SEARCH · Search PubMed

Results for “cyclin‐dependent kinase 6”

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

SourceResearch connectionFrom yearThrough year

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

1,249 records · Page 10Linked to original sources

PubMed2026

Implementation of Mobile Health Intervention Targeting Belongingness and Burdensomeness: An Ecological Momentary Assessment Study of Self-Injurious Thoughts and Behaviors in LGBTQ+ Individuals.

OBJECTIVE: The goal of this paper was to test a mobile health intervention designed to reduce self-injurious thoughts and behaviors in LGBTQ+ individuals. The intervention consisted of brief messages aimed at increasing feelings of belongingness and meaning. METHOD: We recruited LGBTQ+ individuals (N = 55) with past-month self-injurious thoughts and/or behaviors. Participants completed 14 days of ecological momentary assessment (EMA) of minority stress, thwarted belongingness, perceived burdensomeness, and self-injurious thoughts and behaviors. Then, participants were randomly assigned to receive brief messages designed to instill belongingness and meaning/purpose, or no intervention for 14 days. Then, participants completed an additional 14 days of EMA. RESULTS: Our results showed that participants in the control condition had significant increases in self-injurious thoughts and planning over time, whereas those in the intervention condition showed no significant change. For self-injurious behavior, thwarted belongingness, and perceived burdensomeness, there were significant decreases in the intervention condition, but no changes in the control condition. CONCLUSIONS: These results provide support for the interpersonal theory of suicide and indicate a potentially scalable mobile health intervention. PUBLIC HEALTH SIGNIFICANCE: This paper found evidence that a brief mobile health intervention reduced suicidal and non-suicidal self-injurious thoughts and behaviors among LGBTQ+ individuals.

Humans↗

PubMed2026

Biliary Cirrhosis in Myhre Syndrome: The First Case Report of Liver Transplantation and a Review of Reported Hepatic Findings.

Myhre syndrome is a rare autosomal-dominant disorder caused by gain-of-function pathogenic variants in SMAD4 and is now recognized as a progressive multisystem fibrotic disease. Although transforming growth factor-β (TGF-β) signaling plays a central role in hepatic fibrogenesis, hepatobiliary involvement in Myhre syndrome has not been systematically evaluated. We report the first case of Myhre syndrome complicated by rapidly progressive biliary cirrhosis requiring liver transplantation in a 15-year-old male with a confirmed SMAD4 p.Ile500Val variant. Following an infectious episode, the patient developed severe cholestasis with imaging and histopathologic findings consistent with fibro-obliterative cholangiopathy, ultimately necessitating living donor liver transplantation. A systematic review of 55 published reports comprising 217 patients with Myhre syndrome revealed that hepatic evaluation was rarely performed and that previously reported liver abnormalities were mild and secondary, most commonly related to right heart dysfunction or metabolic disease, with no prior cases of progressive biliary fibrosis. This case suggests that dysregulated SMAD4-TGF-β signaling may predispose selected organs to fibro-obliterative injury and that infection-driven inflammation may act as a critical trigger for hepatic fibrosis in Myhre syndrome, expanding the recognized spectrum of organ involvement in this disorder.

Humans↗

PubMed2026

Divergent trajectories of genome architecture and chromosome evolution in ferns and angiosperms.

Ferns and angiosperms represent the two largest vascular plant lineages but exhibit striking genomic and ecological contrasts. We investigated whether differences in genome size, chromosome architecture, GC content, and stomatal traits reveal divergent evolutionary trajectories between these lineages. We assembled the most comprehensive dataset to date, integrating genome size, chromosome number and size, GC content, and stomatal traits for over 1100 fern species and compared it with an extensive angiosperm dataset. Ferns exhibited markedly lower variability and c. 16-fold slower rates of chromosome size evolution than angiosperms. A persistent positive relationship between genome size and chromosome number in ferns suggests limited cytological post-polyploid diploidization. While ferns generally possess larger stomata, this difference disappears after accounting for genome size, indicating that nucleotypic constraints, rather than lineage-specific physiology, dictate stomatal dimensions. Both groups share a unimodal GC-genome size relationship peaking at c. 14 Gbp. Larger fern chromosomes imply lower genome-wide recombination rates, potentially limiting genetic reshuffling and adaptive potential. Our results highlight fundamentally divergent evolutionary trajectories, likely shaped by meiotic symmetry in ferns and meiotic asymmetry, possibly centromere drive, and post-polyploid diploidization in angiosperms, defining the functional and genomic landscapes of these lineages across deep evolutionary timescales.

