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PubMed2026

Efficacy of transcranial alternating current stimulation for musculoskeletal pain and sleep quality: a systematic review and meta-analysis.

BACKGROUND: Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique, emerging as a potential therapeutic option for musculoskeletal pain management. OBJECTIVE: To comprehensively evaluate the efficacy and safety of tACS for alleviating pain and improving sleep quality in adults with musculoskeletal pain. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Seven major databases and other sources were searched from inception until April 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias. A random-effects model was used to pool standardized mean differences (SMDs). The certainty of evidence was evaluated using the Grading of Recommendation Assessment, Development, and Evaluation framework. RESULTS: Six RCTs involving 232 participants were included. Meta-analysis showed that tACS could significantly reduce pain intensity compared to control (SMD = -0.355, 95% CI: -0.625 to -0.084, p = 0.010, I² = 28.7%). However, no significant improvement was found for sleep quality (SMD = 0.004, 95% CI: -0.310-0.317, p = 0.982, I² = 0.0%). Adverse effects were mild and transient, comparable to sham stimulation. The overall certainty of evidence was rated as low for both pain and sleep quality outcomes. CONCLUSION: Current evidence suggests that tACS may be beneficial for musculoskeletal pain; however, the available evidence remains limited and should be interpreted cautiously. The effect of tACS on sleep quality remains uncertain because of the limited number of available studies. Future well-designed RCTs with standardized outcome measures, condition-specific stimulation protocols, and longer follow-up are required to establish the efficacy and long-term safety of tACS.

Humans↗

PubMed2026

Effects of umbilical cord mesenchymal stem cell-derived exosomes on periodontal ligament stem cells: An exploratory study.

OBJECTIVE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) at two osteogenic induction stages (undifferentiated and late-stage) differentially affect periodontal ligament stem cells (PDLSCs), and to explore the potential molecular basis. DESIGN: UCMSCs and PDLSCs were isolated and cultured. Exosomes were harvested from undifferentiated UCMSCs (Exo-D0) and UCMSCs after 14 days of osteogenic induction (Exo-D14). PDLSCs were treated with both exosome types. Proliferation and migration were analyzed using EdU and scratch assays, the latter under serum-free conditions. Early osteogenic differentiation was assessed by alkaline phosphatase staining and quantitative reverse transcription PCR (qRT-PCR). Differentially expressed miRNAs were identified by high-throughput sequencing and further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: Both exosome types promoted PDLSC migration. Exo-D0 enhanced early osteogenic differentiation, whereas Exo-D14 enhanced proliferation but reduced early osteogenic marker expression. Sequencing identified 21 differentially expressed miRNAs (13 upregulated, 8 downregulated). Bioinformatic prediction suggested that the putative target genes were enriched in Ras signal transduction, regulation of kinase activity, and focal adhesion, and further predicted significant enrichment in the MAPK, Ras, and PI3K-Akt signaling pathways, which are central to cell proliferation and osteogenic differentiation. CONCLUSIONS: Exosomes from undifferentiated and osteogenically induced UCMSCs exerted distinct effects on PDLSCs, potentially associated with differentially packaged miRNAs. These findings offer a basis for hypotheses about exosome-mediated mechanisms and support matching exosome sources to the intended therapeutic outcome as potential cell-free strategies for periodontal tissue regeneration and alveolar bone repair.

Humans↗

PubMed2026

Performance comparison of rapid and native barcoding methods for Oxford Nanopore sequencing of Poliovirus Viral Protein 1 (VP1) amplicons.

