Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Patterns Found in the Nuclear Localization Signals (NLSs) Associated with EBV-1 and EBV-2 Provide New Insights into Their Contribution to Different Cell-Type Specificities

Simple Summary The Epstein–Barr virus (EBV) has been implicated in several human neoplastic diseases. The EBV-1 can transform B cells into LCL more efficiently than EBV-2, and EBV-2 preferentially infects T-cell lymphocytes. The EBNA3A oncoprotein has an essential role in B-cell transformation. The six peptide motifs called nuclear localization signals (NLSs) from EBNA3A ensure nucleocytoplasmic protein trafficking. Multiple NLSs have been suggested to enhance EBNA3 function or different specificities to different cell types; however, a comprehensive assessment of their genetic variability has not been addressed. Our objective was to study the NLSs’ variability and their relationship with EBV types. Based on a comprehensive analysis of over a thousand EBNA3A sequences from different clinical manifestations and geographic locations, we found that EBNA3A from EBV-2 has two of the six NLSs altered, and genetic patterns in the NLSs are associated with EBV-1 and EBV-2. Abstract The Epstein–Barr virus (EBV) is a globally dispersed pathogen involved in several human cancers of B-cell and non-B-cell origin. EBV has been classified into EBV-1 and EBV-2, which have differences in their transformative ability. EBV-1 can transform B-cells into LCL more efficiently than EBV-2, and EBV-2 preferentially infects T-cell lymphocytes. The EBNA3A oncoprotein is a transcriptional regulator of virus and host cell genes, and is required in order to transform B-cells. EBNA3A has six peptide motifs called nuclear localization signals (NLSs) that ensure nucleocytoplasmic protein trafficking. The presence of multiple NLSs has been suggested to enhance EBNA3 function or different specificities in different cell types. However, studies about the NLS variability associated with EBV types are scarce. Based on a systematic sequence analysis considering more than a thousand EBNA3A sequences of EBV from different human clinical manifestations and geographic locations, we found differences in NLSs’ nucleotide structures among EBV types. Compared with the EBNA3A EBV-1, EBNA3A EBV-2 has two of the six NLSs altered, and these mutations were possibly acquired by recombination. These genetic patterns in the NLSs associated with EBV-1 and EBV-2 provide new information about the traits of EBNA3A in EBV biology.
Effectiveness of manual therapy in patients with thumb carpometacarpal osteoarthritis: a systematic review and meta-analysis

ABSTRACT Background The effectiveness of Manual Therapy (MT) in thumb carpometacarpal osteoarthritis (OA) is unclear. Objective This study aimed to determine the effectiveness of MT for functional outcomes in patients with thumb carpometacarpal OA. Design Systematic review and meta-analysis of randomized clinical trials. Methods An electronic search was performed in the Medline, Central, Embase, PEDro, Lilacs, Cinahl, SPORTDiscus, and Web of Science databases. The eligibility criteria for selecting studies included randomized clinical trials that compared MT versus other interventions in functional outcomes, such as thumb and/or hand function questionnaires, pinch and/or grip strength, thumb and/or hand range of motion, and pain intensity or pressure pain threshold in patients with thumb carpometacarpal OA. Results Five clinical trials met the eligibility criteria; for the quantitative synthesis, four studies were included. The mean difference (MD) for grip strength was 0.87kg (95% CI = 0.29–1.44, p = .003), for pinch strength was 0.10kg (95% CI = –0.01–0.20, p = .06), and for the pressure pain threshold was 0.64kg/cm2 (95% CI = 0.07–1.20, p = .03). All differences were in favor of the MT group. Conclusions In the short-term, there was moderate to high evidence, with statistically significant differences in the functional outcomes, in favor of MT versus sham interventions in patients with thumb carpometacarpal OA. However, these differences are not clinically important.
Rapid Production and Purification of Dye-Loaded Liposomes by Electrodialysis-Driven Depletion

Liposomes are spherical-shaped vesicles that enclose an aqueous milieu surrounded by bilayer or multilayer membranes formed by self-assembly of lipid molecules. They are intensively exploited as either model membranes for fundamental studies or as vehicles for delivery of active substances in vivo and in vitro. Irrespective of the method adopted for production of loaded liposomes, obtaining the final purified product is often achieved by employing multiple, time consuming steps. To alleviate this problem, we propose a simplified approach for concomitant production and purification of loaded liposomes by exploiting the Electrodialysis-Driven Depletion of charged molecules from solutions. Our investigations show that electrically-driven migration of charged detergent and dye molecules from solutions that include natural or synthetic lipid mixtures leads to rapid self-assembly of loaded, purified liposomes, as inferred from microscopy and fluorescence spectroscopy assessments. In addition, the same procedure was successfully applied for incorporating PEGylated lipids into the membranes for the purpose of enabling long-circulation times needed for potential in vivo applications. Dynamic Light Scattering analyses and comparison of electrically-formed liposomes with liposomes produced by sonication or extrusion suggest potential use for numerous in vitro and in vivo applications.
Novel Flexible PVDF-TrFE and PVDF-TrFE/ZnO Pressure Sensor: Fabrication, Characterization and Investigation

