Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Polydimethylsiloxane in the Molecular Structure of Silica Xerogels Intended for Drug Carriers

The aim of this study was to prepare and examine polymer/oxide xerogels with metronidazole (MT) as delivery systems for the local application of a drug to a bone. The nanoporous SiO2-CaO and PDMS-modified SiO2-CaO xerogel materials with different amounts of the polymer, polydimethylsiloxane (PDMS), were prepared by the sol-gel method. Characterization assays comprised the analysis of the composite materials by using Fourier transform infrared spectroscopy (FTIR), determining the specific surface area of solids (BET), using X-ray powder diffraction (XRD) and scanning electron microscope (SEM) techniques, and further monitoring in the ultraviolet and visible light regions (UV-Vis) of the in vitro release of the drug (metronidazole) over time. According to these results, the bioactive character and chemical stability of PDMS-modified silica xerogels have been proven. The release of MT from xerogels was strongly correlated with the composition of the matrix. In comparison with the pure oxide matrix, PDMS-modified matrices accelerated the release of the drug through its bigger pores, and additionally, on account of weaker interactions with the drug. The obtained results for the xerogel composites suggest that the metronidazole-loaded xerogels could be promising candidates for formulations in local delivery systems particularly to bone.
VMAT2 and dopamine neuron loss in a primate model of Parkinson’s disease

We used positron emission tomography (PET) to measure the earliest change in dopaminergic synapses and glial cell markers in a chronic, low‐dose MPTP non‐human primate model of Parkinson’s disease (PD). In vivo levels of dopamine transporters (DAT), vesicular monoamine transporter‐type 2 (VMAT2), amphetamine‐induced dopamine release (AMPH‐DAR), D2‐dopamine receptors (D2R) and translocator protein 18 kDa (TSPO) were measured longitudinally in the striatum of MPTP‐treated animals. We report an early (2 months) decrease (46%) of striatal VMAT2 in asymptomatic MPTP animals that preceded changes in DAT, D2R, and AMPH‐DAR and was associated with increased TSPO levels indicative of a glial response. Subsequent PET studies showed progressive loss of all pre‐synaptic dopamine markers in the striatum with expression of parkinsonism. However, glial cell activation did not track disease progression. These findings indicate that decreased VMAT2 is a key pathogenic event that precedes nigrostriatal dopamine neuron degeneration. The loss of VMAT2 may result from an association with α‐synuclein aggregation induced by oxidative stress. Disruption of dopamine sequestration by reducing VMAT2 is an early pathogenic event in the dopamine neuron degeneration that occurs in the MPTP non‐human primate model of PD. Genetic or environmental factors that decrease VMAT2 function may be important determinants of PD.
Privacy wizards for social networking sites

Privacy is an enormous problem in online social networking sites. While sites such as Facebook allow users fine-grained control over who can see their profiles, it is difficult for average users to specify this kind of detailed policy. In this paper, we propose a template for the design of a social networking privacy wizard. The intuition for the design comes from the observation that real users conceive their privacy preferences (which friends should be able to see which information) based on an implicit set of rules. Thus, with a limited amount of user input, it is usually possible to build a machine learning model that concisely describes a particular user's preferences, and then use this model to configure the user's privacy settings automatically. As an instance of this general framework, we have built a wizard based on an active learning paradigm called uncertainty sampling. The wizard iteratively asks the user to assign privacy "labels" to selected ("informative") friends, and it uses this input to construct a classifier, which can in turn be used to automatically assign privileges to the rest of the user's (unlabeled) friends. To evaluate our approach, we collected detailed privacy preference data from 45 real Facebook users. Our study revealed two important things. First, real users tend to conceive their privacy preferences in terms of communities, which can easily be extracted from a social network graph using existing techniques. Second, our active learning wizard, using communities as features, is able to recommend high-accuracy privacy settings using less user input than existing policy-specification tools.
A complex containing a 6 b 1 -integrin and phosphorylated focal adhesion kinase between Sertoli cells and elongated spermatids during spermatid release from the seminiferous epithelium

