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PubMed2026

Emergence of a Novel, Phenotypically Difficult-to-Detect Vancomycin-Resistant Enterococcus faecium Clone (ST117/CT7799).

A significant increase of vancomycin-resistant Enterococcus faecium (VREfm) infections was observed in South-Eastern Austria since 2024. The prolonged outbreak is caused by a novel vanB-VREfm clone (ST117/CT7799, "VREfmstyr"). This study characterizes the atypical difficult-to-detect resistance phenotype and assesses the genomic relatedness of the isolates. Patient and outbreak characteristics were investigated including whole genome sequencing of the isolates. Sensitivity of broth microdilution (BMD), gradient tests (GT), disk diffusion (DD), and automated susceptibility testing (VITEK2) was compared. The performance of commercial screening media was evaluated. From sporadic detections in early 2024 case numbers began to rise during the year. In 30/31 (97%) of all cases, intra-hospital transmission was considered likely and an association with invasive procedures was identified in most cases. Core genome multilocus sequence typing revealed only six allelic differences between VREfmstyr isolates collected in a 12-month period, all belonging to the E. faecium ST117/CT7799 lineage. BMD detected vancomycin resistance (MIC > 4 mg/L) in no more than 16/31 (52%) of isolates after 24 h incubation, while GT and DD misclassified all isolates. Only prolonged incubation improved the performance of these assays. VITEK2 analysis, however, correctly classified all 31 isolates. Of four commercially available VRE-screening agars, only one was capable of detecting VREfmstyr after 24 h incubation. The emergence and clonal dissemination of VREfm ST117/CT7799 reveals a serious diagnostic gap as commonly used diagnostic algorithms fail to reliably detect this resistance phenotype. Our findings should help to further evaluate the true geographical distribution and clinical significance of this novel VREfm clone.

Enterococcus faecium↗

PubMed2026

Early proteomic and metabolic signatures of liver and eye in OAT-deficient mice.

Ornithine aminotransferase (OAT) deficiency causes hyperornithinemia and gyrate atrophy (GA) of the choroid and retina, a rare inherited retinal degeneration. To understand the early molecular changes that make the eye susceptible to damage, we performed quantitative proteomic and metabolomic profiling of liver, retina, and retinal pigment epithelium and choroid (RPE/Cho) from OAT-deficient (Oatrhg) mice prior to detectable vision impairment. In addition to reduced OAT expression and elevated ornithine, methylation-related metabolites such as N(6)-methyl-lysine were altered in all examined tissues of Oatrhg mice. In the liver, excess ornithine was directed into urea cycle metabolism, together with altered expression of detoxification enzymes and histone H2B proteins. In contrast, the retina showed minimal proteomic changes but pronounced alterations in amino acid pathways that support glutamate homeostasis. The RPE/Cho demonstrated the most extensive proteomic changes, particularly in mitochondrial metabolism, cytoskeleton, and extracellular matrix, along with changes in metabolites involved in lysine metabolism, energy metabolism, and antioxidant capacity. Incubation with 13C lysine demonstrated that lysine was primarily degraded in RPE/Cho but not the retina, and ornithine enhanced lysine degradation in an OAT-dependent manner. Together, these findings highlight common and tissue-specific impacts of OAT on the liver and ocular tissues and provide insight into early molecular changes that contribute to the selective vulnerability of the eye in GA. Proteomics data are available via ProteomeXchange (PXD063614) and metabolomics data via MassIVE repository (MSV000101103).