Genome, Plant↗

PubMed2026

Evaluating the Efficacy of Electronic Screening, Brief Intervention, and Referral to Treatment (e-SBIRT) for Gambling: An Online Pilot Randomised Trial.

OBJECTIVES: To investigate the efficacy of electronic screening, brief intervention, and referral to treatment (e-SBIRT) at improving gambling outcomes and increasing help-seeking. METHODS: We conducted a two-arm, randomised online pilot trial (n = 83) comparing an e-SBIRT intervention with an active control over 12 weeks. The brief intervention was informed by motivational interviewing and incorporated personalised normative feedback, information provision, and relapse-prevention components. Eligible participants were aged 18 or older, resided in the UK and had scores indicating at least moderate severity gambling. RESULTS: Participants (54 [65.1%] male; mean [SD] age = 40.58 [12.75] years, mean [SD] PGSI = 7.16 [5.58]) in the e-SBIRT and control conditions showed improvements in gambling harms (p = 0.033) and perceived ability to control gambling (p = 0.029). No significant effects of condition assignment or condition x time interactions were observed. However, exploratory analyses of individual model coefficients suggested greater improvement in perceived ability to control gambling among participants receiving e-SBIRT at 12 weeks (p = 0.043). Exploratory analyses also suggested higher rates of help-seeking at 12-week follow-up among participants receiving e-SBIRT. CONCLUSION: Overall, e-SBIRT did not demonstrate clear advantages over assessment and information provision alone. Further research should prioritise refining intervention components and evaluating SBIRT approaches in settings that better reflect its opportunistic delivery model.

Humans↗

PubMed2026

Effect of flavored on!® nicotine pouch products on smoking behaviors: A sequential, multiple assignment, randomized controlled trial.

PURPOSE: To evaluate whether flavored versus unflavored nicotine pouch (NP) access affects cigarette reduction and smoke exposure among adults who smoke daily, and whether delayed flavor introduction affects these outcomes. METHODS: Adults who smoked ≥ 5 cigarettes/day (CPD) with interest in replacing cigarettes with NPs were enrolled in a remote, six-week, sequential multiple assignment randomized trial (n = 402 randomized; n = 400 analyzed). Participants were randomized to immediate access to seven NP flavors (Flavor), unflavored-only access for six weeks (Original), or unflavored-only for three weeks followed by flavor access (Delayed Flavor). Primary outcomes were ≥ 50% reduction in weekly mean expired-air carbon monoxide (CO) from baseline and mean CO at Week 6. Secondary outcomes included ≥ 50% CPD reduction, mean CPD, CO-verified 7-day abstinence, and incident smoke-free days. RESULTS: At Week 6, Flavor and Original did not differ in ≥ 50% CO reduction (14.3% vs 14.2%; IRR=1.0, 95% CI=0.6-1.8) or mean CO (18.3 vs 16.5 ppm; β=1.9, 95% CI=-1.3-5.0). CPD decreased across groups by Week 6, with no differences between Flavor and Original in ≥ 50% CPD reduction (50.3% vs 51.6%; IRR=1.0, 95% CI=0.8-1.2) or CO-verified abstinence (9.3% vs 8.9%; IRR=1.0, 95% CI=0.5-2.2). Flavor increased smoke-free days early, with attenuation over time. Among Week 3 non-responders, delayed flavor access increased ≥ 50% CPD reduction at Week 6 (33.3% vs 18.6%; IRR=1.8, 95% CI=1.0-3.2). CONCLUSIONS: NP access supported cigarette reduction regardless of flavor availability, but flavors may accelerate smoke-free days and improve response among individuals who do not reduce cigarette consumption with unflavored products alone.

