Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Adult Neurogenesis by the Fragile X Family of RNA Binding Proteins

The fragile X mental retardation protein (FMRP) has an important role in neural development. Functional loss of FMRP in humans leads to fragile X syndrome, and it is the most common monogenetic contributor to intellectual disability and autism. FMRP is part of a larger family of RNA-binding proteins known as FXRs, which also includes fragile X related protein 1 (FXR1P) and fragile X related protein 2 (FXR2P). Despite the similarities of the family members, the functions of FXR1P and FXR2P in human diseases remain unclear. Although most studies focus on FMRP’s role in mature neurons, all three FXRs regulate adult neurogenesis. Extensive studies have demonstrated important roles of adult neurogenesis in neuroplasticity, learning, and cognition. Impaired adult neurogenesis is implicated in neuropsychiatric disorders, neurodegenerative diseases, and neurodevelopmental disorders. Interventions aimed at regulating adult neurogenesis are thus being evaluated as potential therapeutic strategies. Here, we review and discuss the functions of FXRs in adult neurogenesis and their known similarities and differences. Understanding the overlapping regulatory functions of FXRs in adult neurogenesis can give us insights into the adult brain and fragile X syndrome.
Feasibility of Cognitive Functions Screened With the Montreal Cognitive Assessment in Determining ADL Dependence Early After Stroke

Objective: To investigate the feasibility of assessing cognitive function using the Montreal Cognitive Assessment (MoCA) given 36–48 h post stroke to explain dependence in activities of daily living (ADL). Methods: This is a cross-sectional, exploratory study. Cognitive function and basic ADL were assessed with the MoCA and the Barthel Index (BI), respectively, within 36–48 h of admission. Neurological functions were assessed with the National Institute of Health Stroke Scale (NIHSS) upon admittance to the hospital. Binary logistic regression analyses were performed to assess the feasibility of the MoCA in explaining ADL dependence. Results: Data were available for 550 patients (42% females, mean age 69 years). Moderate correlations (rs > +0.30, p < 0.001) were found between the total score on the BI, MoCA, and visuospatial/executive functions. The regression analysis model including only MoCA as an independent variable had a high sensitivity for explaining ADL dependence. However, the model with independent variables of MoCA, NIHSS, and age had the best area under the curve value (0.74). Conclusions: Cognitive functions assessed with the MoCA partly explain ADL dependence 36–48 h post stroke. Stroke-related neurological deficits and age should be additional considerations.
Analysis of a large food chemical database: chemical space, diversity, and complexity

Background: Food chemicals are a cornerstone in the food industry. However, its chemical diversity has been explored on a limited basis, for instance, previous analysis of food-related databases were done up to 2,200 molecules. The goal of this work was to quantify the chemical diversity of chemical compounds stored in FooDB, a database with nearly 24,000 food chemicals. Methods: The visual representation of the chemical space of FooDB was done with ChemMaps, a novel approach based on the concept of chemical satellites. The large food chemical database was profiled based on physicochemical properties, molecular complexity and scaffold content. The global diversity of FooDB was characterized using Consensus Diversity Plots. Results: It was found that compounds in FooDB are very diverse in terms of properties and structure, with a large structural complexity. It was also found that one third of the food chemicals are acyclic molecules and ring-containing molecules are mostly monocyclic, with several scaffolds common to natural products in other databases. Conclusions: To the best of our knowledge, this is the first analysis of the chemical diversity and complexity of FooDB. This study represents a step further to the emerging field of “Food Informatics”. Future study should compare directly the chemical structures of the molecules in FooDB with other compound databases, for instance, drug-like databases and natural products collections. An additional future direction of this work is to use the list of 3,228 polyphenolic compounds identified in this work to enhance the on-going polyphenol-protein interactome studies.
Competencies for nursing in a digital world. Methodology, results, and use of the DACH-recommendations for nursing informatics core competency areas in Austria, Germany, and Switzerland

