Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental plasticity of epithelial stem cells in tooth and taste bud renewal

Significance Nearly one-third of adults over the age of 65 have lost all their teeth. We set out to understand tooth renewal in animals that have replacement and regeneration capabilities. Using cichlid fishes and mouse models, we discovered plasticity between tooth and taste bud progenitor cell derivatives, mediated by BMP. Our results suggest that oral organs have surprising regenerative capabilities and can be manipulated to express characteristics of different tissue types. In Lake Malawi cichlids, each tooth is replaced in one-for-one fashion every ∼20 to 50 d, and taste buds (TBs) are continuously renewed as in mammals. These structures are colocalized in the fish mouth and throat, from the point of initiation through adulthood. Here, we found that replacement teeth (RT) share a continuous band of epithelium with adjacent TBs and that both organs coexpress stem cell factors in subsets of label-retaining cells. We used RNA-seq to characterize transcriptomes of RT germs and TB-bearing oral epithelium. Analysis revealed differential usage of developmental pathways in RT compared to TB oral epithelia, as well as a repertoire of genome paralogues expressed complimentarily in each organ. Notably, BMP ligands were expressed in RT but excluded from TBs. Morphant fishes bathed in a BMP chemical antagonist exhibited RT with abrogated shh expression in the inner dental epithelium (IDE) and ectopic expression of calb2 (a TB marker) in these very cells. In the mouse, teeth are located on the jaw margin while TBs and other oral papillae are located on the tongue. Previous study reported that tongue intermolar eminence (IE) oral papillae of Follistatin (a BMP antagonist) mouse mutants exhibited dysmorphic invagination. We used these mutants to demonstrate altered transcriptomes and ectopic expression of dental markers in tongue IE. Our results suggest that vertebrate oral epithelium retains inherent plasticity to form tooth and taste-like cell types, mediated by BMP specification of progenitor cells. These findings indicate underappreciated epithelial cell populations with promising potential in bioengineering and dental therapeutics.
Children in Need—Diagnostics, Epidemiology, Treatment and Outcome of Early Onset Anorexia Nervosa

Knowledge of anorexia nervosa (AN) in childhood is scarce. This review gives a state-of-the-art overview on the definition, classification, epidemiology and etiology of this serious disorder. The typical features of childhood AN in comparison to adolescent AN and avoidant restrictive eating disorder (ARFID) are described. Other important issues discussed in this article are somatic and psychiatric comorbidity, differential diagnoses and medical and psychological assessment of young patients with AN. Special problems in the medical and psychological treatment of AN in children are listed, although very few studies have investigated age-specific treatment strategies. The physical and mental outcomes of childhood AN appear to be worse than those of adolescent AN, although the causes for these outcomes are unclear. There is an urgent need for ongoing intensive research to reduce the consequences of this debilitating disorder of childhood and to help patients recover.
APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer’s Disease Risk in a Multiracial Sample

Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer’s disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10−94; GT: OR = 15.87, p = 2.62 × 10−9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10−108; GT: OR = 12.63, p = 3.44 × 10−64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.
Trace Minerals, Heavy Metals, and Preeclampsia: Findings from the Boston Birth Cohort

Background Preeclampsia is a leading contributor to maternal and perinatal morbidity and mortality. In mice experiments, manganese (Mn) and selenium (Se) are protective whereas cadmium (Cd) is promotive for preeclampsia. Epidemiologic findings on these chemical elements have been inconsistent. To confirm experimental findings in mice, we examined associations of trace minerals (Mn and Se) and heavy metals (Cd, lead [Pb], and mercury [Hg]) with preeclampsia in a birth cohort. Methods and Results A total of 1274 women from the Boston Birth Cohort (enrolled since 1998) had complete data on the exposures and outcome. We measured Mn, Se, Cd, Pb, and Hg from red blood cells collected within 24 to 72 hours after delivery. We ascertained preeclampsia diagnosis from medical records. We used Poisson regression with robust variance models to estimate prevalence ratios (PRs) and 95% CIs. A total of 115 (9.0%) women developed preeclampsia. We observed evidence of a dose–response trend for Mn (P for trend<0.001) and to some extent for Cd (P for trend=0.009) quintiles. After multivariable adjustment, a 1 SD increment in Mn was associated with 32% lower risk of developing preeclampsia (PR=0.68; 95% CI, 0.54–0.86), whereas a 1 SD increment in Cd was associated with 15% higher risk of preeclampsia (PR=1.15; 95% CI, 0.98–1.36). Null associations were observed for Se, Pb, and Hg. Conclusions Findings from our cohort, consistent with evidence from mice experiments and human studies, indicate that women with lower blood concentration of Mn or higher Cd are more likely to develop preeclampsia.
Clinical and Microbiologic Outcomes in Patients with Monomicrobial Stenotrophomonas maltophilia Infections

