Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcomes in Pediatric Autoimmune Hepatitis and Significance of Azathioprine Metabolites

Objectives: Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with azathioprine (AZA). There is no consensus on the target range for AZA active metabolite 6-thioguanine (6-TGN) levels in pediatric AIH. The aim of the present study was to characterize the outcomes of pediatric patients with AIH and determine correlations between AZA dosing or 6-TGN metabolite levels and biochemical remission. Methods: A retrospective chart review was performed and data on presentation, laboratories including AZA metabolite levels, medication use, and outcomes were collected. Results: Between 2002 and 2013, 66 children with AIH were identified (mean age at diagnosis 9.6 ± 5.1 years) with a mean follow-up period of 2.9 ± 3.2 years. Common presenting symptoms included jaundice, fatigue, and abdominal pain. The majority of subjects received steroids for induction and AZA for maintenance of remission. Seventy-nine percent achieved biochemical remission (mean time to remission 6.2 ± 9.2 months), 14% were in the induction phase of therapy, 6% required liver transplantation, and 18% were weaned off immunosuppression and remained in remission. 6-TGN levels ranging from 50 to 250 pmol/8 × 108 red blood cell count were associated with biochemical remission (alanine aminotransferase levels of ⩽50 U/L). Conclusions: The vast majority of children with AIH maintain a sustained remission with AZA monotherapy. Biochemical remission was maintained with 6-TGN levels much lower than that recommended for inflammatory bowel disease. These findings suggest that patients should be maintained at the lowest AZA dose possible that is associated with biochemical remission.
The Center for Epidemiologic Studies Depression Scale: A Review with a Theoretical and Empirical Examination of Item Content and Factor Structure

Background The Center for Epidemiologic Studies Depression Scale (CES-D; Radloff, 1977) is a commonly used freely available self-report measure of depressive symptoms. Despite its popularity, several recent investigations have called into question the robustness and suitability of the commonly used 4-factor 20-item CES-D model. The goal of the current study was to address these concerns by confirming the factorial validity of the CES-D. Methods and Findings Differential item functioning estimates were used to examine sex biases in item responses, and confirmatory factor analyses were used to assess prior CES-D factor structures and new models heeding current theoretical and empirical considerations. Data used for the analyses included undergraduate (n = 948; 74% women), community (n = 254; 71% women), rehabilitation (n = 522; 53% women), clinical (n = 84; 77% women), and National Health and Nutrition Examination Survey (NHANES; n = 2814; 56% women) samples. Differential item functioning identified an item as inflating CES-D scores in women. Comprehensive comparison of the several models supported a novel, psychometrically robust, and unbiased 3-factor 14-item solution, with factors (i.e., negative affect, anhedonia, and somatic symptoms) that are more in line with current diagnostic criteria for depression. Conclusions Researchers and practitioners may benefit from using the novel factor structure of the CES-D and from being cautious in interpreting results from the originally proposed scale. Comprehensive results, implications, and future research directions are discussed.
The Baboon Kidney Transcriptome: Analysis of Transcript Sequence, Splice Variants, and Abundance

The baboon is an invaluable model for the study of human health and disease, including many complex diseases of the kidney. Although scientists have made great progress in developing this animal as a model for numerous areas of biomedical research, genomic resources for the baboon, such as a quality annotated genome, are still lacking. To this end, we characterized the baboon kidney transcriptome using high-throughput cDNA sequencing (RNA-Seq) to identify genes, gene variants, single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (InDels), cellular functions, and key pathways in the baboon kidney to provide a genomic resource for the baboon. Analysis of our sequencing data revealed 45,499 high-confidence SNPs and 29,813 InDels comparing baboon cDNA sequences with the human hg18 reference assembly and identified 35,900 cDNAs in the baboon kidney, including 35,150 transcripts representing 15,369 genic genes that are novel for the baboon. Gene ontology analysis of our sequencing dataset also identified numerous biological functions and canonical pathways that were significant in the baboon kidney, including a large number of metabolic pathways that support known functions of the kidney. The results presented in this study catalogues the transcribed mRNAs, noncoding RNAs, and hypothetical proteins in the baboon kidney and establishes a genomic resource for scientists using the baboon as an experimental model.
Cost of Contraceptive Implant Removal Services Must Be Considered When Responding to the Growing Demand for Removals

