SEARCH · Search PubMed

Results for “Antiretroviral Therapy, Highly Active”

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.

1,164 records · Page 5Linked to original sources

PubMed2026

CAR-T Cell Therapy: Manufacturing Platforms and Clinical Consequences.

Chimeric antigen receptor (CAR) T-cell therapy has transformed hematological cancer care, yet variability in efficacy, durability, and safety cannot be explained solely by antigen selection or patient factors. We propose that manufacturing platforms are active biological determinants of outcome. Viral vectors, used in all licensed products, provide stable genomic integration and durable expression but are limited by cost, cargo capacity, and centralized production. Nonviral strategies, including transposons, CRISPR knock-ins, and messenger RNA delivery, enable faster, less-expensive manufacturing with larger payloads, while introducing distinct safety and persistence profiles. This review presents a three-layer mechanistic framework that reframes manufacturing as biology: integration biology determines genomic risk and transgene stability; clonal fitness shapes persistence, dominance, and exhaustion; and epigenomic imprinting, influenced by gene transfer method, cytokines, and culture stress, preconfigures functional trajectories. Clinical observations link platform choice to immune recovery, where prolonged B-cell aplasia and delayed T-cell reconstitution contribute to infection-related nonrelapse mortality, and hematopoietic reserve at apheresis emerges as a practical predictor. Finally, manufacturing is positioned as the key to democratizing cell therapy. Decentralized, nonviral production aligned with regulatory standards may enable equitable access and transition CAR-T therapy from innovation to sustainable global care.

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

Short-term aerobic exercise as an adjunct treatment for depression in acute geriatric psychiatry: Results of a randomized controlled trial.

BACKGROUND: This randomized controlled trial examined whether short-term aerobic exercise provided additional clinical benefit over an active control in older inpatients with depression in geriatric psychiatry. METHODS: 100 patients (mean age 76 years) were randomized to 2-week supervised aerobic ergometer training (intervention group, IG) or a flexibility program (control group, CG), both delivered in addition to treatment as usual (TAU). Adherence, training exposure and adverse events were recorded to assess feasibility. The primary outcome was clinical improvement measured with the Clinical Global Impression of Change (CGI). Secondary outcomes included depressive symptom severity assessed by the Beck Depression Inventory-II (BDI-II) and clinician-rated Hamilton Rating Scale for Depression (HAMD), physical activity, 6-min walk test (6MWT) performance, and fluoxetine-equivalent antidepressant dose (FLX). RESULTS: Thirty-nine participants attended at least 80% of sessions, with lower adherence in the IG. Weekly training duration differed between groups (74.0 ± 31.9 vs. 95.0 ± 25.3 min/week, p = .003). CGI did not differ between groups (IG: MD -0.31, 95% CI -0.67 to 0.05; p = .069). Depressive symptom severity decreased over time in both groups (p < .001), without significant between-group differences for HAMD (MD -0.22, 95% CI -2.55 to 2.12) or BDI-II (MD -0.62, 95% CI -3.68 to 2.45). 6MWT and FLX increased over time (both p < .001), without group differences (6MWT: MD -1.08 m, 95% CI -20.04 to 17.89; FLX: MD 5.69 mg/day, 95% CI -2.40 to 13.77). CONCLUSION: Short-term aerobic exercise was deliverable, but showed no additional clinical benefit over low-intensity flexibility during TAU. Further research should determine dose, duration and adherence for clinically relevant effects.

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↗

PubMed2026

Exercise with motor cortex high-definition transcranial direct current stimulation enhances cardiovascular efficiency and lower-limb function in multiple sclerosis: A crossover, double-blind, and proof-of-principle study.

