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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

Pre-transport dietary chitosan improves the physiological robustness of juvenile largemouth bass (Micropterus salmoides) by modulating antioxidant and inflammatory responses.

The acute stress caused by long-distance transport can lead to oxidative damage, immune dysfunction, and health deterioration in fish. This study evaluated dietary chitosan as a pre-transport nutritional strategy for juvenile largemouth bass (Micropterus salmoides). Five experimental diets contained chitosan at 0, 2.5, 5.0, 7.5, or 10.0 g/kg, designated as p0, p25, p50, p75, and p100, respectively, for 56 d. The effects of dietary chitosan were evaluated using growth performance, feed utilization, digestive function, antioxidant capacity, nonspecific immunity, and resistance to Aeromonas hydrophila infection. Then, fish from the p0 and p50 groups underwent a 12-h transport stress test, with samples collected before, during, and 7 d after transport. Dietary chitosan improved most of these parameters. Among the treatment groups, p50 and p75 showed the best overall performance. The dose-response analysis further indicated that the appropriate dietary inclusion range was 5.0-7.5 g/kg. Under transport stress, fish in the p50 group exhibited more stable antioxidant enzyme responses and lower lipid peroxidation, as indicated by reduced MDA levels. Consistent with these enzyme responses, antioxidant-related genes remained relatively stable. At the same time, expression patterns related to the Nrf2-Keap1 and NF-κB signaling pathways suggested that 5.0 g/kg chitosan alleviated transport-induced oxidative damage and inflammation. Dietary chitosan also attenuated pro-inflammatory gene induction and altered the temporal expression patterns of anti-inflammatory genes. Overall, 5.0-7.5 g/kg dietary chitosan is suitable for juvenile largemouth bass, and 5.0 g/kg may serve as an effective pre-transport dietary inclusion level.

Animals↗

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

Repetitive transcranial magnetic stimulation in substance use disorders is safe and tolerable: A Systematic review of 141 clinical trials including 4299 participants.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation intervention investigated as a treatment for substance use disorder (SUD) and its co-occurring disorders. As the number of rTMS SUD clinical trials increase, the safety and tolerability profile should be assessed. In this systematic review, we investigate adverse events (AEs) of rTMS in individuals with SUD and factors that may influence their occurrence. METHODS: We performed a systematic PubMed search to identify all controlled trials of rTMS in SUD published up to January 2025. Eligible studies were assessed, and safety information was extracted for analysis. RESULTS: A total of 141 clinical trials with 4299 participants were included in their active arms. rTMS trials recruited participants who were engaged in active substance use, were in the pre-treatment phase, in early recovery, or in sustained recovery. Twenty-two studies explicitly reported no AEs. Sixty-nine studies reported only mild AEs, while only six studies reported moderate AEs. Thirty-five studies did not report safety-outcomes/AEs. As expected, participants reported mild and temporary AEs such as headaches, pain or discomfort under the coil, or dizziness. Only nine studies reported serious AEs (7 studies in active TMS and 2 in sham TMS). Importantly, no seizures attributable to active rTMS were reported in these SUD samples. CONCLUSION: Overall, rTMS in SUD samples is safe and well-tolerated regardless of recovery stage and substance. Most reported side effects were mild, self-limiting, and tolerable. However, AE reporting was incomplete, as 35 of 141 trials reported no safety data, limiting conclusions to reported outcomes. This evidence supports the safety of rTMS as a potential stand-alone or adjunctive treatment for SUD.

Humans↗

PubMed2026

Effect of ketofol versus Fentanyl-Midazolam sedation on neurological recovery in traumatic brain Injury: A randomised study.