ABSTRACT While Nursing Informatics competencies seem essential for the daily work of nurses, they are not formally integrated into nursing education in Austria, Germany and Switzerland, nor are there any national educational recommendations. The aim of this paper is to show how such recommendations can be developed, what competency areas are most relevant in the three countries and how the recommendations can be implemented in practice. To this end, a triple iterative procedure was proposed and applied starting with national health informatics recommendations for other professionals, matching and enriching these findings with topics from the international literature and finally validating them in an expert survey with 87 experts and in focus group sessions. Out of the 24 compiled competency areas, the relevance ratings of the following four recommended areas achieved values above 90%: nursing documentation (including terminologies), principles of nursing informatics, data protection and security, and quality assurance and quality management. As there were no significant differences between the three countries, these findings laid the foundation of the DACH Recommendations of Nursing Informatics as joint German (D), Austrian (A), and Swiss (CH) recommendations in Nursing Informatics. The methodology proposed has been utilized internationally, which demonstrates the added value of this study also outside the confines of Austria, Germany, Switzerland.
Game Theory Meets Network Security: A Tutorial

The increasingly pervasive connectivity of today's information systems brings up new challenges to security. Traditional security has accomplished a long way toward protecting well-defined goals such as confidentiality, integrity, availability, and authenticity. However, with the growing sophistication of the attacks and the complexity of the system, the protection using traditional methods could be cost-prohibitive. A new perspective and a new theoretical foundation are needed to understand security from a strategic and decision-making perspective. Game theory provides a natural framework to capture the adversarial and defensive interactions between an attacker and a defender. It provides a quantitative assessment of security, prediction of security outcomes, and a mechanism design tool that can enable security-by-design and reverse the attacker's advantage. This tutorial provides an overview of diverse methodologies from game theory that includes games of incomplete information, dynamic games, mechanism design theory to offer a modern theoretic underpinning of a science of cybersecurity. The tutorial will also discuss open problems and research challenges that the CCS community can address and contribute with an objective to build a multidisciplinary bridge between cybersecurity, economics, game and decision theory.
Gab1, a therapeutic target for allergic asthma?

The Grb-associated binder (Gab) family of proteins transduce cellular signals between receptors and intracellular downstream effectors, providing a platform for protein-protein interactions. Gab1, a key member of the Gab family (Gab1, Gab2, ad Gab3), has been shown to mediate cell signaling through tyrosine phosphatase SHP2 or phosphatidylinositol-3 (PI3K) kinase in response to a variety of the extracellular stimuli. The association of Gab1 with SHP2 and the p85 subunit of PI3K is essential for the activation of the Erk/MAPK, PI3K/Akt, and JAK/STAT pathways with diversified biological functions (1). Gab1 is also critical in other physiological activities. Conditional Gab1 knockout in mice showed impaired signal transduction with different system dysfunctions. For example, liver-specific Gab1 knockout mice showed defective liver regeneration (2), and cardiomyocyte-specific Gab1 knockout mice displayed an increase in infarct size and a decrease in cardiac function after ischemia/reperfusion injury (3).
Exploring the Adoption of E-Bikes by Different User Groups

Increased e-bike use can potentially support a shift towards more sustainable and active transport systems. This paper outlines the potential of e-bikes for three user groups that have as yet not fully adopted this mode of transportation: commuters, rural residents and students. For each group, some group-specific advantages and limitations are identified that are likely to shape future e-bike mobility. Then, theoretical and methodological advances in transport geography, mobilities studies and environmental psychology are discussed that may form a backdrop for the empirical study of these groups. Based on this analysis, the use of integrative, mixed-methods research approaches is proposed, which consider potential e-bike mobility as the result of individual decision-making and shaped by social and spatial contexts. This approach may provide a base for the development of effective strategies for promoting the adoption of e-bikes among more diverse user groups.
Alterations of Coherent Theta and Gamma Network Oscillations as an Early Biomarker of Temporal Lobe Epilepsy and Alzheimer’s Disease

