The Beneluxa Initiative domain task force health technology assessment: a comparison of member countries' past health technology assessments.

OBJECTIVE: This study aimed to compare assessments between Beneluxa Initiative member countries' assessments and identify alignments and divergences. METHODS: A retrospective comparative analysis was performed that investigated (i) number and type of assessed indications (for Austria (AT), Belgium (BE), Ireland (IE), and the Netherlands (NL)); (ii) added benefit conclusions (for BE, IE, and NL); and (iii) the main arguments underlying differences in conclusions (for BE, IE, and NL). Data were retrieved directly from agency representatives and from public HTA reports. European Medicines Agency approved indications were included for drugs assessed between 2016 and 2020, excluding veterinary drugs, generics, and biosimilars. RESULTS: Only 44 (10 percent) of the 444 included indications were assessed by all four member countries. Between any pair of two countries, the overlap was higher, from 63 (AT-NL) to 188 (BE-IE). Added benefit conclusions matched exactly in 62-74 percent of the indications, depending on the countries compared. In the remaining cases, most often a difference of one added benefit level was observed (e.g., higher vs. equal relative effect). Contradictory outcomes were very rare: only three cases were observed (lower vs. higher effect). When assessing the underlying arguments for seven cases with different outcomes, differences were attributable to slight differences in weighing of evidence and uncertainties rather than disagreement on aspects within the assessment itself. CONCLUSIONS: Despite high variability in European HTA procedures, collaboration on HTA between the Beneluxa Initiative member countries is very feasible and would likely not result in added benefit conclusions that would be very different from added benefit conclusions in national procedures.

Growth period QTL-allele constitution of global soybeans and its differential evolution changes in geographic adaptation versus maturity group extension.

Soybean (Glycine max (L.) Merr.) has been disseminated globally as a photoperiod/temperature-sensitive crop with extremely diverse days to flowering (DTF) and days to maturity (DTM) values. A population with 371 global varieties covering 13 geographic regions and 13 maturity groups (MGs) was analyzed for its DTF and DTM QTL-allele constitution using restricted two-stage multi-locus genome-wide association study (RTM-GWAS). Genotypes with 20 701 genome-wide SNPLDBs (single-nucleotide polymorphism linkage disequilibrium blocks) containing 55 404 haplotypes were observed, and 52 DTF QTLs and 59 DTM QTLs (including 29 and 21 new ones) with 241 and 246 alleles (two to 13 per locus) were detected, explaining 84.8% and 74.4% of the phenotypic variance, respectively. The QTL-allele matrix characterized with all QTL-allele information of each variety in the global population was established and subsequently separated into geographic and MG set submatrices. Direct comparisons among them revealed that the genetic adaptation from the origin to geographic subpopulations was characterized by new allele/new locus emergence (mutation) but little allele exclusion (selection), while that from the primary MG set to emerged early and late MG sets was characterized by allele exclusion without allele emergence. The evolutionary changes involved mainly 72 DTF and 71 DTM alleles on 28 respective loci, 10-12 loci each with three to six alleles being most active. Further recombination potential for faster maturation (12-21 days) or slower maturation (14-56 days) supported allele convergence (recombination) as a constant genetic factor in addition to migration (inheritance). From the QTLs, 44 DTF and 36 DTM candidate genes were annotated and grouped respectively into nine biological processes, indicating multi-functional DTF/DTM genes are involved in a complex gene network. In summary, we identified QTL-alleles relatively thoroughly using RTM-GWAS for direct matrix comparisons and subsequent analysis.

Health-related quality of life (HRQoL), anxiety, and depression in patients with desmoid type fibromatosis.