Humans↗

PubMed2026

Frequency of Human Brucellosis Complications in West Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Brucellosis is a multi-systemic zoonotic infection. The West Asia/Middle East region is an important global hotspot for brucellosis. This systematic review and meta-analysis aimed to aggregate and synthesize all the available evidence regarding the complications of brucellosis in West Asia/Middle East region. METHODS: PubMed, Embase, Scopus, Web of Science, Google Scholar, and Proquest were searched. Selection of studies, data extraction, and the risk of bias assessment were performed in duplicate. Data extraction was performed for 254 complications. Meta-analysis was performed using a random-effects model with Freeman-Tukey double arcsine transformation. Where applicable small-study effects was assessed using funnel plots and Egger's test. Separate by-country, by-age, and by-publication-decade subgroup analyses were performed if feasible. RESULTS: Out of 9518 results, 240 studies (260 references) were included. The majority of the included studies were conducted in Turkey (n = 177). The reported complications varied and different complication categorization systems were detected. The highest pooled estimate was observed for musculoskeletal involvement (50%, 95%CI: 39%-61%, I2 = 96.63%). The evidences is up-to-date until March 4, 2024. CONCLUSIONS: Some complications such as the complications of the eye were not reported in all the countries. Therefore, it's recommended to determine the relative frequency of those complications in regions without such reports. The pooled estimates of different complications of brucellosis were different. There's a need for the standardization of the reporting of the complications of brucellosis to achieve comparability between studies and across different regions.

Brucellosis↗

PubMed2026

Co-Use of Some Substances Associated With Higher Doses in Adolescents: Findings From the Adolescent Brain Cognitive Development Study.

PURPOSE: Adolescence is a critical developmental period marked by heightened vulnerability to initiating substance use, with long-term implications for health and behavior. Nicotine, alcohol, and cannabis are the most commonly used substances among adolescents. Their use often co-occurs but few studies have described or quantified the patterns and doses of substance co-use in this vulnerable population. METHODS: We used data from six waves of the Adolescent Brain Cognitive Development study. Substance use was measured through a web-based timeline followback interview, and outcomes are operationalized into substance use quantity (in standard units), single use, and co-use (use of two substances on the same day) of alcohol, cannabis, and nicotine. Group differences of average dose in standard units between single use and co-use for each substance class were analyzed using linear mixed-effects modeling in years 4-6. RESULTS: The average dose of nicotine was significantly higher when co-used with alcohol (4.32; 95% confidence interval [CI]: 2.55-6.09; p < .001) or when co-used with cannabis (4.41; 95% CI: 2.76-6.05; p < .001) in year 6; nicotine trends were similar in years four and five. In year 6, the average dose of alcohol was higher when co-used with cannabis (1.87; 95% CI: 0.37-3.36; p = .004) or co-used with nicotine (1.64; 95% CI: 0.06-3.22; p = .03) compared to single use of alcohol. The average dose of cannabis was not significantly different when used singularly or co-used with either alcohol or nicotine in our study years. DISCUSSION: During adolescence, the co-use of substances (namely alcohol and nicotine) may lead to higher average doses compared to single-substance use.

