Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of Goiter and Thyroid Nodules before and after Implementation of the Universal Salt Iodization Program in Mainland China from 1985 to 2014: A Systematic Review and Meta-Analysis

Objectives We comprehensively estimated the prevalence of goiter and thyroid nodules (TNs) before and after the implementation of the Universal Salt Iodization (USI) program in mainland China and provided information for creating effective health policies. Methods PubMed, Google Scholar, CNKI, Chinese Wanfang and Chongqing VIP databases were searched for relevant studies from Jan 1985 to Feb 2014. Data from eligible citations were extracted by two independent reviewers. All analyses were performed with Stata 11.0 and SPSS 17.0. Results Eligible articles (N = 31; 4 in English and 27 in Chinese) included 52 studies (15 about goiter rates made before 1996 and 14 afterwards, and 23 about TNs). Our meta-analysis suggests a pooled prevalence for goiter before and after 1996 and for TNs of 22.8% (95% CI: 15.3%, 30.3%), 12.6% (95% CI: 9.4%, 15.8%) and 22.7% (95% CI: 18.3%, 27.0%), respectively. Egger's test of three independent categories revealed no evidence of publication bias (p = 0.101, 0.148 and 0.113, respectively). Conclusions The prevalence of goiter was reduced by almost half after 1996 in mainland China, so the USI program was considered beneficial. However, subgroup analysis suggests that both insufficient and excess iodine may be associated with goiter. The prevalence of goiter and TNs increased significantly after 2002, suggesting a risk of excessive iodine intake. Thus, salt iodization standardizations should be set according to local conditions.
Stage-specific follicular extracellular vesicle uptake and regulation of bovine granulosa cell proliferation†

Abstract Follicular fluid within ovarian antral follicles contains numerous factors, which influence the development of a healthy oocyte including nucleic acids, steroids, proteins, and extracellular vesicles (EVs). Current evidence indicates that follicular EVs promote changes in cellular gene expression and support cumulus–oocyte complex expansion in vitro. In this study, we found EVs from different sized follicles differentially stimulate granulosa cell proliferation and this could be explained by both the differential contents associated, on or within the vesicles and by the preferential uptake of EVs dependent on follicle size from which they were isolated. Antibody array and inhibitor studies indicated that the Src, PI3K/Akt, and MAPK signaling pathways mediate the stimulatory effects of EVs on granulosa cell proliferation. This study demonstrates for the first time that EVs isolated from follicular fluid are capable of stimulating granulosa cell proliferation and that this stimulatory response is associated with the size of antral follicle from which the EVs originated. The study further also provides the first evidence that vesicles released by small antral follicles are preferentially taken up when compared to those isolated from large follicles, suggesting that vesicular surface proteins change during follicular maturation. Summary Sentence Follicular fluid derived extracellular vesicles exhibit differential ability to stimulate granulosa cell proliferation and uptake that is dependent upon the stage of follicle development.
What should an ASP Solver output ? A Multiple Position Paper ?

This position paper raises some issues regarding the output of solvers for Answer Set Programming and discusses experiences made in several different settings. The first set of issues was raised in the context of the first ASP system competition, which led to a first suggestion for a standardised yet miniature output format. We then turn to experiences made in related fields, like Satisfiability Checking, and finally adopt an application point of view by investigating interface issues both with simple tools and in the context of the Semantic Web and query answering.
Pixe, Electron Microprobe Data, and Experimental Archaeology: Tell el-Ajjul and Pilot Studies of Gold Granulation Joining Practices in the Mediterranean Bronze Age

This paper discusses the results of a pilot study using Proton Induced X-ray Emission (PIXE) analysis of gold granulated objects from the Bronze Age site of Tell el-Ajjul in Southern Palestine obtained with the Oxford University proton microprobe. Using modern granulated samples with known smithing processes as points of comparison, it is demonstrated how information on ancient joining practices may be accurately gauged. The importance of characterizing objects of known provenance is emphasized in a discussion of archaeological context. It is argued that the building of a large Mediterranean-wide database of granulation analyses can add new depths to our understanding of temporal, social, cultural and technological relationships in the past.
Antagonists of growth hormone-releasing hormone receptor induce apoptosis specifically in retinoblastoma cells

