340880 research outputs found
Sort by
Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes:a systematic review
No full textCumulative evidence suggests neurodevelopmental disorders are closely related. The risk of these disorders is increased by a series of copy number variant syndromes - phenotypically heterogeneous genetic disorders, present in a minority of the population. Recent models suggest that a disruption in the balance between excitatory and inhibitory neural activity may contribute to the aetiology of neurodevelopmental disorders, and may be additionally disturbed in copy number variant syndromes. In this systematic review, the databases PubMed, Embase, and Scopus were searched for studies of excitation/inhibition imbalance in relation to neurodevelopmental disorders in human copy number variant samples. A total of 53 studies were included, representing a variety of copy number variants and research methodologies. The resulting data suggests excitation/inhibition balance is indeed disrupted in different copy number variant populations, providing insight into a putative mechanism of both idiopathic and genetic neurodevelopmental disorders. However, the high level of heterogeneity in the data set, alongside emerging techniques for excitation/inhibition assessment, prompts further investigation of this field
Diagnosis of treatment-related changes in children and adolescents with brain and spinal tumors:a cost-effectiveness analysis using MRI and [18 F]FET PET
No full textPurposePET using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) has considerable clinical value for follow-up evaluation of central nervous system tumors in children and adolescents. As medical procedures must be justified socio-economically, we determined cost-effectiveness of [18F]FET PET for identification of treatment-related changes.MethodsWe analyzed clinical data from two different studies that assessed the value of FET PET to differentiate between brain and spinal tumor relapse and treatment-related changes in children and adolescents. Cost calculation was based on the German statutory health insurance system perspective. Due to subtle differences in the diagnostic approach of the studies, two separate clinical scenarios including 80 patients with 105 lesions were considered: Decision tree model 1 determined cost-effectiveness of simultaneous [18F]FET PET and MRI in comparison to MRI alone to identify treatment-related changes. Decision tree model 2 determined cost-effectiveness of [18F]FET PET alone to identify treatment-related changes when routine MRI findings were suspicious for tumor relapse. Deterministic and probabilistic sensitivity analyses tested the robustness of the results.ResultsModel 1 revealed that the rate of identified treatment-related changes increased by 52% when adding [18F]FET PET to MRI, resulting in costs of <euro>3,314.51 for each additional correctly identified lesion with treatment-related changes by [18F]FET PET that MRI would have misclassified. Model 2 revealed that [18F]FET PET correctly identified treatment-related changes in 90% of lesions when routine MRI findings were suspicious for tumor relapse, resulting in costs of <euro>1,740.37 for each lesion.ConclusionIntegrating [18F]FET PET in the follow-up of in children and adolescents with brain and spinal tumor may help improving patient care at acceptable costs
Advancing Cryo-EM and Cryo-ET through Innovation in Sample Carriers:A Perspective
No full textCryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) have revolutionized structural biology by enabling high-resolution imaging of biomolecules and cellular structures. However, traditional sample carriers, such as copper grids with carbon films, presented limitations, particularly in cryo-ET workflows. Issues like uneven cell distribution, beam-induced motion, and suboptimal vitrification can compromise data quality. Recent advances in sample carrier design have successfully addressed key challenges, including the development of gold-based supports, graphene coatings, and nanofluidic chips. These innovations have improved mechanical stability, enhanced thermal conductivity, and provided better control over ice layer uniformity, leading to more consistent sample preparation and higher-quality imaging. In this perspective, sample preparation advancements, novel approaches such as titanium autogrids and slot grids with continuous gold foils, and their role toward future cryo-ET applications are discussed. These new designs have the potential to simplify workflows and optimize cell growth environments. Furthermore, this perspective highlights how integrating these cutting-edge technologies with prior advancements in sample carrier design can enhance cryo-ET workflows. Combined, they enable cryo-EM imaging of thicker samples and drive progress in structural biology research
Adipose-Derived Stem-Cell-Derived Exosomes Encapsulated Patch for Modulating Inflammation and Promoting Tissue Regeneration
