Miracle-dz/UniFAR-FTUs huggingface dataset:
Age, Ethnicity, Glucose-6-Phosphate Dehydrogenase Deficiency, Micronutrient Powder Intake, and Biomarkers of Micronutrient Status, Infection, and Inflammation Are Associated with Anemia Among Children 6-59 Months in Nepal.

BACKGROUND Anemia is a major concern for children in Nepal; however, little is known about context-specific causes of anemia. OBJECTIVE We used cross-sectional data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anemia in a nationally representative, population-based sample of children 6-59 mo (n = 1367). METHODS Hemoglobin, biomarkers of iron status and other micronutrients, infection, inflammation, and blood disorders were assessed from venous blood samples. Soil-transmitted helminth (STH) and Helicobacter pylori infections were assessed from stool. Anthropometry was measured with standard procedures. Sociodemographic and household characteristics, diet, micronutrient powder (MNP) intake, pica, and morbidity recall were ascertained by caregiver interview. Multivariable logistic regression that accounted for complex sampling design, determined predictors of anemia (hemoglobin <11.0 g/dL, altitude adjusted); candidate predictors were variables with P < 0.05 in bivariate models. RESULTS Anemia prevalence was 18.6% (95% CI: 15.8, 21.4). MNP intake [adjusted OR (AOR): 0.25, 95% CI: 0.07, 0.86], log (ln) ferritin (μg/L) (AOR: 0.49, 95% CI: 0.38, 0.64), and ln RBP (μmol/L) (AOR: 0.42, 95% CI: 0.18, 0.95) were associated with reduced odds of anemia. Younger age (6-23 mo compared with 24-59 mo; AOR: 2.29, 95% CI: 1.52, 3.46), other Terai ethnicities (AOR: 2.59, 95% CI: 1.25, 5.35) and Muslim ethnicities (AOR: 3.15, 95% CI: 1.30, 7.65) relative to Brahmin/Chhetri ethnicities, recent fever (AOR: 1.68, 95% CI: 1.08, 2.59), ln C-reactive protein (mg/L) (AOR: 1.23, 95% CI: 1.03, 1.45), and glucose-6-phosphate dehydrogenase deficiency (AOR: 2.84, 95% CI: 1.88, 4.30) were associated with increased odds of anemia. CONCLUSION Both nonmodifiable and potentially modifiable factors were associated with anemia. Thus some but not all anemia might be addressed through effective public health policy, programs, and delivery of nutrition and infection prevention and control.
A single-cell map for the transcriptomic signatures of peripheral blood mononuclear cells in end-stage renal disease.

BACKGROUND Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited. METHODS We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types. RESULTS We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRD patients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified. CONCLUSIONS We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD.
Nitrogen-Vacancy Centers in Diamond for High-Performance Detection of Vacuum Ultraviolet, Extreme Ultraviolet and X-Ray.

Fluorescent nanodiamond (FND) containing nitrogen-vacancy (NV) centers as built-in fluorophores exhibits a nearly constant emission profile over 550 - 750 nm upon excitation by vacuum-ultraviolet (VUV), extreme ultraviolet (EUV), and X- radiations from a synchrotron source over the energy (wavelength) range of 6.2 - 1450 eV (0.86 - 200 nm). The photoluminescence (PL) quantum yield of FND increases steadily with the increasing excitation energy, attaining a value as great as 1700% at 700 eV (1.77 nm). Notably, the yield curve is continuous, having no gap in the VUV to X-ray region. In addition, no significant PL intensity decreases were observed for hours. Applying the FND sensor to measure the absorption cross sections of gaseous O2 over 110 - 200 nm and comparing the measurements with the sodium-salicylate scintillator, we obtained results in agreement with each other within 5%. The superb photostability and broad applicability of FND offer a promising solution for the long-standing problem of lacking a robust and reliable detector for VUV, EUV, and X- radiations.
The Novel Adipokine Gremlin 1 Antagonizes Insulin Action and Is Increased in Type 2 Diabetes and NAFLD/NASH

