Miracle-dz/UniFAR-FTUs huggingface dataset:
Adrenal crisis: prevention and management in adult patients

Adrenal crisis is an acute life-threatening emergency contributing to the excess mortality that is reported in patients with adrenal insufficiency. The incidence of adrenal crisis is estimated to be 8 per 100 patient years in patients with adrenal insufficiency. Patients with adrenal crisis present systemically unwell with nonspecific signs and symptoms often leading to misdiagnosis and delayed treatment. An adrenal crisis may be the first presentation of adrenal insufficiency or can occur in patients who have been established on glucocorticoid replacement therapy. Infections are the major precipitating factor, but other causes include physical stress such as a surgical procedure or trauma, forgetting or discontinuing glucocorticoid therapy, pronounced physical activity, and psychological stress. The emergency treatment involves prompt recognition and administration of parenteral hydrocortisone, rehydration and management of electrolyte abnormalities. Prevention is centred around patient education. All patients should be educated on stress dosing and parenteral glucocorticoid administration. They should carry a steroid dependency alert card and wear a medical alert bracelet or similar identification. Despite many improvements in the management of patients with adrenal insufficiency, adrenal crisis continues to occur and represents a major source of morbidity, mortality and distress for patients. Improved patient and clinician education and measures to facilitate parenteral hydrocortisone self-administration in impending crisis are central to the management of this life-threatening event.
Water-Soluble Extract from Actinidia arguta (Siebold & Zucc.) Planch. ex Miq. and Perilla frutescens (L.) Britton, ACTPER, Ameliorates a Dry Skin-Induced Itch in a Mice Model and Promotes Filaggrin Expression by Activating the AhR Signaling in HaCaT Cells

With a complex etiology involving multiple factors, the condition known as itch is a primary symptom of many skin diseases. Current treatment methods are ineffective for addressing itches caused by dry skin, for example. We developed a botanical extract, ACTPER, made from a mixture of Actinidia arguta and Perilla frutescens, which have traditionally been used to treat itch. The quality of ACTPER as a research agent was controlled in our experiment by cell-based bioassays, as well as by high-performance liquid chromatography (HPLC), using two chemical markers. In the acetone-induced dry skin mice model, the oral administration of ACTPER alleviated dry skin-related skin properties and itching behavior. The RNA and protein expression of the filament aggregating protein (filaggrin) gene, a key factor involved in the regulation of skin barrier function, was significantly increased, as measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay. To understand the underlying mechanism(s) at the molecular level, HaCaT cells, a human keratinocyte-derived cell line, were treated with various concentrations of ACTPER. We found that the protein expression of filaggrin was indeed upregulated by ACTPER in a dose dependent manner. Data from experiments involving the reporter plasmid containing the xenobiotic response element (XRE), and the chemical antagonist for the aryl hydrocarbon receptor (AhR), indicated that the ACTPER-mediated upregulation of filaggrin was controlled through the activation of the AhR signaling pathway. The molecular docking simulation study predicted that ACTPER might contain chemical compounds that bind directly to AhR. Taken together, our results suggest that ACTPER may provide the platform, based upon which a variety of safe and effective therapeutic agents can be developed to treat itch.
Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning.

Haplo-identical transplant with posttransplant cyclophosphamide (haplo) and umbilical cord blood transplant supported by third-party CD34 cells (haplo-cord) are competing approaches to alternative donor transplant. We compared, in adults younger than age 60 years, the outcomes of 170 haplo at 1 institution with that of 137 haplo-cord at 2 other institutions. All received reduced intensity conditioning with fludarabine and melphalan ± total body irradiation. GVHD prophylaxis for haplo consisted of cyclophosphamide, tacrolimus, and mycophenolate, whereas haplo-cord received antithymocyte globulin, tacrolimus, and mycophenolate. Haplo transplant used mostly bone marrow, and peripheral blood stem cells were used in haplo-cord transplants. Haplo-cord were older and had more advanced disease. Haplo-cord hastened median time to neutrophil (11 vs 18 days, P = .001) and platelet recovery (22 vs 25 days, P = .03). At 4 years, overall survival (OS) was 50% for haplo-cord vs 49% for haplo. Progression-free survival (PFS) was 40% for haplo-cord vs 45% for haplo. In multivariate analysis, the disease risk index was significant for OS (hazard ratio, 1.8; 95% confidence interval, 1.48-2.17; P = .00) and PFS. Total body irradiation was associated with decreased recurrence and improved PFS, age >40 with increased nonrelapse mortality. The type of transplant had no effect on OS, PFS, relapse, or nonrelapse mortality. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) by day 100 was 16% after haplo-cord vs 33% after haplo (P < .0001), but grade 3-4 GVHD was similar. Chronic GVHD at 1 year was 4% after haplo-cord vs 16% after haplo (P < .0001). Haplo or haplo-cord results in similar and encouraging outcomes. Haplo-cord is associated with more rapid neutrophil and platelet recovery and lower acute and chronic GVHD. Institutional review board authorization for this retrospective study was obtained at each institution. Some patients participated in trials registered at www.clinicaltrials. gov as #NCT01810588 and NCT01050946.
Age-Related Differences in the International Affective Picture System (IAPS) Valence and Arousal Ratings among Japanese Individuals