Alzheimer’s disease (AD) and temporal lobe epilepsy (TLE) are the most common forms of neurodegenerative disorders characterized by the loss of cells and progressive irreversible alteration of cognitive functions, such as attention and memory. AD may be an important cause of epilepsy in the elderly. Early diagnosis of diseases is very important for their successful treatment. Many efforts have been done for defining new biomarkers of these diseases. Significant advances have been made in the searching of some AD and TLE reliable biomarkers, including cerebrospinal fluid and plasma measurements and glucose positron emission tomography. However, there is a great need for the biomarkers that would reflect changes of brain activity within few milliseconds to obtain information about cognitive disturbances. Successful early detection of AD and TLE requires specific biomarkers capable of distinguishing individuals with the progressing disease from ones with other pathologies that affect cognition. In this article, we review recent evidence suggesting that magnetoencephalographic recordings and coherent analysis coupled with behavioral evaluation can be a promising approach to an early detection of AD and TLE. Highlights – Data reviewed include the results of clinical and experimental studies. – Theta and gamma rhythms are disturbed in epilepsy and AD. – Common and different behavioral and oscillatory features of pathologies are compared. – Coherent analysis can be useful for an early diagnostics of diseases.
Nanos2 promotes differentiation of male germ cells basing on the negative regulation of Foxd3 and the treatment of 5‐Azadc and TSA

The transcription factor positioning in promoter regions relate to gene regulation, and the level of DNA methylation and histone acetylation also impact the promoter activity. In this study, we tested and verified the core promoter region and key transcription factor of Nanos2 which is a male‐critical gene in the differentiation of embryonic stem cells to male germ cells, meanwhile, epigenetic effects by mean of 5‐Aza‐2′‐deoxycytidine (5‐Azadc) and Trichostin A (TSA) on the activity of Nanos2 promoter were detected. The results reveal that key transcription factor Foxd3 is a negative regulator of Nanos2, which suggests that loss‐of‐function of Foxd3 causes strong expression of Nanos2 responsive to large amounts of primordial germ cells and spermatogonial stem cells,whereas its overexpression causes the opposite effect. Furthermore, both 5‐Azadc and TSA can provoke responses of Nanos2, but the combination effect of the two is better.
Fighting Bacteria: How Can We Prevent Hospital-Acquired Infections?

Bacteria live with each other in an organized network called a biofilm. The biofilm allows the bacteria to communicate with each other and transfer nutrients and signals from one bacterium to another. This communication provides the bacteria with new properties that allow them to survive, even when they are exposed to harmful compounds that usually kill them (for example, antibiotics). These persistent bacteria can now cause what are called hospital-acquired infections because patients often get them while in a healthcare facility, like a hospital. Hospital-acquired infections obviously endanger the health of patients and may lead to death. So, it is important to find solutions that prevent bacteria from forming biofilms. My research group designed and synthesized a compound that forms a coating on different materials and does not allow bacteria to form biofilm. This compound may be useful in the future as a coating for medical devices, water desalination facilities, and food preparation surfaces.
Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease.

BACKGROUND & AIMS There are limited data on the risk of hepatocellular cancer (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to estimate the risk of incident HCC among patients with NAFLD. METHODS We conducted a retrospective cohort study from a total of 130 facilities in the Veterans Health Administration. Patients with NAFLD diagnosed between January 1, 2004 and December 31, 2008 were included and followed until HCC diagnosis, death, or December 31, 2015. We also identified a sex- and age-matched control cohort without NAFLD. We ascertained all new HCC cases from the Central Cancer Registry and manual chart reviews. We calculated incidence rates for HCC by NAFLD status, as well as in subgroups of NAFLD patients. We used competing risk models to compare the risk of HCC in patients with NAFLD vs those without NAFLD. We reviewed electronic medical records of all HCC cases that developed in NAFLD patients without cirrhosis. RESULTS We compared 296,707 NAFLD patients with 296,707 matched controls. During 2,382,289 person-years [PYs] of follow-up, 490 NAFLD patients developed HCC (0.21/1000 PYs). HCC incidence was significantly higher among NAFLD patients vs controls (0.02/1000 PYs; hazard ratio, 7.62; 95% confidence interval, 5.76-10.09). Among patients with NAFLD, those with cirrhosis had the highest annual incidence of HCC (10.6/1000 PYs). Among patients with NAFLD cirrhosis, HCC risk ranged from 1.6 to 23.7 per 1000 PYs based on other demographic characteristics; risk of HCC was the highest in older Hispanics with cirrhosis. In medical record reviews, 20% of NAFLD patients with HCC had no evidence of cirrhosis. CONCLUSIONS Risk of HCC was higher in NAFLD patients than that observed in general clinical population. Most HCC cases in NAFLD developed in patients with cirrhosis. The absolute risk of HCC was higher than the accepted thresholds for HCC surveillance for most patients with NAFLD cirrhosis.
Microfluidics-based on-a-chip systems for isolating and analysing extracellular vesicles

