Miracle-dz/UniFAR-FTUs huggingface dataset:
Ending AIDS by 2030: the importance of an interlinked approach and meaningful youth leadership

This commentary by authors from the Adolescent HIV Treatment Coalition calls for action to improve advocacy and service delivery for young people by leveraging the interlinkages between HIV and the broader development agenda. The 2030 Agenda for Sustainable Development includes target 3.3 on ending the AIDS epidemic by 2030, and along with the 2016 Political Declaration on HIV and AIDS, this has led to a global renewal of political commitment to the HIV response. However, young people are still being left behind, and to provide an equitable and sustainable response to HIV we must ensure that we are meeting the needs of the 3.9 million young people living with HIV, and the millions more at risk.
Is there potential for therapeutic drug monitoring of biologic agents in rheumatoid arthritis?

The use of biologics has significantly changed the management of rheumatoid arthritis over the last decade, becoming the cornerstone treatment for many patients. The current therapeutic arsenal consists of just under 10 biologic agents, with four different mechanisms of action. Several studies have demonstrated a large interindividual pharmacokinetic variability, which translates to unpredictability in clinical response among individuals. The present review focuses on the pharmacokinetics and pharmacodynamics of biologic agents approved for rheumatoid arthritis. The literature relating to their concentration–effect relationship and the use of pharmacokinetic–pharmacodynamic modelling to optimize drug regimens is analysed. Due to the scarcity and complexity of these studies, the current dosing strategy is based on clinical indexes/aspects. In general, dose individualization for biologics should be implemented increasingly in clinical practice as there is a direct benefit for treated rheumatoid arthritis patients. Moreover, there is an indirect benefit in terms of cost‐effectiveness.
The long non‐coding RNA SPRY4‐IT1: An emerging player in tumorigenesis and osteosarcoma

Accumulating evidence from genome‐wide analysis and functional studies has begun to unveil the important role of long non‐coding RNAs (lncRNAs) in cancer development. The lncRNA SPRY4‐IT1 is derived from an intron of SPRY4 gene and was originally reported to be upregulated in melanoma in which it functioned as an oncogene. Since this discovery, an increasing number of studies have investigated the expression and function of SPRY4‐IT1 in human cancers. Aberrant expression of SPRY4‐IT1 has now been documented in different cancer types, including osteosarcoma, breast, renal, oesophageal and prostate cancers. However, its deregulation and function in lung and gastric cancers remain controversial. Pertinent to clinical practice, SPRY4‐IT1 expression has been shown to predict survival of cancer patients. In this review, we summarize recent evidence concerning SPRY4‐IT1 deregulation and the associated mechanisms in human cancers. We also discuss the potential clinical utilization of this lncRNA as a diagnostic and prognostic biomarker for cancer patients.
The relationship between gestational age and the severity of neonatal abstinence syndrome

BACKGROUND AND AIMS The relationship between gestational age at delivery and the severity of neonatal abstinence syndrome (NAS) is poorly understood. Our objective was to compare the length of pharmacotherapy and hospital stay among opioid-exposed infants born during the late pre-term, early term, full term and late term periods. DESIGN Retrospective cohort study of infants affected by NAS. SETTING MetroHealth Medical Center in Cleveland, OH, USA: an urban tertiary care hospital serving as the referral center for opioid dependency in pregnancy with a level III neonatal intensive care unit. PARTICIPANTS All deliveries complicated by maternal opioid exposure from January 2000 to October 2014; 403 were eligible to be included [n = 102 late pre-term, 34-36 weeks (LP), n = 158 early term, 37-38 weeks (ET), n = 122 full term, 39-40 weeks (FT), n = 21 late term, ≥41 weeks (LT)]. MEASUREMENTS NAS requiring pharmacotherapy with opioids and hospital stay duration were compared between gestational age cohorts. Interaction by type of maternal medication was evaluated. FINDINGS The necessity for pharmacotherapy for NAS was similar in all gestational age groups [LP n = 45/102 (44%), ET n = 65/158 (41%), FT n = 55/122 (45%), LT n = 9/21 (43%); P = 0.92]. However, the median duration of pharmacotherapy for NAS was significantly different between the groups [LP =16.0 median (interquartile range: IQR = 10.0-24.0) days, ET = 22.5 (IQR = 15.0-40.0), FT = 23.0 (IQR = 6.0-38.0), LT = 22.0 (IQR = 6.0-28.0); P = 0.02]. Neonatal intensive care unit admission for NAS (P = 0.07) and total length of stay (P = 0.27), which includes observation for NAS not requiring medication, were not different. There was no significant interaction between gestational age cohorts and maternal medication assisted treatment therapy on the need for or duration of NAS treatment. The results were unchanged when evaluated for potential confounding variables. CONCLUSIONS Gestational age (pre-term, term or late term) at birth appears to be unrelated to the need for pharmacotherapy to treat neonatal abstinence syndrome (NAS) in late pre-term and term infants. If treatment is needed it may tend to be given for longer in term than pre-term or late term infants.
Performance investigation of 12-slot/14-pole PM machines with different winding configurations

