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PubMed2026

Tranexamic acid in spontaneous intracerebral hemorrhage: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tranexamic acid (TXA) is a well-established antifibrinolytic medication in the general population. However, its efficacy and safety for patients with spontaneous intracerebral hemorrhage (ICH) remain inconclusive. Consequently, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of TXA for spontaneous ICH. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following established methodological standards. Our search encompassed eight electronic databases from inception to April 25, 2024. The primary outcome was a reduction in all-cause mortality. The secondary outcomes included improvements in functional independence, neurological impairment, activities of daily living, and reduction in hematoma expansion (HE). Fixed-effects or random-effects model were performed for pooled data where eligible. RESULTS: A total of 9 RCTs that initially enrolled 3,124 patients were included. There were no significant differences observed concerning all-cause mortality (RR, 1.03; 95% CI [0.89-1.18]), hematoma expansion (RR, 0.90; 95% CI [0.80-1.00]), improvement of functional independence (RR, 1.02; 95% CI [0.92-1.12], neurological impairment (MD, -0.88 [95% CI, -2.22-0.45]), or activities in daily living (MD, -0.83 [95% CI, -29.25-12.59]). The pooled data indicated that TXA for ICH was associated with a decrease in hematoma volume from baseline (MD, -1.74; 95% CI [-2.47 to -1.02]). No significant difference in adverse events was observed between the TXA group and the control group. CONCLUSIONS: In summary, TXA does not affect all-cause mortality, functional outcomes, or neurological impairment, nor does it reduce HE, despite reducing hematoma volulume. TXA use for ICH requires careful clinical consideration.

Humans↗

PubMed2026

A randomized trial of omega-3 fatty acids plus inositol versus N-acetylcysteine for the treatment of depression and mania in emotionally dysregulated youth age 5-17 with and without autism traits.

The aim of this study was to assess the effectiveness of the nutraceutical treatments combined omega-3 fatty acid plus inositol (O3I) versus N-acetylcysteine (NAC) in children and adolescents with emotional dysregulation and the impact of the co-occurrence of autism traits (AT). Participants were male and female children (5-17) with emotional dysregulation and the presence/absence of AT, as defined by Child Behavior Checklist score, randomized to receive open-label O3I (1020 mg EPA and 1000-2000 mg Inositol) or NAC (1800-2700 mg) daily for 6 weeks. Clinicians measured severity and improvement of depression and mania with the NIMH Clinical Global Improvement Scale (CGI). Parents completed Parent-Youth Mania Rating Scale (P-YMRS) and Children's Depression Inventory (CDI). Both O3I and NAC resulted in modest improvements in mania and depression and did not differ significantly in between group comparison in their effectiveness. Participants taking O3I, but not NAC, demonstrated statistically significant within group improvement in depression per CDI. Participants taking NAC had a greater decrease in P-YMRS scores versus O3I, but the difference did not reach statistical significance. In the presence of AT, NAC was more effective than O3I for mania but not for depression. Further, participants taking NAC, but not O3I, demonstrated significant within group improvement in SRS and BRIEF scores. These results suggest that O3I and NAC may be beneficial for mania and depression in youth, with trends towards O3I more effective for depression and NAC more effective for mania. The presence of AT in youth with emotional dysregulation may moderate the impact of NAC.

Humans↗

PubMed2026

Genome-wide identification, structural characterization, and evolutionary analysis of growth-related gene families in African catfish (Clarias gariepinus).