Animals↗

PubMed2026

Effects of permissive hypercapnia on intraoperative cerebral oxygenation and early postoperative cognitive function in older patients with fragile brain function during the non-acute phase undergoing laparoscopic colorectal surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Older adults with non-acute fragile brain function (NFBF) may be particularly susceptible to perioperative disturbances in cerebral oxygenation and postoperative neurocognitive decline. Permissive hypercapnia (PHC) may enhance cerebral oxygenation, but its effects in this population remain unclear. We examined whether PHC-based ventilation improves intraoperative regional cerebral oxygen saturation (rSO2) and early postoperative cognitive outcomes in older patients with NFBF undergoing elective laparoscopic colorectal surgery. METHODS: In this single-center, single-blind randomized trial, 76 patients were assigned in a 1:1 ratio to PHC-based or conventional ventilation. The primary outcome was the absolute change in rSO2 from baseline (T0) to the end of surgery (T4). Analyses followed the intention-to-treat principle, with prespecified per-protocol sensitivity analysis. Secondary outcomes included intraoperative rSO2 trajectories, cerebral oxygen extraction-related indices, early postoperative cognitive screening, serum neuron-specific enolase and interleukin-6, and safety outcomes. RESULTS: PHC significantly increased rSO2 relative to conventional ventilation (left: adjusted mean difference [aMD] 10.64, 95% CI 8.96-12.33; right: aMD 10.16, 95% CI 8.22-12.11; both P < 0.001), with consistent sensitivity results. Repeated-measures analyses showed persistently higher intraoperative rSO2 in the PHC group. Cerebral oxygen extraction-related indices were generally lower with PHC. However, early postoperative cognitive outcomes and serum biomarkers did not differ between groups. Emergence time was modestly longer with PHC, whereas adverse events were comparable. CONCLUSIONS: PHC-based ventilation favorably modified intraoperative cerebral oxygenation and oxygen-extraction profiles but did not translate into detectable early postoperative cognitive or biomarker benefits in older adults with NFBF.

Humans↗

PubMed2026

Sitosterolemia: evolving strategies for earlier diagnosis.

PURPOSE OF REVIEW: Sitosterolemia is a rare autosomal recessive lipid disorder caused by biallelic pathogenic variants in ABCG5 or ABCG8 , resulting in excessive intestinal absorption and impaired biliary excretion of plant sterols. Although historically considered exceptionally rare, recent genetic studies suggest the disorder is substantially underdiagnosed, with marked phenotypic heterogeneity ranging from xanthomas and premature atherosclerosis to hematologic abnormalities, and frequently mimics familial hypercholesterolemia. This review summarizes recent advances in the clinical, biological, and genetic diagnosis of sitosterolemia, with a focus on strategies that may facilitate earlier detection. RECENT FINDINGS: Phytosterol quantification, particularly sitosterol, campesterol, and stigmasterol, remains indispensable for accurate diagnosis. Hematologic abnormalities, including hemolytic anemia, stomatocytosis, and macrothrombocytopenia, are increasingly recognized as valuable diagnostic clues complementing the biochemical approach. Expanded variant catalogs for ABCG5/ABCG8 and genome-wide association studies have revealed potentially polygenic contributions to phytosterol metabolism extending beyond these two genes. However, no specific guidelines have yet been established for cascade screening. SUMMARY: Earlier diagnosis requires integration of clinical, biochemical, hematologic, and genetic data. Plasma phytosterol measurement remains the diagnostic cornerstone. Improved disease awareness, broader access to sterol testing, and expanded genetic screening may reduce diagnostic delays and enable timely management, including ezetimibe and dietary phytosterol restriction.

Humans↗

PubMed2026

Comprehensive identification and evolutionary analysis of the Wnt gene family in bivalves: Insights into the larval development of the noble scallop Chlamys nobilis.