Neurological recovery after traumatic brain injury (TBI) is multifactorial, and sedation is a cornerstone of neurocritical care because of its neuroprotective role. Although ketofol is widely used for anaesthesia, its effectiveness as a sedative regimen in the intensive care unit (ICU) has not been well studied. This preliminary exploratory double-blind, randomised study compared ketofol (KP) with fentanyl-midazolam (FM) sedation in adults with moderate-to-severe TBI. Sedation was administered for 72 h and titrated to a Richmond Agitation-Sedation Scale (RASS) score ≤  - 3. The primary outcome was the Extended Glasgow Outcome Scale (GOSE) at 30 days. Secondary outcomes included GOSE at 90 days, incidence of propofol infusion syndrome (PRIS), duration of mechanical ventilation, haemodynamic stability, and ICU and hospital length of stay. Of 120 enrolled patients, 111 were included in the final analysis (57 FM, 54 KP). Baseline characteristics, including injury severity and Marshall CT scores, were comparable. At 30 days, good neurological recovery (GOSE 7-8) was more frequent in the KP group than the FM group (26% vs. 10.5%, p = 0.03). At 90 days, recovery remained higher with KP (44.4% vs. 33.3%), though the difference was not statistically significant (p = 0.16). Multivariate analysis confirmed ketofol as an independent predictor of good recovery at 30 days (adjusted OR 3.63, 95% CI 1.11-11.85, p = 0.033). No PRIS occurred, and secondary outcomes were similar. Ketofol-based sedation was safe and may be associated with improved early neurological recovery compared with fentanyl-midazolam, with a favourable trend toward improved long-term neurological recovery.

Humans↗

PubMed2026

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial.

OBJECTIVES: Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize γ-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS: We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants ≤ 12 weeks postpartum with ≥ 4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving ≥ 80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS: Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p > 0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS: Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. GOV REGISTRATION NUMBER: NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.

Humans↗

PubMed2026

Thoracic paravertebral block with different doses of liposomal bupivacaine versus ropivacaine for postoperative analgesia in single-port thoracoscopic lung surgery: a randomized clinical trial.

OBJECTIVE: To evaluate the analgesic efficacy of thoracic paravertebral block (TPVB) with different doses of liposomal bupivacaine (LB) or ropivacaine in patients undergoing single-port thoracoscopic lung surgery. METHODS: A total of 105 patients scheduled for video-assisted single-port thoracoscopic lung surgery were randomized in a 1:1:1 ratio into three groups: low-dose LB group (group LL), high-dose LB group (group HL), or ropivacaine group (group R). All received ultrasound-guided TPVB at the T5/6 level preoperatively. The primary outcome was the area under the curve (AUC) of NRS of pain at activity (AUC-aNRS) from 1 to 72 h postoperatively. Secondary outcomes included the AUC of NRS of pain at rest (AUC-rNRS) from 1 to 72 h postoperatively, NRS of pain at rest and at activity at 1, 6, 24, 48, and 72 h postoperatively, and the cumulative opioid consumption at 24, 48, and 72 h postoperatively. Additionally, postoperative recovery and adverse events were assessed. RESULTS: AUC-aNRS differed significantly among groups (p = 0.0092), with high-dose LB lower than low-dose LB (p = 0.0071), but not versus ropivacaine. No significant difference was found in AUC-rNRS (p > 0.05). The group-by-time interactions for NRS of pain at rest and at activity were not significant (p > 0.05). Cumulative opioid consumption at 24, 48, and 72 h was lower in group HL versus group LL (all p < 0.017), but not versus ropivacaine. Postoperative recovery and adverse events showed no differences (p > 0.05). CONCLUSION: LB combined with TPVB is not superior to ropivacaine for postoperative analgesia in single-port thoracoscopic lung resection.

