Miracle-dz/UniFAR-FTUs huggingface dataset:
Determinants in Nonstructural Protein 4A of Dengue Virus Required for RNA Replication and Replication Organelle Biogenesis

DENV is the most prevalent mosquito-borne virus, causing around 390 million infections each year. There are no approved therapies to treat DENV infection, and the only available vaccine shows limited efficacy. ABSTRACT Dengue virus (DENV) constitutes one of the most important arboviral pathogens affecting humans. The high prevalence of DENV infections, which cause more than 20,000 deaths annually, and the lack of effective vaccines or direct-acting antiviral drugs make it a global health concern. DENV genome replication occurs in close association with the host endomembrane system, which is remodeled to form the viral replication organelle that originates from endoplasmic reticulum (ER) membranes. To date, the viral and cellular determinants responsible for the biogenesis of DENV replication organelles are still poorly defined. The viral nonstructural protein 4A (NS4A) can remodel membranes and has been shown to associate with numerous host factors in DENV-replicating cells. In the present study, we used reverse and forward genetic screens and identified sites within NS4A required for DENV replication. We also mapped the determinants in NS4A required for interactions with other viral proteins. Moreover, taking advantage of our recently developed polyprotein expression system, we evaluated the role of NS4A in the formation of DENV replication organelles. Together, we report a detailed map of determinants within NS4A required for RNA replication, interaction with other viral proteins, and replication organelle formation. Our results suggest that NS4A might be an attractive target for antiviral therapy. IMPORTANCE DENV is the most prevalent mosquito-borne virus, causing around 390 million infections each year. There are no approved therapies to treat DENV infection, and the only available vaccine shows limited efficacy. The viral nonstructural proteins have emerged as attractive drug targets due to their pivotal role in RNA replication and establishment of virus-induced membranous compartments, designated replication organelles (ROs). The transmembrane protein NS4A, generated by cleavage of the NS4A-2K-4B precursor, contributes to DENV replication by unknown mechanisms. Here, we report a detailed genetic interaction map of NS4A and identify residues required for RNA replication and interaction between NS4A-2K-4B and NS2B-3 as well as NS1. Importantly, by means of an expression-based system, we demonstrate the essential role of NS4A in RO biogenesis and identify determinants in NS4A required for this process. Our data suggest that NS4A is an attractive target for antiviral therapy.
A total cost perspective of type 1 and 2 diabetes mellitus in two South African medical schemes servicing the public healthcare sector.

BACKGROUND Diabetes is increasingly becoming a public health concern in South Africa (SA). There are limited available data on the costs of diabetes. OBJECTIVES To provide a total cost perspective of diabetes using medical scheme claims data from two SA medical schemes servicing the public healthcare sector in 2015 and 2016. METHODS We analysed data from 2 363 diabetes patients. Direct diabetes care costs included medication, consumables, hospitalisation and routine laboratory tests. Indirect costs were calculated by allocating economic costs related to disability-adjusted life years. RESULTS The mean (standard deviation) age was 65.8 (13.4) years and women comprised 51% of the group. Hospitalisation (64.7% in 2015 and 65.5% in 2016) and medication (31.0% in 2015 and 21.1% in 2016) contributed the most to total direct costs. Total direct diabetes care costs mounted to ZAR2 452 per patient in 2015 and ZAR2 486 in 2016. Indirect costs were ZAR17 223 per patient in 2015 and ZAR18 711 in 2016. When direct and indirect costs were combined, the costs accrued to ZAR27.9 billion (ZAR19 675 per patient) in 2015 and ZAR29.9 billion (ZAR21 197 per patient) in 2016, representing 0.688% and 0.689% of the SA gross domestic product over the 2 years, respectively. CONCLUSIONS Diabetes and its associated costs hold significant implications for the healthcare sector and the country's economy. Large numbers of diabetic individuals remain undiagnosed and the true costs of diabetes might even be higher.
Microwave, Ultrasound, and Mechanochemistry: Unconventional Tools that Are Used to Obtain “Smart” Catalysts for CO2 Hydrogenation

: The most recent progress obtained through the precise use of enabling technologies, namely microwave, ultrasound, and mechanochemistry, described in the literature for obtaining improved performance catalysts (and photocatalysts) for CO 2 hydrogenation, are reviewed. In particular, the main advantages (and drawbacks) found in using the proposed methodologies will be discussed and compared by focusing on catalyst design and optimization of clean and efﬁcient (green) synthetic processes. The role of microwaves as a possible activation tool used to improve the reaction yield will also be considered.
AI models and the future of genomic research and medicine: True sons of knowledge?