Humans↗

PubMed2026

Effectiveness of Caregiver-Mediated Spoken Language Interventions for Children Under Five at Risk of Developmental Language Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Caregiver-mediated interventions are commonly used by Speech and Language Therapists to support early language development. Developmental Language Disorder (DLD) is associated with reduced quality of life throughout the lifespan. Understanding factors that predict intervention success is essential for developing appropriate, cost-effective therapy provision for the approximately 12% of preschool children who present with early markers for Developmental Language Disorder (DLD). This systematic review and meta-analysis examined the effectiveness of caregiver-mediated spoken language interventions for under-fives at risk of DLD, and factors influencing intervention effectiveness. METHODS: A systematic review following PRISMA guidelines was conducted. Five electronic databases were searched to identify experimental studies comparing caregiver-mediated spoken language interventions to control conditions in under-fives presenting with risk factors for DLD. Risk factors included prematurity, socioeconomic factors, caregiver language development concerns, and formal or informal language screening or assessment scores. Twenty-six experimental studies with 1407 child participants were included in qualitative synthesis. Meta-analysis was performed on nine Randomised Controlled Trials involving 947 children. RESULTS: Effectiveness was examined for outcomes including child language gains, child wellbeing, inclusion and attainment. Meta-analysis indicated a significant effect of caregiver-mediated spoken language interventions on language outcomes compared to treatment-as-usual, non-language intervention or waitlist control conditions. Non-language outcomes were evaluated via qualitative synthesis. Interventions significantly improved language development trajectories for under-fives presenting with risk factors or early markers for DLD. CONCLUSION AND IMPLICATIONS: This review contributes to the growing evidence base demonstrating that caregiver-mediated interventions can positively impact language development and wellbeing outcomes for children under five at risk of DLD. These findings support the implementation of caregiver-mediated environmental language interventions in clinical practice to maximise accessibility and cost-effectiveness while delivering optimal outcomes for vulnerable populations. WHAT THIS PAPER ADDS: What is already known on this subject Previous research on caregiver-mediated spoken language interventions has highlighted gaps in the evidence regarding the impact of risk factors, demographic characteristics, dosage and intervention components on child language outcomes. Developmental Language Disorder has relatively high population prevalence, estimated at 7%. Prevalence is associated with risk factors including low household socioeconomic status (SES), prematurity and late language emergence. In contrast to its prevalence, there is low public and professional awareness of DLD and a low diagnostic rate. Therefore, a strengthened evidence base and additional insights into the factors affecting success of family-based interventions is important in order to increase the effectiveness of service provision and care planning for this underserved population. Timely and effective intervention with young children presenting with early markers for DLD has the potential to offer lifelong improvement to their wellbeing, inclusion and attainment outcomes. Recent systematic reviews of the effectiveness of caregiver-mediated language interventions had differences in population age range and diagnostic inclusion criteria. What this paper adds to existing knowledge Our review examines the effectiveness of caregiver-mediated early spoken language interventions on child language, attainment and wellbeing, and on caregiver self-efficacy and adherence to language support strategies. Our population was children under five presenting with risk factors for Developmental Language Disorder, in the absence of other neurodevelopmental or genetic conditions such as intellectual disability or autism. This review adds depth and detail to the evidence base supporting the effectiveness of caregiver-mediated spoken language interventions in improving outcomes for this population of young children, and factors that influence their success. What are the potential or actual clinical implications of this work? The high prevalence of Developmental Language Disorder, estimated at around 7% of the population, and the strong association with risk factors including low SES, prematurity and late language emergence, coupled with the low awareness of DLD and low diagnostic rate, mean that a strengthened evidence base and additional insights into the factors affecting success of family-based interventions can increase the effectiveness of service provision and care planning for this population. Timely and effective intervention in this group of young children has the potential to improve wellbeing and attainment outcomes across the lifespan. This review contributes to our understanding of how to implement cost-effective, socially valid and maximally engaging partnership working with families of young children at risk for DLD.

Humans↗

PubMed2026

Histidine Supplementation Stabilizes Hearing and Vision and Improves Growth in HARS1-Related Autosomal Recessive Disorder Associated With Usher-Like Symptoms.

Autosomal recessive HARS1-related disorder (originally described as Usher syndrome type 3B) caused by a homozygous Y454S variant in the histidyl-tRNA synthetase gene (HARS1) is characterized by progressive sensorineural hearing and vision loss and respiratory deterioration with risk for sudden death following febrile illnesses. In-vitro studies have previously shown that histidine can rescue a humanized yeast model for pathogenic HARS alleles. Fourteen children homozygous for HARS Y454S were treated with supplemental oral histidine (50 mg/kg BID) and monitored with bloodwork and physical, visual, and audiometry assessments during a 3-year clinical trial, then followed for more than 4 years on histidine in the post-trial period. Patient fibroblasts were assessed for response to histidine. Hearing and vision remained stable, and growth improved significantly. Children remained healthy, with no severe deteriorations despite exposure to bacterial and viral infections, including COVID-19. Gains in growth were maintained in the post-trial period on varying levels of histidine supplementation. Daily oral histidine supplementation in children with autosomal recessive HARS1-related disorder can ameliorate or slow the progression of disease and is safe, inexpensive, and well tolerated. This study adds to the growing list of autosomal recessive ARSopathies (aminoacyl-tRNA synthetase disorders) that are amenable to amino acid supplementation.

Humans↗

PubMed2026

Efficacy of Oral Baicalin in Canine Atopic Dermatitis: A Randomised Placebo Controlled Trial.