Accurate and timely sequencing of poliovirus is critical for global eradication efforts, particularly for molecular epidemiology based on the typing region of the genome, viral protein 1 (VP1). While Oxford Nanopore Technologies (ONT) sequencing has expanded capabilities for poliovirus surveillance, the relative performance of different ONT library preparation methods, including ligation-based (Native Barcoding) and transposase-based (Rapid Barcoding) approaches, has not been systematically evaluated. In this study, we compared rapid barcoding and native barcoding workflows for sequencing VP1 amplicons from 17 type 2 poliovirus-positive samples, each processed in triplicate. Native barcoding generated significantly more sequencing output, producing approximately 2.3-fold greater total read yield than rapid barcoding, and demonstrated higher run-to-run reproducibility (R2 = 0.979-0.998 vs. 0.847-0.929, respectively; p < 0.001). In addition, native barcoding generated 80% of the total yield achieved by rapid barcoding within approximately 7 h, whereas rapid barcoding required approximately 40 h to reach the same output. Despite these differences, both methods produced identical VP1 consensus sequences across all samples, with comparable read quality (median per-base Q-scores of approximately Q17-Q18). Rapid barcoding provided substantial practical advantages, reducing hands-on library preparation time (55 vs. 200 min) and per-sample cost ($12.82 vs. $16.54), while simplifying workflow and reducing technical complexity. These findings indicate that sequencing yield may not be a determinant of downstream analytical outcomes for poliovirus VP1 ONT sequencing. Rapid barcoding therefore represents a cost-effective and efficient approach for routine poliovirus surveillance, whereas native barcoding remains advantageous in applications requiring rapid data generation or maximal sequencing depth.

Poliovirus↗

PubMed2026

Orthoplastic management of open calcaneal fractures: A systematic review of flap selection and complications.

BACKGROUND: Open calcaneal fractures are rare, high-energy injuries involving extensive soft-tissue loss and comminuted bone disruption. Successful management depends on coordinated orthoplastic reconstruction to achieve stable fixation and durable coverage. Multiple flap types have been described, yet comparative outcomes remain poorly defined. METHODS: A systematic review was performed in accordance with PRISMA guidelines (PROSPERO: CRD420251138394). MEDLINE, Embase, Cochrane CENTRAL, and Scopus were searched from January 2000 to July 2025. Studies reporting flap-based reconstruction for open calcaneal fractures in adults were included. Extracted data included flap type, fixation method, follow-up duration, and complications such as infection, necrosis, vascular crises, flap loss, and amputation. RESULTS: Thirteen studies comprising 88 major flap reconstructions were analysed. Overall flap survival was 97.7%, with two failures (both muscle/myocutaneous). Fasciocutaneous flaps showed the lowest complication rates (8.3%) with no reported cases of infection, while muscle/myocutaneous flaps demonstrated cases of infection (20%) and accounted for both flap failures and the only reported amputation. Chimeric flaps were increasingly used in recent series (n = 32), achieving reliable survival but higher vascular compromise (6.3%). Osteocutaneous flaps were rare (n = 4) and primarily used for defects with bone loss, showing infection in 50% of cases. Meta-analysis was not possible due to heterogeneity and small sample sizes. CONCLUSIONS: Fasciocutaneous flaps provide reliable, low-complication coverage for clean wounds, while muscle flaps remain valuable for contamination or complex cases with extensive tissue loss. Chimeric, and osteocutaneous flaps show promise, but larger, standardised studies are needed to clarify their roles in hindfoot reconstruction.

Humans↗

PubMed2026

Intervention Without Borders - an Automated Self-Guided AI-Enhanced Psychoeducation Intervention for Dementia Caregivers: Parallel-Group Randomized Waitlist-Controlled Trial.

OBJECTIVE: To examine whether a fully automated, self-guided intervention (PDC30) could improve caregiver well-being over a 1-month waitlist control in an international sample. DESIGN: Randomized waitlist-controlled trial. SETTING: Web-based platform accessible globally. PARTICIPANTS: 441 individuals responded to study promotion on the internet, of whom 274 from 43 countries met the study criteria and were randomized. Eligible participants were adults providing ≥10 care hours weekly to community-dwelling relatives with dementia, scoring ≥5 on Patient Health Questionnaire-9 (PHQ-9), and without recent caregiver intervention. INTERVENTION: Available 24/7, PDC30 is a self-guided, automated intervention consisting of a Guidebook, an AI-powered counseling chatbot, and interactive applications for cognitive-behavioral techniques, relaxation, and caregiver-recipient bonding. MEASUREMENTS: At baseline and follow-ups at 1, 2, and 3 months, depression was assessed by PHQ-9. Secondary outcomes were measured with validated brief versions of anxiety, burden, and positive gains. RESULTS: Intent-to-treat analysis using mixed-effects regression showed treatment x time2 effects on all outcomes except anxiety. At 1-month follow-up, coinciding with exclusive access to PDC30, intervention caregivers showed significant improvements in depression (d = -0.37), burden (d = -0.34), and positive gains (d = 0.42). The differences mostly disappeared after control participants received the intervention, while improvements in both groups were sustained thereafter. Participants reported using the website several times weekly, were generally satisfied with it, and found the chatbot most helpful. CONCLUSIONS: The effects on depression and other outcomes were consistent with those observed for in-person programs, suggesting the viability of well-designed automated intervention. The study demonstrates the feasibility, acceptability, and potential global health impact of PDC30.

