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Fractional laser therapy versus microneedling for non-acne scars and scar-like dermal fibrotic lesions.

BACKGROUND: Scarring caused by trauma, burns, surgery, and other dermal fibrotic conditions can lead to functional limitation and cosmetic distress. The comparative effectiveness of fractional laser therapy and microneedling for non-acne scars remains uncertain. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing fractional laser therapy with microneedling for non-acne scars and scar-like dermal fibrotic lesions. Following a PROSPERO-registered protocol and PRISMA guidelines, we searched PubMed, EMBASE, Web of Science, Cochrane Library, and CNKI from inception to May 2026 without language restrictions. Parallel-group and split-body randomized trials were eligible. Random-effects models were used to calculate standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes. RESULTS: Nine randomized controlled trials were included. Fractional laser therapy showed a statistically significant advantage over microneedling in scar scores (SMD = -0.99, 95% CI [-1.83, -0.15], P = 0.02) and collagen fiber regeneration (SMD = -2.14, 95% CI [-3.57, -0.72], P = 0.03). No statistically significant differences were found between the two interventions for elastic fiber improvement, epidermal thickness, or adverse events. Subgroup analyses did not show clear or consistent significant differences according to laser type, including comparisons between traditional and non-traditional fractional lasers and between CO₂ and non-CO₂ fractional laser systems. Substantial heterogeneity was observed across several outcomes, indicating considerable between-study variability. CONCLUSION: Based on currently available randomized evidence, fractional laser therapy may provide superior improvement in overall scar severity and collagen fiber regeneration compared with microneedling for non-acne scars and scar-like dermal fibrotic lesions. However, no clear differences were observed for elastic fiber improvement, epidermal thickness, or adverse-event incidence. Given the substantial heterogeneity, limited sample sizes, and possible reporting bias, these findings should be interpreted cautiously. Further large, standardized trials with longer follow-up are needed.

Humans

Endoscopic Ultrasound-Guided Franseen Fine-Needle Biopsy for Solid Pancreatic Lesions: A Systematic Review and Meta-Analysis.

INTRODUCTION: Accurate tissue acquisition (TA) of solid pancreatic lesions is essential for guiding treatment with endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) being the preferred method. Among FNB designs, the three-pronged Franseen-tip needle demonstrates strong diagnostic performance, though direct head-to-head comparisons with other FNB designs remain limited. METHODOLOGY: This meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251123856). Eligible studies enrolled patients with solid pancreatic lesions who underwent EUS-guided FNB, directly compared the Franseen-tip with other FNB needles. Six databases were systematically searched through July 2025, and study selection, data extraction, and risk of bias assessment (QUADAS-2 tool) were performed independently by two reviewers. Pooled estimates were generated using random-effects and bivariate hierarchical models. RESULTS: Sixteen studies (2,010 Franseen vs. 2,811 comparator) were included. Bivariate analysis showed that sensitivity and specificity of the Franseen needle were comparable to newer-generation comparator needles (sensitivity 91.3% vs. 94.0%; specificity 99.99% vs. 99.15%), whereas older-generation needles demonstrated lower sensitivity (80.8%) and inferior discriminatory performance (Negative Likelihood Ratio [LR⁻] 0.19 vs. 0.09). Diagnostic accuracy was higher with the Franseen needle (RR 1.07, 95% CI 1.01-1.14; I2 = 69%). Sample adequacy was similar overall (RR 1.04, 95% CI 0.95-1.14) but superior to older-generation needles (RR 1.19, 95% CI 1.02-1.41) and in lesions > 30 mm (RR 1.14, 95% CI 1.02-1.28, I2 = 81.2%). The Franseen needle achieved nominally strong diagnostic performance (DOR 116.6), although small-study effects were observed. Primary procedural outcomes were comparable between Franseen and comparator needles, including technical success (RR 1.00, 95% CI 0.98-1.02) and histological core procurement (RR 1.04, 95% CI 0.92-1.17). The Franseen needle had fewer low-cellularity samples (RR 0.56, 95% CI 0.45-0.69) and lower specimen bloodiness (RR 0.48, 95% CI 0.25-0.90) but a slightly higher overall adverse event rate (RR 1.29, 95% CI 1.06-1.57). CONCLUSION: The Franseen needle provides superior diagnostic accuracy and sample adequacy compared to older-generation FNB needles with comparable performance to newer-generation designs. It reduces low-cellularity samples and specimen bloodiness, although adverse events are slightly increased, with other primary procedural outcomes remaining comparable. TRIAL REGISTRATION: PROSPERO (Registration No. CRD420251123856).

