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Humans

Humans: explore 2000 source-linked works published from 2026 to 2026, with original documents and citations.

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Includes records with this source-supplied label or an explicit phrase match in their metadata. Matches indicate a mention, not proof that a paper uses a method or tests a material. Source versions are consolidated by DOI.

Sources: pubmed. Collection updated 2026-09-15. Counts describe this index, not the complete source archives.

PubMed2026

Diurnal differences in the effects of heat exposure on renal function: A randomized controlled crossover trial.

High temperature is a major risk factor for kidney injury, and population exposure to nighttime heat is increasing as the climate warms. However, whether renal responses to heat exposure differ between daytime and nighttime remains unclear. Forty-one healthy adults participated in a randomized crossover experiment conducted in a controlled laboratory setting. Participants were exposed to heat (32°C during daytime; 30°C during nighttime) and thermoneutral conditions (26°C) for 8 h. Blood and urine samples were collected before and after each exposure to examine various renal biomarkers reflecting glomerular filtration function, tubular injury, and early kidney stress. Heat exposure affected both blood and urinary biomarkers of kidney function, with notable diurnal differences in renal responses. Daytime heat exposure primarily affected blood markers of glomerular filtration, increasing creatinine by 7.67% (95% CI: 4.73%-10.61%) and cystatin C by 3.05% (95% CI: 0.17%-5.93%), while reducing estimated glomerular filtration rate by 0.05% (95% CI: 0.02%-0.08%). In contrast, nighttime heat exposure predominantly elevated urinary biomarkers of early kidney stress, including insulin-like growth factor-binding protein 7 (58.40%, 95% CI: 27.66%-89.14%), kidney injury molecule-1 (47.25%, 95% CI: 18.91%-75.59%), and tissue inhibitor of metalloproteinases-2 (51.88%, 95% CI: 22.26%-81.51%). Moreover, increases in insulin-like growth factor-binding protein 7 were significantly greater at night than during the day. Sleep-related parameters, including sleep quality, duration, and heart rate variability, partially mediated nighttime heat effects on renal responses. These results indicated that heat exposure induced different diurnal patterns in renal responses.

Humans↗

PubMed2026

Effect of flavored on!® nicotine pouch products on smoking behaviors: A sequential, multiple assignment, randomized controlled trial.

PURPOSE: To evaluate whether flavored versus unflavored nicotine pouch (NP) access affects cigarette reduction and smoke exposure among adults who smoke daily, and whether delayed flavor introduction affects these outcomes. METHODS: Adults who smoked ≥ 5 cigarettes/day (CPD) with interest in replacing cigarettes with NPs were enrolled in a remote, six-week, sequential multiple assignment randomized trial (n = 402 randomized; n = 400 analyzed). Participants were randomized to immediate access to seven NP flavors (Flavor), unflavored-only access for six weeks (Original), or unflavored-only for three weeks followed by flavor access (Delayed Flavor). Primary outcomes were ≥ 50% reduction in weekly mean expired-air carbon monoxide (CO) from baseline and mean CO at Week 6. Secondary outcomes included ≥ 50% CPD reduction, mean CPD, CO-verified 7-day abstinence, and incident smoke-free days. RESULTS: At Week 6, Flavor and Original did not differ in ≥ 50% CO reduction (14.3% vs 14.2%; IRR=1.0, 95% CI=0.6-1.8) or mean CO (18.3 vs 16.5 ppm; β=1.9, 95% CI=-1.3-5.0). CPD decreased across groups by Week 6, with no differences between Flavor and Original in ≥ 50% CPD reduction (50.3% vs 51.6%; IRR=1.0, 95% CI=0.8-1.2) or CO-verified abstinence (9.3% vs 8.9%; IRR=1.0, 95% CI=0.5-2.2). Flavor increased smoke-free days early, with attenuation over time. Among Week 3 non-responders, delayed flavor access increased ≥ 50% CPD reduction at Week 6 (33.3% vs 18.6%; IRR=1.8, 95% CI=1.0-3.2). CONCLUSIONS: NP access supported cigarette reduction regardless of flavor availability, but flavors may accelerate smoke-free days and improve response among individuals who do not reduce cigarette consumption with unflavored products alone.

Humans↗

PubMed2026

Cross-tissue multi-omics integration highlights BPHL and mitochondrial targets in Alzheimer's disease.

