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PubMed2026

The mighty microproteins: from versatile cellular regulators to precision medicine therapeutics.

Microproteins, are tiny proteins encoded by small open reading frame (sORF), translation of these non-canonical open reading frames (ncORFs) has been implicated in diverse biological processes and diseases. This review summarizes recent developments in the discovery, biogenesis, and functional characterization of microproteins, and their involvement in various disease, with special focus on their roles in cancer, cardiovascular, metabolic, neurodegenerative and immune-related disorders. We emphasize the regulation of key cellular pathways by microproteins, including mitochondrial homeostasis, apoptosis, metabolic reprogramming, and immune signaling, all of which affect disease initiation and progression. Emerging evidence also supports their potential as disease biomarkers and therapeutic candidates for precision medicine. Finally, the review critically discusses the current challenges including discrepancies in microprotein annotation, the limitations of ribosome profiling and proteogenomic approaches, the gap between computationally predicted and experimentally validated microproteins, and the need for rigorous orthogonal validation by means of CRISPR-based genome editing, ribosome release assays, mutational analysis, high-resolution mass spectrometry, and functional studies. Finally, we review recent development of AI-assisted ORF prediction, single-cell translatomics, spatial proteomics, and integrated multi-omics as emerging technologies reshaping. Microprotein discovery and functional annotation. Finally, we discuss the translational potential of microproteins and highlight the remaining challenges to clinical application, including peptide stability, pharmacokinetics, tissue-specific delivery, immunogenicity, and the need for rigorous preclinical and clinical validation. Together, this review provides an updated and critical overview of the rapidly evolving microprotein field and highlights future research priorities for translating these molecules into clinically useful biomarkers and precision therapeutics.

Microproteins↗

PubMed2026

Long-term outcomes of surgical correction of ventral penile curvature in children: Patient-reported measures, surgical results, and decisional regret.

INTRODUCTION: There is a dearth of data on long-term outcomes, including patient-reported outcomes (PROMs), decisional regret, and complication rates for surgical correction of isolated ventral penile curvature in childhood. PATIENTS AND METHODS: Twenty-six children treated for ventral curvature between 1993 and 2008 were identified; 24 met inclusion criteria (isolated ventral curvature without hypospadias or need for urethral reconstruction). Surgical correction consisted of degloving alone or degloving with Nesbit-like dorsal plication when residual curvature >20° persisted after degloving. PROMs were collected via pre-mailed validated questionnaires after puberty: Danish Prostatic Symptom Score (DAN-PSS) for LUTS, Erection Hardness Score (EHS) for erectile function, Penile Perception Score (PPS) for cosmetic perception, and items assessing decisional regret and perceived appropriateness of surgical timing. RESULTS: Curvature was corrected intraoperatively in all 24 patients. Twelve underwent degloving alone and 12 required additional dorsal plication. During long-term follow-up (median 14.2 years), one patient (4%) underwent re-operation for residual curvature, and three (13%) underwent cosmetic revisions; two (8%) underwent cystoscopy for flow concerns. 71% returned PROMs at a median age of 16.2 years. LUTS were uncommon, with low bother scores. Erectile function was favorable: 87% (13/15) reported EHS 4 and 93% (14/15) reported ejaculation. Cosmetic outcomes were favorable, with PPS dissatisfaction rates comparable to controls. Two patients reported dissatisfaction with overall appearance, and one with residual subjective curvature. No patient expressed decisional regret, and 88% felt timing of surgery was appropriate. CONCLUSION: Early surgical correction of isolated ventral penile curvature using degloving with or without dorsal plication provided durable anatomical correction and favorable long-term functional and cosmetic outcomes. These findings support early intervention as an effective approach with sustained patient-perceived benefits.

Humans↗

PubMed2026

Comparative Effectiveness of Oral Ivermectin, 1% Permethrin Shampoo, and 4% Dimethicone Liquid Gel in Treatment of Pediculosis Capitis among School Children in Chachoengsao Province, Thailand.