Stenotrophomonas maltophilia is an opportunistic pathogen observed in nosocomial infections. Due to biofilm production and resistance to numerous antimicrobials, eradication is difficult. This study evaluated outcomes for monomicrobial S. maltophilia infections. Seventy-six patients were included, with 45 patients on trimethoprim-sulfamethoxazole and 31 patients on levofloxacin. Overall clinical cure, microbiological eradication, and 28-day mortality were observed in 79%, 82%, and 14% of patients, respectively. ABSTRACT Stenotrophomonas maltophilia is an opportunistic pathogen observed in nosocomial infections. Due to biofilm production and resistance to numerous antimicrobials, eradication is difficult. This study evaluated outcomes for monomicrobial S. maltophilia infections. Seventy-six patients were included, with 45 patients on trimethoprim-sulfamethoxazole and 31 patients on levofloxacin. Overall clinical cure, microbiological eradication, and 28-day mortality were observed in 79%, 82%, and 14% of patients, respectively. The use of trimethoprim-sulfamethoxazole or levofloxacin resulted in high cure rates; however, a trend toward resistance selection with levofloxacin was identified.
An Empirical National Assessment of the Learning Environment and Factors Associated With Program Culture.

OBJECTIVES To empirically describe surgical residency program culture and assess program characteristics associated with program culture. SUMMARY BACKGROUND DATA Despite concerns about the impact of the learning environment on trainees, empirical data have not been available to examine and compare program-level differences in residency culture. METHODS Following the 2018 American Board of Surgery In-Training Examination, a cross-sectional survey was administered to all US general surgery residents. Survey items were analyzed using principal component analysis to derive composite measures of program culture. Associations between program characteristics and composite measures of culture were assessed. RESULTS Analysis included 7387 residents at 260 training programs (99.3% response rate). Principal component analysis suggested that program culture may be described by 2 components: Wellness and Negative Exposures. Twenty-six programs (10.0%) were in the worst quartile for both Wellness and Negative Exposure components. These programs had significantly higher rates of duty hour violations (23.3% vs 11.1%), verbal/physical abuse (41.6% vs 28.6%), gender discrimination (78.7% vs 64.5%), sexual harassment (30.8% vs 16.7%), burnout (54.9% vs 35.0%), and thoughts of attrition (21.6% vs 10.8%; all P < 0.001). Being in the worst quartile of both components was associated with percentage of female residents in the program (P = 0.011), but not program location, academic affiliation, size, or faculty demographics. CONCLUSIONS Residency culture was characterized by poor resident wellness and frequent negative exposures and was generally not associated with structural program characteristics. Additional qualitative and quantitative studies are needed to explore unmeasured local social dynamics that may underlie measured differences in program culture.
Disturbance Observer-Based Neural Network Control of Cooperative Multiple Manipulators With Input Saturation

In this paper, the complex problems of internal forces and position control are studied simultaneously and a disturbance observer-based radial basis function neural network (RBFNN) control scheme is proposed to: 1) estimate the unknown parameters accurately; 2) approximate the disturbance experienced by the system due to input saturation; and 3) simultaneously improve the robustness of the system. More specifically, the proposed scheme utilizes disturbance observers, neural network (NN) collaborative control with an adaptive law, and full state feedback. Utilizing Lyapunov stability principles, it is shown that semiglobally uniformly bounded stability is guaranteed for all controlled signals of the closed-loop system. The effectiveness of the proposed controller as predicted by the theoretical analysis is verified by comparative experimental studies.
Attentional Demand as a Function of Contextual Factors in Different Traffic Scenarios

Objective To assess the attentional demand of different contextual factors in driving. Background The attentional demand on the driver varies with the situation. One approach for estimating the attentional demand, via spare capacity, is to use visual occlusion. Method Using a 3 × 5 within-subjects design, 33 participants drove in a fixed-base simulator in three scenarios (i.e., urban, rural, and motorway), combined with five fixed occlusion durations (1.0, 1.4, 1.8, 2.2, and 2.6 s). By pressing a microswitch on a finger, the driver initiated each occlusion, which lasted for the same predetermined duration within each trial. Drivers were instructed to occlude their vision as often as possible while still driving safely. Results Stepwise logistic regression per scenario indicated that the occlusion predictors varied with scenario. In the urban environment, infrastructure-related variables had the biggest influence, whereas the distance to oncoming traffic played a major role on the rural road. On the motorway, occlusion duration and time since the last occlusion were the main determinants. Conclusion Spare capacity is dependent on the scenario, selected speed, and individual factors. This is important for developing workload managers, infrastructural design, and aspects related to transfer of control in automated driving. Application Better knowledge of the determinants of spare capacity in the road environment can help improve workload managers, thereby contributing to more efficient and safer interaction with additional tasks.
Physical Activity and Academic Performance: Genetic and Environmental Associations.

