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The activity of functional brain networks is responsible for the emergence of time-varying cognition and behaviour. Accordingly, time-varying correlations (Functional Connectivity) in resting fMRI have been shown to be predictive of behavioural traits, and psychiatric and neurological conditions. Typically, methods that measure time varying Functional Connectivity (FC), such as sliding windows approaches, do not separately model when changes occur in the mean activity levels from when changes occur in the FC, therefore conflating these two distinct types of modulation. We show that this can bias the estimation of time-varying FC to appear more stable over time than it actually is. Here, we propose an alternative approach that models changes in the mean brain activity and in the FC as being able to occur at different times to each other. We refer to this method as the Multi-dynamic Adversarial Generator Encoder (MAGE) model, which includes a model of the network dynamics that captures long-range time dependencies, and is estimated on fMRI data using principles of Generative Adversarial Networks. We evaluated the approach across several simulation studies and resting fMRI data from the Human Connectome Project (1003 subjects), as well as from UK Biobank (13301 subjects). Importantly, we find that separating fluctuations in the mean activity levels from those in the FC reveals much stronger changes in FC over time, and is a better predictor of individual behavioural variability.
Machine learning (ML) has been increasingly used in clinical medicine including studies focused on Clostridioides difficile infection (CDI) to inform to clinical decision making. We aimed to summarize ML choices in studies that used ML to predict CDI or CDI outcomes.
We searched Ovid MEDLINE, Ovid EMBASE, Web of Science, medRxiv, bioRxiv and arXiv from inception to March 18, 2021. We included fully published studies that used ML where CDI constituted the study population, exposure or outcome. Two reviewers independently identified studies and abstracted outcomes. We summarized study characteristics and approaches to CDI definition and ML-specific modelling.
Forty-three studies of prediction (n=21), classification (n=17) or inference (n=5) were included. Approaches to defining CDI were labelling during a clinical study or chart review (n=21), electronic phenotyping (n=13) or not specified (n=9). Ruxolitinib None of the studies using an electronic phenotype described phenotype validation. Almost all studies (n=41, 95phenotype validation was not reported in any study. Methodological approaches were heterogeneous. Validating CDI electronic phenotypes, evaluating performances of CDI models during a silent trial and deploying a CDI classifier to guide clinical practice are important future goals.
Effective use of telehealth offers substantial benefits to older persons and aged care providers. However, data privacy concerns challenge the effective use of telehealth and subsequent business value. Through developing a theoretical model, we explain how privacy concerns can influence the adoption ad use of telehealth in this complex context.
An integrative review of empirical investigations was conducted by linking privacy concerns, telehealth use, and aged care. We searched three major databases (PubMed, Web of Science, and Scopus) for articles published until December 2020. Articles were analyzed and presented using an integrative theoretical model that we labeled CPCPO (Context-Privacy Concerns-Practice-Outcomes).
Our review revealed that privacy concerns are a contextual concept, i.e., different contexts (users, telehealth systems, aged care services, data) produce different privacy concerns. We found that privacy concerns were more voiced in home telecare and were associated with the degree of tn practices. Based on the review results, we suggest avenues for future research.SARS-CoV-2 variants of concern (VOCs) contain several single-nucleotide variants (SNVs) at key sites in the receptor-binding region (RBD) that enhance infectivity and transmission, as well as cause immune escape, resulting in an aggravation of the coronavirus disease 2019 (COVID-19) pandemic. Emerging VOCs have sparked the need for a diagnostic method capable of simultaneously monitoring these SNVs. To date, no highly sensitive, efficient clinical tool exists to monitor SNVs simultaneously. Here, an encodable multiplex microsphere-phase amplification (MMPA) sensing platform that combines primer-coded microsphere technology with dual fluorescence decoding strategy to detect SARS-CoV-2 RNA and simultaneously identify 10 key SNVs in the RBD. MMPA limits the amplification refractory mutation system PCR (ARMS-PCR) reaction for specific target sequence to the surface of a microsphere with specific fluorescence coding. This effectively solves the problem of non-specific amplification among primers and probes in multiplex PCR. For signal detection, specific fluorescence codes inside microspheres are used to determine the corresponding relationship between the microspheres and the SNV sites, while the report probes hybridized with PCR products are used to detect the microsphere amplification intensity. The MMPA platform offers a lower SARS-CoV-2 RNA detection limit of 28 copies/reaction, the ability to detect a respiratory pathogen panel without cross-reactivity, and a SNV analysis accuracy level comparable to that of sequencing. Moreover, this super-multiple parallel SNVs detection method enables a timely updating of the panel of detected SNVs that accompanies changing VOCs, and presents a clinical availability that traditional sequencing methods do not.Conventional and routine diagnostics such as polymerase chain reaction (PCR) and serological tests are less sensitive, costly, and require sample pretreatment procedures. CRISPR/Cas systems that inherently assist bacteria and archaea in destroying invading phage genetic materials via an RNA-mediated interference strategy have been reconstituted in vitro and harnessed for nucleic