Pediculosis capitis remains a persistent public health issue, especially in developing countries where resistance to standard neurotoxic pediculicides like permethrin is increasingly prevalent. This study aimed to compare the effectiveness of alternative treatment options against the standard care in a resource-limited setting. We conducted a single-blind randomized controlled trial involving three primary schools in Chachoengsao Province, Thailand (ClinicalTrials.gov: NCT06332872). Eighty-five female participants ages 6-13 years with active infestations were enrolled. Schools were randomly assigned to three treatment arms: 1) oral ivermectin (200 µg/kg) on Days 0 and 7; 2) 1% permethrin shampoo on Days 0 and 7, or 3) 4% dimethicone liquid gel as a single dose on Day 0. The primary outcome was the cure rate, defined as the absence of live lice and viable nits upon clinical assessment on Day 9. Of the 66 participants included in the final per-protocol analysis, oral ivermectin achieved a cure rate of 95.5% (21/22), which was significantly higher than that of the 1% permethrin standard of care (37.0%; 10/27) and the 4% dimethicone physical suffocant (29.4%; 5/17) (P <0.001). Although dimethicone achieved high initial parasitic clearance on Day 0 (88.2%), a rapid reinfestation rate of 58.8% was observed by Day 9, indicating that a single-dose protocol may be clinically insufficient. Adverse events were mild and temporary across all groups. Oral ivermectin appears significantly more effective than both 1% permethrin and single-dose 4% dimethicone in this population. These findings suggest that permethrin resistance is clinically prevalent and relevant in this area.

Humans↗

PubMed2026

Hyperbaric oxygen for the treatment of traumatic incomplete spinal cord injury: a systematic review and meta-analysis of randomized controlled trials.

The therapeutic efficacy of hyperbaric oxygen therapy for traumatic incomplete spinal cord injury remains a subject of debate. To comprehensively evaluate the impact of hyperbaric oxygen on motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury, we conducted a systematic review and meta-analysis. We performed a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and major Chinese databases for randomized controlled trials published through June 2025. A total of 15 randomized controlled trials were included. The pooled results indicated that hyperbaric oxygen therapy significantly improved the American Spinal Injury Association motor score (mean difference = 10.30, 95% confidence interval: 7.70-12.90), the total American Spinal Injury Association sensory score (mean difference = 29.29, 95% confidence interval: 18.82-39.75), the American Spinal Injury Association light touch score (mean difference = 9.84, 95% confidence interval: 6.15-13.53), and the American Spinal Injury Association pinprick score (mean difference = 8.75, 95% confidence interval: 4.40-13.11). Furthermore, hyperbaric oxygen therapy was associated with significant enhancements in the Barthel Index (mean difference = 16.60, 95% confidence interval: 10.51-22.68) and the Functional Independence Measure (mean difference = 17.41, 95% confidence interval: 10.83-23.98). In conclusion, adjunctive hyperbaric oxygen therapy appears to improve motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury compared to conventional treatments alone. However, due to methodological limitations and potential publication bias in the included studies, these findings should be interpreted with caution, and further high-quality, multi-center randomized controlled trials are warranted.

Humans↗

PubMed2026

A systematic literature review of cultural concepts taught by pharmacist preceptors during pharmacy student experiential placements.