The BMP2/4 antagonist and novel adipokine Gremlin 1 is highly expressed in human adipose cells and increased in hypertrophic obesity. As a secreted antagonist, it inhibits the effect of BMP2/4 on adipose precursor cell commitment/differentiation. We examined mRNA levels of Gremlin 1 in key target tissues for insulin and also measured tissue and serum levels in several carefully phenotyped human cohorts. Gremlin 1 expression was high in adipose tissue, higher in visceral than in subcutaneous tissue, increased in obesity, and further increased in type 2 diabetes (T2D). A similar high expression was seen in liver biopsies, but expression was considerably lower in skeletal muscles. Serum levels were increased in obesity but most prominently in T2D. Transcriptional activation in both adipose tissue and liver as well as serum levels were strongly associated with markers of insulin resistance in vivo (euglycemic clamps and HOMA of insulin resistance), and the presence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We also found Gremlin 1 to antagonize insulin signaling and action in human primary adipocytes, skeletal muscle, and liver cells. Thus, Gremlin 1 is a novel secreted insulin antagonist and biomarker as well as a potential therapeutic target in obesity and its complications T2D and NAFLD/NASH.
Contextual factors and sporting success: The relationship between birth date and place of early development on the progression of Jamaican track and field athletes from junior to senior level

Understanding determinants associated with dropout from sport is important for talent development. This study aimed (i) to determine dropout rates for Jamaican track and field athletes and (ii) to examine contextual factors (i.e., relative age effect and place of development) as potential determinants of junior athletes progressing to the senior level. A sample of 1552 track and field athletes (mean age 18.57±0.41 years) who were finalists at the national high school (junior) championships in Jamaica between 2000 and 2017 were evaluated from the Jamaica Athletics Administrative Association database. The database provided birth date, school attendance and performance results. A retrospective analysis was completed to investigate the relationship between junior and senior successes and dropout rates. Chi-square analyses were conducted to examine the distribution of birth date quartiles based on the selection year. Using the Jamaican census information, the population size of regions where participants attended school were categorized and used as a proxy for athletes’ place of development. Results showed that the majority of the participants did not progress to senior levels (81%). The relative age effect was evident for athletes who progressed to the senior level but was not evident for athletes who did not progress. There was a bias towards participants who attended school in regions with a population size between 5000–29 999. This study illuminates some of the contextual factors that may influence the likelihood of progressing from junior to senior levels which may help to inform talent identification, selection and development in the sport of track and field.
Objective sleep assessment in >80,000 UK mid-life adults: Associations with sociodemographic characteristics, physical activity and caffeine

Study objectives Normal timing and duration of sleep is vital for all physical and mental health. However, many sleep-related studies depend on self-reported sleep measurements, which have limitations. This study aims to investigate the association of physical activity and sociodemographic characteristics including age, gender, coffee intake and social status with objective sleep measurements. Methods A cross-sectional analysis was carried out on 82995 participants within the UK Biobank cohort. Sociodemographic and lifestyle information were collected through touch-screen questionnaires in 2007–2010. Sleep and physical activity parameters were later measured objectively using wrist-worn accelerometers in 2013–2015 (participants were aged 43–79 years and wore watches for 7 days). Participants were divided into 5 groups based on their objective sleep duration per night (<5 hours, 5–6 hours, 6–7 hours, 7–8 hours and >8 hours). Binary logistic models were adjusted for age, gender and Townsend Deprivation Index. Results Participants who slept 6–7 hours/night were the most frequent (33.5%). Females had longer objective sleep duration than males. Short objective sleep duration (<6 hours) correlated with older age, social deprivation and high coffee intake. Finally, those who slept 6–7 hours/night were most physically active. Conclusions Objectively determined short sleep duration was associated with male gender, older age, low social status and high coffee intake. An inverse ‘U-shaped’ relationship between sleep duration and physical activity was also established. Optimal sleep duration for health in those over 60 may therefore be shorter than younger groups.
Transcriptomic Analyses of Inner Ear Sensory Epithelia in Zebrafish