The Wnt gene family regulates fundamental developmental processes in metazoans, but its evolutionary composition and developmental deployment in bivalves remain largely unresolved. Here, we performed a comparative genomic analysis of Wnt genes in 19 bivalve species and examined developmental expression profiles in the noble scallop Chlamys nobilis, with Crassostrea gigas and Chlamys farreri used for cross-species comparison. A total of 235 Wnt genes were identified and assigned to 12 subfamilies. No reliable Wnt3 ortholog was detected in any analyzed bivalve, supporting the view that Wnt3 loss occurred early during lophotrochozoan evolution rather than representing a lineage-specific absence. Most Wnt proteins retained the conserved WNT domain, indicating strong structural conservation, whereas lineage-specific copy-number variation and gene loss were observed among species. C. farreri and C. gigas each retained 12 Wnt genes and lacked Wnt3, whereas C. nobilis lacked Wnt3, Wnt7, and Wnt16. Developmental transcriptome analysis and RT-qPCR revealed clear stage-specific expression patterns. In C. gigas, Wnt2/10/A were highly expressed during earlydevelopment and peaked around the D-shaped larval stage, while Wnt8 and Wnt11 showed distinct stage-specific peaks. By contrast, Wnt1/5/6/9 were more active during later larval development or juvenile formation. These results provide a comparative framework for bivalve Wnt evolution and identify candidate Wnt genes potentially involved in larval development and aquaculture-relevant developmental transitions.

Animals↗

PubMed2026

Delayed maturation of the milk microbiome in women with type 1 diabetes.

AIMS/HYPOTHESIS: The breastmilk microbiome plays a crucial role in gut microbial colonisation and immune development, but little is known about how it is influenced by type 1 diabetes. METHODS: We conducted a longitudinal 16S rRNA gene sequencing study of milk from women with type 1 diabetes (n=69 pregnancies; 174 samples) and women who did not have type 1 diabetes (n=49 pregnancies; 123 samples), collected at seven timepoints from birth to 15 months postpartum. Alpha diversity (richness, inverse Simpson evenness) was analysed by generalised linear mixed models, beta diversity was analysed by Bray-Curtis dissimilarities and PERMANOVA, and differential abundance was analysed by limma. Additionally, we examined associations with maternal genetic risk score (GRS), maternal HLA type, glycaemic management (HbA1c) and breastmilk secretory IgA (sIgA), and performed a parallel analysis for the infant stool microbiome. RESULTS: A significant interaction between type 1 diabetes status and timepoint was observed for alpha diversity, both richness (p=0.01) and inverse Simpson diversity (p=0.003), indicating distinct temporal trajectories between women with and without type 1 diabetes. In those without type 1 diabetes, richness increased significantly between birth and 1 week postpartum, but this early increase was delayed in women with type 1 diabetes to between 1 week and 3 months postpartum (p=0.002). Beta diversity analysis revealed earlier and more extensive compositional shifts in women without type 1 diabetes compared to those with type 1 diabetes. These differences persisted after adjusting for Caesarean delivery, BMI, parity and infant sex, and were not attributable to a delay in initiating breastfeeding. Taxa with delayed enrichment in women with type 1 diabetes included Streptococcus spp. and Rothia mucilaginosa, which metabolise human milk oligosaccharides to short-chain fatty acids to promote development of the infant's gut barrier and immune system. Maternal GRS, HLA, HbA1c or sIgA were not associated with milk microbiota diversity trajectories. In infant stool samples, alpha diversity did not differ between exposure groups, and showed no evidence of delayed maturation. Beta diversity revealed an early compositional shift between birth and 1 week postpartum only in infants born to women without type 1 diabetes. Similarly, significant taxonomic changes between birth and 1 week postpartum were detected only in infants born to women without type 1 diabetes, but with some taxa differing between exposure groups at 1 week. CONCLUSIONS/INTERPRETATION: Maternal type 1 diabetes is associated with delayed early maturation of the breastmilk microbiome. Early compositional differences in microbiota restructuring were also observed in the infant gut, partially mirroring the pattern in the milk microbiome; however, sustained differences in infant gut microbiota diversity were not detected. Further investigation could determine whether these changes affect development of the infant's gut and immune system.

Humans↗

PubMed2026

The role of artificial intelligence in the diagnosis and prognosis of traumatic brain injury based on brain CT scans: a systematic review.

