Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluconazole Resistance in Isolates of Uncommon Pathogenic Yeast Species from the United Kingdom

The triazole drug fluconazole remains one of the most commonly prescribed antifungal drugs, both for prophylaxis in high-risk patients and also as a second-line treatment option for invasive Candida infections. Established susceptibility profiles and clinical interpretive breakpoints are available for fluconazole with Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, which account for the majority of infections due to pathogenic yeast species. ABSTRACT The triazole drug fluconazole remains one of the most commonly prescribed antifungal drugs, both for prophylaxis in high-risk patients and also as a second-line treatment option for invasive Candida infections. Established susceptibility profiles and clinical interpretive breakpoints are available for fluconazole with Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, which account for the majority of infections due to pathogenic yeast species. However, less common species for which only limited susceptibility data are available are increasingly reported in high-risk patients and from breakthrough infections. The UK National Mycology Reference Laboratory performs routine antifungal susceptibility testing of clinical isolates of pathogenic yeast submitted from across the United Kingdom. Between 2002 and 2016, ∼32,000 isolates were referred, encompassing 94 different yeast species. Here, we present fluconazole antifungal susceptibility data generated using a CLSI methodology over this 15-year period for 82 species (2,004 isolates) of less common yeast and yeast-like fungi, and amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and anidulafungin, with members of the Nakaseomyces clade (C. glabrata, Candida nivariensis, and Candida bracarensis). At least 22 different teleomorph genera, comprising 45 species, exhibited high MICs when tested with fluconazole (>20% of isolates with MICs higher than the clinical breakpoint [≥8 mg/liter] proposed for C. albicans). Since several of these species have been reported anecdotally from breakthrough infections and therapeutic failures in patients receiving fluconazole, the current study underscores the importance of rapid and accurate yeast identification and may aid clinicians dealing with infections with rarer yeasts to decide whether fluconazole would be appropriate.
Myocyte enhancer factor 2A delays vascular endothelial cell senescence by activating the PI3K/p-Akt/SIRT1 pathway

Myocyte enhancer factor 2A (MEF2A) dysfunction is closely related to the occurrence of senile diseases such as cardiocerebrovascular diseases, but the underlying molecular mechanism is unclear. Here, we studied the effects of MEF2A on the senescent phenotype of vascular endothelial cells (VEC) and downstream signaling pathway, and the association between plasma MEF2A levels and coronary artery disease (CAD). Results showed that MEF2A silencing promoted cell senescence and down-regulated PI3K/p-AKT/Sirtuin 1 (SIRT1) expression. MEF2A overexpression delayed cell senescence and up-regulated PI3K/p-AKT/SIRT1. Hydrogen peroxide (H2O2) treatment induced cellular senescence and down-regulated the expression of MEF2A and PI3K/p-AKT/SIRT1. MEF2A overexpression inhibited cellular senescence and the down-regulation of PI3K/p-AKT/SIRT1 induced by H2O2. Further study revealed that MEF2A directly up-regulated the expression of PIK3CA and PIK3CG through MEF2 binding sites in the promoter region. Pearson correlation and logistic regression analysis showed that the plasma level of MEF2A was negatively correlated with CAD, and with age in the controls. These results suggested that MEF2A can directly up-regulate PI3K gene expression, and one of the molecular mechanisms of delaying effect of MEF2A on VEC cell senescence was SIRT1-expression activation through the PI3K/p-Akt pathway. Moreover, the plasma MEF2A levels may be a potential biomarker for CAD risk prediction.
A Scientific Overview of Smartphone Applications and Electronic Devices for Weight Management in Adults