Significance Our work demonstrates that the growth hormone-releasing hormone receptor (GHRH-R) is highly expressed in human retinoblastoma (RB) cells, but not in other retinal cells. GHRH-R antagonists induced apoptosis in RB cells, but not other retinal cells, suggesting the specificity of their action of this class of analogs. GHRH-R antagonists also increased the expression of apoptotic genes and suppressed expression of cell proliferation genes. These studies indicate that GHRH-R is involved in the survival and proliferation of RB. GHRH-R antagonists could possibly be developed for RB therapy. Retinoblastoma (RB) is the most common intraocular cancer in children worldwide. Current treatments mainly involve combinations of chemotherapies, cryotherapies, and laser-based therapies. Severe or late-stage disease may require enucleation or lead to fatality. Recently, RB has been shown to arise from cone precursor cells, which have high MDM2 levels to suppress p53-mediated apoptosis. This finding leads to the hypothesis that restoring apoptosis mechanisms in RBs could specifically kill the cancer cells without affecting other retinal cells. We have previously reported involvement of an extrapituitary signaling pathway of the growth hormone-releasing hormone (GHRH) in the retina. Here we show that the GHRH receptor (GHRH-R) is highly expressed in RB cells but not in other retinal cells. We induced specific apoptosis with two different GHRH-R antagonists, MIA-602 and MIA-690. Importantly, these GHRH-R antagonists do not trigger apoptosis in other retinal cells such as retinal pigmented epithelial cells. We delineated the gene expression profiles regulated by GHRH-R antagonists and found that cell proliferation genes and apoptotic genes are down- and up-regulated, respectively. Our results reveal the involvement of GHRH-R in survival and proliferation of RB and demonstrate that GHRH-R antagonists can specifically kill the RB cells.
CKR: Live Demo: Representing an Evolving Scenario by Contexts and Exceptions

Contextualization of knowledge has recently gained interest in the Semantic Web community and a number of logic based solutions have been proposed. In this regard, in our previous works we have introduced the Contextualized Knowledge Repository (CKR) framework: we recently extended CKR with the possibility to reason with defeasible axioms and their exceptions. The goal of this demo is to demonstrate the use of contexts and exceptions in representing evolving situations: the demo visualizes the evolution of a soccer match by showing the (non-monotonic) changes in the knowledge across different events composing the match.
Comprehensive review of visual defects reported with topiramate

Objective The objective of this study was to analyze clinical patterns of visual field defects (VFDs) reported with topiramate treatment and assess possible mechanism of action (MOA) for antiepileptic drug (AED) associated VFDs. Methods A comprehensive topiramate database review included preclinical data, sponsor’s clinical trials database, postmarketing spontaneous reports, and medical literature. All treatment-emergent adverse events (TEAEs) suggestive of retinal dysfunction/damage were summarized. Relative risk (RR) was computed from topiramate double-blind, placebo-controlled trials (DBPCTs) data. Results Preclinical studies and medical literature review suggested that despite sharing gamma-aminobutyric acid (GABA)-ergic MOA with other AEDs, topiramate treatment was not associated with VFDs. TEAEs suggestive of retinal dysfunction/damage were observed in 0.3%–0.7% of adults and pediatric patients with topiramate (N=4,679) versus ≤0.1% with placebo (N=1,834) in DBPCTs for approved indications (epilepsy and migraine prophylaxis); open-label trials (OLTs) and DBPCTs for investigational indications had similar incidence. Overall, 88% TEAEs were mild or moderate in severity. Serious TEAEs were very rare (DBPCTs: 0%; OLTs: ≤0.1%), and most were not treatment limiting, and resolved. The most common visual TEAEs (approved indications) were VFD, scotoma, and optic atrophy. The incidence of TEAEs in DBPCTs (approved and investigational indications) was higher in topiramate-treated (N=9,169) versus placebo-treated patients (N=5,023; 0.36% vs 0.24%), but the RR versus placebo-treated patients was not significant (RR: 1.51 [95% confidence interval: 0.78, 2.91]). Conclusion VFDs do not appear to be a class effect for AEDs with GABA-ergic MOA. The RR for VFDs is not significantly different between topiramate and placebo treatment.
Genetic algorithms based adaptive search area control for real time multiple face detection using neural networks