Traumatic brain injury (TBI) is a leading cause of emergency department visits and a major contributor to injury-related mortality and long-term neurological disability. Non-contrast computed tomography (CT) is the gold-standard imaging modality for the rapid diagnosis of TBI. Clinical outcomes depend strongly on early detection and prompt acute management. Artificial intelligence (AI)-based models may support faster automated identification of traumatic findings and early prediction of patient prognosis. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, IEEE Xplore, ACM Digital Library, and the Cochrane Library in accordance with PRISMA 2020 guidelines to evaluate AI-based models for automated detection of TBI-related findings on CT and for prediction of clinical outcomes. Risk of bias and applicability were assessed using QUADAS-2 for diagnostic accuracy studies and PROBAST + AI for prediction model studies. Twenty-two studies were included. Sixteen studies evaluated diagnostic tasks and 10 evaluated prognostic outcomes, with four studies contributing to both categories. Diagnostic performance was generally high, with many studies reporting AUC values approaching or exceeding 0.90, particularly for larger lesion volumes.Prognostic performance was more variable, with moderate to high discrimination and substantial heterogeneity. Only 9 studies incorporated independent external validation, and performance was frequently lower in external cohorts. All prognostic model studies were judged to be at high overall risk of bias using PROBAST + AI, and most diagnostic accuracy studies also demonstrated high or unclear risk of bias in at least one QUADAS-2 domain, most frequently in patient selection. AI-based models applied to brain CT demonstrate strong technical performance for both diagnostic and prognostic tasks in TBI. However, most studies relied on retrospective designs and lacked independent external validation which limits models generalizability and raises concern for potential overfitting. Prospective, multicenter studies with standardized methodologies and rigorous external validation are required before widespread clinical implementation.

Humans↗

PubMed2026

Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.

INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failure. These conditions may mimic other metabolic diseases detected in newborn screening, complicating early diagnosis. The AKR1D1 gene encodes Δ4-3-oxosteroid 5β-reductase, a key enzyme in primary bile acid synthesis, and pathogenic variants cause bile acid synthesis defect type 2 (OMIM #235555). CASE DESCRIPTION: We report a 3-month-old male infant with severe neonatal cholestasis and a history of elevated tyrosine levels in newborn screening. Pregnancy was high risk and unmonitored, with birth outside a hospital. Parental consanguinity was first-degree. Early metabolic evaluation showed transient normalization of tyrosine levels, but subsequent analyses revealed recurrent hyper-tyrosinemia. Urinary organic acids showed increased 4-hydroxyphenyl metabolites, with absent succinylacetone, excluding tyrosinemia type I. Progressive cholestasis developed, accompanied by coagulopathy, hyperbilirubinemia, hyperammonemia, and markedly elevated alpha-fetoprotein. Imaging revealed no structural liver abnormalities. Clinical exome sequencing identified a novel homozygous start-loss variant in AKR1D1, likely abolishing functional enzyme production. Metabolic studies confirmed increased urinary excretion of 3-oxocholenoic acids consistent with abnormal bile acid synthesis and supporting a diagnosis of bile acid synthesis defect type 2. Oral cholic acid therapy led to stabilization and improvement in clinical and biochemical parameters. DISCUSSION/CONCLUSION: This case illustrates the diagnostic complexity of neonatal cholestasis, particularly when initial metabolic findings suggest alternative etiologies. It highlights the importance of newborn screening as a tool for broader diagnostic suspicion and the critical role of early molecular diagnosis and multidisciplinary care. Timely recognition and targeted therapy can improve outcomes, prevent liver transplantation, and enable accurate genetic counseling, especially in consanguineous families.

Humans↗

PubMed2026

Mapping Wastewater Pathogens and Their Associated Environmental and Public Health Risk Factors: A Systematic Review and Meta-Analysis.