Humans

Faecal Microbiota Transplantation Reduces Lesion Severity and Medication Use in Canine Atopic Dermatitis: A Randomised, Placebo-Controlled, Double-Blinded Clinical Trial.

BACKGROUND: Faecal microbiota transplantation (FMT) is an established therapy for gastrointestinal disease, yet its role in canine atopic dermatitis (cAD) remains unclear. HYPOTHESIS/OBJECTIVES: We hypothesised that adjunctive FMT improves clinical severity and reduces symptomatic medication use in dogs with cAD. The objective was to evaluate efficacy and safety versus placebo. ANIMALS: Forty-six client-owned dogs with naturally occurring cAD were enrolled from a referral hospital population; 40 completed the study (FMT n = 20, placebo n = 20). MATERIALS AND METHODS: Prospective, randomised, placebo-controlled, double-blinded clinical trial. Dogs received daily oral lyophilised FMT capsules for 90 days plus three monthly rectal FMT administrations (Day [D]0, D30, D60) or placebo capsules with sham handling. Concomitant symptomatic therapies were permitted. Outcomes included Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), Medication Score (D0-90) and Owner Global Assessment of Treatment Efficacy (OGATE, D90). RESULTS: CADESI-04 scores were lower with FMT at month (M) 2 (7 ± 6 vs. 16 ± 12; p = 0.006) and month 3 (8 ± 6 vs. 15 ± 12; p = 0.020). Sustained responders (≥ 50% CADESI-04 improvement at M2 and M3) were more frequent with FMT (35% vs. 5%; p = 0.044). In the FMT group, the medication scores were lower at M2 (16 ± 10 vs. 23 ± 11; p = 0.033) and M3 (13 ± 10 vs. 24 ± 15; p = 0.007) compared to placebo. PVAS decreased in both groups without between-group differences. OGATE favoured FMT (p = 0.028). FMT was well tolerated. CONCLUSIONS AND CLINICAL RELEVANCE: Adjunctive FMT reduced lesion severity and medication requirements, supporting its use as a safe microbiome-based add-on therapy in cAD.

Animals

Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial.

BACKGROUND: Artificial intelligence (AI)-based computer-aided detection (CADe) systems improve adenoma detection in average-risk colorectal cancer screening. Meanwhile, evidence in Lynch syndrome surveillance is sparse and inconsistent. We assessed the effect of CADe on adenoma detection during Lynch syndrome surveillance. Computer-aided optical diagnosis (CADx) performance for optical differentiation of colorectal lesions was evaluated as a secondary aim. METHODS: CADLY2 was an international, multicentre, open-label, randomised controlled superiority trial at nine specialised hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome scheduled for surveillance colonoscopy were randomly assigned (1:1) to high-definition white-light (HD-WL) colonoscopy alone or to HD-WL colonoscopy with computer-aided assistance from CAD EYE (Fujifilm, Tokyo, Japan). CAD EYE was used for CADe during withdrawal and for CADx after lesion detection. Randomisation was done centrally through a secure web-based system using Pocock's minimisation algorithm with a stochastic component and was stratified by centre, sex, previous colorectal cancer, underlying pathogenic variant, and interval since previous colonoscopy. Allocation concealment was ensured through the centralised web-based system. Patients were masked to group allocation until the start of withdrawal in procedures with mild sedation, or until completion of the procedure in procedures with propofol-based sedation. Endoscopists were not masked. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma, analysed in the full analysis set (defined as all randomly allocated patients with available data for the primary outcome). The diagnostic performance of the CADx system was evaluated as a secondary outcome. The safety analysis set comprised all randomly allocated patients who underwent a study colonoscopy. This study is registered with the German Clinical Trials Register, DRKS00030695, and is completed. FINDINGS: Between May 9, 2023, and Oct 30, 2025, 757 patients were randomly allocated to HD-WL colonoscopy (377 patients) or to AI-assisted colonoscopy (380 patients); 733 patients were included in the full analysis set (369 HD-WL and 364 AI-assisted). The median age was 49 years (IQR 38-59) in the HD-WL group and 50 years (38-59) in the AI-assisted group; 213 (58%) were female and 156 (42%) male in the HD-WL group, and 207 (57%) were female and 157 (43%) male in the AI-assisted group. The adenoma detection rate was 30·9% (114 of 369 patients) with HD-WL versus 33·8% (123 of 364 patients) with CADe assistance (odds ratio 1·14 [95% CI 0·83-1·57], p=0·41). For CADx differentiation of neoplastic versus non-neoplastic lesions in the paired lesion-level analysis, with histopathology as the reference standard and sessile serrated lesions and traditional serrated adenomas classified as non-neoplastic, CADx sensitivity was 85·9% (95% CI 82·0-89·1) and specificity was 91·4% (89·4-93·0). Three adverse events occurred in the AI-assisted group: two mild post-polypectomy bleedings and one serious pulmonary embolism or deep venous thrombosis unrelated to the procedure. No adverse events occurred in the HD-WL group. INTERPRETATION: CADe-assisted colonoscopy did not show the absolute improvement in adenoma detection rate that was assumed in the prespecified sample-size calculation. CADx did not clearly improve lesion differentiation beyond expert optical diagnosis in expert Lynch syndrome surveillance settings. FUNDING: Third-party research funding of the National Center for Hereditary Tumor Syndromes, University Hospital Bonn.

