Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucocorticoid dose-dependent risk of type 2 diabetes in six immune-mediated inflammatory diseases: a population-based cohort analysis

Introduction In immune-mediated inflammatory diseases, there is a lack of -estimates of glucocorticoid dose–response diabetes risk that consider changes in prescribed dose over time and disease activity. Research design and methods Population-based longitudinal analysis of electronic health records from the UK Clinical Practice Research Datalink, linked to hospital admissions and the mortality registry (1998–2017). We included 100 722 adult patients without diabetes history, diagnosed with giant cell arteritis or polymyalgia rheumatica (n=32 593), inflammatory bowel disease (n=29 272), rheumatoid arthritis (n=28 365), vasculitis (n=6082), or systemic lupus erythematosus (n=4410). We estimated risks and HRs of type 2 diabetes associated with time-variant daily and total cumulative prednisolone-equivalent glucocorticoid dose using Cox regression methods. Results Average patient age was 58.6 years, 65 469 (65.0%) were women and 8858 (22.6%) had a body mass index (BMI) ≥30 kg/m2. Overall, 8137 (8.1%) people developed type 2 diabetes after a median follow-up of 4.9 years. At 1 year, the cumulative risk of diabetes increased from 0.9% during periods of non-use to 5.0% when the daily prednisolone-equivalent dose was ≥25.0 mg. We found strong dose-dependent associations for all immune-mediated diseases, BMI levels and underlying disease duration, even after controlling for periods of active systemic inflammation. Adjusted HR for a <5.0 mg daily dose versus non-use was 1.90, 95% CI 1.44 to 2.50; range 1.70 for rheumatoid arthritis to 2.93 for inflammatory bowel disease. Conclusions We report dose-dependent risks of type 2 diabetes associated with glucocorticoid use for six common immune-mediated inflammatory diseases. These results underline the need for regular diabetic risk assessment and testing during glucocorticoid therapy in these patients.
The temporal ligaments and their bearing on cranial kinesis in lizards

In the lateral temporal opening of the lacertilian skull there are three main types of ligaments: quadratojugal, jugomandibular, and quadratopostfrontal. The quadratojugal and ventral jugomandibular ligaments transmit the retraction force from the lower jaw to the rhinal unit of the maxillary segment. The dorsal jugomandibular ligament causes the coupled kinesis, that results in the protraction of the whole maxillary segment (in the amphikinetic skull with simple streptostyly) or in the protraction of the quadrate-mandibular complex (in the hyperstreptostylic skull), when opening the mouth.
Three‐dimensional printing facilitates surgical planning for resection of an atypical cardiac myxoma

Cardiac myxomas are common and account for 50% of primary intracardiac tumors. Atypical locations of cardiac myxoma increase the risk of intraoperative iatrogenic injuries. Herein, we report a case of using three‐dimensional printing (3D) to facilitate the removal of an atypical cardiac myxoma in a 63‐year‐old woman.
Linear Functions and Slope: How Do Students Understand These Concepts and How Does Reasoning Support Their Understanding?

Abstract The aim of this study was to investigate eighth grade students’ conceptual understanding and types of reasoning about linear functions and slope. This is a mixed method study. Quantitative data were collected with algebra test, and qualitative data were collected using clinical interviews. The participants for the quantitative part of this study included 103 students, and the qualitative part included 10 students selected from these 103 students who were high and middle achievers. Quantitative data were assessed based on the answer key, and their frequency scores were calculated and interpreted, too. Qualitative data were analyzed using the thematic analysis. The majority of the students counted on superficial knowledge of linear functions and slope, they mainly stuck to the slope formula and line equation, and they did not possess correct reasoning types. They also need to improve their use and interpretation of multiple representations. Key words: conceptual understanding; mathematics education; middle school students. --- Sažetak Cilj ovog istraživanja jest ispitati konceptualno razumijevanje ucenika osmog razreda, nacine razmisljanja o linearnim funkcijama i nagibu pravca. U istraživanju se koristila mjesovita metoda. Kvantitativni podatci prikupljali su se s pomocu testa iz algebre, a kvalitativni podatci prikupljali su se s pomocu klinickih intervjua. U kvantitativnom dijelu istraživanja sudjelovala su 103 ucenika, a u kvalitativnom dijelu 10 ucenika koji su bili odabrani između ta 103 ucenika, a imali su visoku i srednju razinu postignuca. Kvantitativni podatci bili su procijenjeni na temelju liste tocnih odgovora, a također su izracunate i interpretirane frekvencije za te odgovore. Vecina ucenika racunala je na povrsno znanje o linearnim funkcijama i nagibu pravca te su se uglavnom pridržavali formula za koeficijent smjera pravca i jednadžbe pravca, a nisu ovladali ispravnim vrstama razmisljanja. Također je bilo potrebno popraviti nacin na koji se koriste raznovrsnim prikazima i interpretiraju ih. Kljucne rijeci: konceptualno razumijevanje; nastava matematike; ucenici osnovne skole.
Role of Mitochondrial Glycerol-3-Phosphate Dehydrogenase in Metabolic Adaptations of Prostate Cancer