Worldwide, there are rising trends in overweight and obesity. Therefore, novel digital tools are discussed to improve health-related behaviors. The use of smartphone applications (apps) and wearables (e.g., activity trackers) for self-monitoring of diet and physical activity might have an impact on body weight. By now, the scientific evaluation of apps and wearables for weight management is limited. Although some intervention studies have already investigated the efficacy of aforementioned digital tools on weight management, there are no clear recommendations for its clinical and therapeutic use. Besides the lack in long-term randomized controlled trials, there are also concerns regarding the scientific quality of apps and wearables (e.g., no standards for development and evaluation). Therefore, the objective of present work is: (1) To address challenges and concerns regarding the current digital health market and (2) to provide a selective overview about intervention studies using apps and activity trackers for weight-related outcomes. Based on cited literature, the efficacy of apps and wearables on weight management is assessed. Finally, it is intended to derive potential recommendations for practical guidance.
Association between medical cannabis laws and opioid overdose mortality has reversed over time

Medical cannabis has been touted as a solution to the US opioid overdose crisis since Bachhuber et al. [M. A. Bachhuber, B. Saloner, C. O. Cunningham, C. L. Barry, JAMA Intern. Med. 174, 1668–1673] found that from 1999 to 2010 states with medical cannabis laws experienced slower increases in opioid analgesic overdose mortality. That research received substantial attention in the scientific literature and popular press and served as a talking point for the cannabis industry and its advocates, despite caveats from the authors and others to exercise caution when using ecological correlations to draw causal, individual-level conclusions. In this study, we used the same methods to extend Bachhuber et al.’s analysis through 2017. Not only did findings from the original analysis not hold over the longer period, but the association between state medical cannabis laws and opioid overdose mortality reversed direction from −21% to +23% and remained positive after accounting for recreational cannabis laws. We also uncovered no evidence that either broader (recreational) or more restrictive (low-tetrahydrocannabinol) cannabis laws were associated with changes in opioid overdose mortality. We find it unlikely that medical cannabis—used by about 2.5% of the US population—has exerted large conflicting effects on opioid overdose mortality. A more plausible interpretation is that this association is spurious. Moreover, if such relationships do exist, they cannot be rigorously discerned with aggregate data. Research into therapeutic potential of cannabis should continue, but the claim that enacting medical cannabis laws will reduce opioid overdose death should be met with skepticism.
The Chandra Deep Field North Survey. Ix. Extended X-ray Sources

The ≈ 1 Ms Chandra Deep Field North observation is used to study the extended X-ray sources in the region surrounding the Hubble Deep Field North (HDF-N), yielding the most sensitive probe of extended X-ray emission at cosmological distances to date. A total of six such sources are detected, the majority of which align with small numbers of optically bright galaxies. Their angular sizes, band ratios, and X-ray luminosities — assuming they lie at the same distances as the galaxies coincident with the X-ray emission — are generally consistent with the properties found for nearby groups of galaxies. One source is notably different and is likely to be a poor-to-moderate X-ray cluster at high redshift (i.e., z 0.7). This source has a large angular extent, a double-peaked X-ray morphology, and an overdensity of unusual objects [Very Red Objects, optically faint (I ≥ 24) radio and X-ray sources]. Another of the six is coincident with several z ≈ 1.01 galaxies located within the HDF-N itself, including the FR I radio galaxy VLA J123644.3+621133, and is likely to be a group or poor cluster of galaxies at that redshift. We are also able to place strong constraints on the optically detected cluster of galaxies ClG 1236+6215 at z = 0.85 and the wide-angle-tail radio galaxy VLA J123725.7+621128 at z ∼ 1–2; both sources are expected to have considerable associated diffuse X-ray emission, and yet they have rest-frame 0.5–2.0 keV X-ray luminosities of 3 × 10 42 erg s −1 and (3–15) × 10 42 erg s −1 , respectively. The environments of both sources are either likely to have a significant deficit of hot intra-cluster gas compared to local clusters of galaxies, or they are X-ray groups. We find the surface density of extended X-ray sources in this observation to be 167
Effects of transcranial direct current stimulation (tDCS) on balance improvement: a systematic review and meta-analysis

