Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of physical and mental health conditions in Medicare-enrolled, autistic older adults

While there is emerging evidence on the prevalence of physical and mental health conditions among autistic adults, less is known about this population’s needs during older adulthood (aged 65+). We conducted a cross-sectional retrospective cohort study of 2016–2017 Medicare data to compare the prevalence of physical and mental health conditions in a national sample of autistic older adults (N = 4685) to a matched population comparison (N = 46,850) cohort. Autistic older adults had significantly greater odds of nearly all physical health conditions including epilepsy (odds ratio = 18.9; 95% confidence interval = 17.2–20.7), Parkinson’s disease (odds ratio = 6.1; 95% confidence interval = 5.3–7.0), and gastrointestinal conditions (odds ratio = 5.2; 95% confidence interval = 4.9–5.5). Most mental health conditions were more common among autistic older adults, including schizophrenia and psychotic disorders (odds ratio = 25.3; 95% confidence interval = 22.4–28.7), attention deficit disorders (odds ratio = 24.4; 95% confidence interval = 16.2–31.0), personality disorders (odds ratio = 24.1; 95% confidence interval = 17.8–32.5), and suicidality or self-inflicted injury (odds ratio = 11.1; 95% confidence interval = 8.9–13.8). Health conditions commonly associated with advanced age in the general population (e.g. osteoporosis, cognitive disorders, heart disease, cancer, cerebrovascular disease, osteoarthritis) were also significantly more common among autistic older adults. By highlighting the significant physical and mental health needs for which autistic older adults require care, our findings can inform healthcare systems, healthcare providers, and public health initiatives seeking to promote well-being in this growing population.
Different Forms of TFF2, A Lectin of the Human Gastric Mucus Barrier: In Vitro Binding Studies

Trefoil factor family 2 (TFF2) and the mucin MUC6 are co-secreted from human gastric and duodenal glands. TFF2 binds MUC6 as a lectin and is a constituent of the gastric mucus. Herein, we investigated human gastric extracts by FPLC and identified mainly high- but also low-molecular-mass forms of TFF2. From the high-molecular-mass forms, TFF2 can be completely released by boiling in SDS or by harsh denaturing extraction. The low-molecular-mass form representing monomeric TFF2 can be washed out in part from gastric mucosa specimens with buffer. Overlay assays with radioactively labeled TFF2 revealed binding to the mucin MUC6 and not MUC5AC. This binding is modulated by Ca2+ and can be blocked by the lectin GSA-II and the monoclonal antibody HIK1083. TFF2 binding was also inhibited by Me-β-Gal, but not the α anomer. Thus, both the α1,4GlcNAc as well as the juxtaperipheral β-galactoside residues of the characteristic GlcNAcα1→4Galβ1→R moiety of human MUC6 are essential for TFF2 binding. Furthermore, there are major differences in the TFF2 binding characteristics when human is compared with the porcine system. Taken together, TFF2 appears to fulfill an important role in stabilizing the inner insoluble gastric mucus barrier layer, particularly by its binding to the mucin MUC6.
Pharmacokinetics of Organic Cation Transporter 1 (OCT1) Substrates in Oct1/2 Knockout Mice and Species Difference in Hepatic OCT1-Mediated Uptake

Organic cation transporter 1 (OCT1) plays a role in hepatic uptake of drugs, affecting in vivo exposure, distinguished primarily through pharmacogenetics of the SLC22A1 gene. The role of OCT1 in vivo has not been confirmed, however, via drug–drug interactions that similarly affect exposure. In the current research, we used Oct1/2 knockout mice to assess the role of Oct1 in hepatic clearance and liver partitioning of clinical substrates and assess the model for predicting an effect of OCT1 function on pharmacokinetics in humans. Four OCT1 substrates (sumatriptan, fenoterol, ondansetron, and tropisetron) were administered to wild-type and knockout mice, and plasma, tissue, and urine were collected. Tissue transporter expression was evaluated using liquid chromatography-mass spectrometry. In vitro, uptake of all compounds in human and mouse hepatocytes and human OCT1- and OCT2-expressing cells was evaluated. The largest effect of knockout was on hepatic clearance and liver partitioning of sumatriptan (2- to 5-fold change), followed by fenoterol, whereas minimal changes in the pharmacokinetics of ondansetron and tropisetron were observed. This aligned with uptake in mouse hepatocytes, in which inhibition of uptake of sumatriptan and fenoterol into mouse hepatocytes by an OCT1 inhibitor was much greater compared with ondansetron and tropisetron. Conversely, inhibition of all four substrates was evident in human hepatocytes, in line with reported clinical pharmacogenetic data. These data confirm the role of Oct1 in the hepatic uptake of the four OCT1 substrates and elucidate species differences in OCT1-mediated hepatocyte uptake that should be considered when utilizing the model to predict effects in humans. SIGNIFICANCE STATEMENT Studies in carriers of SLC22A1 null variants indicate a role of organic cation transporter 1 (OCT1) in the hepatic uptake of therapeutic agents, although OCT1-mediated drug–drug interactions have not been reported. This work used Oct1/2 knockout mice to confirm the role of Oct1 in the hepatic clearance and liver partitioning in mice for OCT1 substrates with reported pharmacogenetic effects. Species differences observed in mouse and human hepatocyte uptake clarify limitations of the knockout model for predicting exposure changes in humans for some OCT1 substrates.
Left atrial diameter in heart failure with left ventricular preserved, mid-range, and reduced ejection fraction