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↗

PubMed2025

Treatment preference for once-weekly versus once-daily DPP-4 inhibitors in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Although once-weekly and once-daily DPP-4 inhibitors have gained widespread market recognition, patient preference differences remain a key focus. This meta-analysis compares treatment preferences for once-weekly versus once-daily DPP-4 inhibitors in T2DM, offering evidence to guide clinical decisions and healthcare policies. METHODS: PubMed, OVID, EBSCO, Web of Science, CNKI, Wanfang, and clinical trial registries were searched up to June 30, 2025. After screening literature against predefined criteria, a systematic review was conducted to compare the effects of once-weekly and once-daily DPP-4 inhibitors on the treatment preferences of patients with T2DM. RESULTS: 8 RCTs with 1,575 participants were analyzed. No significant difference in medication adherence and DTSQ total score between the once-weekly and once-daily groups (p > 0.05). HbA1c percentage (MD = -0.21, 95% CI [-0.42, -0.01], p < 0.05) decreased significantly with once-weekly dosing, while GA and FPG showed no change (p > 0.05), this suggests greater improvement in HbA1c percentage levels following a switch to once-weekly DPP-4 inhibitors. Once-weekly DPP-4 inhibitors showed higher musculoskeletal/connective tissue disorder risk (RR = 2.63; 95% CI [1.18, 5.83]), but no significant differences in other adverse events (p > 0.05). No significant differences in treatment burden between both groups (p > 0.05). CONCLUSION: No statistically significant association between treatment preferences for once-weekly versus once-daily DPP-4 inhibitors among T2DM patients and medication adherence, treatment satisfaction, glycemic level changes, safety, or treatment burden for these two dosing regimens. Further research is needed to elucidate the influence of physician prescribing behavior on these preferences.

Humans↗

PubMed2026

Impact of Albuminuria-Lowering Treatments on Cardiovascular Predictive Ceramides in Diabetes: Post Hoc Analysis of the ROTATE Trials.

AIM: Cardiovascular disease (CVD) is the leading cause of mortality in individuals with diabetes. Diabetic kidney disease, closely related to CVD risk, is prevalent in up to 40% of this population. Emerging evidence suggests ceramide lipids as accurate biomarkers for CVD. We assessed the effect of four albuminuria-lowering drugs on CVD-related ceramides in diabetes by post hoc analysis of the ROTATE trials. MATERIALS AND METHODS: Twenty six adults with type 1 (T1D) as well as 37 with type 2 diabetes (T2D) with a urine albumin-creatinine ratio (UACR) of 30-500 mg/g participated in a 4-week 4-time randomized crossover study with periods of telmisartan, empagliflozin, linagliptin and baricitinib treatment, each separated by a 4-week washout period. Blood samples were collected at the beginning and end of each period and ceramide lipids (Cer16, Cer18, Cer20, Cer22, Cer24 and Cer24:1) were measured. The effect of each treatment was evaluated using linear mixed-effect models. RESULTS: At baseline, individuals with T2D had greater levels of Cer22 and Cer24 compared to the individuals with T1D. Among the treatments, linagliptin was the only drug that demonstrated a reduction of Cer22, Cer24 and Cer24:1 from baseline by 22.6% (95% CI: -33.58; -9.79, p = 0.001), 25.7% (95% CI: -38.94; -9.69, p = 0.003) and 19.6% (95% CI: -31.34; -5.95, p = 0.007), respectively. No changes in the ceramides were observed for the other drugs. CONCLUSION: Our exploratory findings suggest that certain albuminuria-lowering drugs may affect ceramide levels as a secondary effect. However, further mechanistic investigations are needed.

Humans↗

PubMed2026

From buffalo to human: Klebsiella pneumoniae in high-somatic cell count milk as an overlooked link in the one health chain.