Humans

Assessment of atypical glandular cell interpretation in Pap tests using the Hologic Genius Digital Diagnostics System.

Atypical glandular cells (AGC) are a diagnostic challenge. The aim of this study was to evaluate the efficacy and diagnostic performance of AGC detection on the Hologic Genius Digital Diagnostics System (HGDDS). A retrospective analysis of 451 ThinPrep Pap cases was conducted, including 207 cases of AGC, 27 cases of high-grade squamous intraepithelial lesion (HSIL), 25 cases of low-grade squamous intraepithelial lesion (LSIL), and 192 benign cases. All AGC cases had follow-up histologic diagnoses, with 66 cases subsequently diagnosed as adenocarcinoma. The slides were randomized, scanned, and analyzed by the HGDDS. Patient age and HPV test results were provided to reviewers, an experienced cytologist, who screened the cases, followed by two cytopathologists who independently examined the cases on the HGDDS. Diagnostic concordance between the two cytopathologists indicated strong agreement (κ = 0.829). Sensitivity of AGC on Papanicolaou (Pap) tests for adenocarcinoma detection on HGDDS was 98.5% and 95.5%, respectively, comparable to the original ThinPrep interpretation (OTPI). Specificity for adenocarcinoma detection was significantly higher (84.6% and 85.6%) with the HGDDS than 27.7% with OTPI. Overall, the diagnostic performance for AGC/HSIL interpretation to detect CIN2/3/adenocarcinoma appeared to have improved with HGDDS compared with OTPI, particularly for specificity and positive predictive value (PPV). This is the first study evaluating AGC diagnosis using the HGDDS. The findings demonstrate that the sensitivity of adenocarcinoma detection as AGC on HGDDS is comparable to the ThinPrep Imaging System, but the specificity and PPV are improved. This suggests the potential of artificial intelligence to augment the performance of cervical cancer screening.

Humans

Performance of Photon-counting CT for Assessing Pretreatment Breast Cancer: Comparison with Mammography, MRI, and 18F-FDG PET/CT.