INTRODUCTION: Data on the impact of desmoid type fibromatosis (DTF) on emotional distress and health-related quality of life (HRQoL) is sparse. METHODOLOGY: In this prospective cross-sectional study, patients with DTF and healthy controls were asked to fill the EORTC QLQ-C30, GAD-7, and PHQ-9 questionnaires. The objectives were to determine HRQoL, anxiety, and depression in patients with DTF. RESULTS: Two hundred four subjects (102 DTF patients and 102 healthy controls) were recruited. The median age of DTF patients at recruitment into the study was 31 years (IQR, 25-37 years). There was a female preponderance with a male:female ratio of 1:1.83. Appendicular skeleton and abdomen sites were most commonly involved in 59% and 22.5% respectively. About half (54%) of patients were currently on sorafenib and 41% were under active surveillance. The mean global health status in DTF patients was 65.58 ± 22.64, significantly lower than healthy controls. Similarly, DTF patients scored low on all functional scales except cognitive functioning. The symptom scale showed a significantly higher symptom burden of fatigue, pain, insomnia, and financial difficulties. Anxiety and depression was observed in 39.22% and 50% of DTF patients respectively. DTF patients had higher rates of mild, moderate, and severe anxiety and depression compared to healthy controls. CONCLUSION: DTF patients have significant symptom burden, poor functioning, and heightened anxiety and depression as compared to healthy controls. HRQoL, anxiety, and depression should be routinely used to assess symptom burden and treatment efficacy in DTF patients.

Improving EEG-Based Driver Distraction Classification Using Brain Connectivity Estimators.

This paper discusses a novel approach to an EEG (electroencephalogram)-based driver distraction classification by using brain connectivity estimators as features. Ten healthy volunteers with more than one year of driving experience and an average age of 24.3 participated in a virtual reality environment with two conditions, a simple math problem-solving task and a lane-keeping task to mimic the distracted driving task and a non-distracted driving task, respectively. Independent component analysis (ICA) was conducted on the selected epochs of six selected components relevant to the frontal, central, parietal, occipital, left motor, and right motor areas. Granger-Geweke causality (GGC), directed transfer function (DTF), partial directed coherence (PDC), and generalized partial directed coherence (GPDC) brain connectivity estimators were used to calculate the connectivity matrixes. These connectivity matrixes were used as features to train the support vector machine (SVM) with the radial basis function (RBF) and classify the distracted and non-distracted driving tasks. GGC, DTF, PDC, and GPDC connectivity estimators yielded the classification accuracies of 82.27%, 70.02%, 86.19%, and 80.95%, respectively. Further analysis of the PDC connectivity estimator was conducted to determine the best window to differentiate between the distracted and non-distracted driving tasks. This study suggests that the PDC connectivity estimator can yield better classification accuracy for driver distractions.

Task-Oriented Evaluation of the Feasible Kinematic Directional Capabilities for Robot Machining.

Performing the machining of complex surfaces can be a challenging task for a robot, especially in terms of collaborative robotics, where the available motion capabilities are greatly reduced in comparison with conventional industrial robot arms. It is necessary to evaluate these capabilities prior to task execution, for which we need efficient algorithms, especially in the case of flexible robot applications. To provide accurate and physically consistent information about the maximum kinematic capabilities while considering the requirements of the task, an approach called the Decomposed Twist Feasibility (DTF) method is proposed in this study. The evaluation of the maximum feasible end-effector velocity is based on the idea of decomposition into the linear and angular motion capabilities, considering a typical robot machining task with synchronous linear and angular motion. The proposed DTF method is presented by the well-known manipulability polytope concept. Unlike the existing methods that estimate the kinematic performance capabilities in arbitrarily weighted twist space, or separately in the translation and the rotation subspace, our approach offers an accurate and simple solution for the determination of the total kinematic performance capabilities, which is often highly required, especially in the case of robot machining tasks. The numerical results obtained in this study show the effectiveness of the proposed approach. Moreover, the proposed DTF method could represent suitable kinematic performance criteria for the optimal placement of predefined tasks within the robot workspace.

Effective Connectivity for Decoding Electroencephalographic Motor Imagery Using a Probabilistic Neural Network.