BACKGROUND: Cultural concepts such as cultural intelligence, awareness, competency and safety are essential in guiding culturally responsive care in health professional practice. Pharmacist preceptors play a pivotal role in sharing both clinical and cultural safe practice with pharmacy students. Culturally responsive care can contribute to achieving health equity, which is especially important for Indigenous communities. AIM: To review literature on cultural concepts in pharmacist preceptorship practices, and how these concepts are taught and communicated to pharmacy students during experiential learning. METHOD: The systematic review followed the PRISMA 2020 guideline. Scopus, PubMed, and Google Scholar were used to identify articles specific to pharmacist preceptors and pharmacy students published between 2015 and 2025, and available in English. RESULTS: Three full-text articles met the inclusion criteria. Major themes and subthemes were identified; pharmacist preceptors lacked preparedness to teach cultural concepts, resulting in variability in preceptors' understanding of cultural concepts and confidence in fulfilling preceptor responsibilities, underutilised structured frameworks to guide students' learning, challenges with preceptorship due to limited resources and support, and the influence of preceptorship on student learning, which impacted students' learning and competency. CONCLUSION: Pharmacy students had minimal exposure to culturally informed pharmacist preceptorship. It is likely that pharmacist preceptors require country-specific educational resources to support culturally safe preceptorship. Future research is required to substantiate these findings, and to guide culturally responsive practice and promote equitable health outcomes in diverse populations.

Humans↗

PubMed2026

Efficacy and safety of endoscopic ultrasound-guided choledochoduodenostomy compared with endoscopic ultrasound-guided gallbladder drainage for palliation of malignant distal biliary obstruction: a systematic review and meta-analysis.

BACKGROUND AND AIMS: When ERCP is not feasible or fails in the palliation of malignant distal biliary obstruction (MDBO), EUS-guided choledochoduodenostomy (EUS-CDS) and EUS-guided gallbladder drainage (EUS-GBD) are viable alternatives. We conducted a systematic review and meta-analysis comparing the safety and efficacy of the 2 techniques for the palliation of MDBO. METHODS: Multiple databases were searched through November 2025 for studies that reported outcomes of EUS-CDS and EUS-GDB in patients with MDBO. A meta-analysis was performed to determine pooled proportions and relative risk (RR) with 95% CIs. We compared the rates of technical and clinical success, overall adverse events (AEs), and lumen-apposing metal stent dysfunction. A random-effects model was used for our meta-analysis, and heterogeneity was assessed using the I2 (%) statistics. RESULTS: Five studies (352 patients; EUS-CDS: 193 and EUS-GBD: 159) were included. Technical success was 93.3% (95% CI, 70.6-98.8) for EUS-CDS and 95.9% (95% CI, 90.0-98.4) for EUS-GBD (RR, 1.02; 95% CI, 0.94-1.10; P = .6). Clinical success was 90.1% (95% CI, 84.7-93.7) versus 86.6% (95% CI, 80.3-91.0) (RR, 0.97; 95% CI, 0.90-1.05; P = .4). There were no significant differences in overall AEs (19.7% vs 17.6%; RR, 0.93; 95% CI, 0.58-1.48; P = .8), severe AEs (11.0% vs 8.3%; RR, 0.69; 95% CI, 0.33-1.44; P = .3), or stent dysfunction (15.0% vs 14.5%; RR, 0.95; 95% CI, 0.35-2.58; P = .9). CONCLUSIONS: EUS-GBD appears comparable to EUS-CDS in terms of technical and clinical success, AEs, and stent dysfunction. Further prospective studies are warranted to corroborate our findings.