Background Photon-counting CT (PCCT) offers improved spatial resolution, contrast to noise ratio, and dose efficiency, but its clinical utility remains incompletely defined for breast cancer. Purpose To evaluate the feasibility of PCCT for pretreatment breast cancer assessment through comparisons with MRI, full-field digital mammography (FFDM), and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. Materials and Methods In this prospective study (March-May 2025), female participants with breast lesions categorized as Breast Imaging Reporting and Data System 4C or higher at US or FFDM underwent breast MRI and multiphasic contrast-enhanced PCCT. 18F-FDG PET/CT was performed in a subset with locally advanced disease. Four radiologists independently evaluated lesion morphologic characteristics, additional findings, and clinical TNM stage. Agreement was analyzed using intraclass correlation coefficients (ICCs) and κ statistics. The diagnostic performance for additional lesions and nodal metastasis was compared with the reference standard (pathologic examination). Results Among 126 participants (mean age, 58.1 years ± 12.3 [SD]), interreader agreement across PCCT, MRI, and FFDM was good to excellent. PCCT agreed with MRI for lesion characterization (κ = 0.57-0.96) and clinical T categorization (κ = 0.86-0.88), with highest agreement with pathologic size (ICC, 0.70-0.81). For 46 pathologically confirmed additional lesions, PCCT was more sensitive than FFDM (difference, 44% [95% CI: 19, 66]) and similar to MRI (difference, 7% [95% CI: -5, 21]). Additionally, 44% (95% CI: 27, 52) of microcalcifications were missed at PCCT versus FFDM. For pathologically confirmed nodal metastasis, PCCT was more sensitive (difference, 10% [95% CI: 1, 20]) and accurate (difference, 6% [95% CI: 1, 11]) than MRI. For clinical N category, PCCT agreed with PET/CT (κ = 0.82 [95% CI: 0.62, 0.96]; n = 19). Two distant metastases identified at PCCT were consistent with 18F-FDG PET/CT and pathologic findings. Conclusion PCCT demonstrated similar performance to MRI for lesion characterization and detection of additional lesions, with better performance for nodal metastasis evaluation; however, detection of microcalcifications was limited. © RSNA, 2026 Supplemental material is available for this article.

Humans

Bempedoic Acid and First and Recurrent Limb Outcomes in Statin-Intolerant Patients With Peripheral Artery Disease: Insights From the CLEAR Outcomes Trial.

BACKGROUND: Patients with peripheral artery disease (PAD) are at high risk of major adverse limb events (MALE) and major adverse cardiovascular events (MACE). Recently, bempedoic acid was shown to reduce MACE in primary and secondary prevention patients. Whether bempedoic acid reduces the risk of MALE in patients with PAD is unknown. METHODS: CLEAR Outcomes (Cholesterol Lowering via Bempedoic Acid [ETC1002], an ACL-Inhibiting Regimen) randomized 13 970 patients to bempedoic acid 180 mg or placebo from December 22, 2016, to August 14, 2019. The trial primary end point was MACE-4, defined as death resulting from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. A clinical history of PAD was reported by investigators at baseline. Two blinded vascular medicine specialists independently adjudicated MALE, including adverse events indicating worsening PAD symptoms leading to revascularization, chronic limb-threatening ischemia, and acute limb ischemia. Outcomes were assessed as time to first event and total (including recurrent) events with a negative binomial approach. RESULTS: A total of 1624 of the enrolled patients (mean±SD age, 63.9±9.9 years; 915 [56.3%] female) had PAD at baseline. In patients with PAD in the placebo group, 69 (8.3%) had MALE over a median of 40.6 months, with rate of recurrent events of 4.0%/y. Bempedoic acid reduced the risk of MALE by 36% (hazard ratio, 0.64 [95% CI, 0.44-0.93]; P=0.018). Bempedoic acid reduced total MALE by 45% (relative risk, 0.55 [95% CI, 0.35-0.85]; P=0.007). First MACE-4 or MALE was reduced overall by 13% (hazard ratio, 0.87 [95% CI, 0.80-0.95]) with consistent effects with PAD (hazard ratio, 0.82 [95% CI, 0.64-1.04]) and without PAD (hazard ratio, 0.87 [95% CI, 0.79-0.86]; Pinteraction=NS) but not statistically significant within the PAD subgroup alone. Total MACE-4 or MALE was reduced (relative risk, 0.81 [95% CI, 0.73-0.90]) overall with consistent effects in PAD (relative risk, 0.71 [95% CI, 0.54-0.95]) and without PAD (relative risk, 0.82 [95% CI, 0.73-0.92]; Pinteraction=NS). CONCLUSIONS: Patients with PAD are at high risk of MALE and MACE. Bempedoic acid reduces both MACE and MALE in patients with atherosclerotic vascular disease, with notable absolute benefits in patients with PAD. These findings support (1) the importance of lowering low-density lipoprotein cholesterol in patients with PAD to reduce overall vascular risk and (2) the benefits of bempedoic acid in this population.

Humans

Rationale, design, and experiences from the vanguard phase of the bariatric surgery for the reduction of cardiovascular events (BRAVE) trial.

