Search PubMedSearch

SEARCH · Search PubMed

Results for “DNA End-Joining Repair”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

314 records · Page 14Linked to original sources

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

Plant cis-regulatory grammar: Decoding the multidimensional code of transcriptional regulation for programmable crop engineering.

Cis-regulatory elements (CREs) orchestrate the spatiotemporal precision of gene expression that underlies plant development, adaptation, and domestication. Decoding the cis-regulatory grammar of plant genomes remains a central challenge in modern biology, with profound implications for programmable crop engineering. Here, recent conceptual and technological advances are synthesized to reshape our understanding of plant CREs. This review first argues that CRE function is not only an intrinsic property of DNA sequence alone but also emerges from a multidimensional context, including chromatin accessibility, histone modifications, three-dimensional genome topology, and cell type-specific regulatory landscapes. Furthermore, the convergence of single-cell epigenomics, high-throughput functional assays, and CRISPR-based dissection has begun to unravel this contextual grammar, revealing the computational principles governing transcriptional regulation. Critically, we propose that artificial intelligence (AI) platforms are catalyzing an ongoing transition from descriptive discovery to predictive engineering, wherein these platforms outperform natural evolution in designing synthetic CREs. Finally, a roadmap is outlined toward a plant regulatory grammar foundation model, which will enable truly predictive engineering of gene expression when fine-tuned for specific tasks. Collectively, the integration of single-cell resolution maps, precise genome editing, AI-driven design, and regulatory-compliant delivery systems promises to transform our ability to reprogram plant gene regulation for next-generation agriculture, bridging the gap between foundational regulatory biology and tangible crop improvement.

artificial intelligence

Regional and statewide hysterectomy-corrected endometrial cancer incidence and five-year relative survival in Texas.

BACKGROUND: Rising endometrial cancer (EC) incidence nationwide, particularly among Hispanic women, and high prevalence of risk factors such as obesity and comorbidities in Texas, motivated us to estimate EC incidence rates (IRs) and survival by age (<50 years/ early-onset, &#x2265;50 years/late-onset), race-ethnicity (Non-Hispanic-White [NHW], -Black [NHB], Hispanic), histology (endometrioid, non-endometrioid), and area-based socioeconomic (SES) factors across Texas Health Service Regions (HSRs). STUDY DESIGN: Between 2000 and 2019, a total of 42,571 women (20-79 years) with EC were reported from Texas within the Surveillance, Epidemiology, and End Results Program. IRs and 5-year relative survival were calculated using SEER*Stat. IRs were corrected for hysterectomy using Behavioral Risk Factor Surveillance System data. RESULTS: Statewide EC IRs rose from 38.5 (2000-2009) to 44.5 (2010-2019), with the highest increase in the Upper-South (42.6 to 53.8). Across HSRs, Upper-South consistently had higher IRs among women <&#x202f;50 (13.9) and &#x2265;&#x202f;50 years (112.7). Among those <&#x202f;50 years, Hispanics had the highest IRs (12.4), predominantly endometrioid tumors, whereas in women &#x2265;&#x202f;50 years, NHB had the highest IRs (119.2) with a large proportion of non-endometrioid tumors. IRs were higher in areas with lower poverty, and higher education, income, and urbanization. Associations with unemployment were mixed. Worse survival outcomes were observed among NHBs, non-endometrioid, advanced-stage, and lower SES. Central Texas had more favorable survival outcomes compared to other HSR. CONCLUSION: EC IRs and survival rates in Texas largely mirror national trends, with regional differences likely reflecting sociodemographic and histologic distributions.

Humans

Exploring hormonal influences on nicotine craving and use across the perinatal period: A prospective longitudinal study.

