Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated whole exome sequencing and functional approach delineate genetic heterogeneity in cerebellar ataxias

PurposeDisease deconvolution in heterogeneous cerebellar ataxias (CAs) needs a focussed approach to overcome the diagnostic challenges. A diverse clinical presentation with over 100 reported genetic loci, in addition to the various challenges associated with genotype-phenotype correlation complicate the genetic diagnosis in 40-60% of the CA cases that remain uncharacterized. We present here an integrated whole exome sequencing combined with a functional validation approach to delineate the genetic etiology in Indian CA patients.MethodA total of 50 familial and sporadic progressive CA families (negative for CNG expansion) including 101 subjects were recruited for this study. Index patients from 50 families were subjected to singleton whole exome sequencing (S-WES). Family-based WES (F-WES) was carried out for seven S-WES selected families. Protein simulation and docking studies were performed for seven genetic variants identified through WES. A Cell line-based model was used to assess disease signatures for variants in KCNC3 and a new candidate gene, SPTB.ResultsClinically relevant variants identified in 70% (35/50) of the selected families. We achieved a 50% (25/50) definitive diagnostic yield and 14% (7/50) probable diagnostic yield while 6% (3/50) of the families showed variants of uncertain significance. We prioritized compound heterozygous variants in a candidate gene, SPTB for cerebellar ataxia with hereditary spherocytosis. Lymphoblastoid cell line derived from a patient with a KCNC3 variant showed altered disease signatures with induced ROS and elevated unfolded protein response markers at the basal level.ConclusionOur results highlight an extensive experimental design for the genetic diagnosis of CA. Through targeted analysis of ataxia phenotype-derived gene panel in S-WES, new gene identification through F-WES, and revaluation of unsolved families’ WES data, we identified novel, reported and other clinically relevant variants in CA patients. Bioinformatic protein modeling along with the cellular insights into the pathogenicity of novel variants enabled delineation of genetic diagnostics and enhanced the mechanistic understanding of CAs.
Clinical efficacy of hyaluronic acid in post-extraction sockets of impacted mandibular third molar

Background and Objectives: Pain and swelling are the most common complications that occur after surgical removal of impacted third molar. Aim of this study to evaluate the effectiveness of local hyaluronic acid (HA) administration to surgically remove impacted third molar sockets to evaluate pain and swelling.Materials and Methods: A comparative study included 50 healthy patients were subdivided into two equal sub group, aged 18-35 years with impacted lower third molars type of impaction (class II; position B according to Pell–Gregory classification). The procedure has been performed under local anesthesia. In the study group, 0.8% HA (Gengigel®) was applied in the post-extraction sockets of third molars and in the control group nothing was applied to the extraction sockets of third molars. Pain and swelling were evaluated with a visual analogue scale (VAS). Assessments were made on 1st, 2nd, 3th, 4th, 5th, 6th, 7th days after surgery.Results: Statistically significant difference was detected for the pain values between the two treatment groups in different days of the study (p < 0.05). The swelling scores of the hyaluronic acid group were significantly lesser than those of the control group in day 1 (p = 0.008), day 3 (p = 0.006), and day 4 (p = 0.036). In the other days, the scores were less but the differences were not significant. Conclusion: hyaluronic acid appears to offer a beneficial effect in the management of pain and swelling during the immediate postoperative period following impacted third molar surgery.
A Novel Hybrid Deep Learning Model for Sugar Price Forecasting Based on Time Series Decomposition

Sugar price forecasting has attracted extensive attention from policymakers due to its significant impact on people’s daily lives and markets. In this paper, we present a novel hybrid deep learning model that utilizes the merit of a time series decomposition technology empirical mode decomposition (EMD) and a hyperparameter optimization algorithm Tree of Parzen Estimators (TPEs) for sugar price forecasting. The effectiveness of the proposed model was implemented in a case study with the price of London Sugar Futures. Two experiments are conducted to verify the superiority of the EMD and TPE. Moreover, the specific effects of EMD and TPE are analyzed by the DM test and improvement percentage. Finally, empirical results demonstrate that the proposed hybrid model outperforms other models.
Art tourism: definitions, opportunities, and discussions based on a case study from Abu Dhabi