Motor imagery (MI)-based brain-computer interfaces have gained much attention in the last few years. They provide the ability to control external devices, such as prosthetic arms and wheelchairs, by using brain activities. Several researchers have reported the inter-communication of multiple brain regions during motor tasks, thus making it difficult to isolate one or two brain regions in which motor activities take place. Therefore, a deeper understanding of the brain's neural patterns is important for BCI in order to provide more useful and insightful features. Thus, brain connectivity provides a promising approach to solving the stated shortcomings by considering inter-channel/region relationships during motor imagination. This study used effective connectivity in the brain in terms of the partial directed coherence (PDC) and directed transfer function (DTF) as intensively unconventional feature sets for motor imagery (MI) classification. MANOVA-based analysis was performed to identify statistically significant connectivity pairs. Furthermore, the study sought to predict MI patterns by using four classification algorithms-an SVM, KNN, decision tree, and probabilistic neural network. The study provides a comparative analysis of all of the classification methods using two-class MI data extracted from the PhysioNet EEG database. The proposed techniques based on a probabilistic neural network (PNN) as a classifier and PDC as a feature set outperformed the other classification and feature extraction techniques with a superior classification accuracy and a lower error rate. The research findings indicate that when the PDC was used as a feature set, the PNN attained the greatest overall average accuracy of 98.65%, whereas the same classifier was used to attain the greatest accuracy of 82.81% with the DTF. This study validates the activation of multiple brain regions during a motor task by achieving better classification outcomes through brain connectivity as compared to conventional features. Since the PDC outperformed the DTF as a feature set with its superior classification accuracy and low error rate, it has great potential for application in MI-based brain-computer interfaces.

Depressive rumination and the emotional control circuit: An EEG localization and effective connectivity study.

Ruminations are repetitive thoughts associated with symptoms, causes, and consequences of one's negative feelings. The objective of this study was to explore the neuronal basis of depressive rumination in a non-clinical population within the context of emotional control. Participants scoring high or low on the tendency to ruminate scale took part in the EEG experiment. Their EEG data were collected during a state of induced depressive ruminations and compared with positive and neutral conditions. We hypothesized that both groups would differ according to the level of activation and effective connectivity among the structures involved in the emotional control circuit. Clustering of independent components, together with effective connectivity (Directed Transfer Function), was performed using the EEG signal. The main findings involved decreased activation of the left dorsolateral prefrontal cortex (DLPFC) and increased activation of the left temporal lobe structures in the highly ruminating group. The latter result was most pronounced during the ruminative condition. Decreased information from the left DLPFC to the left temporal lobe structures was also found, leading to the conclusion that hypoactivation of the left DLPFC and its inability to modulate the activation of the left temporal lobe structures is crucial for the ruminative tendencies.

Network Analysis of Functional Brain Connectivity Driven by Gamma-Band Auditory Steady-State Response in Auditory Hallucinations.

The auditory steady-state response (ASSR) may reflect activity from different regions of the brain. Particularly, it was reported that the gamma-band ASSR plays an important role in working memory, speech understanding, and recognition. Traditionally, the ASSR has been determined by power spectral density analysis, which cannot detect the exact overall distributed properties of the ASSR. Functional network analysis has recently been applied in electroencephalography studies. Previous studies on resting or working state found a small-world organization of the brain network. Some researchers have studied dysfunctional networks caused by diseases. The present study investigates the brain connection networks of schizophrenia patients with auditory hallucinations during an ASSR task. A directed transfer function is utilized to estimate the brain connectivity patterns. Moreover, the structures of brain networks are analyzed by converting the connectivity matrices into graphs. It is found that for normal subjects, network connections are mainly distributed at the central and frontal-temporal regions. This indicates that the central regions act as transmission hubs of information under ASSR stimulation. For patients, network connections seem unordered. The finding that the path length was larger in patients compared to that in normal subjects under most thresholds provides insight into the structures of connectivity patterns. The results suggest that there are more synchronous oscillations that cover a long distance on the cortex but a less efficient network for patients with auditory hallucinations.

Feedstock and pyrolysis temperature influence biochar properties and its interactions with soil substances: Insights from a DFT calculation.