INTRODUCTION: Perinatal nicotine use is common despite well-documented adverse consequences. We examined associations between reproductive-related hormones with nicotine craving and use during the perinatal period to identify potential novel intervention points. METHODS: All participants reported use of nicotine during the perinatal period. Participants were enrolled at gestational week &#x2265;&#x2009;36 and followed to postpartum week 12 via daily surveys (i.e., nicotine craving via 100-point scale, dichotomous use) and weekly hormone measurement in saliva (cortisol, oxytocin) or dried blood spots (progesterone, estradiol, testosterone, dehydroepiandrosterone sulfate). Bayesian mixed-effects models accounted for within-person correlation while estimating hormone effects. RESULTS: Participants (n&#x2009;=&#x2009;46) were 28.9&#x2009;&#xb1;&#x2009;4.9 years old. During follow-up, exclusive combustible cigarettes (n&#x2009;=&#x2009;20), electronic nicotine delivery systems (ENDS; n&#x2009;=&#x2009;13), or dual (n&#x2009;=&#x2009;2) use was observed, with variability in use and craving across participants and over time. During pregnancy, higher oxytocin was linked to greater craving (&#x3b2;=16.31, 95% CI: 3.71, 28.83). Greater peripartum declines in oxytocin were associated with more craving (&#x3b2;=8.71, 95% CI: 0.75, 16.93) and use (&#x3b2;=1.13, 95% CI: 0.05, 2.43). During postpartum, lower estradiol was linked to more craving (&#x3b2;=-1.17, 95% CI: -2.15, -0.18) and use (&#x3b2;=-0.40, 95% CI: -0.76, -0.03). In models simultaneously evaluating all postpartum hormones, the lone meaningful association was between estradiol and craving (&#x3b2;=-1.66, 95% CI: -2.84, -0.48). CONCLUSIONS: The results of this study suggest that oxytocin and estradiol may contribute to the risk of perinatal nicotine use. Additional research is needed to replicate our observations in more diverse study samples and explore implications for clinical intervention.

Bayesian

Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n&#x202f;=&#x202f;56) compared to Enriched Supportive Therapy (n&#x202f;=&#x202f;43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group&#x202f;&#xd7;&#x202f;time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans

Sustained cognitive and functional effects of pro-cognitive interventions for bipolar disorder: A systematic review of randomised controlled trials.

A substantial proportion of individuals with bipolar disorder (BD) experience considerable cognitive deficits. Existing systematic reviews have evaluated the efficacy of pro-cognitive interventions in BD, but have not established whether any cognitive benefits translate into functional improvements, with evidence for sustained functional effects remaining limited. A systematic search was conducted on MEDLINE, EMBASE, PsycINFO and Cochrane Library from inception until 21 May 2026. Eligible studies were randomised controlled trials (RCTs) in BD reporting cognitive or functional outcomes at three or more months following a pro-cognitive intervention, or examining the translation of cognitive benefits into improvements in functional outcomes at any timepoint. Seven unique RCTs plus three secondary analyses of these trials (n&#xa0;=&#xa0;615) met the inclusion criteria. Approximately 13% (7/55) of RCTs identified in the search of pro-cognitive interventions in adult BD assessed cognitive or functional outcomes at least 3&#xa0;months after treatment end. Of the seven unique RCTs, most evaluated cognitive remediation (CR; k&#xa0;=&#xa0;4). The average follow-up length was 4&#xa0;months (range: 3-6&#xa0;months). Three of the four RCTs examining CR reported cognitive benefits at 3 to 6&#xa0;months, whereas only one CR RCT found consistent functional effects at 3&#xa0;months. Evidence on the translation of cognitive benefits to functional improvements is scarce and inconsistent. Most trials examining pro-cognitive interventions do not examine whether potential benefits are sustained or whether they translate into improvements in real-world functioning. CR appears to be a promising intervention for achieving durable cognitive gains in BD, although evidence for sustained effects of other interventions is limited.

Humans

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the nicotine metabolite ratio (NMR) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear. This study aims to investigate how NMR affects cessation outcomes under different medications to guide personalized treatment. METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with NMR data. Data were synthesized using random-effects models, with heterogeneity assessment. The primary outcome was verified smoking cessation rate at the end of treatment or the closest time-point. RESULTS: Eleven RCTs with accessible full text were included in the qualitative analyses and nine were included in the quantitative synthesis. For non-titratable nicotine replacement therapy (NRT), normal/fast metabolizers demonstrated lower odds of smoking cessation than slow metabolizers (Odds Ratio, OR=0.81, 95% confidence interval, CI=0.68-0.96; 5 studies, I&#xb2;=62.5%). No significant associations were shown between normal/fast and slow metabolizers using titratable NRT (OR=1.04, 95% CI=0.95-1.14; 2 studies, I&#xb2;=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I&#xb2;=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I&#xb2;=59.8%). CONCLUSION: Current evidence demonstrates that NMR moderates' treatment efficacy among those who smoke using non-titratable NRT, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers. Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Humans

Uncovering hidden complexity in the Apis mellifera mitotranscriptome: a polyadenylation-centered perspective.