No full textRepairing tissue, especially in chronic wounds, is a major clinical challenge. Traditional treatments often lead to slow recovery and poor biocompatibility. Adipose-derived stem cell exosomes (ADSC-exo) offer a promising solution for tissue regeneration due to their anti-inflammatory and immunomodulatory effects. However, directly injecting stem cells results in a low survival and function loss. This study introduces a Janus G-Avs patch that promotes tissue repair by releasing ADSC-exo and prevents postoperative tissue adhesion. The patch's top layer, created via coaxial electrospinning, acts as an ADSC-exo delivery system with a core-shell structure by incorporating ADSC-exo and hyaluronic acid (HA) into methacrylate gelatin (GelMA) to prolong exosome release. The bottom layer consists of a 4arm-PLGA(4aPLGA)-Glu/PCL electrospun membrane, offering a lubricated antifouling surface that prevents protein adsorption and provides mechanical support. In rat models, the G-Avs patch has demonstrated its ability to enhance cell proliferation, promote angiogenesis, and encourage macrophage polarization toward the M2 phenotype, thereby mitigating inflammatory responses and promoting tissue repair. Transcriptomic analysis indicates that the G-Avs patch augments cellular energy metabolism by upregulating metabolic pathways and downregulating immune-inflammatory pathways, collectively supporting tissue repair. In summary, the Janus G-Avs patch has a strong clinical potential
The effect of biperiden on episodic memory:Testing the serial position effect
No full textBiperiden (BIP), a muscarinic type 1 (M1) receptor antagonist, has been proposed as a pharmacological model for episodic memory impairment in mild cognitive impairment (MCI) and early stages of Alzheimer's disease (AD). Understanding the effects of BIP on memory could also be relevant for the development of M1 agonists to improve memory. In this study, we specifically examined how BIP affected the serial position effect (SPE) in a word learning task. Since MCI and AD show memory deficits for the first words of a list (primacy effect) we predicted a similar effect for BIP. Data from four previous studies were collated in which the effects of BIP or placebo treatment was tested a double-blind randomized design. For testing the SPE effect, we calculated the average of the first 3 words (primacy), the last 3 words (recency) and the middle 10 words. To control for the level of performance in the different studies, z-scores were calculated. Overall, the analyses revealed a clear SPE effect. BIP did not impair the primacy or recency effect but was found to impair the memory for the middle 10 words in the delayed recall test. These findings indicate that blocking the M1 receptor not does impair the primacy or the recency effect in the SPE. Although BIP treatment has an overall impairing effect on episodic memory, it does not model primacy effect deficits in MCI and AD. However, M1 receptors appear to modulate the memory for weakly encoded/stored information suggesting that M1 agonist could improve verbal episodic memory
Digitalization in the Spotlight of Subdisciplines - Part I:Rhythmology
No full textDigitalization has emerged as a pivotal aspect in the field of rhythmology. The use of wearables enables guideline-conform diagnosis of atrial fibrillation, the establishment of a symptom-rhythm correlation, and monitoring of arrhythmia burden. Through utilization of telemonitoring and digital devices, digital sensors, and innovations such as vocal biomarkers, the monitoring of heart failure patients can be optimized. Thus, through early detection and timely intervention, hospitalizations can potentially be prevented. Moreover, the application of artificial intelligence in rhythmology not only has the potential to enhance ECG diagnostics but also to enable early detection or even prediction of relevant diseases. Next to its potential, limitations and challenges of digitalization must be addressed to facilitate integration of these novel tools into daily clinical practice
Accelerated and accurate cervical cancer diagnosis using a novel stacking ensemble method with explainable AI
No full textCervical cancer is a preventable yet life-threatening disease that claims hundreds of thousands of lives each year, particularly in low-resource settings where timely screening is scarce. Current Deep Learning (DL) approaches for automated cervical cytology classification encounter challenges such as class imbalance, computational inefficiency, and inadequate generalizability. This study proposes a novel CerviXEnsemble model that integrates multiple pre-trained DL architectures (Inception-ResNetV2, EfficientNet-B6, ResNet152, Inception-ResNetV2, EfficientNet-B6, DenseNet201, and NASNetMobile) as base learners, along with a dense-layer meta-learner that refines and consolidates predictions for improved robustness. Unlike traditional single-CNN models, our stacking ensemble approach utilizes diverse feature representations to enhance classification stability and generalization across multiple cytology datasets. To validate the model, we experimented with the Herlev and SIPaKMeD benchmark datasets in this study. Techniques like contrast enhancement and data augmentation were employed to optimize feature extraction. The model achieved state-of-the-art performance, attaining an accuracy of 99.38 % and an F1-score of 98.49 % on the Herlev dataset and an accuracy of 98.71 % and an F1-score of 97.53 % on SIPaKMeD. These performances are superior to previous studies in controlling class imbalance and providing stable predictions over different samples. Additionally, Explainable AI (XAI) techniques were incorporated to ensure transparent and interpretable predictions, aiding clinicians in their decision-making processes. An interpratable web application was developed for real-time Pap smear analysis to reduce the diagnostic workload for pathologists by identifying high-risk samples. This solution shows great promise for use in various healthcare settings, maintaining high diagnostic accuracy while requiring minimal computational resources, making it suitable for both urban hospitals and rural clinics
