing on the Tyrrhenian biogeographic province. Using target-capture sequencing with the universal Angiosperms353 kit, we generated genomic data for 272 individuals representing 18 putative taxa. Our findings reveal genetic groups that align with current taxonomy, the existence of cryptic divergence, and highlight the role of hybridization. Furthermore, analysis of intra-individual genetic diversity suggests one or several allopolyploid origins for Mediterranean Romulea. Four taxa (R. assumptionis, R. revelieri, R. ligustica, R. rollii) are consistently well differentiated across nuclear and plastid datasets, supporting their recognition as distinct species. In contrast, the widespread species R. ramiflora and R. columnae contain well-differentiated groups that may represent cryptic speciation. Several other taxa, including R. x melitensis, R. corsica, and R. bulbocodium, exhibit genomic signatures consistent with hybrid origins. Plastid and nuclear variation patterns are consistent with a hypothesis of rapid radiation in the Tyrrhenian region. These results provide a primary genomic framework for the integrative taxonomy of Romulea.

Genetic Variation↗

The effect of antiretroviral therapy adherence on viral load suppression rate among people living with HIV in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: Antiretroviral therapy (ART) adherence is a key determinant of viral load suppression among people living with HIV (PLHIV). In Ethiopia, evidence on the magnitude of ART adherence and its effect on virological outcomes remains fragmented. This systematic review and meta-analysis aimed to estimate the pooled prevalence of ART adherence and viral load suppression, and to measure the association between adherence and viral suppression among PLHIV in Ethiopia. METHODS: This systematic review and meta-analysis used the PRISMA checklist for systematic reviews and meta-analyses. The review protocol has been registered onPROSPERO:(CRD420251125899). PubMed, ScienceDirect, Scopus, Epistemonikos, and Google Scholar were searched. The quality of included articles has been evaluated with a Newcastle-Ottawa Scale (NOS), adapted for observational studies. A random-effects model using restricted maximum likelihood (REML) with Knapp-Hartung adjustment was used to estimate pooled prevalence and odds ratio. Heterogeneity was assessed using I2, &#x3c4;2, and Cochran's Q test. RESULTS: A total of 39 studies were included in the final analysis. The pooled prevalence of good ART adherence was 79.4% (95% CI: 74.8%-83.4%), while the pooled viral load suppression rate was 77.5% (95% CI: 72.5%-81.8%). The pooled odds ratio showed that good ART adherence was strongly associated with viral load suppression (OR = 6.30, 95% CI: 4.84-8.19). Substantial heterogeneity was observed across studies for both adherence and viral suppression outcomes (I2&#x2009;>&#x2009;90%). CONCLUSIONS: ART adherence and viral load suppression among PLHIV in Ethiopia are relatively high but remain below global targets. Good adherence was significantly associated with virologic suppression, highlighting adherence as a critical modifiable factor for achieving optimal treatment outcomes. Strengthening adherence support interventions is essential to improve virological success and advance progress toward HIV epidemic control.

Humans↗

Shared genetic basis and spatial cellular atlas of psoriasis and metabolic syndrome.

