Miracle-dz/UniFAR-FTUs huggingface dataset:
HDAC6 Regulates Radiosensitivity of Non-Small Cell Lung Cancer by Promoting Degradation of Chk1

We previously discovered that HDAC6 regulates the DNA damage response via modulating the homeostasis of a DNA mismatch repair protein, MSH2, through HDAC6’s ubiquitin E3 ligase activity. Here, we have reported HDAC6’s second E3 ligase substrate, a critical cell cycle checkpoint protein, Chk1. We have found that HDAC6 and Chk1 directly interact, and that HDAC6 ubiquitinates Chk1 in vivo. Typical Chk1 protein levels fluctuate, peaking at G2 and subsequently resolving via the ubiquitin-proteasome pathway. However, in HDAC6 knockdown cells, Chk1 is constitutively active and fails to resolve post-ionizing radiation (IR), leading to increased radiation sensitivity. Upon IR treatment, a greater proportion of HDAC6 knockdown cells accumulated at G2/M phase when compared with control cells. Depletion or inhibition of Chk1 in HDAC6 knockdown cells renders those cells radiosensitive, suggesting that persistently high level of Chk1 could lead cells to arrest at G2/M phase and eventually, apoptosis. Clinically, we found that high levels of phosphorylated Chk1 (p-Ser317) are associated with a better overall survival in a cohort of non-small cell lung cancer (NSCLC) patients, suggesting a link between active Chk1 and lung cancer development. Overall, our results highlight a novel mechanism of Chk1 regulation at the protein level, and a possible strategy for sensitizing NSCLC to radiation via inhibiting the activity of HDAC6’s E3 ligase.
LYVE-1 and the response of lymphatic vessel endothelium to inflammation

The lymphatic system provides a conduit for the delivery of antigen-presenting cells from peripheral tissues to draining lymph nodes, both constitutively and during inflammation, when a dramatic increase in the number of trafficking events occurs. This thesis is concerned with the role played by the lymphatic endothelium under pro-inflammatory conditions and the mechanisms regulating entry of leukocytes into the lymphatic capillaries. Monoclonal antibodies against the lymphatic vessel endothelial-specific receptor for hyaluronan, LYVE-1, were raised in rat against the mouse orthologue, for use both as a marker for lymphatics in mouse tissue and to investigate the physiological role of this protein. LYVE-1 was found to be dramatically and specifically down-regulated by TNFa and TNFp, by rapid internalisation and transcriptional down-regulation in primary lymphatic endothelial cells. A significant reduction in LYVE-1 expression was also recorded in intact lymphatic vessels in response to TNFa and in an allergen-induced mouse model of skin inflammation. Furthermore, lymphatic endothelial cells were found to respond to this pro-inflammatory cytokine by instigating a distinct expression programme characterised by up-regulation of the key leukocyte adhesion receptors VCAM-1, ICAM-1 and E-selectin; chemokines and other potential regulators of leukocyte entry. Moreover, the major components of this programme were confirmed in dermal lymphatic vessels in the allergen-induced mouse model of skin inflammation, simultaneous with the down-modulation of LYVE-1 and lymphatic accumulation of migrating leukocytes. The results described in this thesis provide the first evidence that lymphatic endothelial cells play an active role in inflammation. In addition these data indicate that the lymphatic and blood vascular systems share components of the same address code for specific vascular targeting.
ESPAD 2015: EuropeanSchoolSurveyProject on Alcohol &Other Drugs in Ireland

This report is based on data gathered for the European Schools Project for Alcohol and Other Drugs (ESPAD) Survey carried out in Ireland in 2015. The ESPAD survey takes place concurrently every four years in more than 35 European countries and is based on a common set of questions and methodology. This series of studies began in 1995 following an initiative by the Swedish Council for Information on Alcohol and Other Drugs (CAN) to connect with researchers in other European countries, including Ireland, with a view to conducting a common survey on the usage of tobacco, alcohol and illegal drugs in the school-going population. The main aim of the ESPAD survey is to monitor trends in alcohol and other drug use among 15-16 year-olds and to compare trends between countries and groups of countries. In doing so, researchers compile a large database of information that can play an integral role in the planning and implementation of future initiatives and policies. The 2015 data collection wave marked the 20th anniversary of the first ESPAD survey and Ireland has participated in every phase of data collection since the launch in 1995 (Hibell et al, 1997, 2001, 2004; Morgan et al., 2008, 2012).
Modeling gene expression evolution with EvoGeneX uncovers differences in evolution of species, organs and sexes