The somatotropic axis encompassing growth hormone (GH), insulin-like growth factor (IGF), myostatin (MSTN), and prolactin (PRL) signalling cascades is the master regulator of somatic growth, metabolism, and development in vertebrates. African catfish (Clarias gariepinus), a commercially pivotal aquaculture species, now possesses a chromosome-level reference genome (CGAR_prim_01v2); however, a systematic, genome-wide characterization spanning all five interconnected growth-related gene families has not previously been undertaken in this species. Here, we identified and characterized 15 growth-related genes spanning gh1, ghra, ghrb, Igf1, Igf2a, Igf2b, igf1ra, Igf1rb, Igf2r, Mstna, Mstnb, prl, prlra, prlrb, and smtlb distributed across 13 chromosomes. Complete one-to-one orthology with zebrafish confirmed strong dosage-balance conservation across >120 million years of teleost divergence. Physicochemical analysis resolved a clear biochemical dichotomy between compact, basic secreted ligands (19.88-45.81 kDa; pI up to 10.02) and large, acidic, heavily glycosylated membrane receptors (56.82-270.80 kDa; pI 4.85-5.97). Phylogenetic analysis confirmed 3R whole-genome duplication origins for all paralog pairs, while synteny analysis revealed a disruption of the ancestral gh1-prl chromosomal block in C. gariepinus, a finding that warrants further comparative and functional investigation. This genomic atlas provides the sequence and structural information including exon-intron boundaries, domain architecture, and chromosomal coordinates needed as a prerequisite for future marker-assisted selection and CRISPR-based myostatin-editing efforts in African catfish aquaculture, though translation into applied breeding outcomes will require subsequent functional and expression studies.

Animals↗

PubMed2026

Integrated proteomic and acetylomic analyses reveal the metabolic reprogramming associated with increased tylosin-equivalent concentration in Streptomyces xinghaiensis sf106-B1.

Deciphering the metabolic basis of high-yield antibiotic production in Streptomyces is crucial for strain optimization. Atmospheric and room-temperature plasma (ARTP) mutagenesis of Streptomyces xinghaiensis sf106 generated a mutant with a 30% increase in tylosin-equivalent concentration (μg/mL). 4D-FastDIA quantitative proteomics identified 279 differentially abundant proteins enriched in the Type I polyketide synthase (PKS) pathway, with increased abundance of key macrolide-biosynthesis-related proteins. Lysine-acetylome profiling identified 1152 differentially abundant acetylation sites and revealed altered acetylation of enzymes involved in fatty acid metabolism and the tricarboxylic acid (TCA) cycle, suggesting adjustments in central metabolism associated with acyl-CoA precursor availability and energy generation. Integration of proteomic and acetylomic data suggests coordinated changes in protein abundance and lysine acetylation associated with the increased tylosin-equivalent concentration. These results highlight candidate nodes for rational metabolic engineering of S. xinghaiensis.

Streptomyces↗

PubMed2025

UV-based homogeneous disinfection process for removal of antibiotic resistance genes: Efficiency, mechanisms and influencing factors.

The proliferation and dissemination of antibiotic resistance genes (ARGs) in aquatic environments pose a serious threat to global public health. Ultraviolet-driven homogeneous advanced oxidation processes (UV-AOPs) represent a prospective suite of technologies for the efficient removal of ARGs. This review critically assesses recent advances in the application of UV-AOPs, specifically UV/hydrogen peroxide (UV/H2O2), UV/peracetic acid (UV/PAA), UV/persulfate (UV/PS), and UV/chlorine (UV/Cl), for the elimination of extracellular ARGs and intracellular ARGs. The underlying mechanisms involve direct ultraviolet-induced DNA damage, including pyrimidine dimer formation and strand breakage, as well as oxidation mediated by radicals such as hydroxyl radicals, sulfate radicals, carbon-centered radicals, and reactive chlorine species. The relative contribution of radical and non-radical pathways is strongly influenced by water chemistry and process conditions. We further expound on the critical operational and environmental factors governing ARG removal kinetics, including UV wavelength and fluence, oxidant type and dosage, ARG sequence characteristics, pH, ubiquitous anions, and dissolved organic matter, which collectively affect radical generation, quenching, and reaction microenvironments. Notably, for i-ARGs, UV-AOPs facilitate degradation not only through direct radical attack but also by disrupting cellular integrity and permeabilizing membranes, thereby enhancing the exposure of genetic materials to oxidative and photolytic damage. This review synthesizes current understanding to provide a mechanistic basis for the design and optimization of UV-AOP systems, highlighting their potential as effective barriers against the dissemination of antibiotic resistance in water reuse and purification scenarios.

Disinfection↗

PubMed2026

Performance comparison of rapid and native barcoding methods for Oxford Nanopore sequencing of Poliovirus Viral Protein 1 (VP1) amplicons.