Analysis of gene expression has the potential to assist in the understanding of multiple cellular processes including proliferation, cell‐fate specification, senesence, and activity in both healthy and disease states. Zebrafish model has been increasingly used to understand the process of hearing and the development of the vertebrate auditory system. Within the zebrafish inner ear, there are three otolith organs, each containing a sensory macula of hair cells. The saccular macula is primarily involved in hearing, the utricular macula is primarily involved in balance and the function of the lagenar macula is not completely understood. The goal of this study is to understand the transcriptional differences in the sensory macula associated with different otolith organs with the intention of understanding the genetic mechanisms responsible for the distinct role each organ plays in sensory perception. The sensory maculae of the saccule, utricle, and lagena were dissected out of adult Et(krt4:GFP)sqet4 zebrafish expressing green fluorescent protein in hair cells for transcriptional analysis. The total RNAs of the maculae were isolated and analyzed by RNA GeneChip microarray. Several of the differentially expressed genes are known to be involved in deafness, otolith development and balance. Gene expression among these otolith organs was very well conserved with less than 10% of genes showing differential expression. Data from this study will help to elucidate which genes are involved in hearing and balance. Furthermore, the findings of this study will assist in the development of the zebrafish model for human hearing and balance disorders. Anat Rec, 303:527–543, 2020. © 2019 American Association for Anatomy
Writing in the air: Facilitative effects of finger writing in older adults

Kūsho, which refers to a behavior in which one moves the index finger as a substitute for a pen in the air or on a surface, mostly used when trying to recall the shape of a written character or the spelling of a word, has been known to facilitate cognitive task performance among kanji writing-system users. This study investigates whether the facilitative effect of kūsho, the existence of which has been exclusively confirmed in younger adults, is present in old age. Moreover, to further understand the interaction between finger movement and cognitive processing, we analyzed the correlation between the kūsho effect and factors such as age, mini-mental state examination (MMSE) score, and number of years of education. The kūsho effect was assessed by a task where participants mentally assembled a set of kanji subparts to form an actual character. The results showed a significant facilitative effect of kūsho and a strong negative correlation between kūsho effect and education. This study confirms the benefits of finger movement for solving cognitive tasks involving visual processing of written language among older adults and suggests the kūsho effect may be mediated by education.
Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease

The solute carrier (SLC) superfamily comprises more than 400 transport proteins mediating the influx and efflux of substances such as ions, nucleotides, and sugars across biological membranes. Over 80 SLC transporters have been linked to human diseases, including obesity and type 2 diabetes (T2D). This observation highlights the importance of SLCs for human (patho)physiology. Yet, only a small number of SLC proteins are validated drug targets. The most recent drug class approved for the treatment of T2D targets sodium–glucose cotransporter 2, product of the SLC5A2 gene. There is great interest in identifying other SLC transporters as potential targets for the treatment of metabolic diseases. Finding better treatments will prove essential in future years, given the enormous personal and socioeconomic burden posed by more than 500 million patients with T2D by 2040 worldwide. In this review, we summarize the evidence for SLC transporters as target structures in metabolic disease. To this end, we identified SLC13A5/sodium-coupled citrate transporter, and recent proof-of-concept studies confirm its therapeutic potential in T2D and nonalcoholic fatty liver disease. Further SLC transporters were linked in multiple genome-wide association studies to T2D or related metabolic disorders. In addition to presenting better-characterized potential therapeutic targets, we discuss the likely unnoticed link between other SLC transporters and metabolic disease. Recognition of their potential may promote research on these proteins for future medical management of human metabolic diseases such as obesity, fatty liver disease, and T2D. SIGNIFICANCE STATEMENT Given the fact that the prevalence of human metabolic diseases such as obesity and type 2 diabetes has dramatically risen, pharmacological intervention will be a key future approach to managing their burden and reducing mortality. In this review, we present the evidence for solute carrier (SLC) genes associated with human metabolic diseases and discuss the potential of SLC transporters as therapeutic target structures.
Effects of Sleep Deprivation on Blood Glucose, Food Cravings, and Affect in a Non-Diabetic: An N-of-1 Randomized Pilot Study

