Miracle-dz/UniFAR-FTUs huggingface dataset:
Birthweight, body size, and growth during childhood and risks of rheumatoid arthritis: a large Danish cohort study

Objectives Adult obesity may be positively associated with risks of rheumatoid arthritis (RA), but associations with early life body size are unknown. We examined whether birthweight, childhood body mass index (BMI), height, and changes in BMI and height were associated with risks of adult RA. Method A cohort of 346 602 children (171 127 girls) from the Copenhagen School Health Records Register, born in 1930–1996, with measured weights and heights from 7 to 13 years of age, were included. Information on RA, including serological status, came from national registers from 1977 to 2017. Cox regressions were performed. Results During a median of 35.1 years of observation time per person, 4991 individuals (3565 women) were registered with RA. Among girls, per BMI z-score, risks of RA and seropositive RA increased by 4–9% and 6–10%, respectively. Girls with overweight had higher risks of RA than girls without overweight. Girls who became overweight by 13 years of age had increased risks of RA compared to girls without overweight at 7 or 13 years (hazard ratio = 1.40, 95% confidence interval 1.19–1.66). For boys, associations between BMI and RA (including seropositive RA) were not statistically significant. Height was not associated with RA (any type) in girls. Taller boys had higher risks of RA, especially seropositive RA. Birthweight was not associated with RA. Conclusions Among women, childhood adiposity was associated with increased risks of RA. Among men, childhood height was positively associated with risks of RA. These findings support the hypothesis that early life factors may be important in the aetiology of RA.
Utilizing Age of Menarche to Optimize Pediatric Rhinoplasty

Background/Purpose: Pediatric septorhinoplasty has sparked controversial debate amongst craniofacial surgeons, particularly due to its potential growth disturbances of the face and nose. The purpose of this study is (1) to conduct a systematic literature review that explores unique considerations and limitations associated with performing rhinoplasty in the pediatric population; (2) to discuss objective indicators for determining craniofacial skeleton maturation; (3) to perform a case series to further understand whether the age of menarche serves as a good proxy for estimating the time of facial growth maturation, and by extension, whether a post-menarchal patient is a suitable candidate for rhinoplasty. Methods: Systematic literature review was performed in order to assess unique considerations and limitations of pediatric rhinoplasty. Retrospective chart review and anthropometric (9 linear, 3 angular, 6 indices) measurements were performed for ten pediatric female patients who underwent open septo-rhinoplasty. Follow-up times ranged from 66 to 103 weeks. Patients were separated into 2 cohorts according to age at the time of menarche. Cohort 1 consisted of patients who had undergone menses for longer than 2 years at the time of rhinoplasty, whereas Cohort 2 comprised of patients who either had menses within 2 years of rhinoplasty or did not have menses at the time of rhinoplasty. Data included demographic factors, procedural variables, revision surgeries, and complications. Measurements were conducted using VECTRA software (Canfield Scientific, Parsippany, NJ). Differences in measurements between the 2 postoperative timepoints were compared. Results: Literature review yielded 17 articles, which had conflicting opinions regarding pediatric rhinoplasty and ultimately, highlighting the need for a more objective tool for guiding the decision to perform rhinoplasty. Patients in Cohort 1 had minimal deviations in measurements over time, within the exception of an increase in nasal tip projection and a decrease in nasolabial angle and facial width. Patients in Cohort 2 had decreases in facial height, upper facial height, nasal tip angle, and nasofrontal angle. Nasolabial angle decreased for both cohorts. Of the ten patients, 1 in Cohort 2 underwent revision rhinoplasty. Conclusions: Our case series suggests that anthropometric measurements remain relatively more stable for patients who have undergone menses for more than 2 years, compared to those who have not. Although this study has limitations, further investigation is warranted in order to determine whether age of menarche may serve as a useful tool for craniofacial surgeons in guiding the decision to perform rhinoplasty.
The Effect of Explanations on Trust in an Assistance System for Public Transport Users and the Role of the Propensity to Trust