BACKGROUND: Wastewater-based epidemiology (WBE) has emerged as a critical tool for public health surveillance, yet its application across diverse pathogens and geographical settings remains inconsistent. This systematic review synthesizes global evidence on wastewater surveillance to identify associated risk factors. METHODS: Following PRISMA 2020 guidelines (PROSPERO: CRD420261297382), a systematic search was conducted across PubMed, Scopus, Google Scholar, and Web of Science for studies published between 2000 and 2025. RESULTS: Thirty-nine peer-reviewed studies were included. The evidence base is geographically skewed toward the European Region (48.7%) and the Americas (23.1%), with significant underrepresentation in LMICs. Viruses were the primary biological target (89.7%), followed by bacteria (7.7%) and parasites (2.6%). A proportion meta-analysis of 31 eligible studies demonstrated a pooled wastewater pathogen detection prevalence of 62% (95% CI: 47.5-74.6%), with the European Region yielding the highest regional estimate (73%) and the African Region the lowest (8.3%). Conventional PCR and sequencing methods showed higher pooled detection rates (92.4% and 90.1%, respectively) than RT-qPCR (47.9%). CONCLUSION: WBE provides a robust early-warning system indicating a need for broader pathogen diversity, incorporating bacterial and parasitic surveillance and expansion into rural and resource-limited regions.

Contamination↗

PubMed2026

The effects of visuomotor training and tDCS stimulation on visuomotor integration and visual processing: an electrophysiological approach.

BACKGROUND: Visuomotor integration coordinates visual and motor cortical activity to produce goal-directed responses and can be indexed by Rolandic Mu-rhythm suppression and visual evoked potential (VEP) P100 parameters. Perceptual-motor training improves visuomotor performance, and transcranial direct current stimulation (tDCS) over primary motor cortex (M1) has been reported to enhance motor learning when paired with training. This study examined whether anodal M1 tDCS augments the effects of Senaptec visuomotor training in healthy adults. METHODS: Sixty participants were randomized to active anodal tDCS (five 10-minute sessions, 1 mA; n = 31) or sham (n = 29) over M1 immediately before each Senaptec training session; 53 completed all sessions and post-testing. Outcomes were Mu-suppression ratios, VEP P100 latency and amplitude, and Senaptec measures of visual sensitivity and visuomotor control. RESULTS: Active tDCS produced no augmentation of any outcome, with no significant group × time interaction for any measure, consistent across composite and task-level analyses. Training alone produced no change in Mu suppression or visuomotor control. By contrast, both groups showed significant training-related gains in visual sensitivity, including near-far quickness and stereopsis, accompanied by shorter P100 latencies and larger amplitudes, indicating more efficient early visual processing. CONCLUSIONS: A clear dissociation emerged: training produced robust improvements in early visual processing, whereas neither tDCS nor training altered sensorimotor (Mu) or visuomotor-control measures. The tDCS results should be interpreted cautiously given the modest dose and limited power to detect small effects, rather than as evidence of inefficacy. Tablet-based perceptual training enhanced visual processing independent of neuromodulation.

Humans↗

PubMed2026

Herd-level heterogeneity of antimicrobial resistance in commensal Escherichia coli: A nationwide high-throughput survey of Australian pig herds.

Antimicrobial resistance in commensal Escherichia coli provides a useful indicator for overall antimicrobial resistance burden. We applied this approach to assess antimicrobial resistance within and between commercial pig herds across Australia. A high-throughput robotic workflow was used to isolate 2730 E. coli colonies from rectal contents collected in 2022 from healthy slaughter pigs (n = 300) representing 30 herds (∼70% of national production). Up to 94 isolates per herd underwent antimicrobial susceptibility testing using the Robotic Antimicrobial Susceptibility Platform. Isolate- and herd-level antimicrobial resistance indices were calculated, weighting antimicrobials by their human health importance. Resistance to first-line agents was widespread: ampicillin 77% and tetracycline 79%. By contrast, resistance to critically important antimicrobials was rare (ciprofloxacin 0.11%; extended-spectrum cephalosporins 0.04%), and no clinical resistance to carbapenems or colistin was detected. Overall, 56.9% of isolates were multi-class resistant. Herd-level antimicrobial resistance within indices ranged from 1.51 to 5.76, revealing substantial between-herd heterogeneity. Three herds carried critically important antimicrobials-resistant isolates that would likely have been missed using conventional, lower-density sampling approaches. Whole-genome sequencing identified fluoroquinolone-resistant isolates belonging to ST10 and ST69 (both qnrS1), and ST744 (Quinolone Resistance Determining Region mutations plus blaCTX-M-27). By testing approximately tenfold more isolates than conventional surveys, we uncovered considerable antimicrobial resistance with heterogeneity within and between animals and herds, including farm-specific variability. This expanded sampling also enabled detection of critically important antimicrobial resistance at very low prevalence. In conclusion, high-throughput, high-density testing offers a practical early-warning system and herd-level benchmark to inform surveillance and targeted interventions.

