SEARCH · Search PubMed

Results for “Local dynamic stability”

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.

348 records · Page 3Linked to original sources

PubMed2026

Influence of Concave Versus Convex Emergence Profiles on Midfacial Mucosal Stability-A Systematic Review With Meta-Analysis.

OBJECTIVES: To systematically evaluate the influence of concave versus convex emergence profiles on midfacial mucosal stability in partially edentulous patients restored with implant-supported single restorations. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted and registered in PROSPERO (CRD420251139042). An electronic search in MEDLINE (PubMed) and Embase was performed up to May 7, 2026. Eligible studies included RCTs comparing concave (test group) and convex (control group) transmucosal prosthetic designs and reporting midfacial mucosal level changes (mm). Data extraction and risk of bias assessment (RoB 2) were performed independently. A random-effects meta-analysis was conducted using weighted mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic and sensitivity analyses were performed to evaluate the robustness of the findings. RESULTS: Four RCTs including 144 implants with a 12-month follow-up were included. Of these, 128 implants contributed to the quantitative synthesis, with 66 implants allocated to the concave/modified emergence profile group and 62 implants allocated to the convex/non-concave emergence profile group. The pooled analysis demonstrated a mean difference of -0.31 mm (95% CI -0.63 to 0.02; p = 0.064), indicating a trend toward greater midfacial mucosal recession with convex emergence profiles compared with concave designs. Between-study heterogeneity was low to moderate (I2 = 28%), suggesting consistent findings across studies. Sensitivity analyses confirmed the direction of the effect, with pooled estimates ranging from -0.12 to -0.43 mm. Exclusion of one study resulted in a statistically significant difference favoring concave emergence profiles (-0.43 mm; 95% CI -0.70 to -0.16; p = 0.002). CONCLUSIONS: Convex emergence profiles are associated with a tendency toward increased midfacial mucosal recession. Concave profiles are preferable to support peri-implant soft-tissue stability. CLINICAL RELEVANCE: Emergence profile design should be considered an integral component of prosthetic and surgical planning. The use of concave transmucosal contours during provisionalization and definitive restoration may contribute to improved peri-implant soft tissue stability and enhanced esthetic outcomes.

Humans↗

PubMed2026

Optimizing focal vibration therapy for balance and gait: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of focal (localized) vibration therapy (FVT) applied to muscles/tendons on balance, gait, and mobility, with a specific focus on defining optimal vibration protocols (frequency, amplitude, dosing) and muscle-targeting strategies to maximize sensorimotor recovery. METHODS: A systematic review was conducted across six databases (CINHAL, Embase, Medline, Web of Science, Scopus, CENTRAL) from January 2000 to May 2025. Studies were included if they involved human participants, applied FVT therapeutically, and reported balance, gait, or mobility outcomes. Data extraction included study characteristics, intervention protocols, and outcomes. Methodological quality was assessed using the PEDro scale. RESULTS: Sixty-two studies (n = 2090 participants) were included. Methodological quality assessment (PEDro scale) indicated 44% of studies met high-quality standards. Biomechanical analysis identified the quadriceps, gastrocnemius/soleus, and plantar muscles as the most effective vibration sites, given their critical roles in gait propulsion and postural stability. The synthesis of protocol data indicated a promising therapeutic window characterized by a vibration frequency of 80-120 Hz (primarily fixed sinusoidal waveforms at a single frequency) and an amplitude of 0.2-0.5 mm (reported only in 12 studies; amplitude was not reported in 23 studies), applied bilaterally for a minimum of 3 sessions per week over 4-12 weeks, which could lead to improved balance and gait performance with benefits sustained for up to 5 months. CONCLUSION: FVT shows potential to improve gait and balance, particularly when targeting lower-extremity muscles with optimized vibration parameters. To advance the field, future research must prioritize the development of standardized protocols and investigate neurophysiological mechanisms to refine FVT as a precision bioengineering solution for mobility deficits.

Humans↗

PubMed2026

Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

Humans↗

PubMed2026

Modelling the effects of biological intervention in a dynamical gene network.

