Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Antibacterial Activity of Febuxostat, an FDA-Approved Antigout Drug against Mycobacterium tuberculosis Infection

Accumulating evidence suggests that drug repurposing has drawn attention as an anticipative strategy for controlling tuberculosis (TB), considering the dwindling drug discovery and development pipeline. In this study, we explored the antigout drug febuxostat and evaluated its antibacterial activity against Mycobacterium species. ABSTRACT Accumulating evidence suggests that drug repurposing has drawn attention as an anticipative strategy for controlling tuberculosis (TB), considering the dwindling drug discovery and development pipeline. In this study, we explored the antigout drug febuxostat and evaluated its antibacterial activity against Mycobacterium species. Based on MIC evaluation, we found that febuxostat treatment significantly inhibited mycobacterial growth, especially that of Mycobacterium tuberculosis (Mtb) and its phylogenetically close neighbors, M. bovis, M. kansasii, and M. shinjukuense, but these microorganisms were not affected by allopurinol and topiroxostat, which belong to a similar category of antigout drugs. Febuxostat concentration-dependently affected Mtb and durably mediated inhibitory functions (duration, 10 weeks maximum), as evidenced by resazurin microtiter assay, time-kill curve analysis, phenotypic susceptibility test, and the Bactec MGIT 960 system. Based on these results, we determined whether the drug shows antimycobacterial activity against Mtb inside murine bone marrow-derived macrophages (BMDMs). Notably, febuxostat markedly suppressed the intracellular growth of Mtb in a dose-dependent manner without affecting the viability of BMDMs. Moreover, orally administered febuxostat was efficacious in a murine model of TB with reduced bacterial loads in both the lung and spleen without the exacerbation of lung inflammation, which highlights the drug potency. Taken together, unexpectedly, our data demonstrated that febuxostat has the potential for treating TB.
DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype

Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug-tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte-specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, microphthalmia-associated transcription factor (MITF) and SRY-box transcription factor 10 (SOX10), important in melanoma development and progression, have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation, and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF-methylated cultures were subdivided in 2 distinct subtypes. Examining mRNA levels of neural crest–associated genes, we found that 1 subtype had lost the expression of several lineage genes, including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF-methylated melanoma cells using CRISPR/Cas9 supported these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.
Simultaneous detection of JAK2, CALR, and MPL mutations and quantitation of JAK2 V617F allele burden in myeloproliferative neoplasms using the quenching probe‐Tm method in i‐densy IS‐5320

Accurate detection of myeloproliferative neoplasms (MPN)‐associated gene mutations is necessary to correctly diagnose MPN. However, conventional gene testing has various limitations, including the requirement of skilled technicians, cumbersome experimental procedures, and turnaround time of several days. The gene analyzer i‐densy IS‐5320 allows gene testing using the quenching probe‐Tm method. Specifically, pretreatment of samples including DNA extraction, amplification and detection of genes, and analysis of results are performed in a fully automatic manner after samples and test reagents are added into this system, which is compact and can be easily installed in a laboratory. The aim of this study is to investigate the sensitivity and specificity associated with the simultaneous detection of MPN‐associated gene mutations.
Percolation network of growing V2O5 nanowires

Percolation network of the growing V2O5 nanowires was demonstrated by devising a simple but practical method to investigate the percolation phenomena. As the reaction proceeded in the ammonium(meta)vanadate solution at room temperature, the lengths of V2O5 nanowires increased at a speed of 0. 13μm∕day at an early stage of the growth and 0. 03μm∕day on the average up to 3 months. Percolation network was made by abruptly freezing the homogeneously dispersed aqueous solutions of V2O5 nanowires in liquid nitrogen. After 7h of aging time, an abrupt increase of the conductance was observed, revealing the satisfaction of the percolation threshold (pc∼0.17) at the average wire length of 40nm.
Factors influencing the elderly’s behavioural intention to use smart home technologies in Saudi Arabia

In recent years, smart home technologies have offered opportunities for elderly people to manage their daily health-related activities. Despite the advancement in smart home technology (SHT), the level of end-user acceptance among elderly people is still low. This study proposes an SHT framework by examining the determinants of elderly behavioural intention (BI) to use smart home technologies by extending the Unified Theory of Acceptance and Use of Technology (UTAUT) model. This study uses the quantitative approach to survey about 486 elderly people in Saudi Arabia, and it applies the Partial Least Square Structural Equation Model (PLS-SEM) technique to perform the data analysis. Findings reveal that culture influence and technology awareness are significant factors in determining the BI to use SHT among elderly people. The study also finds that attitude mediates the relationships between performance expectancy, effort expectancy, and behavioural intention. We find that region and education moderate the relationships between culture influence, technology awareness, and behavioural intention. This study theoretically extends the UTAUT theory by including external constructs: culture influence, technology awareness, attitude, education, and region.
Depressive Symptoms and Caregiving Intensity Before and After Onset of Dementia in Partners