ABSTRACT Extracellular vesicles (EVs), which can be found in almost all body fluids, consist of a lipid bilayer enclosing proteins and nucleic acids from their cells of origin. EVs can transport their cargo to target cells and have therefore emerged as key players in intercellular communication. Their potential as either diagnostic and prognostic biomarkers or therapeutic drug delivery systems (DDSs) has generated considerable interest in recent years. However, conventional methods used to study EVs still have significant limitations including the time-consuming and low throughput techniques required, while at the same time the demand for better research tools is getting stronger and stronger. In the past few years, microfluidics-based technologies have gradually emerged and have come to play an essential role in the isolation, detection and analysis of EVs. Such technologies have several advantages, including low cost, low sample volumes, high throughput and precision. This review summarizes recent advances in microfluidics-based technologies, compares conventional and microfluidics-based technologies, and includes a brief survey of recent progress towards integrated “on-a-chip” systems. In addition, this review also discusses the potential clinical applications of “on-a-chip” systems, including both “liquid biopsies” for personalized medicine and DDS devices for precision medicine, and then anticipates the possible future participation of cloud-based portable disease diagnosis and monitoring systems, possibly with the participation of artificial intelligence (AI).
GoT-WAVE: Temporal network alignment using graphlet-orbit transitions

Global pairwise network alignment (GPNA) aims to find a one-to-one node mapping between two networks that identifies conserved network regions. GPNA algorithms optimize node conservation (NC) and edge conservation (EC). NC quantifies topological similarity between nodes. Graphlet-based degree vectors (GDVs) are a state-of-the-art topological NC measure. Dynamic GDVs (DGDVs) were used as a dynamic NC measure within the first-ever algorithms for GPNA of temporal networks: DynaMAGNA++ and DynaWAVE. The latter is superior for larger networks. We recently developed a different graphlet-based measure of temporal node similarity, graphlet-orbit transitions (GoTs). Here, we use GoTs instead of DGDVs as a new dynamic NC measure within DynaWAVE, resulting in a new approach, GoT-WAVE. On synthetic networks, GoT-WAVE improves DynaWAVE's accuracy by 25% and speed by 64%. On real networks, when optimizing only dynamic NC, each method is superior ~50% of the time. While DynaWAVE benefits more from also optimizing dynamic EC, only GoT-WAVE can support directed edges. Hence, GoT-WAVE is a promising new temporal GPNA algorithm, which efficiently optimizes dynamic NC. Future work on better incorporating dynamic EC may yield further improvements.
Lactic Acid Bacterium Population Dynamics in Artisan Sourdoughs Over One Year of Daily Propagations Is Mainly Driven by Flour Microbiota and Nutrients

This study aimed to: (i) assess at what extent traditional, daily propagated, sourdough can be considered a stable microbial ecosystem; (ii) ascertain the drivers of stability/variability. For this purpose, samples of sourdough, flour and environment were collected over 1 year from three different bakeries located in Altamura, Castellana Grotte, and Matera. Culture-dependent and –independent analyses were carried out on all the samples. In addition, sourdough and flour were subjected to biochemical characterization. In all the sourdoughs sampled at the same bakery, cell density of lactic acid bacteria fluctuated of one-two log cycles. However, 16S metagenetic analysis showed that sourdough bacterial microbiota was remarkably stable, in terms of species. Yet, some differences were found during time at intra-specific level. Indeed, bacterial strains succeeded in a 1-year lapse of time or even in 6-months, such as in the case of strains isolated from Altamura sourdough samples. Residual carbohydrates, lactic acid, ethanol and free amino acids varied in the same sourdough collected at different sampling times. These variations could be attributed to combination of various factors, such as fermentation temperature and strain succession. In addition, concentration of flour nutrients varied over 1 year and, in some cases, in a shorter time lapse. This may have favored certain strains over others. For this reason and also because of its inherent contamination by lactic acid bacteria, we found flour as the major driver of strains succession.
Biological evaluations of newly-designed Pt(II) and Pd(II) complexes using spectroscopic and molecular docking approaches