Mitochondrial transcription is gaining increasing attention as researchers seek to better understand the full coding potential of mitochondrial DNA (mtDNA). Emerging evidence suggests that mtDNA may encode additional elements beyond classical oxidative phosphorylation genes, pointing to a more complex transcriptional architecture than previously recognized. In this study, we explored the mitochondrial transcriptome of Apis mellifera (Insecta: Hymenoptera), with a particular focus on polyadenylation-associated features. Our analysis revealed that both sense and antisense transcripts undergo polyadenylation, although transcript abundance and poly(A) tail lengths varied markedly across mitochondrial genes. Several transcripts exhibited alternative isoforms, either extended or truncated, frequently including intergenic regions. These regions may represent functional non-coding elements or structural variants rather than conventional untranslated regions (UTRs). Interestingly, some transcripts also contained non-templated nucleotide additions particularly cytosine residues immediately upstream of the poly(A) tails. Monocistronic units that included portions of downstream intergenic regions were among the most abundantly represented, suggesting a possible regulatory role for these sequences. To experimentally validate our in silico findings, we performed RT-qPCR to assess relative gene expression and applied 3' RACE-PCR to define transcript boundaries. These approaches confirmed the presence of multiple transcript isoforms and supported the involvement of polyadenylation in shaping mitochondrial RNA diversity. Together, our findings reveal a previously underappreciated level of complexity in the A. mellifera mitochondrial transcriptome and highlight the potential regulatory significance of polyadenylation dynamics and intergenic region transcription.

Animals

Muscle mechanical and architectural adaptations in response to different endurance training modalities in older adults.

INTRODUCTION: This study examined the effects of various cycling endurance training modalities, matched for total workload, on muscle mechanical and architectural characteristics in older adults. METHODS: Fifty healthy participants (25 females, 59-79&#xa0;yrs) were randomly assigned to five age and sex matched groups: one control and four workload-matched training groups (moderate-intensity continuous, heavy-intensity continuous, high-intensity interval, and heavy-intensity continuous in eccentric cycling). Training consisted of three weekly sessions over 8&#xa0;weeks, with evaluations conducted at the beginning and end of the intervention with maximal voluntary isometric contractions at five different knee angles (90, 75, 60, 45, 30&#xb0;) and maximal concentric and eccentric isokinetic contractions at five different knee angular velocities (45, 90, 150, 210, 250&#xb0;/s). Maximum voluntary isometric torque (Tmax) and optimal knee angle (KAopt) were obtained from the isometric contractions; eccentric torque (Tecc) and maximum concentric knee angular velocity (Vmax) were obtained from the isokinetic contractions. The muscle architecture of vastus lateralis (VL) at rest (muscle thickness, pennation angle, and fascicle length) was investigated as well. RESULTS: No statistical differences were detected between groups or time points in VL architecture, in KAopt and in Vmax. A main effect of time was observed for Tmax (p&#xa0;<&#xa0;0.001, &#x3b7;2p&#xa0;=&#xa0;0.458) and Tecc (p&#xa0;=&#xa0;0.002, &#x3b7;2p&#xa0;=&#xa0;0.191) in all the investigated training groups. The within-group comparisons indicate significant increases in Tmax in the training groups, but not in the control group. CONCLUSIONS: Commonly applied endurance exercises improve muscle mechanical capacity (Tmax and Tecc) in older adults, with no structural (architectural) muscle remodelling, when matched for workload.

Humans

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 &#x3b2;-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

Migration intentions among nigerian neurosurgeons: a national survey of workforce retention.