In a recently published article in Global Health: Science and Practice, “Accessible contraceptive implant removal services: an essential element of quality service delivery and scale-up,” Christofield and Lacoste emphasized the growing unmet need for quality implant removal services. The authors projected the numbers of implant removals in 69 Family Planning 2020 (FP2020) focus countries to more than double between 2015 and 2018 (from 2.2 million to between 4.9 and 5.8 million). The Implant Removal Task Force of the Implants Access Program Operations Group is developing best practices and solutions to meet this increasing demand. In addition to the sheer numbers of implants that will require removal in coming years, the cost of removal services must also be considered. To begin to understand this impending resource need, we conducted a modeling exercise to forecast potential demand for contraceptive implant removals between 2016 and 2020 in the 5 countries with the highest levels of implant procurement in 2015 (Tanzania, Nigeria, Ethiopia, Kenya, and Zambia). We then applied a direct cost (supplies and labor) of US$2.41 per removal derived from projections based on previously developed cost estimates for Kenya. Our analysis differed fromChristofield and Lacoste in 2 ways:
Meiofauna Metabolism in Suboxic Sediments: Currently Overestimated

Oxygen is recognized as a structuring factor of metazoan communities in marine sediments. The importance of oxygen as a controlling factor on meiofauna (32 µm-1 mm in size) respiration rates is however less clear. Typically, respiration rates are measured under oxic conditions, after which these rates are used in food web studies to quantify the role of meiofauna in sediment carbon turnover. Sediment oxygen concentration ([O2]) is generally far from saturated, implying that (1) current estimates of the role of meiofauna in carbon cycling may be biased and (2) meiofaunal organisms need strategies to survive in oxygen-stressed environments. Two main survival strategies are often hypothesized: 1) frequent migration to oxic layers and 2) morphological adaptation. To evaluate these hypotheses, we (1) used a model of oxygen turnover in the meiofauna body as a function of ambient [O2], and (2) performed respiration measurements at a range of [O2] conditions. The oxygen turnover model predicts a tight coupling between ambient [O2] and meiofauna body [O2] with oxygen within the body being consumed in seconds. This fast turnover favors long and slender organisms in sediments with low ambient [O2] but even then frequent migration between suboxic and oxic layers is for most organisms not a viable strategy to alleviate oxygen limitation. Respiration rates of all measured meiofauna organisms slowed down in response to decreasing ambient [O2], with Nematoda displaying the highest metabolic sensitivity for declining [O2] followed by Foraminifera and juvenile Gastropoda. Ostracoda showed a behavioral stress response when ambient [O2] reached a critical level. Reduced respiration at low ambient [O2] implies that meiofauna in natural, i.e. suboxic, sediments must have a lower metabolism than inferred from earlier respiration rates conducted under oxic conditions. The implications of these findings are discussed for the contribution of meiofauna to carbon cycling in marine sediments.
Cyclic Mechanical Stretch Induced Smooth Muscle Cell Changes in Cerebral Aneurysm Progress by Reducing Collagen Type IV and Collagen Type VI Levels