Fast and automatic face detection from visual scenes is a vital preprocessing step in many face applications like recognition, authentication, analysis, etc. While detection of a single face can be accomplished with good accuracy, multiple faces detection in real time is more challenging not only because of different face sizes and orientations, but also due to limits of the processing power available. In this paper, we propose a real time multiple face detection method using multiple neural networks and an adaptive search area control method base on genetic algorithms. Although, neural networks and genetic algorithms may not be suitable for real time application because of their long processing times, we show that high detection accuracies and fast speeds can be achieved using small sized effective neural networks and a genetic algorithm with a small population size that requires few generations to converge. The proposed method subdivides the face into several small regions, each connected to an individual neural network. The subdivision guarantees small size networks and presents the ability to learn different face regions features using region-specialized input coding methods. The genetic algorithm is used during the real time search to extract possible face samples from face candidates. The fitness of the face samples is calculated using the neural networks. In the successive frames, the search area is adaptively controlled based on the information inherited from the proceeding frames. To prove the effectiveness of our approach we performed real time simulation using an inexpensive USB camera.
Large-Scale Patterns of Turnover and Basal Area Change in Andean Forests

General patterns of forest dynamics and productivity in the Andes Mountains are poorly characterized. Here we present the first large-scale study of Andean forest dynamics using a set of 63 permanent forest plots assembled over the past two decades. In the North-Central Andes tree turnover (mortality and recruitment) and tree growth declined with increasing elevation and decreasing temperature. In addition, basal area increased in Lower Montane Moist Forests but did not change in Higher Montane Humid Forests. However, at higher elevations the lack of net basal area change and excess of mortality over recruitment suggests negative environmental impacts. In North-Western Argentina, forest dynamics appear to be influenced by land use history in addition to environmental variation. Taken together, our results indicate that combinations of abiotic and biotic factors that vary across elevation gradients are important determinants of tree turnover and productivity in the Andes. More extensive and longer-term monitoring and analyses of forest dynamics in permanent plots will be necessary to understand how demographic processes and woody biomass are responding to changing environmental conditions along elevation gradients through this century.
CRISPR as a strong gene editing tool

Clustered regularly-interspaced short palindromic repeats (CRISPR) is a new and effective genetic editing tool. CRISPR was initially found in bacteria to protect it from virus invasions. In the first step, specific DNA strands of virus are identified by guide RNA that is composed of crRNA and tracrRNA. Then RNAse III is required for producing crRNA from pre-crRNA. In The second step, a crRNA:tracrRNA:Cas9 complex guides RNase III to cleave target DNA. After cleavage of DNA by CRISPR-Cas9, DNA can be fixed by Non-Homologous End Joining (NHEJ) and Homology Directed Repair (HDR). Whereas NHEJ is simple and random, HDR is much more complex and accurate. Gene editing by CRISPR is able to be applied to various biological field such as agriculture and treating genetic diseases in human.
Connectivity Maps via Function-on-Scalar Regression

Functional connectivity of an individual human brain is often studied by acquiring a resting state functional magnetic resonance imaging scan, and mapping the correlation of each voxel’s BOLD time series with that of a seed region. As large collections of such maps become available, including multisite data sets, there is an increasing need for ways to distill the information in these maps in a readily visualized form. Here we propose a two-step analytic strategy. First, we construct connectivity-distance profiles, which summarize the connectivity of each voxel in the brain as a function of distance from the seed, a functional relationship that has attracted much recent interest. Next, these profile functions are regressed on predictors of interest, whether categorical (e.g., acquisition site or diagnostic group) or continuous (e.g., age). This procedure can provide insight into the roles of multiple sources of variation, and detect large-scale patterns not easily available from conventional analyses. We illustrate the proposed methods with a resting state data set pooled across four imaging sites.
The importance of protecting surgical instrument tables from intraoperative contamination in clean surgeries.