Background: Caring for a partner with dementia poses significant emotional burden and high care demands, but changes in impacts before and after dementia onset is unclear. Objective: Examine changes in depressive symptoms and hours of care provided by caregivers through the course of their partners’ cognitive decline. Methods: Retrospective, observational study using household survey data from 2000–2016 Health and Retirement Study and count models to evaluate older individuals’ (ages ≥51 y) depressive symptoms (measured using the shortened Center for Epidemiologic Studies Depression Scale) and weekly caregiving in the 10 years before and after their partners’ dementia onset (identified using Telephone Interview Cognitive Status screening). Relationships were examined overall and by sex and race. Results: We identified 8298 observations for 1836 older caregivers whose partners developed dementia. From before to after partners’ dementia onset, caregivers’ mean (SD) depressive symptoms increased from 1.4 (1.9) to 1.9 (2.1) (P<0.001) and weekly caregiving increased from 4.4 (19.7) to 20.8 (44.1) (P<0.001) hours. Depressive symptoms and caregiving hours were higher for women compared with men. Depressive symptoms were higher for Blacks compared with Whites, while caregiving hours were higher for Whites. The expected count of caregivers’ depressive symptoms and caregiving hours increased by 3% (P<0.001) and 9% (P=0.001) before partners’ dementia onset and decreased by 2% (P<0.001) and 1% (P=0.63) following partners’ dementia onset. No differences observed by sex or race. Discussion: Depressive symptoms and instrumental burdens for caregivers increase substantially before the onset of dementia in partners. Early referral to specialty services is critical.
Integrating genomic and epidemiologic data to accelerate progress toward schistosomiasis elimination

The global community has adopted ambitious goals to eliminate schistosomiasis as a public health problem, and new tools are needed to achieve them. Mass drug administration programs, for example, have reduced the burden of schistosomiasis, but the identification of hotspots of persistent and reemergent transmission threaten progress toward elimination and underscore the need to couple treatment with interventions that reduce transmission. Recent advances in DNA sequencing technologies make whole-genome sequencing a valuable and increasingly feasible option for population-based studies of complex parasites such as schistosomes. Here, we focus on leveraging genomic data to tailor interventions to distinct social and ecological circumstances. We consider two priority questions that can be addressed by integrating epidemiological, ecological, and genomic information: (1) how often do non-human host species contribute to human schistosome infection? and (2) what is the importance of locally acquired versus imported infections in driving transmission at different stages of elimination? These questions address processes that can undermine control programs, especially those that rely heavily on treatment with praziquantel. Until recently, these questions were difficult to answer with sufficient precision to inform public health decision-making. We review the literature related to these questions and discuss how whole-genome approaches can identify the geographic and taxonomic sources of infection, and how such information can inform context-specific efforts that advance schistosomiasis control efforts and minimize the risk of reemergence.
Biomechanical Energetics of Terrestrial Locomotion in California Sea Lions (Zalophus californianus).

Pinnipedia, an order of semi-aquatic marine mammals, adapted a body design that allows for efficient aquatic locomotion but limited terrestrial locomotion. Otariids, like the California sea lion (Zalophus californianus), have enlarged forelimbs and can bring their hindlimbs under the body to locomote quadrupedally on land. Phocids (true seals) have reduced forelimbs and are unable to bring their hindlimbs beneath them during terrestrial locomotion. Due to these differences, phocids are expected have greater energetic costs when moving on land compared to otariids. The mechanical costs of transport and power outputs of terrestrial locomotion were first obtained from one male and two female adult California sea lions through video recording locomotion sequences across a level runway. The center of mass, along with six other anatomical points, were digitized to obtain variables such as velocity (V), amplitude of heave (A), and the frequency (f) of oscillations during the locomotion cycle. These variables represent the principal parameters of a biomechanical model that computes the power output of individuals. The three California sea lions in this study averaged a power output of 112.04 watts and a Cost of Transport of 0.63 J kg-1 m-1. This footage was compared against video footage previously recorded of three phocid species (harbor seal, gray seal, and northern elephant seal). Power output and mechanical Cost of Transport were compared between all four pinniped species following the animals' center of mass. The quadrupedal gait of sea lions showed lower vertical displacements of the center of mass, and higher velocities compared to the terrestrial gait of phocids. Northern elephant seals, gray seal, and the harbor seal showed significantly higher Costs of Transport and power outputs from the sea lions. California sea lions locomote with lower energetic costs, and thus higher efficiency compared to phocids, proving that they are a mechanically intermediate species on land between terrestrial mammals and phocids. This study provides novel information on the mechanical energy exerted by pinnipeds, particularly California sea lions, to then be used in future research to better understand the limitations of these aquatic mammals.
Theory & Methods: Residual Diagnostic Plots for Checking for Model Mis‐specification in Time Series Regression