Cellular response to environmental and internal signals can be modeled by dynamical gene regulatory networks (GRN). In the literature, three main classes of gene network models can be distinguished: (1) non-quantitative (or data-based) models which do not describe the probability distribution of gene expressions; (2) quantitative models which fully describe the probability distribution of all genes co-expression; and (3) mechanistic models which allow for a causal interpretation of gene interactions. We propose two rigorous frameworks to model gene alteration in a dynamical GRN, depending on whether the network model is quantitative or mechanistic. We explain how these models can be used for design of experiment, or, if additional alteration data are available, for validation purposes or to improve the parameter estimation of the original model. We apply these methods to the Gaussian graphical model, which is quantitative but non-mechanistic, and to mechanistic models of Bayesian networks and penalized linear regression.

Gene Regulatory Networks↗

PubMed2026

Discovery of NAT-6-321056 as a novel modulator of VEGFR2 signaling to suppress tumor angiogenesis.

Vascular endothelial growth factor receptor 2 (VEGFR2) is a master regulator of angiogenesis and cancer progression. However, current VEGFR2 modulators face significant challenges, including off-target toxicity and acquired resistance, underscoring the urgent need for novel therapeutic agents with improved efficacy and safety profiles. Here, we reported that virtual screening of 39,442 natural products from the ZINC natural products-derived library, coupled with molecular docking and molecular dynamics (MD) simulations to evaluate the binding stability of candidate compounds, identified NAT-6-321056 as a highly promising modulator of VEGFR2 signaling. Biological evaluations demonstrated that NAT-6-321056 exerted potent inhibition on the growth of a broad spectrum of cancer cells, including both solid tumors and hematological malignancies. In EA.hy 926 endothelial cells and SK-N-DZ neuroblast cells, the compound significantly suppressed proliferation, migration, and invasion. Microscale thermophoresis (MST) confirmed direct binding of NAT-6-321056 to VEGFR2 with favorable affinity. Kinase profiling against a panel of 33 kinases indicated that NAT-6-321056 exhibited a multi-kinase modulation profile. Mechanistic studies revealed that NAT-6-321056 suppressed the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and was associated with reduced VEGFR2 phosphorylation and attenuation of the downstream ERK/JNK/AKT signaling pathways. Moreover, NAT-6-321056 exhibited robust in vivo anti-angiogenic effects in both the chick chorioallantoic membrane (CAM) assay and transgenic zebrafish vascular fluorescence imaging models. Computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction suggested acceptable drug-like properties. Collectively, these findings demonstrated that NAT-6-321056 is a promising modulator of VEGFR2 signaling with potent anti-angiogenic activity and represents a viable candidate for cancer therapy.

Vascular Endothelial Growth Factor Receptor-2↗

PubMed2026

Morbidity and mortality from local anesthetics: localized and systemic toxicity.

PURPOSE OF THE REVIEW: Local anesthetics remain vital to modern medicine, yet their narrow therapeutic window continues to result in complications. This review synthesizes recent literature to define the current landscape of local anesthetic-associated adverse events. RECENT FINDINGS: Perioperative mortality attributable to local anesthetics persists despite sustained safety initiatives and professional society recommendations. Pharmacovigilance and case data identify lidocaine (oropharyngeal, topical, and via local infiltration) as the predominant contributor to adverse outcomes, including death. Local anesthetic systemic toxicity remains an issue, with a recent shift in epidemiology: an increasing proportion of toxic events originates from surgeon- and proceduralist-administered analgesia. Anesthesiologist-controlled methods also cause toxicity via catheter-based delivery and nerve blocks in highly vascular regions. Localized toxicity in the form of high neuraxial contributes to morbidity, with recent reviews reinforcing known risk factors; whereas localized neurotoxicity appears less troublesome when managed appropriately. SUMMARY: The cumulative evidence identifies shifts in the patterns of systemic and localized toxicities. Bupivacaine-based peripheral nerve blocks no longer represent the principal cause of complications because of the advent of ultrasound guidance and lipid emulsion therapy. In contrast, high neuraxial techniques persist as a cause of morbidity, accompanied by intravenous/oropharyngeal lidocaine, proceduralist-administered local infiltration analgesia, and catheter-based delivery.