BACKGROUND: Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), yet specific molecular targets remain to be fully characterized. METHODS: A summary-data-based Mendelian randomization (SMR) framework integrated AD genome-wide association study (GWAS) statistics (39,918 cases) with blood DNA methylation quantitative trait loci (mQTL), gene expression (eQTL), and protein (pQTL) data for 1136 mitochondria-related genes. Associations were assessed using Bayesian colocalization and HEIDI testing. Tissue relevance was evaluated in four brain regions (hippocampus, amygdala, cortex, frontal cortex) using GTEx and external transcriptomic datasets. RESULTS: Screening identified eight candidates supported across blood mQTL and eQTL layers. Stepwise central nervous system (CNS) evaluation singled out biphenyl hydrolase-like (BPHL) as the consistent candidate. Higher genetically predicted BPHL expression was associated with reduced AD risk across the hippocampus (OR=0.920, 95% CI 0.873-0.970), amygdala (OR=0.925, 95%CI 0.880-0.973), cortex (OR=0.943, 95% CI 0.908-0.978), and frontal cortex (OR=0.938, 95%CI 0.901-0.976). These findings aligned with protein-protein interactions connecting BPHL to respiratory complexes and lower BPHL expression in independent AD brains. Functional enrichment converged on oxidative phosphorylation pathways. CONCLUSIONS: By integrating multi-omics data with tissue-specific validation, this study nominates BPHL as a consistent protective candidate in the brain. These findings provide genetic support for mitochondrial molecular perturbations in AD, offering insights for future validation.

Alzheimer Disease↗

PubMed2026

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans↗

PubMed2026

Chemoradiotherapy versus short-course radiotherapy for response-adapted organ preservation in early-stage and intermediate-stage rectal cancer (STAR-TREC): 12-month results of an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial.

BACKGROUND: Total mesorectal excision (TME) is the standard treatment for most early-stage and intermediate-stage rectal cancer but can cause substantial perioperative morbidity, functional impairment, and reduced quality of life. We assessed whether long-course chemoradiotherapy (LCCRT) or short-course radiotherapy (SCRT) could increase organ preservation and reduce surgery, toxicity, and quality-of-life harms without compromising oncological outcomes. METHODS: STAR-TREC is an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial in five European countries. Eligible patients were aged 16 years or older in the UK or aged 18 years or older elsewhere, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and rectal adenocarcinoma (≤40 mm staged as mrT1-T3bN0). In phase 2, participants were randomly assigned (1:1:1) to LCCRT-based organ preservation (LCCRT-OP; 50 Gy in 25 fractions plus oral capecitabine 825 mg/m2 twice daily), SCRT-based organ preservation (SCRT-OP; 25 Gy in five fractions), or primary TME. Phase 2 assessed feasibility, with recruitment at months 12 and 24 as the primary endpoint and feasibility thresholds of four or more and six or more randomisations per month, respectively. Phase 3 adopted a partially randomised patient-preference design, allowing participants to choose either organ preservation or TME. Participants that chose organ preservation were randomly assigned (1:1) to receive LCCRT-OP or SCRT-OP using centralised, computer-generated assignment, with stratification by country and MRI T category (≤T3a vs T3b) using minimisation. The phase 3 primary endpoint was organ-preservation 30 months after treatment initiation, defined as absence of TME, stoma, or local recurrence, which was assessed in the modified intention-to-treat population, which included participants in phase 2 and phase 3. After a planned interim analysis of unmasked phase 2 data, the trial steering committee and independent data monitoring committee recommended reporting a 12-month, modified intention-to-treat analysis of implementation outcomes for participants recruited before Aug 8, 2023. This study is registered with ISRCTN (14240288) and is closed. FINDINGS: Between June 14, 2017, and April 8, 2024, 503 participants were enrolled at 37 sites. Phase 2 enrolled 120 participants, with recruitment rates of three and six participants per month at months 12 and 24, respectively. Overall, 12-month TME-free survival was 60% (47 of 78 participants). After phase 3 recruitment ended, interim analysis of unmasked phase 2 data showed an early TME-free survival benefit with LCCRT versus SCRT (12-month median TME-free survival not reached [95% CI not reached-not reached] vs 7·6 months [95% CI 6·4-not reached]; hazard ratio [HR] 3·7 [95% CI 1·7-8·0]; posterior probability of superiority >99·5%). The trial steering committee and independent data monitoring committee therefore recommended expanded analysis of 426 participants recruited before Aug 8, 2023: 120 from phase 2 and 306 from phase 3. 17 participants withdrew before treatment, leaving 409 in the modified intention-to-treat population: 163 allocated to LCCRT, 168 to SCRT, and 78 to primary TME. 116 (28%) participants were female and 293 (72%) were male. Among participants who opted for organ preservation, 12-month TME-free survival was 78·5% (95% CI 72·4-85·1) with LCCRT and 60·6% (53·6-68·4) with SCRT (HR 1·90 [95% CI 1·29-2·81]). The most common grade 3-4 serious adverse events were gastrointestinal disorders (four [2%] with LCCRT vs six [4%] with SCRT vs six [8%] with TME) and procedural complications (three [2%] with LCCRT vs five [3%] with SCRT vs five [6%] with TME). One participant allocated to primary TME died after an anastomotic leak. INTERPRETATION: These early results support a response-adapted organ-preservation approach, with LCCRT appearing more effective than SCRT at 12 months. Organ-preservation might also reduce treatment-related toxicity compared with primary TME. Longer follow-up is needed for the prespecified 30-month endpoint and definitive functional and oncological outcomes. FUNDING: Cancer Research UK, Stand Up to Cancer, Dutch Cancer Society, Danish Cancer Society, Kom Op Tegen Kanker, Cancerfonden, ALF Region Stockholm, RCC Region Stockholm.