While DNA sequence evolution has been well studied, the expression of genes is also subject to evolution, yet the evolution of gene expression is currently not well understood. Recently, new tissue/organ-specific gene expression datasets spanning several organisms across the tree of life, have become available, providing the opportunity to study gene expression evolution in more detail. While a theoretical model to study the evolution of continuous traits exists, in practice computational methods often cannot confidently distinguish between alternative evolutionary scenarios. This lack of power has been attributed to modest numbers of species considered in these studies. We hypothesised that biological replicates can be used to increase predictive power of these models. With this in mind, we introduce EvoGeneX, a computationally efficient method to uncover the mode of gene expression evolution based on the Ornstein-Uhlenbeck process. Importantly, in addition to modelling expression variations between species, EvoGeneX models within-species variation. Furthermore, to facilitate comparative analysis of gene expression evolution, we introduce a formal approach, based on Michaelis-Menten equation, to measure the dynamics of evolutionary divergence of a group of genes in terms of group’s asymptotic divergence level and rate. Finally, we used these tools to preform the first analysis the evolution of gene expression across different body parts, species, and sexes of the Drosophila genus. Our analysis revealed that neutral expression evolution can be confidently rejected in favor of purifying selection in nearly half of the genes. In addition, we quantified differences in the evolutionary dynamics of male and female gonads and uncovered interesting examples of adaptive gene expression evolution.
Social and Environmental Determinants of Dengue Infection Risk in North Sumatera Province, Indonesia

The incidence rate of dengue hemorrhagic fever in North Sumatera Province remains high. Socio-demographic and socio-cultural factors, as well as knowledge, attitudes, practices and environmental factors, influence incidence of dengue hemorrhagic fever. For effective control measures, effort should be concentrated on the disease risk factors. The objective of this study was to determine the risk factors for dengue hemorrhagic fever incidence based on their socio-demographic and socio-cultural factors, as well as knowledge, attitudes, practices and environmental factors and to determine whether the characteristics of caregivers influence the risk of dengue hemorrhagic fever. The study was designed as a case cohort study. The total number of study recruits was 682 at a case: sub-cohort ratio of 1:1 and all subjects were selected via purposeful and systematic sampling. Data analysis was performed using simple and multiple logistic regressions with α at 5% to determine the predictors of dengue hemorrhagic fever incidence in North Sumatera Province. The results of the study revealed that history of dengue hemorrhagic fever in the family, travel history of family members, frequency of garbage disposal and source of drinking water were the determinant factors for dengue hemorrhagic fever incidence in North Sumatera Province. Moreover, education and knowledge regarding dengue achieved through the involvement of caregivers played an important role in reducing the incidence of dengue hemorrhagic fever. Based on these findings, it is recommended to enhance health promotion regarding dengue prevention in the community.
SNAP timing and food insecurity

This paper makes several contributions to the literature regarding the measurement of food insecurity and implications for estimating factors that affect this outcome. First, we show that receipt of benefits from the Supplemental Nutrition Assistance Program (SNAP) has a systematic effect on responses to questions in the 12-month food security module (FSM). We find that the probability of affirming more severe food hardships items, and the probability of being classified as having very low food security (VLFS), is higher just before and just after households receive their benefits. This leads to an under-estimate of VLFS by 3.2 percentage points for the SNAP sample (about 17 percent of prevalence). We also provide informative bounds on the relationship between SNAP and VLFS and show that the treatment effect of SNAP on VLFS is also likely underestimated.
Karakteristik dan Efektivitas Salep Madu Klanceng dari Lebah Trigona sp. Sebagai Antibakteri dan Penyembuh Luka Sayat