Prostate cancer is one of the most prominent cancers diagnosed in males. Contrasting with other cancer types, glucose utilization is not increased in prostate carcinoma cells as they employ different metabolic adaptations involving mitochondria as a source of energy and intermediates required for rapid cell growth. In this regard, prostate cancer cells were associated with higher activity of mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH), the key rate limiting component of the glycerophosphate shuttle, which connects mitochondrial and cytosolic processes and plays significant role in cellular bioenergetics. Our research focused on the role of mGPDH biogenesis and regulation in prostate cancer compared to healthy cells. We show that the 42 amino acid presequence is cleaved from N-terminus during mGPDH biogenesis. Only the processed form is part of the mGPDH dimer that is the prominent functional enzyme entity. We demonstrate that mGPDH overexpression enhances the wound healing ability in prostate cancer cells. As mGPDH is at the crossroad of glycolysis, lipogenesis and oxidative metabolism, regulation of its activity by intramitochondrial processing might represent rapid means of cellular metabolic adaptations.
Protection to tomato wilt disease conferred by the non-pathogen Fusarium oxysporum Fo47 is more effective than that conferred by avirulent strains.

Although the vascular pathogen Fusarium oxysporum (Fo) is notorious for being the causal agent of Fusarium wilt disease, the vast majority of Fo strains are harmless soil and root colonisers. The latter Fo's are often endophytes colonising roots intracellularly without negatively affecting plant fitness. Actually, most of them, like Fo47, are beneficial providing biocontrol to various root pathogens. Interestingly, also pathogenic Fo inoculated on a resistant host (i.e. avirulent Fol) can reduce susceptibility to virulent Fo strains via a mechanism called "cross protection". It has been hypothesised that cross protection is based on activation of a resistance protein of the host upon recognition of a cognate Avirulence (Avr) protein of the pathogen. Currently, it is unknown whether the biocontrol activity of Fo endophytes utilizes similar mechanisms as cross protection conferred by avirulent pathogens, and whether both provide a quantitative similar level of protection. Here, we show that in tomato biocontrol activity of the Fo47 endophyte to the pathogen Fo f.sp. lycopersici (Fol) is more effective than cross protection induced by avirulent Fol strains activating either I, I-2 or both resistance proteins upon recognition of respectively Avr1 or the Avr2/Six5 pair. These findings imply that cross protection and biocontrol utilize different mechanisms to reduce susceptibility of the host to subsequent infections.
Assessment of the Fairness of Privacy Policies of Mobile Health Apps: Scale Development and Evaluation in Cancer Apps

Background Cancer patients are increasingly using mobile health (mHealth) apps to take control of their health. Many studies have explored their efficiency, content, usability, and adherence; however, these apps have created a new set of privacy challenges, as they store personal and sensitive data. Objective The purpose of this study was to refine and evaluate a scale based on the General Data Protection Regulation and assess the fairness of privacy policies of mHealth apps. Methods Based on the experience gained from our previous work, we redefined some of the items and scores of our privacy scale. Using the new version of our scale, we conducted a case study in which we analyzed the privacy policies of cancer Android apps. A systematic search of cancer mobile apps was performed in the Spanish version of the Google Play website. Results The redefinition of certain items reduced discrepancies between reviewers. Thus, use of the scale was made easier, not only for the reviewers but also for any other potential users of our scale. Assessment of the privacy policies revealed that 29% (9/31) of the apps included in the study did not have a privacy policy, 32% (10/31) had a score over 50 out of a maximum of 100 points, and 39% (12/31) scored fewer than 50 points. Conclusions In this paper, we present a scale for the assessment of mHealth apps that is an improved version of our previous scale with adjusted scores. The results showed a lack of fairness in the mHealth app privacy policies that we examined, and the scale provides developers with a tool to evaluate their privacy policies.
Efeitos de indicadores e dias de coleta na digestibilidade dos nutrientes e nas estimativas do valor energético de alimentos para vacas alimentadas com diferentes fontes de proteína

