SEARCH · Search PubMed

Results for “Neuromuscular Blocking Agents”

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.

SourceResearch connectionFrom yearThrough year

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

431 records · Page 7Linked to original sources

PubMed2026

Metformin Adherence and Risk of Polyneuropathy in Type 2 Diabetes Mellitus: An International Matched Cohort Study with Independent Validation.

BACKGROUND: Metformin is a popular first-line glucose-lowering medication for type 2 diabetes mellitus (T2DM). Although metformin reduces the risks of various complications of diabetes, its potential to cause polyneuropathy by depleting vitamin B12 levels is concerning. This study investigated whether the adherence or discontinuation of metformin after adding-on a second-line antiglycemic agent increases the risk of polyneuropathy in patients with T2DM. METHODS: Data from TriNetX were obtained, and patients with T2DM who were receiving second-line antiglycemic agents were divided into metformin-adherent and metformin-nonadherent groups based on prescription claims data. Neuropathy incidence was evaluated using diagnostic claims and nerve conduction examinations. For independent confirmation and external validation of the primary findings, we used data from the National Health Insurance Research Database (NHIRD) of Taiwan. RESULTS: After matching, 58,027 patients were included in each group. Compared with metformin adherent patients, metformin nonadherent patients had a higher risk of polyneuropathy (adjusted hazard ratios [aHR] 1.26; 95% confidence interval [CI] 1.23-1.29; P < 0.001). Risks of diabetic foot ulcer, amputation, neuropathy-related medication use, and bone fracture were also higher among nonadherent patients. Sensitivity analyses confirmed the robustness of findings. In the validation NHIRD cohort (31,384 matched pairs), metformin nonadherence remained associated with increased polyneuropathy risk (aHR 1.25; 95% CI 1.10-1.42; P < 0.001). CONCLUSIONS: Metformin adherence in patients with T2DM who require second-line treatment may reduce the risk of polyneuropathy; vitamin B supplementation may enhance this benefit.

Humans↗

PubMed2026

The Effect of Pulsed Electromagnetic Field on Pain and Foot Function Index in Patients With Plantar Fasciitis.

The plantar fascia is a thick band of connective tissue that originates from the heel, and its inflammation is the most common cause of heel pain in adults. The Pulsed Electromagnetic Field (PEMF) is a non-invasive modality in the field of physiotherapy. This study aimed to determine the effects of PEMF on pain scores and the Foot Function Index (FFI) in patients with plantar fasciitis (PF). In this clinical trial study, 40 patients with PF, aged between 20 and 68 years, were randomly assigned in a block design into two groups: the Conventional Physiotherapy (CP) group and the CP plus PEMF (CPP) group. The Numerical Pain Rating Scale (NPRS) and the FFI questionnaire were used to assess the pain score (morning and evening pain) and foot function, respectively. Assessments were conducted before the study, at the tenth session of the CP and CPP groups, and 4 weeks later. The study variables in both the CP and CPP groups changed significantly (p < 0.05). In comparing the results between the two groups, the reduction in evening pain scores in the CPP group was significant compared to the CP group (p < 0.05). In comparison, there was no significant difference in morning pain scores between the two groups. The FFI score in the CPP group significantly decreased compared to the CP group. Both CP and CPP are effective in reducing pain and the FFI in patients with PF. The addition of PEMF to CP demonstrates a more significant effect on reducing evening pain and somewhat on reducing the FFI in patients compared to CP alone. However, it did not have an additional effect on reducing morning pain. Bioelectromagnetics. 00:00-00, 2026. © 2026 Bioelectromagnetics Society.

Humans↗

PubMed2026

Pre-clinical evaluation of the anticaries effect of an experimental Malva sylvestris extract mouthwash using a cariogenic model in situ.