Animals↗

PubMed2026

Screening for neurofibromatosis type 1-related optic pathway gliomas: a systematic review.

BACKGROUND: Neurofibromatosis-type 1 (NF1) is a genetic disorder characterized by developing optic pathway gliomas (OPGs) in 15%-20% of patients with higher estimates where consanguinity is prevalent. Clinically, NF1-OPG might be unpredictable with the risk of OPG progression and visual impairment. The optimal time for screening is controversial. We aim to identify the mean/median age at diagnosis of NF1-OPG and its clinical spectrum. METHODS: A systematic review of PubMed, Web of Science, and Embase databases was conducted for English-language publications from January 1993 to October 2025, exploring the visual screening of OPGs in NF1 patients, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews (PROSPERO ID: CRD420251036244). Inclusion criteria focused on studies reporting the age at OPG diagnosis and visual manifestations in NF1 patients. Data were extracted on demographics, age at NF1 and OPG diagnosis, tumour location (using the Dodge classification), and presenting symptoms. Sixteen studies met the inclusion criteria. RESULTS: Among 4 739 NF1 patients, 818 had OPGs, with prevalence ranging from 4.2% to 46.7%. The age at NF1 diagnosis ranged from 0 to 132 months (mean: 18-38 months), and at OPG diagnosis from 0-240 months (median: 29-58 months). Approximately 58.4% of OPGs were asymptomatic, and 25% were above the age of 5 years. Among symptomatic patients, the most frequent presentations included decreased visual acuity (62%), abnormal optic disc (45%), proptosis (20%), strabismus (12%), and visual field defects (7%). CONCLUSIONS: NF1-related OPGs typically present early within 6 years of age. Early ophthalmologic and/or radiologic screening at the time of NF1 diagnosis enhances the detection of silent OPGs.

Humans↗

PubMed2026

Multi-omic biomarkers in cardiovascular disease: Discovery to clinical translation.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, necessitating improved risk stratification and early detection strategies. Multiomics approaches that integrate genomics, transcriptomics, proteomics, metabolomics, and epigenomics offer unprecedented opportunities for biomarker discovery and precision medicine in cardiovascular care. This narrative review examines the current landscape of multiomics biomarkers for CVD, tracing their evolution from discovery to clinical translation. We synthesize evidence from recent studies evaluating the clinical utility of integrated omics approaches across diverse cardiovascular conditions, including atherosclerotic cardiovascular disease, heart failure, and atrial fibrillation. High-throughput proteomics has identified novel protein signatures that enhance cardiovascular risk prediction beyond traditional risk factors. Metabolomics has revealed pathway-specific biomarkers, including trimethylamine N-oxide and lipid species, associated with atherogenesis. Polygenic risk scores derived from genomic data demonstrate incremental value when combined with clinical risk scores. Multiomics biomarkers represent a transformative approach to cardiovascular risk assessment and disease management.

Humans↗

PubMed2026

Dissemination of blaKPC-3-harbouring Klebsiella pneumoniae across ST48 and ST628 in multiple healthcare facilities in the Republic of Korea.