Humans↗

PubMed2026

Examining early-phase symptom trajectories in interpersonal psychotherapy versus antidepressant medication for adults with depression: A dynamic time warp network analysis.

BACKGROUND: Depression is characterized by substantial symptom heterogeneity, which is often concealed when examining total severity scores. Analyzing symptom-level change can improve our understanding of treatment effects and recovery processes. This study, therefore, examined dynamic symptom networks during early-phase interpersonal psychotherapy (IPT) and selective serotonin reuptake inhibitor (SSRI) antidepressant treatment, assessing patterns of symptom change across as well as differences between treatments. METHODS: Using weekly item-level Hamilton Depression Rating Scale (HAM-D) data from a randomized clinical trial comparing IPT and SSRIs for adults with depression, this preregistered study examined symptom trajectories in the first six weeks of treatment with Dynamic Time Warping (DTW). RESULTS: Depressive symptom trajectories and DTW-based symptom networks were largely similar for IPT and SSRI. In both conditions, changes in somatic symptoms of anxiety and middle insomnia tended to precede improvements in depressed mood. CONCLUSIONS: Early symptom change may occur outside the core affective domain, underscoring the importance of monitoring symptoms broadly. Symptom-level patterns may reflect patients' stage of recovery and provide clinically relevant information beyond total severity scores. The absence of differences in improvement patterns between IPT and SSRI suggest few indications for treatment selection based on baseline symptom profiles. Future research should replicate and extend these findings to subsequent treatment phases using more frequent assessments and a broader range of interventions.

Humans↗

PubMed2026

A Dynamic Nomogram to Predict Metabolic Dysfunction-Associated Fatty Liver Disease in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) involves multiple metabolic disorders. This study aimed to identify high-risk populations for metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with MetS and to establish a dynamic predictive nomogram. METHODS: A total of 627 patients with MetS from six regions in Zhejiang Province were enrolled and categorized into MAFLD and non-MAFLD groups, then randomly assigned to training and validation sets at a ratio of 7:3. Independent predictors of MAFLD were identified using least absolute shrinkage and selection operator regression and multivariable logistic regression analyses. These predictors were then used to construct a dynamic nomogram. RESULTS: A total of 627 patients with MetS were included in the final analysis, of whom 77.0% (483/627) were diagnosed with MAFLD. Multivariable logistic regression analysis identified body mass index (BMI), waist circumference (WC), total cholesterol (TC), alanine aminotransferase (ALT), MetS-defined dysglycemia, and education level as independent risk factors for MAFLD. MetS-defined dysglycemia showed the highest odds ratio (OR) for MAFLD development [OR = 1.87, 95% confidence interval (CI): 1.07-3.29]. Although the number of MetS components and the metabolic syndrome score were significantly associated with MAFLD in univariate analysis, they were not independently associated with MAFLD in the multivariate model. A dynamic nomogram for predicting MAFLD risk in patients with MetS was developed and internally validated. The area under the receiver operating characteristic curve was 0.834 (95% CI: 0.787-0.880) in the training set and 0.839 (95% CI: 0.771-0.899) in the validation set, indicating strong predictive performance. Bootstrap internal validation demonstrated good agreement between predicted and observed outcomes in calibration curves. Decision curve analysis further indicated favorable clinical applicability of the nomogram. CONCLUSION: BMI, WC, TC, ALT, MetS-defined dysglycemia, and education level are independent risk factors for MAFLD. A dynamic nomogram for predicting MAFLD risk in patients with MetS was successfully developed and validated.

Humans↗

PubMed2026

The future of TCR-Treg therapies is renewables.