BACKGROUND: Baicalin has shown efficacy in various dermatitis models in animals. However, its therapeutic effects on naturally occurring canine atopic dermatitis (cAD) have not been evaluated. OBJECTIVE: To evaluate the efficacy and safety of baicalin in dogs with cAD. ANIMALS: 56 client-owned dogs were enrolled. MATERIALS AND METHODS: All dogs were randomly divided to receive oral baicalin or placebo over a 90day period. All subjects had veterinary evaluations using the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) during the trial and owners were requested to evaluate itching using the pruritus Visual Analog Scale (PVAS) and to complete a quality-of-life (QoL) questionnaire at Day (D)0 and D90. Additionally, the transepidermal water loss (TEWL), total serum IgE levels (IgE), complete blood count and serum biochemical results were measured at D0 and D90. RESULTS: The significant decreases in CADESI-04 (p < 0.001), PVAS (p < 0.001), TEWL (p = 0.014), IgE (p < 0.001) and QoL scores (p < 0.001) were observed in the baicalin group D90 compared to baseline. When compared to placebo, the baicalin group had significantly lower scores in CADESI-4 and PVAS (p < 0.001). A significantly higher proportion of subjects in the baicalin group showed a good-to-excellent treatment response (82.1%) compared to those in the placebo group (35.7%). The treatment was well tolerated. CONCLUSIONS AND RELEVANCE: Baicalin had a significant benefit in alleviating pruritus and reducing clinical signs in dogs with mild-to-moderate cAD and was well tolerated.

Animals↗

PubMed2026

Intraskeletal Variation in Cortical Bone Quantity in a Medieval Italian Sample: A Multivariate Exploratory Approach.

Bioarcheologists interpret skeletal health by examining variability within and between individuals. Studies of bone loss have generated contradictory and conflicting results regarding the onset and severity of age-related bone loss on a global and temporal scale, perhaps due to mismatched methodologies. Intraskeletal comparisons of bone tissue prove challenging precisely because of heterogeneous baselines in quantity and remodeling of cortical bone throughout the skeleton, as well as evolutionary histories and environmental impacts on growth and development. Here we analyze cortical bone indicators from the rib, metacarpal, and femoral cortical bone in a subset of individuals (n = 72) regions from the medieval Italian archaeological site of Pieve di Pava. To facilitate intraskeletal comparisons across elements with different biological baselines, we standardize cortical bone parameters using z-scores. Variation in relative intraskeletal cortical bone was assessed using accessible multivariate methods (principal component analysis and hierarchical cluster analysis). Results suggest an association between femoral and metacarpal cortical bone values, with stochastic trends in metacarpal and femoral relative bone quantity in relation to the rib bone quantity at the sample level. Our study demonstrates that while intraskeletal analyses are challenging, they are made more robust by synthesizing multivariate methods alongside exploratory data analysis (EDA) methods to tack between sample-level and individual-level scales and variability. Ultimately, we advocate for leveraging multivariate techniques not as a final step, but rather as a means of generating new hypotheses and challenging tendencies to a priori establish typological groups in the research process.

Skeleton↗

PubMed2026

Screening of Estrogenic and Antiestrogenic Effects of Estradiol, Bisphenol A, and Fulvestrant Using 2D and 3D Breast Cancer Cell Systems With a Luciferase Reporter Gene Assay.

Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) pose health risks by interfering with hormones. This study develops and utilizes in vitro 2D and 3D cell models to evaluate the estrogenic and antiestrogenic properties of compounds. Human breast cancer cell lines T47D and MCF7, stably transfected with a luciferase reporter gene (ERE-LUC), were first compared in 2D. Due to the significantly higher sensitivity and responsiveness observed in the T47D line during preliminary 2D screenings, this cell line was exclusively selected for the development of the 3D spheroid model. Cells were treated with 17β-estradiol (E2), BPA, and Fulvestrant (FUL) to assess cell viability and luciferase activity. In 2D models, T47D ERE-LUC cells showed higher responsiveness than MCF7 ERE-LUC, which failed to show significant luciferase induction with E2. In the 3D T47D model, cells exhibited significant and robust changes in luciferase activity in response to E2 and BPA, highlighting the enhanced fidelity of 3D cultures in replicating tissue conditions compared to their 2D counterparts. The study highlights the effectiveness of 3D models over 2D in evaluating estrogenic activity. Specifically, the 3D T47D ERE-LUC system serves as a superior, sensitive, and reliable platform for screening EDCs, offering benefits in cost, data speed, and reduced in vivo reliance.

Humans↗

PubMed2026

Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.