OBJECTIVE: The aim of this study was to evaluate the antimicrobial and anticariogenic potential of Malva sylvestris extract on enamel and dentin in situ. METHODS: A double-blind crossover in situ study was conducted with 12 participants wearing palatal appliances containing two bovine enamel and two dentin specimens per 3 phases, a total of 72 enamel and dentin specimens. Biofilm formation and daily sucrose exposure were allowed. Treatments were applied twice daily in three phases: Malva sylvestris (2.5%, MS); fluoride (225 ppm, F); and placebo (P). After seven days, biofilm was collected from the bovine specimens for analysis of Lactobacillus spp. and mutans streptococci by Colony Forming Unit counts (CFU log₁₀/mL). Dental demineralization of the bovine specimens was assessed by transverse microradiography (TMR). RESULTS: MS did not reduce Lactobacillus spp. counts (CFU log₁₀/mL: enamel 6.63±0.81; dentin 6.68±0.92) compared to P (6.63±0.70; 6.62±0.51). F also did not differ (6.29±0.75; 6.32±0.41; ANOVA/Tukey, p>0.38). Mutans streptococci data were inconclusive. In enamel, both MS (2320.8±768.2 %vol·µm; 101.6±27.0 µm) and F (1777.3±733.3 %vol·µm; 95.8±23.5 µm) significantly reduced integrated mineral loss and lesion depth compared to P (3517.2±1119.9 %vol·µm; 138.6±19.5 µm; ANOVA/Tukey, p≤0.0003). In dentin, MS significantly reduced integrated mineral loss (322.5 [250-580] %vol·µm) and lesion depth (30.1 [15-42.2] µm) compared to P (880 [580-1705]; 58.3 [32.2-88.6] µm; Kruskal-Wallis/Dunn, p≤0.001), while F (587.5 [305-720]; 25.2 [16.5-38.8] µm) did not differ significantly (p>0.05). CONCLUSIONS: Malva sylvestris extract had no antimicrobial effect on Lactobacillus spp. counts, but significantly reduced enamel and dentin demineralization, showing anticaries effect comparable to fluoride. CLINICAL RELEVANCE: Malva sylvestris has demonstrated promising biological activity. This study investigates the antimicrobial efficacy of Malva sylvestris against cariogenic microorganisms in situ. Our findings provide relevant evidence that M. sylvestris exert significant anticaries effects using an in situ model.

Biofilms↗

PubMed2026

Genome-Wide Impact of Human DBR1 Depletion on RNA Processing Networks Reveal a Connection Between Pre-mRNA Splicing, mRNA Surveillance and Stress Granule Dynamics.

The RNA lariat debranching enzyme DBR1 is essential for intron turnover and RNA metabolism, yet its broader impact on transcriptome regulation remains incompletely defined. To elucidate the consequences of DBR1 depletion, we performed transcriptome-wide RNA sequencing of DBR1-knockdown and wild-type HEK293 cells. Differential expression analysis revealed widespread perturbations in pathways linked to RNA splicing, mRNA surveillance, translational control, and stress-granule biology. Many of the most significantly altered transcripts encode splicing factors and RNA quality-control components, underscoring DBR1's influence on post-transcriptional regulation. Alternative splicing analysis showed changes across multiple event types, with exon skipping accounting for >50% of events, followed by mutually exclusive exons, alternative 5' and 3' splice sites, and retained introns, indicating that DBR1 depletion induces pervasive splicing defects. Direct spliceosome inhibition using isoginkgetin (blocks tri-snRNP recruitment) and pladienolide B (targets SF3B1) reproduced the DBR1-KD mis-splicing patterns of cell signaling genes and factors involved in RNA metabolism, supporting a functional link between DBR1 activity and alternative splicing. Notably, DBR1 knockdown revealed a subset of transcripts that are both NMD-sensitive and enriched within stress granules. Consistent with this observation, G3BP1 immunopurification and confocal microscopy further support a role for DBR1 and UPF1 in stress-granule dynamics, suggesting that these factors may participate at distinct stages to influence mRNA fate under stress conditions. Together, these findings indicate that DBR1 functions beyond lariat RNA turnover as a common regulator of RNA processing, transcriptome stability, and stress granule homeostasis, revealing intricate crosstalk between RNA splicing and RNA quality control pathways in human cells.

Humans↗

PubMed2025

Preoperative Patient Education on Opioid Use and Pain After Surgery: A Randomized Trial.

OBJECTIVE: To evaluate the impact of preoperative analgesic education on postoperative opioid consumption, pain scores, and patient satisfaction with analgesia. BACKGROUND: Effective postoperative pain management is crucial for patient recovery and satisfaction, yet opioid use poses risks of tolerance and addiction. Preoperative patient education offers a potential avenue to mitigate opioid reliance and improve pain management outcomes. METHODS: This single-center randomized trial was conducted at the Cleveland Clinic Main Campus between October 2021 and October 2023. Adult patients scheduled for hip arthroplasty or laparoscopic-assisted abdominal surgery with an ASA physical status of 1 to 4 were eligible. Patients with a history of prolonged opioid use, planned regional block or epidural analgesia, or limited English fluency were excluded. Participants were randomized 1:1 to receive either an analgesic educational video or a generic video about surgery and hospitalization. The primary outcome was opioid consumption during the initial 72 postoperative hours. Secondary outcomes included time-weighted average pain scores and patient satisfaction with analgesia. RESULTS: Among 957 analyzed patients, preoperative analgesic education did not significantly reduce opioid consumption (adjusted ratio of geometric means, 1.01; 95% CI, 0.86-1.18; P =0.890) or improve pain scores (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P =0.617). Patient satisfaction scores also did not differ significantly between groups (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P = 0.611). CONCLUSIONS: Preoperative analgesic education did not result in clinically meaningful reductions in opioid consumption or improvements in pain management outcomes. Further research may explore more intensive educational interventions to optimize postoperative pain management strategies.

