Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Features and Clinical Management of Patients with Hereditary Pancreatic Cancer Syndromes and Familial Pancreatic Cancer

Pancreatic cancer (PC) is one of the most devastating malignancies; it has a 5-year survival rate of only 9%, and novel treatment strategies are urgently needed. While most PC cases occur sporadically, PC associated with hereditary syndromes or familial PC (FPC; defined as an individual having two or more first-degree relatives diagnosed with PC) accounts for about 10% of cases. Hereditary cancer syndromes associated with increased risk for PC include Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma, familial adenomatous polyposis, Lynch syndrome and hereditary breast and ovarian cancer syndrome. Next-generation sequencing of FPC patients has uncovered new susceptibility genes such as PALB2 and ATM, which participate in homologous recombination repair, and further investigations are in progress. Previous studies have demonstrated that some sporadic cases that do not fulfil FPC criteria also harbor similar mutations, and so genomic testing based on family history might overlook some susceptibility gene carriers. There are no established screening procedures for high-risk unaffected cases, and it is not clear whether surveillance programs would have clinical benefits. In terms of treatment, poly (ADP-ribose) polymerase inhibitors for BRCA-mutated cases or immune checkpoint inhibitors for mismatch repair deficient cases are promising, and clinical trials of these agents are underway.
Tailoring Electro/Optical Properties of Transparent Boron-Doped Carbon Nanowalls Grown on Quartz

Carbon nanowalls (CNWs) have attracted much attention for numerous applications in electrical devices because of their peculiar structural characteristics. However, it is possible to set synthesis parameters to vary the electrical and optical properties of such CNWs. In this paper, we demonstrate the direct growth of highly transparent boron-doped nanowalls (B-CNWs) on optical grade fused quartz. The effect of growth temperature and boron doping on the behavior of boron-doped carbon nanowalls grown on quartz was studied in particular. Temperature and boron inclusion doping level allow for direct tuning of CNW morphology. It is possible to operate with both parameters to obtain a transparent and conductive film; however, boron doping is a preferred factor to maintain the transparency in the visible region, while a higher growth temperature is more effective to improve conductance. Light transmittance and electrical conductivity are mainly influenced by growth temperature and then by boron doping. Tailoring B-CNWs has important implications for potential applications of such electrically conductive transparent electrodes designed for energy conversion and storage devices.
Impact of Adolescents’ Screen Time and Nocturnal Mobile Phone-Related Awakenings on Sleep and General Health Symptoms: A Prospective Cohort Study

Nocturnal media use has been linked to adolescents’ sleeping problems in cross-sectional studies which do not address reverse causality. To prospectively assess the new occurrence of sleep problems or health symptoms in relation to electronic media use and nocturnal mobile phone use, we used data from the longitudinal Swiss HERMES (Health Effects Related to Mobile phone usE in adolescentS) cohort on 843 children from 7th to 9th grade. Logistic regression models were fitted and adjusted for relevant confounders. Adolescents reporting at baseline and follow-up at least one nocturnal awakenings from their own mobile phone per month were more likely to have developed restless sleep (Odds Ratio (OR): 5.66, 95% Confidence Interval: 2.24–14.26) and problems falling asleep (3.51, 1.05–11.74) within one year compared to adolescents without nocturnal awakenings. A similar pattern was observed for developing symptoms, although somewhat less pronounced in terms of the magnitude of the odds ratios. With respect to high screen time at baseline and follow-up, associations were observed for falling asleep (2.41, 1.41–4.13), exhaustibility (1.76, 1.02–3.03), lack of energy (1.76, 1.04–2.96) and lack of concentration (2.90, 1.55–5.42). Our results suggest a detrimental effect of screen time and mobile phone-related awakenings on sleep problems and related health symptoms. However, the results should be interpreted cautiously with respect to adolescents’ natural changes in circadian rhythm, which may coincidence with an increase in mobile phone and media use.
THE IMPACT OF TREATED LEMON PULP WITH YEAST ON GROWTH PERFORMANCE, NUTRITIVE VALUE, TOTAL ANTI-OXIDANT ENZYME AND IMMUNE RESPONSE OF GROWING RABBITS