Penggunaan antibiotik secara terus menerus dapat menimbulkan resistensi pada bakteri. Salah satu bahan alami yang dapat menjadi alternatif pengobatan adalah madu klanceng. Penelitian ini bertujuan untuk mengetahui sediaan salep madu klanceng yang optimal dan efeknya terhadap penyembuhan luka dan infeksi yang disebabkan oleh bakteri. Tahapan penelitian ini terdiri dari uji fitokimia madu, pembuatan salep, uji sediaan salep, uji kemurnian bakteri, uji zona hambat, dan uji bioassay pada kelinci. Madu klanceng yang diuji mengandung senyawa alkaloid. Variasi salep madu dibuat dengan perbandingan basis salep dan madu adalah 1:1, 1:2, 1:5, dan 5:1. Hasil salep berbentuk semi padat, berwarna kuning, pH sekitar 4,8, belum homogen, memiliki daya lekat sekitar 265,4 detik, dan daya sebar sebesar 1,76 cm. Salep madu mampu menghambat bakteri S. aureus dan P. aeruginosa dengan diameter sebesar 1,2 mm. Salep madu ini juga memberikan efek menyembuhkan luka hingga 0,3 cm.
Evaluation of the Antifibrillatory Drug Interactions between Amiodarone and Diltiazem in Isolated Perfused Rabbit Hearts

The alarming reports of the proarrhythmic effects of several antiarrhythmic agents have stimulated our interest to study the antifibrillatory drug interactions that may occur when antiarrhythmic drugs from different classes are combined. Hearts isolated from New Zealand white rabbits of either sex weighing 1.5 to 2 kg were perfused by the Langendorff method with McEwen's solution. We used the serial-shock method of measuring VFT (ventricular fibrillation threshold), a method that have proved reliable in quantitatively assessing the antifibrillatory potency of many antiarrhythmic drugs we have studied during the last three decades. Perfusion with either amiodarone or diltiazem produced significant, dose-dependent increase in VFT. In addition, there was significant difference in the increase in VFT produced by the combined infusion of 1 μmol of amiodarone and 0.02 μmol of diltiazem and the summation of the increases produced by the separate infusion of these two concentrations. This synergistic antifibrillatory interactions between amiodarone and diltiazem may suggest that catuion has to be taken when amiodarone and diltiazem are combined in the treatment of cardiac arrhythmias as this may lead to a proarrhythmic effect. However, further studies are required to establish this in the clinical setup.
Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: Safety and clinical activity.

5533Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab in patients (pts) with recurrent/refractory ovarian cancer (OC; NCT01772004). Methods: Pts with advanced OC unselected for PD-L1 expression received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1). Unconfirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry. Results: As of Oct 23, 2015, 124 pts were treated with avelumab (median 12 wks [range 2-54]) and followed for a median of 54 wks (range 11-101). Median age was 62 y (range 27-84), ECOG PS was 0 (47.6%) or 1 (52.4%), and median number of prior therapies was 4 (range 1-13). Treatment-related (TR) AEs occurred in 82 pts (66.1%); most common (≥10%) w.
Learning from Imbalanced Data, with a Case Study in Finance

This thesis investigates some of the challenges with classifying imbalanced data sets, and logistic regression and random forests are the chosen algorithms. The main issue to deal with when classifying imbalanced data is the fact that most algorithms tend to maximize accuracy, which means that few of the minority class observations are correctly classified. Resampling techniques like undersampling, oversampling and SMOTE were used to balance the data set in order to improve the performance of the classifiers. A simplified version of SMOTE was implemented and used here. The performance was measured by balanced accuracy, and all three resampling methods seemed to yield quite similar results in many cases. For random forests, undersampling seemed to behave differently from oversampling and SMOTE. When applied to logistic regression, the resampling techniques all performed quite evenly. A data set was provided by Sparebank 1 Kredittkort AS, with the aim of identifying which customers might seek refinancing of their credit card debt from competing banks. Undersampling increased the balanced accuracy of random forests on this data set from 0.77 to 0.82. Logistic regression achieved a balanced accuracy of roughly 0.79 with no resampling, and 0.81 with resampling. Oversampling and SMOTE appeared to be slightly more effective on logistic regression than undersampling.
Primary Dysmenorrhea in the Schools of Parakou: Prevalence, Impact and Therapeutic Approach