Physician emigration from low- and middle-income countries creates critical workforce shortages. This study explored factors influencing migration intentions among Nigerian neurosurgeons and trainees. We conducted an anonymized survey of consultant neurosurgeons, fellows, and residents practicing in Nigeria. Invitations were sent by email and professional messaging platforms, and snowball sampling was used to increase participation. The survey included quantitative and open-ended questions on demographics, income, migration plans, and retention factors. Seventy-nine respondents participated (61.5&#xa0;% consultants; 93.7&#xa0;% male; median age: 44&#xa0;years). Nearly all practiced general neurosurgery (97.3&#xa0;%), and many also performed trauma (65.3&#xa0;%) and spine (61.3&#xa0;%) neurosurgery. Most (85.7&#xa0;%) reported that their earnings were insufficient to support their families. Nearly 40&#xa0;% were considering emigration, most often citing financial pressures (88.5&#xa0;%) and poor working conditions (63.5&#xa0;%) as push factors. By contrast, personal or family ties (63.0&#xa0;%) and relocation costs (45.2&#xa0;%) were cited as reasons to stay. Respondents identified higher salaries (58.1&#xa0;%) and greater investment in the health sector (51.4&#xa0;%) as key measures to improve retention. In univariable analyses, younger age, income insufficiency, income dissatisfaction, and feeling undervalued at work were associated with migration intention. Financial insecurity emerged as the dominant driver of migration intentions among Nigerian neurosurgeons. In addition to salary increases, sustained investment in healthcare infrastructure and workforce support is essential to improve retention. International partnerships may complement these efforts by building neurosurgical capacity and mitigating brain drain.

Humans

Fructophilic lactic acid bacteria as a window into multi-scale convergent evolution.

Fructophilic lactic acid bacteria (FLAB) are a group of lactic acid bacteria with unique growth characteristics, that is, poor growth on glucose. Their growth is enhanced in the presence of fructose or external electron acceptors. These organisms inhabit fructose-rich environments such as flowers, fruits, and pollinating insects, particularly honey bees. Apilactobacillus spp. and Fructobacillus spp. are representatives of FLAB, although they belong to phylogenetically distant clades. These organisms commonly possess markedly small genomes with a low number of coding DNA sequences. Furthermore, their genomes are characterized by a markedly reduced number of genes involved in carbohydrate transport and metabolism. Genome reduction in FLAB reflects convergent adaptation to fructose-rich environments rather than general genome streamlining. The two distinct FLAB genera, Fructobacillus and Apilactobacillus, independently lost more than 100 genes in statistically similar orders. In contrast, genes involved in carbohydrate and amino acid metabolism exhibited reversed orders of loss between the two genera. Furthermore, FLAB genomes lack an intact bifunctional alcohol/aldehyde dehydrogenase gene (adhE), which causes their poor growth on glucose. A comparative genomic study suggested the evolutionary process underlying adhE gene decay during adaptation to the fructose-rich environments, including pollinating insects. In conclusion, FLAB represent a unique example of habitat-driven convergent reductive evolution that can be investigated across multiple biological scales - from individual genes to whole genomes - in the diverse LAB group with a wide range of habitats, and partially share the fructophilic evolution with eukaryotic yeasts found in fructose-rich habitats.

Fructose

Effects of Lactiplantibacillus plantarum KABP051 Probiotic on Body Composition, Microbiome and Mood in Healthy Overweight Adults.

Obesity and mental health disorders are among the greatest public health challenges of the 21st century. Interestingly, an altered microbiome profile has been associated with both conditions. The aim of this randomized, double-blind, placebo-controlled clinical trial was to evaluate the effects of dietary supplementation with a specific probiotic strain (Lactiplantibacillus plantarum KABP051) on body composition and gut microbiome balance, together with measures of mood state, in a population of healthy overweight subjects. Sixty healthy, moderately stressed, nondepressed and overweight or obese volunteers were supplemented for 12 weeks with probiotic (L. plantarum KABP051; 1 billion colony forming units/day) or placebo (microcrystalline cellulose). The KABP051 group experienced significantly greater improvements compared with placebo on body composition measurements, including a reduction in body weight and waist circumference, which decreased in 1.97 &#xb1; 0.77 (mean &#xb1; SE) kg and 2.15 &#xb1; 0.81 (mean &#xb1; SE) cm versus placebo at the end of the intervention (both P < .05, mixed model for repeated measures [MMRM] and post-hoc analysis). Microbiome composition improved in KABP051 group, with significant increase in the relative abundance of Lactiplantibacillus spp. versus placebo. Body fat percentage, profile of mood states fatigue, and confusion sub-scores showed a global trend toward improvement compared with placebo, with the change at 12 weeks being significant in the three measurements in post-hoc analysis (P = .015, P = .014, and P = .016, respectively). No serious adverse events were registered during the intervention period. These results suggest that a specific strain of probiotic bacteria (L. plantarum KABP051) may have both metabolic and psychobiotic effects and may be beneficial for enhancing weight loss and body composition, improving energy (less fatigue) and mood levels while embarking on a healthy lifestyle regimen. ClinicalTrials.gov identifier: NCT06808061.

