Miracle-dz/UniFAR-FTUs huggingface dataset:
Fine-Mapping of 5q12.1–13.3 Unveils New Genetic Contributors to Caries

Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1–5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries.
Caregiver acceptance of a patient navigation program to increase human papillomavirus vaccination in pediatric clinics: a qualitative program evaluation

ABSTRACT Objective: The purpose of this evaluation was to examine the acceptability of a multi-component patient navigator (PN) intervention program designed to decrease barriers to human papillomavirus (HPV) vaccination among caregivers of adolescents. We sought to understand the most important components of the program from the caregivers’ perspective and to evaluate remaining barriers to vaccination. Method: Caregivers of children 9–17 years old (N = 102) participated in qualitative semi-structured interviews with questions informed by the Theory of Planned Behavior. These interviews assessed experiences with a PN program which offered HPV vaccination, scheduling, and reminders in pediatric clinics. We included randomly selected 46 program participant transcripts and 11 decliner transcripts. A thematic approach was used to analyze transcripts for themes related to acceptability of HPV vaccination, important program components, and any problems encountered. Results: Major themes included: reasons for making HPV vaccination decision, helpful program components and suggestions for improvement, and remaining barriers to vaccination. Those who declined vaccination stated that their child was too young or not ready to think about sex, or they did not have enough information to make a decision. However, they felt that PNs were respectful of their decision. Program participants felt that vaccination was an important way to prevent cancer. Program participants had often not been aware of the vaccine and felt that having it explained was very helpful. Conclusion: This program evaluation found that caregivers of pediatric patients, even those who declined the HPV vaccine, appreciated the program and felt it provided important information about the vaccine.
Fifty shades of brown: Macroevolution of plumage brightness in the Furnariida, a large clade of drab Neotropical passerines

Both natural and sexual selection are thought to affect the evolution of bird color. Most studies of the topic have focused on sexually dichromatic taxa and showy plumages, which are expected to be more influenced by social selection and usually result in increased conspicuousness. However, many bird clades display dull brown or gray plumages that vary greatly in brightness (lightness), but little in hue (shade). Here, we examine the macroevolution of brightness in one such clade, the Furnariida. We make comparisons across light environments, body parts, monochromatic lineages, and each sex of dichromatic lineages. We found that support for models including light environments is greater for the dorsum than for the venter, and that brightness evolution is more constrained in the former than in the latter. Plumages in this clade have evolved to be darker in darker habitats, consistent with natural selection for increased crypsis. Finally, the features of brightness macroevolution are broadly similar across the sexes of the dichromatic clade, challenging the view that sexual dichromatism is driven by different evolutionary processes acting in each sex. We conclude that, in the Furnariida, light environments and dorsal–ventral variation are more important than sex as axes of color evolution.
Upper bound on the biological effects of 50/60 Hz magnetic fields mediated by radical pairs

Prolonged exposure to weak (~1 μT) extremely-low-frequency (ELF, 50/60 Hz) magnetic fields has been associated with an increased risk of childhood leukaemia. One of the few biophysical mechanisms that might account for this link involves short-lived chemical reaction intermediates known as radical pairs. In this report, we use spin dynamics simulations to derive an upper bound of 10 parts per million on the effect of a 1 μT ELF magnetic field on the yield of a radical pair reaction. By comparing this figure with the corresponding effects of changes in the strength of the Earth’s magnetic field, we conclude that if exposure to such weak 50/60 Hz magnetic fields has any effect on human biology, and results from a radical pair mechanism, then the risk should be no greater than travelling a few kilometres towards or away from the geomagnetic north or south pole.
Comparison of the Antiviral Activity of Bictegravir against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 Mutants

We compared the activity of the integrase inhibitor bictegravir against HIV-1 and HIV-2 using a culture-based, single-cycle assay. Values of 50% effective concentrations ranged from 1.2 to 2.5 nM for 9 HIV-1 isolates and 1.4 to 5.6 nM for 15 HIV-2 isolates. ABSTRACT We compared the activity of the integrase inhibitor bictegravir against HIV-1 and HIV-2 using a culture-based, single-cycle assay. Values of 50% effective concentrations ranged from 1.2 to 2.5 nM for 9 HIV-1 isolates and 1.4 to 5.6 nM for 15 HIV-2 isolates. HIV-2 integrase mutants G140S/Q148R and G140S/Q148H were 34- and 110-fold resistant to bictegravir, respectively; other resistance-associated mutations conferred ≤5-fold changes in bictegravir susceptibility. Our findings indicate that bictegravir-based antiretroviral therapy should be evaluated in HIV-2-infected individuals.
Early adversity in rural India impacts the brain networks underlying visual working memory