The present study aimed to investigate whether explanations increase trust in an assistance system. Moreover, we wanted to take the role of the individual propensity to trust in technology into account. We conducted an empirical study in a virtual reality environment where 40 participants interacted with a specific assistance system for public transport users. The study was in a 2x2 mixed design with the within-subject factor assistance system feature (trip planner and connection request) and the between-subject factor explanation (with or without). We measured trust as explicit trust via a questionnaire and as implicit trust via an operationalization of the participants’ behavior. The results showed that trust propensity predicted explicit trust, and explanations increased explicit trust significantly. This was not the case for implicit trust, though, suggesting that explicit and implicit trust do not necessarily coincide. In conclusion, our results complement the literature on explainable artificial intelligence and trust in automation and provide topics for future research regarding the effect of explanations on trust in assistance systems or other technologies.
A Distributed Virtual Reality Study Under COVID-19 Conditions – Comparing Continuous and Non-Continuous Locomotion Techniques in Mobile VR

The ongoing COVID-19 pandemic complicates empirical virtual reality (VR) research and especially laboratory studies. As an alternative study design, we conducted a distributed VR study that took place in the participants’ homes, using mobile VR goggles and personal smartphones. We investigated the influence of two different locomotion techniques on presence, usability, and cybersickness. Subjects were asked to solve a navigation task once with the continuous “Look-Down-to-Move” technique and once with the non-continuous “Point-And-Teleport” technique. Surprisingly, the two locomotion techniques performed comparably well on all variables assessed. The study design showed to be understandable and conductible for the subjects. However, we found that (1) hardware limitations of the used smartphones and (2) confounding factors that are beyond the control of the experimenters could have distorted the results of the study. We propose using uniform hardware and imposing stricter rules for participation to achieve more controlled conditions. Our results hint that the impact of the continuity of locomotion on presence, usability, and cybersickness may be less severe in the context of mobile VR than in immersive high-end VR devices. If these findings are corroborated by subsequent studies, they could provide designers of mobile virtual environments (VEs) with more flexibility when developing a suitable locomotion technique for their application.
Female pupils’ attitudes to computing in early adolescence

Female students are under-represented in optional Computer Science qualifications in England’s schools. We know that educational and career choices are affected by students’ attitudes towards the subject and perceptions of their own ability, as well as societal factors. In the current study, a validated survey was adapted and administered to 960 pupils in 7th Grade (age 12-13; 788 female) and 356 pupils in 5th Grade (age 10-11; 171 female). The survey comprised five scales concerning attitudes towards computing: confidence, interest, feelings of belonging, perceptions of usefulness of the subject, and feelings of encouragement to take the subject. Higher scores represent more positive attitudes. We found a significant difference between female and male pupils, with females scoring lower across all scales of the survey in both year groups. Female pupils in mixed-sex high schools reported lower scores for feelings of belonging compared to those in single-sex schools (a statistically significant difference), but did not differ for any of the other scales. These results suggest that less positive attitudes towards computing are evident in female pupils early in their education, and may be associated with differences in their school environment. This is likely to affect their later engagement with computing and choice of optional Computer Science qualifications. Early interventions focusing on confidence, attitudes and perceptions are therefore of great importance in increasing the representation of female pupils in Computer Science.
Visualizing Muscle Sialic Acid Expression in the GNED207VTgGne-/- Cmah-/- Model of GNE Myopathy: A Comparison of Dietary and Gene Therapy Approaches.