Humans↗

PubMed2026

Bergamottin, a bioactive component of bergamot: dual inhibition of Japanese encephalitis virus internalization and genome replication.

Japanese encephalitis virus (JEV) is associated with high mortality and severe neurological sequelae, and existing prevention and control strategies remain insufficient. Therefore, the development of novel antiviral agents is of critical public health importance. This study systematically evaluated the antiviral activity and underlying mechanism of bergamottin, a natural product. Bergamottin exhibited significant dose-dependent inhibitory effects against JEV in multiple cell lines, including BHK-21, HuH-7, and Vero cells, demonstrating potent antiviral efficacy. Mechanistic investigations revealed that bergamottin primarily targeted the internalization and replication stages of the JEV life cycle, thereby effectively suppressing viral proliferation. Additionally, adaptive mutation screening indicated that the D389G mutation in envelope protein E confers drug resistance by potentially changing E protein conformation or reducing endocytic efficiency. In vivo experiment, bergamottin significantly reduced viral loads in mouse brain tissue and effectively improved the survival rate of infected mice. Our findings indicated that bergamottin exerted antiviral activity by dual targeting of key steps in the viral life cycle, making it a highly promising candidate for anti-JEV therapy. Further exploration of the antiviral properties of bergamottin is expected to facilitate its clinical development as a treatment for JEV infection.

Animals↗

PubMed2026

Chalcone-indole hybrid scaffolds as promising anticancer drug candidates: a mini-review.

Cancer treatment is hampered by severe systemic side effects, poor tumor selectivity, and multidrug resistance (MDR). Molecular hybridization integrates chalcone and indole, two privileged antitumor pharmacophores, into one scaffold to generate chalcone-indole hybrids that synergistically enhance antitumor potency, improve tumor targeting, and reverse MDR. This mini-review analyzes literature from 2020 to 2026 on chalcone-indole anticancer hybrids. Based on structural modification patterns, the reported hybrids are categorized into four subgroups: simple substituted, α/β-position modified, N-1 fatty acid-substituted, and multi-pharmacophore fused hybrids. For each category, we summarize structure-activity relationships (SARs), antiproliferative activity, selective toxicity, molecular mechanisms, and in vivo xenograft performance. Most lead compounds exert tumor-suppressive effects via tubulin polymerization inhibition, G2/M cell cycle arrest, ROS overaccumulation, and mitochondrial-dependent apoptosis. Representative hybrids 10a, 12a, 21a, and 25a exhibit remarkable efficacy against drug-resistant colorectal, lung, and breast tumors with favorable in vivo safety. We highlight the application potential of different subtypes for specific malignancies, including α/β-modified analogues for resistant colorectal cancer, N-1 fatty acid-platinum conjugates for platinum-resistant lung cancer, NLRP3 inhibitor 7a for oral cancer, and multi-pharmacophore fused derivatives for broad-spectrum activity. Current bottlenecks limiting clinical transformation are discussed. This review provides structural design rules for developing novel chalcone-indole targeted anticancer agents.

Humans↗

PubMed2025

Feasibility, Acceptability, and Preliminary Effectiveness of Family Navigation for Low-income Ethnoracially Diverse Preschoolers with Developmental Concern.