Humans↗

PubMed2026

Liquid biopsy-based detection of circulating and exfoliated cholangiocarcinoma tumor cells from blood and bile using heparan sulfate octasaccharides on integrated microfluidic systems.

Early diagnosis of cholangiocarcinoma (CCA) remains challenging because existing diagnostic approaches often lack sufficient sensitivity for reliable detection of early-stage disease. Circulating tumor cells (CTCs) in blood and exfoliated tumor cells (ETCs) in bile represent valuable targets for liquid biopsy-based detection; however, their low abundance and the complexity of clinical sample analysis pose substantial technical challenges for reliable enrichment and identification. Herein, we present a reproducible workflow for isolating and identifying CCA tumor cells from blood for CTCs and bile for ETCs using synthetic cell-surface heparan sulfate (HS) octasaccharide-functionalized magnetic beads (MBs) on integrated microfluidic systems. The method combined sample pre-processing, magnetic bead-based enrichment, controlled low-shear mixing and immunofluorescence-based identification into a unified workflow compatible with distinct clinical sample types. Key operational parameters, including MB concentration, mixing frequency, and pressure settings, were detailed to facilitate consistent performance. Using this workflow, tumor cell capture rates of approximately 70% in bile (for ETCs) and blood (for CTCs) were achieved, with a total processing time of 60-90 min per sample under clinically relevant low-abundance conditions. The platform enables reliable detection of as few as 1 tumor cell per mL of blood or bile. This method provides a practical and adaptable strategy for glycosaminoglycan-mediated liquid biopsy applications and may be extended to other tumor-cell enrichment workflows involving heterogeneous cell-surface interactions.

Humans↗

PubMed2026

Effects of umbilical cord mesenchymal stem cell-derived exosomes on periodontal ligament stem cells: An exploratory study.

OBJECTIVE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) at two osteogenic induction stages (undifferentiated and late-stage) differentially affect periodontal ligament stem cells (PDLSCs), and to explore the potential molecular basis. DESIGN: UCMSCs and PDLSCs were isolated and cultured. Exosomes were harvested from undifferentiated UCMSCs (Exo-D0) and UCMSCs after 14 days of osteogenic induction (Exo-D14). PDLSCs were treated with both exosome types. Proliferation and migration were analyzed using EdU and scratch assays, the latter under serum-free conditions. Early osteogenic differentiation was assessed by alkaline phosphatase staining and quantitative reverse transcription PCR (qRT-PCR). Differentially expressed miRNAs were identified by high-throughput sequencing and further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: Both exosome types promoted PDLSC migration. Exo-D0 enhanced early osteogenic differentiation, whereas Exo-D14 enhanced proliferation but reduced early osteogenic marker expression. Sequencing identified 21 differentially expressed miRNAs (13 upregulated, 8 downregulated). Bioinformatic prediction suggested that the putative target genes were enriched in Ras signal transduction, regulation of kinase activity, and focal adhesion, and further predicted significant enrichment in the MAPK, Ras, and PI3K-Akt signaling pathways, which are central to cell proliferation and osteogenic differentiation. CONCLUSIONS: Exosomes from undifferentiated and osteogenically induced UCMSCs exerted distinct effects on PDLSCs, potentially associated with differentially packaged miRNAs. These findings offer a basis for hypotheses about exosome-mediated mechanisms and support matching exosome sources to the intended therapeutic outcome as potential cell-free strategies for periodontal tissue regeneration and alveolar bone repair.