The use of biochar for soil improvement and emission reduction has been widely recognized for its excellent performance. However, the choice of feedstock and pyrolysis temperature for biochar production significantly affects its surface parameters and interactions with soil substances. In this study, we retrieved 465 peer-reviewed papers on the application of biochar in reducing greenhouse gas emissions and nutrient losses in soil and analyzed the changes in biochar physicochemical parameters from different feedstock and pyrolytic temperatures. Molecular simulation computing technology was also used to explore the impacts of these changes on the interaction between biochar and soil substances. The statistical results from the peer-reviewed papers indicated that biochar derived from wood-based feedstock exhibits superior physical characteristics, such as increased porosity and specific surface area. Conversely, biochar derived from straw-based feedstock was found to contain excellent element content, such as O, N, and H, and biochar derived from straw and produced at low pyrolysis temperatures contains a significant number of functional groups that enhance the charge transfer potential and adsorption stability by increasing surface charge density, charge distribution and bonding orbitals. However, it should be noted that this enhancement may also activate certain recalcitrant C compounds and promote biochar decomposition. Taken together, these results have significant implications for biochar practitioners when selecting suitable feedstock and pyrolysis temperatures based on agricultural needs and increasing their understanding of the interaction mechanism between biochar and soil substances.

Neuromuscular choristoma and circumferential nerve territory desmoid-type fibromatosis: imaging findings supporting a nerve-driven mechanism.

OBJECTIVE: Neuromuscular choristoma (NMC) is a rare developmental malformation of peripheral nerve that is frequently associated with the development of a desmoid-type fibromatosis (DTF). Both NMC and NMC-DTF typically contain pathogenic CTNNB1 mutations and NMC-DTF develop only within the NMC-affected nerve territory. The authors aimed to determine if there is a nerve-driven mechanism involved in the formation of NMC-DTF from the underlying NMC-affected nerve. METHODS: Retrospective review was performed for patients evaluated in the authors' institution with a diagnosis of NMC-DTF in the sciatic nerve (or lumbosacral plexus). MRI and FDG PET/CT studies were reviewed to determine the specific relationship and configuration of NMC and DTF lesions along the sciatic nerve. RESULTS: Ten patients were identified with sciatic nerve NMC and NMC-DTF involving the lumbosacral plexus, sciatic nerve, or sciatic nerve branches. All primary NMC-DTF lesions were located in the sciatic nerve territory. Eight cases of NMC-DTF demonstrated circumferential encasement of the sciatic nerve, and one abutted the sciatic nerve. One patient had a primary DTF remote from the sciatic nerve, but subsequently developed multifocal DTF within the NMC nerve territory, including 2 satellite DTFs that circumferentially encased the parent nerve. Five patients had a total of 8 satellite DTFs, 4 of which abutted the parent nerve and 3 that circumferentially involved the parent nerve. CONCLUSIONS: Based on clinical and radiological data, a novel mechanism of NMC-DTF development from soft tissues innervated by NMC-affected nerve segments is proposed, reflecting their shared molecular genetic alteration. The authors believe the DTF develops outward from the NMC in a radial fashion or it arises in the NMC and wraps around it as it grows. In either scenario, NMC-DTF develops directly from the nerve, likely arising from (myo)fibroblasts within the stromal microenvironment of the NMC and grows outward into the surrounding soft tissues. Clinical implications for patient diagnosis and treatment are presented based on the proposed pathogenetic mechanism.

Reaction Mechanism and Performance of Innovative 2D Germanane-Silicane Alloys: SixGe1- xH Electrodes in Lithium-Ion Batteries.