Abstract Left atrial (LA) remodeling has been identified to predict atrial fibrillation (AF) and heart failure. However, the role of LA diameter (LAD) in patients with heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) remains poorly understood. A total of 142 patients including 71 subjects with AF (21 of HFpEF, 22 of HFmrEF, and 28 of HFrEF) and 71 ejection fraction (EF)-matched subjects with sinus rhythm (SR) were included in the study. Baseline characteristics and echocardiographic parameters including LAD were compared between both groups as well as among HFpEF, HFmrEF, and HFrEF. In receiver-operating characteristic (ROC) analyses, LAD predicted AF in HFpEF, HFmrEF, and HFrEF [area under the curve (AUC): 0.646; P = . 03]. LAD was negatively association with left ventricular ejection fraction while positively with Nt-proNP and left ventricular end-diastolic diameter (regression coefficient: −0.239, P = .004; regression coefficient: 0.191, P = .023; regression coefficient: 0.357, P < .001). In ROC analyses, LAD predicted HFrEF among the 3 categories (AUC: 0.629, P = .01). In the setting of HF, LAD was higher in AF than in and SR, and predicted AF. Furthermore, LAD was associated with severity of HF in HFpEF, HFmrEF, and HFrEF, and also predicted HFrEF.
The relation between circulating levels of vitamin D and parathyroid hormone in children and adolescents with overweight or obesity: Quest for a threshold

The level of serum 25-hydroxyvitamin D (25(OH)D) at which intact parathyroid hormone (iPTH) is maximally suppressed (suppression point) and below which PTH begins to rise (inflection point) has been used to define optimum 25(OH)D concentration. We aimed to study the association of circulating iPTH with 25(OH)D concentrations and to determine a 25(OH)D threshold associated with a significant iPTH suppression. This cross-sectional study was conducted on 198 boys and 180 girls, aged 6–13 years with BMI ≥ 1SD (WHO criteria) recruited from primary schools. Adjusted iPTH for BMI z-score, pubertal status, and dietary calcium was used. Nonlinear regression was used to model the relationship between 25(OH)D and iPTH and identify a suppression point for 25(OH)D at which iPTH reached a plateau. Piecewise regression analysis with a single knot for all possible values of 25(OH)D were fitted. Furthermore, 95% confidence intervals (95%CI) for those point had been calculated. The mean age (SD) of girls and boys was 9.1 (1.6) and 9.4 (1.7) years, respectively. Median 25(OH)D and iPTH were 13.8 ng/mL and 33.9 pg/mL in boys and 9.9 ng/mL and 47.8 ng/mL in girls, respectively. The equation in girls was: log-iPTH = 3.598+0.868 exp[(-0.190×25(OH)D. The point for near maximal suppression of iPTH by 25(OH)D for girls occurred at a 25(OH)D concentration of 20 ng/mL (95% CI: 7.1 to 32.2). No point of maximal suppression was found for boys. We also found a 25(OH)D threshold of 10 ng/mL (95% CI: 4.6 to 22.5) for girls (f: 9.8) by linear piecewise regression modeling of adjusted iPTH. No significant inflection point for boys was observed. In overweight/obese girls, when the concentration of 25(OH)D was higher than 20 ng/mL, an iPTH mean plateau level is reached, and when its concentrations approach 10 ng/mL, the slope of iPTH concentration has been accelerated.
Role of integrons in the proliferation of multiple drug resistance in selected bacteria occurring in poultry production