INTRODUCTION Physical activity and academic performance are believed to be associated. Though both traits are partially heritable, it remains unclear whether these traits also share a genetic and/or environmental background in common. We aimed to examine to what extent leisure-time physical activity and academic performance share genetic and environmental effects from early adolescence to young adulthood. METHODS Participants were Finnish twins (2543-2693 individuals/study wave) who reported their leisure-time physical activity at ages 12, 14, 17 and 24. Academic performance was assessed with teacher-reported grade point averages at ages 12 and 14 and by self-reported educational levels at ages 17 and 24. Bivariate quantitative genetic modeling at each age and between different ages was performed to decompose the trait correlation between academic performance and physical activity into genetic and environmental components. RESULTS The trait correlations between leisure-time physical activity and academic performance were positive, but modest at most (rtrait=0.08-0.22 in males, and 0.07-0.18 in females). The genetic correlations between leisure-time physical activity and academic performance were higher than the trait correlations (rA=0.17-0.43 in males, and 0.15-0.25 in females). Common genetic influences explained 43-100% of the trait correlations. Environmental influences shared by co-twins between leisure-time physical activity and academic performance were also correlated (rC=0.27-0.54 in males, and 0.21-0.69 in females) explaining 41-100% of the trait correlations. Unique environmental influences were correlated only in females (rE=0.10-0.15). CONCLUSION Both common genetic background and shared family environment (i.e., familial background) partially account for the associations observed between leisure-time physical activity and academic performance. However, the estimates vary in magnitude by age.
Effects of the dutasteride and sildenafil association in the penis of a benign prostatic hyperplasia animal model

Abstract Objective The aim of this study was to investigate whether concomitant treatment of dutasteride and sildenafil could prevent structural changes in the penis of a BPH rodent model. Methods Thirty-two adult male rats were divided into the following groups: Ctrl, untreated control rats; BPH, untreated spontaneously hypertensive rats (SHRs); BPH + D, SHRs treated with dutasteride; and BPH + DS, SHRs treated with dutasteride and sildenafil. All treatments were performed during 40 days, following which the penises were collected for histomorphometrical analysis. The results were compared via one-way ANOVA with Bonferroni’s post-test, considering p values <. 05 as significant. Results The smooth muscle density decreased by 28.6% and 21.4% in BPH + D and BPH + DS, respectively, when compared to the BPH group. The sinusoid space density reduced by 32.2% in BPH, when compared to the Ctrl group; this density was also reduced by 22.6% in BPH + D, when compared to the BPH group. The density of the elastic fibers increased 51.6% and 65.6% in BPH + D and BPH + DS, when compared to the BPH group. Conclusion Treatment with dutasteride promoted morphological changes in the corpus cavernous of this BPH model. Concomitant treatment with sildenafil did not prevent the morphological changes caused by dutasteride; on the contrary, it also promoted a further increase in elastic fibers.
The association between antihypertensive therapy and the incidence of Parkinson's disease in patients followed in general practices in Germany .

AIM The aim of this study was to investigate the potential association between antihypertensive therapy and the incidence of Parkinson's disease (PD) in patients followed in general practices in Germany. MATERIALS AND METHODS This study included patients aged ≥ 40 who had received initial diagnoses of PD in 1,203 general practices in Germany between January 2013 and December 2017 (index date). After applying similar inclusion criteria, PD cases were matched to non-PD controls using propensity scores based on age, sex, and treating physician. The primary outcome of the study was the incidence of PD as a function of the use of antihypertensive drugs (diuretics, β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers). Logistic regression models were conducted to study the association between the use of antihypertensive drugs and the incidence of PD after adjusting for codiagnoses and antihypertensive cotherapy. RESULTS The present study included 9,127 patients with PD and 9,127 patients without PD (mean age: 75.8 years; 48.4% women). The at-least-once use of diuretics (44.8% versus 38.4%; odds ratio (OR) = 1.23 (1.15-1.32)) was associated with an increased incidence of PD. However, this effect was not maintained for a therapy duration of at least 3 years, and no association was observed between the diuretic therapy duration and PD incidence. For all other antihypertensive drug classes, we found no significant associations with PD incidence. CONCLUSION No association was found between antihypertensive therapy duration and PD incidence. Further epidemiological studies are needed to compare the effects of subclasses of antihypertensives on PD.
A survey of perceptions, attitudes and practices regarding the antibiotic prescription among Iranian physicians