Combining exercise with high-definition transcranial direct current stimulation (HD-tDCS) could offer a strategy to help people with Multiple Sclerosis improve outcomes. In this crossover study, participants with MS (Expanded Disability Status Scale ≥3.0, n = 12) and controls (n = 10) completed baseline testing, followed by three randomized experimental conditions: 1) exercise+active HD-tDCS; 2) exercise+sham HD-tDCS; and 3) HD-tDCS alone. Exercise performance metrics [heart rate, work rate, heart rate-to-work rate (HR/WR) ratio, and perceived exertion] were compared across the exercise conditions. Secondary outcomes included the Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25F), Nine-Hole Peg Test (9HPT), and acute symptom ratings (fatigue and pain), assessed pre-, immediately post-, and 1h-Post. Cardiovascular efficiency (HR/WR ratio) significantly improved during exercise+HD-tDCS compared to exercise alone, particularly in older MS participants (p = 0.010). SDMT declined immediately post HD-tDCS alone, 1h-post-exercise alone, and at both time points during exercise+active HD-tDCS (p < 0.05). Both groups increased walking speed only post-exercise+active HD-tDCS, while no condition affected upper-limb function (p < 0.05). These results are in line with the tDCS literature in the general population, suggesting that tDCS improves exercise performance and selectively improves engaged motor function. The trade-off between physical and cognitive outcomes underscores the importance of personalized neuromodulation strategies in neurorehabilitation to maximize therapeutic benefits while minimizing adverse effects, and warrants further large-scale, long-term investigations of this approach in MS.

Humans↗

PubMed2026

Adding Rib Mobilization to Diaphragm Release Techniques in Patients With Non-Specific Neck Pain: Randomized Controlled Trial.

BACKGROUND: Non-specific neck pain (NSNP) is a frequent issue that can negatively affect both mobility and function. Recently, there has been growing interest in newer therapeutic approaches, including rib mobilization and diaphragm release techniques, as potential ways to address NSNP and support better outcomes for those affected. PURPOSE: To find out the immediate effects of how (DRT) combined with (RMT) affects the level of pain and the extent to which patients' functional abilities are improved in cases of NSNP. METHODS: For this prospective RCT, 96 participants aged 20 to 45 years were randomly assigned to one of three equal groups based on their pain score (VAS). Group B engaged in (DRT) for 40 minutes, three times weekly for 8 weeks, in contrast to Group A, which got both RMT combined with DRT. Group C (active control) received advice and some exercises. Measurements were collected before and after the intervention; the primary outcomes included pain severity, evaluated using a visual analog scale (VAS); active neck range of motion (ROM), measured with a cervical range of motion (CROM) device; and neck flexion endurance. Additionally, the secondary outcome of neck-related disability was assessed using the Neck Disability Index (NDI). RESULTS: No statistically significant difference was identified among the three groups at baseline; nevertheless, a treatment effect emerged after 8 weeks (p = 0.001 and f-value = 4.15, ƞ2 = 0.306). A statistically significant time-treatment interaction was seen when comparing the pre- and post-treatment periods in groups A and B (p = 0.001, f-value = 3.16, ƞ2 = 0.251). CONCLUSION: The addition of rib mobilization to diaphragm release techniques in patients with non-specific neck pain resulted in statistically significant improvements in pain intensity, cervical flexion, right lateral rotation, left lateral rotation, right rotation, and neck flexor endurance, with moderate to large effect sizes for pain reduction and cervical motion. However, no statistically significant differences were observed between groups for cervical extension, left rotation, or the Neck Disability Index (NDI), and only a marginal clinical improvement in NDI was noted in Group A. The observed benefits in the combined intervention group may not be attributable solely to rib mobilization. The increased treatment complexity and greater therapist interaction inherent in the combined approach could also have influenced the outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07133646.

Humans↗

PubMed2026

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p = 0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p = 0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

Humans↗

PubMed2026

Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings. METHODS: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK. RESULTS: Fourteen studies involving 4,944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2,492 patients received IVT in an extended time window (4.5-24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25-1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11-1.40]), and recanalization (OR: 3.28 [95% CI 2.09-5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95-1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47-4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06-3.64) compared with alteplase (OR: 5.29, 95% CI 1.80-15.57); however, the subgroup difference was not significant (p = 0.11). DISCUSSION: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.

Humans↗

PubMed2026

Effect of Baseline ASPECTS on Tenecteplase Efficacy Before Thrombectomy in Acute Large-Vessel Occlusion Stroke: A Post Hoc Analysis of the BRIDGE-TNK Randomized Trial.