Spermiation is the ﬁnal step of spermatogenesis and culminates in the disengagement (release) of elongated spermatids from Sertoli cells into the seminiferous tubule lumen. Spermiation failure, wherein spermatids are retained by Sertoli cells instead of releasing, occurs after hormone suppression. The mechanisms involved in spermatid disengagement and retention are not well understood. We previously showed that b 1 -integrin is associated with spermatids until the point of disengagement, but the ectoplasmic specialisation junction (ES) is not. The aims of this paper are to further characterise the complex that is present immediately prior to spermatid disengagement by identifying the a -integrin form dimerised with b 1 -integrin, localising focal adhesion kinase (FAK) and determining if microtubules are involved. Adult Sprague–Dawley rats received testosterone and oestradiol implants and an FSH antibody for 7 days to suppress testicular testosterone and FSH and induce spermiation failure. Control rats were treated with saline. Immunohistochemical analysis showed that a 6 -integrin and a phosphorylated form of FAK (FAK-Tyr 397 ) are present between late spermatids and Sertoli cells after ES removal, until the point of disengagement, and both proteins remain associated with retained spermatids after spermiation failure induced by hormone suppression. Using dual-label immunoﬂuorescence, tubulins (and thus microtubules) were observed to co-localise with ES, but were neither associated with elongated spermatids just prior to release nor with retained spermatids following hormone suppression. These results suggest that microtubules are not involved in the ﬁnal release of spermatids from Sertoli cells. We conclude that spermatid release during spermiation is mediated by a ‘disengagement complex’ containing a 6 b 1 -integrin and phospho-FAK, the function of which can be affected by gonadotrophin suppression.
Patterns of Cis Regulatory Variation in Diverse Human Populations

The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs) after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for the transferability of complex trait variants across populations.
Endocrine Therapy Initiation and Medical Oncologist Utilization Among Women Diagnosed with Ductal Carcinoma in Situ.

BACKGROUND Though randomized clinical trials have demonstrated a reduction in second breast events with endocrine therapy among women with ductal carcinoma in situ (DCIS), use of these therapies remains highly variable. The purpose of this study was to evaluate patient and treatment-related factors associated with endocrine therapy initiation and medical oncology specialty utilization after DCIS. MATERIALS AND METHODS We identified women with a DCIS diagnosis during 2006-2010 in the North Carolina Central Cancer Registry with linked public and private insurance claims in the University of North Carolina Integrated Cancer Information Surveillance System data resource. Multivariable generalized linear regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) for endocrine therapy initiation in the year following DCIS diagnosis. RESULTS Among 2,090 women with a DCIS diagnosis, 37% initiated endocrine therapy. Initiation was less common among women aged 75+ at diagnosis (RR = 0.79; 95% CI: 0.64-0.97 vs. age 45-54) and women treated with breast-conserving surgery (BCS) who did not receive radiation (RR = 0.63; 95% CI: 0.50-0.78 vs. BCS plus radiation). Consultation with a medical oncologist was strongly associated with endocrine therapy initiation (RR = 1.40; 95% CI: 1.23-1.61). Women who saw a medical oncologist more often had private insurance, higher census tract-level income, hormone receptor positive disease, and treatment with BCS and radiation. CONCLUSION Treatment strategies for DCIS remain controversial. Our data suggest that endocrine therapy is more often used in addition to standard therapies such as BCS plus radiation, rather than as an alternative to radiation. The Oncologist 2017;22:535-541 IMPLICATIONS FOR PRACTICE: Randomized trials have demonstrated a reduction in second breast cancer events with use of endocrine therapy for ductal carcinoma in situ (DCIS). However, notable variation exists in the uptake of these therapies among DCIS patients. In this study, factors associated with endocrine therapy initiation in the year following a DCIS diagnosis included consultation with a medical oncologist and treatment with breast-conserving surgery with radiation. Our findings help to explain the wide variation in endocrine therapy initiation and suggest the need for clear guidelines in the treatment of DCIS.
Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task

Individuals with high‐functioning autism sometimes exhibit intact or superior performance on visuospatial tasks, in contrast to impaired functioning in other domains such as language comprehension, executive tasks, and social functions. The goal of the current study was to investigate the neural bases of preserved visuospatial processing in high‐functioning autism from the perspective of the cortical underconnectivity theory. We used a combination of behavioral, functional magnetic resonance imaging, functional connectivity, and corpus callosum morphometric methodological tools. Thirteen participants with high‐functioning autism and 13 controls (age‐, IQ‐, and gender‐matched) were scanned while performing an Embedded Figures Task. Despite the ability of the autism group to attain behavioral performance comparable to the control group, the brain imaging results revealed several group differences consistent with the cortical underconnectivity account of autism. First, relative to controls, the autism group showed less activation in the left dorsolateral prefrontal and inferior parietal areas and more activation in visuospatial (bilateral superior parietal extending to inferior parietal and right occipital) areas. Second, the autism group demonstrated lower functional connectivity between higher‐order working memory/executive areas and visuospatial regions (between frontal and parietal‐occipital). Third, the size of the corpus callosum (an index of anatomical connectivity) was positively correlated with frontal–posterior (parietal and occipital) functional connectivity in the autism group. Thus, even in the visuospatial domain, where preserved performance among people with autism is observed, the neuroimaging signatures of cortical underconnectivity persist.
The Burden Attributable to Mental and Substance Use Disorders as Risk Factors for Suicide: Findings from the Global Burden of Disease Study 2010