The Assessment of Burden of Chronic Conditions (ABCC-) tool:A valid and reliable tool for hip, knee, hand, wrist, foot and ankle osteoarthritis
No full textObjective: The Assessment of Burden of Chronic Conditions (ABCC-) tool was developed to provide a comprehensive, holistic evaluation of disease burden on physical, emotional and social level in patients with one or more chronic conditions. This study aimed to assess the validity and reliability of the recently developed module for the ABCC-tool for osteoarthritis (OA). Design: A cross-sectional questionnaire-based study was conducted among patients with hip, knee, hand, wrist, foot and ankle OA. Validity was assessed as (1) the convergent validity with three OA-joint-specific questionnaires measuring pain and stiffness amongst others; (2) the discriminant validity with radiographic Kellgren-Lawrence (KL) scores; and (3) known-groups validity (groups: number of affected joints, and the presence/absence of anxiety, depression, kinesiophobia, and pain catastrophizing). Reliability was assessed as the (1) internal consistency; and (2) test-retest with a two-week interval. Results: 409 OA patients were included. For all joints its convergent validity was according to the hypothesis, i.e. r ?= ?0.7 (hip OA r ?= ?-0.73; knee OA r ?= ?-0.75; hand and wrist OA r ?= ?0.74; foot and ankle OA r ?= ?-0.41). As expected according to the hypothesis, no correlation between burden of OA and KL-scores was found for the discriminant validity. The ABCC-tool was able to distinguish all predefined known-groups (all p ?< ?0.05). The ABCC-tool demonstrated good internal consistency across all domains and joints (total scale in all joints =0.87). Test-retest reliability was high (all ICC =0.81). Conclusion: The ABCC-tool is a valid and reliable tool for assessing the multidimensional burden of OA across different joints
Routine Imaging after Resection of Pancreatic Ductal Adenocarcinoma:Nationwide Utilization and Survival Analysis
No full textObjective: To evaluate the utilization of routine imaging and the impact on survival after resection of pancreatic ductal adenocarcinoma (PDAC). Background: Evidence on the benefit of routine imaging after resection of PDAC on early detection and treatment of disease recurrence is currently lacking. The availability of more effective treatment options for PDAC recurrence may have increased the utilization of routine imaging in daily clinical practice. Methods: Patients who underwent resection of PDAC in the Netherlands (2014-2019) were included in this nationwide observational cohort study (NCT04605237). Patients were stratified based on surveillance strategy. Median overall survival (OS) was assessed using Kaplan-Meier survival curves. The association between surveillance strategy and asymptomatic recurrence, recurrence treatment, and OS was assessed using multivariable logistic regression and Cox proportional hazard analysis, respectively. Results: A total of 1311 patients were included, with a median follow-up of 45 (IQR 34-61) months. Routine imaging was used in 139 patients (11%), with a median OS of 43 (IQR 35-not reached) months, compared to 22 (IQR 21-24) months in 1172 patients (89%) with a symptomatic surveillance (P<0.001). Routine imaging was associated with asymptomatic recurrence (OR 3.79 [95% CI 2.27-6.32]; P<0.001), recurrence treatment (OR 2.50 [95% CI 1.21-5.18]; P=0.01) and improved OS (HR 0.56 [95% CI 0.44-0.71]; P<0.001). Conclusion: Routine imaging after resection of PDAC was independently associated with the detection of asymptomatic disease recurrence, recurrence treatment and improved survival, which further advocates towards inclusion of routine imaging after PDAC resection in clinical guidelines.</p
Heart rate variability in patients with cardiovascular diseases
No full textHeart rate variability (HRV) has been reported to predict overall mortality and the risk of cardiovascular disease events in patients, including those with heart failure. However, inconsistent methods of recording and analyzing HRV parameters, along with a lack of randomized data substantiating its clinical efficacy and potential to guide treatment decisions for improved patient outcomes, have limited its use in clinical settings. With the advancements in technologies such as artificial intelligence and machine learning, and emergence of ablation procedures that can alter autonomic function, this article re-explores HRV assessment methods, their potential for clinical application, the issues encountered in using them in clinical research, and potential approaches to studying HRV in the future (Graphical Abstract)