ABSTRACT 1. The increase in microbial resistance, and in particular multiple drug resistance (MDR), is an increasing threat to public health. The uncontrolled use of antibiotics and antibacterial chemotherapeutics in the poultry industry, especially in concentrations too low to cause inhibition, and the occurrence of residues in feed and in the environment play a significant role in the development of resistance among zoonotic food-borne microorganisms. 2. Determining the presence and transmission methods of resistance in bacteria is crucial for tracking and preventing antibiotic resistance. Horizontal transfer of genetic elements responsible for drug resistance is considered to be the main mechanism for the spread of antibiotic resistance. 3. Of the many well-known genetic elements responsible for horizontal gene transfer, integrons are among the most important factors contributing to multiple drug resistance. The mechanism of bacterial drug resistance acquisition through integrons is one of the essential elements of MDR prevention in animal production.
Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma.

PURPOSE Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG). PATIENTS AND METHODS In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1,100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial. RESULTS Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%. CONCLUSION The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM.
Does vaccination with 4CMenB convey protection against meningococcal serogroup B strains not predicted to be covered by MATS? A study of the UK clonal complex cc269

ABSTRACT The Meningococcal Antigen Typing System (MATS) has been developed as an hSBA surrogate to evaluate potential coverage afforded by the 4-component meningococcal serogroup B vaccine (4CMenB: Bexsero, GSK). We investigated whether the lower value of MATS coverage among invasive Meningococcus serogroup B clonal complex 269 strains from the United Kingdom (53% in 2014–2015 versus 73% in 2007–2008) reflected the lower bactericidal activity of the vaccine against these isolates. A total of 34 MATS-negative strains (31 were cc269 or closely related) were tested against pooled sera from 32 or 72 4CMenB-vaccinated infants in a serum bactericidal antibody assay in presence of human complement (hSBA). All infants had received four 4CMenB doses in the first 2 y of life. Baseline sera comprised 180 pooled samples from healthy-unvaccinated 2-month-old infants. Twenty of the 34 (59%) MATS-negative strains were killed in hSBA with titers ≥4 by pooled sera from vaccinated infants. There were 13/34 strains with hSBA titers ≥4 and at least a 4-fold rise in titer with respect to pooled baseline sera, and 10/34 with hSBA titers ≥8 and at least a 4-fold rise in titer with respect to baseline. These data confirm MATS as a conservative estimate for predicting strain coverage by 4CMenB.
Treatment of extensive alopecia areata with oral prednisolone mini-pulse regimen

Background Systemic steroids in mini doses have been reported effective in the treatment of alopecia areata. Objective To evaluate the efficacy of oral prednisolone in mini pulse regimen in the treatment of severe forms of alopecia areata. Patients and methods This open uncontrolled study was conducted at the Department of Dermatology and Medicine,LiaquatUniversityHospital,Hyderabad from June, 2007 to July, 2008. All adult patients of both genders not receiving any topical or systemic treatment were enrolled in study. Non-probability convenience technique was used for sampling. After recording personal data and short history regarding the onset, duration and treatment received; thorough cutaneous and systemic examination was done. The patients were assessed clinically and with photographs at all visits. All patients received 30 mg oral prednisolone for 3 consecutive days in a week for 6 months. They were assessed for response and side effects at monthly intervals. The post treatment follow-up was done for 6 months. The findings were recorded on close ended proforma. The data were analyzed using SPSS software version 11.0. Results Fourteen male and 8 female patients aged between 16 and 40 years (mean 25.5 years) were enrolled for study. The duration of the disease at the time of presentation was from 6 months to 10 years (mean 3.6 years). Fourteen patients had extensive alopecia of scalp, 6 alopecia totalis while 2 alopecia universalis. Eight (15.7%) patients showed excellent response and 5 (9.8%) good response. The response was satisfactory in 7 (13.7%) and unsatisfactory in 2 (3.9%) patients. Conclusion Low dose steroids in mini-pulse regimen are an effective treatment modality for treating AA.
Mortality Among Referral Patients With Hypertrophic Cardiomyopathy vs the General European Population.

Importance It is unclear whether hypertrophic cardiomyopathy (HCM) conveys excess mortality when compared with the general population. Objective To compare the survival of patients with HCM with that of the general European population. Design, Setting, and Participants Retrospective cohort study of 4893 consecutive adult patients with HCM presenting at 7 European referral centers between 1980 and 2013. The data were analyzed between April 2018 and August 2019. Main Outcomes and Measures Survival was compared using standardized mortality ratios (SMRs) calculated with data from Eurostat, stratified by study period, country, sex, and age, and using a composite end point in the HCM cohort of all-cause mortality, aborted sudden cardiac death, and heart transplant. