Miracle-dz/UniFAR-FTUs huggingface dataset:
The rise of transcutaneous drug delivery for the management of alopecia: a review of existing literature and an eye towards the future

ABSTRACT Introduction: Fractional lasers and microneedling devices are increasingly used with topical drugs to treat various conditions, including alopecia, as they grant access to dermal structures such as hair follicles and cutaneous vasculature. Objective: To perform a comprehensive review on transcutaneous drug delivery for the management of alopecia. Methods: PubMed, Embase, and Ovid Medline databases were searched using terms including: alopecia, microneedling, lasers, androgenetic alopecia (AGA), alopecia areata (AA), drug delivery. Articles were examined for inclusion criteria: diagnosis of alopecia regardless of type, use of fractional laser or microneedling devices, and subsequent administration of topical medication. Results: 8 studies, 6 prospective clinical trials and 2 case series, examining either AA or AGA were identified. For AA, five studies examined microneedling together with topical triamcinolone in three of these, while two studies used photodynamic therapy. Regarding AGA, two studies used topical minoxidil plus microneedling, and one examined topical finasteride with fractional erbium glass laser. Improvement was seen in 6 of the 8 studies. Discussion: Transcutaneous drug delivery via fractional laser and microneedling is a promising modality with preliminary evidence for increased hair regrowth over topical therapy alone. Further studies are needed to elucidate treatment parameters and appropriate device selection for drug delivery.
Oral Coadministration of an Intramuscular DNA/Modified Vaccinia Ankara Vaccine for Simian Immunodeficiency Virus Is Associated with Better Control of Infection in Orally Exposed Infant Macaques.

The majority of human immunodeficiency virus (HIV) type 1 infections in infants are acquired orally through breastfeeding. Toward development of a pediatric HIV vaccine to prevent breastmilk transmission, we tested the efficacy of a simultaneous oral and intramuscular (IM) vaccination regimen for preventing oral simian immunodeficiency virus (SIV) transmission in infant rhesus macaques. Two groups of neonatal macaques were immunized with DNA encoding SIV virus-like particles (DNA-SIV) on weeks 0 and 3, then boosted with modified vaccinia Ankara (MVA) virus expressing SIV antigens (MVA-SIV) on weeks 6 and 9. One group was prime/boosted by the IM route only. Another group was immunized with DNA by both the IM and topical oral (O) buccal routes, and boosted with MVA-SIV by both the IM and sublingual (SL) routes. A third group of control animals received saline by O + IM routes on weeks 0 and 3, and empty MVA by SL + IM routes on weeks 6 and 9. On week 12, infants were orally challenged once weekly with SIVmac251 until infected. The vaccine regimen that included oral routes resulted in reduced peak viremia. The rate of infection acquisition in vaccinated infants was found to be associated with prechallenge intestinal immunoglobulin G (IgG) responses to SIV gp120 and V1V2. Peak viremia was inversely correlated with postinfection intestinal IgG responses to gp120, gp41, and V1V2. These results suggest that codelivery of a pediatric HIV vaccine by an oral route may be superior to IM-only regimens for generating mucosal antibodies and preventing HIV breastmilk transmission in neonates.
Uncured PDMS Inhibits Myosin In Vitro Motility in a Microfluidic Flow Cell

The myosin motor powers cardiac contraction and is frequently implicated in hereditary heart disease by its mutation. Principal motor function characteristics include myosin unitary step size, duty cycle, and force-velocity relationship for translating actin under load. These characteristics are sometimes measured in vitro with a motility assay detecting fluorescent labeled actin filament gliding velocity over a planar array of surface immobilized myosin. Assay miniaturization in a polydimethylsiloxane/glass (PDMS/glass) hybrid microfluidic flow channel is an essential component to a small sample volume assay applicable to costly protein samples however the PDMS substrate dramatically inhibits myosin motility. Myosin in vitro motility in a PDMS/glass hybrid microfluidic flow cell was tested under a variety of conditions to identify and mitigate the effect of PDMS on myosin. Substantial contamination by the monomeric species in polymerized PDMS flow cells is shown to be the cause of myosin motility inhibition. Normal myosin motility recovers by either extended cell aging (∼20 days) to allow more complete polymerization or by direct chemical extraction of the free monomers from the polymer substrate. PDMS flow cell aging is the low cost alternative compatible with the other PDMS and glass modifications needed for in vitro myosin motility assaying.
Usefulness of OLGA and OLGIM system not only for intestinal type but also for diffuse type of gastric cancer, and no interaction among the gastric cancer risk factors