BACKGROUND GNE myopathy (GNEM) is a rare, adult-onset, inclusion body myopathy that results from partial loss of function mutations in the GNE gene. GNE encodes UDP-GlcNAc epimerase/Mannose-6 kinase, a protein with two enzymatic activities that comprise the committed step in biosynthesis of sialic acid (SA), an essential glycan that appears on the terminal positions of many extracellular oligosaccharide chains. These GNE mutations can cause a reduction of SA in many tissues, although pathology is restricted to skeletal muscles through a poorly understood mechanism. OBJECTIVE Despite recent advances in the field, it remains unclear which therapeutic avenue is most promising for the restoration of SA level in skeletal muscle affected by GNEM. Our objective was to assess dietary and gene therapy strategies for GNEM in Cmah-deficient GNED207VTgGne-/- mice, a model that allows for the visualization of orally delivered N-glycolylneuraminic acid (Neu5Gc), one of the two predominant SA forms in muscle. METHODS Methods included in situ physiology studies of the tibialis anterior muscle, studies of ambulation and limb grip strength, and muscle staining using MAA, SNA, and anti-Neu5Gc antibody, along with qPCR, qRT-PCR, western blot, and HPLC studies to assess virally introduced DNA, GNE gene expression, GNE protein expression, and SA expression. RESULTS We found that a diet enriched in Neu5Gc-containing glycoproteins had no impact on Neu5Gc immunostaining in muscles of GNEM model mice. Delivery of a single high dose oral Neu5Gc therapy, however, did increase Neu5Gc immunostaining, though to levels below those found in wild type mice. Delivery of a single dose of GNE gene therapy using a recombinant Adeno Associated Virus (rAAV) vector with a liver-specific or a muscle-specific promoter both caused increased muscle Neu5Gc immunostaining that exceeded that seen with single dose monosaccharide therapy. CONCLUSIONS Our findings indicate that dietary loading of Neu5Gc-containing glycoproteins is not effective in increasing muscle Neu5Gc expression, while single dose oral Neu5Gc monosaccharide or GNE gene therapy are. Neu5Gc immunostaining, however, showed greater changes than did lectin staining or HPLC analysis. Taken together, these results suggest that Neu5Gc immunostaining may be more sensitive technique to follow SA expression than other more commonly used methods and that liver expression of GNE may contribute overall muscle SA content.
Development of a novel tau propagation mouse model endogenously expressing 3 and 4 repeat tau isoforms.

The phenomenon of "prion-like propagation" in which aggregates of abnormal amyloid-fibrilized protein propagate between neurons and spread pathology, is attracting attention as a new mechanism in neurodegenerative diseases. There is a strong correlation between the accumulation or spread of abnormal tau aggregates and the clinical symptoms of tauopathies. Microtubule-associated protein of tau contains a microtubule-binding domain which consists of 3-repeats or 4-repeats due to alternative mRNA splicing of transcripts for the Microtubule-associated protein of tau gene. Although a number of models for tau propagation have been reported, most utilize 4-repeat human tau transgenic mice or adult wild-type mice expressing only endogenous 4-repeat tau and these models have not been able to reproduce the pathology of Alzheimer's disease in which 3-repeat and 4-repeat tau accumulate simultaneously, or that of Pick's disease in which only 3-repeat tau is aggregated. These deficiencies may reflect differences between human and rodent tau isoforms in the brain. To overcome this problem, we used genome editing techniques to generate mice that express an equal ratio of endogenous 3-repeat and 4-repeat tau, even after they become adults. We injected these mice with sarkosyl-insoluble fractions derived from the brains of human tauopathy patients such as those afflicted with Alzheimer's disease (3- and 4-repeat tauopathy), corticobasal degeneration (4-repeat tauopathy) or Pick's disease (3-repeat tauopathy). At 8-9 months following intracerebral injection of mice, histopathological and biochemical analyses revealed that the abnormal accumulation of tau was seed-dependent, with 3- and 4-repeat tau in Alzheimer's disease-injected brains, 4-repeat tau only in corticobasal degeneration-injected brains, and 3-repeat tau only in Pick disease-injected brains, all of which contained isoforms related to those found in the injected seeds. The injected abnormal tau was seeded, and accumulated at the site of injection and at neural connections, predominantly within the same site. The abnormal tau newly accumulated was found to be endogenous in these mice and to have crossed the species barrier. Of particular importance, Pick's body-like inclusions were observed in Pick's disease-injected mice, and accumulations characteristic of Pick's disease were reproduced, suggesting that we have developed the first model that recapitulates the pathology of Pick's disease. These models are not only useful for elucidating the mechanism of propagation of tau pathology involving both 3- and 4-repeat-isoforms, but can also reproduce the pathology of tauopathies, which should lead to the discovery of new therapeutic agents.
A functional cerebral endothelium is necessary to protect against cognitive decline