ABSTRACT Study Context: The question of whether relationships between valence and arousal might differ among older and younger adults has not yet been totally clarified. Previous studies focused on only age-related mean-differences, but in the current study mean differences and variance in emotional ratings for the International Affective Picture Systems (IAPS) were both examined in Japanese older and younger adults. Methods: Participants were 31 older adults (69 ± 5.17 years) and 31 younger adults (19 ± 0.77 years). Each picture was projected on the screen for about 5 s in random order and participants subsequently rated its valence from “unhappy” to “happy” and its arousal from “calm” to “exciting,” using 9-point scales. Results: Pearson’s correlation analysis showed that positive and negative valence tended to be negatively correlated with arousal in both age groups. The 95% Confidence Intervals for positive arousal in older adults included those of younger adults. Arousal ratings for negative pictures were higher than those for neutral pictures, and those for neutral pictures were higher than those for positive pictures in older adults. There were no significant differences between arousal ratings for neutral pictures and positive pictures in younger adults. Conclusion: Older adults tended to rate the pictures as more arousing, with higher arousal ratings for negative pictures than for positive pictures, and the variance of positive arousal in older adults was the highest variance for all conditions. The results of this study suggest that older adults may be sensitive to harmful negative experiences in order to make them less aversive.
Estimation of Total Usual Dietary Intakes of Pregnant Women in the United States

Key Points Question How do the usual dietary intakes of pregnant US women compare with the National Academies of Science, Engineering, and Medicine Dietary Reference Intakes for nutritional adequacy and excess? Findings This cross-sectional analysis of 1003 pregnant US women found that many pregnant women did not consume enough key nutrients during pregnancy, specifically, vitamins A, C, D, E, K, and B6, as well as folate, choline, and minerals including iron, potassium, calcium, magnesium, and zinc. Almost all pregnant women consumed excessive sodium, and many were at risk of excessive consumption of folic acid and iron. Meaning Improved dietary guidance appears to be warranted to help pregnant women to meet but not exceed dietary recommendations.
Factors influencing young women's contraceptive choices.

BACKGROUND AND OBJECTIVES Australia's high rate of unintended pregnancy could be lowered by increasing long-acting reversible contraception (LARC) use. Influences on Australian women's choice of less effective methods are not well understood. This qualitative study explored factors that influence young women's contraceptive choices. METHOD Semi-structured interviews were conducted with women aged 18-24 years until data saturation. Interviews were audio-recorded, transcribed and thematically analysed. RESULTS Contraceptive choice was influenced by factors including contraceptive knowledge, side effects, cultural norms, fear, control and social context. Women often initiated contraceptive use for non contraceptive purposes such as management of acne or period pain, and failed to reconsider new methods when needing contraception, revealing one possible explanation for low LARC use. DISCUSSION Findings indicate that women's contraceptive choices need regular review. Information about relative efficacy of contraceptive methods is necessary should women's reasons for using contraception include birth control in addition to non-contraceptive benefits.
Standardizing T-Cell Biomarkers in Type 1 Diabetes: Challenges and Recent Advances

Type 1 diabetes (T1D) results from the progressive destruction of pancreatic β-cells in a process mediated primarily by T lymphocytes. The T1D research community has made dramatic progress in understanding the genetic basis of the disease as well as in the development of standardized autoantibody assays that inform both disease risk and progression. Despite these advances, there remains a paucity of robust and accepted biomarkers that can effectively inform on the activity of T cells during the natural history of the disease or in response to treatment. In this article, we discuss biomarker development and validation efforts for evaluation of T-cell responses in patients with and at risk for T1D as well as emerging technologies. It is expected that with systematic planning and execution of a well-conceived biomarker development pipeline, T-cell–related biomarkers would rapidly accelerate disease progression monitoring efforts and the evaluation of intervention therapies in T1D.
First Estimation of the Spontaneous Mutation Rate in Diatoms