The operative link on gastric atrophy (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) stages have been suggested for risk estimation of gastric cancer (GC). However, usefulness of OLGA/OLGIM systems in diffuse type of GC was not investigated so far. The aims of this study were to evaluate the OLGA/OLGIM systems in estimating the GC risk according to Lauren's classification and to investigate the interaction among the risk factors.
Stress Echocardiography: Need to Optimize its Appropriate Use in Suspected Angina and a Review of Available Additional Tools for its Clinical Application in 2018: First do no Harm! Second do it at the Highest Possible Accuracy

There is a need to reassess the most appropriate indications for stress echocardiography in the current era, in patients with suspect or known coronary artery disease (CAD), and also the most helpful additional parameters that can be easily calculated in clinical practice to increase the known suboptimal sensitivity for obstructive CAD of this test. The current review tries to clarify what is and what should be the proper role for functional testing in general, but specifically regarding modern stress echocardiography in the current practice, for suspected CAD and/or atypical chest pain. Few candidate additional parameters beyond wall motion assessment are here suggested to improve diagnostic accuracy of stress echocardiography, and pertinent literature is briefly reviewed, together with a more personal view of the author regarding the characteristics of each parameter, as far as ease of acquisition, cost, and true diagnostic or prognostic clinical usefulness are concerned. The reviewed additional parameters, which can be acquired during stress echocardiography, are Doppler coronary flow reserve in the left anterior descending artery, cardiac calcium score, global longitudinal strain, ventricular elastance, and contrast myocardial perfusion. Each of them finds a potential place in the current practice or may find a place in the future practice of stress echocardiography.
Three-Dimensional Kinematics and Power Output in Elite Para-Kayakers and Elite Able-Bodied Flat-Water Kayakers.

Trunk, pelvis, and leg movements are important for performance in sprint kayaking. Para-kayaking is a new Paralympic sport in which athletes with trunk and/or leg impairment compete in 3 classification groups. The purpose of this study was to identify how physical impairments impact on performance by examining: differences in 3-dimensional joint range of motion (RM) between 10 (4 females and 6 males) elite able-bodied kayakers and 41 (13 females and 28 males) elite para-kayakers from the 3 classification groups, and which joint angles were correlated with power output during high-intensity kayak ergometer paddling. There were significant differences in RM between the able-bodied kayakers and the 3 para-kayak groups for the shoulders (flexion, rotation: able-bodied kayakers < para-kayakers); trunk and pelvis (rotation: able-bodied kayakers > para-kayakers); and legs (hip, knee, and ankle flexion: able-bodied kayakers > para-kayakers) during paddling. Furthermore, athletes with greater impairment exhibited lower trunk and leg RM compared with those with less impairment. Significant positive correlations were observed for both males and females between power output and peak shoulder and trunk flexion; trunk and pelvis rotation RM; and hip, knee, and ankle flexion RM. This information is important for understanding how key kinematic and kinetic variables for para-kayaking performance vary between athletes from different classification groups.
Expression of AR-V7 and ARv567es in Circulating Tumor Cells Correlates with Outcomes to Taxane Therapy in Men with Metastatic Prostate Cancer Treated in TAXYNERGY

Purpose: Biomarkers aiding treatment optimization in metastatic castration-resistant prostate cancer (mCRPC) are scarce. The presence or absence of androgen receptor (AR) splice variants, AR-V7 and ARv567es, in mCRPC patient circulating tumor cells (CTC) may be associated with taxane treatment outcomes. Experimental Design: A novel digital droplet PCR (ddPCR) assay assessed AR-splice variant expression in CTCs from patients receiving docetaxel or cabazitaxel in TAXYNERGY (NCT01718353). Patient outcomes were examined according to AR-splice variant expression, including prostate-specific antigen (PSA)50 response and progression-free survival (PFS). Results: Of the 54 evaluable patients, 36 (67%) were AR-V7+, 42 (78%) were ARv567es+, 29 (54%) were double positive, and 5 (9%) were double negative. PSA50 response rates at any time were numerically higher for AR-V7− versus AR-V7+ (78% vs. 58%; P = 0.23) and for ARv567es− versus ARv567es+ (92% vs. 57%; P = 0.04) patients. When AR-V mRNA status was correlated with change in nuclear AR from cycle 1 day 1 to day 8 (n = 24), AR-V7+ patients (n = 16) had a 0.4% decrease versus a 12.9% and 26.7% decrease in AR-V7−/ARv567es− (n = 3) and AR-V7−/ARv567es+ (n = 5) patients, respectively, suggesting a dominant role for AR-V7 over ARv567es. Median PFS was 12.02 versus 8.48 months for AR-V7− versus AR-V7+ (HR = 0.38; P = 0.01), and 12.71 versus 7.29 months for ARv567es− versus ARv567es+ (HR = 0.37; P = 0.02). For AR-V7+, AR-V7−/ARv567es+, and AR-V7−/ARv567es− patients, median PFS was 8.48, 11.17, and 16.62 months, respectively (P = 0.0013 for trend). Conclusions: Although detection of both CTC-specific AR-V7 and ARv567es by ddPCR influenced taxane outcomes, AR-V7 primarily mediated the prognostic impact. The absence of both variants was associated with the best response and PFS with taxane treatment. See related commentary by Dehm et al., p. 1696
Integrated network analysis and machine learning approach for the identification of key genes of triple‐negative breast cancer