ABSTRACT By presenting the case of Abu Dhabi, with newly opened Louvre, the position of art tourism in the context of cultural tourism is discussed in this paper. Abu Dhabi, the capital of the United Arab Emirates, aims to position the city as the region’s arts and culture hub. Emirati artists and art-related projects play an important role in up-scaling the art experience for tourists in the region. To understand the views of Emirati artists, thirteen e-interviews were conducted to study the current role of art tourism and the levels of optimism observed among local artists. Interview questions focused on perceptions of art tourism, on the role of artists, and on the relation between art and culture in this fifty years old country. Findings exhibit a sense of optimism especially in relation to the newly opened Louvre, which has boosted art tourism in the UAE. However, the real art market is neglected and under-researched, but the predictions are generally auspicious.
DFlow: A Data Flow Analysis Tool for C/C++

Abstract syntax trees (ASTs), control flow graphs (CFGs), and data flow analysis (DFA) are prerequisites for static and dynamic analysis and vulnerability detection for programs; thus, obtaining them is significant. Recently, many tools related to generating ASTs, CFGs, and DFA have been proposed. However, most tools can only construct ASTs, very few can construct ASTs and CFGs, and almost none can construct all three. The vast majority of AST, CFG, and DFA tools are for other languages (e.g., Java and Python), and while a few are for C/C++, they are implemented in other languages, creating complex working environments, and overreliance on other language‐related libraries. To address these shortcomings, we present a DFA tool, DFlow, for C/C++. First, a lexical/grammatical analyzer generated by Flex and Bison is used to analyze the program. Second, an AST is constructed from the results; then, a CFG is obtained from the analysis results and the information from the AST. Finally, based on the AST and CFG, DFA is performed, and the vulnerabilities of simple programs are determined. We test some common vulnerable code and common weakness enumeration slicing code, which show the effectiveness of DFlow in program data flow analysis and vulnerability checking. The results show that our tool can implement ASTs, CFGs, and DFA, and we add some rules to the tool for vulnerability detection. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Ambient PM2.5 and Daily Hospital Admissions for Acute Respiratory Infections: Effect Modification by Weight Status of Child

The high level of ambient particulate matter in many developing countries constitutes a major health burden, but evidence on its impact on children’s health is still limited in these regions. We conducted a time-stratified case-crossover analysis to quantify the short-term association between fine particulate matter (PM2.5) and hospital admissions due to acute respiratory infections (ARI) among children in Bhaktapur district, Nepal, and to investigate the potential modification of the effect by nutritional characteristic. We analyzed 258 children admitted to the pediatric hospital for ARI between February 2014 to February 2015. We observed evidence of increased risk on the same (lag 0) and preceding day (lag 1). The cumulative estimate of their average (lag 01) suggested each 10 μg/m3 increase in PM2.5 was associated with a relative risk (RR) of 1.16 (95% confidence interval [CI]: 1.02–1.31). The strongest evidence from a stratified analysis of three categories of weights was observed in the overweight group (RR: 1.77; 95% CI: 1.17–2.69) at lag 01, while the estimates for the normal weight and underweight groups were closer to the non-stratified estimates for all-ARI cases. The findings suggests that pediatric ARI is an important morbidity associated with inhalable PM2.5 and that more research is needed to elucidate and validate the observed dissimilarity by weight.
Comparison of anthocyanin and polyphenolics in purple sweetpotato (Ipomoea batatas Lam.) grown in different locations in Japan