Abstract Mutations are the origin of genetic diversity, and the mutation rate is a fundamental parameter to understand all aspects of molecular evolution. The combination of mutation–accumulation experiments and high-throughput sequencing enabled the estimation of mutation rates in most model organisms, but several major eukaryotic lineages remain unexplored. Here, we report the first estimation of the spontaneous mutation rate in a model unicellular eukaryote from the Stramenopile kingdom, the diatom Phaeodactylum tricornutum (strain RCC2967). We sequenced 36 mutation accumulation lines for an average of 181 generations per line and identified 156 de novo mutations. The base substitution mutation rate per site per generation is μbs = 4.77 × 10−10 and the insertion–deletion mutation rate is μid = 1.58 × 10−11. The mutation rate varies as a function of the nucleotide context and is biased toward an excess of mutations from GC to AT, consistent with previous observations in other species. Interestingly, the mutation rates between the genomes of organelles and the nucleus differ, with a significantly higher mutation rate in the mitochondria. This confirms previous claims based on indirect estimations of the mutation rate in mitochondria of photosynthetic eukaryotes that acquired their plastid through a secondary endosymbiosis. This novel estimate enables us to infer the effective population size of P. tricornutum to be Ne∼8.72 × 106.
Survival outcomes of diffuse large B-cell lymphoma by association with concurrent or antecedent follicular lymphoma and double hit status

Abstract Diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL) (tDLBCL) has been traditionally associated with an aggressive course, but more recent studies have shown longer survivals. The clinical significance of concurrent FL at the time of diagnosis of DLBCL (cDLBCL/FL) is less clear. We compared outcomes of tDLBCL, cDLBCL/FL, and de novo DLBCL (dDLBCL) and then evaluated the impact of double hit (DH) rearrangements (MYC with BCL2 and/or BCL6) in these subgroups’ outcomes. The progression free survival (PFS) and overall survival (OS) were not significantly different among the three groups (dDLBCL, tDLBCL, and cDLBCL/FL). The effect of DH on survival was then analyzed in two subgroups: (1) dDLBCL and (2) tDLBCL + cDLBCL/FL. PFS and OS were significantly shorter in lymphomas with DH in each of these two subgroups. We conclude that DH status drives outcomes in all DLBCLs, regardless of their transformation status.
Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction.

RATIONALE Myofibroblasts (MFs) have roles in tissue repair following damage associated with ischemia, aging, and inflammation, and also promote fibrosis and tissue stiffening, causing organ dysfunction. One source of MFs is mesenchymal stromal/stem cells (MSCs) that exist as resident fibroblasts in multiple tissues. We previously identified meflin, a glycosylphosphatidylinositol-anchored membrane protein, as a specific marker of MSCs and a regulator of their undifferentiated state. The roles of meflin in the development of heart disease, however, have not been investigated. OBJECTIVE We examined the expression of meflin in the heart and its involvement in cardiac repair after ischemia, fibrosis, and the development of heart failure (HF). METHODS AND RESULTS We found that meflin has an inhibitory role in MF differentiation of cultured MSCs. Meflin expression was downregulated by stimulation with transforming growth factor (TGF)-β, substrate stiffness, hypoxia, and aging. Histological analysis revealed that meflin-positive fibroblastic cells and their lineage cells proliferated in the hearts after acute myocardial infarction (MI) and pressure-overload HF mouse models. Analysis of meflin knockout (KO) mice revealed that meflin is essential for the increase in the number of cells that highly express type I collagen in the heart walls after MI induction. When subjected to pressure overload by transverse aortic constriction, meflin KO mice developed marked cardiac interstitial fibrosis with defective compensation mechanisms. Analysis with atomic force microscopy and hemodynamic catheterization revealed that meflin KO mice developed stiff failing hearts with diastolic dysfunction. Mechanistically, we found that meflin interacts with bone morphogenetic protein 7, an anti-fibrotic cytokine that counteracts the action of TGF-β and augments its intracellular signaling. CONCLUSIONS These data suggested that meflin is involved in cardiac tissue repair after injury and has an inhibitory role in MF differentiation of cardiac fibroblastic cells and the development of cardiac fibrosis.
TRPM7 channel inhibition exacerbates pulmonary arterial hypertension through MEK/ERK pathway

Cellular senescence is an important mechanism of autonomous tumor suppression, while its consequence such as the senescence-associated secretory phenotype (SASP) may drive tumorigenesis and age-related diseases. Therefore, controlling the cell fate optimally when encountering senescence stress is helpful for anti-cancer or anti-aging treatments. To identify genes essential for senescence establishment or maintenance, we carried out a CRISPR-based screen with a deliberately designed single-guide RNA (sgRNA) library. The library comprised of about 12,000 kinds of sgRNAs targeting 1378 senescence-associated genes selected by integrating the information of literature mining, protein-protein interaction network, and differential gene expression. We successfully detected a dozen gene deficiencies potentially causing senescence bypass, and their phenotypes were further validated with a high true positive rate. RNA-seq analysis showed distinct transcriptome patterns of these bypass cells. Interestingly, in the bypass cells, the expression of SASP genes was maintained or elevated with CHEK2, HAS1, or MDK deficiency; but neutralized with MTOR, CRISPLD2, or MORF4L1 deficiency. Pathways of some age-related neurodegenerative disorders were also downregulated with MTOR, CRISPLD2, or MORF4L1 deficiency. The results demonstrated that disturbing these genes could lead to distinct cell fates as a consequence of senescence bypass, suggesting that they may play essential roles in cellular senescence.
Predictors of muscularity-oriented disordered eating behaviors in U.S. young adults: A prospective cohort study.