Triple‐negative breast cancer (TNBC) has attracted more attention compared with other breast cancer subtypes due to its aggressive nature, poor prognosis, and chemotherapy remains the mainstay of treatment with no other approved targeted therapy. Therefore, the study aimed to discover more promising therapeutic targets and investigating new insights of biological mechanism of TNBC. Six microarray data sets consisting of 463 non‐TNBC and 405 TNBC samples were mined from Gene Expression Omnibus. The data sets were integrated by meta‐analysis and identified 1075 differentially expressed genes. Protein‐protein interaction network was constructed which consists of 486 nodes and 1932 edges, where 29 hub genes were obtained with high topological measures. Further, 16 features (hub genes), 12 upregulated (AURKB, CCNB2, CDC20, DDX18, EGFR, ENO1, MYC, NUP88, PLK1, PML, POLR2F, and SKP2) and four downregulated ( CCND1, GLI3, SKP1, and TGFB3) were selected through machine learning correlation based feature selection method on training data set. A naïve Bayes based classifier built using the expression profiles of 16 features (hub genes) accurately and reliably classify TNBC from non‐TNBC samples in the validation test data set with a receiver operating curve of 0.93 to 0.98. Subsequently, Gene Ontology analysis revealed that the hub genes were enriched in mitotic cell cycle processes and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that they were enriched in cell cycle pathways. Thus, the identified key hub genes and pathways highlighted in the study would enhance the understanding of molecular mechanism of TNBC which may serve as potential therapeutic target.
Learning Converged Propagations With Deep Prior Ensemble for Image Enhancement

Enhancing the visual qualities of images plays very important roles in various vision and learning applications. In the past few years, both knowledge-driven maximum a posterior (MAP) with prior modelings and fully data-dependent convolutional neural network (CNN) techniques have been investigated to address specific enhancement tasks. In this paper, by exploiting the advantages of these two types of mechanisms within a complementary propagation perspective, we propose a unified framework, named deep prior ensemble (DPE) for solving various image enhancement tasks. Specifically, we first establish the basic propagation scheme based on the fundamental image modeling cues and then introduce residual CNNs to help predicting the propagation direction at each stage. By designing prior projections to perform feedback control, we theoretically prove that even with experience-inspired CNNs, DPE is definitely converged and the output will always satisfy our fundamental task constraints. The main advantage against the conventional optimization-based MAP approaches is that our descent directions are learned from collected training data, thus are much more robust to unwanted local minimums. While, compared with existing CNN type networks, which are often designed in heuristic manners without theoretical guarantees, DPE is able to gain advantages from rich task cues investigated on the bases of domain knowledges. Therefore, the DPE actually provides a generic ensemble methodology to integrate both knowledge and data-based cues for different image enhancement tasks. More importantly, our theoretical investigations verify that the feed-forward propagations of DPE are properly controlled toward our desired solution. Experimental results demonstrate that the proposed DPE outperforms the state-of-the-arts on a variety of image enhancement tasks in terms of both quantitative measure and visual perception quality.
First Replication of the Involvement of OTUD6B in Intellectual Disability Syndrome With Seizures and Dysmorphic Features

Biallelic mutations in the ovarian tumor domain-containing 6B (OTUD6B) gene, coding for a deubiquitinating enzyme, were recently described to cause an intellectual disability syndrome characterized by seizures and dysmorphic features in six families worldwide. We here report on a 6-year-old Italian girl, presenting mild intellectual disability, speech and motor delay, and recurrent seizures, who came to our attention after being screened for genes responsible for Rubinstein–Taybi syndrome, Kabuki syndrome, and epilepsy. We hence submitted the proband’s DNA to whole-exome sequencing, disclosing two candidate heterozygous splicing mutations in the OTUD6B gene: c.324+1G>C and c.405+1G>A. Both variants are reported in the GnomAD database with a frequency lower than the 10−5 and affect the donor splicing site, of exons 2 and 3, respectively. Sanger sequencing confirmed the segregation of the variants in the family, showing that both parents are carriers of one mutation. RT-PCR experiments demonstrated that both variants affect OTUD6B splicing and lead to the production of aberrant transcripts, the major ones being, in both cases, the skipping of the upstream exon. Quantitative analysis performed by competitive-fluorescent RT-PCR on the patient RNA showed that the proband presents less than 1% of wild-type transcripts, further strengthening the causative role of these variants. This represents the first replication of the involvement of the OTUD6B gene in this syndrome and points to the appropriateness of screening OTUD6B in suspected Rubinstein–Taybi syndrome patients with negative results after the screening of the major genes.
Life Course Effects of Socioeconomic and Lifestyle Factors on Metabolic Syndrome and 10-Year Risk of Cardiovascular Disease: A Longitudinal Study in Taiwan Adults