Twelve lactating dairy cows (Holstein and crossbred Holstein x Zebu) were blocked by days in milk and randomly assigned to three replicate 4 x 4 Latin squares to compare two schedules of total fecal collection (two versus six days) and the reliability of two internal markers [indigestible neutral detergent fiber (INDF) or indigestible acid detergent fiber (IADF)] to estimate fecal DM excretion (FDME), apparent total tract digestibility of nutrients, and the total digestible nutrients (TDN) content of the diets. The summative equations from the NRC (2001) model were also used to estimate the energy value of feeds. A diet containing 60% of corn silage (DM basis) plus one of the following proteins sources was fed to animals: soybean meal (SM), 38% CP cottonseed meal (CM38), 28% CP cottonseed meal (CM28), or SM plus 5% of urea/ammonium sulfate in the concentrate DM (SMU). Fecal collection schedule and markers had no effect on the estimates of FDME, nutrient digestibility, and dietary TDN. The summative equations from the NRC (2001) overestimated the intake of digestible CP and NDF and underestimated that of digestible NFC, EE, and TDN. It was concluded that INDF was the most precise marker and two days of total fecal collection was enough to estimate FDME, nutrient digestibility and dietary TDN. The NRC (2001) summative equations did not reliably predict the energy value of tropical feeds.
Taxonomic revision of the Taractrocera ilia (Waterhouse) complex (Lepidoptera : Hesperiidae) from north-western Australia and mainland New Guinea based on morphological and molecular data

Abstract. The taxonomy of the Taractrocera ilia complex is revised based on evidence from multiple sources, including phenotypic characters (wing colour pattern elements, morphology of adult and immature stages), ecology and molecular data. Three species are recognised in the complex: T. psammopetra Braby, sp. nov. is restricted to north-western Australia where it has a disjunct distribution (Kimberley and the central Arnhem Land plateau); T. ilia (Waterhouse, 1932) sensu stricto is endemic to the central Arnhem Land plateau where it is narrowly sympatric with T. psammopetra; while T. beta Evans, 1934, stat. nov. is allopatric and endemic to mainland New Guinea. Each species is illustrated and diagnosed based on comparative morphology of the adult stage, including androconia and male and female genitalia, and information on type material, biology, distribution and habitat is summarised and discussed. A phylogenetic hypothesis of the Australian species of Taractrocera based on combined analysis of molecular data (2.6 kb: mitochondrial COI and nuclear CAD, MDH, wingless) revealed that T. psammopetra is monophyletic and sister to T. ilia, with an overall mean divergence of 3.4% between the two species; the genus Taractrocera, however, emerged as polyphyletic. For T. psammopetra and T. ilia, the life history, including details of larval food plant specialisation and morphology of the immature stages, is described for the first time. Larvae of T. psammopetra and T. ilia specialise on ‘resurrection’ grasses, Micraira spp. (Poaceae), which typically grow as moss-like, mat-forming pioneer plants on shallow rock surfaces comprising open sandstone pavements or on rock ledges and under rock overhangs of sandstone cliffs. These food plants, together with the butterflies that they support, are a characteristic element of the sandstone plateaux of the Kimberley and central Arnhem Land, and they exemplify patterns of diversification, endemism and adaptation to these unique environments within the Australian monsoon tropics. Facultative larval diapause is recorded for both T. psammopetra and T. ilia in which larvae (all instars, but particularly the final instar) may suspend feeding for up to six months during the dry season when the food plants typically dehydrate. It is hypothesised that larval diapause may be the most flexible strategy to ameliorate seasonal adversity of the dry season and the onset, duration and inter-annual cycle of monsoon rainfall during the wet season, which is highly variable and unpredictable, given that Micraira can revive rapidly from a desiccated state after rainfall.
Comparison of total and activity energy expenditure estimates from physical activity questionnaires and doubly labelled water: a systematic review and meta-analysis