ABSTRACT The health benefits of purple sweetpotato, which is used as an edible food in its natural state and in processed foods and as a natural color pigment, have been recognized. In Japan, sweetpotato has been economically produced in regions below 36°4ʹN latitude; however, cultivation areas are beginning to expand further north. The anthocyanin and polyphenolics in three purple sweetpotatoes cultivated in different locations; I (42°92ʹN, 143°04ʹE) and II (31°72ʹN, 131°03ʹE), were compared over two years. Total anthocyanin and polyphenolic contents in purple sweetpotatoes tended to be high in location I. The anthocyanin and polyphenolic compositions differed between locations. The peonidin/cyanidin ratios were higher in location II compared with I in all varieties. The relative amount of 3,4- and 4,5-di-O-caffeoyolquinic acids were higher in location II. Their contents and composition also differed between years. These results suggest that the variability of the anthocyanin and polyphenolic content and composition was influenced by climate conditions, probably temperature during cultivation. This study indicates that northern areas in Japan are an alternative production area and may yield higher amounts of anthocyanin and polyphenolics. Graphical abstract
Circulating Gremlin-1 is elevated in systemic sclerosis patients

Introduction: Systemic sclerosis is an autoimmune connective tissue disease in which there is activation of the immune system, vascular disease and fibrosis. Activation of quiescent fibroblasts to myofibroblasts is key to disease pathogenesis. Gremlin-1 is a bone morphogenetic protein antagonist which is important in development and we recently reported in skin fibrosis. The aim of this study was to determine the serum circulating levels of Gremlin-1 in early diffuse systemic sclerosis. Methods: Twenty-one early diffuse systemic sclerosis patients (less than 2 years from first non-Raynaud’s symptom) were included and age and sex-matched healthy controls. Serum was isolated from blood and measured with a specific enzyme-linked immunoassay for Gremlin-1. Clinical variables were also measured. Results: Significantly elevated Gremlin-1 was found in sera of early diffuse systemic sclerosis patients (p < 0.001). In patients with interstitial lung disease, this compared to systemic sclerosis without evidence of interstitial lung disease, Gremlin-1 was significantly elevated (p < 0.0007). A correlation was found between circulating Gremlin-1 and modified Rodnan Skin Score, albeit weak. Discussion: In early diffuse systemic sclerosis patients, elevated Gremlin-1 is found in serum. This is particularly prominent in systemic sclerosis–associated interstitial lung disease. This suggests that Gremlin-1 may be a biomarker for systemic sclerosis interstitial lung disease.
Associations of Sperm mtDNA Copy Number, DNA Fragmentation Index, and Reactive Oxygen Species With Clinical Outcomes in ART Treatments

Recent studies have suggested that sperm mitochondrial DNA copy number (mtDNA-CN), DNA fragmentation index (DFI), and reactive oxygen species (ROS) content are crucial to sperm function. However, the associations between these measurements and embryo development and pregnancy outcomes in assisted reproductive technology (ART) remain unclear. Semen samples were collected from 401 participants, and seminal quality, parameters of sperm concentration, motility, and morphology were analyzed by a computer-assisted sperm analysis system. DFI, mtDNA-CN, and ROS levels were measured using sperm chromatin structure assay, real-time quantitative polymerase chain reaction, and ROS assay, respectively. Among the participants, 126 couples underwent ART treatments, including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and 79 of the couples had embryos transferred. In 401 semen samples, elevated mtDNA-CN and DFI were associated with poor seminal quality. In 126 ART couples, only mtDNA-CN was negatively correlated with the fertilization rate, but this correlation was not significant after adjusting for male age, female age, seminal quality, ART strategy, number of retrieved oocytes, controlled stimulation protocols, and cycle rank. Regarding pregnancy outcomes, sperm mtDNA-CN, ROS, and DFI were not associated with the clinical pregnancy rate or live birth rate in 79 transferred cases. In conclusion, increased mtDNA-CN and DFI in sperm jointly contributed to poor seminal quality, but sperm mtDNA-CN, ROS, and DFI were not associated with clinical outcomes in ART.
On the dynamics of a meniscus inside capillaries during imbibition and drainage processes: A generalized model, effect of inertia, and a numerical algorithm

