Miracle-dz/UniFAR-FTUs huggingface dataset:
Prednisone for the Prevention of Paradoxical Tuberculosis‐Associated IRIS

BACKGROUND Early initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–infected patients who have tuberculosis reduces mortality among patients with low CD4 counts, but it increases the risk of paradoxical tuberculosis‐associated immune reconstitution inflammatory syndrome (IRIS). METHODS We conducted this randomized, double‐blind, placebo‐controlled trial to assess whether prophylactic prednisone can safely reduce the incidence of paradoxical tuberculosis‐associated IRIS in patients at high risk for the syndrome. We enrolled HIV‐infected patients who were initiating ART (and had not previously received ART), had started tuberculosis treatment within 30 days before initiating ART, and had a CD4 count of 100 cells or fewer per microliter. Patients received either prednisone (at a dose of 40 mg per day for 14 days, then 20 mg per day for 14 days) or placebo. The primary end point was the development of tuberculosis‐associated IRIS within 12 weeks after initiating ART, as adjudicated by an independent committee. RESULTS Among the 240 patients who were enrolled, the median age was 36 (interquartile range, 30 to 42), 60% were men, and 73% had microbiologically confirmed tuberculosis; the median CD4 count was 49 cells per microliter (interquartile range, 24 to 86), and the median HIV type 1 RNA viral load was 5.5 log10 copies per milliliter (interquartile range, 5.2 to 5.9). A total of 120 patients were assigned to each group, and 18 patients were lost to follow‐up or withdrew. Tuberculosis‐associated IRIS was diagnosed in 39 patients (32.5%) in the prednisone group and in 56 (46.7%) in the placebo group (relative risk, 0.70; 95% confidence interval [CI], 0.51 to 0.96; P=0.03). Open‐label glucocorticoids were prescribed to treat tuberculosis‐associated IRIS in 16 patients (13.3%) in the prednisone group and in 34 (28.3%) in the placebo group (relative risk, 0.47; 95% CI, 0.27 to 0.81). There were five deaths in the prednisone group and four in the placebo group (P=1.00). Severe infections (acquired immunodeficiency syndrome–defining illnesses or invasive bacterial infections) occurred in 11 patients in the prednisone group and in 18 patients in the placebo group (P=0.23). One case of Kaposi's sarcoma occurred in the placebo group. CONCLUSIONS Prednisone treatment during the first 4 weeks after the initiation of ART for HIV infection resulted in a lower incidence of tuberculosis‐associated IRIS than placebo, without evidence of an increased risk of severe infections or cancers. (Funded by the European and Developing Countries Clinical Trials Partnership and others; PredART ClinicalTrials.gov number, NCT01924286.)
Is digital upskilling the next generation our ‘pipeline to prosperity’?

The British government is claiming digital skills will deliver economic growth to the country and social mobility to young people: its ministers call it ‘a pipeline to prosperity’. While declaring this pipeline, the government assumes the needs of the economy and young people’s needs are (or should be) synchronised. We challenge this assumption and the policy it sustains with data from questionnaires, workshops and interviews with 50 young people from communities in South Wales (including a former mining town and a deprived inner city area) about digital technology’s role in their everyday life. We use a new typography to compare the reality of their socially and economically structured lives to the governmental policy discourse that makes them responsible for their country’s future economic success. To explain these young people’s creative and transgressive use of technology, we also make an empirically grounded contribution to the ongoing theoretical debates about structure and agency.
Thermal Expansion of Single-Crystal H_{2}O and D_{2}O Ice Ih.

Thermal expansion of H_{2}O and D_{2}O ice Ih with relative resolution of 1 ppb is reported. A large transition in the thermal expansion coefficient at 101 K in H_{2}O moves to 125 K in D_{2}O, revealing one of the largest-known isotope effects. Rotational oscillatory modes that couple poorly to phonons, i.e., lattice solitons, may be responsible.
Changing to a Low-Polyphenol Diet Alters Vascular Biomarkers in Healthy Men after Only Two Weeks