ABSTRACT Background: Over-prescription and overuse of antibiotics are a major cause of concern in terms of healthcare and economic implications, as well as the emergence of microbial resistance worldwide. So far, efforts have been administered by many countries to regulate the consumption of antibiotics and overcome the rapid emergence of resistant bacteria. Assessment of the perspectives and behavior of physicians can play a major role in achieving this objective. Objectives: The objective of the present study was to assess the perspectives on the antibiotic prescription practice of physicians and evaluate their tendency to receive feedback on their performance in outpatient settings. Materials and methods: Attitudes and practices of 330 physicians on antibiotics prescription were evaluated using a validated questionnaire in 2014 in Mashhad, Iran. Results: 94% of physicians asserted that the prescription rate of antibiotics in Iran is higher than the global average. Physicians noted that “patients’ tendency to prescribe antibiotics“ is the primary reason of excessive prescription of antibiotics. Approximately, 84% of physicians were keen on receiving performance feedback. More than 71% of participants specified Short Message Service (SMS) notification as their preferred medium for receiving feedback. Conclusions: The dominant viewpoint of physicians was that the rate of antibiotics prescription in Iran is larger than the global average, which can lead to adverse economic and bacterial resistance consequences. Interventions such as ‘performance feedback’ have the potential to reduce antibiotics over-prescription.
Protective effects of a standardized extract (HemoHIM) using indomethacin- and ethanol/HCl-induced gastric mucosal injury models

Abstract Context: HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia japonica Miyabe (Paeoniaceae) developed for immune regulation. HemoHIM has been investigated for its ability to enhance tissue self-renewal and stimulate immune systems. To date, studies on the protective effects of HemoHIM against gastritis and gastric ulcers have not been conducted. Objective: The protective effects of HemoHIM using models of indomethacin and ethanol/hydrochloric acid (EtOH/HCl)-induced gastric mucosal injury were investigated. Materials and methods: Rats were divided into five groups (n = 10): control, indomethacin, or EtOH/HCl groups, HemoHIM 250, 500 mg kg−1, and cimetidine 100 mg kg−1, respectively. Indomethacin (80 mg kg−1) and 60% EtOH/150 mM HCl were administered orally 1 h after the administration of samples and rats were anesthetized 3 h after induction. The lesion area (%), inhibition ratio (%), and total acidity were investigated, and tissues were histopathologically analyzed using hematoxylin and-eosin (H&E) staining. Results: HemoHIM significantly reduced gastric injury in indomethacin-induced model (250 and 500 mg kg−1; 64.30% and 67.75%, p < 0.001) compared to indomethacin group. In the EtOH/HCl-induced model, HemoHIM reduced gastric lesion (250 and 500 mg kg−1; 61.05% and 73.37%, p < 0.001) and gastric acidity (250 and 500 mg kg−1; 37.80 and 45.20 meq L−1, p < 0.001) compared to EtOH/HCl group. H&E staining of the gastric mucosa showed decreased erosion and hemorrhage in HemoHIM group compared to EtOH/HCl group. Discussion and conclusions: Based on the results, HemoHIM is potential candidate for the treatment of gastritis and gastric ulcers.
Sexually Transmitted Infections and Associated Factors in Homosexuals and Bisexuals in Granada (Spain) during the Period 2000–2015

Sexually transmitted infections (STIs) are a major public health issue. Previous research shows the vulnerability of the homosexual and bisexual population, as well as the influence of economic, political, and cultural determinants. The aim of this study was to describe the socio-demographic healthcare profile and the main risk factors associated with STIs in homosexuals and bisexuals seen at the STI clinic in Granada (Spain) during the years 2000–2015. Infection prevalences were compared between the economic crisis period (2008–2014) and the rest of the years analysed. A cross-sectional observational and analytical study was conducted by reviewing 261 clinical records of individuals with suspected or present infection. Univariate, bivariate, and multivariate analyses were performed. 91.2% of the individuals were men, and 8.8% were women, with the mean age being 28.61 (SD = 9.35, Range = 17–74) years old. The prevailing sexual orientation identity was homosexual. 94.2% were single. The main reason for consultation was HIV. Differences in prevalence were found between crisis and non-crisis years (OR = 3.91; 95% CI = 1.73–9.19). In conclusion, their profile was that of a young, single man suspecting possible HIV infection. STI prevalence was significantly higher in the years of economic recession in comparison to the rest of the years.
The importance of 12R‐lipoxygenase and transglutaminase activities in the hydration‐dependent ex vivo maturation of corneocyte envelopes

Terminally differentiated keratinocytes acquire corneocyte protein envelopes (CPE) complexed with corneocyte lipid envelopes (CLE). These two structural components of the corneocyte envelopes (CEs) undergo maturation by gaining in hydrophobicity, rigidity and surface area. Linoleoyl acylceramides are processed by 12R‐lipoxygenase (12R‐LOX) and other enzymes before transglutaminase (TG) attaches ω‐hydroxyceramides to involucrin in the CPE. Concurrently, structural proteins are cross‐linked by TG that has been activated by cathepsin D (CathD).