OBJECTIVE: To assess for feasibility, acceptability, and preliminary effectiveness of an ethnoracially-matched family navigation intervention aimed at reducing barriers to developmental evaluations for preschoolers with developmental concern attending Head Start. METHODS: Fifty-eight parents of Head Start preschoolers who were identified as at risk for developmental delay were assigned using stratified block random sampling to the family navigation intervention (n = 28) and 30 controls (usual care). Key outcomes included the percentage of children who completed the planned intervention visits, satisfaction with the intervention, and the proportion of children guided by family navigators who completed developmental evaluations. RESULTS: Of the 28 families, 21 parents completed the family navigation intervention visits. The intervention sample was diverse, including 57% Black, 24% White, and 19% Latino(a) parents. Ninety percent of Head Start educators (n = 18) and 100% of healthcare providers (n = 6) were satisfied with the intervention. Parents qualitatively reported that they valued the advocacy support from the family navigators and navigators (n = 7) valued their role in "giving back." Sixty-six percent of the intervention group were seen by a healthcare provider to discuss developmental concerns showing preliminary effectiveness for completion of healthcare evaluations. However, there was no significant difference between those in the intervention and control group completing Head Start recommended evaluations, and over half of all participants were not referred for educational evaluations. CONCLUSION: Results support the feasibility, acceptability, and preliminary effectiveness of an ethnoracially matched family navigation intervention to reduce barriers to developmental healthcare evaluations for preschoolers at risk for developmental delays. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03499405; Date of Registration: April 9, 2018.

Humans↗

PubMed2026

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans↗

PubMed2026

In Vitro comparison of herbal and conventional antifungals against Candida strains in Oral candidiasis: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically review and meta-analyze the in vitro antifungal activity of herbal and conventional antifungals against Candida strains. DESIGN: In vitro studies were identified through PubMed, Embase, Scopus, and Web of Science up until May 2026. This review is registered with Prospero (CRD420251128404). Eligibility was determined using the Population, Intervention, Comparison, and Outcome (PICO) framework, with specific inclusion and exclusion criteria focused on in vitro antifungal investigations comparing herbal antifungals with conventional antifungals. The risk of bias was assessed using the modified Quality Assessment Tool for In Vitro Studies (QUIN Tool). A meta-analysis was performed, with the primary outcome measure being the ratio of means (RoM). RESULTS: The systematic review included twenty-five articles. Most studies showed different results in inhibition zones or minimum inhibitory concentrations between herbal and conventional agents. The meta-analysis indicates that certain herbal antifungals are equally effective as or more effective than conventional antifungals against Candida dubliniensis, Candida lusitaniae, and Candida tropicalis. While the efficacy of herbal antifungals for Candida albicans and Candida glabrata was modest, Piper betle L. demonstrated significant inhibitory potential. In contrast, conventional antifungals outperformed herbal antifungals against Candida krusei and Candida parapsilosis. CONCLUSIONS: This systematic review and meta-analysis highlight herbal medicine as a potential antifungal therapy for oral candidiasis, emphasizing the need for new strategies due to resistance to conventional antifungals.

Humans↗

PubMed2026

Effect of Perioperative Sucralfate Administration on Pain Control After Tonsillectomy: A Systemic Review and Meta-Analysis.

OBJECTIVES: This study evaluated the efficacy of perioperative intraoral sucralfate in reducing postoperative pain following tonsillectomy through a systematic review and meta-analysis. METHODS: A comprehensive search of PubMed, SCOPUS, Embase, Web of Science, and Cochrane up to September 2025 identified 13 studies comparing perioperative intraoral sucralfate with placebo or no treatment. Outcomes included throat pain, otalgia, swallowing pain, analgesic consumption, and perioperative morbidities. RESULTS: Sucralfate increased the proportion of patients reporting no or mild throat pain and otalgia, improved mucosal healing at 5 to 7 days, and reduced throat pain, swallowing pain, otalgia, analgesic use, and time to resume >50% of a regular diet. No significant differences were observed in postoperative bleeding or nausea/vomiting. CONCLUSION: Perioperative intraoral sucralfate may be an effective adjuvant therapy that improves postoperative pain control, enhances wound healing, reduces analgesic requirements, and facilitates earlier dietary resumption after tonsillectomy.

Humans↗

PubMed2026

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

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

Streptomyces↗

PubMed2026

Optimizing Initial Dosing for Tacrolimus and Mycophenolate in Living Donor Liver Transplantation: A Systematic Critical Review.