Humans↗

PubMed2026

Routine methods misidentify Serratia spp.: Limitations of MALDI-TOF MS revealed by whole-genome sequencing.

Accurate species-level identification within the genus Serratia remains challenging due to extensive phenotypic overlap and high genomic relatedness among closely related and recently described taxa. This study presents an evaluation of routine and genome-based identification approaches applied to clinical Serratia isolates, integrating phenotypic assays, MALDI-TOF MS (Bruker Daltonics), 16S rRNA gene sequencing, and Whole-Genome Sequencing (WGS). A total of 103 isolates collected from a teaching hospital were analyzed. WGS was performed on a subset of isolates. Conventional biochemical methods classified all isolates as Serratia marcescens, whereas MALDI-TOF MS identified 60.1% as S. marcescens, 11.6% as S. ureilytica, and 28.1% just at the genus level. Peak analysis from MALDI-TOF MS revealed specific peaks associated with S. marcescens and S. ureilytica, but limited discriminatory power. WGS of six isolates initially identified as S. ureilytica by MALDI-TOF MS revealed reclassification as Serratia sarumanii (n = 5) and Serratia montpellierensis (n = 1), supported by Average Nucleotide Identity (ANI), Average Amino Acid Identity (AAI), and Digital DNA-DNA Hybridization (dDDH) thresholds. In contrast, 16S rRNA analysis showed limited species-level resolution. Phylogenomic and SNP-based analyses confirmed these classifications with strong support. Overall, this study underscores the critical role of high-resolution genomic approaches for precise species identification and highlights the need for continuous expansion and curation of MALDI-TOF MS reference databases to support reliable clinical diagnostics and epidemiological surveillance of emerging Serratia species.

Spectrometry, Mass, Matrix-Assisted Laser Desorpti↗

PubMed2026

CoLchicine for Treatment of OsteoArthritis of the Knee (CLOAK): Clinical and biochemical outcomes from a three-month double-blind, placebo-controlled study.

OBJECTIVE: Knee osteoarthritis (KOA) causes pain and progressive disability, but pharmacologic treatments are limited. Colchicine inhibits inflammation that might modulate KOA, but efficacy trials have yielded mixed results. We tested whether colchicine, without concurrent NSAIDs, improved KOA pain, function, synovial effusion size, and OA-associated inflammatory serum biomarkers. METHODS: Participants with symptomatic KOA and radiographic Kellgren-Lawrence grades 2/3 were randomized to receive three months of daily colchicine or placebo in a double-blind manner, with no concurrent NSAID use. The primary outcome was between-group change in visual analog score (VAS) for index knee pain. Secondary outcomes included changes in Knee Osteoarthritis Outcome Scores (KOOS), size (depth in millimeters) of sonographically-identified effusions, acetaminophen use, and changes in OA-related serum biomarkers. RESULTS: From baseline to end of study of 120 enrolled participants, no significant differences were observed in improvement of VAS pain, KOOS scores or effusion size. Subsets of participants with more severe VAS pain, worse radiographic disease, or higher hsCRP or serum urate levels at baseline also showed no significant clinical benefit from colchicine compared to placebo. In contrast to the clinical outcomes, colchicine treatment was associated with significant or trending improvement in multiple OA-related serum biomarkers including hsCRP and β-NGF (p < 0.05) and PGE2, IL-1ra, IL-8, and VEGF (p < 0.16). CONCLUSION: This double-blind placebo-controlled trial of colchicine for KOA failed to demonstrate improvement in pain, function, or synovial effusion size in comparison to placebo at three months. Early improvement in OA-associated inflammatory biomarkers suggests a possible longer-term clinical benefit. Clinical Trials Registration No NCT03913442.