BACKGROUND AND OBJECTIVES: The impact of ischemic extent on the efficacy and safety of intravenous thrombolysis before thrombectomy remains uncertain. The aim of this study was to evaluate whether the baseline ischemic extent, measured by the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), modifies outcomes of intravenous tenecteplase administered before endovascular thrombectomy. METHODS: This was a post hoc analysis of the BRIDGE-TNK (thrombectomy with vs without rhTNK-tPA in stroke) trial, conducted across China from May 2022 to September 2024. We compared the efficacy and safety of intravenous tenecteplase plus thrombectomy vs thrombectomy alone in acute large-vessel occlusion stroke patients within 4.5 hours of last known well, stratified by baseline ASPECTS (<8 vs 8-10). The outcomes included 90-day functional independence (modified Rankin Scale score of 0-2), 48-hour symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Regression models incorporating a treatment-by-ASPECTS interaction term were used for analysis. RESULTS: Among 550 patients, 241 (43.8%) had ASPECTS <8 (median [interquartile range, IQR] age, 69 [61-77] years; 56.4% male) and 309 had ASPECTS 8-10 (median [IQR] age, 70 [61-77] years; 59.5% male). The rate of functional independence was significantly higher in the tenecteplase plus thrombectomy group than in the thrombectomy-alone group in the ASPECTS <8 subgroup (adjusted risk ratio [aRR], 1.67; 95% CI 1.18-2.35), but not in the ASPECTS 8-10 subgroup (aRR, 0.99; 95% CI 0.84-1.17; pinteraction = 0.007). Rates of sICH did not differ significantly between treatment groups in either ASPECTS subgroups (ASPECTS <8: 10.0% vs 11.2%; ASPECTS 8-10: 7.5% vs 2.8%; pinteraction = 0.11). Ninety-day mortality was comparable between treatment groups in the ASPECTS <8 subgroup, but numerically higher with tenecteplase plus thrombectomy in the ASPECTS 8-10 subgroup (aRR = 1.89, 95% CI 0.99-3.61, pinteraction = 0.04). DISCUSSION: In this exploratory post hoc analysis, a signal of benefit was observed in patients with ASPECTS <8 who received intravenous tenecteplase before thrombectomy, whereas no functional improvement and possible safety concerns were seen in those with ASPECTS 8-10. Prospective confirmation in randomized trials is required before practice change. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Unique identifier: NCT04733742.

Humans↗

PubMed2026

Metabolic and endocrine modulation of the gut-adipose tissue axis via pro-, pre-, and postbiotics in overweight dogs: A systematic review.

Canine obesity is a complex metabolic disorder driven by luminal dysbiosis, impaired gut barrier function, and metaflammation. Following PRISMA 2020 guidelines, this systematic review evaluated the efficacy of pro-, pre-, and postbiotics in modulating the gut-adipose tissue axis in overweight dogs (BCS ≥ 6/9) or diet-induced obesity models. Searches across PubMed and Dimensions (April 2026) identified seven eligible experimental trials. Results suggest that postbiotic Bifidobacterium animalis subsp. lactis CECT 8145 reduced postprandial glucose AUC by 6 % strictly during energy restriction. Pasteurized Akkermansia muciniphila postbiotics limited diet-induced weight gain, though glucoregulatory impacts were highly strain-specific (AKK2 reduced fasting glucose and insulin resistance indexes, whereas EB-AMDK19 exerted no significant effect). Specific probiotics (including Enterococcus faecium, Bifidobacterium lactis, Lactiplantibacillus plantarum and Bifidobacterium breve) attenuated fasting hyperinsulinemia and preserved circulating adiponectin, but lipid profile improvements (triglycerides and total cholesterol) were inconsistent across trials. In dogs, increased luminal short-chain fatty acids are not consistently mirrored by endocrine responses, so the coupling between microbial metabolites and incretin signaling remains incomplete. A critical lack of standardized reporting for species-validated insulin sensitivity metrics was identified. In conclusion, microbiome-targeted therapies, particularly inanimate postbiotics, may represent useful adjunctive strategies to mitigate metabolic dysregulation in obesogenic environments. However, clinical efficacy remains strictly strain-specific and dependent on host energy balance. Given the scarcity of high-certainty evidence, future trials must integrate dynamic physiological assessments with species-validated surrogate indexes alongside standardized dietary controls.

Animals↗

PubMed2026

The future of precision oncology and artificial intelligence in Belgium: scenarios and policy responses.