BACKGROUND: The pharmacokinetics (PK) of immunosuppressive agents in living donor liver transplantation (LDLT) recipients are expected to differ from those in deceased donor liver transplantation (DDLT) recipients because of the smaller initial liver volume transplanted and pathophysiological changes during liver regeneration. Consequently, the hepatic metabolism, CYP enzyme activity, and glucuronidation may be reduced. The PK of tacrolimus (metabolized by CYP3A5) and mycophenolate (metabolized through glucuronidation) are expected to be affected early post-LDLT. However, the initial dosing recommendations for post-LDLT remain unclear. PURPOSE: This study aimed to recommend initial dosing approaches for tacrolimus and mycophenolate in LDLT recipients based on available PK data in humans. METHODS: A PubMed search was conducted in March 2025 to identify studies investigating the PK data of immediate-release tacrolimus and mycophenolate in pediatric or adult LDLT recipients. RESULTS: After screening, 8 and 8 articles on tacrolimus and mycophenolates, respectively, met the review criteria. The current literature suggests that LDLT recipients require lower tacrolimus doses than DDLT recipients, particularly in the early post-transplant period. In addition, CYP3A5 polymorphisms in both donors and recipients contribute to interindividual variability in tacrolimus exposure, further complicating tacrolimus management. Studies on mycophenolate use in LDLT recipients are limited, with insufficient evidence to support dose reduction. CONCLUSIONS: Reducing the initial tacrolimus dose in LDLT recipients by 30%-50% compared with that in DDLT recipients would be reasonable while maintaining the same initial dose of mycophenolate between LDLT and DDLT recipients.

Humans↗

PubMed2026

Frontline therapies for adult patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia: a systematic literature review.

OBJECTIVES: Philadelphia (Ph) chromosome-negative B-cell acute lymphoblastic leukemia (B-ALL) is the most common ALL in adults. Overall survival (OS) with frontline chemotherapy remains poor. Blinatumomab is currently the only targeted agent approved for frontline treatment. METHODS: We systematically reviewed 96 studies (43 interventional, 53 observational) between 2012-2026 evaluating frontline pharmacologic therapy in adults with Ph- B-ALL. RESULTS: Across chemotherapy studies, nearly half of patients relapsed within 3 years, and only 49%-69% survived beyond 3 years. Blinatumomab demonstrated robust and consistent efficacy in first complete response (CR1), supported by 2 randomized controlled trials (RCT) and 16 single-arm trials (SAT). In one RCT, blinatumomab reduced the risk of death by 59% versus chemotherapy alone (HR 0.41) when added to frontline consolidation in minimal residual disease (MRD) negative patients. Median OS reached 41.2 months in a SAT where blinatumomab monotherapy was administered to patients in MRD-positive CR1. SATs showed consistent efficacy outcomes regardless of age, MRD status, or chemotherapy backbone. DISCUSSION: Additional targeted therapies still under investigation have shown mixed results. CONCLUSION: Frontline inotuzumab (±blinatumomab) plus chemotherapy showed promise in older populations, while the efficacy benefit of rituximab was inconclusive. No new safety signals were identified in the frontline setting for targeted therapies.

Humans↗

PubMed2026

Association between SGLT2 inhibitors and reporting of phimosis/paraphimosis: a comparative pharmacovigilance analysis of the WHO database.

PURPOSE: Recent data have discussed occurrence of phimosis with Sodium-glucose co-transporter-2 (SGLT2) inhibitors. However, the potential risk among the different SGLT2 inhibitors is unknown. METHODS: Using Individual Case Safety Reports (ICSRs) registered in the WHO pharmacovigilance database (01/01/2000-30/06/2025), comparisons between the different SGLT2 inhibitors and versus other drugs used in diabetes (DUD) were performed. Results are shown as Reporting Odds Ratios (ROR). RESULTS: Among 11 342 810 ICSRs, 227 were phimosis/paraphimosis with SGLT2 inhibitors, mainly between 45 and 64 years. The higher ROR value was found with empagliflozin followed by dapagliflozin and canagliflozin. ROR for SGLT2 inhibitors was higher that of all other DUD [34.72 (25.86-46.62)]. The reporting risk of phimosis/paraphimosis with SGLT2 inhibitors was also higher than that of each pharmacological class of DUD. CONCLUSION: The results suggest an association between SGLT2 inhibitors use and phimosis ICSRs. Empagliflozin had the higher reporting risk.

Humans↗

PubMed2026

Whole-Genome Deep Learning Predicts Chemotherapy Response in Colorectal Cancer.

Chemotherapy response in colorectal cancer (CRC) exhibits significant heterogeneity, with current clinical predictors failing to capture complex genomic determinants of resistance. We developed a hybrid deep learning framework integrating convolutional neural networks (CNNs) and bidirectional long short-term memory (BiLSTM) networks to analyze whole-genome somatic mutations, evolutionary conservation, chromatin accessibility, and 3D genome architecture in 2,546 TCGA patients. An attention mechanism identified predictive genomic regions. The model achieved an AUC of 0.92 (95% CI: 0.89-0.94) in cross-validation and 0.88 (95% CI: 0.85-0.91) in independent validation, outperforming clinical models (ΔAUC = +0.18, p < 0.001). Key predictors included non-coding variants in TP53, KRAS, and PIK3CA regulatory regions. Triple-positive patients (mutations in all 3 regions) had significantly worse progression-free survival (HR = 4.7, p < 0.001). Our framework enables accurate chemotherapy response prediction and reveals novel non-coding resistance mechanisms, advancing precision oncology in CRC.