Abstract There is a growing need to understand the global impact of poverty on early brain and behavioural development, particularly with regard to key cognitive processes that emerge in early development. Although the impact of adversity on brain development can trap children in an intergenerational cycle of poverty, the massive potential for brain plasticity is also a source of hope: reliable, accessible, culturally agnostic methods to assess early brain development in low resource settings might be used to measure the impact of early adversity, identify infants for timely intervention and guide the development and monitor the effectiveness of early interventions. Visual working memory (VWM) is an early marker of cognitive capacity that has been assessed reliably in early infancy and is predictive of later academic achievement in Western countries. Here, we localized the functional brain networks that underlie VWM in early development in rural India using a portable neuroimaging system, and we assessed the impact of adversity on these brain networks. We recorded functional brain activity as young children aged 4–48 months performed a VWM task. Brain imaging results revealed localized activation in the frontal cortex, replicating findings from a Midwestern US sample. Critically, children from families with low maternal education and income showed weaker brain activity and poorer distractor suppression in canonical working memory areas in the left frontal cortex. Implications of this work are far‐reaching: it is now cost‐effective to localize functional brain networks in early development in low‐resource settings, paving the way for novel intervention and assessment methods.
The lack of effect of insulin on luteinizing hormone pulsatility in healthy male volunteers provides evidence of a sexual dimorphism in the metabolic regulation of reproductive hormones.

BACKGROUND The activity of the neuroendocrine reproductive axis is closely related to nutritional status. This link is particularly important in healthy women, in whom insulin is a positive signal for the reproductive system. In contrast, very little is known regarding this relation in men. OBJECTIVES This study was designed to evaluate the effect of insulin on the reproductive axis of young male volunteers and to study the effect of short-term hypercaloric feeding on this modulation. DESIGN The activity of the neuroendocrine reproductive axis was characterized by the pattern of endogenous luteinizing hormone (LH) secretion on the basis of frequent blood sampling protocols. The effect of insulin was tested by comparing the LH secretion pattern between a baseline study and a hyperinsulinemic euglycemic clamp. These studies were performed first in subjects fed a controlled isocaloric diet for 6 d (calculated as 1.5 times their resting metabolic rate) then in the same subjects fed a controlled hypercaloric diet in which 30% extra calories were provided as fat and fructose (3 g · kg(-1) · d(-1)) before undergoing identical protocols. Serum gonadotropins, sex steroids, glucose, insulin, ghrelin, and leptin concentrations were assessed, and the HOMA-IR was calculated. RESULTS The LH secretion pattern was not affected by insulin or by hypercaloric feeding. Insulin decreased ghrelin and increased leptin concentrations but had no additional effect of hypercaloric feeding despite significantly lower HOMA-IR indexes. CONCLUSIONS Our data indicate that neither insulin nor short-term hypercaloric feeding has any effect on the activity of the male reproductive axis. They also further support the association between ghrelin and insulin and glucose metabolism. This trial was registered at clinicaltrials.gov as NCT01058681.
Dental caries lesions in primary teeth without obvious cavitation: Treatment decision-making process.

BACKGROUND Dental caries diagnosis and management have changed over time. AIM To identify the treatment decision-making process performed by paediatric dentists, after caries detection using CAST instrument (Caries Assessment Spectrum and Treatment), for enamel (CAST 3) and non-cavitated dentin caries lesions (CAST 4) before and after analysing radiographic images. DESIGN Seventy-four paediatric dentists were invited to participate. Twelve clinical cases were presented online, and treatment decisions before and after the analysis of bitewing radiographs were evaluated. RESULTS Sixty-one specialists answered the questionnaire. The necessity for radiographs was significantly associated with the presence and depth of the caries lesion (P < 0.0001). CAST 3 lesions were preferentially monitored before and after the radiographic assessment. For CAST 4 lesions limited to the outer half of dentin, treatments indicated before and after radiographic analysis were sealant (33%) and restoration (40%). For the lesions in the inner half of dentin, restoration was the most cited before (45%) and after (84%) radiographs. The radiographic depth was the only significant independent variable when "change in the treatment option" was analysed by the regression model (P < 0.001). CONCLUSIONS Enamel lesions were treated through less invasive treatments. Radiographs influenced the decision, especially for the lesions that involved the inner half of dentin.
Person-centred inpatient care - A quasi-experimental study in an internal medicine context.