Bioactive dietary compounds play a critical role in health maintenance. The relation between bioactive compound intake and cardiovascular health-related biomarkers has been demonstrated in several studies, although mainly with participants who have altered biochemical parameters (high blood pressure, high cholesterol, metabolic syndrome, etc.). The aim of this study was to evaluate if adopting a diet low in polyphenol-rich food for two weeks would affect vascular biomarkers in healthy men. In a crossover study, 22 healthy men were randomly assigned to their usual diet (UD), consuming healthy food rich in polyphenols, or to a low antioxidant diet (LAD), with less than two servings of fruit and vegetables per day and avoiding the intake of cocoa products, coffee and tea. As a marker of compliance, total polyphenols in urine were significantly lower after the LAD than after the UD (79 ± 43 vs. 123 ± 58 mg GAE/g creatinine). Nitric oxide levels were also reduced (52 ± 28 in LAD vs. 80 ± 34 µM in UD), although no significant changes in cellular adhesion molecules and eicosanoids were observed; however, an increasing ratio between thromboxane A2 (TXA2) and prostaglandin I2 (PGI2) was reached (p = 0.048). Thus, a slight dietary modification, reducing the consumption of polyphenol-rich food, may affect vascular biomarkers even in healthy individuals.
Mobility Programs for the Hospitalized Older Adult: A Scoping Review

Objectives: This scoping review (a) describes programs to improve mobility in hospitalized adults and (b) determines the methods used to measure mobility. Method: The Joanna Briggs Institute Methodology for Scoping Reviews was used to conduct this review. Results: Our findings suggest that using a multidisciplinary approach may be the most effective way to promote mobility in hospitalized older adults. Most studies did not articulate how physical activity was measured, indicating that more research is needed. Discussion: The literature shows that implementation of protocols designed to improve the early and regular implementation of physical mobility activities improves the health outcomes of hospitalized older people. Costs associated with healthcare utilization are also reduced, including hospital length of stay. Mobility programs that quantified mobility through validated measurement tools or accelerometers are the most promising as they provide feedback that reinforces progress of the patient and the expected benefits of early mobility.
Zoster vaccination inequalities: A population based cohort study using linked data from the UK Clinical Practice Research Datalink

Objective To quantify inequalities in zoster vaccine uptake by determining its association with socio-demographic factors: age, gender, ethnicity, immigration status, deprivation (at Lower-layer Super Output Area-level), care home residence and living arrangements. Method This population-based cohort study utilised anonymised primary care electronic health records from England (Clinical Practice Research Datalink) linked to deprivation and hospitalisation data. Data from 35,333 individuals from 277 general practices in England and eligible for zoster vaccination during the two-year period (2013–2015) after vaccine introduction were analysed. Logistic regression was used to obtain adjusted odds ratios (aOR) for the association of socio-demographic factors with zoster vaccine uptake for adults aged 70 years (main target group) and adults aged 79 years (catch-up group). Results Amongst those eligible for vaccination, 52.4% (n = 18,499) received the vaccine. Socio-demographic factors independently associated with lower zoster vaccine uptake in multivariable analyses were: being older (catch-up group: aged 79 years) aOR = 0.89 (95% confidence interval (CI):0.85–0.93), care home residence (aOR = 0.64 (95%CI: 0.57–0.73)) and living alone (aOR = 0.85 (95%CI: 0.81–0.90)). Uptake decreased with increasing levels of deprivation (p-value for trend<0.0001; aOR most deprived versus least deprived areas = 0.69 (95%CI: 0.64–0.75)). Uptake was also lower amongst those of non-White ethnicities (for example, Black versus White ethnicity: aOR = 0.61 (95%CI: 0.49–0.75)) but was not lower among immigrants after adjusting for ethnicity. Lower uptake was also seen amongst females compared to men in the catch-up group. Conclusions Inequalities in zoster vaccine uptake exist in England; with lower uptake among those of non-White ethnicities, and among those living alone, in a care home and in more deprived areas. Tailored interventions to increase uptake in these social groups should assist in realising the aim of mitigating vaccination inequalities. As care home residents are also at higher risk of zoster, improving the uptake of zoster vaccination in this group will also mitigate inequalities in zoster burden.
Ubiquilin 2 modulates ALS/FTD-linked FUS–RNA complex dynamics and stress granule formation