Objective: Assess prevalence, associated factors, impact of primary dysmenorrhea and therapeutic approach available for Parakou high schools facing primary dysmenorrhea. Method: It is a cross-sectional, descriptive and analytical study carried out through a survey from 25 May to 30 August, 2014 among 425 girl students from public high schools in the town of Parakou. Probabilistic sampling served as research tool and information was collected using a self-administered questionnaire. Findings: Prevalence of primary dysmenorrhea was 78.35% with 95% CI [74.07% – 82.11%]. It was light in 33.3% of the cases; moderate in 37.8% and severe in 28.8%. Irritability and fatigue were the most associated signs respectively in 60.1% and 51.6% of the cases. Dysmenorrhea was significantly associated with adolescents’ age and family history of dysmenorrhea. Absenteeism in class was noted in 30% of the cases, declining concentration in 63.7% of the cases and participation to sports activities in 55% of the cases. Among the students suffering from dysmenorrhea 11% consulted a medical doctor for pain relief and 89% used either self-medication (68%) or traditional medicine (21%). Complementary treatments were performed and consisted of hot baths (29%), rest (67%), and scarifications (9%). Conclusion: Prevalence of dysmenorrhea in the schools is high in Parakou. It requires a particular attention for lack of information impacts on its persistent under-treatment.
Aerosol Impacts on Mesoscale Convective Systems Forming Under Different Vertical Wind Shear Conditions

Following our previous study of wind shear effect on mesoscale convective system (MCS) organization under a clean atmospheric condition using the Weather Research and Forecasting model coupled with spectral‐bin microphysics, we conduct sensitivity simulations by increasing cloud condensation nuclei concentration to investigate aerosol impacts on MCSs forming under different wind shear conditions. We find that increased aerosols induce stronger updrafts and downdrafts in all MCSs. The stronger updrafts and enlarged convective core area contribute to larger vertical mass fluxes and enhance precipitation. The enhanced updrafts and vertical mass fluxes indicate convective invigoration. Increased updraft speed below 8‐km altitude is attributed to enhanced condensational heating, except for the weak wind shear and strong low‐level shear cases in which the enhanced low‐level convergence is another contributing factor. Interestingly, above 8‐km altitude, we see reduced updraft speed by the increased aerosols due to reduced vertical pressure perturbation gradient force. The accumulated rainfall and mean rain rate are increased with a greater occurrence frequency of heavy rain. Larger rain rate is seen in both convective and stratiform regions. In general, we see a higher frequency of deep clouds in the polluted condition because of invigorated convection, and more stratiform/anvil clouds, but a lower frequency of shallow warm clouds, with a larger significance for more organized MCSs. The consistently invigorated MCSs by aerosols under various wind shear conditions revealed by this study have important implications to weather and climate in warm and humid regions that are influenced by pollution.
Accumulated oxygen deficit and running performance in man.

Until recently there has been no generally accepted non-invasive method for determining energy expenditure during high intensity exercise. However, Medbo et al. (1988) have suggested that an individual’s total energy (ATP) production from anaerobic metabolism may be determined by measuring the Accumulated Oxygen Deficit (AOD; ml O2 equivalents.kg-1 ). In recent studies it has been reported that there are strong correlations between AOD and anaerobic energy supply determined from changes in muscle metabolites during small muscle group (Bangsbo et al., 1990) and whole body cycle ergometer exercise (Medbo and Tabata, 1993; Withers et al., 1991). The purpose of the present thesis was: (i) to extend the limited information on AOD during running exercise for subjects with differing training backgrounds and particularly for women for whom no data are available; (ii) to investigate the relationship between AOD and human performance; and (iii) as determination of AOD is a time-consuming and costly laboratory procedure to develop a simple field test which accurately reflects AOD and thus anaerobic energy supply. [Continues. ]
Design and Analysis of Step-Up Interleaved DC–DC Converter for Different Duty Regions