The main target of current study was evaluated effect of incorporation of treated lemon pulp by Saccharomyces cerevisiae yeast (LPT) in growing rabbit diets on productive performance, anti-oxidant enzyme and immune response. Forty eight cross bred (New Zealand White (NZW) X California), 6 weeks age with live body weight ranging from 730.00 to 733.30g were divided into four experimental diet groups (twelve rabbits in each). Each treatment group was replicate six times and each replicates (2 rabbits in each replicate). Thesewere divided into basal diet without LPT as a control group, while 3%, 6% and 9%LPT (replacement basal diet protein by three different levels of LPT protein) as the second, third, and fourth group, respectively. The results showed no significant differences in final body weight (FBW, g), daily body weight gain [BWG (g/rabbit/day)], daily feed intake [FI (g/rabbit/day)] and feed conversion ratio [FCR, g feed/g gain] were observed among rabbit groups and control group. Moreover, no significant differences were observed in DM, OM, CP, CF, EE, NFE% digestibility and nutritive value among experimental groups. The total lipid (TL) value increased (P≤0.05) with rabbits fed 3and 6%LPT diets groups when compared to control and 9%LPT diets. While increasing LPT up to 9% decreased (P≤0.05) the concentrate of cholesterol and triglycerides in experimental groups as compared to control group. The lowest (P≤0.05) value of aspartate aminotransferase (AST) was observed with 6%LPT group when compared to control and 3% treated groups. The alanine aminotransferase (ALT) decreased (P≤0.05) with 6% LPT group when compared to 3 and 9% LPT dietary groups, while, no significant differences between treated groups and control group. The rabbit fed 6%LPT diet increased (P≤0.05) in blood urea value when compared to rabbit fed control diet. No significant difference was detected in creatinine between LPT dietary groups and control group. The total anti-oxidant enzyme values were significantly (P ≤ 0.05) increased with rabbits fed on all LPT levels when compared to control group. Immunoglobulin titer IgG significantly (P ≤ 0.05) increased with rabbit fed 9%LPT as compared to control and other experimental groups. Immunoglobulin titer IgM was insignificantly difference between LPT dietary groups and control group. Conclusively, suggesting that can be using LPT in growing rabbit diets up to 9% possible without any adverse effects on performance, digestibility and can be improvement of total anti-oxidant enzyme and immune response.
Cucurbitacin B Induces the Lysosomal Degradation of EGFR and Suppresses the CIP2A/PP2A/Akt Signaling Axis in Gefitinib-Resistant Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) patients carrying an epidermal growth factor receptor (EGFR) mutation are initially sensitive to EGFR-tyrosine kinase inhibitors (TKIs) treatment, but soon develop an acquired resistance. The treatment effect of EGFR-TKIs-resistant NSCLC patients still faces challenges. Cucurbitacin B (CuB), a triterpene hydrocarbon compound isolated from plants of various families and genera, elicits anticancer effects in a variety of cancer types. However, whether CuB is a viable treatment option for gefitinib-resistant (GR) NSCLC remains unclear. Here, we investigated the anticancer effects and underlying mechanisms of CuB. We report that CuB inhibited the growth and invasion of GR NSCLC cells and induced apoptosis. The inhibitory effect of CuB occurred through its promotion of the lysosomal degradation of EGFR and the downregulation of the cancerous inhibitor of protein phosphatase 2A/protein phosphatase 2A/Akt (CIP2A/PP2A/Akt) signaling axis. CuB and cisplatin synergistically inhibited tumor growth. A xenograft tumor model indicated that CuB inhibited tumor growth in vivo. Immunohistochemistry results further demonstrated that CuB decreased EGFR and CIP2A levels in vivo. These findings suggested that CuB could suppress the growth and invasion of GR NSCLC cells by inducing the lysosomal degradation of EGFR and by downregulating the CIP2A/PP2A/Akt signaling axis. Thus, CuB may be a new drug candidate for the treatment of GR NSCLC.
CCR5/CXCR4 Dual Antagonism for the Improvement of HIV Infection Therapy