BACKGROUND: Observational studies suggest that metabolic/bariatric surgery (MBS) reduces mortality and major adverse cardiovascular events in patients with obesity, but adequately powered randomized trials (RCTs) are lacking. The Bariatric Surgery for the Reduction of Cardiovascular Events (BRAVE) trial was designed to address this evidence gap. METHODS: BRAVE is an investigator-initiated, multi-center, open-label RCT with blinded endpoint adjudication comparing MBS vs guideline-based medical weight management (MWM) in adults with obesity and high-risk cardiovascular disease (CVD). Eligible participants have a body-mass index ≥35 kg/m² or ≥30 kg/m² with type 2 diabetes or age >55 years, and prior myocardial infarction (MI), coronary intervention, heart failure (HF), atrial fibrillation (AF) with elevated CHA₂DS₂-VASc score, cerebrovascular disease, or peripheral arterial disease. Participants are randomized 1:1 to MBS (sleeve gastrectomy, Roux-en-Y gastric bypass, or duodenal switch) or MWM, which includes dietary, behavioral, and pharmacologic therapies. The primary outcome is the composite of all-cause death, MI, stroke, HF events, coronary revascularization, AF hospitalization, and renal events. A vanguard phase of 200 participants was implemented to optimize recruitment and logistics. RESULTS: As of October 2025, 2,514 individuals have been screened from 17 centers in Canada, Brazil, Italy and Spain, with 444 entered MBS work-up, and 200 have been randomized. The randomized cohort (mean age 59.8 years; 37% female; mean BMI 44.0 kg m⁻²) has high burden of hypertension (82%), diabetes (45%), coronary artery disease (44%), HF (39%), and AF (48%). Recruitment barriers were identified and addressed through targeted education and enhanced patient engagement. CONCLUSIONS: BRAVE is the first large RCT evaluating whether MBS safely reduces major cardiovascular events compared with medical therapy in high-risk patients with obesity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05531474.

Humans

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5 months, 5-year PFS and OS for the whole cohort (n = 86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR = 3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR = 4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n = 59; 89.7%-58.3%). OS differed across groups (log-rank p = 0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein–Barr virus DNA

Portable metagenomics for preventive surveillance and outbreak control in livestock and poultry: Pathogen detection, resistome profiling, and antimicrobial stewardship.

Conventional diagnostics for livestock and poultry outbreaks commonly rely on culture or targeted PCR panels, which may be too slow or too narrow to guide early control decisions. Portable metagenomics, particularly real-time nanopore sequencing, offers a route to broad pathogen detection, antimicrobial-resistance gene profiling, and outbreak investigation within an integrated workflow. This implementation-focused review evaluates how near-point-of-care metagenomics may support preventive veterinary medicine through earlier detection, surveillance, cohorting, biosecurity decisions, and antimicrobial stewardship. We synthesize sample-to-answer workflows for enteric and respiratory disease in food-producing animals, including sampling, nucleic-acid extraction, host depletion or target enrichment, library preparation, sequencing, bioinformatics, quality control, and interpretation. Applications in calf diarrhea, bovine respiratory disease, poultry outbreaks, mastitis, and resistome monitoring are considered alongside the central limitation that detection alone does not establish causation. Pathogen and resistance-gene signals must therefore be interpreted with clinical signs, lesions, epidemiology, controls, and confirmatory testing. We also propose a minimum reporting checklist, intended as a practical framework rather than a validated consensus standard. Portable metagenomics is not a replacement for conventional diagnostics, but appropriately validated workflows can reduce uncertainty during time-sensitive outbreaks and support more judicious antimicrobial use.

Animals

Paramedian supracerebellar transtentorial approach for Yaşargil T2 tentorial incisura meningiomas.