Significance Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating neurodegenerative diseases for which there are few treatments. ALS/FTD has been genetically and pathologically linked to both protein quality control (PQC) factors and RNA homeostasis, but the molecular players that bridge these pathways are not well characterized. Here, we identify a role for the ALS/FTD-linked PQC protein ubiquilin 2 (UBQLN2) in maintaining the solubility of RNA binding protein FUS in response to stress. UBQLN2 increases the dynamics of FUS–RNA complex formation, resulting in the negative regulation of stress granule (SG) formation. Because SGs potentially seed toxic inclusions of patients with ALS/FTD, these findings have implications for understanding ALS/FTD pathogenesis and designing new treatments for these diseases. The ubiquitin-like protein ubiquilin 2 (UBQLN2) has been genetically and pathologically linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but its normal cellular functions are not well understood. In a search for UBQLN2-interacting proteins, we found an enrichment of stress granule (SG) components, including ALS/FTD-linked heterogeneous ribonucleoprotein fused in sarcoma (FUS). Through the use of an optimized SG detection method, we observed UBQLN2 and its interactors at SGs. A low complexity, Sti1-like repeat region in UBQLN2 was sufficient for its localization to SGs. Functionally, UBQLN2 negatively regulated SG formation. UBQLN2 increased the dynamics of FUS–RNA interaction and promoted the fluidity of FUS–RNA complexes at a single-molecule level. This solubilizing effect corresponded to a dispersal of FUS liquid droplets in vitro and a suppression of FUS SG formation in cells. ALS-linked mutations in UBQLN2 reduced its association with FUS and impaired its function in regulating FUS–RNA complex dynamics and SG formation. These results reveal a previously unrecognized role for UBQLN2 in regulating the early stages of liquid–liquid phase separation by directly modulating the fluidity of protein–RNA complexes and the dynamics of SG formation.
Measurement of torque generated during intracanal instrumentation in vivo

AIM To compare two different clinical techniques when using endodontic rotary instruments by monitoring the torque in vivo. METHODOLOGY Ten single-rooted maxillary anterior teeth were prepared by an endodontist using size 25, . 06 taper TF rotary instruments (KerrEndo, Orange, CA, USA). All instruments were rotated at 500 rpm with maximum torque set at 2.5 N cm using an endodontic motor (Kavo, Biberach, Germany), which automatically recorded the torque values every 1/10 of a second. Instruments were used with two modi operandi: (i) Inward action: short-length intermittent progression with slight apical pressure aiming to reach the working length (also known as pecking motion), followed by (ii) Outward action: lateral brushing action selectively directed to address the canal circumference whilst removing instruments in the coronal direction. The mean, maximum and accumulated torque values were recorded and analysed statistically (t-test and Wilcoxon test) with a significance level set at 5%. None of the recorded values exceeded the selected torque limit. RESULTS A significant difference between inward and outward actions was found regarding the evaluated parameters (P < 0.05). The outward action (brushing) was significantly safer (requiring less torque) compared to the inward action (pecking). CONCLUSIONS Torque measurements during in vivo instrumentation provided useful information regarding the techniques evaluated. Although the torque limit was not reached by any of the two actions, the technique impacted significantly on the torque applied to the instrument.
Metal Oxide Nanoparticle Based Electrochemical Sensor for Total Antioxidant Capacity (TAC) Detection in Wine Samples

A single-use electrochemical screen-printed electrode is reported based on biomimetic properties of nanoceria particles (CeNPs). The developed tool showed an easy approach compared to the classical spectrophotometric methods reported in literature in terms of ease of use, cost, portability, and unnecessary secondary reagents. The sensor allowed the detection of the total antioxidant capacity (TAC) in wine samples. The sensor has been optimized and characterized electrochemically and then tested with antioxidant compounds occurred in wine samples. The electrochemical CeNPs modified sensor has been used for detection of TAC in white and red commercial wines and the data compared to the 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS)-based spectrophotometric method. Finally, the obtained results have demonstrated that the proposed sensor was suitable for the simple and quick evaluation of TAC in beverage samples.
Phylogeny and Mycotoxin Characterization of Alternaria Species Isolated from Wheat Grown in Tuscany, Italy