Humans↗

PubMed2026

Donor Human Milk Utilization in a Level 1 Newborn Unit of a High-Volume Delivery Hospital: A Cautionary Tale.

INTRODUCTION: Donor human milk (DHM) is an alternative to formula for supplementation of breastfed newborns and has been associated with higher in-hospital exclusive breast milk feeding rates. Its use has increased substantially, most recently among term newborns, yet there is scarce data to describe patient characteristics and volumes administered. We aimed to characterize DHM utilization in our level 1 nursery. METHODS: We conducted a retrospective cross-sectional study of newborns discharged in 2022 from the level 1 nursery. Variables included sex, gestational age, birth weight, delivery type, hypoglycemia diagnosis, DHM volume, and length of stay. DHM use was compared across preferred language, race, ethnicity, and payer type using chi-square testing. RESULTS: A total of 10,432 discharges were reviewed-those transferred to Neonatal Intensive Care Unit (NICU) or another unit were excluded. Of 9,074 newborns receiving level 1 care, 1,094 (12.1%) received DHM. Newborns born between 35 and 37 weeks gestation, delivered by cesarean section, or diagnosed with hypoglycemia or small for gestational age were more likely to receive DHM (p < 0.05). DHM was also more common among newborns whose birth parent preferred the English language, identified as White or non-Hispanic, or had non-Medicaid insurance (p < 0.05). 6,552.6 ounces were consumed, with a total median of 3.9 ounces per newborn (dose range 2-50 mL). CONCLUSIONS: DHM use in the level 1 nursery varied by clinical and sociodemographic factors, revealing inequities. In addition, some doses exceeded recommended supplemental volumes. Future efforts should focus on ensuring equitable access to DHM, standardized dosing and discontinuation guidelines, and evaluation of impacts on exclusive breastfeeding rates.

Humans↗

PubMed2026

Photothermal-Activated Platelet-Rich Plasma Versus Conventional Platelet-Rich Plasma for Melasma: A Split-Face, Double-Blind Randomized Controlled Trial.

BACKGROUND: Melasma is a common acquired pigmentary disorder that predominantly affects women with darker skin types and substantially impairs quality of life. Current treatments are limited by variable efficacy, adverse effects, and frequent recurrence. Platelet-rich plasma (PRP) has emerged as a potential regenerative treatment through growth-factor-mediated modulation of melanogenesis. Photothermal activation, which combines photobiomodulation with controlled hypothermic conditioning, has been hypothesized to promote a more sustained growth-factor release than conventional PRP. This study compared the efficacy and safety of photothermal-activated PRP (PT-PRP) and conventional PRP (C-PRP) for melasma treatment. METHODS: This split-face, double-blind, randomized controlled trial included 26 women with epidermal or mixed-type melasma. Each participant received three monthly sessions of intradermal PRP, with PT-PRP and C-PRP injected into opposite facial sides. Outcomes were assessed at weeks 0, 4, 8, and 12 using the modified Melasma Area and Severity Index (mMASI), Mexameter melanin and erythema indices, patient satisfaction, overall improvement, and adverse events. RESULTS: Both treatments significantly reduced mMASI by week 12, with no significant between-group differences at any time point. C-PRP showed significant mMASI improvement from week 4, whereas PT-PRP reached significance from week 8. For the melanin index, PT-PRP produced a significant within-group reduction at week 12, while C-PRP did not. At week 12, PT-PRP showed a significantly lower melanin index than C-PRP. Mild injection-site bruising was the only adverse event. CONCLUSION: PT-PRP and C-PRP produced comparable clinical improvement, but PT-PRP achieved greater objective melanin reduction at week 12. PT-PRP may represent a safe alternative treatment for melasma. TRIAL REGISTRATION: Thai Clinical Trials Registry: TCTR20260318004.

Humans↗

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↗

PubMed2026

Novel splice site variants in GBA1 are associated with Gaucher disease and genotype-phenotype correlations.