The objective of the study was to explore the dynamic effects of socioeconomic status (SES) and lifestyle behaviors on the risks of metabolic syndrome (MS) or cardiovascular disease (CVD) in life course. The data of 12,825 subjects (6616 males and 6209 females) who underwent repeated examinations and answered repeated questionnaires from 2006 to 2014 at the Major Health Screening Center in Taiwan, was collected and analyzed. The trajectory of trends in the subjects’ SES and lifestyle mobility over time was observed, and the effects of factors with potential impacts on health were tested and analyzed using multiple logistic regression and a generalized estimated equation model. A 10% increase in MS prevalence was observed over the nine-year period. The average Framingham CVD score for people with MS was estimated to be about 1.4% (SD = 1.5%). Except for middle-aged women, marriage was found to raise the risk of CVD, whereas increasing education and work promotions independently reduced CVD risk for the majority of subjects. However, the risk of CVD was raised by half for young men who had a job or lost a job in comparison to continuously unemployed young men. Physical activity was only found to be advantageous for disease prevention in those aged less than 40 years; increased exercise levels were useless for reducing CVD risk among older men. Alcohol drinking and betel chewing caused increased CVD risk in the old and young subjects, respectively, whereas vegetarian diets and vitamin C/E intake were helpful in preventing CVD, even if those habits were ceased in later life. For middle-aged women, getting sufficient sleep reduced CVD risk. We concluded that SES and lifestyle behaviors may have different effects on health over time, among various populations. Accordingly, suggestions can be provided to healthcare workers in designing health promotion courses for people at different life stages.
From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.
Efficient Two-Step Adversarial Defense for Deep Neural Networks

In recent years, deep neural networks have demonstrated outstanding performance in many machine learning tasks. However, researchers have discovered that these state-of-the-art models are vulnerable to adversarial examples: legitimate examples added by small perturbations which are unnoticeable to human eyes. Adversarial training, which augments the training data with adversarial examples during the training process, is a well known defense to improve the robustness of the model against adversarial attacks. However, this robustness is only effective to the same attack method used for adversarial training. Madry et al.(2017) suggest that effectiveness of iterative multi-step adversarial attacks and particularly that projected gradient descent (PGD) may be considered the universal first order adversary and applying the adversarial training with PGD implies resistance against many other first order attacks. However, the computational cost of the adversarial training with PGD and other multi-step adversarial examples is much higher than that of the adversarial training with other simpler attack techniques. In this paper, we show how strong adversarial examples can be generated only at a cost similar to that of two runs of the fast gradient sign method (FGSM), allowing defense against adversarial attacks with a robustness level comparable to that of the adversarial training with multi-step adversarial examples. We empirically demonstrate the effectiveness of the proposed two-step defense approach against different attack methods and its improvements over existing defense strategies.
Understanding premarital pregnancies among adolescents and young women in Ouagadougou, Burkina Faso

Abstract In developing countries, young women between 15 and 24 years of age account for more than 40% of unsafe abortions due to the high number of unwanted and/or out-of-wedlock pregnancies. However, much about the profile of adolescents and young women who usually experience premarital pregnancies remains unknown. This study sought to understand the risk of pregnancy before marriage among adolescents and young women in Ouagadougou, Burkina Faso. By using longitudinal data from a demographic surveillance system, we tested the explanatory power of two theoretical assumptions on premarital childbearing in sub-Saharan Africa, which assumptions are the cultural inheritance model and the social capital model. The results confirmed the explanatory power of the cultural inheritance model on the one hand and partially confirmed the power of the social capital model on the other hand. These results highlight the need for a multipronged approach to sexual and reproductive health for young people. Efforts against premarital pregnancies among adolescents and young women would be more effective if they were based on participatory approaches, incorporating actions at both community and institutional levels, as suggested by the recent Global Accelerated Action for the Health of Adolescents logical framework.