This paper presents an Comparative investigation of three 12-slot/14-pole surface-mounted permanent-magnet (SPM) machines with different winding configurations by finite element analysis (FEA). Three winding distributions for machines are investigated. For the first two situations, machines have equal teeth width, with one having all teeth wound and the other having alternative teeth wound. For the third case, also alternative teeth winding are adopted while the teeth having coils are narrower than these without coils. Firstly, we analyzed flux linkage flux density and back electromotive force (back-EMF) of the machines. Then we studied their torque characteristics including electromagnetic torque and cogging torque. In addition, we studied the fault tolerant capability of machines. The results show that machine with alternative teeth wound on unequal teeth has the highest torque capability although with a slightly higher ripple torque. The cogging torque and ripple torque of machine with all teeth wound are the lowest. Machines with alternative teeth wound either on equal teeth or unequal teeth have better fault tolerant capability.
The Isl1-Lhx3 Complex Promotes Motor Neuron Specification by Activating Transcriptional Pathways that Enhance Its Own Expression and Formation

Abstract Motor neuron (MN) progenitor cells rapidly induce high expression of the transcription factors Islet-1 (Isl1), LIM-homeobox 3 (Lhx3), and the transcriptional regulator LMO4, as they differentiate. While these factors are critical for MN specification, the mechanisms regulating their precise temporal and spatial expression patterns are not well characterized. Isl1 and Lhx3 form the Isl1-Lhx3 complex, which induces the transcription of genes critical for MN specification and maturation. Here, we report that Isl1, Lhx3, and Lmo4 are direct target genes of the Isl1-Lhx3 complex. Our results show that specific genomic loci associated with these genes recruit the Isl1-Lhx3 complex to activate the transcription of Isl1, Lhx3, and Lmo4 in embryonic MNs of chick and mouse. These findings support a model in which the Isl1-Lhx3 complex amplifies its own expression through a potent autoregulatory feedback loop and simultaneously enhances the transcription of Lmo4. LMO4 blocks the formation of the V2 interneuron-specifying Lhx3 complex. In developing MNs, this action inhibits the expression of V2 interneuron genes and increases the pool of unbound Lhx3 available to incorporate into the Isl1-Lhx3 complex. Identifying the pathways that regulate the expression of these key factors provides important insights into the genetic strategies utilized to promote MN differentiation and maturation.
Lignin degradation: microorganisms, enzymes involved, genomes analysis and evolution

Abstract Extensive research efforts have been dedicated to describing degradation of wood, which is a complex process; hence, microorganisms have evolved different enzymatic and non-enzymatic strategies to utilize this plentiful plant material. This review describes a number of fungal and bacterial organisms which have developed both competitive and mutualistic strategies for the decomposition of wood and to thrive in different ecological niches. Through the analysis of the enzymatic machinery engaged in wood degradation, it was possible to elucidate different strategies of wood decomposition which often depend on ecological niches inhabited by given organism. Moreover, a detailed description of low molecular weight compounds is presented, which gives these organisms not only an advantage in wood degradation processes, but seems rather to be a new evolutionatory alternative to enzymatic combustion. Through analysis of genomics and secretomic data, it was possible to underline the probable importance of certain wood-degrading enzymes produced by different fungal organisms, potentially giving them advantage in their ecological niches. The paper highlights different fungal strategies of wood degradation, which possibly correlates to the number of genes coding for secretory enzymes. Furthermore, investigation of the evolution of wood-degrading organisms has been described.
Visual structures for image browsing