OBJECTIVE To determine adolescent predictors of muscularity-oriented disordered eating behaviors in young men and women using a nationally representative longitudinal sample in the United States and to examine differences by sex. METHOD We used nationally representative longitudinal cohort data collected from baseline (11-18 years old, 1994-1995) and 7-year follow-up (18-24 years old, 2001-2002) of the National Longitudinal Study of Adolescent to Adult Health. We examined adolescent demographic, behavioral, and mental health predictors of young adult muscularity-oriented disordered eating behaviors defined as eating more or differently to gain weight or bulk up, supplements to gain weight or bulk up, or androgenic anabolic steroid use at 7-year follow-up. RESULTS Of the 14,891 included participants, 22% of males and 5% of females reported any muscularity-oriented disordered eating behavior at follow-up in young adulthood. Factors recorded at adolescence that were prospectively associated with higher odds of muscularity-oriented disordered eating in both sexes included black race, exercising to gain weight, self-perception of being underweight, and lower body mass index z-score. In addition, participation in weightlifting; roller-blading, roller-skating, skate-boarding, or bicycling; and alcohol among males and depressive symptoms among females during adolescence were associated with higher odds of muscularity-oriented disordered eating in young adulthood. CONCLUSIONS Interventions to prevent muscularity-oriented disordered eating behaviors may target at-risk youth, particularly those of black race or who engage in exercise to gain weight. Future research should examine longitudinal health outcomes associated with muscularity-oriented disordered eating behaviors.
Delivery of microRNAs by Extracellular Vesicles in Viral Infections: Could the News be Packaged?

Extracellular vesicles (EVs) are released by various cells and recently have attracted attention because they constitute a refined system of cell–cell communication. EVs deliver a diverse array of biomolecules including messenger RNAs (mRNAs), microRNAs (miRNAs), proteins and lipids, and they can be used as potential biomarkers in normal and pathological conditions. The cargo of EVs is a snapshot of the donor cell profile; thus, in viral infections, EVs produced by infected cells could be a central player in disease pathogenesis. In this context, miRNAs incorporated into EVs can affect the immune recognition of viruses and promote or restrict their replication in target cells. In this review, we provide an updated overview of the roles played by EV-delivered miRNAs in viral infections and discuss the potential consequences for the host response. The full understanding of the functions of EVs and miRNAs can turn into useful biomarkers for infection detection and monitoring and/or uncover potential therapeutic targets.
Consequences of recombination for the evolution of the mating type locus in Chlamydomonas reinhardtii

Rationale Recombination suppression in sex chromosomes and mating type loci can lead to degeneration due to reduced selection efficacy and Muller’s ratchet effects. However, genetic exchange in the form of non-crossover gene conversions may still take place within crossover-suppressed regions. Recent work has found evidence that gene conversion may explain the low levels of allelic differentiation in the dimorphic mating type locus (MT) of the isogamous alga Chlamydomonas reinhardtii. However, no one has tested whether gene conversion is sufficient to avoid the degeneration of functional sequence within MT. Methods Here, we calculate levels of linkage disequilibrium (LD) across MT as a proxy for recombination rate and investigate its relationship to patterns of population genetic variation and the efficacy of selection in the region. Results We find that levels of LD predict selection efficacy across MT, and that purifying selection is stronger in shared genes than MT-limited genes to the point of being equivalent to that of autosomal genes. Conclusions We argue that isogamous systems without secondary sexual characteristics exhibit reduced selective pressure to differentiate sex chromosomes, and that recombination via gene conversion plays an important role in both reducing differentiation and preventing degeneration of crossover suppressed mating type loci.
Tuples and multiple return values in C

A generic tuple class, capable of storing an arbitrary number of elements each being of arbitrary type, is presented. The class offers a concise means to return multiple values from a function. Instead of using refrerence parameters to pass data out of functions, the function return type is an instantiation of the tuple template, grouping the values to be returned. The semantics of the tuple class is analogous to the pair template in the C++ standard library, thus the usage of tuples is convenient and intuitive. The implementation is described in details. Efficiency considerations are addressed. It is shown that with modern C++ compilers, there is no extra runtime overhead caused by using tuples. However, due to excessive template instantiatons, there is some effect on compilation times and memory usage during compilation. This effect is unlikely to be significant in real programs.