Abstract Background: Transcranial direct current stimulation (tDCS) has emerged as a promising therapeutic tool to improve balance and optimize rehabilitation strategies. However, current literature shows the methodological heterogeneity of tDCS protocols and results, hindering any clear conclusions about the effects of tDCS on postural control. Objective: Evaluate the effectiveness of tDCS on postural control, and identify the most beneficial target brain areas and the effect on different populations. Methods: Two independent reviewers selected randomized tDCS clinical-trials studies from PubMed, Scopus, Web of Science, and reference lists of retrieved articles published between 1998 and 2017. Most frequently reported centre of pressure (COP) variables were selected for meta-analysis. Other postural control outcomes were discussed in the review. Results: Thirty studies were included in the systematic review, and 11 were submitted to a meta-analysis. A reduction of COP displacement area has been significantly achieved by tDCS, evidencing an improvement in balance control. Individuals with cerebral palsy (CP) and healthy young adults are mostly affected by stimulation. The analysis of the impact of tDCS over different brain areas revealed a significant effect after primary motor cortex (M1) stimulation, however, with no clear results after cerebellar stimulation due to divergent results among studies. Conclusions: tDCS appears to improve balance control, more evident in healthy and CP subjects. Effects are observed when primary MI is stimulated. Cerebellar stimulation should be better investigated.
The inner rod of virulence‐associated type III secretion systems constitutes a needle adapter of one helical turn that is deeply integrated into the system's export apparatus

Type III secretion injectisomes are essential virulence factors for many pathogenic bacteria by mediating the transport of effector proteins into eukaryotic host cells. The secretion conduit of injectisomes is formed by a helical assembly of three hydrophobic proteins (SctR, SctS and SctT), an inner rod (SctI) and a needle filament (SctF). SctI is thought to play a role in switching between the secretion of different substrate classes and assembly of the inner rod has been implicated in regulating the length of the needle filament. While high‐resolution structures of the hydrophobic components and of the needle filament have been solved, little is known about the structure and the assembly of the inner rod, which impedes the deeper assessment of its function. Here we show by exhaustive in vivo photocrosslinking that SctI engages in extensive interactions with SctR and SctT throughout its entire length. Our data imply that the inner rod serves as an adapter between the export apparatus and the needle filament by forming one helical turn. We show that assembly of the inner rod does not play a role in needle length control nor in substrate specificity switching. Instead, our findings imply that inner rod assembly must precede assembly of the needle filament.
MiR-21 Regulates Keloid Formation by Downregulating Smad7 via the TGF- β/Smad Signaling Pathway.

A keloid is a benign fibroproliferative skin tumor that results from abnormal wound healing after injury and tends to grow beyond the boundary of the original wound; the mechanism of keloid formation is still unclear. MiR-21 is a representative miRNA that plays a key role in a variety of fibrotic diseases via the TGF-β/Smad signaling pathway. The aim of our study was to explore the mechanism of keloid formation. First, we found that the expression of miR-21 in keloids and keloid-fibroblasts was significantly upregulated by miRNA microarray and RT-PCR. Additionally, at the protein level, our study confirmed that the overexpression of miR-21 could promote the process of keloid fibrosis to some extent and also indicated that a low expression of miR-21 could inhibit the process of keloid fibrosis. Finally, the results proved that miR-21 could participate in the keloid fibrosis process through negative regulation of its downstream target gene Smad7 via the TGF-β/Smad signaling pathway, which provides a guiding framework for further studies and new theoretical support for keloid clinical treatment.
Education rather than age structure brings demographic dividend