OBJECTIVE to compare the degree of bacterial contamination of surgical instrument tables used in clean surgical procedures, either protected with plastic fields, sterilized with ethylene oxide, or disinfected with 70% alcohol and 1% iodine solutions. This is a randomized clinical trial in which samples were collected from the surfaces of surgical instrument tables before and after each procedure. Microbiological analysis was performed to identify microorganisms and their respective antimicrobial resistance. RESULTS Bacterial growth in the surgeries using sterilized plastic was 5.71% before and 28.6% after surgery and, 2.9% and 45.7% respectively in surgeries using disinfection with 70% alcohol and 1% iodine solutions; no statistical difference was found between the methods. CONCLUSION both methods present similar protection, however, 70% alcohol and 1% iodine do not generate solid waste.
UGT1A1 Genetic Variations and a Haplotype Associated with Neonatal Hyperbilirubinemia in Indonesian Population

Neonatal hyperbilirubinemia (NH) is a common finding in newborn babies in Indonesia. Common and rare variants of UGT1A1 have been known to contribute to NH etiology. This study aims to identify UGT1A1 genetic variation and haplotype associated with NH in Indonesian population. DNA was isolated from 116 cases and 115 controls and a targeted-deep sequencing approach was performed on the promoter, UTRs, and exonic regions of UGT1A1. Determining association of common variants and haplotype analysis were performed using PLINK and Haploview. Ten and 4 rare variants were identified in cases and controls, respectively. The UGT1A1 rare variants frequency in cases (5.17%) was higher than that in controls (1.7%). Four of those rare variants in cases (p.Ala61Thr, p.His300Arg, p.Lys407Asn, and p.Tyr514Asn) and three in controls (p.Tyr79X, p.Ala346Val, and p.Thr412Ser) are novel variants. The frequencies of p.Gly71Arg, p.Pro229Gln, and TA7 common variants were not significantly different between cases and controls. A haplotype, consisting of 3 major alleles of 3′ UTRs common variants (rs8330C>G, rs10929303C>T, and rs1042640C>G), was associated with NH incidence (p = 0.025) in this population. Using targeted-deep sequencing and haplotype analysis, we identified novel UGT1A1 rare variants and disease-associated haplotype in NH in Indonesian population.
Machine Learning for the Deterioration of Patients on Hospital Wards

Early Warning Score Systems assign scores to a patient’s vital signs to detect adverse events in order to secure timely medical response. However, most systems do not account for variations in vital signs due to aging changes or sex differences, which affects the accuracy of current systems for different deteriorating patient sub-groups. We aimed to develop an Ageand Sex-Based Early Warning Score derived from statistical distributions of vital signs across ages and sexes. The data is obtained from four hospitals in Oxford, United Kingdom, which contains a total of 48,433 patient admissions to the wards with documented sex and age, including 3,182 patient admissions with at least one adverse event. Vital sign distributions were compared at each year of age (age, 16 yr to 99 yr) as well as sexes (females and males) using aggregated cumulative distribution functions. The centiles of the vital sign distributions modeled the normal ranges of the Ageand Sexbased Early Warning Score. An adverse event was defined as the occurrence of in-hospital mortality, cardiac arrest or ICU admission within the first 24 hours of stay. The area under the receiver operating curve for the Ageand Sex-Based Early Warning Score was higher than that of existing systems, namely Centile-based Early Warning Score (0.828 vs 0.730; p <0.001), the National Early Warning Score (0.828 vs 0.808; p <0.001) and the Modified Centile-based Early Warning Score (0.828 vs. 0.825; p <0.001). The Ageand Sex-Based Early Warning Score also outperformed the current systems over the nonelderly patients (age, 16 yr to 40 yr), and amongst both sexes, females and males. Our results suggest that accounting for ageand sex-related vital sign changes more can accurately detect deterioration of non-elderly patients prior to an adverse event than current methods. Further investigations of ageand sexspecific methods are necessary to decrease preventable deaths.
Role of the JNK Pathway in Varicella-Zoster Virus Lytic Infection and Reactivation