The increasing availability of large‐scale, complex data has made research into how human genomes determine physiology in health and disease, as well as its application to drug development and medicine, an attractive field for artificial intelligence (AI) approaches. Looking at recent developments, we explore how such approaches interconnect and may conflict with needs for and notions of causal knowledge in molecular genetics and genomic medicine. We provide reasons to suggest that—while capable of generating predictive knowledge at unprecedented pace and scale—if and how these approaches will be integrated with prevailing causal concepts will not only determine the future of scientific understanding and self‐conceptions in these fields. But these questions will also be key to develop differentiated policies, such as for education and regulation, in order to harness societal benefits of AI for genomic research and medicine.
A Hybrid clustering and classification technique for forecasting short‐term energy consumption

This paper presents a hybrid approach to predict the electric energy usage of weather‐sensitive loads. The presented method utilizes the clustering paradigm along with ANN and SVM approaches for accurate short‐term prediction of electric energy usage, using weather data. Since the methodology being invoked in this research is based on CRISP data mining, data preparation has received a great deal of attention in this research. Once data pre‐processing was done, the underlying pattern of electric energy consumption was extracted by the means of machine learning methods to precisely forecast short‐term energy consumption. The proposed approach (CBA‐ANN‐SVM) was applied to real load data and resulting higher accuracy comparing to the existing models. © 2018 American Institute of Chemical Engineers Environ Prog, 38: 66–76, 2019
Comprehensively Improved Performance of β-Ga2O3 Solar-Blind Photodetector Enabled by a Homojunction with Unique Passivation Mechanisms.

Ga2O3-based solar-blind photodetectors have been extensively investigated for a wide range of applications. However, to date, a lot of research has focused on optimizing the epitaxial technique or constructing a heterojunction, and studies concerning surface passivation, a key technique in electronic and optoelectronic devices, are severely lacking. Here, we report an ultrasensitive metal-semiconductor-metal photodetector employing a β-Ga2O3 homojunction structure realized by low-energy surface fluorine plasma treatment, in which an ultrathin fluorine-doped layer served for surface passivation. Without inserting/capping a foreign layer, this strategy utilized fluorine dopants to both passivate local oxygen vacancies and suppress surface chemisorption. The dual effects have opposite impacts on device current magnitude (by suppressing metal/semiconductor junction leakage and inhibiting surface-chemisorption-induced carrier consumption) but dominate in dark and under illumination, respectively. By means of such unique mechanisms, the simultaneous improvement on dark and photo current characteristics was achieved, leading to the sensitivity enhanced by nearly 1 order of magnitude. Accordingly, the 15 min treated sample exhibited striking competitiveness in terms of comprehensive properties, including a dark current as low as 6 pA, a responsivity of 18.43 A/W, an external quantum efficiency approaching 1 × 106%, a specific detectivity of 2.48 × 1014 Jones, and a solar-blind/UV rejection ratio close to 1 × 105. Furthermore, the response speed was effectively accelerated because of the reduction on metal/semiconductor interface trap states. Our findings provide a facile, economical, and contamination-free surface passivation technique, which unlocks the potential for comprehensively improving the performance of β-Ga2O3 solar-blind metal-semiconductor-metal photodetectors.
Readiness for scale-up: lessons learned from the Public Health Agency of Canada’s Innovation Strategy