HIV entry in the host cell requires the interaction with the CD4 membrane receptor, and depends on the activation of one or both co-receptors CCR5 and CXCR4. Former selective co-receptor antagonists, acting at early stages of infection, are able to impair the receptor functions, preventing the viral spread toward AIDS. Due to the capability of HIV to develop resistance by switching from CCR5 to CXCR4, dual co-receptor antagonists could represent the next generation of AIDS prophylaxis drugs. We herein present a survey on relevant results published in the last few years on compounds acting simultaneously on both co-receptors, potentially useful as preventing agents or in combination with classical anti-retroviral drugs based therapy.
Trend and projection of mortality rate due to non-communicable diseases in Iran: A modeling study

Background Following the epidemiologic and demographic transition, non-communicable disease mortality is the leading cause of death in Iran. Projecting mortality trend can provide valuable tools for policy makers and planners. In this article, we have estimated the trend of non-communicable disease mortality during 2001–2015 and have projected it until 2030 at national and subnational levels in Iran. Methods The data employed was gathered from the Iranian death registration system and using the Spatio-temporal model, the trends of 4 major categories of non-communicable diseases (cancers, cardiovascular diseases, asthma and COPD, and diabetes) by 2030 were projected at the national and subnational levels. Results The results indicated that age standardized mortality rate for cancers, CVDs, and Asthma and COPD will continue to decrease in both sexes (cancers: from 81.8 in 2015 to 45.2 in 2030, CVDs: 307.3 to 173.0, and Asthma and COPD: from 52.1 to 46.6); however, in terms of diabetes, there is a steady trend in both sexes at national level (from 16.6 to 16.5). Age standardized mortality rates for cancers and CVDs, in males and females, were high in all provinces in 2001. The variation between the provinces is clearer in 2015, and it is expected to significantly decrease in all provinces by 2030. Conclusion Generally, the age standardized mortality rate from NCDs will decrease by 2030. Of course, given the experience of the past two decades in Iran, believing that the mortality rate will decrease may not be an easy notion to understand. However hard to believe, this decrease may be the result of better management of risk factors and early detection of patients due to more comprehensive care in all segments of society, as well as improved literacy and awareness across the country.
Recombination rate variation shapes barriers to introgression across butterfly genomes

Hybridisation and introgression can dramatically alter the relationships among groups of species, leading to phylogenetic discordance across the genome and between populations. Introgression can also erode species differences over time, but selection against introgression at certain loci acts to maintain post-mating species barriers. Theory predicts that species barriers made up of many loci throughout the genome should lead to a broad correlation between introgression and recombination rate, which determines the extent to which selection on deleterious foreign alleles will affect neutral alleles at physically linked loci. Here we describe the variation in genealogical relationships across the genome among three species of Heliconius butterflies: H. melpomene, H. cydno and H. timareta, using whole genomes of 92 individuals, and ask whether this variation can be explained by heterogeneous barriers to introgression. We find that species relationships vary predictably at the chromosomal scale. By quantifying recombination rate and admixture proportions, we then show that rates of introgression are predicted by variation in recombination rate. This implies that species barriers are highly polygenic, with selection acting against introgressed alleles across most of the genome. In addition, long chromosomes, which have lower recombination rates, produce stronger barriers on average than short chromosomes. Finally, we find a consistent difference between two species pairs on either side of the Andes, which suggests differences in the architecture of the species barriers. Our findings illustrate how the combined effects of hybridisation, recombination and natural selection, acting at multitudes of loci over long periods, can dramatically sculpt the phylogenetic relationships among species.
Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in high-risk populations, Spain, 2016