Background/Aims: Cerebral aneurysm growth is characterized by continuous structural weakness of local smooth muscle cells, though the mechanism is unclear. In this study, we examine protein changes in cerebral aneurysm and human brain vascular smooth muscle cells after cyclic mechanical stretch. We further explore the relationship between the smooth muscle cell changes and reductions in the levels of collagen types IV and VI. Methods: Saccular cerebral aneurysms (n=10) were collected, and temporal artery samples were used as controls. Quantitative proteomics were analyzed and histopathological changes were examined. Smooth muscle cells were cultured in a flexible silicone chamber and subjected to 15% cyclic mechanical stretch. The effect of stretch on the cell viability, function, gene and protein expression were further studied for the understanding the molecular mechanism of aneurysm development. Results: Proteomics analysis revealed 92 proteins with increased expression and 88 proteins with decreased expression compared to the controls (p<0.05). KEGG pathway analysis showed that the change in focal adhesion and extracellular matrix-receptor interaction, suggesting the involvement of collagen type IV and VI. The aneurysm tissue exhibited fewer smooth muscle cells and lower levels of collagen type IV and VI. Human brain vascular smooth muscle cell culture showed spindle-like cells and obvious smooth muscle cell layer. Cell proteomics analysis showed that decreased expression of 118 proteins and increased expression of 32 proteins in smooth muscle cells after cyclic mechanical stretch. KEGG pathway analysis indicated that focal adhesion and ECM-receptor interaction were involved. After cyclic mechanical stretch, collagen type IV and IV expression were decreased. Moreover, the stretch induced MMP-1 and MMP-3 expression elevation. Conclusion: We demonstrated that collagen type IV and VI were decreased in cerebral aneurysms and continuous cyclic mechanical stretch induced smooth muscle cell changes. Smooth muscle cell protection provides an additional therapeutic option to prevent the growth of cerebral aneurysms.
E-Filing Behaviour among Academics in Perak State in Malaysia

Perak State government in Malaysia has been promoting an Internet tax filing called electronic filing as part of its e-government initiative. Starting in year 2006, Malaysia Inland Revenue Board (IRBM) has launched the e-filing method for individual taxpayers and from that point of time, Malaysia’s citizens are provided with the option to choose their tax filing method either in the way of manual tax-filing method or e-filing method. This study focuses on the Perak State academics’ intention and behavior to adopt e-filing tax system. The target population for this study is academic staff in Perak State in Malaysia. 116 usable questionnaires were collected from three public institutions and two private institutions of higher learning in Perak State in Malaysia and the data analyzed through the SPSS. The findings show that perceived use of use, perceived usefulness, perceived security, and perceived credibility do influence the Perak State academic’s e-filing adoption intention. However, perceived service and information quality has not influenced their e-filing adoption intention. This study provides several important implications for building and promoting effective e-filing system by the IRBM.
An application of methylcellulose-whey protein films on Japanese persimmon

Enzymatic and non-enzymatic browning reactions, water loss, oxidation and microbial growth can cause decreases in the quality of fresh fruits. Packaging can be an effective way to control and prevent these undesirable changes. Edible films and coatings having low water vapor permeability (WVP) are used to extend the shelf life of these perishable foods. Use of the methylcellulose-whey protein (MCWP) based edible films which have low WVP may retard ripening and softening of fruits. In this study, Japanese persimmons (Diospyros kaki L.) were wrapped with MC-WP films and stored at 10 and 25°C. Changes in the weight and firmness of the fruits during storage were investigated. Wrapping had no effect on weight losses and firmness of the fruits stored at 10°C. On the other hand, wrapping had no significant effect on firmness but caused an increase in weight loss of the fruits stored at 25oC. The wrapped fruits showed higher weight loss than non-wrapped ones at 25°C after the 10 days. The appearance of wrapped fruits was better than non-wrapped ones at the end of storage, since mold growth on non-wrapped fruits was observed.
Plasmodium Infections in Natural Populations of Anolis sagrei Reflect Tolerance Rather Than Susceptibility