Accurate and timely sequencing of poliovirus is critical for global eradication efforts, particularly for molecular epidemiology based on the typing region of the genome, viral protein 1 (VP1). While Oxford Nanopore Technologies (ONT) sequencing has expanded capabilities for poliovirus surveillance, the relative performance of different ONT library preparation methods, including ligation-based (Native Barcoding) and transposase-based (Rapid Barcoding) approaches, has not been systematically evaluated. In this study, we compared rapid barcoding and native barcoding workflows for sequencing VP1 amplicons from 17 type 2 poliovirus-positive samples, each processed in triplicate. Native barcoding generated significantly more sequencing output, producing approximately 2.3-fold greater total read yield than rapid barcoding, and demonstrated higher run-to-run reproducibility (R2 = 0.979-0.998 vs. 0.847-0.929, respectively; p < 0.001). In addition, native barcoding generated 80% of the total yield achieved by rapid barcoding within approximately 7 h, whereas rapid barcoding required approximately 40 h to reach the same output. Despite these differences, both methods produced identical VP1 consensus sequences across all samples, with comparable read quality (median per-base Q-scores of approximately Q17-Q18). Rapid barcoding provided substantial practical advantages, reducing hands-on library preparation time (55 vs. 200 min) and per-sample cost ($12.82 vs. $16.54), while simplifying workflow and reducing technical complexity. These findings indicate that sequencing yield may not be a determinant of downstream analytical outcomes for poliovirus VP1 ONT sequencing. Rapid barcoding therefore represents a cost-effective and efficient approach for routine poliovirus surveillance, whereas native barcoding remains advantageous in applications requiring rapid data generation or maximal sequencing depth.

Poliovirus↗

PubMed2025

Diagnostic and clinical utility of exome sequencing and chromosomal microarray in children with GDD/iD: a meta-analysis.

BACKGROUND: Global developmental delay/intellectual disability (GDD/ID) is among the most common neurodevelopmental disorders, with up to half of cases are attributed to genetic factors. Chromosome microarray (CMA) has traditionally been the primary genetic test for idiopathic GDD/ID. However, whole exome sequencing (WES) and whole genome sequencing (WGS) have recently emerged, substantially increasing diagnostic yields in these populations. METHODS: We conducted a comprehensive literature search of PubMed, Scopus, EMBASE, and the Cochrane Library from inception to April 29, 2025. Studies reporting the diagnostic utility of these tests in children with GDD/ID were included and analyzed. RESULTS: A total of 102 studies, comprising 55,752 children, were reviewed. The pooled diagnostic yield of WES was 0.37 (95% CI: 0.33-0.41; I2 = 93%), significantly higher than that of CMA at 0.19 (95% CI: 0.16-0.21; I2 = 95%). Subgroup analyses showed that WES yielded significantly higher diagnostic rates than CMA in both same-sample comparisons (OR = 2.27, 95% CI: 1.08-4.78) and different-sample comparisons (OR = 1.65, 95% CI: 1.15-2.37). Only one study evaluated WGS, reporting a diagnostic yield of 0.27. Meta-regression revealed a significant association between CMA diagnostic yield and the proportion of male participants (p < 0.01), but not with WES. No significant difference in diagnostic utility was observed between isolated GDD/ID and GDD/ID with comorbidities. CONCLUSION: In children with unexplained GDD/ID, WES demonstrates superior diagnostic and clinical utility compared to CMA. Incorporating WES as a first-line investigation in the diagnostic evaluation of GDD/ID may be warranted.

Humans↗

PubMed2026

Prognostic effect of serum glial fibrillary acidic protein and neurofilament light chain for predicting progression independent of relapse activity in multiple sclerosis: A systematic review.

BACKGROUND: Progression independent of relapse activity (PIRA) is increasingly appreciated as one of the important factors contributing to disability accumulation in MS. sGFAP and sNfL could represent markers reflecting two separate biological processes related to relapse-independent progression in MS. OBJECTIVE: To perform a systematic review of the literature on blood GFAP and/or NfL measured in relation to PIRA or other similar relapse-independent progression endpoints in people with MS. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to 1 June 2026. The eligible studies were original human studies measuring blood GFAP and/or NfL concentrations in serum, plasma, or any other type of blood-derived material and assessing PIRA, PIRMA, CDP/CDW without relapses, relapse-free EDSS progression, non-inflammatory progression, or comparable relapse-independent disability worsening outcomes. Methodological quality was assessed according to the Newcastle-Ottawa scale and the QUIPS instrument for bias detection in the body of evidence on prognostic factors. Due to heterogeneity of outcomes, biomarker measurements and effect estimates, results were synthesized qualitatively rather than quantitatively. RESULTS: After removing duplicates, 1206 records were screened, followed by full-text review of 120 reports. A total of 18 reports were included. Overall, sGFAP was associated more frequently with PIRA or PIRA-like disability progression, particularly in cohorts with suppressed or limited overt inflammatory activity. Evidence for sNfL was more variable and context-dependent: several studies reported associations with PIRA-like or relapse-independent disability worsening when acute inflammatory activity was absent, suppressed, or analytically separated, whereas other studies reported negative or inconclusive findings. Negative or inconclusive results were reported by several articles, particularly when broad outcomes were evaluated or the study population was small. CONCLUSION: Blood GFAP and NfL give complementary but non-interchangeable information concerning PIRA in MS patients. The existing evidence base does not allow us to perform meta-analysis because of heterogeneity in terms of outcomes, standardization of biomarkers, and treatment context. Further prospective investigations with uniform criteria will be necessary for their use as biomarkers of PIRA in clinical settings.

Humans↗

PubMed2026

Whole genome sequencing of unusual Hepatitis C virus subtypes and drug resistance analysis during direct-acting antiviral therapy in India.

INTRODUCTION AND OBJECTIVES: Pangenotypic direct-acting antivirals (DAA) are effective against highly prevalent Hepatitis C virus (HCV) subtypes, but have been clinically validated almost exclusively in high-income countries. Unusual HCV subtypes may carry natural polymorphisms, potentially impacting DAA susceptibility. We conducted full-genome characterization and resistance analysis of unusual HCV subtypes in patients receiving DAA treatment. PATIENTS AND METHODS: In this prospective hospital-based study, eligible patients were screened for anti-HCV antibodies and active infection was confirmed by diagnostic 5'NCR-based HCV RNA detection. Genotyping was performed by core region sequencing, and viral load quantified by real-time PCR. For whole genome sequencing, multiplex primers were designed using alignments of global reference sequences. Sequencing was carried out using the Oxford Nanopore Technology platform. Phylogenetic analysis used multiple sequence alignment and the HCV-GLUE resource for resistance-associated substitution (RAS) analysis. RESULTS: Predominant genotype was genotype 3 in 64.3% (n = 45); genotype 6 in 21.4% (n = 15); and genotype 1 in 14.2% (n = 10). Unusual HCV subtype 6xa was detected in two patients and showed no NS5A resistance mutations. One genotype 3b patient relapsed at 24 weeks post-DAA treatment completion and carried NS5A resistance-associated substitutions 30 K and 31 M both at baseline and at relapse, conferring high-level resistance to NS5A inhibitors. CONCLUSION: This is the first report from India of whole genome sequencing of HCV subtype 6xa. The identification of NS5A resistance mutations in the 3b relapse case underscores challenges for global HCV elimination strategies.

Humans↗

PubMed2026

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-κB, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans↗

PubMed2026

Health bill beneath the plastic feast: A phthalate contamination alert from takeout food containers.