Humans↗

PubMed2026

Neuromodulation for Subjective Tinnitus: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To evaluate the effectiveness and safety of neuromodulation and bimodal stimulation for chronic subjective tinnitus in randomized controlled trials (RCTs). DATA SOURCES: PubMed/MEDLINE, Web of Science, and EMBASE (January 2015-December 2025) searched per PRISMA 2020. REVIEW METHODS: Adult RCTs (≥ 18 years) with chronic subjective tinnitus (> 3 months) assessing validated outcomes (THI, TFI, TQ) for neuromodulation/bimodal interventions vs. sham/controls. Two-stage screening, Cochrane RoB-2 risk-of-bias assessment. Random-effects meta-analyses (REML) were performed when ≥ 3 comparable trials were available; effects reported as standardized mean differences (SMD) with 95% CIs. Main Outcomes and measures included change in tinnitus severity (THI/TFI/TQ) while secondary outcomes included loudness (VAS/NRS), durability, and adverse events. RESULTS: Twenty-six RCTs (n = 1576) met criteria: tES (11; n = 372), rTMS (8; n = 432), acoustic coordinated reset (1; n = 100), vagus nerve stimulation (2; n = 90), and bimodal stimulation (4; n = 582). Meta-analysis showed a nonsignificant pooled effect for tDCS (SMD -0.36; 95% CI -0.75 to 0.02; I 2 = 51%) and rTMS (SMD -0.15; 95% CI -0.37 to 0.07; I 2 = 0%). Single-trial evidence for coordinated reset showed no advantage over broadband noise. VNS demonstrated modest benefits with safety concerns limited to implanted approaches. Bimodal stimulation yielded consistent, clinically meaningful reductions (often ≥ 10-20 points on THI/TFI), with durability up to 12 months. Adverse events were mild/transient across noninvasive modalities. CONCLUSIONS: Noninvasive neuromodulation appears safe with average benefits; among modalities, bimodal stimulation shows the most consistent and durable clinical improvements. Standardized, adequately powered RCTs with harmonized protocols and long-term follow-up are needed to refine targets and dosing.

Humans↗

PubMed2026

Comparative safety of lipid-lowering drugs alone or in combination: insights from a systematic review and network meta-analysis.

BACKGROUND AND AIMS: Although the safety profile of lipid-lowering therapies (LLTs) is known, there are no comprehensive comparative assessments. We aimed to compare the risk of muscle-related events, diabetes, liver dysfunction, and cognitive disorders among LLTs through a network meta-analysis. METHODS AND RESULTS: Databases were searched from inception to May 2025. Eligible studies included adult patients, using statins, ezetimibe, PCSK9 monoclonal antibodies (PCSK9mAbs), inclisiran, bempedoic acid, or their combinations as intervention, reporting the information about any of the selected adverse events, a total sample size of ≥200 subjects, and had ≥1 month of intervention. Pooled estimates were assessed by fixed effects model within a frequentist setting. Pooled relative risks (RR) and their 95% confidence interval were estimated. A total of 303,397 subjects from 153 RCTs were included. Bempedoic acid ranked the lowest risk of myalgia (vs PCSK9mAbs, RR 0.80 [0.69, 0.93]). PCSK9mAbs were associated with lower incidence of creatine kinase (CK) elevation, diabetes, and liver dysfunction comparing to statins (statins vs PCSK9mAbs, RR 1.44 [1.14, 1.81], RR 1.13 [1.05, 1.22], and RR 1.38 [1.17, 1.62], respectively). In terms of muscle-related events and cognitive disorders, no significant risk differences were found among treatments and their combinations. CONCLUSIONS: PCSK9mAbs appear to have a more favourable safety profile regarding the risk of CK elevation, diabetes, and liver dysfunction. Bempedoic acid seem to be a better choice for subjects with high risk of myalgia. This information can be valuable when selecting therapy for specific patient subgroups at higher risk of certain adverse events.

Humans↗

PubMed2026

Dietary approaches for glycemic management in type 1 diabetes: A systematic review of Mediterranean and low-carbohydrate diets.

BACKGROUND/OBJECTIVES: Specific dietary approaches for better management of type 1 diabetes (T1D) have not been thoroughly investigated. We conducted a systematic review to evaluate the Mediterranean and low-carbohydrate diets for glycemic management in people with T1D. METHODS: We examined longitudinal studies (cohort studies and clinical trials) including individuals with T1D who followed low-carbohydrate diets (<26% calories from carbohydrates and/or <130 g of carbohydrates per day) and/or a Mediterranean diet, while hemoglobin A1c (HbA1c) and/or time in range (TIR) were measured. Additional eligibility criteria included publication in English and availability of a full-text primary research article. Non-longitudinal studies, abstracts, and studies published in languages other than English were excluded. Results were synthesized narratively, and the GRADEpro Guideline Development Tool was used to assess article quality. RESULTS: A total of 565 studies were identified from PubMed, the Web of Science, and citation chasing. After removal of duplicates and further evaluation, 22 studies (6 cohort studies and 16 clinical trials; total n = 3284) were included in this review. The search was initially completed in May 2024, and updated February 2026. Low-carbohydrate diets were associated with better glycemic management when compared to usual diets or baseline glycemic parameters. Studies using CGM were overall underpowered. The impact of Mediterranean diets was less clear, but generally appeared to be less effective at improving glycemic management than low-carbohydrate diets. DISCUSSION: Although structured dietary interventions for T1D hold promise for improving glycemic outcomes, further research is needed to determine exactly which dietary intervention is most beneficial for this population. The evidence provided by included studies is limited by small sample sizes and short durations; better powered, longer-term studies are required to inform clinical recommendations.