Introduction: Although human papillomavirus (HPV) routine vaccination programmes have been implemented around the world and recommendations have been expanded to include other high-risk individuals, current recommendations often differ between countries in Europe, as well as worldwide. Aim: To find and summarise the best available evidence of HPV vaccination in high-risk patients aiding clinicians and public health workers in the day-to-day vaccine decisions relating to HPV in Spain. Methods: We conducted a systematic review of the immunogenicity, safety and efficacy/effectiveness of HPV vaccination in high-risk populations between January 2006 and June 2016. HPV vaccination recommendations were established with levels of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: A strong recommendation about HPV vaccination was made in the following groups: HIV infected patients aged 9–26 years; men who have sex with men aged 9–26 years; women with precancerous cervical lesions; patients with congenital bone marrow failure syndrome; women who have received a solid organ transplant or hematopoietic stem cell transplantation aged 9–26 years; and patients diagnosed with recurrent respiratory papillomatosis. Conclusions: Data concerning non-routine HPV vaccination in populations with a high risk of HPV infection and associated lesions were scarce. We have developed a document to evaluate and establish evidence-based guidelines on HPV vaccination in high-risk populations in Spain, based on best available scientific evidence.
Smartphone-Based Activity Recognition for Indoor Localization Using a Convolutional Neural Network †

In the indoor environment, the activity of the pedestrian can reflect some semantic information. These activities can be used as the landmarks for indoor localization. In this paper, we propose a pedestrian activities recognition method based on a convolutional neural network. A new convolutional neural network has been designed to learn the proper features automatically. Experiments show that the proposed method achieves approximately 98% accuracy in about 2 s in identifying nine types of activities, including still, walk, upstairs, up elevator, up escalator, down elevator, down escalator, downstairs and turning. Moreover, we have built a pedestrian activity database, which contains more than 6 GB of data of accelerometers, magnetometers, gyroscopes and barometers collected with various types of smartphones. We will make it public to contribute to academic research.
Skin Electrical Resistance Measurement of Oxygen-Containing Terpenes as Penetration Enhancers: Role of Stratum Corneum Lipids

The measurement of skin electrical resistance (SER) has drawn a great deal of attention for the rapid screening of transdermal penetration enhancers (PEs). However, the mechanisms underlying the SER measurement are still unclear. This study was to investigate the effects and mechanisms of seven oxygen-containing terpenes on the SER kinetics. Stratum corneum (SC) lipids were proved to play a key role in SER measurement. Then, the factors affecting the SER measurement were optimized. By the determination of SER kinetics, cyclic terpenes (1,8-cineole, terpinen-4-ol, menthol and α-terpineol) were demonstrated to possess higher enhancement ratio (ER) values compared with linear terpenes (linalool, geraniol and citral). For the first time, the linear correlation was found between ER of terpenes and the interaction energy of terpene–ceramide complexes revealed by molecular simulation. The attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis revealed that the effect of cyclic terpenes on SC lipid arrangement was obviously stronger than that of linear terpenes. In addition, by evaluating HaCaT skin cell viability, little difference was found between the toxicities of cyclic and linear terpenes. In conclusion, measurement of SER could be a feasible approach for the efficient evaluation of the PEs that mainly act on SC lipids.
Development of a human milk concentrate with human milk lyophilizate for feeding very low birth weight preterm infants: A preclinical experimental study

Breast milk is considered the gold standard nutritional resource for very low birth weight (VLBW) infants in terms of nutrients and protective factors. If mother's milk is not available, the second choice is donated and fortified human milk (HM) from the Human Milk Bank (HMB). This study hypothesized that HM could be lyophilized and used as an additive to increase the levels of macronutrients and micronutrients available to VLBW infants. This study aimed to constitute a lyophilized HM concentrate and determine the osmolality and the concentration of macronutrients and micronutrients in HM samples at “baseline” and in “HM concentrates”, analyzed immediately (HMCI), and after 3 (HMC3m) and 6 (HMC6m) months of freezing. Osmolality was verified using the freezing point osmometric method. Macronutrient quantification was performed using the MIRIS Human Milk Analyzer. Micronutrients were determined by Flame Atomic Absorption Spectrophotometry and by the automated colorimetric method. Bayesian linear mixed effect models were adjusted using OpenBUGS to estimate mean differences and 95% credibility intervals (CrI) of osmolality and of macro- and micronutrients between the types of HM samples. A comparison of dosage values showed a significant increase between HM baseline and HMCI, HMC3m, and HMC6m. Comparing HM baseline and HMCI highlighted the increase in energy content and the concentration of carbohydrates and total lipids. The Ca and P contents increased and the levels of energy, total lipids, and Cu were reduced in HMC3m compared to HMCI. Ca, Mg, K, Zn, and P increased and the levels of energy, total lipids, and Cu were reduced in HMC6m, compared to HMCI. The present study confirms the possibility of formulation and utilization of the immediate concentrate. Partial stability of HM concentrates generated from freeze-drying of donated milk do not recommend storage.
Association between PM2.5 Exposure and All-Cause, Non-Accidental, Accidental, Different Respiratory Diseases, Sex and Age Mortality in Shenzhen, China