AIM The aim of this study was to evaluate effects of person-centred inpatient care on care processes in terms of satisfaction with care and person-centred content in medical records, and to evaluate effects on self-reported health and self-efficacy. BACKGROUND Internal medicine inpatient care is complex, covering patients varying in age, medical conditions, health status, and other aspects. There has been limited research on the impact of person-centred care (PCC) on satisfaction with care and health outcomes in internal medicine care environments regardless of diagnosis and care pathway. DESIGN A quasi-experimental study with pre- and postmeasurements. METHODS Adult patients admitted to an internal medicine inpatient unit were consecutively included over 16 weeks in 2014 and 24 weeks in 2015-2016. Data were collected before a person-centred inpatient care intervention (N = 204) and 12 months after the intervention was implemented (N = 177). Data on satisfaction with care and self-reported health were collected at discharge and medical records were reviewed. The intervention included systematically applied person-centred assessment, health plans, and persistent PCC. RESULTS After the intervention, patients rated higher satisfaction with care regarding essential components of PCC and more patients had received effective pain relief. There were no differences in information on self-care or medications, self-rated health, or self-efficacy. CONCLUSION Care focused on the foundations of person-centredness seems to enhance both patients' perceptions of satisfaction and symptom management. Situational aspects such as care pathways should be considered when implementing person-centred inpatient care. TRIAL REGISTRATION CLINICALTRIALS. GOV, REGISTRATION NUMBER NCT03725813.
The Effect of Microfluidic Geometry on Myoblast Migration

In vitro systems comprised of wells interconnected by microchannels have emerged as a platform for the study of cell migration or multicellular models. In the present study, we systematically evaluated the effect of microchannel width on spontaneous myoblast migration across these microchannels—from the proximal to the distal chamber. Myoblast migration was examined in microfluidic devices with varying microchannel widths of 1.5–20 µm, and in chips with uniform microchannel widths over time spans that are relevant for myoblast-to-myofiber differentiation in vitro. We found that the likelihood of spontaneous myoblast migration was microchannel width dependent and that a width of 3 µm was necessary to limit spontaneous migration below 5% of cells in the seeded well after 48 h. These results inform the future design of Polydimethylsiloxane (PDMS) microchannel-based co-culture platforms as well as future in vitro studies of myoblast migration.
Modeling Heterogeneity in the Genetic Architecture of Ethnically Diverse Groups Using Random Effect Interaction Models

In humans, most genome-wide association studies have been conducted using data from Caucasians and many of the reported findings have not replicated in other populations. This lack of replication may be due to statistical issues (small sample sizes or confounding) or perhaps more fundamentally to differences in the genetic architecture of traits between ethnically diverse subpopulations. What aspects of the genetic architecture of traits vary between subpopulations and how can this be quantified? We consider studying effect heterogeneity using Bayesian random effect interaction models. The proposed methodology can be applied using shrinkage and variable selection methods, and produces useful information about effect heterogeneity in the form of whole-genome summaries (e.g., the proportions of variance of a complex trait explained by a set of SNPs and the average correlation of effects) as well as SNP-specific attributes. Using simulations, we show that the proposed methodology yields (nearly) unbiased estimates when the sample size is not too small relative to the number of SNPs used. Subsequently, we used the methodology for the analyses of four complex human traits (standing height, high-density lipoprotein, low-density lipoprotein, and serum urate levels) in European-Americans (EAs) and African-Americans (AAs). The estimated correlations of effects between the two subpopulations were well below unity for all the traits, ranging from 0.73 to 0.50. The extent of effect heterogeneity varied between traits and SNP sets. Height showed less differences in SNP effects between AAs and EAs whereas HDL, a trait highly influenced by lifestyle, exhibited a greater extent of effect heterogeneity. For all the traits, we observed substantial variability in effect heterogeneity across SNPs, suggesting that effect heterogeneity varies between regions of the genome.
Automatic recognition of corneal nerve structures in images from confocal microscopy.