Abstract To perform biological evaluations of newly-designed Pt(II) and Pd(II) complexes, the present study was conducted with targeted protein human serum albumin (HSA) and HCT116 cell line as model of human colorectal carcinoma. The binding of Pt(II) and Pd(II) complexes to HSA was analyzed using fluorescence spectroscopy and molecular docking. The thermal stability and alterations in the secondary structure of HSA in the presence of Pt(II) and Pd(II) complexes were investigated using the thermal denaturation method and circular dichroism (CD) spectroscopy. The cytotoxicity of the Pt(II) and Pd(II) complexes was studied against the HCT116 cell line using MTT assay. The binding analysis revealed that the fluorescence findings were well in agreement with docking results such that there is only one binding site for each complex on HSA. Binding constants of 8.7 × 103 M−1, 2.65 × 103 M−1, 0.3 × 103 M−1, and 4.4 × 103 M−1 were determined for Pd(II) and Pt(II) complexes (I–IV) at temperature of 25 °C, respectively. Also, binding constants of 1.9 × 103 M−1, 15.17 × 103 M−1, 1.9 × 103 M−1, and 13.1 × 103 M−1 were determined for Pd(II) and Pt(II) complexes (I–IV) at temperature of 37 °C, respectively. The results of CD and thermal denaturation showed that the molecular structure of HSA affected by interaction with Pt(II) and Pd(II) complexes is stable. Cytotoxicity studies represented the growth suppression effect of the Pt(II) and Pd(II) complexes toward the human colorectal carcinoma cell line. Therefore, the results suggest that the new designed Pt(II) and Pd(II) complexes are well promising candidates for use in cancer treatment, particularly for human colorectal cancer. Communicated by Ramaswamy H. Sarma
Paclitaxel Plus Cetuximab as 1st Line Chemotherapy in Platinum-Based Chemoradiotherapy-Refractory Patients With Squamous Cell Carcinoma of the Head and Neck

Purpose: We sought to evaluate the efficacy and safety of the combination of cetuximab (Cmab) and paclitaxel (PTX) in patients with squamous cell carcinoma of the head and neck (SCCHN) who had unresectable recurrent or metastatic (R/M) disease after platinum-based chemoradiotherapy. Materials and Methods: Data on 23 patients with SCCHN who received paclitaxel and cetuximab (Cmab) for R/M disease no more than 6 months after CRT completion were retrospectively reviewed. PTX and Cmab were given in a 28-day cycle (PTX, 80 mg/m2 on days 1, 8, and 15; Cmab, loading dose 400 mg/m2 followed by a weekly 250 mg/m2). The differences in prognosis between subgroups in different clinical settings were also assessed. Results: CRT had been delivered as definitive treatment in 13 cases (57%) and as adjuvant treatment in 10 (43%). Median time from CRT completion to disease recurrence or metastasis was 73 days (1–152). The best objective response and disease control rates were 52 and 83%, respectively, with 12 partial responses and seven cases of stable disease by Response Evaluation Criteria in Solid Tumors (RECIST). A total of 17 of 23 patients (74%) achieved a degree of tumor shrinkage. Median progression-free survival (PFS) and overall survival (OS) were 7.0 (95% confidence interval [CI]: 3.7–8.4) and 16.3 months (95% CI: 7.8–23.3), respectively. Patients with a longer duration (≥60 d) from CRT completion to disease progression had a statistically significantly longer OS than the others (median OS 22.3 vs. 8.1 months, log-rank test; p = 0.034). Main Grade 3 toxicities included neutropenia (13%), anemia (13%), and hypomagnesemia (13%). No Grade 4 toxicity or treatment-related death was seen. Conclusion: PTX and Cmab is a tolerable and effective option in SCCHN patients with symptomatic CRT-refractory disease. Its favorable effects on tumor shrinkage will help relieve tumor-associated symptoms.