This paper considers residuals for time series regression. Despite much literature on visual diagnostics for uncorrelated data, there is little on the autocorrelated case. To examine various aspects of the fitted time series regression model, three residuals are considered. The fitted regression model can be checked using orthogonal residuals; the time series error model can be analysed using marginal residuals; and the white noise error component can be tested using conditional residuals. When used together, these residuals allow identification of outliers, model mis‐specification and mean shifts. Due to the sensitivity of conditional residuals to model mis‐specification, it is suggested that the orthogonal and marginal residuals be examined first.
Novel antiinflammatory biologics shaped by parasite–host coevolution

Significance Inflammatory bowel diseases (IBD) are on the rise. Many studies have highlighted an inverse correlation between infection with parasitic helminths and the incidence of immune-mediated inflammatory diseases, such as IBD. The mechanisms by which parasitic helminths suppress inflammation and prevent the onset of inflammatory diseases is not well understood. This study describes a discovery and validation pipeline of antiinflammatory biologics from the recombinant secretome of gut-dwelling hookworms as novel and safe drug leads. Numerous proteins from distinct families protected mice against inducible colitis, and lead proteins suppressed production of inflammatory cytokines from IBD patient gut biopsy T cells ex vivo, highlighting a gold mine of new biologics inspired by coevolution of humans and their macrobiome.
Identification of cap-dependent endonuclease inhibitors with broad-spectrum activity against bunyaviruses

Significance Bunyaviruses, like influenza viruses, possess a cap-dependent endonuclease (CEN) that mediates the critical cap-snatching step of viral RNA transcription. We identified the antibunyavirus compounds among influenza CEN inhibitors and identified specific structures involved in the inhibitory mechanism. These were 100- to 1,000-fold more active in vitro than ribavirin against bunyaviruses, including Lassa virus, lymphocytic choriomeningitis virus (LCMV), and Junin virus. In LCMV-infected mice, the compounds significantly decreased blood viral load, suppressed symptoms such as thrombocytopenia and hepatic dysfunction, and improved survival rates. Since effective compounds against other bunyaviruses including La Crosse virus, severe fever with thrombocytopenia syndrome virus, and hantavirus were also identified, we demonstrated the potential clinical utility of CEN inhibitors for the treatment of viral hemorrhagic diseases.
Na0.5K0.5NbO3/SiO2/Si thin film varactor

Perfectly c-axis oriented micrometer thickNa 0.5 K 0.5 NbO 3 (NKN) films have been prepared on a thermally grown ultrathinSiO 2 template layer onto a Si(001) wafer by the pulsed laser deposition technique. A x-ray diffraction θ–2θ scan reveals multiple-cell structuring of single phase NKN film along the polar axis, while filmsgrown onto amorphous ceramic (Corning) glass show a mixture of slightly c-axis oriented NKN and pyrochlore phases. This implies a small amount ofSiO 2 crystallites distributed in an amorphous matrix inherit Si(001) orientation and promotes highly oriented NKN film growth. NKN filmdielectric permittivitye ′ was found to vary from 114.0 to 107.2 in the frequency range 1 kHz–1 MHz, while the resistivity was on the order of2.6×10 10 Ω cm @ 20 kV/cm. The planar interdigital variable reactance device (varactor) based on theNKN/SiO 2 /Si thin film structure possesses a dissipation factor of 0.8% at 1 MHz and zero bias, electrical tunability of 3.1%, and nA order leakage current at 20 V bias at room temperature.
Deep Spatio-Temporal Attention-Based Recurrent Network From Dynamic Adaptive Functional Connectivity for MCI Identification