Content-Based Image Retrieval (CBIR) presents several challenges and has been subject to extensive research from many domains, such as image processing or database systems. Database researchers are concerned with indexing and querying, whereas image processing experts worry about extracting appropriate image descriptors. Comparatively little work has been done on designing user interfaces for CBIR systems. This, in turn, has a profound effect on these systems since the concept of image similarity is strongly influenced by user perception. This paper describes an initial effort to fill this gap, combining recent research in CBIR and Information Visualization, studied from a Human-Computer Interface perspective. It presents two visualization techniques based on Spiral and Concentric Rings implemented in a CBIR system to explore query results. The approach is centered on keeping user focus on both the query image, and the most similar retrieved images. Experiments conducted so far suggest that the proposed visualization strategies improves system usability.
Compile-Time Techniques for Improving Scalar Access Performance in Parallel Memories

Compile-time techniques for storage allocation of scalar values into memory modules that limit run-time memory-access conflicts are presented. The allocation approach is applicable to those operands in instructions that can be predicted at compile-time, where an instruction is composed of the multiple operations and corresponding operands that execute in parallel. Algorithms to schedule data transfers among memory modules to avoid conflicts that cannot be eliminated by the distribution of values alone are developed. The techniques have been implemented as part of a compiler for a reconfigurable long instruction word architecture. Results of experiments are presented demonstrating that a very high percentage of memory access conflicts can be avoided by scheduling a very low number of data transfers. >
Robust nonparametric estimation of monotone regression functions with interval‐censored observations

Nonparametric estimation of monotone regression functions is a classical problem of practical importance. Robust estimation of monotone regression functions in situations involving interval‐censored data is a challenging yet unresolved problem. Herein, we propose a nonparametric estimation method based on the principle of isotonic regression. Using empirical process theory, we show that the proposed estimator is asymptotically consistent under a specific metric. We further conduct a simulation study to evaluate the performance of the estimator in finite sample situations. As an illustration, we use the proposed method to estimate the mean body weight functions in a group of adolescents after they reach pubertal growth spurt.
Individual differences in normal body temperature: longitudinal big data analysis of patient records

Abstract Objective To estimate individual level body temperature and to correlate it with other measures of physiology and health. Design Observational cohort study. Setting Outpatient clinics of a large academic hospital, 2009-14. Participants 35 488 patients who neither received a diagnosis for infections nor were prescribed antibiotics, in whom temperature was expected to be within normal limits. Main outcome measures Baseline temperatures at individual level, estimated using random effects regression and controlling for ambient conditions at the time of measurement, body site, and time factors. Baseline temperatures were correlated with demographics, medical comorbidities, vital signs, and subsequent one year mortality. Results In a diverse cohort of 35 488 patients (mean age 52.9 years, 64% women, 41% non-white race) with 243 506 temperature measurements, mean temperature was 36.6°C (95% range 35.7-37.3°C, 99% range 35.3-37.7°C). Several demographic factors were linked to individual level temperature, with older people the coolest (–0.021°C for every decade, P<0.001) and African-American women the hottest (versus white men: 0.052°C, P<0.001). Several comorbidities were linked to lower temperature (eg, hypothyroidism: –0.013°C, P=0.01) or higher temperature (eg, cancer: 0.020, P<0.001), as were physiological measurements (eg, body mass index: 0.002 per m/kg2, P<0.001). Overall, measured factors collectively explained only 8.2% of individual temperature variation. Despite this, unexplained temperature variation was a significant predictor of subsequent mortality: controlling for all measured factors, an increase of 0.149°C (1 SD of individual temperature in the data) was linked to 8.4% higher one year mortality (P=0.014). Conclusions Individuals’ baseline temperatures showed meaningful variation that was not due solely to measurement error or environmental factors. Baseline temperatures correlated with demographics, comorbid conditions, and physiology, but these factors explained only a small part of individual temperature variation. Unexplained variation in baseline temperature, however, strongly predicted mortality.
Need (more than) two to Tango: Multiple tools to adapt to changes in oxygen availability