A vascular insult occurring early in disease onset may initiate cognitive decline leading to dementia, while pharmacological and lifestyle interventions can prevent this progression. Mice with a selective, tamoxifen-inducible deletion of NF-κB essential modulator (Nemo) in brain endothelial cells were studied as a model of vascular cognitive impairment. Groups included NemoFl controls and three NemobeKO groups: One untreated, and two treated with simvastatin or exercise. Social preference and nesting were impaired in NemobeKO mice and were not countered by treatments. Cerebrovascular function was compromised in NemobeKO groups regardless of treatment, with decreased changes in sensory-evoked cerebral blood flow and total hemoglobin levels, and impaired endothelium-dependent vasodilation. NemobeKO mice had increased string vessel pathology, blood-brain barrier disruption, neuroinflammation, and reduced cortical somatostatin-containing interneurons. These alterations were reversed when endothelial function was recovered. Findings strongly suggest that damage to the cerebral endothelium can trigger pathologies associated with dementia and its functional integrity should be an effective target in future therapeutic efforts.
Shortening of time‐to‐peak left ventricular pressure rise (Td) in cardiac resynchronization therapy

We tested the hypothesis that shortening of time‐to‐peak left ventricular pressure rise (Td) reflect resynchronization in an animal model and that Td measured in patients will be helpful to identify long‐term volumetric responders [end‐systolic volume (ESV) decrease >15%] in cardiac resynchronization therapy (CRT).
Identification of Selenoprotein H Isoforms and Impact of Selenoprotein H Overexpression on Protein But Not mRNA Levels of 2 Other Selenoproteins in 293T Cells.

BACKGROUND Selenoprotein H (SELONOH), a member of the thioredoxin-like family proteins, is prioritized to degradation in selenium (Se) insufficiency. Recent studies implicate protective roles of SELENOH in oxidative stress, cellular senescence, and intestinal tumorigenesis. Although the nonselenoprotein H0YE28 is suggested as shortened SELENOH according to genomic and proteomic data repositories, this variant has not been verified biochemically. OBJECTIVES We sought to identify SELENOH isoforms and explore the impact of Se flux on selenoprotein expression in SELENOH-overexpressing cells. METHODS A vector expressing a FLAG (the DYKDDDDK sequence) tag on the N-terminal end of wild-type SELENOH was constructed and transiently transfected into 293T cells incubated with graded concentrations of Na2SeO3 (0-200 nM). Cells were subjected to immunoprecipitation, LC-MS/MS protein analysis, immunoblotting, qRT-PCR, and senescence assays. Data were analyzed by 1-way or 2-way ANOVA. RESULTS Results of anti-FLAG immunoblotting showed that FLAG-SELENOH transfection increased (3.7-fold; P < 0.05) protein levels of the long, but not the short, SELENOH variants in the presence of Na2SeO3 (100 nM). By contrast, SELENOH mRNA levels were increased by 53-fold upon FLAG-SELENOH transfection but were comparable with or without supplemental Se (100 nM). LC-MS/MS analyses of anti-FLAG immunoprecipitates designated both anti-FLAG bands as SELENOH and co-identified three 60S ribosomal and 9 other proteins. Overexpression of FLAG-SELENOH 1) reduced glutathione peroxidase 1 and thioredoxin reductase 1 expression at the protein rather than the mRNA level in the absence but not presence of supplemental Se (100 nM; P < 0.05); 2) increased mRNA levels of 3 heat shock proteins (HSP27, HSP70-1A, and HSP70-1B; P < 0.05); and 3) reduced senescence induced by H2O2 (20 μM, 4 hours; P < 0.05). CONCLUSIONS These cellular studies demonstrate a Se-independent, shortened SELENOH variant and suggest competition of overexpressed FLAG-SELENOH with 2 other selenoproteins for the expression at the protein but not the mRNA level in Se insufficiency.
Risk factors of musculoskeletal symptoms among mobile device users during work from home