Klebsiella pneumoniae carbapenemase-3 (KPC-3) remains rare in South Korea, where KPC-2 is the dominant carbapenemase, making the repeated detection of a concentrated blaKPC-3 signal over five years notable. We performed genomic analyses of blaKPC-3-harbouring K. pneumoniae from a regional healthcare network. Two chromosomally distinct lineages with concordant capsule loci (ST628/KL15 and ST48/KL62) presented multidrug-resistant phenotypes, and the virulence-associated loci were confined to ST48. Single-nucleotide polymorphism (SNP) analyses revealed near-clonal relatedness within lineages, with 0-38 pairwise SNPs among ST628 isolates and 8 SNPs between the two ST48 isolates. Core-genome multilocus sequence typing (cgMLST) supported this structure, as ST628 isolates were assigned to complex type 19149 with 0-7 allelic differences, and ST48 isolates were assigned to complex type 19150 with 5 allelic differences. These patterns support vertical spread via clonal expansion across multiple facilities. Despite substantial chromosomal separation, most isolates carried the same IncFII(K) plasmid backbone and blaKPC-3, and they were nearly indistinguishable from a plasmid previously reported in South Korea. One isolate carried blaKPC-3 on a distinct multireplicon IncFIB(K)/IncFII(K) plasmid, indicating that the signal was not confined to a single plasmid backbone. In both plasmids, blaKPC-3 was embedded within Tn4401b. These findings indicate that a rare blaKPC-3 genotype can persist regionally through sustained clonal dissemination and that cross-lineage linkage is compatible with past horizontal transfer involving a conserved plasmid. These findings underscore the need for subtype-resolved, regionally coordinated genomic surveillance in connected healthcare networks to detect uncommon carbapenemase variants early.

Klebsiella pneumoniae↗

PubMed2026

HPV circulating tumor DNA as a potential prognostic and predictive biomarker in head and neck squamous cell carcinoma: a systematic review.

PURPOSE: Human papillomavirus circulating tumor DNA (HPVctDNA) has emerged as a promising prognostic biomarker in HPV-related head and neck squamous cell carcinoma (HNSCC). This systematic review aimed to synthesize current evidence on the diagnostic accuracy and prognostic value of HPVctDNA in HNSCC management. MATERIAL/METHODS: We systematically reviewed a PubMed-indexed database of studies published between January 2012 and September 2025. Eligible studies were assessed for design, primary tumor site and stage, treatment modality, HPVctDNA detection method, diagnostic accuracy (sensitivity and specificity), and reported clinical endpoints. Descriptive syntheses were performed; sensitivity and specificity were standardized to proportions and summarized as median values per group. RESULTS: A total of 60 studies, including 8,234 patients were analyzed, of which 41 (68.3%) focused exclusively on oropharyngeal squamous cell carcinoma (OPSCC) and 17 (28.3%) included mixed HPV-related HNSCC subsites and HPV-positive cancers of unknown primary. The median follow-up across the included studies was 23 months. Among the included studies, 19 were retrospective (31.7%) and 33 were prospective (55.0%), with a small proportion of cross-sectional and randomized clinical trials. Overall, 40 (66.7%) evaluated the role of HPVctDNA in a curative setting. Plasma was the most common sample type, analyzed in 55 studies (91.7%), while 5 studies also included saliva. Detection methods varied: 40 employed droplet digital PCR (ddPCR), 16 used quantitative PCR (qPCR) and 4 applied NGS-based assays. Most of these studies (38, 63.3%) evaluated the prognostic utility of HPVctDNA, while only 4 (6.7%) assessed HPVctDNA in a screening or diagnostic setting. Regarding diagnostic accuracy, the median sensitivity across evaluable studies was 91.1%, while the median specificity was 99.4%. In OPSCC-only cohorts, the median sensitivity and specificity were 89.4% and 99.4%, respectively. Dynamic changes in HPVctDNA levels during or after treatment were consistently associated with outcomes: clearance or sustained negativity correlated with higher response rates, improved progression-free survival and overall survival, while persistent positivity or increasing levels predicted disease progression and recurrence. CONCLUSIONS: HPVctDNA demonstrates high diagnostic and prognostic accuracy in HPV-related HNSCC, especially OPSCC, supporting its use for prognosis, treatment monitoring and early detection of recurrence. However, prospective interventional studies are still required to demonstrate that HPVctDNA-guided treatment decisions improve clinical outcomes before routine implementation.