Background The Global Burden of Disease Study 2010 (GBD 2010) identified mental and substance use disorders as the 5th leading contributor of burden in 2010, measured by disability adjusted life years (DALYs). This estimate was incomplete as it excluded burden resulting from the increased risk of suicide captured elsewhere in GBD 2010's mutually exclusive list of diseases and injuries. Here, we estimate suicide DALYs attributable to mental and substance use disorders. Methods Relative-risk estimates of suicide due to mental and substance use disorders and the global prevalence of each disorder were used to estimate population attributable fractions. These were adjusted for global differences in the proportion of suicide due to mental and substance use disorders compared to other causes then multiplied by suicide DALYs reported in GBD 2010 to estimate attributable DALYs (with 95% uncertainty). Results Mental and substance use disorders were responsible for 22.5 million (14.8–29.8 million) of the 36.2 million (26.5–44.3 million) DALYs allocated to suicide in 2010. Depression was responsible for the largest proportion of suicide DALYs (46.1% (28.0%–60.8%)) and anorexia nervosa the lowest (0.2% (0.02%–0.5%)). DALYs occurred throughout the lifespan, with the largest proportion found in Eastern Europe and Asia, and males aged 20–30 years. The inclusion of attributable suicide DALYs would have increased the overall burden of mental and substance use disorders (assigned to them in GBD 2010 as a direct cause) from 7.4% (6.2%–8.6%) to 8.3% (7.1%–9.6%) of global DALYs, and would have changed the global ranking from 5th to 3rd leading cause of burden. Conclusions Capturing the suicide burden attributable to mental and substance use disorders allows for more accurate estimates of burden. More consideration needs to be given to interventions targeted to populations with, or at risk for, mental and substance use disorders as an effective strategy for suicide prevention.
Head lice infestation: single drug versus combination therapy with one percent permethrin and trimethoprim/sulfamethoxazole.

BACKGROUND Head lice infestation (HLI) is a vexing problem for pediatricians and families because lice are becoming resistant to approved antipediculosis agents. OBJECTIVE This study compared the efficacy of 3 different treatments for HLI and determined whether combination therapy reduced treatment failures. DESIGN AND SETTING A randomized, clinical trial performed in 3 private practices. PARTICIPANTS The population was children ranging in age from 2 to 13 years. METHODS HLI was diagnosed by direct inspection of the hair and scalp. Children were assigned to 1 of 3 groups: 1) 1% permethrin creme rinse (1% PER; n = 39); 2) oral administration of trimethoprim/sulfamethoxazole (TMP/SMX; n = 36); and 3) a combination of 1% PER and TMP/SMX (n = 40). Follow-up visits were done 2 and 4 weeks later, and parents or caregivers of those who did not return were interviewed by telephone. If HLI was present at the 2-week follow-up, the child was retreated per their protocol. We defined successful treatment as the absence of adult lice and nymphal stage or eggs (nits). The presence of nits alone was not considered a treatment failure. RESULTS At the 2-week follow-up visit, successful treatment for groups 1, 2, and 3 was 79.5%, 83%, and 95%, respectively. At the 4-week follow-up, successful treatment was 72%, 78%, and 92.5% for groups 1, 2, and 3, respectively. The absolute risk reduction for recurrence comparing group 1 versus group 2 was 6%, group 2 versus group 3 was 14%, and group 1 versus group 3 was 20%. No major adverse complications were seen in any treatment group. CONCLUSION Our findings indicate that a combination of 1% PER and TMP/SMX is an effective alternative therapy for HLI. We recommend that the dual therapy with 1% PER and oral TMP/SMX be used and reserved in cases of multiple treatment failures or suspected cases of lice-related resistance to therapy.
MAPS: multiresolution adaptive parameterization of surfaces