Humans↗

PubMed2026

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans↗

PubMed2026

Diagnostic value of blood p-tau subtypes in Alzheimer's disease progression and pathology: systematic review and meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease and the most likely to lead to dementia. With the availability of the latest therapies, the need for Alzheimer's disease diagnosis is now gradually increasing. Whereas blood phosphorylated-tau (p-tau) has demonstrated excellent performance in the prediction and diagnosis of disease progression and Aβ positivity in AD, there are differences between different p-tau subtypes. Therefore, a pooled analysis of different blood p-tau subtypes is of more important clinical value. METHOD: Relevant literature was screened by complete search in four databases, Pubmed, Embase, Cochrane Library and Scopus. Relevant data and AUC and their confidence intervals of the included literature were extracted and analyzed by classification according to p-tau subtypes. Quality assessment was performed using the QUADAS-2 tool. RESULT: Our results reveal that p-tau217 performs better in the diagnostic performance in most stages of AD, which is consistent with the guidelines. However, our results concluded that p-tau217 has poorer diagnostic performance in the stages of cognitive unimpaired or less cognitively impaired, especially in the Aβ positivity diagnosis of SCD and CU. Head-to-head meta-analyses formally confirmed that p-tau217 significantly outperforms p-tau181 across AD dementia, Aβ positivity, tau positivity, and biological staging (all P < 0.05), whereas no significant difference was observed between p-tau231 and p-tau181. CONCLUSION: By integrating single-arm pooled AUC estimates with formal head-to-head statistical comparisons, our study provides evidence-based support for plasma p-tau217 as the subtype with the most robust diagnostic performance across AD pathology and biological staging. Head-to-head analyses formally confirmed that p-tau217 significantly outperforms p-tau181 in Aβ positivity, Tau positivity, and biological staging.

Humans↗

PubMed2026

Sex- and age-specific associations of VEGFA polymorphisms with multiple sclerosis susceptibility.

AIM: To evaluate six VEGFA polymorphisms (rs1570360, rs699947, rs3025033, rs2146323, rs1413711 and rs833061) and serum VEGFA concentrations in 270 Lithuanian patients with multiple sclerosis (MS) and 270 matched healthy controls. METHODS: Genotyping was performed using real-time PCR, and serum VEGFA levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were conducted using IBM SPSS version 31.0. RESULTS: Nominal differences in VEGFA genotype and allele distributions were observed in sex- and age-stratified analyses. Among females, the rs1413711 C allele was more frequent (p = 0.005), whereas the rs833061 C allele was less frequent (p = 0.006), in MS patients than controls. In participants aged >38 years, the rs1413711 C allele was also more frequent in MS cases (57.5% vs. 46.0%, p = 0.008). Logistic regression identified nominal associations, particularly for rs1413711, rs699947 and rs833061, but none remained significant after correction for multiple testing. Serum VEGFA levels were higher in MS patients than controls (p = 0.004). Nominal genotype-related differences in serum VEGFA levels and haplotype associations with reduced MS odds were also observed, but did not remain significant after multiple-testing correction. No consistent associations were found between VEGFA variants and clinical parameters. CONCLUSION: VEGFA genetic variation and elevated serum VEGFA may be associated with MS, but the genetic findings require confirmation in larger independent cohorts.

Humans↗

PubMed2026

Opioid-sparing anesthesia based on opioid-free principles for early recovery after total knee arthroplasty: A randomized controlled trial.

OBJECTIVE: To evaluate whether an opioid-sparing anesthesia strategy (OSA), based on opioid-free anesthesia (OFA), improves early postoperative recovery quality and optimizes functional outcomes after total knee arthroplasty (TKA), compared with conventional opioid-based anesthesia (OBA). DESIGN: A randomized controlled trial with blinding of patients, surgeons, and outcome assessors. SETTING: Single center, July 2025 to February 2026. PATIENTS: 98 adult patients scheduled for elective unilateral TKA. INTERVENTION: Patients were randomized to the OSA or OBA group. The OSA regimen used esketamine and dexmedetomidine as the primary analgesic backbone, whereas the OBA regimen was opioid-based. Both groups received preoperative femoral nerve block and were administered oxycodone at skin incision and closure. Postoperatively, both groups received the same multimodal analgesia and patient-controlled analgesia. MEASUREMENTS: The primary outcome was the 24-h postoperative Quality of Recovery-15 (QoR-15) score. Secondary outcomes included 48-h QoR-15; Oxford Knee Score (OKS) and EQ-5D-3L at 1 and 3 months; high pain at 1 month and chronic postsurgical pain at 3 months. Exploratory outcomes included postoperative C-reactive protein (CRP), and postoperative nausea and vomiting (PONV), among others. RESULTS: At 24 h postoperatively, QoR-15 was higher in the OSA group than in the OBA group (118.4 ± 11.5 vs 113.3 ± 12.2; adjusted difference 5.12, 95% CI 0.51-9.74; P = 0.029), and this advantage persisted at 48 h (adjusted difference 5.54, 95% CI 1.57-9.52; P = 0.007). The OSA group had a lower incidence of PONV (P = 0.025) and lower postoperative CRP levels (P = 0.001). At 1 month, OKS was higher in the OSA group (adjusted difference 2.31, 95% CI 0.34-4.27; P = 0.022), with no significant differences in other secondary outcomes. CONCLUSION: In TKA, this OFA-based OSA strategy improved early postoperative QoR-15 scores. However, the QoR-15 difference did not reach the minimal clinically important difference, so its clinical relevance remains uncertain.