Humans↗

PubMed2026

Venomous Lepidoptera: defensive toxin systems, venom composition, and clinical significance.

Venomous Lepidoptera constitute an underrecognized yet medically significant group of toxin-producing arthropods that employ contact-mediated defensive envenomation through specialized integumentary structures such as setae, spines, and scoli. Unlike actively stinging arthropods, these insects deliver venom passively upon contact, eliciting a diverse spectrum of clinical manifestations collectively termed lepidopterism. Clinical outcomes range from localized pain and dermatitis to severe systemic effects, including hemorrhagic syndromes, complement activation, and chronic inflammatory disorders. Recent advances in proteomic and transcriptomic technologies have transformed our understanding of lepidopteran venoms, revealing unexpectedly complex toxin repertoires comprising serine proteases, phospholipases, pore-forming proteins, disulfide-rich peptides, neuroactive RF-amide peptides, and immune-modulating components. These findings have provided new insights into the molecular basis of toxicity, host-pathogen interactions, and the evolutionary diversification of venom systems within Lepidoptera. This review synthesizes current knowledge on the morphology of venom-delivery structures, venom composition, mechanisms of action, and associated clinical manifestations, while highlighting medically important taxa, particularly species of the genus Lonomia. The successful development of antivenom against Lonomia envenomation underscores the translational relevance of lepidopteran toxin research and its potential for therapeutic innovation. By integrating molecular, clinical, and evolutionary perspectives, this review repositions venomous Lepidoptera as a legitimate and important component of arthropod toxinology. Furthermore, it identifies critical methodological limitations and key knowledge gaps, providing a framework for future investigations aimed at advancing our understanding of toxin biology, immunopathology, and the development of novel biomedical applications.

Animals↗

PubMed2026

A genome-wide coverage-based pipeline for the identification of host-derived candidate DNA biomarkers from cell-free blood.

We have created a new data-analysis pipeline for the discovery of host-specific candidate DNA biomarkers derived from sequencing data of cell-free blood. Unlike approaches that rely on specific molecular or genetic signatures, our method leverages the coverage distribution of cell-free DNA sequences mapped to a reference genome, applying statistical analyses to identify informative short genomic regions for biomarker discovery. The pipeline is applicable to diverse diseases and can be used to analyze cell-free DNA sequences from plasma or serum to identify candidate biomarkers that are characteristic of disease states in mammals. Core functionalities were developed in Java and integrated with open-source software tools for the preprocessing of raw sequencing data, complemented by Python scripts for the machine-learning analysis and statistical validation. The pipeline is designed for HPC use and users can access the pipeline through a Galaxy workflow, which offers a user-friendly web interface for input selection prior to execution and analysis progress monitoring. Performance tests, carried out using duplicate sets of COVID-19 samples and controls, showed linear scalability of execution time with an increasing dataset size, as well as a substantial reduction in execution time through parallelized computation, whereby each HPC node is used to process the data of one chromosome. Further statistical tests confirmed the quality of the pipeline's results by showing that the set of identified candidate biomarkers remained stable across varying dataset sizes.

Biomarkers↗

PubMed2026

Optimizing eco-engineering pedogenesis of bauxite residues: Synergistic effects of humus and FeSO4/sulfur on microbial community and function.