ABSTRACT Mechanisms of neuronal infection by varicella-zoster virus (VZV) have been challenging to study due to the relatively strict human tropism of the virus and the paucity of tractable experimental models. Cellular mitogen-activated protein kinases (MAPKs) have been shown to play a role in VZV infection of nonneuronal cells, with distinct consequences for infectivity in different cell types. Here, we utilize several human neuronal culture systems to investigate the role of one such MAPK, the c-Jun N-terminal kinase (JNK), in VZV lytic infection and reactivation. We find that the JNK pathway is specifically activated following infection of human embryonic stem cell-derived neurons and that this activation of JNK is essential for efficient viral protein expression and replication. Inhibition of the JNK pathway blocked viral replication in a manner distinct from that of acyclovir, and an acyclovir-resistant VZV isolate was as sensitive to the effects of JNK inhibition as an acyclovir-sensitive VZV isolate in neurons. Moreover, in a microfluidic-based human neuronal model of viral latency and reactivation, we found that inhibition of the JNK pathway resulted in a marked reduction in reactivation of VZV. Finally, we utilized a novel technique to efficiently generate cells expressing markers of human sensory neurons from neural crest cells and established a critical role for the JNK pathway in infection of these cells. In summary, the JNK pathway plays an important role in lytic infection and reactivation of VZV in physiologically relevant cell types and may provide an alternative target for antiviral therapy. IMPORTANCE Varicella-zoster virus (VZV) has infected over 90% of people worldwide. While primary infection leads to the typically self-limiting condition of chickenpox, the virus can remain dormant in the nervous system and may reactivate later in life, leading to shingles or inflammatory diseases of the nervous system and eye with potentially severe consequences. Here, we take advantage of newer stem cell-based technologies to study the mechanisms by which VZV infects human neurons. We find that the c-Jun N-terminal kinase (JNK) pathway is activated by VZV infection and that blockade of this pathway limits lytic replication (as occurs during primary infection). In addition, JNK inhibition limits viral reactivation, exhibiting parallels with herpes simplex virus reactivation. The identification of the role of the JNK pathway in VZV infection of neurons reveals potential avenues for the development of alternate antiviral drugs.
The small GTPase Rab8 interacts with VAMP-3 to regulate the delivery of recycling T-cell receptors to the immune synapse

ABSTRACT IFT20, a component of the intraflagellar transport (IFT) system that controls ciliogenesis, regulates immune synapse assembly in the non-ciliated T-cell by promoting T-cell receptor (TCR) recycling. Here, we have addressed the role of Rab8 (for which there are two isoforms Rab8a and Rab8b), a small GTPase implicated in ciliogenesis, in TCR traffic to the immune synapse. We show that Rab8, which colocalizes with IFT20 in Rab11+ endosomes, is required for TCR recycling. Interestingly, as opposed to in IFT20-deficient T-cells, TCR+ endosomes polarized normally beneath the immune synapse membrane in the presence of dominant-negative Rab8, but were unable to undergo the final docking or fusion step. This could be accounted for by the inability of the vesicular (v)-SNARE VAMP-3 to cluster at the immune synapse in the absence of functional Rab8, which is responsible for its recruitment. Of note, and similar to in T-cells, VAMP-3 interacts with Rab8 at the base of the cilium in NIH-3T3 cells, where it regulates ciliary growth and targeting of the protein smoothened. The results identify Rab8 as a new player in vesicular traffic to the immune synapse and provide insight into the pathways co-opted by different cell types for immune synapse assembly and ciliogenesis. Highlighted Article: The ciliary regulator Rab8 is co-opted by T-cells during the assembly of the immune synapse to promote the VAMP-3-dependent step of polarized T-cell receptor recycling.