Abstract Physical activity questionnaires (PAQ) could be suitable tools in free-living people for measures of physical activity, total and activity energy expenditure (TEE and AEE). This meta-analysis was performed to determine valid PAQ for estimating TEE and AEE using doubly labelled water (DLW). We identified data from relevant studies by searching Google Scholar, PubMed and Scopus databases. This revealed thirty-eight studies that had validated PAQ with DLW and reported the mean differences between PAQ and DLW measures of TEE (TEEDLW − TEEPAQ) and AEE (AEEDLW − AEEPAQ). We assessed seventy-eight PAQ consisting of fifty-nine PAQ that assessed TEE and thirty-five PAQ that examined AEE. There was no significant difference between TEEPAQ and TEEDLW with a weighted mean difference of –243·3 and a range of –841·4 to 354·6 kJ/d, and a significant weighted mean difference of AEEDLW – AEE PAQ 414·6 and a range of 78·7–750·5. To determine whether any PAQ was a valid tool for estimating TEE and AEE, we carried out a subgroup analysis by type of PAQ. Only Active-Q, administered in two seasons, and 3-d PA diaries were correlated with TEE by DLW at the population level; however, these two PAQ did not demonstrate an acceptable limit of agreement at individual level. For AEE, no PAQ was correlated with DLW either at the population or at the individual levels. Active-Q and 3-d PA diaries were identified as the only valid PAQ for TEE estimation. Further well-designed studies are needed to verify this result and identify additional valid PAQ. Abstract
Incidence and prevalence of multiple sclerosis in Hungary based on record linkage of nationwide multiple healthcare administrative data

Objectives As there were only regional studies in Hungary about the prevalence of multiple sclerosis (MS), we aimed to estimate its epidemiological features using data of Hungary’s single-payer health insurance system. Methods Pseudonymized database of claims reported by hospitals and outpatient services between 2004–2016 was analyzed and linked with an independent database of outpatient pharmacy refills between 2010–2016. We established an administrative case definition of MS and validated it on medical records of 309 consecutive patients. A subject was defined as MS-patient if received MS diagnosis (International Classification of Diseases, 10th edition, code G35) on three or more occasions at least in 2 calendar years and at least once documented by a neurologist. Patients were counted as incident cases in the year of the first submitted claim for MS. We allowed a 6-year-long run-in period, so only data between 2010–2015 are discussed. Results Sensitivity of the administrative case definition turned out to be 99%, while specificity was >99%. Crude prevalence of MS has increased from 109.3/100,000 in 2010 to 130.8/100,000 in 2015 (p-value = 0.000003). Crude incidence declined from 7.1/100,000 (2010) to 5.4/100,000 (2015) (p-value = 0.018). Direct standardization − based on European standard population and results of nationwide Hungarian census of 2011 − revealed that age standardized prevalence was 105.2/100,000 (2010), which has grown to 127.2/100,000 (2015) (p-value = 0.000001). Age standardized incidence rate declined from 6.7/100,000 (2010) to 5.1/100,000 (2015) (p-value = 0.016). The ratio of MS-patients receiving ≥1 prescription for disease modifying treatment increased from 0.19 (2010) to 0.29 (2015) (p-value = 0.0051). The female/male ratio of prevalent cases remained 2.6. Discussion The prevalence of MS in Hungary is higher than previously reported, the incidence rate is moderate. The prevalence is rising, the incidence rate shows decline. The proportion of patients receiving disease modifying treatment grows but was still around 30% in 2015.
Premarital relationships and condom use among young people in Suva, Fiji.