The rapid growth of takeout food consumption in China has raised concerns regarding exposure to phthalic acid esters (PAEs) from food packaging. This study investigated the presence, source, contribution, and health risk of PAEs in commonly used takeout containers. Widespread contamination was observed, with total PAE concentrations ranging from below the limit of detection to 222,000 ng/g. Diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), and bis(2-ethylhexyl) phthalate (DEHP) were identified as the predominant compounds, accounting for 7.50 %, 14.7 %, and 18.7 % of the total concentration, respectively. These PAEs may originated from additives during manufacturing and potential contamination of raw materials. Human exposure assessment showed that daily exposure doses of DIBP, DBP, and DEHP via container ranged from 0.00 to 2340 ng/(kg·day) among frequent takeout consumers, contributing substantially to overall PAE body burdens. To further assess exposure and associated risks, a nationwide online questionnaire survey was conducted across China. Based on this national-scale behavioral dataset, the health risks among Chinese residents were evaluated. Although the modeled non-carcinogenic risks of DIBP, DBP, and DEHP remained within acceptable limits, the simulation suggested that approximately 70 % of participants may experience potential exceedance of the carcinogenic risk threshold for DEHP. The frequency of takeout food consumption was identified as the most important factor affecting PAE exposure. These findings underscore the importance of limiting takeout frequency and reducing reliance on plastic containers to mitigate health risks. This study provides scientific evidence to support the development of safer packaging materials and informs public health strategies.

Phthalic Acids↗

PubMed2026

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1α axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans↗

PubMed2026

Nanopore-based epigenomic profiling reveals the absence of widespread CpG methylation in the African swine fever virus genome.

DNA methylation is a critical epigenetic mechanism implicated in regulating replication and transcription in DNA viruses. However, the epigenetic landscape of African swine fever virus (ASFV), a large double-stranded DNA virus infecting pigs, remains controversial. Here, we systematically profiled the DNA methylome of the first ASFV strain isolated in Hong Kong (HK_NT_202103) using Oxford Nanopore Technologies (ONT) R10.4.1 sequencing. We employed a paired design: native whole-genome sequencing (WGS) against a methylation-free whole-genome amplification (WGA) control. Using conservative thresholds, we found no evidence of 5-methylcytosine (5mC), especially typical CpG methylation, across the viral genome. Importantly, clear CpG methylation signals were successfully detected in the host genome from WGS data, confirming the functionality of the workflow to detect 5mC at CG sites. While widespread 5mC seems absent, a small number of putative N6-methyladenine (6mA) loci were identified. A specific 6mA candidate exhibited raw ionic current disruptions and gene-level intersection with another ASFV isolate (CAS19-01/2019), although it lacked single-base consensus across different methylation callers or between the two isolates. Although our biological findings are restricted to a single isolate under specific experimental conditions, this study introduces a novel, highly rigorous ONT framework for viral epigenomics research. Furthermore, the absence of ASFV CpG methylation indicates that host CpG-depletion remains a viable strategy for viral metagenomic enrichment. Ultimately, our work offers a critical methodological baseline for ASFV surveillance and highlights the necessity of targeted experimental validation for rare viral modifications.

African Swine Fever Virus↗

PubMed2026

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals↗

PubMed2026

Comparison of paralog identification methods and their impact on species tree topologies in target capture phylogenomics within the Sindora clade (Detarioideae: Leguminosae).

Target capture is a common method of generating high throughput DNA sequencing data for phylogenetic reconstruction of species relationships, for which single copy genes are usually most informative. However, a pervasive problem with target capture is that putatively single copy genes may in fact be paralogs resulting from gene duplication, which are problematic for phylogenetic inference because their evolutionary history may differ from the divergence history of species. Here, we use as a case study a target enrichment dataset of 88 species of Detarioideae (Leguminosae) with a focus on the Sindora clade to examine approaches for handling paralogs, including the built-in paralog handling functions in HybPiper and CAPTUS, plus subsequent steps using Putative Paralog Detection and the tree-based Yang & Smith orthology inference approach. We compare the paralogs flagged using these methods and verify their performance with BLAST mapping against a reference genome sequence of Sindora glabra, and then subsequently compare the species tree topologies produced across these methods. Our comparisons of paralogs flagged across the Sindora clade show that the Putative Paralog Detection pipeline was the most accurate in identifying paralogs in terms of its similarity to the BLAST mapping, followed by the built-in paralog identification function of CAPTUS. However, the results we recovered for the Detarioideae subfamily suggest that the largest differences in species tree topology resulted from the use of paralog-filtered alignments (such as with the Putative Paralog Detection pipeline and the Yang & Smith orthology inference approaches) rather than just by removing the sequences of identified paralogous genes. This was the true for HybPiper-assembled datasets but was not seen in CAPTUS-assembled datasets. In all comparisons, the topological differences caused by different paralog handling methods tended to be confined to clades where processes such as hybridisation and introgression are prevalent. Our study provides a roadmap to establish the best approach to identify, eliminate or separate paralogs in the absence of a chromosomally contiguous reference genome for a study group, and highlights the importance of careful data inspection and processing in addition to understanding the extent of paralogy and paralog characteristics (e.g. sequence divergence between copies) for their study group.