In imbibition or drainage processes, a fluid displaces another immiscible one. If the displacing fluid is wetting, this is an imbibition process and is drainage if otherwise. While imbibition can proceed without the action of external force (e.g., pressure), drainage cannot unless sufficient external force is applied. One of the most important phenomena in this regard is related to the estimation of the location of the meniscus inside the tube and its velocity with time. This has been the topic of extensive research works for which analytical expressions exist for some special cases including the case in which the displaced fluid is air. Recently, a generalization to this approach has been developed, which accounts for the more general scenario in which the displaced fluid assumes considerable viscosity and density contrasts compared with the displacing one. However, in this recently developed model, and even in most of the previously studied special cases, an inherent assumption was made to ignore inertial effects. While this assumption is reasonable given the relatively slow advancement of the meniscus in capillaries, it results in the velocity to jump at the start of the imbibition process to a relatively higher value before declining as the meniscus advances. In fact, in actual imbibition experiments, velocity develops from zero to a maximum value in a short period of time before it declines as the meniscus continues to advance. In this work, a generalized model is developed, which accounts for the inertia of the fluids inside the tube. A nonlinear ordinary differential equation is developed, which accounts for the acceleration of the fluid and the contrasts of viscosity and density of the two fluids in capillaries. A numerical algorithm is also developed where the differential equation is linearized to facilitate the numerical solution. Verifications of the numerical algorithm are conducted to build confidence in the computational approach.
Diagnosis Support System for General Diseases by Implementing a Novel Machine Learning Based Classifier

: Millions of folks around the earth are affliction from late disease identification and diagnosis. An incredible amount of health information has been obtained by the latest technologies in digital medical services and information communication technologies. Disease diagnosis and artificially intelligent decision support systems have drawn tremendous attention from many scientists and research community worldwide. Various algorithms developed and applied with the aid of machine learning techniques that can substantially lead to the resolution of the system of health care and can help personnel involved in the early diagnosis of diseases. This research paper will propose an artificial intelligent algorithm which helps us to effectively, rapidly and accurately classify the information. The Proposed Disease Diagnosis Support Systems (DDSS) can assist clinicians to monitor the information, facilitate their evaluation by means of a preparatory treatment and decrease evaluation time per patient. The patients may inevitably be notified and recommended dietary suggestions also. This system will allow clinicians to focus on attending patients in accordance with their homeostasis. It decreases the volume of work of doctors and enables them to define patients who need to be examined more urgently or meticulously. Even with the widespread growth of such systems security of digital data and its privacy is still a major challenge yet to solve.
The impact of risk factors on South African consumers’ attitude towards online shopping

Online shopping has been an increasing trend worldwide, especially in countries with a welldeveloped infrastructure for online marketing activities. Online shopping involves purchasing goods and services over the internet (Malapane 2019:1). Consumers can now conveniently purchase products from anywhere, at any time (Arora & Sahney 2018:1040), with an abundance of information. Given the benefits of online shopping, online transactions’ high cart abandonment rates remain a concern (Statista 2020). This is because consumers often prefer to shop at physical retailers because of the ability to touch and feel products physically, instant possession, online distrust and the perceived risk associated with online purchases (Arora & Sahney 2018:1040). Because of these concerns, online shopping is used to make price and product feature comparisons; however, the decision and actual purchases are made in store, after the physical evaluation (Wolny & Charoensuksai 2014:324). This challenge presents an opportunity for online retailers and marketing practitioners to evaluate further the impact that perceived risk has on online buying behaviour and to comprehend online shopping through consumers’ eyes. This is supported by Yang, Sarathy and Lee (2016:75), who stated that future research should take a more consumer-centric approach and try to understand better the impact of online shopping risk factors on consumers’ purchasing behaviour.
Circulating tumor cells and circulating cancer stem cells and their detection by the method of flow cytometry