Humans↗

PubMed2026

Novel splice site variants in GBA1 are associated with Gaucher disease and genotype-phenotype correlations.

BACKGROUND: Variants in GBA1 are associated with neurodegenerative disease. This study aimed to explore pathogenic GBA1 variants. METHODS: Four patients with progressive myoclonic epilepsy (PME) and extremely low β-glucosidase levels were recruited. Whole-exome sequencing and long-range PCR were performed to identify GBA1 variants. Bioinformatic analyses were used to predict the impact of the identified variants. A literature review was performed to explore the genotype-phenotype correlations. GBA1 expression data across different brain regions and developmental stages were analyzed using the BrainSpan database. RT-PCR was performed to verify the splicing effects. RESULTS: Compound heterozygous GBA1 variants were identified in four patients. Five distinct variants were detected, including two novel splice site variants (c.308-2A>G and c.762-2A>C) and three previously reported variants. All identified variants were rare or absent in gnomAD. Splice site variants c.308-2A>G and c.762-2A>C were predicted to cause aberrant splicing. Minigene-based splicing assays coupled with RT-PCR and Sanger sequencing confirmed that both variants cause complete exon skipping (exon 4 and exon 7, respectively). All patients presented with PME onset in childhood/adolescence, intellectual regression, low β-glucosidase, and diffuse brain atrophy and were subsequently diagnosed with Gaucher disease type 3. GBA1 expression in the brain showed two distinct peaks: one in infancy and another after five years of age. The onset age of PME aligned with the second GBA1 expression peak (after five years of age). CONCLUSION: This study identified compound heterozygous GBA1 variants, including two novel candidate pathogenic splice site variants, in Gaucher disease type 3 patients, expanding the known mutational spectrum.

Humans↗

PubMed2026

Systematic review of the mutations in the active antigenic site Ø of the prefusion F protein of the Respiratory Syncytial Virus (RSV) following the implementation of monoclonal antibody prophylaxis.

BACKGROUND: Monoclonal antibody (mAb) nirsevimab, which targets the antigenic site Ø of the prefusion F protein (pre-F) of RSV, was introduced for RSV prophylaxis in several countries. METHODS: A systematic search was conducted between January 1, 2022, and July 31, 2026 for studies analyzing substitutions within the epitope of pre-F RSV protein, which is the target of nirsevimab, after the implementation of the mAb. We searched across PubMed, Scopus, Web of Science and ClinicalTrial.gov for studies involving children with confirmed RSV infection, that conducted genomic analysis. RESULTS: Seven studies (five observational and two randomized controlled trials) including 2156 RSV-positive samples (RSV-A: 1347, RSV-B: 809) were analyzed. RSV-A strains showed limited variability within antigenic site Ø, with K65R being the most common substitution and K209E being the only intermediate-resistance RSV-A substitution. RSV-B strains demonstrated substantially higher substitution frequencies, particularly involving I206M, Q209R, and S211N. Most identified substitutions appeared to represent naturally occurring polymorphisms and retained susceptibility to nirsevimab, while multiple RSV-B substitutions and combinations involving residues 64-68 and 204-208 demonstrated reduced susceptibility or high-level resistance. Resistance-associated variants were detected in 28 of 2156 (1.3%) RSV-positive samples and exclusively among nirsevimab breakthrough infections. In a sub-analysis restricted to nirsevimab-treated individuals, resistance-associated variants were significantly more frequent among RSV-B than RSV-A (9.8% vs 0.5%; p < 0.001). CONCLUSION: Most substitutions that were detected within the nirsevimab antigenic site reflect ongoing natural RSV evolution and do not significantly affect nirsevimab susceptibility. However, detection of resistance-associated variants highlights the importance of continuous genomic and phenotypic surveillance.