A step-up interleaved dc–dc converter (IDC) operated in three different duty regions (<inline-formula><tex-math notation="LaTeX">$0 \leq D < 0.5$</tex-math></inline-formula>, <inline-formula><tex-math notation="LaTeX">$0.5 \leq D < 1,$</tex-math></inline-formula> and <inline-formula><tex-math notation="LaTeX">$0 \leq D < 1$</tex-math></inline-formula>) at a reduced number of elements is presented in this article. The IDC is capable of giving different voltage-gain characteristics in the three regions. The elements of IDC have different voltage and current stresses because of the three duty regions, which leads to cost-effective device selection according to the voltage-gain requirement of a particular application. Detailed mathematical modeling of the IDC is carried out in the three regions. Moreover, a comparison is made among the reported converters and IDC in terms of component count, voltage-gain, component voltage stresses, nature of input current and output voltages, and a discussion is carried out on their pros and cons. A laboratory prototype is developed to validate the performance of IDC in the three duty regions. Also, power loss and efficiency analysis of the IDC is carried out to show its effectiveness.
Comparing the Quality of Life in Patients With Multiple Sclerosis Consuming Fingolimod and Cinnovex

Background: Multiple Sclerosis (MS) is a chronic demyelinating, inflammatory, and degenerative disease of the central nervous system. MS gradually limits and deteriorates the patients’ quality of life. Objectives: This study aimed to evaluate and compare the quality of life in patients with MS consuming Fingolimod and Cinnovex. Materials & Methods: In an analytical cross-sectional study, 106 patients with Relapsing-Remitting MS (RRMS) referred to specialized neurology clinics of Guilan University of Medical Sciences were selected for the study using a convenience sampling method (52 patients consuming Fingolimod and 54 patients consuming Cinnovex). Then, we collected their demographic information and medical profile. The patients were assessed by the Hamburg quality of life questionnaire in MS. The obtained data were analyzed in SPSS V. 22 using the Chi-square test, independent t-test, Mann-Whitney U, one-way and multivariate analysis of covariance. Results: There was a significant difference between the two groups in terms of age, number of attacks in the last 6 months, and educational level (P<0.05). After controlling confounding variables, it was found that consumers of Fingolimod had a better quality of life. At the subscales level, this difference was significant only in the mood dimension (F=6.931, P=0.011, η=0.12). Conclusion: Patients consuming Fingolimod reported a better quality of life compared to consumers of Cinnovex. This improvement was mainly found in mood scores.
Body Image, Beliefs About Appearance, and Leisure Constraints Among Taiwanese Female Adolescents: Does Leisure Self-Efficacy Matter?

Abstract Body image among female adolescents has gained increasing attention of leisure researchers. However, very few studies have specifically answered how to tackle leisure constraints imposed by body image. This study investigated how body image and beliefs about appearance related to leisure constraints as well as the moderating effect of leisure self-efficacy. Survey data were collected from 388 female adolescents in Taiwan. The results indicate that body image dissatisfaction and negative beliefs about appearance are positively related to leisure constraints. Furthermore, the presence of leisure self-efficacy weakens the relationships of body image dissatisfaction and negative beliefs about appearance to leisure constraints. The implications of these findings and recommendations for future research are discussed subsequently.
Results of the Patent Ductus Arteriosus Closure Using the Video-Assisted Thoracoscopic Surgery

Background: Video-assisted thoracoscopic surgery (VATS) has been shown to be a safe and effective method for the patent ductus arteriosus (PDA) closure. This study aimed at evaluating the patients with PDA who underwent the VATS closure. Methods: In this retrospective descriptive study, the medical records of 129 patients with the mean age of 35.44 months who underwent VATS were assessed during 2003 - 2016. Demographic data, mortality rate and surgery events were also recorded and reported. Results: The results showed that 9.3 of the patients had conversion to thoracotomy and less than 2.3 (3 cases) of the patients developed pulmonary complications: two chylothorax and one residual shunt. The mortality rate of these patients was zero. Conclusions: Results of this study showed that the PDA surgery using the VATS method could reduce the mortality rate, complications and side effects. © 2017, Iranian Journal of Pediatrics.