High somatic cell count (SCC) is a critical indicator of udder health and milk quality in buffalo milk production. However, in many low-income regions, SCC monitoring is often underemphasized, allowing a proportion of high-SCC buffalo milk to enter the food chain and potentially compromising food safety and public health. Klebsiella pneumoniae (K. pneumoniae) is a common zoonotic pathogen found in high-SCC milk, yet systematic investigations into the prevalence and characteristics in high-SCC buffalo milk remain limited. In this study, 23 K. pneumoniae strains were screened out from 460 bacterial isolates obtained from high-SCC buffalo milk samples from Guangxi, China, with an isolation rate of 5.0%. These isolates were comprehensively characterized using whole-genome sequencing and comparative genomic analyses. The results revealed that 78.26% (18/23) of the isolates shared high genomic similarity with the human reference strain ATCC 13883, and the ST37 clone exhibited a pronounced potential of cross-species transmission. All isolates harbored core adhesion factors and intrinsic resistance genes. Notably, several strains displayed high-risk features: strain 419 carried the K1 capsular serotype, strain 326 possessed a complete yersiniabactin synthesis gene cluster, and strain 320 exhibited a multidrug-resistant phenotype. Phenotypic assays further demonstrated a positive correlation between biofilm formation capacity and virulence in Galleria mellonella. Metabolic pathway enrichment analyses suggested that K. pneumoniae has undergone substantial adaptation to the nutrient-rich buffalo milk environment. Collectively, these findings confirm that raw high-SCC buffalo milk serves as a significant reservoir for high-risk zoonotic K. pneumoniae. While industrial thermal processing effectively eliminates viable pathogens, the resilient antimicrobial resistance determinants within these isolates pose a persistent risk of horizontal gene dissemination along the food chain, providing critical evidence for enhancing pre-processing milk quality regulations within a One Health framework.

Animals↗

PubMed2026

Regional genomic analysis of lineage distribution and transferable multidrug resistance among chicken-associated Salmonella Kentucky isolates in China.

Salmonella enterica serovar Kentucky is an important multidrug-resistant foodborne pathogen in the poultry meat supply chain. Although recent broader genomic studies have elucidated the population structure and epidemiological significance of major lineages in China (e.g., ST198 and ST314), the regional dynamics within local poultry supply chains remain insufficiently characterized. In this study, 31 chicken meat-derived isolates from Shanghai and 39 publicly available genomes from China were analyzed using antimicrobial susceptibility testing, whole-genome sequencing, phylogenetic analysis, conjugation experiments, and complete sequencing of representative plasmids. This enabled a systematic characterization of the molecular epidemiological features of the population and the mechanisms underlying resistance dissemination. Population genomic analysis revealed a lineage composition markedly different from the global epidemiological pattern: ST314 was the predominant sequence type among the Shanghai chicken-derived isolates (74.2%), whereas the internationally recognized high-risk clone ST198 accounted for only 25.8% of the local isolates. However, risk stratification analysis indicated that although ST198 was detected less frequently, it carried a significantly greater burden of acquired resistance genes and therefore represented a higher-risk resistant lineage. Functional and structural validation further elucidated the molecular basis of resistance dissemination within this high-risk lineage. Conjugation experiments confirmed the co-transfer of a multidrug resistance module carrying blaTEM-1 and blaCTX-M-267 to the recipient strain Escherichia coli J53. Complete plasmid analysis revealed that these two β-lactam resistance genes were co-localized on a 242-kb transferable plasmid flanked by Tn1331, Tn3, and multiple transposase-associated elements, thereby providing a structural basis for their horizontal transfer. This study provides important molecular epidemiological evidence for lineage-specific surveillance and risk-stratified control of resistant Salmonella in the poultry meat supply chain and further underscores the need for continuous monitoring of mobile genetic elements within a One Health framework.

Animals↗

PubMed2026

E-cigarette product characteristics and packaging features and interest in e-cigarette use: Results from a randomized within-person trial nested in three prospective cohorts.