Phase 2 (and phase 1 dose expansion, which we label phase 2 for the purposes of this study) cancer trials are the first direct tests of a new drug's efficacy. Because efficacy evidence is lacking, the therapeutic status of drug administration during ethical review is uncertain. We compared the efficacy and safety of cancer monotherapies in phase 2 with phase 3, where clinical equipoise underwrites a therapeutic status for drug administration. In this systematic review and meta-analysis, we searched Clinicaltrials.gov for phase 2 and 3 investigational monotherapy drug trials in six solid malignancies, with primary completion dates 2015-2020, inclusive. Two independent reviewers completed data extraction. Effects were estimated using an inverse-variance weighted random-effects model meta-analysis of proportions using the R package meta. We analyzed 130 phase 2 and 52 phase 3 trial arms, enrolling 6665 and 18,694 patients. The pooled objective response rate was 7% (95% CI 5%-11%) in phase 2 versus 24% in phase 3 (95% CI 17%-31%; p < 0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43 months, p < 0.0001; 9.46 vs. 14.44 months, p = 0.0001). The pooled rate of drug-related grade 3-4 adverse events was 30% (95% CI 23%-37%) in phase 2 and 25% (95% CI 19%-32%) in phase 3. Monotherapies delivered in phase 2 cancer trials present diminished risk-benefit compared with phase 3 and align with historic estimates for phase 1. Though there may be exceptions, risks for drug administration in phase 2 should generally be justified by appeals to research rather than therapeutic value.

Humans↗

PubMed2026

Chemotherapy-Induced Nausea and Vomiting in Early Breast Cancer Patients Receiving Adjuvant Chemotherapy With Fluorouracil, Epirubicin, Cyclophosphamide Followed by Docetaxel Versus an Anthracycline-Free Regimen With Docetaxel, Cyclophosphamide-Results From a Randomized Clinical Trial.

Chemotherapy-induced nausea and vomiting (CINV) remains an important side effect despite new antiemetic drugs. This study tried to understand the occurrence of CINV in patients receiving two different chemotherapy regimens. As part of the randomized controlled clinical trial SUCCESS C (NCT00847444), 1582 of the 3463 patients completed CINV diaries. Patients were randomized to receive either chemotherapy with FEC (5-fluorouracil, epirubicin, cyclophosphamide followed by docetaxel) or TC (docetaxel, cyclophosphamide). CINV was evaluated hourly using a specially designed questionnaire. Endpoints of the study were complete response (no emesis) and total control (no nausea and no emesis) and were assessed with Kaplan-Meier curves and Cox regression analyses over three chemotherapy cycles. Eight hundred fourteen patients received FEC and 768 received TC; patients and tumor characteristics were similar in both groups. Patients receiving FEC had significantly more nausea and vomiting, with the main difference in the first 12 h. In the first cycle, the 0-12-h nausea/emesis-free rates were 70%/41% for FEC and 91/76% for TC. By 24 h after chemotherapy, the rates were 65%/33% (FEC) and 85%/60% (TC). The differences were similar in cycles 2 and 3. The detailed analysis of CINV in the study is unique and paves the way for modern CINV analysis of new therapeutics such as antibody-drug conjugates.

Adult↗

PubMed2026

Factors Impacting Overall Survival Post-Relapse in High-Risk Neuroblastoma: Children's Oncology Group Outcomes From 2000 to 2019.

PURPOSE: Prior studies of features impacting post-relapse survival in high-risk neuroblastoma (HRNB) evaluated patient cohorts that did not receive contemporary high-risk or relapse therapies. We describe overall survival (OS) after first progression or first relapse of HRNB in a modern cohort. METHODS: Patients with HRNB enrolled on COG ANBL00B1(NCT00904241) between 2000 and 2019, who had relapsed or progressive disease were eligible. Clinical and molecular risk factors at diagnosis, therapy era, clinical trial enrollment, and clinical features at relapse, including site of and time to relapse, were evaluated. OS post-relapse was compared between groups using log-rank tests and Cox models. RESULTS: Among 4253 eligible HRNB patients, 1616 had relapse or progression as a first event. Five-year OS post-relapse was 19.1 ± 1.1%. The risk group with the lowest post-relapse survival was observed in patients with INSS Stage 4 or 4S disease < 18 months of age at diagnosis with MYCN amplified (MYCN-A) tumors. The other significant most unfavorable factors at diagnosis included diagnosis 2000-2004, tumor MYCN-A, 1p loss of heterozygosity (LOH), and elevated LDH or ferritin. Unfavorable factors at relapse included the time to relapse < 36 months from diagnosis, and combined local and metastatic disease at relapse. Multivariable analysis indicated that those with tumors harboring 1p LOH, age ≤ 5 years at diagnosis, or earlier treatment therapy era (2000-2004) had a higher risk of post-relapse death. CONCLUSIONS: While the 5-year OS rate was low in this cohort, there are subsets of patients with relapsed HRNB who demonstrate long-term survival. TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00904241.