Significance Global environmental change and discussions about the drivers of international migration lead to renewed interest in population growth and global demographic change. The notion of the demographic dividend was introduced to highlight the benefits of fertility decline, yet, among African leaders, it is also often interpreted as describing the benefits of their youthful populations. Due to its controversial nature, the topic of population was not explicitly included in the Sustainable Development Goals. In this controversial discussion, this paper provides a systematic reassessment about what aspects of demographic change have beneficial consequences for economic growth and sustainable development. The relationship between population changes and economic growth has been debated since Malthus. Initially focusing on population growth, the notion of demographic dividend has shifted the attention to changes in age structures with an assumed window of opportunity that opens when falling birth rates lead to a relatively higher proportion of the working-age population. This has become the dominant paradigm in the field of population and development, and an advocacy tool for highlighting the benefits of family planning and fertility decline. While this view acknowledges that the dividend can only be realized if associated with investments in human capital, its causal trigger is still seen in exogenous fertility decline. In contrast, unified growth theory has established human capital as a trigger of both demographic transition and economic growth. We assess the relative importance of changing age structure and increasing human capital for economic growth for a panel of 165 countries during the time period of 1980–2015. The results show a clear dominance of improving education over age structure and give evidence that the demographic dividend is driven by human capital. Declining youth dependency ratios even show negative impacts on income growth when combined with low education. Based on a multidimensional understanding of demography that considers education in addition to age, and with a view to the additional effects of education on health and general resilience, we conclude that the true demographic dividend is a human capital dividend. Global population policies should thus focus on strengthening the human resource base for sustainable development.
Rapid Increase in Carbapenemase-Producing Enterobacteriaceae in Retail Meat Driven by the Spread of the blaNDM-5-Carrying IncX3 Plasmid in China from 2016 to 2018

The presence and molecular characteristics of carbapenemase-producing Enterobacteriaceae (CPE) among meat products in China were investigated. A total of 110 carbapenem-resistant Enterobacteriaceae (CRE) isolates, including 94 Escherichia coli and 10 Klebsiella pneumoniae isolates, were identified from 105 of 794 (13.2%) samples. The positive rates markedly increased from 2016 (9.4%) to 2018 (22.2%). Only blaNDM genes were detected; 79.1% of blaNDM genes were carried by IncX3 plasmids. ABSTRACT The presence and molecular characteristics of carbapenemase-producing Enterobacteriaceae (CPE) among meat products in China were investigated. A total of 110 carbapenem-resistant Enterobacteriaceae (CRE) isolates, including 94 Escherichia coli and 10 Klebsiella pneumoniae isolates, were identified from 105 of 794 (13.2%) samples. The positive rates markedly increased from 2016 (9.4%) to 2018 (22.2%). Only blaNDM genes were detected; 79.1% of blaNDM genes were carried by IncX3 plasmids. Routine monitoring of carbapenemase-producing Enterobacteriaceae in the animal food supply is highly recommended.
Inhalation exposure to volatile organic compounds in the printing industry

ABSTRACT This study reports on the occupational inhalation exposure to VOCs of workers in the Kuwaiti printing industry. Using the evacuated canister methodology, we targeted 72 VOCs in three printeries and compared the concentrations to previous reports and relevant occupational exposure levels (OELs). We found that recent efforts in the printing industry to reduce VOC usage had been successful, as concentrations of key hazardous VOCs were substantially lower than anticipated. On the other hand, nearly all target VOCs were found. Non-production areas were sampled along with the offset printing areas, another strength of this study, and revealed exposures to hazardous VOCs among administers and digital printer and CTP operators. Exposure to ototoxic VOCs amounted to 1–3% of the OEL, consisting mostly of ethylbenzene, which was likely in use in two of the study printeries. Exposure to carcinogenic or probably carcinogenic VOCs was 15–20% of the OEL at four locations across the three printeries, consisting mostly of vinyl chloride and benzyl chloride. Vinyl chloride VOC was partially sourced from outdoors, but was also likely used inside the study printeries. Interestingly, concentrations of vinyl chloride were similar in most sampling locations to that of CFC-114, a CFC banned by the Montreal Protocol and not commonly used as a refrigerant. This unexpected finding suggests further study is warranted to identify the use of these VOCs in printeries. Exposure to hazardous VOCs up to nearly 50% of the OEL, consisting largely of bromoform and vinyl chloride. Bromoform was found in all the study printeries, sourced partially from outdoor air. The higher concentrations found inside the study printeries likely resulted from the use of the desalinated water for washing. This finding raises of emissions from sources other than blanket washes, and inks, etc. adding to the total VOC load in printery indoor air. Implications: Results from this study indicate that efforts to reduce worker exposure to VOCs particularly dangerous to human health in recent years have been successful, but there is still much to be done to protect workers. Exposures to ototoxic and carcinogenic VOCs were identified, among both production and non-production workers. Unexpected findings included the apparent use in printing activities of the carcinogen vinyl chloride and CFC-114, banned under the Montreal Protocol. Observed lapses in safety procedures included failure to utilize ventilation systems and closing doors between work areas, indicating management and worker education should remain a priority.
Chromogranin B regulates early-stage insulin granule trafficking from the Golgi in pancreatic islet β-cells