Sleep deprivation is a prevalent and rising health concern, one with known effects on blood glucose (BG) levels, mood, and calorie consumption. However, the mechanisms by which sleep deprivation affects calorie consumption (e.g., measured via self-reported types of craved food) are unclear, and may be highly idiographic (i.e., individual-specific). Single-case or “n-of-1” randomized trials (N1RT) are useful in exploring such effects by exposing each subject to both sleep deprivation and baseline conditions, thereby characterizing effects specific to that individual. We had two objectives: (1) To test and generate individual-specific N1RT hypotheses of the effects of sleep deprivation on next-day BG level, mood, and food cravings in two non-diabetic individuals; (2) To refine and guide a future n-of-1 study design for testing and generating such idiographic hypotheses for personalized management of sleep behavior in particular, and for chronic health conditions more broadly. We initially did not find evidence for idiographic effects of sleep deprivation, but better-refined post hoc findings indicate that sleep deprivation may have increased BG fluctuations, cravings, and negative emotions. We also introduce an application of mixed-effects models and pancit plots to assess idiographic effects over time.
Sex associations and computed tomography coronary angiography-guided management in patients with stable chest pain

Abstract Aims The relative benefits of computed tomography coronary angiography (CTCA)-guided management in women and men with suspected angina due to coronary heart disease (CHD) are uncertain. Methods and results In this post hoc analysis of an open-label parallel-group multicentre trial, we recruited 4146 patients referred for assessment of suspected angina from 12 cardiology clinics across the UK. We randomly assigned (1:1) participants to standard care alone or standard care plus CTCA. Fewer women had typical chest pain symptoms (n = 582, 32.0%) when compared with men (n = 880, 37.9%; P < 0.001). Amongst the CTCA-guided group, more women had normal coronary arteries [386 (49.6%) vs. 263 (26.2%)] and less obstructive CHD [105 (11.5%) vs. 347 (29.8%)]. A CTCA-guided strategy resulted in more women than men being reclassified as not having CHD {19.2% vs. 13.1%; absolute risk difference, 5.7 [95% confidence interval (CI): 2.7–8.7, P < 0.001]} or having angina due to CHD [15.0% vs. 9.0%; absolute risk difference, 5.6 (2.3–8.9, P = 0.001)]. After a median of 4.8 years follow-up, CTCA-guided management was associated with similar reductions in the risk of CHD death or non-fatal myocardial infarction in women [hazard ratio (HR) 0.50, 95% CI 0.24–1.04], and men (HR 0.63, 95% CI 0.42–0.95; Pinteraction = 0.572). Conclusion Following the addition of CTCA, women were more likely to be found to have normal coronary arteries than men. This led to more women being reclassified as not having CHD, resulting in more downstream tests and treatments being cancelled. There were similar prognostic benefits of CTCA for women and men.
Stromal Collagen Arrangement Correlates with Stiffness of the Canine Cornea

The cornea is the most external layer of the eye and serves two important roles in (1) the refraction of light and (2) protection from the outside environment, both of which are highly dependent on the collagen assembly of the corneal stroma. This study sought to determine the collagen fiber arrangement of the canine corneal stroma and correlate the stromal organization with tissue stiffness in the anterior and posterior cornea. Collagen organization of the canine cornea was visualized through second-harmonic generation (SHG) imaging, and tissue stiffness of the anterior and posterior corneal stroma was determined by atomic force microscopy. Analysis of the canine anterior corneal stroma using SHG imaging documented intertwining of the collagen fibers with a high degree of fiber branching, with a more lamellar and non-branching posterior stroma. The anterior stroma had significantly higher tissue stiffness in both dogs and humans, when compared with the posterior corneal stroma (canine median: 1.3 kPa vs. 0.3 kPa; human median: 14.6 kPa vs. 2.1 kPa, respectively). There was a direct correlation between corneal collagen stromal organization and tissue stiffness in the dog, which was consistent with other mammalian species previously examined and likely reflects the need for maintenance of rigidity and corneal curvature.
Feedback Regulation of Syk by Protein Kinase C in Human Platelets