OBJECTIVE: Tentorial incisura meningiomas, particularly those arising from the middle incisural region (Yaşargil T2), are surgically challenging because of their deep location and compression of critical neurovascular structures. These lesions typically have supratentorial or infratentorial extension but can also extend across both compartments. Although approach selection is often guided by the dominant compartment of tumor extension, for lesions with supratentorial-dominant extension, the optimal approach remains controversial, and a standardized strategy has not been established. Authors of this study evaluated the feasibility and outcomes of the paramedian supracerebellar transtentorial (PST) approach for Yaşargil T2 tentorial incisura meningiomas with a supratentorial-dominant or combined extension. METHODS: The authors retrospectively reviewed data from consecutive patients with radiographic and intraoperative findings consistent with a Yaşargil T2 tentorial incisura lesion treated via the PST approach from September 2005 through December 2025. Patients were placed in a semisitting position whenever feasible and in a semilateral position when semisitting was contraindicated. Collected data included demographics, tumor extension patterns, extent of resection on postoperative MRI, neurological outcomes, histopathology, rate of recurrence, and follow-up. RESULTS: Six patients, 1 male and 5 female, with an overall mean age of 43 years, underwent resection via the PST approach. Four lesions had predominantly supratentorial extension, and 2 had combined supra- and infratentorial growth, with no cases of isolated infratentorial extension. Five patients had been placed in the semisitting position and 1 in a semilateral position because of a cardiac contraindication to the semisitting position. No new permanent neurological deficits were observed. Postoperative MRI showed Simpson grade I resection in all 6 patients. The mean follow-up was 8.6 years. Histopathological analysis revealed 3 WHO grade 1 meningiomas, 1 WHO grade 2 meningioma (clear cell), and 2 solitary fibrous tumors (meningioma mimics). These diagnoses were evaluated according to the 2021 WHO classification. CONCLUSIONS: In this consecutive series, the PST approach was a viable single-corridor strategy for Yaşargil T2 tentorial incisura lesions, including supratentorial-dominant tumors, achieving Simpson grade I resection with no permanent neurological deficits. By providing early devascularization at the tentorial attachment and a gravity-assisted, retractorless working corridor with favorable deep venous visualization, the PST approach challenges compartment dominance as the primary determinant of approach selection.

Humans

Linked-color imaging with computer-aided detection and the proximal adenoma miss rate: a randomized tandem trial.

BACKGROUND AND AIMS: Linked-color imaging (LCI) aids the detection and characterization of lesions. Computer-aided detection (CADe) systems have been introduced to improve lesion detection during colonoscopy. Although several studies have been reported regarding LCI, few have investigated the combination of LCI and CADe. This study aimed to evaluate the efficacy of LCI with CADe colonoscopy compared to conventional white-light colonoscopy. METHODS: A single-center, randomized tandem trial was conducted. Participants referred for first-time colonoscopy after fecal immunochemical test (FIT)-positive, asymptomatic screening, or surveillance colonoscopy were randomized (1:1) to undergo CADe-assisted colonoscopy of LCI or white-light imaging (WLI) in the right side of the colon. The primary outcome was adenoma miss rate (AMR) in the right side of the colon. Secondary outcomes included polyp miss rate (PMR), diminutive adenoma miss rate (dAMR), sessile serrated lesion miss rate (SSLMR), advanced adenoma miss rate, advanced neoplasia miss rate, flat-type lesion miss rate (FMR), and the differences in miss rates based on expertise. RESULTS: Among 232 randomized participants, 209 were analyzed (LCI/CADe: 102; WLI: 107). AMR (WLI: 39% vs LCI/CADe: 20%; P = .001), PMR (42% vs 18%; P < .001), and dAMR (42% vs 21%; P = .003) were significantly lower in the LCI/CADe arm, particularly among experts. SSLMR (46% vs 0%), advanced AMR (30% vs 0%), advanced neoplasia miss rate (25% vs 0%), and FMR (27% vs 5.6%) were lower in LCI/CADe, although without statistical significance. CONCLUSIONS: Compared to conventional colonoscopy, LCI with CADe colonoscopy resulted in a statistically significant decrease, especially in AMR. (UMIN 000050685).

Humans

The Effect of Breastfeeding on Cervical Dysplasias.

OBJECTIVE: This study aimed to investigate the relationship between breastfeeding and precancerous cervical lesions. MATERIALS AND METHODS: A case control study was conducted at a tertiary training and research hospital between September 1 and November 1, 2023. A total of 168 patients who attended the gynecology outpatient clinic and reported their breastfeeding experiences were included. Patients with abnormal cervical cytology formed the study group (n = 37), while patients with normal cytology formed the control group (n = 131). Breastfeeding duration and patterns were compared between groups. RESULTS: The control group had normal smear results. In the study group, 15 patients had high-grade squamous intraepithelial lesions, and 22 patients had low-grade squamous intraepithelial lesions. Human papillomavirus (HPV) was positive in 54.1% of the study group versus 9.2% of the control group. The mean breastfeeding duration was shorter in the study group (9.18 &#xb1; 3.43 months) than the control group (23.6 &#xb1; 3.35 months; p < 0.05). Most control group patients breastfed for 13-36 months (35.1%), while most study group patients breastfed for <6 months (48.6%; p < 0.05). Shorter breastfeeding (<6 months) and HPV positivity were the strongest predictors of abnormal cytology. Breastfeeding <6 months increased the risk 9.883-fold compared with >36 months, while HPV positivity increased the risk 27.612-fold. CONCLUSION: Breastfeeding and longer breastfeeding duration appear to be associated with a lower risk of cervical intraepithelial neoplasia. Given its multiple health benefits, including prevention of gynecological cancers, promoting breastfeeding through public health policies is strongly recommended. Early recognition and prevention of precancerous lesions remain essential to reducing the risk of cervical cancer.