The adjustable structures and remarkable physicochemical properties of 2D monoelemental materials, such as silicene and germanene, have attracted significant attention in recent years. They can be transformed into silicane (SiH) and germanane (GeH) through covalent functionalization via hydrogen atom termination. However, synthesizing these materials with a scalable and low-cost fabrication process to achieve high-quality 2D SiH and GeH poses challenges. Herein, groundbreaking 2D SiH and GeH materials with varying compositions, specifically Si0.25Ge0.75H, Si0.50Ge0.50H, and Si0.75Ge0.25H, are prepared through a simple and efficient chemical exfoliation of their Zintl phases. These 2D materials offer significant advantages, including their large surface area, high mechanical flexibility, rapid electron mobility, and defect-rich loose-layered structures. Among these compositions, the Si0.50Ge0.50H electrode demonstrates the highest discharge capacity, reaching up to 1059 mAh g-1 after 60 cycles at a current density of 75 mA g-1. A comprehensive ex-situ electrochemical analysis is conducted to investigate the reaction mechanisms of lithiation/delithiation in Si0.50Ge0.50H. Subsequently, an initial assessment of the c-Li15(SixGe1- x)4 phase after lithiation and the a-Si0.50Ge0.50 phase after delithiation is presented. Hence, this study contributes crucial insights into the (de)lithiation reaction mechanisms within germanane-silicane alloys. Such understanding is pivotal for mastering promising materials that amalgamate the finest properties of silicon and germanium.

Current management of familial adenomatous polyposis.

INTRODUCTION: APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers. AREAS COVERED: The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices. EXPERT OPINION: FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals.

Unrecognized neuromuscular choristoma with recurrent desmoid-type fibromatosis and Marjolin ulcer: expanding the spectrum of neuromuscular choristoma sequelae within the nerve territory? Illustrative case.

BACKGROUND: Neuromuscular choristoma (NMC) is a rare congenital lesion in which muscle tissue is admixed with nerve fascicles within a peripheral nerve. Patients commonly present in early childhood with neuropathy, plexopathy, or chronic undergrowth in the distribution of the affected nerve. OBSERVATIONS: The authors present the case of a 35-year-old man with unrecognized neuromuscular NMC of the sciatic nerve, which resulted in recurrent, multicentric NMC-associated desmoid-type fibromatosis (NMC-DTF) within the nerve territory in association with a Marjolin ulcer, a cutaneous malignancy. LESSONS: Based on anatomical and pathophysiological findings described in this case report, the authors support the association between NMC-DTF and Marjolin ulcer.

Efficacy and tolerability of sorafenib in desmoid-type fibromatosis: A need to review dose.

BACKGROUND: Sorafenib is currently one of the recommended treatments for symptomatic patients with desmoid-type fibromatosis (DTF). In this study, we aim to assess the clinical efficacy and tolerability of sorafenib in DTF patients. METHODOLOGY: Patients aged>18 years with a histological diagnosis of DTF and who have received sorafenib were enroled in this prospective observational study. Demographic data, clinical profile, the initial dose of sorafenib, treatment-related toxicities, dose modifications, and responses were recorded. The primary objective was to assess the objective response rate (ORR). The secondary objectives were to evaluate progression-free survival (PFS), tolerability, and adverse effects of sorafenib. Response assessment was based on response evaluation criteria in solid tumours 1.1 criteria. Adverse effects were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 criteria. Time to event was calculated by Kaplan-Meier analysis, and survival was compared by log-rank test. Univariate and multivariable cox regression analysis were used to find independent predictors of relapse. RESULTS: A total of 104 patients were enroled in the study. The median age of the study population was 32 (range, 18-81) years, and 66.35% of patients were females. On response assessment, ORR was 46.1% and stable disease was observed in 31.7% patients. ORR was higher in the appendicular site (51.7%) compared to the abdominal site (27.2%). PFS at 1 and 2 years was 86.6% (79.6-92.7%) and 73.7% (62.4-82.8%), respectively. Two-thirds (66.6%) of patients had already received some form of treatment. At the time of analysis, 70 (67.3%) patients were continuing sorafenib. Only 4.8% stopped sorafenib due to progression, 10.5% due to intolerable adverse effects, and 17.3% due to other reasons. The common treatment-related toxicities were hand-foot skin reaction (HFSR) (89.4%), fatigue (79.8%), alopecia (70.1%), and diarrhoea (48.0%). In the patients with a starting dose of ≥400 mg (48.0% of patients), discontinuation was necessitated in 12% of patients, and further dose reduction was required in 58%, while only about 13% required dose reduction or discontinuation at a starting dose of 200 mg (51.9% of patients). Responses were not compromised due to lower starting doses. CONCLUSIONS: Sorafenib has good activity in DTF, but it is associated with significant toxicity. The adverse effect profile is distinct in Indian patients with higher HFSR and alopecia. Due to the high rate of dose reduction/discontinuation with a starting dose of 400 mg, a starting dose of 200 mg may be recommended in Indian patients.