An irregular connectivity mesh representative of a surface having an arbitrary topology is processed to generate a parameterization which maps points in a coarse base domain to points in the mesh. An illustrative embodiment uses a multi-level mesh simplification process in conjunction with conformal mapping to efficiently construct a parameterization of a mesh comprising a large number of triangles over a base domain comprising a smaller number of triangles. The parameterization in this embodiment corresponds to the inverse of function mapping each point in the original mesh to one of the triangles of the base domain, such that the original mesh can be reconstructed from the base domain and the parameterization. The mapping function is generated as a combination of a number of sub-functions, each of which relates data points in a mesh of one level in a simplification hierarchy to data points in a mesh of the next coarser level of the simplification hierarchy. The parameterization can also be used to construct, from the original irregular connectivity mesh, an adaptive remesh having a regular connectivity which is substantially easier to process than the original mesh.
The gradient projection algorithm with adaptive mutation step length for non-probabilistic reliability index

Original scientific paper Aiming at the problems of selection parameter step-size and premature convergence that occurred when searching the local area in the optimal design of adaptive gradient projection algorithm in this paper, adaptive variable step-size mechanism strategy and adaptive variable step-size mechanism were established. They were introduced into the gradient projection algorithm, and were used to control iteration step length. Through the examples of non-probabilistic reliability index, it can be showed that the method could quickly and accurately calculate the reliability index when the model had multiple variables and complex limit state function. To compare and contrast this algorithm with the simple gradient projection algorithm, this algorithm is not sensitive to the initial point position. And it not only takes into account both local performance and global search ability, but also has fast convergence speed and high precision. So it is an efficient and practical optimization algorithm.
Host Alternation Is Necessary to Maintain the Genome Stability of Rift Valley Fever Virus

Background Most arthropod-borne viruses (arboviruses) are RNA viruses, which are maintained in nature by replication cycles that alternate between arthropod and vertebrate hosts. Arboviruses appear to experience lower rates of evolution than RNA viruses that replicate in a single host. This genetic stability is assumed to result from a fitness trade-off imposed by host alternation, which constrains arbovirus genome evolution. To test this hypothesis, we used Rift Valley fever virus (RVFV), an arbovirus that can be transmitted either directly (between vertebrates during the manipulation of infected tissues, and between mosquitoes by vertical transmission) or indirectly (from one vertebrate to another by mosquito-borne transmission). Methodology/Principal Findings RVFV was serially passaged in BHK21 (hamster) or Aag2 (Aedes aegypti) cells, or in alternation between the two cell types. After 30 passages, these single host-passaged viruses lost their virulence and induced protective effects against a challenge with a virulent virus. Large deletions in the NSs gene that encodes the virulence factor were detectable from the 15th serial passage onwards in BHK21 cells and from the 10th passage in Aag2 cells. The phosphoprotein NSs is not essential to viral replication allowing clones carrying deletions in NSs to predominate as they replicate slightly more rapidly. No genetic changes were found in viruses that were passaged alternately between arthropod and vertebrate cells. Furthermore, alternating passaged viruses presenting complete NSs gene remained virulent after 30 passages. Conclusions/Significance Our results strongly support the view that alternating replication is necessary to maintain the virulence factor carried by the NSs phosphoprotein.
Evaluating the impact of genotype errors on rare variant tests of association

The new class of rare variant tests has usually been evaluated assuming perfect genotype information. In reality, rare variant genotypes may be incorrect, and so rare variant tests should be robust to imperfect data. Errors and uncertainty in SNP genotyping are already known to dramatically impact statistical power for single marker tests on common variants and, in some cases, inflate the type I error rate. Recent results show that uncertainty in genotype calls derived from sequencing reads are dependent on several factors, including read depth, calling algorithm, number of alleles present in the sample, and the frequency at which an allele segregates in the population. We have recently proposed a general framework for the evaluation and investigation of rare variant tests of association, classifying most rare variant tests into one of two broad categories (length or joint tests). We use this framework to relate factors affecting genotype uncertainty to the power and type I error rate of rare variant tests. We find that non-differential genotype errors (an error process that occurs independent of phenotype) decrease power, with larger decreases for extremely rare variants, and for the common homozygote to heterozygote error. Differential genotype errors (an error process that is associated with phenotype status), lead to inflated type I error rates which are more likely to occur at sites with more common homozygote to heterozygote errors than vice versa. Finally, our work suggests that certain rare variant tests and study designs may be more robust to the inclusion of genotype errors. Further work is needed to directly integrate genotype calling algorithm decisions, study costs and test statistic choices to provide comprehensive design and analysis advice which appropriately accounts for the impact of genotype errors.