This review describes the circulating cancer stem cells (CCSCs) and circulating tumor cells (CTCs). CCSCs are one of the main initiators of recurrent cancer and thus make them an important target for the development of new treatment methods. CTCs are relatively new biomarkers for the early diagnosis of metastasis. CTCs provide doctors with valuable information about each stages of cancer treatments: diagnostic of early-stage disease, early detection of recurrent cancer, the efficiency of chemotherapy, and makes it possible to select an individual sensitive drug.The most informative and frequently used markers for the detection of CSCs and CSCs were described. The mechanism of two models of tumor formation is considered: clonal and hierarchical. The known mechanisms of epithelial-mesenchymal transition of tumor cells are described. The most widely used specific cell surface markers for the detection and isolation of CTCs and CCSCs are described. The efficiency of a sensitive high-precision method of multicolor flow cytometry using specific fluorescent dye-labeled monoclonal antibodies for the detection of CCSCs and CTCs in the blood of cancer patients is analyzed. Detection of CTCs and CCSCs provides important information for the early diagnosis of metastasis and open a possibility to personalized treatment, and to monitoring of all stages cancers.
The Hidden Role of Contract Terms: The Case of Credit Card Minimum Payments in Mexico

This paper argues that thresholds in financial contracts act as implicit nudges in consumers’ decisions. Exploiting a regulatory change to credit card minimum payments in Mexico, we find that a 1-percentage point change in minimum payments leads to a 0.87-percentage point change in actual payments, both expressed as a percentage of total balances. We decompose the effect of minimum payments into a constraining effect and a reference effect. The former captures the effect of minimum payments as a binding constraint and accounts for 59% of its total effect. The latter captures any remaining impact of changes in minimum payments beyond their constraining effect and represents 41% of the total. In turn, 67% of the reference effect is explained by the multiple heuristic: the tendency of consumers to pay whole-number multiples of the minimum payment. This paper was accepted by Kay Giesecke, finance.
Producción de eritadenina por Lentinula edodes en fermentación en estado sólido

Antecedentes: Lentinula edodes es un hongo comestible de importancia económica en México, produce un compuesto reductor de colesterol llamado eritadenina, el cual se ha obtenido del cuerpo fructífero y micelio del hongo. Su producción se ha evaluado en fermentación sumergida, pero hasta ahora no se ha evaluado la fermentación en estado sólido. Objetivos: Determinar si la fermentación en estado sólido de L. edodes mejora la producción de eritadenina. Métodos: Se realizó una fermentación en estado sólido con espuma de poliuretano y un medio enriquecido para determinar la producción de eritadenina, biomasa y consumo de sustrato; la eritadenina se detectó por HPLC-DAD a 260 nm. Resultados y conclusiones: La biomasa máxima fue de 3.6 ± 0.11 g/L, con una tasa de crecimiento específico de 0.015 ± 0.002 h-1. La eritadenina se produjo en la biomasa y se liberó al medio de cultivo; a las 168 h de incubación se incrementó 2.8 y 2.4 veces, respectivamente. Se encontró una relación proporcional entre la producción de eritadenina y biomasa. No hubo relación entre el consumo de sustrato y la producción de eritadenina. La fermentación en estado sólido es una alternativa para producir y recuperar la eritadenina.
Do Concerns about Immigration Change after Adolescence? How Education and Critical Life Events Affect Concerns about Immigration

This study investigates whether critical life events that typically occur during early adulthood (i.e., labor market entry, unemployment, parenthood) impact concerns about immigration. Two mechanisms suggest that these critical life events lead to a widening of education-specific differences: First, the amplification of ethnic competition following critical life events may be more pronounced for individuals with low educational attainment. Second, psychological adaptation processes of individuals with low levels of education may more frequently result in scapegoating. These mechanisms provide a rationale for the education-as-buffer hypothesis, according to which individuals with lower educational attainment are more prone to exhibit increasing concerns about immigration following critical life events. Estimations of distributed fixed effects models relying on data from the German Socio-Economic Panel Study (1999–2017) show that labor market entry, unemployment, and parenthood increase concerns about immigration more strongly for individuals with low educational attainment. Replicating significant impact differences between educational groups for the three critical life events makes a strong case for the education-as-buffer hypothesis. Overall, this study demonstrates that concerns about immigration are responsive to critical life events and calls for further theorizing as to how educational attainment may shape attitudes towards immigration over the life course.