BACKGROUND: Variants in GBA1 are associated with neurodegenerative disease. This study aimed to explore pathogenic GBA1 variants. METHODS: Four patients with progressive myoclonic epilepsy (PME) and extremely low β-glucosidase levels were recruited. Whole-exome sequencing and long-range PCR were performed to identify GBA1 variants. Bioinformatic analyses were used to predict the impact of the identified variants. A literature review was performed to explore the genotype-phenotype correlations. GBA1 expression data across different brain regions and developmental stages were analyzed using the BrainSpan database. RT-PCR was performed to verify the splicing effects. RESULTS: Compound heterozygous GBA1 variants were identified in four patients. Five distinct variants were detected, including two novel splice site variants (c.308-2A>G and c.762-2A>C) and three previously reported variants. All identified variants were rare or absent in gnomAD. Splice site variants c.308-2A>G and c.762-2A>C were predicted to cause aberrant splicing. Minigene-based splicing assays coupled with RT-PCR and Sanger sequencing confirmed that both variants cause complete exon skipping (exon 4 and exon 7, respectively). All patients presented with PME onset in childhood/adolescence, intellectual regression, low β-glucosidase, and diffuse brain atrophy and were subsequently diagnosed with Gaucher disease type 3. GBA1 expression in the brain showed two distinct peaks: one in infancy and another after five years of age. The onset age of PME aligned with the second GBA1 expression peak (after five years of age). CONCLUSION: This study identified compound heterozygous GBA1 variants, including two novel candidate pathogenic splice site variants, in Gaucher disease type 3 patients, expanding the known mutational spectrum.

Humans↗

PubMed2026

Determination of 13 per- and polyfluoroalkyl substances in human plasma samples using LC-MS/MS: application to capillary microsamples.

Per- and polyfluoroalkyl substances (PFAS) are chemicals widely applied in industrial processes and highly persistent in the environment, whose extensive use has been linked to adverse health effects. Venous plasma is the conventional matrix for PFAS assessment in blood, and LC-MS/MS is the most used quantification technique. Despite the relevance of this topic, biomonitoring data on human exposure to PFAS in Brazil remain limited. This study validated an LC-MS/MS method for determination of 13 PFAS in human plasma. Blood samples were collected from volunteers by phlebotomy, followed by protein precipitation with acetonitrile containing 1% formic acid (v/v) and solid-phase extraction. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column. The assay was linear over a calibration range of 0.2-20 ng/mL. Intra- and inter-assay precision (CV%) were within the ranges of 2.06-12.0% and 0.25-10.7%, respectively. As for accuracy, results were 89.0-112.9%. Matrix effect ranged from -1.31 to 0.05%. Stability after four freeze/thaw cycles and under autosampler conditions were also confirmed for all analytes. The method was applied to 40 paired venous and capillary plasma samples. Both measures exhibited high correlation (r = 0.926). PFOS was the only compound detected at concentrations ≥0.2 ng/mL (LLOQ) in all samples, with capillary plasma concentrations of 0.85-13.50 ng/mL. In summary, the method showed good validation performance and demonstrated the suitability of capillary plasma samples as an alternative matrix for PFAS quantification.

Humans↗

PubMed2026

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↗

PubMed2026

Effectiveness and moderators of PE and CPT in adult PTSD treatment: a systematic review and meta-analysis.

Background: Posttraumatic Stress Disorder (PTSD) is a prevalent and debilitating condition that challenges mental health services worldwide. Effective psychological interventions are crucial for treatment, among which Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT) are prominent. Comparative analyses of these treatments, considering moderators such as patient demographics and treatment specifics, are necessary to tailor interventions effectively.Objective: This meta-analysis synthesised findings from 175 treatment arms across 163 studies to evaluate the comparative effectiveness of PE and CPT for PTSD. Effect sizes were calculated as Hedges' g for between-group (treatment vs. control) and within-group (pre-post) comparisons.Results: Using a random-effects model, the overall pooled effect size was large (Hedges' g = 1.67, 95% CI [1.56, 1.79]), suggesting substantial treatment-related symptom improvement. Multivariate meta-regression revealed, across the full sample, none of the main effects or interactions was significant. A sensitivity analysis excluding 10 influential outliers reduced the overall effect size (g = 1.55), indicating that PE was associated with larger effects than CPT among non-military samples, and larger effects were observed in studies with a higher proportion of female participants, military samples, and samples with lower proportions of sexual trauma. Treatment-by-sample-characteristic interactions were not significant in the trimmed model.Conclusions: Findings suggest that PE and CPT produce large effects in reducing PTSD symptoms, with some variation across treatment type and sample characteristics. Results underscore the importance of examining contextual moderators such as treatment setting and population type and highlight the need for transparent reporting of key sample features to improve future meta-analytic precision.