Cell therapy has longstanding roots in haematopoietic stem cell transplantation and early immune cell transfers in infectious disease and transplantation, where patient- or donor-derived cells have achieved therapeutic benefit in selected contexts. The modern era has been driven largely by oncology, with engineered modalities such as tumour-infiltrating lymphocytes, CAR-T cells and TCR-engineered T cells delivering transformative responses but requiring complex, costly manufacturing. These platforms are now being adapted for autoimmune diseases to induce durable, antigen-specific immune tolerance, yet broad application is limited by safety concerns, process complexity and access. Non-engineered cell therapies for autoimmunity, including mesenchymal stem cells, polyclonal regulatory T cells and tolerogenic dendritic cells, have shown acceptable safety and proof-of-principle for immune re-education, but clinical responses have been modest and inconsistent, with limited scalability. Engineered approaches such as CAR-T cells can induce reversible B cell depletion in B cell-mediated rheumatic diseases but only addresses antibody-driven pathology and not T cell-mediated autoimmunity. TCR-engineered Tregs have emerged as a promising antigen-specific strategy, offering localized, antigen-linked suppression with bystander tolerance. Preclinical and early clinical data suggest superior potency, stability and disease control compared with polyclonal Tregs at similar or lower doses, but translation is constrained by the rarity and fragility of Tregs and by labour-intensive, CAR-T-like manufacturing. This review highlights emerging solutions for closed, automated and decentralised production, and discusses allogeneic approaches using gene-edited or banked Tregs with HLA engineering or matching. Together, these advances support the development of scalable, "off-the-shelf" TCR-Treg products with potential to provide safe, affordable tolerance-restoring therapies for autoimmune disease.

Humans↗

PubMed2026

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7 days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals↗

PubMed2026

Retinoid dynamics in immune cells during age-related diseases.

Retinoids comprise vitamin A and its structurally related natural and synthetic derivatives. Retinoid dynamics involves multiple retinoid forms, carrier proteins, and enzymes that orchestrate the absorption, transport, storage and biotransformation of dietary vitamin A. Beyond their canonical metabolic functions, metabolites and proteins involved in retinoid metabolism also play distinct roles in signal transduction and transcriptome reprogramming, broadening the mechanisms that influence immune cell fate decisions. Age‑related changes in retinoid bioavailability and signaling intensity alter immune cell polarization and function, thereby contributing to the pathogenesis of chronic inflammation in neurodegenerative diseases, cardiovascular diseases, osteoarthritis, and other age-related diseases. In this review, we focus on age-related alterations in the retinoid metabolic pathway and their impact on inflammation and the progression of age-related diseases. This review highlights the pivotal role of retinoid metabolism in anti-ageing interventions and considers future directions and challenges in this field.

Humans↗

PubMed2026

Utility of Dynamic MRI in Surgical Outcome of Patients With Degenerative Cervical Myelopathy: A Single-Center, Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: The utility of dynamic MRI (dMRI) in surgical planning and outcomes for degenerative cervical myelopathy (DCM) has not been validated in any prospective randomized trials. METHODS: In this hospital-based randomized controlled trial conducted between February 2023 and December 2024, patients with DCM were randomized into 2 groups: the Static MRI Group, where surgery was guided by conventional static MRI alone, and the dMRI Group, in which dMRI was performed, with the potential to alter the surgical approach. The primary outcome was recovery rate (RR) at 3 months. Secondary outcomes included postoperative changes in modified Japanese Orthopaedic Association scores and Nurick grades, surgical plan alterations, comparison of surgical approaches, and complication rates. RESULTS: Seventy-four patients were analyzed at a 3-month follow-up. The dMRI group had a significantly higher mean RR (55.42% ± 29.05%) than the Static group (46.76% ± 29.51%) ( P = .044). A RR of ≥50% was observed in 91.9% of patients in the dMRI group, compared with 59.4% in the static MRI group ( P = .002). Modified Japanese Orthopaedic Association scores improved more in the dMRI group (15.47 ± 2.62 vs 13.77 ± 2.66, P = .007). While Nurick grades improved in both groups, the intergroup difference was not statistically significant ( P = .151). dMRI altered the surgical plan in 59.5% of cases. Anterior approaches yielded better RR but had more complications. By contrast, posterior approaches had fewer but more severe complications including mortality. CONCLUSION: dMRI enhances the detection of clinically significant cord compression and may aid in surgical decision-making, potentially contributing to superior functional outcomes in DCM. Further studies are required to determine its impact on long-term functional outcomes.