The Public Health Agency of Canada Innovation Strategy (PHAC-IS) funded the development and delivery of interventions that addressed priority population health issues over a 10-year period between 2009 and 2020. The design of the PHAC-IS funding program integrated the intentional effort of scale-up to increase the reach and impact of proven population health promotion interventions towards long-term, sustained impact benefit at individual, community, and systems levels. Recognizing that social innovation and adaptive cycles are necessary for effective scale-up, the PHAC-IS developed and applied a Scale-up Readiness Assessment Tool (SRAT) to assess the level of scale-up readiness of a funded project. Development of the SRAT included identifying predictors of success for the scale-up of effective population health interventions, organized into eight common characteristics among projects that indicated scale-up readiness: (1) intervention evidence and evaluation, (2) reach and scale, (3) organizational capacity, (4) partnership development, (5) system readiness, (6) community context, (7) cost factors, and (8) knowledge development and exchange. Although the SRAT was not a standalone decision-making rubric, it was a key part of a framework for review, consideration, and assessment for scale-up along a phased approach to funding. The development and application of the SRAT to measure readiness for scale-up provides insights into domains that can be used by funding organizations to inform scale-up decisions or for community organizations to assess their own readiness for scale-up.
No influence of hepatic steatosis on the 3‐year outcomes of patients with quiescent chronic hepatitis B

The influence of hepatic steatosis on the natural history of chronic hepatitis B (CHB) virus is unclear. Therefore, we investigated whether concurrent steatosis in patients with CHB influences the probability of hepatitis B surface antigen (HBsAg) loss, fibrosis progression and hepatocellular carcinoma (HCC) development. This study enrolled treatment‐naïve patients with virologically (HBV DNA <2,000 IU/ml) and biochemically (alanine aminotransferase level <40 IU/L) quiescent CHB who underwent transient elastography between January 2004 and December 2015 and completed 3 years of follow‐up.
Evaluation of a Tool for Measuring Temporal Modulation Detection

Objectives: A software tool (EasyMDT) that measures temporal modulation detection thresholds of a broadband noise carrier is presented. EasyMDT is designed to be both easy and quick to promote the use in environments where testing time is limited, and testers may not have extensive technical expertise to use typical research software. In addition, by providing a standardized stimulus and protocol, data collected by all groups using the software can be compared directly. Details of EasyMDT, including a description of the protocol, stimuli, interface and how to obtain the software, are provided along with representative sample data from both normal-hearing listeners and cochlear implant (CI) users. Performance with the EasyMDT is compared with speech understanding metrics as well as a metric of spectral-temporal resolution. Design: A “Full Curve” of modulation detection thresholds is measured using a three-interval forced-choice adaptive task in a single block for 7 modulation frequencies (10, 50, 75, 100, 150, 200, and 300 Hz). Similarly, the modulation detection thresholds were measured for only one modulation frequency in a block (either 100 Hz or 150 Hz). Modulation detection thresholds and block duration were recorded. In addition, performance on speech recognition tasks (CNC words, consonant identification, vowel identification, and AzBio sentences in noise) and a spectral-temporal resolution task (SMRT; Aronoff and Landsberger) were measured. Modulation detection thresholds were measured for both normal-hearing listeners and CI users. Only CI users participated in the speech and spectral-temporal tests. Results: Modulation detection thresholds measured with EasyMDT were consistent with those previously reported from other laboratories. Modulation detection thresholds at a single modulation frequency (100 Hz or 150 Hz) were predictive of modulation detection thresholds measured as part of the Full Curve consisting of all 7 modulation frequencies. Testing durations for CI users dropped from an average of over 18 minutes for the Full Curve to under 3 minutes for either of the single modulation frequency measures. Modulation detection thresholds at 100 Hz correlated with CNC words, consonant identification, and AzBio sentences in noise, but not vowel identification. No correlations were found between modulation detection and spectral-temporal resolution. Conclusions: The EasyMDT is designed to be an easy-to-use tool that provides a nonlinguistic measure that can predict speech understanding. The test duration is short enough that it can be incorporated into clinical practice or as part of an experimental battery. The software is available for free download at https://www.ear-lab.org/software-downloads.html. The software is designed to have a minimum barrier of entry as well as provide a standardized protocol allowing direct comparison of modulation detection thresholds across studies and groups.
Pinch Loss Ameliorates Obesity, Glucose Intolerance, and Fatty Liver by Modulating Adipocyte Apoptosis in Mice