Wheat, the main source of carbohydrates worldwide, can be attacked by a wide number of phytopathogenic fungi, included Alternaria species. Alternaria species commonly occur on wheat worldwide and produce several mycotoxins such as tenuazonic acid (TA), alternariol (AOH), alternariol-monomethyl ether (AME), and altenuene (ALT), provided of haemato-toxic, genotoxic, and mutagenic activities. The contamination by Alternaria species of wheat kernels, collected in Tuscany, Italy, from 2013 to 2016, was evaluated. Alternaria contamination was detected in 93 out of 100 field samples, with values ranging between 1 and 73% (mean of 18%). Selected strains were genetically characterized by multi-locus gene sequencing approach through combined sequences of allergen alt1a, glyceraldeyde-3-phosphate dehydrogenase, and translation elongation factor 1α genes. Two well defined groups were generated; namely sections Alternaria and Infectoriae. Representative strains were analyzed for mycotoxin production. A different mycotoxin profile between the sections was shown. Of the 54 strains analyzed for mycotoxins, all strains included in Section Alternaria produced AOH and AME, 40 strains (99%) produced TA, and 26 strains (63%) produced ALT. On the other hand, only a very low capability to produce both AOH and AME was recorded among the Section Infectoriae strains. These data show that a potential mycotoxin risk related to the consumption of Alternaria contaminated wheat is high.
Bioinformatics and Functional Assessment of Toxin-Antitoxin Systems in Staphylococcus aureus

Staphylococcus aureus is a nosocomial pathogen that can cause chronic to persistent infections. Among different mediators of pathogenesis, toxin-antitoxin (TA) systems are emerging as the most prominent. These systems are frequently studied in Escherichia coli and Mycobacterial species but rarely explored in S. aureus. In the present study, we thoroughly analyzed the S. aureus genome and screened all possible TA systems using the Rasta bacteria and toxin-antitoxin database. We further searched E. coli and Mycobacterial TA homologs and selected 67 TA loci as putative TA systems in S. aureus. The host inhibition of growth (HigBA) TA family was predominantly detected in S. aureus. In addition, we detected seven pathogenicity islands in the S. aureus genome that are enriched with virulence genes and contain 26 out of 67 TA systems. We ectopically expressed multiple TA genes in E. coli and S. aureus that exhibited bacteriostatic and bactericidal effects on cell growth. The type I Fst toxin created holes in the cell wall while the TxpA toxin reduced cell size and induced cell wall septation. Besides, we identified a new TA system whose antitoxin functions as a transcriptional autoregulator while the toxin functions as an inhibitor of autoregulation. Altogether, this study provides a plethora of new as well as previously known TA systems that will revitalize the research on S. aureus TA systems.
A salutogenic inquiry into positive aging – a longitudinal analysis

Abstract Objectives: Based on a gero-salutogenic approach, we investigated the stability of the sense of coherence over a time span of four years in active older individuals and long-term effects of this life orientation on three different indicators of positive aging—subjective well-being, psychological health and physical health. This is the first study to explore associations between gain in sense of coherence and future positive aging. Methods: Our longitudinal sample consisted of 125 physically active individuals (73.5% women) at the mean age of 71 years at follow-up (range: 64 to 87 years; response rate: 73.5%), who completed our questionnaire twice. There were no systematic differences between the follow-up responders and non-responders. Results: The sense of coherence increased over four years, disclosing a small effect size. The baseline sense of coherence had a substantial predictive value for future subjective well-being and psychological health, but not for physical health. Stepwise hierarchical regression analyses showed that both the baseline sense of coherence and gain in sense of coherence predicted future subjective well-being and psychological health. With respect to future physical health, only gain in sense of coherence was significant. Conclusion: Consistent with gero-salutogenic theory, the baseline sense of coherence is an effective predictor of future positive aging, and growth in sense of coherence within a time span of four years is reflected in improved positive aging. It is important to encourage experiences in older age that cultivate the three components of the sense of coherence—feelings of comprehensibility, manageability and meaningfulness.
Structural and functional analysis of single‐nucleotide polymorphic variants of purine‐rich element‐binding protein B