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

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

Generation of spCAS9 expressing human mesenchymal stem cell line to study gene function during osteoblast differentiation.

Human bone marrow-derived stromal cells (hMSCs) are a great resource for studying how genes influence cell fate and differentiation into various cell types like osteoblasts, adipocytes, and chondrocytes, among other cell types. However, genetic manipulation of primary hMSCs has been challenging due to their short lifespan and cellular senescence after limited passaging. Their low and unstable transfection efficiency also complicates gene delivery or inactivation, hindering long-term functional studies. The limited lifespan has been effectively solved by immortalizing hMSCs with telomerase reverse transcriptase (hMSCs-TERT). The use of these cells is ideal for functional studies of osteoblast and adipocyte differentiation through genetic manipulation, providing a stable and reliable model. Here, we have engineered a stable CAS9 expressing hMSC-TERT cell line (hMSC-TERTCAS9) via lentiviral transduction. The constitutive expression of spCas9 enables efficient and reproducible gene editing. We demonstrate the potential of these hMSC-TERTCAS9 cells for generating gene disruptions using plasmid delivery of guide RNAs as a fast and efficient strategy for targeted genome editing. The edited cells can be sorted and expanded as single cells to obtain homogenous clonal cell lines with mono- as well as bi-allelic gene deletions, a crucial step for producing reliable experimental results. We further validate this cell line as a powerful tool for studying gene function during hMSC proliferation and differentiation, providing 3 distinct examples of its utility. Through the generation of indels, single-cell sorting, and clonal selection, we have efficiently inactivated the vitamin D receptor and created both larger (256 nucleotides) gene disruptions in Forkhead box protein O1 and precise removals of a small genomic sequence (73 nucleotides) coding for microRNA MIR675. This novel hMSC-TERTCAS9 cell line represents a significant advancement, offering a stable, efficient, and versatile platform for advanced genetic studies, high-throughput screening, and the creation of reliable cellular disease models.

CRISPR-Cas9↗

PubMed2026

Complexity in disguise: a systematic review of fractal analysis in psychiatric neuroimaging.

OBJECTIVES: Psychiatric diagnosis and fractal studies are complex processes that extend beyond clinical evaluation and require careful methodological considerations in neuroimaging. Over the years, fractals have helped reduce these complexities in research, but they still cannot grant clinical diagnoses. Thus, the main objective was a systematic review exploring the potential applications of fractal analysis in characterizing psychiatric conditions through neuroimaging techniques-including both functional and structural MRI. MATERIALS AND METHODS: A systematic literature review was conducted on PubMed, identifying thirty-nine original studies that met the inclusion criteria. Areas showing statistical significance (p < 0.05) were reported. These studies were categorized according to DSM-V classification and examined for the description of psychiatric conditions through the fractal analysis. RESULTS: The review primarily focuses on young adults with psychiatric conditions compared to control groups. Schizophrenia and Autism Spectrum Disorder are major areas of investigation, and fractal dimension (FD) is the primary analysis method used to reflect brain patterns. Studies that calculated whole-brain FD may have underestimated local abnormalities due to the inclusion of a high percentage of tissue, potentially resulting in overlooked findings. Notably, abnormalities in the frontal cortex represent a common neurobiological feature across several psychiatric conditions. CONCLUSIONS: The findings from this systematic review shed light on the use of fractal analysis to quantify complex brain patterns in both psychiatric patients and healthy individuals. However, it is essential to recognize the need for further research to elucidate a fractal analysis protocol that allows for optimal extraction of psychiatric insights. KEY POINTS: Question Fractal analysis applied to structural and functional MRI help characterize brain alterations across psychiatric conditions. Findings This review shows consistent fractal patterns across multiple psychiatric disorders, especially in frontal regions. Despite heterogeneous methodologies, results highlight shared structural and functional abnormalities. Clinical relevance Fractal analysis may offer complementary characterization of subtle brain organization across psychiatric disorders. Its potential clinical utility-such as improving diagnostic characterization, earlier detection, among others-remains limited by the current absence of a standardized protocol.