PURPOSE To devise a method for automatically tracing corneal nerves in confocal microscopy images. METHODS Images were acquired with a confocal microscope. They were normalized and enhanced in luminosity and contrast. The nerves were recognized by applying a novel tracing algorithm, which includes Gabor filtering to enhance nerve visibility and postprocessing procedures to remove false recognitions and to link sparse segments into continuous structures. A prototype of the algorithm was implemented in commercial software and run on a personal computer. RESULTS A retrospective evaluation of the automatic procedure was performed on a data set containing 90 images, from normal and non-normal subjects. The average percentage of correctly recognized nerves length with respect to total manually traced lengths of visible nerves was 80.4% in normal subjects and 83.8% on non-normal subjects; the average rate of false nerve length recognition (with respect to the total automatically traced length) was 6.5% in normal subjects and 9.1% in non-normal subjects. Correlation coefficients between manual and automatic lengths on the same image were 0.94, 0.95, and 0.86 in all, normal, and non-normal subjects, respectively. A further evaluation was performed on an independent set of 80 normal subject images, resulting in a correlation coefficient of 0.89 between manual and automatic nerve lengths. CONCLUSIONS Automatic and manual length estimations on the same image were very well correlated, indicating that the automatic procedure is capable of correctly reproducing the differences in nerve length between different subjects.
Non-HIV Comorbid Conditions and Polypharmacy Among People Living with HIV Age 65 or Older Compared with HIV-Negative Individuals Age 65 or Older in the United States: A Retrospective Claims-Based Analysis.

The number of people living with HIV (PLWH) ≥65 years is increasing in the United States. By 2035, the proportion of PLWH in this age group is projected to be 27%. As PLWH live longer, they face age-related comorbidities. We compared non-HIV disease and medication burden among PLWH (n = 2359) and HIV-negative individuals (n = 2,010,513) ≥65 years using MarketScan® Medicare Supplemental health insurance claims from 2009 to 2015. Outcomes were common diagnoses and medication classes, prevalence of non-HIV conditions, number of non-HIV conditions, and daily non-antiretroviral therapy (ART) medications over a 1-year period. We examined age-standardized prevalence rates and prevalence ratios (PRs) and fit multivariable generalized linear models, stratified by sex. PLWH were younger (mean 71 vs. 76 years) and a larger proportion were men (81% vs. 45%). The most common diagnoses among both cohorts were hypertension and dyslipidemia. Most non-HIV conditions were more prevalent among PLWH. The largest absolute difference was in anemia (29.6 cases per 100 people vs.11.7) and the largest relative difference was in hepatitis C (PR = 22.0). Unadjusted mean number of non-HIV conditions and daily non-ART medications were higher for PLWH (4.61 conditions and 3.79 medications) than HIV-negative individuals (3.94 and 3.41). In models, PLWH had significantly more non-HIV conditions than HIV-negative individuals [ratios: men = 1.272, (95% confidence interval, 1.233-1.312); women = 1.326 (1.245-1.413)]. Among those with >0 daily non-ART medications, men with HIV had significantly more non-ART medications than HIV-negative men [ratio = 1.178 (1.133-1.226)]. The disease burden associated with aging is substantially higher among PLWH, who may require additional services to effectively manage HIV and comorbid conditions.
Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, a Mechanism for Vitamin D Deficiency in Diabetes

Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes; however, the mechanisms remain uncertain. Here, we show that nutritional deprivation–responsive mechanisms regulate vitamin D metabolism. Both fasting and diabetes suppressed hepatic cytochrome P450 (CYP) 2R1, the main vitamin D 25-hydroxylase responsible for the first bioactivation step. Overexpression of coactivator peroxisome proliferator–activated receptor γ coactivator 1-α (PGC-1α), induced physiologically by fasting and pathologically in diabetes, resulted in dramatic downregulation of CYP2R1 in mouse hepatocytes in an estrogen-related receptor α (ERRα)–dependent manner. However, PGC-1α knockout did not prevent fasting-induced suppression of CYP2R1 in the liver, indicating that additional factors contribute to the CYP2R1 repression. Furthermore, glucocorticoid receptor (GR) activation repressed the liver CYP2R1, suggesting GR involvement in the regulation of CYP2R1. GR antagonist mifepristone partially prevented CYP2R1 repression during fasting, suggesting that glucocorticoids and GR contribute to the CYP2R1 repression during fasting. Moreover, fasting upregulated the vitamin D catabolizing CYP24A1 in the kidney through the PGC-1α-ERRα pathway. Our study uncovers a molecular mechanism for vitamin D deficiency in diabetes and reveals a novel negative feedback mechanism that controls crosstalk between energy homeostasis and the vitamin D pathway.
Immature granulocytes index as early marker of sepsis

Sepsis induces the recruitment of immature neutrophils into the circulation. An immature granulocyte percentage (IG%) count greater than 3% has been shown to be an indicator for the risk of sepsis. The aim of this study was to evaluate the IG% as predictor of sepsis compared to blood culture results and sepsis diagnostic confirmation.