Humans

Risk factors for loss of skeletal muscle mass in patients with chronic kidney disease on a low-protein diet.

OBJECTIVES: A low-protein diet (LPD) is recommended for patients with chronic kidney disease (CKD) to prevent a further decline in renal function. However, its impact on muscle mass in these patients remains unclear. This study investigated the risk factors for loss of muscle mass in patients with CKD on an LPD. METHODS: Eighty-four patients with predialysis CKD (59 men, mean age 61.9 &#xb1; 11.5 y) who participated in a multicenter randomized controlled trial initiated in 2014 were retrospectively reviewed. We collected data on baseline blood and urine tests, body composition, and dietary records at the start and end of the observation period. We evaluated muscle mass using the skeletal muscle index (SMI) and analyzed risk factors for a decrease in SMI during the 24-wk observation period, using logistic regression analysis. Variables with an association (P < 0.1) in univariate analysis, as well as age, sex, use of low-protein rice, and changes in protein intake, were subjected to multivariate analysis. RESULTS: SMI decreased in 50 patients (59.5%) during the observation period. Multivariate analysis identified significant associations of the SMI with serum albumin at baseline (odds ratio 0.11, 95% confidence interval 0.02-0.52, P = 0.004) and changes in energy intake while on the LPD (odds ratio 3.39, 95% confidence interval 1.00-11.43, P = 0.049). CONCLUSIONS: Risk factors for reduced SMI in patients with CKD on an LPD were malnutrition when initiating the LPD and reduced energy intake during its implementation. Clinicians should optimize nutritional status before initiation of an LPD and ensure adequate energy intake throughout treatment.

Humans

Proteomics-based analysis of the defense mechanisms of disease-resistant grass carp against Aeromonas veronii.

Sustainable aquaculture of grass carp (Ctenopharyngodon idella, GC) is consistently threatened by bacterial diseases, particularly those caused by Aeromonas veronii. A disease-resistant grass carp (DR-GC) has been developed by backcrossing female gynogenetic GC with normal male GC, exhibiting improved resistance. However, the systemic molecular mechanisms of DR-GC defending against Aeromonas veronii infection remain largely unexplored. Here, a label-free quantitative proteomics approach was employed to systematically compare proteomic profiles across five tissues (intestine, liver, muscle, skin, and kidney) in DR-GC and GC under healthy and infected conditions. The intestine was identified as the central defense tissue, exhibiting the highest number of differentially abundant proteins (DAPs). In DR-GC, A0A3N0YEK7 (small ribosomal subunit protein eS28), A0A3N0YGT8 (ATP synthase-coupling factor 6) and A0A3N0YNS7 (apolipoprotein A-I) were significantly upregulated in intestine, while D5KZW6 (GCHV-induced protein), A0A3N0Z0A1 and Q8JH84 (hemoglobin subunit alpha) were significantly dysregulated across multiple tissues, which playing the critical roles in defense mechanisms at the protein level. Furthermore, cytochrome P450-associated pathways, cytosolic DNA-sensing and RIG-I-like receptor signaling pathways were identified as crucial coordinators mediating immune and metabolic responses. This study provides the first comprehensive proteomic view of multi-tissue defense mechanisms in DR-GC, and identifies key DAPs and pathways for subsequent functional validation.

Animals

Program to Avoid Cerebrovascular Events Through Systematic Electronic Tracking and Tailoring of an Eminent Risk Factor: A&#xa0;Randomized Trial.