Synopsis Parasites can represent formidable selection pressures for hosts, but the cost of infection is sometimes difficult to demonstrate in natural populations. While parasite exploitation strategies may, in some instances, actually inflict low costs on their hosts, the response of hosts to infection is also likely to determine whether or not these costs can be detected. Indeed, costs of infection may be obscured if infected individuals in the wild are those that are the most tolerant, rather than the most susceptible, to infection. Here we test this hypothesis in two natural populations of Anolis sagrei, one of the most common anole lizard of the Bahamas. Plasmodium parasites were detected in > 7% of individuals and belonged to two distinct clades: P. mexicanum and P. floriensis. Infected individuals displayed greater body condition than non-infected ones and we found no association between infection status, stamina, and survival to the end of the breeding season. Furthermore, we found no significant difference in the immuno-competence (measured as a response to phytohemagglutinin challenge) of infected versus non-infected individuals. Taken together, our results suggest that the infected individuals that are caught in the wild are those most able to withstand the cost of the infection and that susceptible, infected individuals have been removed from the population (i.e., through disease-induced mortality). This study highlights the need for caution when interpreting estimates of infection costs in natural populations, as costs may appear low either when parasites exploitation strategies truly inflict low costs on their hosts or when those costs are so high that susceptible hosts are removed from the population.
Factors associated with cognitive impairment in patients with newly diagnosed type 2 diabetes: a cross-sectional study

Objectives: Type 2 diabetes (T2DM) is strongly associated with cognitive impairment but the factors within T2DM that predispose to cognitive impairment are less well understood, while previous studies have investigated samples with T2DM of widely varying duration. We aimed to investigate the factors associated with cognitive impairment in patients with newly diagnosed T2DM. Method: In a multi-ethnic sample with T2DM diagnosed in the last 6 months, we assessed cognitive function using the 13-item modified telephone interview for cognitive status (TICS-M). Cognitive function was assessed both categorically (impairment defined as lowest 10% of scores with the remainder as controls) and as continuous TICS-M score. Its associations were tested in univariate and multivariate analyses with a range of biological, psychological and sociodemographic factors. Results: Of 1790 participants, 1680 had a complete TICS-M assessment at baseline. After controlling for covariates, older age (p < 0.001) and lower verbal intelligence (p < 0.001) were associated with both cognitive impairment and lower TICS-M scores, while non-white ethnicity (p < 0.001), female gender (p = 0.02) and higher HbA1c (p = 0.002) were associated with lower TICS-M scores. Depression (defined as Patient Health Questionnaire-9 score ≥10), elevated inflammatory markers and body mass index were not associated with cognitive function after controlling for covariates. Conclusion: Age, verbal intelligence, female gender and HbA1c are associated with cognitive performance in T2DM soon after diagnosis. Previously reported associations with depression and inflammatory markers may occur later as causes or consequences of T2DM. Longitudinal analyses are needed to assess potentially modifiable factors predicting cognitive decline in early T2DM.
Effect of Heavy Atoms on the Thermal Stability of α-Amylase from Aspergillus oryzae

Currently, there are no versatile and established methods for improving stability of proteins. In an entirely different approach from conventional techniques such as mutagenesis, we attempted to enhance enzyme stability of α-amylase from Aspergillus oryzae using a heavy-atom derivatization technique. We evaluated changes in stability using differential scanning calorimetry (DSC). Candidate heavy atoms were identified using the Heavy-Atom Database System HATODAS, a Web-based tool designed to assist in heavy-atom derivatization of proteins for X-ray crystallography. The denaturation temperature of α-amylase derivatized with gadolinium (Gd) or samarium (Sm) ions increased by 6.2 or 5.7°C, respectively, compared to that of the native protein (60.6°C). The binding of six Gd ions was confirmed by X-ray crystallography of the enzyme at 1.5 Å resolution. DSC and dynamic light-scattering data revealed a correlation between stability and the aggregation state upon addition of Gd ions. These results show that HATODAS search is an effective tool for selecting heavy atoms for stabilization of this protein.
Heterologous Expression of AtBBX21 Enhances the Rate of Photosynthesis and Alleviates Photoinhibition in Solanum tuberosum1[OPEN]