Eco-engineered pedogenesis represents a promising approach for soil amelioration of bauxite residues (BRs) through exogenous organic matter. However, the role of humus in mediating this process remains poorly understood, significantly impeding the eco-engineering rehabilitation of BRs. In this study, we conducted pot experiments and subsequent microbial analysis to evaluate the individual improvement of humic acid (HA), fulvic acid (FA), and corn straw (SWZ) on the BRs' pedogenesis. High-throughput sequencing analysis revealed that both FA and SWZ were more effective than HA in steering microbial community assembly, as community diversity, dominant taxa enrichment, and species' interaction were all significantly higher (p < 0.05) in the FA/SWZ treatments than in HA treatments. Notably, the combination of FA with FeSO4 specifically enriched halophilic taxa, while FA coupled with sulfur (S) significantly improved the connectivity and complexity of the microbial network, as the average connection degree increasing from 1.008 to 1.113. Hydrolytic enzyme activity assays further indicated that FA, especially when combined with S, was the most effective treatment in restoring microbial function during BR pedogenesis. These findings highlight FA as a critical driver of microbial restructuring and functional recovery in BRs. Moreover, its efficacy can be enhanced by co-amendment with FeSO4 or S. This study provides important theoretical and practical insights for optimizing organic-inorganic amendment strategies to accelerate the eco-engineering pedogenesis of bauxite residues.

Humic Substances↗

PubMed2026

Durability and Safety of Imeglimin as an Add-On to DPP-4 Inhibitors in Japanese Type 2 Diabetes: The 104-Week FAMILIAR Trial.

AIMS: To evaluate the long-term efficacy and safety of imeglimin added to dipeptidyl peptidase-4 (DPP-4) inhibitors in Japanese patients with type 2 diabetes, focusing on glycemic durability and safety in elderly patients over 104 weeks. MATERIALS AND METHODS: This multicenter, randomized, placebo-controlled trial comprised a 24-week double-blind phase (imeglimin 1000 mg or placebo twice daily) followed by an 80-week open-label extension in which all patients received imeglimin. Eligible patients had inadequate glycemic control despite DPP-4 inhibitor monotherapy. The main assessment measured HbA1c changes from baseline to week 104. Secondary assessments included meal tolerance tests (MTT) for evaluating physiological changes in β-cell function and insulin resistance and safety monitoring. RESULTS: Of 117 randomized patients, 81 completed 104 weeks. In the early-start group that received imeglimin from week 0, the significant HbA1c reduction observed at week 24 (-0.65%) was maintained through week 104 (-0.55%; p < 0.001 vs. baseline). The delayed-start group that switched to imeglimin at week 24 achieved similar glycemic control thereafter. Elderly patients (≥ 65 years) in the early-start group maintained stable HbA1c reduction (-0.58%) without hypoglycemic events over 2 years. MTT analysis in the early-start group showed sustained improvements in glucose AUC and insulin sensitivity without unnecessary insulin secretion over time. CONCLUSIONS: Imeglimin added to DPP-4 inhibitors appeared to improve glycemic control for 104 weeks, without clear attenuation. The combination was well-tolerated with a low risk of hypoglycemia even in elderly patients. The long-term effect may be associated with improvements in insulin sensitivity. TRIAL REGISTRATION: jRCTs061210082.

Humans↗

PubMed2026

Effectiveness of high-power laser use in the removal of esthetic restorations: a systematic review.

This systematic review aimed to evaluate the effectiveness of high-power lasers in the removal of esthetic restorations compared with conventional methods. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in PROSPERO (registration number: CRD420251055736). A comprehensive electronic search was performed in MEDLINE, Scopus, Embase, Web of Science, and the Cochrane Library. Study selection, data extraction, and methodological quality assessment were independently performed by four reviewers using QUIN tool for in vitro studies. A total of 2.384 records were identified, of which 19 in vitro studies conducted on extracted human permanent teeth met the eligibility criteria and were included in the qualitative synthesis. The included studies evaluated different high-power laser systems, predominantly Er: YAG and Er, Cr: YSGG lasers, as well as CO₂ lasers. Five studies were classified as high quality, whereas the remaining fourteen studies were classified as moderate quality. Available laboratory evidence suggests that laser-assisted techniques may represent a potential alternative approach for removing esthetic restorations, with advantages including conservative tissue removal, reduced damage to underlying tooth structures, and intrapulpal temperature increases within acceptable limits. The Er: YAG laser was the most frequently investigated system, with power settings ranging from 1.5 to 5.9 W, showing particularly favorable laboratorial performance in the removal of lithium disilicate restorations, especially in thinner substrates. Within the limitations of the available evidence, high-power lasers appear to be a promising and minimally invasive alternative to conventional methods for the removal of esthetic restorations. However, the predominance of in vitro studies highlights the need for well-designed clinical trials to confirm these findings and support their clinical application.

Humans↗

PubMed2026

Stretched penile length in boys with hypospadias: Population-based analysis using validated nomogram.

BACKGROUND: Hypospadias affects 1 in 200-300 male births. Parents are often concerned about penile adequacy beyond the urethral defect itself, yet few studies have systematically compared stretched penile length (SPL) in hypospadias against population-based reference standards. OBJECTIVE: To evaluate SPL distribution patterns in boys with Types I and II hypospadias and compare them with established normative data. METHODS: The authors studied 876 consecutive boys aged 1-14 years with unoperated Types I (distal) and II (mid-shaft) hypospadias. Two observers independently measured SPL using the validated SPLINT technique. The SPL measurements were compared against age-matched normative data from 1276 Indian children. Exact binomial probability tests were used for percentile distributions, chi-square tests for subtype comparisons and t-tests for mean deviations. RESULTS: The cohort included 479 Type I and 397 Type II cases. SPL distribution showed a marked leftward shift: 71% fell below the 50th percentile (expected 50%, p < 0.001) and 41.5% below the 25th percentile. Lower percentiles were overrepresented, 20.7% were below the 10th percentile and 20.8% in the 10th-25th range. Upper percentiles were depleted: only 7.4% in the 75th-90th range and 1.7% above the 90th percentile (all p < 0.001). Mean SPL was reduced by 6.8% (95% CI: -8.18 to -5.42%) in Type I and 7.5% (95% CI: -9.05 to -5.92%) in Type II. The two subtypes showed no significant distributional difference (χ2 = 6.22, p = 0.18), suggesting that meatal position does not predict SPL reduction. CONCLUSIONS: Boys with distal and mid-shaft hypospadias show clinically meaningful SPL reduction that follows a continuous distribution rather than an all-or-none pattern. SPL reduction appears independent of meatal position. These findings support routine SPL assessment using population-specific references and can guide preoperative counselling.

Humans↗

PubMed2026

Plant species identification by genome skimming across the vascular plant tree of life.

Accurate species identification is essential for biodiversity conservation and sustainable use, yet standard plant DNA barcoding often fails to achieve species-level resolution. We present a large-scale empirical evaluation of genome skimming as a tool to improve plant species discrimination. Using standardised data from 1969 individuals representing 475 species from 32 genera across major lineages of the vascular plant tree of life, we compare conventional plastid + internal transcribed spacer (ITS) barcodes with genome skimming approaches. Standard barcoding using rbcL, matK, trnH-psbA and ITS resolved about half of species (49.3%), with six genera showing < 25% species discrimination. By contrast, genome skimming enabled the recovery of complete plastid genomes, yielding 57.6% species discrimination. It also generated sufficient nuclear genomic data for additional resolution from k-mer analysis, achieving 66.8% species discrimination - an average gain of 17.5% over standard barcodes - while eliminating cases of extreme failure (< 25% resolution). The recovery of complete plastomes and ribosomal DNAs from genome skims also ensures backward compatibility with existing barcode datasets. Our results demonstrate that genome skimming provides data that substantially improves species-level resolution across diverse plant lineages and offers a scalable, high-throughput approach for building comprehensive reference resources to support global biodiversity initiatives.