The mammalian focal adhesion proteins Pinch1/2 activate integrins and promote cell–extracellular matrix adhesion and migration; however, their roles in adipose tissue and metabolism are unclear. Here we find that high-fat diet (HFD) feeding dramatically increases expression of Pinch1/2 proteins in white adipose tissue (WAT) in mice. Furthermore, expression of Pinch1 is largely upregulated in WAT in leptin-deficient ob/ob type 2 diabetic mice and obese humans. While mice with loss of Pinch1 in adipocytes or global Pinch2 do not display any notable phenotypes, deleting Pinch1 in adipocytes and Pinch2 globally significantly decreases body weight and WAT mass, but not brown adipose tissue mass, in HFD-fed, but not normal chow diet–fed, mice. Pinch loss ameliorates HFD-induced glucose intolerance and fatty liver. After HFD challenge, Pinch loss slightly but significantly accelerates energy expenditure. While Pinch loss decreases adipocyte size and alters adipocyte size distribution, it greatly accelerates cell apoptosis primarily in epididymal WAT and to a lesser extent in subcutaneous WAT. In vitro studies demonstrate that Pinch loss accelerates adipocyte apoptosis by activating the Bim/Caspase-8 pathway. In vivo, genetic ablation of Caspase-8 expression in adipocytes essentially abolishes the ameliorating effects of Pinch deficiency on obesity, glucose intolerance, and fatty liver in mice. Thus, we demonstrate a previously unknown function of Pinch in control of adipose mass, glucose, and fat metabolism via modulation of adipocyte apoptosis. We may define a novel target for the prevention and treatment of metabolic diseases, such as obesity and diabetes.
Coastal darkening substantially limits the contribution of kelp to coastal carbon cycles

Macroalgal‐dominated habitats are rapidly gaining recognition as important contributors to marine carbon cycles and sequestration. Despite this recognition, relatively little is known about the production and fate of carbon originating from these highly productive ecosystems, or how anthropogenic‐ and climate‐related stressors affect the role of macroalgae in marine carbon cycles. Here, we examine the impact of increasing turbidity on carbon storage, fixation and loss in southern hemisphere kelp forests. We quantified net primary production (NPP) and biomass accumulation (BA), and estimated carbon release via detritus and dissolved organic carbon (DOC) across a large‐scale turbidity gradient. We show that increased turbidity, resulting in a 63% reduction in light, can result in a 95% reduction in kelp productivity. When averaged annually, estimates of NPP and BA per plant at high‐light sites were nearly six and two times greater than those at low‐light sites, respectively. Furthermore, the quantity of carbon fixed annually by kelp forests was up to 4.7 times greater than that stored as average annual standing stock. At low‐light sites, the majority of C goes directly into tissue growth and is subsequently eroded. In contrast, excess production at high‐light sites accounts for up to 39% of the total carbon fixed and is likely released as DOC. Turbidity is expected to increase in response to climate change and our results suggest this will have significant impacts on the capacity of kelp forests to contribute to carbon sequestration pathways. In addition to demonstrating that turbidity significantly reduces the quantity of carbon fixed by kelp forests, and subsequently released as detritus, our results highlight the negative impacts of turbidity on a large source of previously unaccounted for carbon.
Phytophthora capsici CBM1‐containing protein CBP3 is an apoplastic effector with plant immunity‐inducing activity

Abstract Carbohydrate‐binding module family 1 (CBM1) is a cellulose‐binding domain that is almost exclusively found in fungi and oomycetes. CBM1‐containing proteins (CBPs) have diverse domain architectures and play pivotal roles in the plant–microbe interaction. However, only a few CBPs have been functionally investigated. In this study, we identified PcCBP3 in an oomycete pathogen, Phytophthora capsici. PcCBP3 contains two tandem CBM1 domains and its orthologs from other Phytophthora species exhibit diversity including gene loss, pseudogenization, variations in sequences, and domain structures. PcCBP3 is upregulated during infection and knockout of PcCBP3 results in significantly decreased virulence. Moreover, PcCBP3 requires signal peptide to induce BAK1‐dependent cell death in Nicotiana benthamiana. Further studies indicate that PcCBP3‐triggered cell death and plant immunity require its N‐terminal region, which is conserved in CBM1‐containing proteins and other small, secreted, cysteine‐rich protein from oomycetes. These results suggest that PcCBP3 is an apoplastic effector and could be perceived by the plant immune system.
Clinical success between tilted and axial implants in edentulous maxilla: A systematic review and meta-analysis