Humans

Comparative analysis of DDR-related genes and microRNA expression during rice germination: Implications for salinity susceptibility screening.

Soil salinity poses a significant threat to the agri-food sector and particularly to rice cultivation. High salinity during germination induces overproduction of reactive oxygen species (ROS) that cause lesions in the DNA resulting in reduced vigor. MicroRNAs (miRNAs) are known to modulate stress response in plants, however, studies focusing on its relation with the expression of the DNA damage response (DDR)-related genes are not thoroughly explored. In this regard, the aim of this work was to investigate the link between the expression of miRNAs and putative targeted DDR-related genes in response to salinity stress during germination. Eight varieties representative of indica and japonica rice subspecies were categorized into clusters through a principal component analysis (PCA) based on their germination performance and stress tolerance index under varying concentrations of NaCl. Subsequently, the expression patterns of six miRNAs and their putative targeted DDR genes were measured in two contrastive cultivars through quantitative real-time PCR (qRT-PCR) while correlations were examined through Pearson's analysis. Results showed distinct expression profiles between halotolerant and sensitive cultivars. Two miRNAs were further investigated in mature dry seeds of all the cultivars to verify their earliest, seed-specific discriminative potential. The distinct miR414 expression pattern may represent a potential biomarker for identifying salinity-susceptible cultivars during early-stage breeding screening.

Oryza

Presentation, management, and outcomes of anterior inferior cerebellar artery dissecting and fusiform aneurysms: a systematic review and institutional case series.

Dissecting and fusiform aneurysms of the anterior inferior cerebellar artery (AICA) are rare and poorly characterized lesions. This study provides a comprehensive patient-level synthesis to date, combining a systematic review with institutional data to describe their clinical presentation, diagnostic workup, management strategies, and outcomes.&#xa0;A systematic review was conducted according to PRISMA guidelines. Studies were included if they reported on dissecting or fusiform AICA aneurysms. Individual patient data were extracted and supplemented with a single-institution case series. Outcomes, complications, and radiological evolution were analyzed descriptively.&#xa0;Forty-nine patients from 36 studies and 6 patients from our institution were included in this study. In the systematic review cohort, most aneurysms presented with subarachnoid hemorrhage (n&#x2009;=&#x2009;38/49, 77.6%). Compressive cranial neuropathies, particularly including the vestibulocochlear system, were common in patients with unruptured aneurysms. Diagnosis often required digital subtraction angiography after the initial non-invasive imaging. Endovascular treatment, most commonly parent artery occlusion, was employed in 61.2% (n&#x2009;=&#x2009;30/49) of cases. However, ischemic complications occurred in 23.3% (n&#x2009;=&#x2009;7/30), especially in proximal (A1-A2) lesions. Bypass surgery was reported selectively for proximal aneurysms with inadequate collateral flow. As an alternative surgical approach, decompression or trapping was pursued based on aneurysm morphology or clinical context. Conservative management was typically reserved for select patients with poor-grade SAH, high procedural risk, or patient refusal of intervention. Overall, 81.4% (n&#x2009;=&#x2009;35/43) of patients with available follow-up achieved good functional outcomes.&#xa0;Management of AICA dissecting and fusiform aneurysms is highly individualized. Endovascular approaches were frequently used to secure ruptured lesions or lesions considered at high risk, but periprocedural ischemic risk in perforator-rich segments remains a notable concern. Bypass procedures were reported in selected proximal aneurysms with limited collateralization. Conservative management was reserved for highly selected high-risk or anatomically inaccessible cases. Clinical trial registration: This study is not a clinical trial.

Humans

Somatic mutations: recent advances in brain aging and neurodegeneration.