BACKGROUND: Product characteristics and packaging may be key targets for regulation to reduce e-cigarette use among youth, but existing data are limited. METHODS: Data are from an experimental study (2018-2020) nested within three prospective cohorts (age 14-26) in southern California (N = 3565). Participants were shown five e-cigarette (e-liquid) packages in a random order that varied in flavor (sweet vs. tobacco), flavor name (descriptive ["blueberry cheesecake"] vs. concept ["smurf cake"] vs. none [number only]), and cartoon image on package (yes/no). For each stimuli, survey items assessed the following outcomes: product appeal (self-enjoyment, others' enjoyment; Likert scale [1-5]), susceptibility to use (use if friends offered, curiosity; 4 ordered responses [definitely not-definitely yes]), peer acceptability (definitely not-definitely yes), and perceived harm (definitely not-definitely yes). Mixed effects proportional odds models evaluated within-person effects of each factor (flavor, flavor name, cartoon) with each outcome. RESULTS: Participants reported greater appeal, susceptibility, and peer acceptability (OR range=3.7-16.9; ps<0.05), and lower perceived harm (OR=0.61; 95%CI=0.53, 0.70) for sweet (vs. tobacco-flavored) e-cigarettes; effects were progressively stronger for younger cohorts. The descriptive flavor name rated higher than the concept flavor (OR range=1.13-2.02; ps<0.05) or number only (OR range=1.18-1.69; ps<0.05) for appeal and susceptibility measures; no differences for concept vs. number were found. The cartoon image rated higher for appeal, curiosity, and peer acceptability (OR range=1.24-1.51; ps<0.05). CONCLUSIONS: Sweet flavors, descriptive flavor names, and cartoon images may increase the appeal of e-cigarettes among youth and young adults with no history of e-cigarette use, and are key targets for regulation.

Humans↗

PubMed2026

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

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

Safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in USA and Puerto Rico: Results from a Phase III, randomized, active-controlled study.

MenACYW-TT, a quadrivalent meningococcal tetanus toxoid-conjugate vaccine, is approved for prevention of invasive meningococcal disease in infants ≥ 6 weeks of age in the USA. This Phase III study (NCT03673462; September 17, 2018 - March 16, 2023) evaluated the safety of MenACYW-TT compared with a licensed quadrivalent meningococcal oligosaccharide diphtheria CRM197-conjugate vaccine (MenACWY-CRM) when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in a four-dose series (3+1 schedule). Participants were randomized 3:1 to receive MenACYW-TT (Group 1; n = 2080) or MenACWY-CRM (Group 2; n = 697) at 2, 4, 6, and 12 months of age, with concomitant administration of routine pediatric vaccines (DTaP5-IPV/Hib, PCV13, rotavirus, hepatitis B, MMR, and varicella vaccines). Safety assessments included immediate unsolicited adverse events within 30 minutes post-vaccination, solicited injection site and systemic reactions within 7d, unsolicited AEs within 30d, serious adverse events (SAEs) including adverse events of special interest (AESIs), and medically attended adverse events (MAAEs) throughout the study. MenACYW-TT and MenACWY-CRM were overall well tolerated, and safety profiles were comparable. Solicited injection site reactions occurred in 84.9% and 84.6% of participants in Groups 1 and 2, respectively; solicited systemic reactions in 87.1% and 88.2%, respectively. During the entire study, 5.2% in Group 1 and 3.0% in Group 2 experienced at least one SAE; 0.9% and 0.1%, respectively, reported at least one AESI. Three deaths occurred in Group 1. All SAEs, AESIs, and deaths were unrelated to study vaccines. This study supports the safety profile of MenACYW-TT in infants and toddlers aged ≥ 6 weeks.Study registration: Clinicaltrials.gov: NCT03673462; EudraCT: 2019-004459-35.

Child, Preschool↗

PubMed2026

Comparative effectiveness of percutaneous coronary intervention strategies for coronary small-vessel disease: a network meta-analysis of randomized trials.