Humans↗

PubMed2026

Dynamic lysine acetylation and succinylation of platelet proteins regulates platelet storage lesion: mechanistic insights from multi-omics.

OBJECTIVES: Platelet storage lesion (PSL) severely impairs platelet function during storage, presenting a major hurdle in transfusion medicine; however, the dynamic interplay between global proteomic changes and post-translational modifications (PTMs) underlying these functional deteriorations remains insufficiently characterized. Here, we report the first comprehensive multi-omics analysis integrating global proteomics, acetylomics, and succinylomics to dissect the molecular dynamics during platelet storage. METHODS: We performed quantification of global proteomics, acetylome and succinylome based on TMT-labeled LC-MS/MS analysis, combined with antibody-affinity enrichment and purification. Dynamic molecular changes and functional transformation of platelet were also characterized under proper conditions stored for 1, 3, 5, 7 days, respectively. RESULTS: We systematically characterized 3,609 proteins, 1,308 acetylation sites, and 1,947 succinylation sites across multiple storage time points (D1, D3, D5, D7). We distinct temporal patterns of post-translational modifications, with succinylation showing more extensive coverage than acetylation in platelets. Pathway enrichment analysis revealed extensive metabolic reprogramming involving complement activation, energy metabolism, and cellular detoxification processes. The identification of specific motif patterns provided mechanistic insights into the functional specificity of these modifications. Random forest machine learning identified 20 core regulatory proteins representing critical nodes in PSL development. Furthermore, we employed real - time quantitative polymerase chain reaction (RT - QPCR) to measure the expression levels of key genes related to platelet function and PTM - associated pathways. CONCLUSION: By mapping the interplay between proteomic abundance shifts and PTM dynamics, this study provides a multidimensional understanding of PSL, establishing a foundational framework for optimizing storage protocols and enhancing transfusion safety.

Blood Platelets↗

PubMed2026

Dynamics of antibiotic resistance genes co-occurrence with pathogenic and non-pathogenic bacteria throughout wastewater treatment processes.

Wastewater treatment plants (WWTPs) are recognized hotspots for antibiotic resistance genes (ARGs) and pathogenic bacteria. Despite advancements in treatment technologies, the persistence of ARGs and pathogenic bacteria remains a concern. In this study, we analyzed the dynamic changes in ARGs and bacterial communities throughout the treatment processes within an anaerobic-anoxic-oxic (AAO) WWTP over one week by using HT-qPCR coupled with 16S rRNA gene amplicon sequencing. The connectedness index, based on network analysis, showed that the dynamics of ARGs and mobile genetic elements (MGEs) were more strongly associated with potentially pathogenic bacteria than with non-pathogenic bacteria, suggesting that ARG immigration and dissemination in the WWTP were likely driven by potentially pathogenic taxa. The AAO treatment significantly reduced ARGs in final effluent (EF) (∼64 %) and residual sludge (RS) (∼81 %); however, potential hosts of ARGs such as Comamonas testosteroni and Clostridioides difficile persisted with minimal changes in relative abundance and remained detectable in EF and RS. Notably, the abundance of ARGs was lower in RS than in EF, and source tracking analysis identified influent as the primary source of ARGs and potentially pathogenic taxa in EF, underscoring the greater health risks associated with effluent discharge.

Wastewater↗

PubMed2026

Integrated widely targeted metabolomics and GC-IMS reveal dynamic flavor, nutritional, functional, and metabolic profiles in macadamia kernels during processing.