Somatic mutations are genetic variants that occur after the single-cell phase of development and have been implicated in disease pathogenesis. While most DNA lesions are detected and repaired, examination of healthy tissue has revealed that some lesions escape repair, leading to somatic mutations that accumulate at a consistent rate, including in human brain tissue and postmitotic neurons. Emerging methodological and analytical advances have revealed the presence of persistent mutagenic mechanisms during healthy brain aging as well as mutational pattern shifts in the context of neurodegenerative diseases. Here, we highlight recent methodological advances, summarize our current understanding of somatic mutagenesis in neurotypical brain aging, and examine the role of somatic mutations in neurodegenerative diseases.

Humans

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

BACKGROUND: Ponesimod demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) in 24-week phase-2 core study, further confirmed by an interim combined analysis of the core and open-label long-term extension (LTE) studies (NCT01093326; up to 8 years). Current study evaluated safety and efficacy of ponesimod using combined core and LTE studies data for up to 13 years. METHODS: Of 393 participants completing the core study, 353 (90%) entered LTE, having 3 treatment periods (TP). In TP1 (&#x223c;1.85 years), participants continued core treatment (ponesimod: 10, 20, or 40&#x202f;mg QD) whereas placebo-treated participants were re-randomized (1:1:1) to respective ponesimod doses. In TP2 (TP2 and TP3 combined duration: &#x223c;10.4 years), participants on 40&#x202f;mg were re-randomized (1:1) to 10/20&#x202f;mg, while others continued same dose; in TP3 all participants received 20&#x202f;mg. Study outcomes included safety and efficacy (ARR, time-to 24-week confirmed-disability-accumulation [24-week CDA], total T1-weighted Gadolinium-enhanced (T1 Gd+) lesions, new/enlarging T2 lesions and Combined Unique Active Lesions [CUALs]). RESULTS: For 20&#x202f;mg dose, total 92.4% participants experienced &#x2265;1 TEAEs (73.1% mild/moderate severity) and 19 (13%) participants discontinued study. Mean (95% CI) ARR=0.14 (0.10-0.20); Kaplan-Meier estimate (95% CI) of confirmed relapse and 24-week CDA=52.5% (42.3-63.5) and 31.3% (22.6-42.3). Mean [SD] T1 Gd+ lesions decreased from ponesimod baseline (2.62 [7.06]) to 12.4 years (0.26 [1.48]), mean (95% CI) CUALs per participant/year=3.97 (2.75-5.73). CONCLUSION: Ponesimod treatment for up to 13 years was not associated with new safety concerns. Participants continued to experience low levels of disease activity consistently across clinical and MRI outcomes.

Humans

HPV Testing Versus Cytology for Cervical Cancer Screening&#xa0;Among Women 50&#x2009;Years and Older: Evidence From the HPV FOCAL Randomized Controlled Trial.

Evidence on the comparative effectiveness of HPV testing versus cytology specifically in women aged &#x2265;&#x2009;50&#x2009;years who are approaching screening cessation remains limited. This analysis included 6471 women aged &#x2265;&#x2009;50 at baseline screening in the HPV FOCAL randomized clinical trial. Women were randomly allocated to receive cytology (Control Group, n&#x2009;=&#x2009;3248, 50.19%) or HPV testing (Intervention Group, n&#x2009;=&#x2009;3223, 49.81%) at baseline, with co-testing at 48-month exit. We calculated incidence rates and risk ratios for CIN2+ detection over follow-up and compared missed lesions at exit by screening method. At the 48-month exit, CIN2+ detection was lower among HPV baseline-negative women than among those in the cytology group (1.61/1000 [95% CI, 0.52-3.76] vs. 3.15/1000 [95% CI, 1.51-5.78]; risk ratio, 0.51 [95% CI, 0.11-0.91]), reflecting higher baseline detection with HPV testing and fewer prevalent lesions at exit. Even with cytology re-screening at 2&#x2009;years, 50% of CIN2+ cases were missed compared to 30% with HPV testing. After adjusting for age, education, smoking status, and lifetime sexual partners, the hazard ratio for CIN2+ comparing HPV to cytology was 0.44 (95% CI, 0.22-0.88). Among women aged &#x2265;&#x2009;50&#x2009;years, HPV primary screening was more effective than cytology at detecting CIN2+ lesions and was associated with a continued lower subsequent risk following a negative HPV test, supporting its use in cervical cancer screening programs in this age cohort.

Aged