Phylogeny↗

PubMed2026

Conserved host-exclusive oligonucleotide motifs enriched in pathogenic genes of human oncogenic viruses.

Comparative viral genomics can reveal sequence-level constraints influencing virus-host interactions. Relative minimal absent words (rMAWs) are short oligonucleotide motifs present in viral genomes but completely absent from the host, potentially reflecting selective pressures related to host adaptation and immune evasion. Using the EAGLE algorithm and the GRCh38 human reference genome, we systematically screened for prevalent rMAWs (prMAWs) across six major human oncogenic viruses: Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), human T-cell leukemia virus type 1 (HTLV-1), and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV). highly conserved 11- and 12-bp prMAWs were identified in EBV, HBV, HTLV-1, and HHV-8/KSHV, with sequence prevalences ranging from 91.5% to 97.9%. Conversely, no short prMAWs were detected in HCV or HPV, likely reflecting differences in genome architecture, mutation rates, and long-term host adaptation to the human host. Importantly, the identified host-exclusive motifs exhibited non-random genomic distribution and were preferentially embedded within viral genes central to replication, persistence, immune modulation, and oncogenesis, including EBNA-1 (EBV), HBx (HBV), Tax-associated regions (HTLV-1), and lytic replication genes of HHV-8/KSHV. Notably, all detected prMAWs were enriched in GC nucleotides and exhibited marked CpG over-representation, suggesting sequence constraints associated with epigenetic regulation and viral persistence. Collectively, these highly conserved, host-exclusive signatures offer promising, candidates for sequence-directed approaches in the diagnosis, monitoring, and investigation of virus-associated cancers.

Humans↗

PubMed2026

Mitochondrial DNA diversity in Ecuadorian populations: Recurrence of variant 16136 within haplogroup B2.

The identification of lineage-defining variants, frequently found in the coding region of mitochondrial DNA (mtDNA), is essential for refining haplogroup classification. Most mtDNA studies in South American populations have focused on the control region (CR), which has provided important insights into population structure and maternal lineage origins, although information needed for more robust phylogenetic resolution has been neglected. This study investigates the maternal genetic structure of Ecuadorian populations by combining CR and whole mitogenome analyses. Sequences from the mtDNA CR were obtained from 461 individuals (253 Mestizos and 208 Native Americans), while complete mitogenomes were sequenced for 127 individuals to improve phylogenetic resolution by identifying lineage-defining variants present in coding region. Most mtDNA haplogroups in the two population groups analyzed were of Native American origin (A2, B2, B4, C1, D1, D4), with significant differences in the distribution of specific lineages between them. Among Mestizos, African haplogroups (all within the L branches) and Eurasian haplogroups (H, K, R, U) were detected at low frequencies, whereas no African lineages were observed among Native Americans. The results obtained highlighted a heterogeneity within Ecuadorian populations that must be considered when developing mtDNA haplotype databases for forensic purposes. Whole mitogenome sequences enabled the identification of variants that refined haplogroup classifications, provided a more accurate reconstruction of the maternal genetic diversity, and improve the discrimination between Native American and Asian maternal lineages within haplogroup B4b.

Humans↗

PubMed2026

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n = 48), meningitis (TI-; n = 80), (cranial) nerve palsies/polyradiculitis (PND; n = 61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p < 0.001/sGFAP p = 0.0083; CSF-NfL p = 0.003/sNfL p = 0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p = 0.0049/sGFAP p = 0.003). The overall group effect (p ≤ 0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p = 0.012/sNfL p = 0.002; CSF-GFAP p < 0.0001/CSF-NfL p = 0.0001), which also predicted unfavorable outcome at discharge (sGFAP p = 0.006/sNfL p = 0.004; CSF-GFAP p = 0.003/CSF-NfL p = 0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

Humans↗