Oxygen is a fundamental element for the life of a large number of living organisms allowing an efficient energetic utilization of substrates. Organisms relying on oxygen evolved complex structures for oxygen delivery and biochemical machineries dealing with its safe utilization and the ability to overcome the potentially harmful consequences of changes in oxygen availability. On fact, cells composing complex Eukaryotic organisms are set to live within an optimum narrow range of oxygen, quite specific for each cell type. Minute modifications of oxygen availability, either positive or negative, induce the expression of specific genes, the major actors of this responses being the transcription factors HIF and Nrf2 that control the attempt to cope with low oxygen (hypoxia) or to either high oxygen or to an oxygen “overflow,” respectively. This review describes the interaction between these two transcription factors and their interaction with the transcription factor NF‐κB acting as a pivotal determinant of final cell response. © 2018 BioFactors, 44(3):207–218, 2018
Association of C5L2 genetic polymorphisms with coronary artery disease in a Han population in Xinjiang, China

Background C5aR-like receptor 2 (C5L2) has been identified as a receptor for the inflammatory factor Complement 5a (C5a) and acylation-stimulating protein (ASP). ASP binding to C5L2 leading to a net accumulation of TG stores and glucose transporter. The aim of the present study is to evaluate the association of the SNPs of C5L2 gene with coronary artery disease (CAD) in a Chinese population. Methods We examined the role of the tagging single nucleotide polymorphisms (SNPs) of C5L2 gene for CAD using a case-control design. We determined the prevalence of C5L2 genotypes in 505 CAD patients and 469 age and sex-matched healthy control subjects of Han population. Results There was significant difference in genotype distributions of rs2972607 and rs8112962 between CAD patients and control subjects. The rs2972607 was found to be associated with CAD in a dominant model (AA vs. AG + GG, P<0.001). Similarly, the rs8112962 was found to be associated with CAD in a dominant model (TT vs CT + CC, P=0.016). The difference remained statistically significant after multivariate adjustment (OR =1.401, 95% confidence interval [CI]:1.026~1.914, P=0.034; OR = 1.541, 95%CI:1.093~ 2.172, P=0.014; respectively). Conclusion The results of this study indicate that both rs2972607 and rs8112962 of C5L2 gene are associated with CAD in a Han population of China.
A common African variant of human connexin 37 is associated with Caucasian primary ovarian insufficiency and has a deleterious effect in vitro

Folliculogenesis requires communication between granulosa cells and oocytes, mediated by connexin-based gap junctions. Connexin 37 (Cx37)-deficient female mice are infertile. The present study assessed Cx37 deficiency in patients with primary ovarian insufficiency (POI). A candidate gene study was performed in patients and controls from the National Genotyping Center (Evry, France) including 58 Caucasian patients with idiopathic isolated POI and 142 Caucasian controls. Direct genomic sequencing of the coding regions of the GJA4 gene (encoding Cx37) was performed with the aim to identify a deleterious variant associated with POI and absent in ethnically matched controls. A single Cx37 variant absent in the control population was identified, namely a c.946G>A heterozygous substitution leading to a p.Gly316Ser variant that was present in two POI patients. This variant was absent in all Caucasian controls from various databases, and has been observed exclusively in African populations. This variant was identified to have a dominant negative effect in HeLa cells in vitro to alter connexon function (by 67.2±7.17%), as determined by Gap-fluorescence recovery after photobleaching. The alteration principally resulted from a decrease of cell surface connexons due to altered trafficking (by 47.73±8.59%). In marked contrast to this observation, a p.Pro258Ser variant frequent in all ethnic populations in databases had no functional effect in vitro. In conclusion, the present study reported on a Cx37 variant in two Caucasian POI patients, which was absent in control Caucasian populations, and which had a deleterious effect in vitro. It is therefore suggested that in the genetic context of the Caucasian population, this variant may contribute to POI.
The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line.

BACKGROUND The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or α-L-Guluronic Acid is a new NSAID with immunomodulatory features. OBJECTIVES Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. METHODS HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. RESULTS We found that concentrations of ≤125 µg/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 µg/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). CONCLUSION The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.
CONSORT for Reporting Randomized Controlled Trials in Journal and Conference Abstracts: Explanation and Elaboration

Background Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract. Methods and Findings We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item. Conclusions CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help authors of abstracts of these trials provide the detail and clarity needed by readers wishing to assess a trial's validity and the applicability of its results.