Aim: This systematic review and meta-analysis evaluated the clinical survival of axial and tilted implants in atrophic edentulous maxilla after three years of immediate loading and also the corresponding marginal bone loss. Setting and Design: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA). Materials and Methods: The relevant studies were retrieved from MEDLINE(PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), Science Direct, Google Scholar databases. The search was limited to studies published in the English language with no date restrictions. A further hand search was conducted on individual journals and reference lists of studies. The risk of bias in included studies was assessed by using the Evidence Project risk of bias tool. Statistical Analysis Used: Statistical meta-analysis was conducted using RevMan 5.4 software. The assessment for the level of evidence was done using GRADEpro software. Results: Eleven studies were finalised. All were included in the meta-analysis for implant survival, while only seven studies were included in the meta-analysis of marginal bone loss. After three years, the meta-analysis results for implant survival showed no statistical difference between axial and tilted implants, with the forest plot neither favouring axial nor tilted implants (RR = 1.00 (95% CI: 0.98-1.01); P-value = 0.59). After three years, the meta-analysis results for marginal bone showed no statistical difference between axial and tilted implants, with the forest plot neither favouring axial nor tilted implants (MD = -0.02; 95% CI; -0.09-0.06; P-value = 0.69). Conclusion: In the immediately loaded rehabilitation of completely edentulous atrophic maxillae, tilting of implants did not induce any significant alteration in their survival and their corresponding marginal bone loss levels compared to conventionally placed axial implants even after three years of function.
What is the likelihood of nonpulmonary metastasis occurring in the absence of lung metastasis in bone and soft tissue sarcoma? A nested case‐control from a sarcoma referral centre

Nonpulmonary metastases (NPM) are rare, associated with a poorer prognosis, and maybe missed on conventional chest imaging for sarcoma surveillance. We determined (1) the proportion of NPM occurring in isolation or with synchronous or prior pulmonary metastases (PM), and (2) if initial NPM would have been recognized with a standard surveillance protocol.
Thymic and Peripheral T-cell Polarization in an Experimental Model of Russell’s Viper Venom-induced Acute Kidney Injury

ABSTRACT Venom pathology is not restricted to the direct toxic effects of venom. Immunoinflammatory alteration as the etiology of snake venom-induced acute kidney injury (SAKI) is a less trodden path toward the development of alternative therapeutic approach. In the present study, we have associated the crest of renal damage stage to the immunological alteration, as reflected in thymic and peripheral T cell polarization in the murine model of SAKI. Renal injury in mice was confirmed from significant dysuresis and adversely altered biochemical renal markers. Histopathological alterations, as revealed by marked tubular and glomerular damage, reaffirmed kidney injury. SAKI is accompanied by significant inflammatory changes as indicated by neutrophilic leucocytosis, increased neutrophil to lymphocyte ratio and plasma CRP levels. Thymic immunophenotyping revealed significantly increased CD8+ cytotoxic T cell, and CD25+ both single positive population (p = .017–0.010) and CD44−CD25+ double negative population (DN3) (p = .002) accompanied by an insignificantly reduced CD4+ helper T cells (p = .451). Peripheral immunophenotyping revealed similar pattern as indicated by reduced helper T cells (p = .002) associated with significantly elevated cytotoxic T cells (p = .009) and CD25+ subset of both helper (p = .002) and cytotoxic (p = .024) T cells. The IL-10+ subset of both CD25+ and CD25− T cells were also found to be significantly elevated in the SAKI group (p ≤ 0.020) suggesting an immunosuppressive phenotype in SAKI. It can be concluded that T cells responds to venom-induced renal injury particularly through IL-10+ reparative phenotypes which are known for their immunosuppressive and anti-inflammatory activity.