ABSTRACT Chromogranin B (CgB, also known as CHGB) is abundantly expressed in dense core secretory granules of multiple endocrine tissues and has been suggested to regulate granule biogenesis in some cell types, including the pancreatic islet β-cell, though the mechanisms are poorly understood. Here, we demonstrate a critical role for CgB in regulating secretory granule trafficking in the β-cell. Loss of CgB impairs glucose-stimulated insulin secretion, impedes proinsulin processing to yield increased proinsulin content, and alters the density of insulin-containing granules. Using an in situ fluorescent pulse-chase strategy to track nascent proinsulin, we show that loss of CgB impairs Golgi budding of proinsulin-containing secretory granules, resulting in a substantial delay in trafficking of nascent granules to the plasma membrane with an overall decrease in total plasma membrane-associated granules. These studies demonstrate that CgB is necessary for efficient trafficking of secretory proteins into the budding granule, which impacts the availability of insulin-containing secretory granules for exocytic release. This article has an associated First Person interview with the first author of the paper. Summary: A novel fluorescent pulse-chase technology is used to demonstrate that CgB regulates granule budding in the islet β-cell.
Perceived barriers to accessing Female Community Health Volunteers’ (FCHV) services among ethnic minority women in Nepal: A qualitative study

Despite the efforts of community health workers to increase access to healthcare among ethnic minority groups in low- and -middle income countries, members of ethnic minorities are less likely than women from other ethnic groups to use maternal and child healthcare services. However, much less is known about the factors that limit access of ethnic minorities to healthcare services, including the services of community health workers in Nepal, who are known as Female Community Health Volunteers (FCHVs). To address this issue, we conducted a qualitative study to explore perceived barriers to accessing maternal and child healthcare services among ethnic minority groups in two different geographical locations (the hill and Terai regions- flatland bordering south India) with varying degrees of access to local healthcare centres. Between April 2014 and September 2014, semi-structured interviews were conducted with twenty FCHVs, 26 women service users and 11 paid local health workers. In addition, 15 FCHVs participated in four focus group discussions. A thematic analysis of the data identified five major themes underlying barriers to accessing available maternal and child healthcare services by ethnic minority groups such as Dalits, Madhesi, Muslim, Chepang and Tamang. These themes include: a) lack of knowledge among service users; b) lack of trust in volunteers; c) traditional beliefs and healthcare practices; d) low decision-making power of women; and e) perceived indignities experienced when using health centres. We conclude that community health programmes should focus on increasing awareness of healthcare services among ethnic minority groups, and the programmes should involve family members (husband and mothers-in-law) and traditional health practitioners. Both the FCHVs and local healthcare providers should be trained to communicate effectively in order to deliver respectful care among ethnic minorities if we want to achieve universal healthcare coverage for maternal and child health in low- and -middle income countries.