Objectives. Coronavirus (COVID-19) is affecting people throughout the world. People are forced to conduct various activities at home using mobile devices (MDs) as a result of the outbreak. In this case, prolonged use of MDs is the major cause for work-related health problems. Methods. We used systematic cluster random sampling to sample a diverse group of Indians from India’s various states. Subjects filled out a questionnaire with questions about their demographics, MD usage and musculoskeletal symptoms (MSSs) faced. The relationship between MSSs and various factors was investigated using χ2 and binomial logistic regression analysis. Results. An online survey yielded 720 responses. More than half of employees registered MSSs in their upper body regions. Age, gender and MD usage were correlated with MSSs in various body regions. According to the binomial logistic regression findings, gender was significantly linked to MSSs in each body region. Conclusions. Results show that MDs can be used effectively in intermediate leisure activities if they are used in accordance with their basic needs.
Psychometric Evaluation of the Moral Injury Events Scale in Two Canadian Armed Forces Samples

Moral injury (MI) is defined as the profound psychological distress experienced in response to perpetrating, failing to prevent, or witnessing acts that transgress personal moral standards or values. Given the elevated risk of adverse mental health outcomes in response to exposure to morally injurious experiences in military members, it is critical to implement valid and reliable measures of MI in military populations. We evaluated the reliability, convergent, and discriminant validity, as well as the factor structure of the commonly used Moral Injury Events Scale (MIES) across two separate active duty and released Canadian Armed Forces samples. In Study 1, convergent and discriminant validity were demonstrated through correlations between MIES scores and depression, anxiety, posttraumatic stress disorder, anger, adverse childhood experiences, and combat experiences. Across studies, internal consistency reliability was high. However, dimensionality of the MIES remained unclear, and model fit was poor across active and released Canadian Armed Forces samples. Practical and theoretical implications are discussed.
Metformin – a new approach

Metformin is a widely used biguanide drug recommended as a first-line antidiabetic for type 2 diabetes. Currently, metformin is used not only in the treatment of diabetes but also in other diseases. Some studies have shown that metformin causes weight loss in insulin-sensitive and insulin-resistant overweight and obese patients. Metformin is an effective and safe option for women with gestational diabetes and type 2 diabetes in pregnancy, and it may also increase the ovulation rate in patients with polycystic ovary syndrome (PCOS). Longer survival times have been observed in cancer patients using metformin. Metformin has been shown to significantly correlate with lower mortality in obese or type 2 diabetic women hospitalized for COVID-19. It also has a protective effect on the development and progression of many types of cancer. The mechanisms of action of metformin are complex and still not fully understood. Metformin has been shown to act through both AMP-activated protein kinase (AMPK)-dependent mechanisms and AMPK-independent mechanisms. This paper presents the benefits of using metformin in the treatment of various diseases.
Contraceptive and Infertility Target DataBase: a contraceptive drug development tool for targeting and analysis of human reproductive specific tissues

Abstract The long and challenging drug development process begins with discovery biology for the selection of an appropriate target for a specific indication. Target is a broad term that can be applied to a range of biological entities such as proteins, genes, and ribonucleic acids (RNAs). Although there are numerous databases available for mining biological entities, publicly available searchable, downloadable databases to aid in target selection for a specific disease or indication (e.g., developing contraceptives and infertility treatments) are limited. We report the development of the Contraceptive and Infertility Target DataBase (https://www.citdbase.org), which provides investigators an interface to mine existing transcriptomic and proteomic resources to identify high-quality contraceptive/infertility targets. The development of similar databases is applicable to the identification of targets for other diseases and conditions. Summary sentence Contraceptive and Infertility Target DataBase is a searchable and downloadable database open to the public for the identification of contraceptive/infertility transcriptomic and proteomic targets. Graphical Abstract