Background: China is at its most important stage of air pollution control. Research on the association between air pollutants and human health is very important and necessary. The purpose of this study was to evaluate the association between PM2.5 concentrations and residents’ mortality and to compare the effect of PM2.5 on the different diseases, accidental deaths, sex or age of residents from high polluted areas with less polluted areas. Methods: The semi-parametric generalized additive model (GAM) with Poisson distribution of time series analysis was used. The excess risk (ER) of mortality with the incremental increase of 10 µg/m3 in PM2.5 concentration was calculated. Concentration-response relationship curves and autocorrelation between different lags of PM2.5 were also evaluated. Results: PM2.5 exposure was significantly associated with the mortality of residents. The strongest ERs per 10 µg/m3 increase in PM2.5 were 0.74% (95% CI: 0.11–1.38%) for all-cause, 0.67% (95% CI: 0.01–1.33%) for non-accidental, 1.81% (95% CI: 0.22–3.42%) for accidental, 3.04% (95% CI: 0.60–5.55%) for total respiratory disease, 6.38% (95% CI: 2.78–10.11%) for chronic lower respiratory disease (CLRD), 8.24% (95% CI: 3.53–13.17%) for chronic obstructive pulmonary disease (COPD), 1.04% (95% CI: 0.25–1.84%) for male and 1.32% (95% CI: 0.46–2.19%) for elderly. Furthermore, important information on the concentration-response relationship curves was provided. Conclusions: PM2.5 can increase the risk of residents’ mortality, even in places with less air pollution and developed economy in China.
Detection of municipalities at-risk of Lyme disease using passive surveillance of Ixodes scapularis as an early signal: A province-specific indicator in Canada

Lyme disease, the most commonly reported vector-borne disease in North America, is caused by the spirochete Borrelia burgdorferi sensu stricto, which is transmitted by Ixodes scapularis in eastern Canada and Ixodes pacificus in western Canada. Recently, the northward range expansion of I. scapularis ticks, in south-eastern Canada, has resulted in a dramatic increase in the incidence of human Lyme disease. Detecting emerging areas of Lyme disease risk allows public health to target disease prevention efforts. We analysed passive tick surveillance data from Ontario and Manitoba to i) assess the relationship between the total numbers of I. scapularis submissions in passive surveillance from humans, and the number of human Lyme disease cases, and ii) develop province-specific acarological indicators of risk that can be used to generate surveillance-based risk maps. We also assessed associations between numbers of nymphal I. scapularis tick submissions only and Lyme disease case incidence. Using General Estimating Equation regression, the relationship between I. scapularis submissions (total numbers and numbers of nymphs only) in each census sub-division (CSD) and the number of reported Lyme disease cases was positively correlated and highly significant in the two provinces (P ≤ 0.001). The numbers of I. scapularis submissions over five years discriminated CSDs with ≥ 3 Lyme disease cases from those with < 3 cases with high accuracy when using total numbers of tick submission (Receiver Operating Characteristics area under the curve [AUC] = 0.89) and moderate accuracy (AUC = 0.78) when using nymphal tick submissions only. In Ontario the optimal cut-off point was a total 12 tick submissions from a CSD over five years (Sensitivity = 0.82, Specificity = 0.84), while in Manitoba the cut-off point was five ticks (Sensitivity = 0.71, Specificity = 0.79) suggesting regional variability of the risk of acquiring Lyme disease from an I. scapularis bite. The performances of the acarological indicators developed in this study for Ontario and Manitoba support the ability of passive tick surveillance to provide an early signal of the existence Lyme disease risk areas in regions where ticks and the pathogens they transmit are expanding their range.