Humans↗

PubMed2026

Mapping the immune-genetic architecture of Epstein-Barr virus-related phenotypes and multiple sclerosis through a single-cell genetic framework for target prioritization and pharmacologic hypothesis generation.

BACKGROUND: Multiple sclerosis (MS) is a severe neuroinflammatory disease causing substantial long-term disability. Strong epidemiologic evidence links Epstein-Barr virus (EBV) exposure with MS risk, but genetic evidence for immune target prioritization in EBV-related phenotypes remains limited. METHODS: We integrated single-cell cis-eQTL data from 14 immune cell types with GWASs of an EBV-related clinical phenotype and MS using a single-cell Mendelian randomization framework with colocalization analyses. Candidate eGenes were evaluated in independent cohorts. For multi-SNP instruments, we performed heterogeneity, pleiotropy, MR-Egger, weighted median, mode-based, and MR-PRESSO sensitivity analyses. We also conducted phenome-wide association analyses and queried DrugBank to annotate candidate compounds targeting prioritized genes. RESULTS: We prioritized 43 immune-cell-specific candidate eGenes with convergent genetic support, including 6 for the EBV-related phenotype and 37 for MS. SERPINB1 in NK cells was associated with increased risk of the EBV-related phenotype, whereas HLA-G was associated with decreased risk. For MS, APOM and MSH5 showed protective associations, while AHI1 showed cell-type-dependent, bidirectional associations across immune lineages. Colocalization and independent cohort evaluation supported these findings. Among FDR-significant multi-SNP associations, MR-Egger intercept tests did not indicate directional pleiotropy, although a small subset showed heterogeneity or MR-PRESSO signals. Phenome-wide analyses identified no significant adverse phenotypic associations among evaluable genes at the prespecified threshold. DrugBank annotation nominated sodium nitroprusside, fasudil, artenimol, and choline as hypothesis-generating compounds for experimental follow-up. CONCLUSIONS: This study provides a single-cell genetic framework for prioritizing immune-cell-specific candidate targets for EBV-related phenotypes and MS, and nominates genetically supported targets and pharmacologic hypotheses for experimental investigation.

Humans↗

PubMed2026

Effectiveness of Yoga and Combined Exercise in Female With Rheumatoid Arthritis: Randomized Controlled Trial.

BACKGROUND: Although exercise is beneficial for Rheumatoid Arthritis (RA), the comparative efficacy of different modalities for patients in clinical remission remains unclear. This study compared the short- and long-term effects of yoga versus a combined exercise programme on pain, balance, mobility, fatigue, depression, and quality of life in females with RA in remission. METHODS: In this single-blind, randomized controlled trial, 74 female participants were allocated to yoga (n = 25), combined exercise (n = 25), or a usual care control group (n = 24). The intervention groups underwent an 8-week supervised programme. Clinical assessments, including the Visual Analogue Scale (pain), Berg Balance Scale, Timed Up and Go Test, Beck Depression Inventory, Fatigue Severity Scale, and Short Form-36, were conducted at baseline, post-intervention (8 weeks), and follow-up (20 weeks). RESULTS: Both intervention groups demonstrated significant improvements in all outcome measures compared with the control group at post-treatment and follow-up (p < 0.05). Notably, the yoga group exhibited superior outcomes compared to the combined exercise group in reducing pain intensity (median reduction of 4.00 vs. 2.00 points; p < 0.001, η2 = 0.724), as well as in physical function, balance, fatigue, depression, and quality of life at the 20-week follow-up. These benefits may be partly attributed to the incorporation of breathing and relaxation techniques inherent to yoga practice. CONCLUSIONS: Both 8-week yoga and combined exercise programs are effective in managing residual symptoms in females with RA in clinical remission. However, yoga appears to provide superior benefits in pain management and psychosocial well-being, supporting its integration into multidisciplinary RA management protocols, particularly for addressing psychosocial burden in patients achieving remission. TRIAL REGISTRATION: This study was retrospectively registered at NCT07072754 (clinicaltrials.gov).

Humans↗