Monitoring the Awake and Anesthetized Unconscious States Using Bispectral Index and Electroencephalographic Connectivity Measures.

Objective. Our objective was to compare three electroencephalography (EEG)-based methods with anesthesiologist clinical judgment of the awake and anesthetized unconscious states. Methods. EEG recorded from 25 channels and from four channel bilateral Bispectral index (BIS) electrodes were collected from 20 patients undergoing surgery with general anesthesia. To measure connectivity we applied Directed Transfer Function (DTF) in eight channels of the EEG, and extracted data from BIS over the same time segments. Shannon's entropy was applied to assess the complexity of the EEG signal. Discriminant analysis was used to evaluate the data in relation to clinical judgment. Results. Assessing anesthetic state relative clinical judgment, the bilateral BIS gave the highest accuracy (ACC) (95.4%) and lowest false positive discovery rate (FDR) (0.5%) . Equivalent DTF gave 94.5% for ACC and 2.6% for FDR. Combining all methods gave ACC = 94.9% and FDR = 1%. Generally, entropy scored lower on ACC and higher on FDR than the other methods (ACC 90.87% and FDR 4.6%). BIS showed at least a one minute delay in 18 of the 20 patients. Conclusions. Our results show that BIS and DTF both have a high ACC and low FDR. Because of time delays in BIS values, we recommend combining the two methods.

Remarkable Structural Modifications of Tialite Solid Solutions Obtained by Different Methods.

The structural changes occurring in tialite due to the formation of magnesium-titanate-aluminum-titanate solid solutions were determined. For this purpose, a DFT simulation of the structural changes was performed. The simulation proposed a number of possible atomic substitutions occurring in the elementary cells of the tialite, along with calculations of the lattice parameter changes in this material. Next, the actual changes occurring in the structure of the tialite due to the formation of solid solutions, obtained in different ways, were investigated. After comparing the obtained results, it was possible to confirm the mechanism of the formation of tialite solid solutions, through which one magnesium atom and one titanium atom substituted two aluminum atoms simultaneously. The results of this experimental work were confirmed by theoretical calculations (the differences in the values of the lattice parameters, measured in the experiment and calculated in the simulation, were less than 0.5%), through which changes in the lattice parameters with Mg and Ti substitution were observed.

Investigation of the combustion process of fish scales from Northeast Brazil in a drop tube furnace (DTF).

The waste generated by the global fishing industry, such as fish scales, is mostly considered useless and discarded in a disorderly and/or unplanned way in inappropriate places, posing serious risks to both the environment and human health. This study proposes the use of fish scales in combustion processes as an alternative for such residues and to avoid their exposure in urban areas. Combustion experiments were conducted in a drop tube furnace (DTF), and the factors temperature, residence time, and sample particle size were investigated. The main atmospheric pollutants (CO, NO, CO2, and SO2) and the residues generated from the combustion processes were characterized by FTIR, EDS and ICP-OES analyses, and SEM images. The samples showed better performance at 1100 °C and 500 -ms residence time, when the burnout reached 96%, and particle size greater than 300-µm and 300-ms residence time led to the worst combustion performance (24.45% burnout), with the highest CO and NO peaks, indicating incomplete combustion of the fish scales. The analysis of the residues revealed total decomposition of the organic matter at temperatures above 700 °C and formation of hydroxyapatite. According to the DTF results, the use of fish scales in firing processes is a viable treatment of the residues, generating energy and avoiding environmental problems caused by inadequate disposal.