Humans↗

PubMed2026

Aflibercept With Versus Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: Optical Coherence Tomography Angiographic Changes From a Randomized Clinical Trial.

OBJECTIVES: To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fluence PDT. DESIGN: Image analysis of a double-masked, sham-controlled, randomized clinical trial. SUBJECTS: 55 eyes of 55 treatment-naïve participants with symptomatic macular PCV completing 52 weeks of follow-up. METHODS: Participants underwent protocolized, multimodal imaging, including OCT, OCTA, fluorescein angiography, and indocyanine green angiography at baseline, week 12, and week 52. Quantitative OCTA parameters included total lesion area, branching neovascular network (BNN) area, and BNN vessel density (VD). Qualitative features included trunk vessel presence and OCTA signal within the polypoidal lesion (PL). Eyes were categorized by treatment arm and PL closure at week 52. MAIN OUTCOME MEASURES: Longitudinal OCTA changes and predictors of PL closure at week 52. RESULTS: We included 55 eyes (28 combination therapy and 27 monotherapy). Total lesion area decreased at week 12 but returned toward baseline at week 52 (combination: 3.72 ± 3.01mm2 at baseline, 2.86 ± 2.50mm2 at week 12, 3.59 ± 3.26mm2 at week 52; monotherapy: 3.77 ± 2.23mm2 at baseline, 3.27 ± 2.36mm2 at week 12, and 3.47 ± 2.58mm2 at week 52). BNN area decreased at week 12 and remained reduced at week 52 in both treatment arms (combination: 2.29 ± 2.08 mm2 at baseline, 1.46 ± 1.36mm2 at week 12, and 1.53 ± 1.32mm2 at week 52; monotherapy: 2.39 ± 1.85mm2 at baseline, 1.87 ± 1.68mm2 at week 12, and 1.82 ± 1.38mm2 at week 52). BNN VD reduction was greater in the combination arm at week 12 (-10 ± 15% vs - 3 ± 12%, P = .02). The proportion of eyes with trunk vessels increased over time in both arms (combination: 35.7% at baseline, 59.3% at week 12, and 67.8% at week 52; monotherapy: 25.9% at baseline, 44.4% at week 12, and 71.4% at week 52). In multivariable analysis, baseline BCVA predicted BCVA change at week 52 (β=-0.96 [-1.21 to -0.72], P < .01), and baseline CST predicted CST change (β=0.93 [0.75 to 1.10], P < .01). Greater reduction in BNN VD at week 12 was independently associated with PL closure at week 52 (OR 0.62 [0.39 to 0.97], P = .03). CONCLUSIONS: Early reduction in BNN vessel density, rather than reduction in lesion size, was associated with subsequent PL closure. OCTA-derived vascular changes may serve as noninvasive biomarkers for predicting treatment response in PCV.

Humans↗

PubMed2025

Detoxifying biotransformation of chloramphenicol by Exiguobacterium sp. CAP4 and its bioaugmentation of chloramphenicol biodegradation in simulated wastewater.

The extensive use of chloramphenicol (CAP) in livestock leads the accumulation of CAP in livestock manures, threatening environmental and human health. Therefore, eliminating or reducing CAP concentration in manures before its re-utilization and application through microbial remediation is necessary. Exiguobacterium sp. CAP4, isolated from the plastisphere in duck manures, was capable of degrading CAP with the biodegradation efficiency of 97.8 % at initial CAP concentration of 5 mg/L within 4 days. A total of twenty-four biotransformation products were determined, including two novel transformation products, TP166 and TP203, enriched the integrity of CAP biodegradation pathways. Furthermore, the biotransformation process was proposed as a detoxifying process through biotransformation products toxicity evaluation. Notably, Exiguobacterium sp. CAP4 successfully colonized in the cow manures after inoculation, and bioaugmented the biodegradation of CAP in virgin cow manures. This study significantly extended our understanding of the CAP biotransformation fate, and provided a promising bacterial strain for bioremediation of CAP containing wastewater in situ.

Chloramphenicol↗