BACKGROUND: Individuals residing in the southeastern United States experience disproportionately worse stroke outcomes. Although blood pressure (BP) reduction is among the most effective strategies for improving stroke outcomes, fewer than one third of survivors of stroke achieve BP control within 1 year of the index event. METHODS: The PACESETTER (Program to Avoid Cerebrovascular Events Through Systematic Electronic Tracking and Tailoring of an Eminent Risk Factor) trial enrolled patients with stroke and uncontrolled BP from 3 safety-net health care systems in South Carolina. Patients were randomized 1:1 to the PACESETTER intervention, which included a Bluetooth-enabled electronic pill tray, a BP monitor, and a smartphone application for automated data transmission of medication adherence and BP data to a central server or to usual care. The primary outcome was systolic BP <130&#x2009;mm&#x2009;Hg at 12 months, analyzed according to the intention-to-treat principle. RESULTS: The trial was stopped early due to low recruitment during the COVID-19 and funding constraints. Between September 2019 and February 2023, 120 participants were randomized to PACESETTER (n=60) or the usual care arm (n=60). At 4&#xa0;months, systolic BP <130&#x2009;mm&#x2009;Hg favored the PACESETTER arm (48.8% versus 29.3%, P=0.07), but no significant difference was observed at 12 months (50% versus 47.2%, P=0.82). CONCLUSIONS: Because the trial was terminated prematurely, the effect of the PACESETTER intervention on 12-month BP control after stroke remains uncertain. A trial completed to its full term and sufficiently powered to also evaluate key short-term end points is needed. REGISTRATION: URL: https://www.clinicalstrial.org; Unique Identifier: NCT03401489.

Aged

Incidence of silent cerebral lesions during pulsed field ablation for paroxysmal atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is a first-line treatment for paroxysmal atrial fibrillation (PAF). Complications such as silent cerebral lesion (SCL) may occur during ablation. Pulsed field ablation (PFA) is a non-thermal method thatablates cardiac tissue via irreversible electroporation. Limited studies have reported the incidence of SCL during PFA, with highly variable results. However, randomized controlled trials (RCTs) remain scarce. The objective of this study was to compare perioperative SCL incidence between PFA and RFCA, and to identify risk factors for SCL during PFA. METHODS: In this prospective pilot RCT (ChiCTR2400088774), 62 patients with PAF were randomized 1:1 to undergo PFA or RFCA. Cerebral MRI (3.0 T) was performed preoperatively and 24-48h postoperatively. SCL was defined as a new acute brain lesion on MRI without neurological deficits. Baseline and surgical data of the patients were collected. RESULTS: SCL was detected post-procedure in 6.45% (2/31) in the RFCA group, 12.90% (4/31) in the PFA group. No statistically significant difference in the incidence of postoperative SCL was detected between the two groups (p&#x2009;=&#x2009;0.67). Left atrium dimension (LAD), left atrial operation time (LAOT), left ventricular end-diastolic dimension (LVEDD), and total operation time (TOT) were significantly higher in SCL group than those in no-SCL group (p&#x2009;<&#x2009;0.05) through univariate analyses. CONCLUSIONS: SCL incidence was 12.90% in the PFA group versus 6.45% in the RFCA group. While no statistically significant difference was detected between two groups, the numerically higher rate in the PFA group warrants larger studies to evaluate cerebral safety associated with PFA.

Humans

Cancer statistics for Asian American, Native Hawaiian, and Pacific Islander people, 2026.

BACKGROUND: Cancer statistics for Asian American and Native Hawaiian and Pacific Islander (NHPI) people are usually aggregated, masking substantial variation within this heterogeneous population. Herein, the American Cancer Society reports cancer incidence and survival for 8 Asian American and 3 NHPI ethnic groups. METHODS: The authors used population-based cancer registry data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, for Asian American and NHPI ethnic groups from 2000 through 2022. RESULTS: During 2018-2022, overall cancer incidence ranged from 218.3 per 100,000 Kampuchean people to 474.5 per 100,000 Native Hawaiian people, which was 1.5 times higher than the rate for the aggregated Asian American and NHPI population (307.3 per 100,000). High incidence among Native Hawaiian people is largely driven by the highest rates of female breast, colorectal, and prostate cancers, whereas infection-related cancers were highest among Asian American ethnic groups. For example, liver and stomach cancer incidence is highest among Vietnamese (22.2 per 100,000) and Korean people (17.8 per 100,000), respectively, both of which were nearly twice that in Native Hawaiian people (12.9 and 9.6 per 100,000, respectively). Native Hawaiian and Samoan women are twice and 3 times as likely, respectively, to be diagnosed with uterine corpus cancer as aggregated Asian American and NHPI women or White women. Five-year relative survival ranges from 42% in Laotians to 74% in Asian Indians/Pakistanis, with largest differences for colorectal (43% in Laotians to 72% in Asian Indians/Pakistanis) and prostate (63% in Kampucheans to 97% in Japanese) cancers. CONCLUSIONS: Wide variation in cancer risk within the Asian American and NHPI population highlights the critical need for disaggregated data to effectively target cancer prevention and control interventions.

Adolescent