BACKGROUND: Coronary small-vessel disease (SVD) remains challenging for percutaneous coronary intervention (PCI) because small lumens magnify restenosis and ischemic risk. Multiple devices are available, yet their comparative performance is uncertain. This study evaluated and ranked PCI strategies for SVD. METHODS: A systematic review and network meta-analysis was conducted in accordance with PRISMA. PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar were searched from inception to 15 August 2025. Eligible studies were English-language randomized controlled trials enrolling adults with angiographic SVD defined as reference vessel diameter ≤3.0 mm, comparing PCI strategies, and reporting target lesion revascularization (TLR), binary restenosis (BR), or myocardial infarction (MI). A frequentist random-effects network meta-analysis generated odds ratios (ORs) with 95% confidence intervals (CIs) and treatment rankings using the surface under the cumulative ranking curve (SUCRA). RESULTS: Thirty-nine trials including 14,503 patients met the criteria. For TLR (37 studies; 11,980 patients), the highest SUCRA values were observed with sirolimus-eluting stents (SES 90.1%), zotarolimus-eluting stents (ZES 83.9%), and everolimus-eluting stents (EES 82.2%). For BR (32; 6,468), SES, ZES, and paclitaxel-coated balloons (DCB-PTX) ranked highest (95.0%, 80.0%, and 78.3%). For MI (37; 11,602), SES, DCB-PTX, and ZES ranked highest (79.0%, 78.7%, and 68.5%). Representative effects showed SES reduced TLR versus bare-metal stents (BMS) (OR, 0.25; 95% CI, 0.15-0.43) and MI versus BMS (OR, 0.41; 95% CI, 0.21-0.79). Conventional approaches such as BMS, plain old balloon angioplasty (POBA), and gold-plated balloon angioplasty (GPBA) ranked lowest across outcomes. CONCLUSION: SES provides the most consistent clinical benefit for coronary SVD. ZES, EES, and DCB-PTX are effective alternatives in selected settings, whereas BMS, POBA, and GPBA are less effective. These findings offer comparative evidence to guide device selection in SVD.

Humans↗

PubMed2026

Outcomes and Associated Prognostic Factors for Orthograde Canal Obturation Using Ortho MTA III: A Randomised Prospective Clinical Trial.

AIM: To prospectively compare treatment outcomes for orthograde canal obturation using Ortho MTA III (OMTA) with the continuous wave of compaction (CWC) using gutta-percha (GP) and AH Plus sealer, and to identify associated predictive factors. METHODOLOGY: Informed consent was obtained (110 patients), and single- or two-rooted permanent teeth (n = 120) diagnosed with pulp necrosis (or previously treated) and asymptomatic apical periodontitis or chronic apical abscess (periapical index, PAI ≥ 3) were randomly assigned to two groups (n = 60/group). The canals were prepared to a minimal apical size #40 (ISO) based on their initial file size, disinfected and obturated by either CWC or OMTA using an enhanced disinfection protocol (GP disinfected, new gloves after each intraoperative radiograph and before starting obturation). Clinical and periapical radiographic examinations were conducted by two calibrated, independent endodontists during follow-up periods of at least 12 months. Success rates and associated predictive factors (tooth-, operator- and patient-related) were analysed statistically using binary and multiple logistic regression (p < 0.05). RESULTS: The median recall period was 30 months (14-48 months), and 104 teeth were finally analysed (recall rate: 86.67%). No significant differences in success rate were observed between the groups (p > 0.05) under both loose (OMTA: 88.24%, CWC: 83.02%) and strict criteria (OMTA: 64.71%, CWC: 58.49%). Multivariate analysis revealed that age (OR = 5.735, 95% CI: 1.286-25.577, p = 0.022), periapical lesion size (OR = 6.596, 95% CI: 1.397-31.138, p = 0.017) and PAI score (OR = 2.081, 95% CI: 1.047-4.136, p = 0.036) were significant predictors of treatment failure. CONCLUSIONS: Orthograde obturation of infected canals with Ortho MTA III demonstrated comparable success and treatment outcomes to those filled with GP and sealer by CWC, supporting its potential as a clinically viable alternative for the obturation of infected root canals. TRIAL REGISTRATION: cris.nih.go.kr registration number: KCT00099939.

Humans↗