With the development of human healthcare devices, smart sensors, e-skins, and pressure sensors with outstanding sensitivity, flexibility, durability and biocompatibility have attracted more and more attention. In this paper, to develop a novel flexible pressure sensor with high sensitivity, different poly (vinylidene fluoride-trifluoroethylene) (PVDF-TrFE)-based composite membranes were fabricated, characterized and tested. To improve the β-phase crystallinity and piezoelectricity of the membranes, and for the purpose of comparison, nano ZnO particles with different concentrations (99:1, 9:1 in a weight ratio of PVDF-TrFE to ZnO) were, respectively added into PVDF-TrFE polymer acting as a nucleating agent and dielectric material. To facilitate the formation of β-phase crystal, the membranes were fabricated by electrospinning method. After the electrospinning, an annealing process was conducted to the fabricated membranes to increase the size and content of β-phase crystal. Then, the fabricated PVDF-TrFE membranes, acting as the core sensing layer, were, respectively built into multiple prototype sensors in a sandwich structure. The sensitivity of the prototype sensors was tested by an auto-clicker. The stimulation of the auto-clicker on the prototype sensors generated electrical signals, and the electrical signals were collected by a self-built testing platform powered by LabVIEW. As a result, combining the addition of ZnO nanofillers and the annealing process, a highly sensitive pressure sensor was fabricated. The optimal peak-to-peak voltage response generated from the prototype sensor was 1.788 V which shows a 75% increase compared to that of the pristine PVDF-TrFE sensor. Furthermore, a human pulse waveform was captured by a prototype sensor which exhibits tremendous prospects for application in healthcare devices.
Searching for New Model of Digital Informatics for Human–Computer Interaction: Testing the Institution-Based Technology Acceptance Model (ITAM)

The fourth industrial revolution has produced new information technology (IT) that is widely used in the healthcare industry. Although the nature of the institution affects IT adoption, the Technology Acceptance Model (TAM), a dominant theory, has dismissed its role and influence. Our research investigates how institutions influence the adoption of new IT by using the Institution-based Technology Acceptance Model (ITAM). We conducted an empirical test by using survey data collected from 300 employees in the public sector. Structural equation modeling was applied to test the proposed hypotheses. The results showed the total effect of institutions on the intention to use new IT is positive and significant. Second, IT adoption is not only affected by external institutions but also by type of institution; the external institution takes a greater role in inducing perceived usefulness, perceived ease of use, and intention to use than does the internal. Third, perceived ease of use and perceived usefulness play mediating roles between institution and IT adoption. Fourth, an alternative expanded model to which more individual and organizational factors were added confirmed the results of the base model. We concluded that institutions have a strong impact on the level of intention for IT use through perceived ease of use and perceived usefulness.
Effects of Rapid Weight Loss on Kidney Function in Combat Sport Athletes

Even though scientific literature shows numerous heath complications and performance decrements associated with rapid weight loss (RWL), its prevalence remains exceedingly high across various combat sports. The aim of this study was to thoroughly search the existing literature to explore the influence of RWL on kidney function in Olympic and non-Olympic combat sport athletes. PubMed and Web of Science were searched for the relevant studies. Only original articles published from 2005 onwards, written in English, that included healthy males and females who prompted ~5% weight loss within a week or less, were included in the study. Retrieved studies showed that creatinine, blood urea nitrogen and urine specific gravity values were significantly increased after RWL in the majority of the included studies. This observation indicates that RWL caused dehydration and subsequent acute kidney damage despite various degrees of weight lost during the RWL phase, which can lead to adverse events in other body systems. Alternative methods of weight reduction that prioritize athletes’ health should be considered.
Effectiveness of internet-based cognitive behavioral therapy for suicide: a systematic review and meta-analysis of RCTs