Most existing methods of constructing dynamic functional connectivity (dFC) network obtain the connectivity strength via the sliding window correlation (SWC) method, which estimates the connectivity strength at each time segment, rather than at each time point, and thus is difficult to produce accurate dFC network due to the influence of the window type and window width. Furthermore, the deep learning methods may not capture the discriminative spatio-temporal information that is closely related to disease, thus impacting the performance of mild cognitive impairment (MCI) identification. In this paper, a novel spatio-temporal attention-based bidirectional gated recurrent unit (STA-BiGRU) network is proposed to extract inherent spatio-temporal information from a dynamic adaptive functional connectivity (dAFC) network for MCI diagnosis. Specifically, we adopt a group lasso-based Kalman filter algorithm to obtain the dAFC network with more accurate connectivity strength at each time step. Then a spatial attention module with self-attention and a temporal attention module with multiple temporal attention vectors are incorporated into the BiGRU network to extract more discriminative disease-related spatio-temporal information. Finally, the spatio-temporal regularizations are employed to better guide the attention learning of STA-BiGRU network to enhance the robustness of the deep network. Experimental results show that the proposed framework achieves mean accuracies of 90.2%, 90.0%, and 81.5%, respectively, for three MCI classification tasks. This study provides a more effective deep spatio-temporal attention-based recurrent network and obtains good performance and interpretability of deep learning for psychiatry diagnosis research.
The impact of climate change and urban growth on urban climate and heat stress in a subtropical city The impact of climate change and urban growth on heat stress

Urban residents face increasing risk of heat stress due to the combined impact of climate change and intensification of the urban heat island (UHI) associated with urban growth. Considering the combined effect of urban growth and climate change is vital to understanding how temperatures in urban areas will change in the future. This study investigated the impact of urban growth and climate change on the UHI and heat stress in a sub-tropical city (Brisbane, Australia) in the present day (1991-2000) and medium term (2041-2050; RCP8.5) during summer. A Control and Urban Growth scenario were used to compare the temperature increase from climate change alone with the temperature increase from climate change and urban growth. Average and minimum temperatures increased more with climate change and urban growth combined than with climate change alone, indicating that if urban growth is ignored, future urban temperatures could be under-estimated. Under climate change alone, rural temperatures increased more than urban temperatures, decreasing the effect of the UHI by 0.4°C at night and increasing the urban cool island by 0.8°C during the day. With climate change, the number of hot days and nights doubled in urban and rural areas in 2041-2050 as compared to 1991-2000. The number of hot nights was higher in urban areas and with urban growth. Dangerous heat stress, defined as Apparent Temperature above This article is protected by copyright. All rights reserved. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/joc.5998 A cc ep te d A rt ic le 40°C, increased with climate change, and occurred on average 1-2 days every summer during 2041-2050, even in shaded conditions. There was higher temperature increases with urban growth and climate change than with climate change alone, indicating that reducing the effect of the UHI is vital to ensuring urban growth does not increase the heat stress risks that urban residents will face in the future.
Which children with chest-indrawing pneumonia can be safely treated at home, and under what conditions is it safe to do so? A systematic review of evidence from low- and middle-income countries

Background WHO pneumonia guidelines recommend that children (aged 2-59 months) with chest indrawing pneumonia and without any “general danger sign” can be treated with oral amoxicillin without hospital admission. This recommendation was based on trial data from limited contexts whose generalisability is unclear. This review aimed to identify which children with chest-indrawing pneumonia in low- and middle-income countries can be safely treated at home, and under what conditions is it safe to do so. Methods We searched MEDLINE, EMBASE, and PubMed for observational and interventional studies of home-based management of children (aged 28 days to four years) with chest-indrawing pneumonia in low- or middle-income countries. Results We included 14 studies, including seven randomised trials, from a variety of urban and rural contexts in 11 countries. Two community-based and two hospital-based trials in Pakistan and India found that home treatment of chest-indrawing pneumonia was associated with similar or superior treatment outcomes to hospital admission. Evidence from trials (n = 3) and observational (n = 6) studies in these and other countries confirms the acceptability and feasibility of home management of chest-indrawing pneumonia in low-risk cases, so long as safeguards are in place. Risk assessment includes clinical danger signs, oxygen saturation, and the presence of comorbidities such as undernutrition, anaemia, or HIV. Pulse oximetry is a critical risk-assessment tool that is currently not widely available and can identify severely ill patients with hypoxaemia otherwise possibly missed by clinical assessment alone. Additional safeguards include caregiver understanding and ability to return for review. Conclusions Home treatment of chest-indrawing pneumonia can be safe but should only be recommended for children confirmed to be low-risk and in contexts where appropriate care and safety measures are in place.
The comet light curve atlas (the comet light curve catalogue/atlas. III : The atlas)

The comet light curve atlas is a compilation of light curves of periodic comets, covering the period 1899-1989, except for P/Encke, which also has the period 1832-1989 included. The magnitudes have been taken from a compilation of a large number of observations. The different corrections applied to the magnitudes are described. These corrections are colour corrections, a delta effect correction, telescope aperture corrections and corrections for sky conditions