Purine‐rich element‐binding protein B (Purβ) inhibits myofibroblast differentiation by repressing the expression of the smooth muscle α‐actin gene (Acta2). Several reports have identified the structural domains in Purβ that enable its characteristic interaction with purine‐rich single‐stranded DNA (ssDNA) sequences in the Acta2 promoter. However, little is known about the physical and functional effects of single‐nucleotide polymorphisms that alter individual amino acid residues in Purβ. This study evaluated seven rare single amino acid variants of human PURB engineered into the homologous mouse Purβ protein. Mapping the location of variant residues on a homology model of the Purβ homodimer suggested that most of the altered residues are remote from the predicted ssDNA‐binding regions of the protein. The repressor activity of each Purβ variant was assessed in transfected fibroblasts and smooth muscle cells via Acta2 promoter‐reporter assays. A Q64* nonsense variant was completely inactive while missense variants exhibited repressor activity that ranged from ~1.5‐fold greater to ~2‐fold less than wild‐type Purβ. Lower activity variants P223L and R297Q were expressed in bacteria and purified to homogeneity. Each variant was physically indistinguishable from wild‐type Purβ in terms of quaternary structure and thermostability. Results of DNA and protein‐binding assays indicated that the P223L and R297Q variants retained high affinity and specificity for purine‐rich ssDNA sequences but differed in their interaction with other Acta2 regulatory proteins. These findings suggest that the presence of certain variant residues affects the Acta2 repressor activity of Purβ by altering its interaction with other transcription factors but not with ssDNA.
Autochthonous Bacillus licheniformis: Probiotic potential and survival ability in low‐fishmeal extruded pellet aquafeed

In recent years, Bacillus spp. have garnered attention as probiotic supplements in aquafeed owing to the production of heat stable and low pH resistant spores. Herein, we isolated and characterized an autochthonous Bacillus licheniformis KCCM 43270 from the intestine of olive flounder (Paralichthys olivaceus) for supplementation in low‐fishmeal extruded aquafeeds. The KCCM 43270 was screened based on amylase, protease, cellulase, and lipase as well as non‐hemolytic activities. The isolate was able to grow in carboxymethyl cellulose (CMC), xylan, and soybean meal (SBM) when used as a single carbon source in the minimal nutrient M9 medium. The KCCM 43270 spores displayed complete survival in acid (pH 2.5) and bile (0.3%, w/v) for 3 hr, strong biofilm formation, and nearly 50% adhesion with intestinal mucus. The spores of the isolate also showed significant survival ability at 80, 90, 100°C for 60, 30, and 1 min, respectively. In addition, the spores in a blend of SBM complex carrier showed significant heat stability at 120°C for 5 min and under different drying conditions. Furthermore, the spores also survived the extrusion process during low‐fishmeal aquafeed manufacturing, implying the potential application of B. licheniformis KCCM 43270 in aquafeed industry.
Light-driven fine chemical production in yeast biohybrids

Light-powered cell factories Bacteria and fungi are used industrially to produce commodity fine chemicals at vast scale. Sugars are an economical feedstock, but many of the desired products require enzymatic reduction, meaning that some of the sugar must be diverted to regenerate the cellular reductant NADPH (reduced form of nicotinamide adenine dinucleotide phosphate). Guo et al. show that electrons from light-sensitive nanoparticles can drive reduction of cellular NADPH in yeast, which can then be used for reductive biosynthetic reactions. This system can reduce diversion of carbon to NADPH regeneration and should be compatible with many existing engineered strains of yeast. Science, this issue p. 813 Light-harvesting nanoparticles power reduction reactions in genetically engineered yeast. Inorganic-biological hybrid systems have potential to be sustainable, efficient, and versatile chemical synthesis platforms by integrating the light-harvesting properties of semiconductors with the synthetic potential of biological cells. We have developed a modular bioinorganic hybrid platform that consists of highly efficient light-harvesting indium phosphide nanoparticles and genetically engineered Saccharomyces cerevisiae, a workhorse microorganism in biomanufacturing. The yeast harvests photogenerated electrons from the illuminated nanoparticles and uses them for the cytosolic regeneration of redox cofactors. This process enables the decoupling of biosynthesis and cofactor regeneration, facilitating a carbon- and energy-efficient production of the metabolite shikimic acid, a common precursor for several drugs and fine chemicals. Our work provides a platform for the rational design of biohybrids for efficient biomanufacturing processes with higher complexity and functionality.