ABSTRACT Suicidal individuals rarely seek help and receive professional psychological intervention on their initiative. Internet-based cognitive behavioral therapy(iCBT) can increase availability and reduce stigma compared to face-to-face interventions for suicide.However, conclusions about the effectiveness of iCBT on suicide are controversial. The review aimed to determine the effectiveness of iCBT on reducing suicidal ideation (primary outcomes) and other outcomes related to suicide like suicide attempts(secondary outcomes). PubMed, the Cochrane Library, EMBASEwere searched up to March 2020 for RCTs of iCBT which aimed to reduce suicide.The potential bias was assessed by the Cochrane risk of bias tool. Data analyses wereperformed by RevMan5.3. Four studies meeting the eligibility criteria were included which reported data on a total of 1225 participants. We found iCBT was associated with reducing an individual’s suicidal ideation, and first indications suggest that the treatment effect might be even more pronounced in the short term and in adults.Additionally, there was insufficient evidence to prove its effectiveness in reducing suicide attempts and suicide death.Overall, iCBT can overcome the disadvantages of traditional interventions and show promise on suicidal ideation. While ensuring safety and ethics, further studies are warranted, focusing on suicide specific behavior like suicide attempts.
Predicting Malnutrition Risk with Data from Routinely Measured Clinical Biochemical Diagnostic Tests in Free-Living Older Populations

Malnutrition (undernutrition) in older adults is often not diagnosed before its adverse consequences have occurred, despite the existence of established screening tools. As a potential method of early detection, we examined whether readily available and routinely measured clinical biochemical diagnostic test data could predict poor nutritional status. We combined 2008–2017 data of 1518 free-living individuals ≥50 years from the United Kingdom National Diet and Nutrition Survey (NDNS) and used logistic regression to determine associations between routine biochemical diagnostic test data, micronutrient deficiency biomarkers, and established malnutrition indicators (components of screening tools) in a three-step validation process. A prediction model was created to determine how effectively routine biochemical diagnostic tests and established malnutrition indicators predicted poor nutritional status (defined by ≥1 micronutrient deficiency in blood of vitamins B6, B12 and C; selenium; or zinc). Significant predictors of poor nutritional status were low concentrations of total cholesterol, haemoglobin, HbA1c, ferritin and vitamin D status, and high concentrations of C-reactive protein; except for HbA1c, these were also associated with established malnutrition indicators. Additional validation was provided by the significant association of established malnutrition indicators (low protein, fruit/vegetable and fluid intake) with biochemically defined poor nutritional status. The prediction model (including biochemical tests, established malnutrition indicators and covariates) showed an AUC of 0.79 (95% CI: 0.76–0.81), sensitivity of 66.0% and specificity of 78.1%. Clinical routine biochemical diagnostic test data have the potential to facilitate early detection of malnutrition risk in free-living older populations. However, further validation in different settings and against established malnutrition screening tools is warranted.
Direct and Indirect Impact of COVID-19 for Patients with Immune-Mediated Inflammatory Diseases: A Retrospective Cohort Study

Importance: Since the beginning of the Coronavirus Disease-19 (COVID-19) pandemic, Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2) infection has been a serious challenge for immune-compromised patients with immune-mediated inflammatory diseases (IMIDs). Objective: Our aim was to investigate the impact of COVID-19 in terms of risks of infection, hospitalization and mortality in a cohort of patients with rheumatoid arthritis (RA), psoriasis (PSO) or inflammatory bowel disease (IBD). Furthermore, we studied the impact of SARS-CoV-2 infection on the prescribed drug regimen in these patients. Methods: Through the record linkage between health information systems, a cohort of patients, ≥18 years old, assisted in the Lazio region and who had suffered from immune-mediated inflammatory diseases (RA, PSO, IBD) between 2007 and 2019, was identified. The risk of infection, hospitalization or mortality for COVID-19, was assessed by logistic regression models, and reported in an Odds Ratio (ORs; CI 95%), adjusting for sex, age and the Charlson Comorbidity Index. We also estimated these risks separately by IMID and in the subgroup of prevalent biologic drug users. We investigated deferral of biological treatments in the study population by comparing the prevalence of weekly use of biologicals (2019–2020) before and during the pandemic periods. Findings: Within the 65,230 patients with IMIDs, the cumulative incidence for COVID-19 was 303/10,000 ab. In this cohort of patients, we observed a significantly higher risk of SARS-CoV-2 infection than the general population: OR = 1.17 (95% CI 1.12–1.22). The risk was higher even considering separately each disease and in the subgroup of prevalent biologic drug users. This last subgroup of patients showed a higher risk of death related to COVID-19 (OR 1.89; 95% CI 1.04–3.33) than the general population. However, no differences in terms of risks of hospitalization or death related to COVID-19 were recorded in patients with the IMIDs. Comparing the 2019–2020 prevalence of weekly biological drug treatments in prevalent biologic drug users, we found a decrease (−19.6%) during the lockdown, probably due to pandemic restrictions. Conclusions and Relevance: Patients with IMIDs seem to have a higher risk of SARS-CoV2 infection. However, other than for patients with prevalent biologic drug treatment, no significant differences in terms of hospitalization and mortality were reported compared to the general populations; further investigation is warranted on account of unmeasured confounding. In addition, during the lockdown period, the COVID-19 emergency highlighted a lower use of biologic drugs; this phenomenon requires strict pharmacological monitoring as it could be a proxy of forthcoming long-term clinical progression.
Design and Characterization of Backside Termination Structures for Thick Fully-Depleted MAPS