Background:Young people in Fiji experience high rates of sexually transmissible infections and early pregnancy. Despite being identified as a key priority group in national strategies, little is known about use of condoms among young people in premarital relationships. This study aimed to enhance understandings of premarital sex and condom use practices among young people in Fiji. Methods: Focus group discussions with 33 young women and men aged 18-29 years and 17 interviews with young women aged 18-26 years in an urban setting in Fiji were conducted. Inductive thematic analysis examined condom use practices. Results: Participants described a range of contextual influences inhibiting or enabling condom use. Factors inhibiting condom use included sociocultural expectations regarding premarital abstinence; young people's engagement in hidden sexual relationships; limited intergenerational dialogue about sexual health issues; judgmental attitude of staff at condom access points; male dominance of condom use preferences; and belief condoms disrupt intimacy, reduce sexual pleasure and infer a lack of trust. Factors that enhanced condom use included accessing condoms through discreet methods; adult beliefs that supported safe sex practices; and refusing to have sex without a condom. Conclusion: Findings broaden understandings of young people's condom use practices in Suva, Fiji. The findings illustrate the need for culturally appropriate youth-centred sexual and reproductive health (SRH) programs and services. Specific strategies that might enhance young people's condom use include community- and youth-led responses; peer condom distribution; provision of condom dispensers in community settings; scaling up of youth-friendly SRH services; and the delivery of comprehensive sexuality and relationships education.
Maize Thymidine Kinase Activity Is Present throughout Plant Development and Its Heterologous Expression Confers Tolerance to an Organellar DNA-Damaging Agent

Thymidine kinase 1 (TK1) phosphorylates thymidine nucleosides to generate thymidine monophosphate. This reaction belongs to the pyrimidine salvage route that is phylogenetically conserved. In the model plant Arabidopsis thaliana, TK activity contributes to maintain nuclear and organellar genome integrity by providing deoxythymidine-triphosphate (dTTP) for DNA synthesis. Arabidopsis has two TK1 genes (TK1a and TK1b) and double mutants show an albino phenotype and develop poorly. In contrast, maize (Zea mays L.) has a single TK1 (ZmTK1) gene and mutant plants are albino and display reduced genome copy number in chloroplasts. We studied the role of ZmTK1 during development and genotoxic stress response by assessing its activity at different developmental stages and by complementing Arabidopsis tk1 mutants. We found that ZmTK1 transcripts and activity are present during germination and throughout maize development. We show that ZmTK1 translocation to chloroplasts depends on a 72-amino-acid N-signal and its plastid localization is consistent with its ability to complement Arabidopsis tk1b mutants which are hypersensitive to ciprofloxacin (CIP), a genotoxic agent to organellar DNA. Also, ZmTK1 partly complemented the Arabidopsis double mutant plants during development. Our results contribute to the understanding of TK1 function in monocot species as an organellar enzyme for genome replication and repair.
A CRAF/glutathione-S-transferase P1 complex sustains autocrine growth of cancers with KRAS and BRAF mutations

Significance A strategy to overcome therapeutic obstacles of mKRAS and mBRAF cancers is devised based on the finding, here, that the RAF/MEK/ERK cascade is by-passed by an autocrine signal loop established by interaction of CRAF with GSTP1. The interaction evokes stabilization of CRAF from proteosomal degradation and facilitation of RAF-dimer formation. Thus, blocking CRAF/GSTP1 interactions should generate additive antiproliferative effects. The Ras/RAF/MEK/ERK pathway is an essential signaling cascade for various refractory cancers, such as those with mutant KRAS (mKRAS) and BRAF (mBRAF). However, there are unsolved ambiguities underlying mechanisms for this growth signaling thereby creating therapeutic complications. This study shows that a vital component of the pathway CRAF is directly impacted by an end product of the cascade, glutathione transferases (GST) P1 (GSTP1), driving a previously unrecognized autocrine cycle that sustains proliferation of mKRAS and mBRAF cancer cells, independent of oncogenic stimuli. The CRAF interaction with GSTP1 occurs at its N-terminal regulatory domain, CR1 motif, resulting in its stabilization, enhanced dimerization, and augmented catalytic activity. Consistent with the autocrine cycle scheme, silencing GSTP1 brought about significant suppression of proliferation of mKRAS and mBRAF cells in vitro and suppressed tumorigenesis of the xenografted mKRAS tumor in vivo. GSTP1 knockout mice showed significantly impaired carcinogenesis of mKRAS colon cancer. Consequently, hindering the autocrine loop by targeting CRAF/GSTP1 interactions should provide innovative therapeutic modalities for these cancers.