BACKGROUND: Psoriasis (PS) and metabolic syndrome (MetS) frequently co-occur. Characterizing their shared genetic architecture and spatially enriched cellular populations may clarify the context of their co-occurrence and generate hypotheses for functional validation. METHODS: We integrated genome-wide association study (GWAS) summary statistics for PS, MetS, and five related components with spatially resolved single-cell transcriptomic data. Global and local genetic correlations were assessed using linkage disequilibrium score regression, genetic covariance analysis, high-definition likelihood, and local analysis of variant association. A bivariate causal mixture model quantified polygenic overlap. Conditional/conjunctional false discovery rate and composite-null pleiotropy analyses identified shared susceptibility loci. Finally, gsMap evaluated trait-associated enrichment across annotated embryonic tissues at single-cell resolution. RESULTS: Genetic approaches identified significant genome-wide correlations and polygenic sharing between PS, MetS, and its components. Local and cross-trait analyses identified region-specific signals and cross-validated shared loci. gsMap revealed trait-specific tissue enrichment. PS showed the strongest enrichment in the epidermis (pCauchy&#x2009;=&#x2009;1.0573&#x2009;&#xd7;&#x2009;10&#x2009; -&#x2009;&#x2074;), adipose tissue (pCauchy&#x2009;=&#x2009;1.5366&#x2009;&#xd7;&#x2009;10&#x2009;-&#x2009;&#x2074;), and liver (pCauchy&#x2009;=&#x2009;1.0167&#x2009;&#xd7;&#x2009;10&#x2009;-&#x2009;&#xb3;). Across MetS, FBG, HDL-C, hypertension, and TG, enriched regions mainly involved the liver, adipose tissue, and epidermis. WC enrichment was predominantly observed in adipose tissue (pCauchy&#x2009;=&#x2009;1.7823&#x2009;&#xd7;&#x2009;10&#x2009;-&#x2009;&#x2074;), with no significant liver or epidermal enrichment. CONCLUSION: Integrating GWAS with single-cell transcriptomic and spatial information characterized shared genetic architecture between PS and MetS-related phenotypes and their spatial enrichment patterns. These findings provide a framework for generating testable hypotheses about comorbidity biology and guiding future functional and clinical validation.

Psoriasis↗

Dual regulation of the receptor-like kinase BIR1 involves site-directed transcript cleavage and 5'-leader-mediated translational control.

In Arabidopsis, BRASSINOSTEROID INSENSITIVE1-ASSOCIATED RECEPTOR KINASE 1 (BAK1)-INTERACTING RECEPTOR-LIKE KINASE 1 (BIR1) is a negative regulator of plant immunity and cell death. BIR1 was earlier described as a target of epigenetic and post-transcriptional degradation. During virus infections, degradome analysis of BIR1 transcripts mapped predominant mRNA cleavage sites at the 5'-untranslated leader region (site A) and the protein-coding sequence (sites B and C). Here, we identified another virus-associated cleavage site (D) within the BIR1 coding region and investigated the contribution of site-directed mRNA cleavage to BIR1 regulation. Mutations at B, C, and D sites enhanced mRNA stability by impairing transcript cleavage, resulting in increased BIR1 mRNA and protein accumulation. This regulation is disrupted in RNA silencing mutants, supporting a model of cis-directed small interfering RNA (siRNA)-mediated degradation. We next demonstrate that virus infection reduces BIR1 translation in Arabidopsis. Furthermore, our data reveal a repressive role for the 5'-leader in regulating BIR1 translation, potentially mediated by upstream open reading frames (uORFs) and a virus-responsive long non-coding RNA (lncRNA) derived from the natural antisense At4g39838 locus. Together, these findings reveal a multilayered regulatory mechanism that integrates sRNA-mediated cleavage with translational control, with broader implications for the fine-tuning of stress-responsive gene expression during infection.

Arabidopsis↗

Genomic epidemiology of coxsackievirus A24 variant during the 2024 acute hemorrhagic conjunctivitis outbreak in Coastal Kenya.

Several African countries experienced a surge in acute hemorrhagic conjunctivitis (AHC) cases in 2024. Investigations in Kenya, Mayotte (an Indian Ocean island) and Tanzania identified coxsackievirus A24 variant (CVA24v) as the causative agent. To date, however, limited genomic data exist to elucidate the sources, epidemiology, and evolution of CVA24v in Africa. We generated 245 CVA24v genomes from samples collected between January and September 2024 in coastal Kenya, representing the largest outbreak CVA24v genomic data set available globally. Phylogenetic analysis showed that these viruses belonged to genotype IV, falling into two major clusters that differed by 52 nucleotide and five amino acid changes, and with an inter-species recombination event involving another enterovirus in the 3Dpol gene. Notably, the Kenyan sequences clustered closely with contemporaneous Africa (2024) sequences, specifically Mayotte and Malawi, reflecting a regionally connected CVA24v outbreak, but were distinct from those sampled previously in Asia in 2023, with phylodynamic analysis revealing that the Most Recent Common Ancestor of Kenyan sequences existed between June and October 2023. In summary, this study provides the first detailed genomic analysis of CVA24v from Africa to inform future surveillance and control strategies.

Journal Article↗