Impact of repetitive transcranial magnetic stimulation on the directed connectivity of autism EEG signals: a pilot study.

To compare the differences in directed connectivity between typically developing (TD) and autism spectrum disorder (ASD) children and identify the potential effects of repetitive transcranial magnetic stimulation (rTMS) on brain connectivity and behavior of children with ASD; 26 TD children (18 males/8 females; the average age was 6.34 ± 0.45) and 30 ASD children (21 males/9 females; the average age was 6.42 ± 0.17) participated in the experiment. ASD children were divided randomly into an experimental group and a control group. The experimental group received 18 rTMS sessions (twice a week for nine weeks), whereas the control group received the same procedures with sham stimulation. Directed transfer function (DTF) was used to calculate the effective connectivity as a way of investigating differences between ASD and TD children while simultaneously evaluating the effectiveness of rTMS for ASD. The results illustrate that the DTF of TD children in the frontal lobe (Fp1, Fp2, F7, F8) and temporal lobe (T7, T8) is higher than that of ASD children in all frequency bands; however, the DTF of ASD children is higher than TD in the midline (Fz, Cz), central lobe (C3, C4), and parietal lobe (P3, P4). In the experimental group of ASD children, the effective connectivity decreased from O1 to T7 and from P7 to Fp1 in the alpha band and from Pz to T8 in the gamma band after stimulation. Significant changes in Autism Behavior Checklist (ABC) scores were also found in social behaviors. Effective connectivity derived from DTF distinguishes ASD from TD children. rTMS provides changes in connectivity and behavior, suggesting its potential use as a viable treatment option for ASD individuals.

Linear and Nonlinear Directed Connectivity Analysis of the Cardio-Respiratory System in Type 1 Diabetes.

In this study, we explored the possibility of developing non-invasive biomarkers for patients with type 1 diabetes (T1D) by quantifying the directional couplings between the cardiac, vascular, and respiratory systems, treating them as interconnected nodes in a network configuration. Towards this goal, we employed a linear directional connectivity measure, the directed transfer function (DTF), estimated by a linear multivariate autoregressive modelling of ECG, respiratory and skin perfusion signals, and a nonlinear method, the dynamical Bayesian inference (DBI) analysis of bivariate phase interactions. The physiological data were recorded concurrently for a relatively short time period (5 min) from 10 healthy control subjects and 10 T1D patients. We found that, in both control and T1D subjects, breathing had greater influence on the heart and perfusion with respect to the opposite coupling direction and that, by both employed methods of analysis, the causal influence of breathing on the heart was significantly decreased (p < 0.05) in T1D patients compared to the control group. These preliminary results, although obtained from a limited number of subjects, provide a strong indication for the usefulness of a network-based multi-modal analysis for the development of biomarkers of T1D-related complications from short-duration data, as well as their potential in the exploration of the pathophysiological mechanisms that underlie this devastating and very widespread disease.

Functional Source Separation-Identified Epileptic Network: Analysis Pipeline.

This proof-of-concept (PoC) study presents a pipeline made by two blocks: 1. the identification of the network that generates interictal epileptic activity; and 2. the study of the time course of the electrical activity that it generates, called neurodynamics, and the study of its functional connectivity to the other parts of the brain. Network identification is achieved with the Functional Source Separation (FSS) algorithm applied to electroencephalographic (EEG) recordings, the neurodynamics quantified through signal complexity with the Higuchi Fractal Dimension (HFD), and functional connectivity with the Directed Transfer Function (DTF). This PoC is enhanced by the data collected before and after neuromodulation via transcranial Direct Current Stimulation (tDCS, both Real and Sham) in a single drug-resistant epileptic person. We observed that the signal complexity of the epileptogenic network, reduced in the pre-Real, pre-Sham, and post-Sham, reached the level of the rest of the brain post-Real tDCS. DTF changes post-Real tDCS were maintained after one month. The proposed approach can represent a valuable tool to enhance understanding of the relationship between brain neurodynamics characteristics, the effects of non-invasive brain stimulation, and epileptic symptoms.