The spleen tyrosine kinase (Syk) is essential for immunoreceptor tyrosine-based activation motif (ITAM)-dependent platelet activation, and it is stimulated by Src-family kinase (SFK)-/Syk-mediated phosphorylation of Y352 (interdomain-B) and Y525/526 (kinase domain). Additional sites for Syk phosphorylation and protein interactions are known but remain elusive. Since Syk S297 phosphorylation (interdomain-B) was detected in platelets, we hypothesized that this phosphorylation site regulates Syk activity via protein kinase C (PKC)-and cyclic adenosine monophosphate (cAMP)-dependent pathways. ADP, the GPVI-agonist convulxin, and the GPIbα-agonist echicetin beads (EB) were used to stimulate human platelets with/without effectors. Platelet aggregation and intracellular messengers were analyzed, along with phosphoproteins, by immunoblotting using phosphosite-specific antibodies or phos-tags. ADP, convulxin, and EB upregulated Syk S297 phosphorylation, which was inhibited by iloprost (cAMP pathway). Convulxin-stimulated Syk S297 phosphorylation was stoichiometric, transient, abolished by the PKC inhibitor GF109203X, and mimicked by the PKC activator PDBu. Convulxin/EB stimulated Syk S297, Y352, and Y525/526 phosphorylation, which was inhibited by SFK and Syk inhibitors. GFX and iloprost inhibited convulxin/EB-induced Syk S297 phosphorylation but enhanced Syk tyrosine (Y352/Y525/526) and substrate (linker adaptor for T cells (LAT), phospholipase γ2 (PLC γ2)) phosphorylation. GFX enhanced convulxin/EB-increases of inositol monophosphate/Ca2+. ITAM-activated Syk stimulates PKC-dependent Syk S297 phosphorylation, which is reduced by SFK/Syk/PKC inhibition and cAMP. Inhibition of Syk S297 phosphorylation coincides with enhanced Syk activation, suggesting that S297 phosphorylation represents a mechanism for feedback inhibition in human platelets.
Molecular characterization of pulmonary defenses against bacterial invasion in allergic asthma: The role of Foxa2 in regulation of β-defensin 1

Allergic asthma, characterized by chronic airway Th2-dominated inflammation, is associated with an increased risk of infection; however, the underlying mechanisms are unclear. Forkhead box protein A2 (Foxa2) plays a critical role in Th2 inflammation and is associated with pulmonary defenses. To determining the role of Foxa2 in Th2-dominated lung inflammation against the invading bacteria, we established a mouse OVA-sensitized model, an Escherichia coli lung invasion model, and mice with conditional deletion of Foxa2 in respiratory epithelial cells. The number of bacteria in the lung tissue was counted to assess clearance ability of lung. Lung inflammation and histopathology was evaluated using HE and PAS staining. It was found that OVA-sensitized mice had decreased E. coli clearance, reduced Foxa2 expression, and decreased DEFB1 secretion. Conditional deletion of Foxa2 in respiratory epithelial cells led to decreased clearance of E. coli and impaired secretion of DEFB1, similar to the OVA-induced allergic condition. The impaired secretion of DEFB1 may be responsible for the increased risk of infection in the Th2-dominated airway inflammation. Dual luciferase assay demonstrated that Foxa2 regulates DEFB1 expression by affecting its promoter activity in HBE cells. Our study indicated that Foxa2 plays an important role in Th2-dominated airway inflammation against invading bacteria. Conditional deletion of Foxa2 in respiratory epithelial cells can reduce pulmonary’s defense against bacterial invasion by inhibiting DEFB1expression.