PURPOSE: Precision medicine, also known as personalized medicine, enables the provision of tailored health services to patients. In the prevention, early detection, and treatment of cancers, precision medicine is highly promising, given the increasing use of genomic profiling for diagnosis and adapting therapies in several tumor types. Artificial Intelligence (AI) can support this process by analyzing vast amounts of relevant data. However, high-quality data and financial investments in the health system are essential for the implementation of precision medicine and AI solutions in routine cancer care. DESIGN/METHODOLOGY/APPROACH: Building on the quantitative outcomes of a foresight exercise published in another study, this article collects qualitative data to gain more detailed insights into the future of precision oncology in Belgium and discusses the role of AI in this field. It reports the results of a series of expert workshops, focusing on four hypothetical future scenarios that are centered around technological and economic issues that must be overcome for the widespread use of precision oncology in Belgium. FINDINGS: The study concludes that all four scenarios discussed in the workshops would require supportive policy measures in Belgium, which should go beyond mere technological and economic considerations, such as involving patient associations and the public in policy design or creating multi-disciplinary expert groups for precision medicine. ORIGINALITY/VALUE: To the best of our knowledge, this is the first study to employ foresight methodology to illustrate possible future scenarios, scrutinize feasible approaches for implementing precision oncology in Belgium, and discuss the use of AI in this context.

Belgium↗

PubMed2026

Engineered MXene-based nanozyme platform: NIR-II photothermal and dual enzyme-mimetic potentiated chemodynamic synergy for precision tumor eradication.

The antioxidant defense barrier in the tumor microenvironment, particularly glutathione (GSH), considerably restricts the therapeutic efficacy of chemodynamic therapy (CDT). Moreover, CDT generally exhibits relatively mild therapeutic efficacy owing to its intrinsic reaction kinetics, making it difficult to achieve complete tumor eradication within a short time. To address these issues, we construct a functionalized nanotherapeutic platform, Nb2CTx@Ru-PEG2000-FA (NCRPF), for tumor photothermal ablation and enhanced CDT resulting from GSH depletion. NCRPF possesses three key advantages: 1. Efficient near-infrared II photothermal conversion (η = 42.08%), raising the tumor temperature above 45 °C within 90 s for rapid ablation; 2. Dual peroxidase-like and glutathione peroxidase-like activities, simultaneously depleting GSH and generating a burst of ·OH to eliminate residual tumors; 3. Targeted tumor accumulation with 2.9-fold higher efficiency than passive diffusion. Both in vitro and in vivo results confirm that this combined strategy achieves complete tumor eradication with favorable biosafety. Collectively, the NCRPF nanotherapeutic system provides a powerful new paradigm with high translational potential for the complete eradication of breast cancer.

Animals↗

PubMed2026

Hand Pain and Sensory Deficits: Carpal Tunnel Syndrome: 2026 Revision. Using the Evidence to Guide Musculoskeletal Rehabilitation Practice.

SYNOPSIS: Carpal tunnel syndrome is common in women, manual laborers, and during pregnancy; it is often associated with medical conditions such as obesity and diabetes. The musculoskeletal rehabilitation clinician's approach to managing hand pain and sensory deficits associated with carpal tunnel syndrome should include prescribing a neutral-positioned wrist orthosis plus instructing the patient on how to modify activities, adjust ergonomics, and reduce exposure to risk factors. Here, we present for clinicians the most up-to-date information to guide their work in managing hand pain and sensory deficits associated with carpal tunnel syndrome. J Orthop Sports Phys Ther 2026;56(9):622-623. doi:10.2519/jospt.2026.0502.

Humans↗

PubMed2026

Efficacy and safety of Ruxolitinib-based combination therapy in the patients with Myelofibrosis (MF): a systematic review and meta-analysis.