Different processing stages influence the color, flavor, and antioxidant activities of macadamia kernels. However, the biochemical mechanisms that occur during processing are not well known. This study integrated widely targeted metabolomics (UPLC-MS/MS) with GC-IMS to systematically characterize non-volatile and volatile compounds in macadamia kernels across key three sample groups: fresh kernels (FMN), low-temperature-dried kernels (DMN), and roasted kernels (BMN). A total of 622 non-volatile metabolites and 52 volatile compounds were identified. Low-temperature drying promoted the accumulation of phenolic acids and flavonoids, enhancing antioxidant capacity. Roasting degraded heat-sensitive nutrients but generated flavor compounds via Maillard reaction and lipid oxidation, shifting aroma from green to nutty notes. Nutritional assessment confirmed that roasting significantly reduced antioxidant activities and bile acid binding capacity. Pearson correlation analysis verified the key metabolite-antioxidant relationships. These findings provide critical insights into metabolic dynamics during nut processing and establish a scientific basis for optimizing thermal processing strategies.

Metabolomics↗

PubMed2026

The effect of hip abductor or external rotator strength on dynamic knee valgus in healthy subjects-a systematic review with partial meta-analysis.

BACKGROUND: Weak hip abductors and external rotators (ER) have long been suggested to cause increased dynamic knee valgus. Patients are often prescribed strengthening of these muscles with the expectation that it will reduce their risk of pain and injury. The validity of this claim remains unclear. METHOD: We conducted a systematic review and partial meta-analysis assessing the association between hip strength and knee valgus in healthy subjects. An online search was conducted in May 2026. Databases included Medline, EMBASE, CINAHL and Google Scholar. INCLUSION CRITERIA: English language, asymptomatic subjects, dynamometric hip strength, single or multi-camera kinematic analysis, and statistical tests of difference or correlations between hip abductor or ER strength and dynamic valgus. Data were extracted concerning study design, subject characteristics, relevant outcome measures and statistics. RESULTS: 22 papers qualified for inclusion. Hip abductor correlations: 12 papers found no significant correlation, 2 supported the hypothesis and 2 found evidence contrary. Hip ER correlations: 8 papers found no significant correlation, 2 supported the hypothesis and 2 were contrary. Group differences for hip abduction strength: 3 papers found no difference, 2 found significant differences in support of the hypothesis, 1 found significant difference to contrary. Group differences for ER strength: 1 paper found no significant difference. None of the partial meta-analyses achieved statistical significance. CONCLUSION: Weakness in hip abductors or external rotators may not result in increased dynamic knee valgus in healthy subjects. While continued research may further illuminate our understanding, we discuss alternative explanations.

Humans↗

PubMed2026

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p < 0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p < 0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans↗

PubMed2026

Reinforcement learning-based dynamic ensemble for missense variant effect prediction and tiered prioritization of VUS.

BACKGROUND: Accurate classification of missense variants remains a challenging task despite major advances in genomics. Numerous computational models have been developed to assist in variant classification, but often require repeated integration and benchmarking efforts. Ensemble methods have been proposed to overcome the limitations of single predictors, but mostly rely on fixed, predefined weights that constrain their ability to capture interactions among predictive signals. METHODS: We present GenixRL, a dynamic ensemble framework that reformulates model fusion as a reinforcement learning optimization problem. GenixRL uses a Q-learning agent to learn a policy that dynamically weights the probabilistic outputs of complementary predictors, including BayesDel (addAF and noAF), ClinPred, and MetaRNN. Replacing static weighting with policy learning allows GenixRL to adaptively identify optimal weightings and substantially improve classification accuracy. RESULTS: In benchmark evaluation against 25 state-of-the-art predictors, GenixRL achieved an AUROC of 0.9644 on an independent ClinVar dataset. On saturation genome editing assays for BRCA1 and BRCA2, GenixRL achieved the best performance and ranked highest on 14 of 17 clinically significant genes in a zero-shot evaluation. Applied to uncertain and conflicting ClinVar variants, GenixRL enabled tiered, evidence-based prioritization of hundreds of thousands of variants as likely pathogenic or pathogenic with high confidence, supported by orthogonal population evidence from gnomAD. CONCLUSION: GenixRL advances pathogenicity prediction for missense variants and provides an adaptive ensemble that sorts variants of uncertain significance into tiered candidates for expert curation and functional validation.

Mutation, Missense↗