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

Effects of Dynamic Neck Sensorimotor Biofeedback Training in Individuals With Mechanical Neck Pain: A Pilot Randomized Controlled Trial.

Mechanical neck pain (MNP) is commonly accompanied by pain-related functional limitations, sensorimotor disturbances, and fear of movement, which together may contribute to persistent disability. This preliminary randomized controlled trial study investigated the short-term effects of dynamic neck sensorimotor-based biofeedback training in individuals with MNP. 20 MNP patients from outpatient clinics were assigned to a biofeedback training group or a control group. The training group underwent dynamic biofeedback exercises twice weekly for 2 weeks, whereas the control group performed repeated cervical movements without biofeedback. Outcomes included cervical kinematics as repositioning errors (RPE), movement units (MU), maximal range of motion (ROM), and subjective measures, including pain intensity, Neck Disability Index (NDI), and Fear-Avoidance Beliefs Questionnaire (FABQ). All participants completed post-intervention assessments; adherence in the training group was 100%, with no missing data and no adverse events reported. Within the biofeedback training group, participants receiving biofeedback training demonstrated greater improvements in cervical repositioning accuracy during flexion (51.95%, p = 0.04) and extension (46.67%, p = 0.02), along with reductions in fear-avoidance beliefs related to physical activity and work (p < 0.05); these changes were less apparent in the active control group. Exploratory regression analyses suggested associations between improvements in repositioning accuracy and pain reduction, and between increased cervical range of motion and improvements in fear-avoidance beliefs related to physical activity. These pilot findings suggest that dynamic sensorimotor biofeedback training may improve proprioceptive acuity and fear-avoidance beliefs in individuals with MNP, supporting further evaluation in an adequately powered randomized trial.

Humans↗

PubMed2026

Genotype II Live-Attenuated ASFV Vaccine Bearing 24 Genes Deletion in 3 Independent Regions Is Able to Provide Complete Protection Against Homologous Lethal Challenge.

African swine fever (ASF) is an acute, febrile, and highly contagious infectious disease of swine with the etiological agent of African swine fever virus (ASFV). The mortality rate of virulent strains is as high as 100%. Strengthening biosafety is so far the most effective way to prevent and control ASF. Therefore, it is urgent to develop a safe and effective vaccine. In this study, a Genotype II live-attenuated ASF vaccine bearing 24 genes deletion in 3 independent regions was constructed based on the highly virulent Eurasian strain ASFV CN/GS 2018 backbone. The resulting mutant ASFV-Δ24 is characterized by complete deletion of 24 genes distributed in 3 genomic positions of 852 to 11 468, 19 732 to 22 929, and 179 519 to 180 617, among which MGF100 and whole MGF300 families are pioneeringly removed. The ASFV-Δ24 displayed a delayed and reduced replication kinetics as well as aberrant icosahedral empty particles devoid of a nucleoid when compared to the parental virus. Animal experiments showed that ASFV-Δ24 was completely attenuated in animals as evidenced by stable body temperature and no ASF-compatible clinical signs in vaccinated pigs. The ASFV-Δ24 could provide complete homologous protection against lethal challenge, as vaccinated pigs demonstrated boosted antibody response, transient but low levels of viremia in blood and virus titers in organs as well as almost undetectable viral shedding. Gene deletions in multiple regions are helpful for prevention of virulence reversion. These results indicate that ASFV-Δ24 can be used as an effective and promising candidate vaccine to control the spread of ASFV.

Animals↗

Results for “cyclin&#x2010;dependent kinase 6”

Results for “cyclin‐dependent kinase 6”