BACKGROUND: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm. Although Ruxolitinib, a JAK1/2 inhibitor, remains the cornerstone of MF treatment, it does not reverse disease progression, and resistance frequently emerges. These limitations have prompted investigation into combination therapies targeting pathways beyond the JAK-STAT axis. This meta-analysis aims to evaluate the efficacy and safety of Ruxolitinib-based combination therapies in patients with MF. METHODS: We conducted a systematic search of databases for studies published through August 1, 2025. Thirteen distinct Ruxolitinib-based combination regimens were included. Primary efficacy endpoints were ≥35% spleen volume reduction at 24 weeks (SVR35) and ≥50% reduction in total symptom score (TSS50). Safety endpoints focused on the incidence of grade 3/4 thrombocytopenia and anemia. Subgroup analyses were performed based on prior JAK inhibitor exposure and therapeutic mechanism of action. RESULTS: A total of 19 studies comprising 1,088 patients were included in the meta-analysis. Among JAK inhibitor-naïve patients, the combination of Ruxolitinib with Selinexor demonstrated the highest efficacy (SVR35: 92%; TSS50: 78%), followed by Ruxolitinib plus BMS-986158 (SVR35: 90%). For patients with prior JAK inhibitor exposure, Ruxolitinib plus Siremadlin (SVR35: 45%) showed notable activity. CONCLUSION: For JAK inhibitor-naïve patients, Ruxolitinib-based combination regimens demonstrated satisfactory clinical responses and the potential for meaningful disease control. For patients with prior JAK inhibitor exposure, the addition of combination therapy drugs may further enhance the efficacy. Personalized treatment selection remains essential, as therapeutic efficacy is significantly influenced by prior JAK inhibitor exposure.

Humans↗

PubMed2026

User Engagement and Feature Preferences in an AI-Powered mHealth Intervention for Diabetes Prevention: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Prediabetes is highly prevalent and increasing globally, yet lifestyle interventions remain underused. AI-driven mobile health (mHealth) tools can help scale diabetes prevention efforts, but the key factors driving their success are not well understood. OBJECTIVE: This post hoc secondary analysis of a randomized controlled trial (RCT) aimed to characterize the most valued features and the role of user engagement in outcomes of a fully automated mHealth intervention for diabetes prevention. METHODS: Data from 151 participants with prediabetes and overweight or obesity who were assigned to an AI-based diabetes prevention program (Sweetch) in a parent RCT (NCT05056376) were analyzed. Engagement (defined as the total number of days the app was used) was categorized into tertiles (low, medium, and high). Baseline characteristics were compared across engagement groups using ANOVA, Kruskal-Wallis, and chi-square tests, and regression models assessed the association between engagement and achievement of diabetes risk reduction outcomes (≥5% weight loss, ≥4% weight loss with ≥150 min/week of physical activity, or ≥0.2 percentage point reduction in hemoglobin A1c [HbA1c] at 12 months). Perceived usefulness of intervention features was surveyed at 12 months. RESULTS: Median engagement was 98 (IQR 34-232) days. Older age (P<.001) and lower baseline BMI (P=.04) were significantly associated with higher engagement. Compared with low engagement, high engagement was associated with greater odds of achieving the composite diabetes risk reduction outcome (odds ratio [OR] 2.59, 95% CI 1.11-6.01; P=.03), ≥5% weight loss (OR 3.31, 95% CI 1.16-9.42; P=.03), and ≥0.2 percentage point reduction in HbA1c (OR 3.57, 95% CI 1.19-10.75; P=.02). Participants most frequently rated weight tracking, physical activity tracking, and the digital body weight scale as the features that were most helpful for achieving their health goals. CONCLUSIONS: Higher engagement with an AI-driven intervention requiring no human intervention was associated with improved diabetes risk reduction. Contrary to concerns about lower digital literacy, older adults engaged with the intervention more than younger adults. Features related to weight and physical activity tracking were most valued by patients in the program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05056376; https://clinicaltrials.gov/study/NCT05056376.

Humans↗

PubMed2025

Social Responsiveness as a Mediator in Adapted Cognitive Behavioral Therapy for Autistic Youth with Maladaptive and Interfering Anxiety.