Humans↗

PubMed2026

Integrated salivary proteomic and metabolomic analyses reveal molecular characterization and novel biomarker panels of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by chronic inflammation, oxidative stress, and metabolic dysregulation. The lack of convenient and easily-accessible non-invasive diagnostic approaches remains a major clinical challenge. This study applied an integrated saliva-based proteomic and untargeted metabolomic strategy to identify potential biomarkers for COPD classification. Comprehensive multi-omics analyses identified 225 differentially abundant proteins and 60 differentially abundant metabolites between patients with COPD and healthy controls, including 24 biologically relevant endogenous metabolites. Functional enrichment analyses revealed pronounced dysregulation of mitochondrial energy metabolism, redox homeostasis, lipid remodeling, and inflammatory-related pathways in COPD. By integrating salivary proteomic and metabolomic biomarkers, a stepwise feature selection combined with LASSO logistic regression was used to construct diagnostic models, yielding an optimized biomarker panel consisting of 11 proteins and 2 endogenous metabolites. This integrated model achieved excellent diagnostic performance, with an area under the ROC curve of 0.96. Collectively, these findings demonstrate that integrated salivary proteomic and metabolomic profiling provides a robust, non-invasive approach for COPD classification and offers a promising foundation for the development of biosensor-based diagnostic platforms and early disease detection. SIGNIFICANCE: Chronic obstructive pulmonary disease (COPD) remains a major global health burden. Current diagnostic approaches rely largely on spirometry and clinical assessment, which are limited in sensitivity for early-stage disease and unsuitable for large-scale screening. This study employs an integrated saliva-based proteomic and metabolomic strategy to identify non-invasive biomarkers for COPD classification. Our findings reveal coordinated dysregulation of mitochondrial energy metabolism, redox homeostasis, and lipid remodeling in COPD, highlighting the interconnected roles of metabolic reprogramming, oxidative stress, and inflammation in disease pathophysiology. Notably, a robust diagnostic panel comprising 11 proteins and 2 endogenous metabolites was established, achieving excellent classification performance (AUC of 0.96). To our knowledge, the integrated application of salivary proteomics and metabolomics for COPD diagnosis remains largely unexplored, underscoring the significance and translational potential of our findings.

Humans↗

PubMed2026

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p = 0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p = 0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

Humans↗

PubMed2026

From host response to genomic targets: electrochemical biosensing of tuberculosis biomarkers.

Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, with timely diagnosis continuing to be a major challenge, particularly in resource-limited settings. Conventional TB diagnostic methods are limited by low sensitivity, long turnaround times, and an inability to reliably differentiate latent from active disease. Biomarker-based diagnostic strategies have therefore gained increasing attention as they offer the potential to improve early detection, disease differentiation, and treatment monitoring. Herein, we examine electrochemical biosensing strategies for TB diagnostics using a biomarker-class-driven framework, covering host-response biomarkers (IFN-γ and TNF-α), pathogen-derived antigens (ESAT6, CFP10, CFP10-ESAT6, MPT64, Ag85, HspX and LpqH), cell-wall signatures and whole-cell markers (LAM and whole cell Mtb), and genomic markers (Mtb DNA and IS6110). Through structured comparison of recognition elements, biointerface designs, signal amplification strategies, electrochemical techniques, matrices, and validation levels, this review identifies the most promising technical approaches for different TB biomarker classes. It further highlights key translational bottlenecks, including limited clinical validation, buffer-based testing, complex multistep amplification, redox-probe dependence, matrix fouling, and insufficient evidence of manufacturability. This review therefore provides practical guidance for developing electrochemical TB biosensors that are analytically sensitive, clinically relevant, and suitable for decentralized diagnostic applications.

Biosensing Techniques↗