DNA Barcoding, Taxonomic↗

PubMed2026

Proteomic characterization of the acquired enamel pellicle under acidic challenges at early and mature formation stages.

OBJECTIVES: This study aimed to characterize acquired enamel pellicle (AEP) proteomic changes after exposure to citric acid (CA) and hydrochloric acid (HCl) under different pellicle formation times (3 and 120 min) in the same volunteers. DESIGN: Nine healthy volunteers participated in this randomized crossover in vivo study. The AEP was allowed to form for 3 or 120 min and subsequently exposed for 10 s to deionized water (control), 1% CA (pH 2.5), or 0.01 M HCl (pH 2.0). Pellicle samples were collected, followed by protein extraction, tryptic digestion, and analysis by nanoliquid chromatography (nanoLC) coupled to mass spectrometry (MS) with MSE (data-independent acquisition; nanoLC-MSᴱ). Label-free quantitative proteomics were performed for relative quantification using t-test (p < 0.05). RESULTS: At 120 min, CA exposure markedly reduced several typical AEP proteins, especially acidic proline-rich proteins (PRPs). Conversely, basic PRPs were upregulated, suggesting acid-resistance protein signature. At 3 min, basal-layer proteins (PRPs, cystatins, histatins and mucins) were more abundant. Hemoglobins increased 6-8-fold (up to 150-fold in 3 min control), suggesting association with early pellicle formation and an acid-resistant protein signature. CA exposures for 120 min also upregulated typical AEP proteins (PRPs, mucins, cystatins, immunoglobulins), while HCl exposure depleted albumins and lactotransferrin. CONCLUSION: Intrinsic and extrinsic acids induce distinct proteomic signatures in the AEP. Hemoglobin and PRPs appear consistently enriched in the early pellicle layer, reflecting an initial acid-resistant protein signature. These findings provide new insights into the molecular remodeling of the AEP following intrinsic and extrinsic acid exposure, highlighting proteins potentially involved in early-stage pellicle formation.

Humans↗

PubMed2026

Post-intervention effectiveness of a computerized personalized cognitive stimulation program adapted according to cognitive reserve in older adults without cognitive impairment in Primary Care: A randomized clinical trial.

BACKGROUND: Cognitive reserve may influence responsiveness to cognitive interventions, yet it is rarely used to tailor computerized stimulation. OBJECTIVE: To evaluate the effectiveness of a computerized cognitive stimulation program personalized according to cognitive reserve on cognition, reserve-related activities, and digital competence in community-dwelling older adults without cognitive impairment in Primary Care. METHODS: In this randomized clinical trial, 102 adults aged ≥65 years with normal cognitive performance were recruited from three primary care centers in Zaragoza, Spain, and stratified by cognitive reserve level before random allocation to intervention or control. The intervention comprised digital literacy sessions followed by 8 weeks of home-based computerized cognitive stimulation tailored to participants' cognitive reserve profiles and life history. Controls received a single group-based health education session focused on maintaining everyday cognitive activity. Outcomes were assessed at baseline and post-intervention using global cognition (MEC-35), the Cognitive Reserve Questionnaire, the Mobile Device Proficiency Questionnaire-16, and domain-specific neuropsychological tests. A total of 100 participants completed the final evaluation and were included in complete-case analyses. RESULTS: Compared with controls, the intervention group showed greater adjusted post-intervention improvements in global cognition (MEC-35 between-group difference: 1.8 points) and several cognitive measures, including temporal orientation, calculation, attention, praxis, verbal fluency, processing speed, executive functions, and verbal learning. CRQ scores and digital competence also improved, with small-to-large effect sizes. CONCLUSIONS: A computerized cognitive stimulation program adapted according to cognitive reserve appears feasible in Primary Care and may improve cognition, engagement in reserve-related activities, and digital competence in older adults without cognitive impairment.

Humans↗