Fully Depleted Monolithic Active Pixel Sensors (FD-MAPS) represent an appealing alternative to hybrid detectors for radiation imaging applications. We have recently demonstrated the feasibility of FD-MAPS based on a commercial 110 nm CMOS technology, adapted using high-resistivity substrates and backside post-processing. A p/n junction diode, fabricated on the detector backside using low-temperature processing steps after the completion of the front-side Back End of Line (BEOL), is reverse-biased to achieve the full depletion of the substrate and thus fast charge collection by drift. Test diodes including termination structures with different numbers of floating guard rings and different pitches were fabricated together with other Process Control Monitor structures. In this paper, we present the design of the backside diodes, together with results from the electrical characterization of the test devices, aiming to improve understanding of the strengths and limitations of the proposed approach. Characterization results obtained on several wafers demonstrate the effectiveness of the termination rings in increasing the breakdown voltage of the backside diodes and in coping with the variability of the passivation layer characteristics. A breakdown voltage exceeding 400 V in the worst case was demonstrated in devices with 30 guard rings with 6 μm pitch, thus enabling the full depletion of high-resistivity substrates with a thickness larger than or equal to 300 μm. Additionally, we show the first direct comparison for this technology of measured pixel characteristics with 3D TCAD simulations, proving a good agreement in the extracted operating voltages.
Biosynthesis of fosfomycin in pseudomonads reveals an unexpected enzymatic activity in the metallohydrolase superfamily

Significance Fosfomycin is an antibiotic used for the treatment of cystitis. Its activity against both gram-positive and gram-negative pathogens has received strong recent interest. The compound is biosynthesized by both pseudomonads and streptomycetes via two different pathways that converge in the last step to form the natural product. This study investigated the biosynthesis of fosfomycin by Pseudomonas and revealed an oxidative decarboxylation activity within this pathway. Structural and sequence analysis of the enzyme identified key residues important for its activity and demonstrated its role in the biosynthesis of other phosphonate natural products. This newly characterized protein family expands the chemical space of catalysis by metallohydrolase superfamily enzymes. The epoxide-containing phosphonate natural product fosfomycin is a broad-spectrum antibiotic used in the treatment of cystitis. Fosfomycin is produced by both the plant pathogen Pseudomonas syringae and soil-dwelling streptomycetes. While the streptomycete pathway has recently been fully elucidated, the pseudomonad pathway is still mostly elusive. Through a systematic evaluation of heterologous expression of putative biosynthetic enzymes, we identified the central enzyme responsible for completing the biosynthetic pathway in pseudomonads. The missing transformation involves the oxidative decarboxylation of the intermediate 2-phosphonomethylmalate to a new intermediate, 3-oxo-4-phosphonobutanoate, by PsfC. Crystallographic studies reveal that PsfC unexpectedly belongs to a new class of diiron metalloenzymes that are part of the polymerase and histidinol phosphatase superfamily.
Dynamics of Bacterial Community Structure in the Rhizosphere and Root Nodule of Soybean: Impacts of Growth Stages and Varieties

Bacterial communities in rhizosphere and root nodules have significant contributions to the growth and productivity of the soybean (Glycine max (L.) Merr. ). In this report, we analyzed the physiological properties and dynamics of bacterial community structure in rhizosphere and root nodules at different growth stages using BioLog EcoPlate and high-throughput sequencing technology, respectively. The BioLog assay found that the metabolic capability of rhizosphere is in increasing trend in the growth of soybeans as compared to the bulk soil. As a result of the Illumina sequencing analysis, the microbial community structure of rhizosphere and root nodules was found to be influenced by the variety and growth stage of the soybean. At the phylum level, Actinobacteria were the most abundant in rhizosphere at all growth stages, followed by Alphaproteobacteria and Acidobacteria, and the phylum Bacteroidetes showed the greatest change. But, in the root nodules Alphaproteobacteria were dominant. The results of the OTU analysis exhibited the dominance of Bradyrhizobium during the entire stage of growth, but the ratio of non-rhizobial bacteria showed an increasing trend as the soybean growth progressed. These findings revealed that bacterial community in the rhizosphere and root nodules changed according to both the variety and growth stages of soybean in the field.
Solid Form and Phase Transformation Properties of Fexofenadine Hydrochloride during Wet Granulation Process

The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was <15% w/w. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.