and non-nucleic acid diagnostics. CRISPR/Cas-based diagnostics (CRISPR-Dx) are cost-effective, possess excellent sensitivity (attomolar) and specificity (single base distinction), exhibit fast turnaround response, and support nucleic acid extraction-free workflow. However, CRISPR-Dx still needs to address various challenges to translate the laboratory work into end-user tailored solutions. In this perspective, we review the relevant progress of CRISPR/Cas systems-based diagnostics, focusing on the comprehensive customization and applications of leading and trending CRISPR/Cas systems as platform technologies for fluorescence, colorimetric, and electrical signal detection. The impact of the CRISPR game-changing technology on the COVID-19 pandemic is highlighted. We also demonstrate the role of CRISPR/Cas systems for carryover contamination prevention. The advancements in signal amplification strategies using engineered crRNAs, novel reporters, nanoparticles, artificial genetic circuits, microfluidics, and smartphones are also covered. Furthermore, we critically discuss the translation of CRISPR-Dx's basic research into end-user diagnostics for commercialization success in the near future. Finally, we discuss the complex challenges and alternative solutions to harness the CRISPR/Cas potential in detail.Protein kinases play crucial regulatory roles in the physiological activities in the human body. Understanding protein kinase activity and its inhibition is essential for the management of human diseases. Considering the limitations of the existing protein kinase-related analysis methods, the aim of the present study was to develop a fluorescent biosensor based on Eu(BTC) (H2O)6 (BTC = 1,3,5-Benzenetricarboxylic acid) for evaluating protein kinase activity and the relevant inhibitors. A fluorophore-labelled substrate polypeptide was phosphorylated under the catalysis of protein kinase. This phosphorylated peptide can be coordinated explicitly with the europium site of Eu(BTC) (H2O)6 to detect the protein kinase. The developed biosensor performed well, with a detection limit of 0.00003 U μL-1, and it showed good selectivity and universality. Protein kinase activity could also be detected in MCF-7 cells using this method. Furthermore, in terms of inhibitor screening using the Eu(BTC) (H2O)6-based sensor, both H-89 and ellagic acid were found to inhibit protein kinase activity with IC50 values of 1.09 and 19.88 nmol L-1, respectively. Overall, this biosensor has broad application prospects in monitoring and controlling protein kinase activity.A simple ionic chromatography method for nitrite analysis in processed food products was developed and validated. Nitrite in the sample was extracted using 80 °C distilled deionized water and centrifuged. Purification of nitrite from sample solution was performed using OnGuard II Ag, OnGuard II RP and OnGuard II Na cartridge connected in order. Determination of nitrite was carried out using IonPac AG9-HC (4 × 50 mm) and IonPac AS9-HC (4 × 250 mm) columns and a 9 mM sodium carbonate mobile phase. The validated results showed good linearity (r2 > 0.999), recoveries (83.7-107.6%) and precision (1.3-5.1%). The levels of nitrite in processed food products were between n.d. to 33.5 mg/kg, and nitrite was detected in ham, sausage and bacon products. The mean nitrite intake was 2.7% of the Acceptable Daily Intake (ADI, 0.07 mg/kg bw/day) for the Korean population. The method was suitable for the analysis of nitrite in processed foods.Tartary buckwheat is rich in flavonoids and starch, and the interaction between these two components affects the structural and digestive properties of the food product. In this study, we analyze the effects of thermal gelatinization (GT), ultrasonic treatment (UT), and high hydrostatic pressure treatment (HHP) on the compounding degree of starch and flavonoids in Tartary buckwheat and on the properties of the starch/flavonoid complex system (HBS-BF). Based on scanning electron microscope (SEM) and X-ray diffraction (XRD) analyses, the surface of HBS-BF becomes rough after GT or UT, and many small cavities appear. Comparatively, HHP treatment is less damaging to HBS-BF. Moreover, HHP maintains the original A-type crystal morphology of buckwheat starch in HBS-BF, whereas GT and UT change to V-type. Repeated HHP further improves the crystallinity and digestion resistance of HBS-BF. According to the recorded Fourier transform infrared (FT-IR) spectra, HBS-BF by different methods does not exhibit new covalent bonds. Practical application The results reported herein promote the application of Tartary buckwheat starch and flavonoids in the food industry by providing a theoretical basis for the development of starch anti-digestion mechanisms and the preparation of resistant starch.
Body-mass index is a major determinant of left-ventricular-mass (LVM). Bariatric-metabolic surgery (BMS) reduces cardiovascular mortality. Its mechanism of action, however, often encompasses a weight-dependent effect. In this translational study, we aimed at investigating the mechanisms by which BMS leads to LVM reduction and functional improvement.
Twenty patients (45.2±8.5years) were studied with echocardiography at baseline and at 1,6,12 and 48 months after sleeve-gastrectomy (SG). Ten Wistar rats aged 10-weeks received high-fat diet ad libitum for 10 weeks before and 4 weeks after SG or sham-operation. An oral-glucose-tolerance-test was performed to measure whole-body insulin-sensitivity. Plasma metabolomics was analysed in both human and rodent samples. RNA quantitative Real-Time PCR and western blots were performed in rodent heart biopsies. The best-fitted partial-least-square discriminant-analysis model was used to explore the variable importance in the projection score of all metabolites.
Echocardiographic LVM (-12%,-23%,-28% and -43% at 1,6,12 and 48 months, respectively) and epicardial fat decreased overtime after SG in humans while insulin-sensitivity improved.
Read More: https://www.selleckchem.com/products/INCB18424.html
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