Humans↗

PubMed2026

TWIST2-dependent transcriptional activation of TPI1 mediates TGF-β1-driven fibroblast activation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by aberrant profibrotic signaling and excessive extracellular matrix deposition, accompanied by fibroblast-to-myofibroblast transition. Despite extensive investigation, the molecular mechanisms underlying IPF pathogenesis remain incompletely understood. Here, we investigated the role of triosephosphate isomerase 1 (TPI1) in IPF progression and its regulation by transforming growth factor-β (TGF-β) signaling. Loss-of-function analyses identified TPI1 as a downstream effector of TGF-β1, as its knockdown markedly suppressed fibrotic marker expression, fibroblast proliferation, and migration. Mechanistically, TWIST2 was shown to function as a direct transcriptional regulator of TPI1, binding to its promoter and promoting transcriptional activation. Rescue experiments further confirmed that the TWIST2-TPI1 axis is central to the progression of pulmonary fibrosis. Notably, knockdown of either TPI1 or TWIST2 effectively attenuated TGF-β1-induced fibrotic phenotypes. Collectively, these findings define the TGF-β1/TWIST2/TPI1 signaling axis as an important regulator of pathogenic fibroblast behavior and pro-fibrotic responses through transcriptional control of TPI1, highlighting its potential as a therapeutic target for IPF.

Twist-Related Protein 1↗

PubMed2026

Ensemble DNA methylation clock demonstrates Immune-metabolic aging signatures associated with mortality.

Aging is a multifactorial process that is best described in terms of the progressive acquisition of multiple layers of phenotypic changes, such as epigenetic modifications, inflammation, and metabolic dysregulation. DNA methylation clocks have been extensively used to construct epigenetic clocks based on the DNAm profiles that can be used to estimate biological age and predict age-associated outcomes. Nevertheless, the vast majority of clocks constructed so far have been based on linear models, which are unlikely to fully account for the heterogeneity and non-linearity of survival-related DNAm signatures. In this work, we constructed a heterogeneous stacked ensemble survival model based on DNAm data obtained from the Framingham Heart Study. We first identified 190 CpG loci using elastic net Cox regression and subsequently constructed a survival prediction model based on the fusion of five complementary survival models by means of a neural network meta-learner. The prediction power of the survival model was evaluated in an external validation cohort, where we observed strong performance for predicting all-cause mortality that significantly exceeded PhenoAge and was statistically comparable to GrimAge. These performance estimates were derived in cohorts of European ancestry and externally validated in postmenopausal women aged 50-79 years, and should therefore be interpreted as applicable only to demographically similar populations.

Humans↗

PubMed2026

Efferocytosis regulatory factors in atherosclerosis: A preclinical systematic review.

BACKGROUND: Impaired efferocytosis is a key driver of plaque instability during atherosclerosis progression. Efficient clearance of apoptotic cells through efferocytosis relies on the coordinated action of multiple regulatory factors. METHODS: PubMed, Web of Science, ScienceDirect, OVID MEDLINE, and Scopus were searched for studies published up to February 7, 2026. Eligible preclinical studies were systematically reviewed to identify endogenous factors that regulate efferocytosis in atherosclerosis. Clinical evidence was also incorporated to enable a preliminary translational assessment of these regulatory factors. RESULTS: Thirty-five endogenous regulatory factors were identified from 36 included studies, and their functional roles across distinct stages of efferocytosis were characterized. Notably, metabolic regulators such as PKM2, PFKFB3, GLS1, and Drp1 were involved in distinct efferocytosis stages. This suggests that metabolic reprogramming may provide the metabolic support require for efficient efferocytosis and inflammation resolution. Ten factors were supported by preliminary clinical evidence consistent with preclinical data. PKM2 was the only candidate biomarker with prospective observational data. However, its independent predictive value still requires validation in multicenter prospective studies. CONCLUSIONS: This review provides a systematic synthesis of 35 endogenous efferocytosis regulators and elucidates their regulatory network in atherosclerosis based on a functional stage framework. Metabolic reprogramming is identified as a central hub linking efferocytosis efficiency to inflammation resolution. This review offers a new theoretical basis for efferocytosis-targeted intervention strategies.

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