Expression of AtBBX21 in potato causes morphological and physiological changes that improve photosynthetic rates in high-irradiance conditions without negatively affecting water use efficiency. B-box (BBX) proteins are zinc-finger transcription factors containing one or two B-box motifs. BBX proteins act as key factors in the networks regulating growth and development. The relevance of BBX21 to light and abscisic acid signaling in seedling development is well established; however, its importance in adult plant development and agronomic species is poorly understood. Therefore, we studied the effect of heterologous expression of Arabidopsis (Arabidopsis thaliana) BBX21 in potato (Solanum tuberosum) var Spunta. Three independent AtBBX21-expressing lines and the wild-type control were cultivated under sunlight and at controlled temperatures in a greenhouse. By anatomical, physiological, biochemical, and gene expression analysis, we demonstrated that AtBBX21-expressing plants were more robust and produced more tubers than wild-type plants. Interestingly, AtBBX21-expressing plants had higher rates of photosynthesis, with a significant increase in photosynthetic gene expression, and higher stomatal conductance, with increased size of the stomatal opening, without any associated decline in water use efficiency. Furthermore, AtBBX21-expressing potato plants had reduced photoinhibition associated with higher production of anthocyanins and phenolic compounds, and higher expression of genes in the phenylpropanoid biosynthesis pathway. To gain insights into the mechanism of BBX21, we evaluated the molecular, morphological, metabolic, and photosynthetic behavior in adult BBX21-overexpressing Arabidopsis. We conclude that BBX21 overexpression improved morphological and physiological attributes, and photosynthetic rates in nonoptimal, high-irradiance conditions, without associated impairment of water use efficiency. These characteristics of BBX21 may be useful for increasing production of potatoes, and potentially of other crops.
Epidemiology of cervical cancer with special focus on India

Cervical cancer is on the declining trend in India according to the population-based registries; yet it continues to be a major public health problem for women in India. Multifactorial causation, potential for prevention, and the sheer threat it poses make cervical cancer an important disease for in-depth studies, as has been attempted by this paper. This paper attempts to review the available knowledge regarding the epidemiology and pattern of cervical cancer; types of HPV (human papilloma virus) prevalent among cervical cancer patients and among women in general, high-risk groups such as commercial sex workers, and HIV (human immunodeficiency virus)-positive women; and the role of the national program on cancer in control efforts. The peak age of incidence of cervical cancer is 55–59 years, and a considerable proportion of women report in the late stages of disease. Specific types of oncogenic HPV-16, 18 have been identified in patients with cervical cancer. Other epidemiological risk factors are early age at marriage, multiple sexual partners, multiple pregnancies, poor genital hygiene, malnutrition, use of oral contraceptives, and lack of awareness. A multipronged approach is necessary which can target areas of high prevalence identified by registries with a combination of behavior change communication exercises and routine early screening with VIA. Sensitizing the people of the area, including menfolk, is necessary to increase uptake levels. Vaccination against types 16 and 18 can also be undertaken after taking into confidence all stakeholders, including the parents of adolescent girls. Preventing and treating cervical cancer and reducing the burden are possible by targeting resources to the areas with high prevalence.
Isobutylhydroxyamides from Sichuan Pepper and Their Protective Activity on PC12 Cells Damaged by Corticosterone.

The pericarp of Zanthoxylum bungeanum Maxim. , commonly known as Sichuan pepper, is a widely used spice to remove fishy odor and add palatable taste. A phytochemical investigation of the 95% ethanol extract of Sichuan pepper resulted in the isolation of 21 isobutylhydroxyamides, including 8 new ones named ZP-amides G-N, among which the chiral resolution of racemic ZP-amide A and ZP-amide B was successfully accomplished. The protective activity on corticosterone-treated PC12 cells of the isolated isobutylhydroxyamides was also evaluated. The new compounds 3-5 and the known compounds 1, 1a, 2, 2a, 11, and 15 improved the survival rate of PC12 cells. The bioactivity studies disclosed the potential of Sichuan pepper to be developed as new neuroprotective functional food.