Numerous adaptations to interventions have been included in cognitive behavioral therapy (CBT) for autistic youth. This study examines the degree to which CBT adapted to the social needs of autistic youth confers significant benefit by promoting social responsiveness. A secondary analysis was conducted on a multisite randomized clinical trial (Wood et al. in JAMA Psychiatry 77:474-483, 2020) comparing adapted CBT with standard-of-practice CBT and treatment-as-usual (TA). Autistic youth (N = 167; aged 7-13) with maladaptive and interfering anxiety participated. The adapted CBT (BIACA) uses a modular format, with an emphasis on supplementing common CBT practice elements (reframing and graded exposure) with social skill supports. The primary outcome measure was the Pediatric Anxiety Rating Scale. Social responsiveness was assessed with the Social Responsiveness Scale, Second Edition. Participants' general mental health was assessed as a secondary outcome using the Brief Problem Checklist. Mediation was tested using the SPSS PROCESS macro. Analyses suggested that the effect of adapted CBT on anxiety was mediated by its effects on social responsiveness, with a statistically significant indirect effect. Youth randomly assigned to adapted CBT exhibited better overall mental health at posttreatment compared to those randomized to the other conditions, and this effect was also mediated by improved social responsiveness. CBT adapted to address some of the social needs of autistic youth may enhance mental health outcomes by supporting social responsiveness, perhaps increasing the ease and effectiveness with which some youth can navigate potentially stressful situations such as entering and participating in group activities.

Humans↗

PubMed2026

Antimicrobial photodynamic therapy mediated by phenothiazine photosensitizers against Candida albicans and Candida auris: a systematic review.

Fungal infections caused by Candida albicans and Candida auris represent an increasing clinical challenge, particularly due to biofilm formation and rising antifungal resistance. Antimicrobial photodynamic therapy (aPDT) has emerged as a potential alternative strategy, with phenothiazine-based photosensitizers being among the most extensively investigated compounds. This systematic review aimed to evaluate the application of phenothiazine-mediated aPDT in in vitro studies against C. albicans and C. auris. A comprehensive search was conducted in PubMed, Embase, and Scopus, including studies published within the last 10 years. Forty in vitro studies met the eligibility criteria and were synthesized descriptively due to substantial methodological heterogeneity. Overall, aPDT was associated with reductions in fungal viability, with generally greater effects reported in planktonic models compared with biofilms. Methylene blue was the most frequently investigated photosensitizer, applied across a broad range of concentrations and dosimetric parameters, resulting in variable antifungal responses. Other phenothiazine derivatives, including toluidine blue O, dimethyl methylene blue, new methylene blue, and S137, were also associated with antifungal activity under specific experimental conditions but remain comparatively underexplored. Studies involving C. auris were less frequent and suggested lower susceptibility compared with C. albicans, particularly in biofilm models. Given the substantial variability in experimental protocols, especially regarding photosensitizer concentration, light parameters, and biofilm maturation, the findings should be interpreted with caution and limit direct comparison across studies. These findings support the antifungal potential of phenothiazine-mediated aPDT while emphasizing the need for methodological standardization and expanded investigation of C. auris.

Photochemotherapy↗

PubMed2026

Relationships among mechanisms in psychosocial treatments for chronic pain: mechanism to mechanism lagged effects and relationships with outcomes.

Results suggest that psychosocial treatments for chronic pain work via several mechanisms, and that they often do so to similar degrees and in similar ways. Extant research, however, has focused on individual and/or independent effects of mechanisms on outcomes. Whether successful outcomes are also partly because of sequential and meaningful relationships among and between mechanisms-mechanism-to-mechanism effects-has not been examined. Secondary analyses were conducted of an RCT that compared cognitive therapy, mindfulness-based stress reduction, and behavior therapy to treatment as usual in a sample (N = 521) of people with chronic low back pain. Results of hierarchical linear modeling revealed that (1) Treatment Condition × Mechanism interactions predicting changes in other mechanisms were nonsignificant; (2) lagged prior session mechanism changes predicted next session changes in another mechanism; (3) lagged relationships between pain catastrophizing and pain self-efficacy were reciprocal, whereas links between lagged pain catastrophizing and mindfulness changes and lagged pain catastrophizing changes and behavioral activation changes were unidirectional; and (4) individual differences in the strengths of mechanism-to-mechanism relationships predicted pre- to post-treatment changes in outcomes. Results reveal heretofore hidden therapeutic processes that cognitive therapy, mindfulness-based stress reduction, and behavior therapy may share. Namely, that mechanism-to-mechanism lagged effects do indeed emerge beyond mechanism-to-outcome effects. Findings show not only that mechanisms may change in definable sequences relative to each other but that individual differences in the strengths of mechanism-to-mechanism relationships may themselves be predictive of outcomes.

Humans↗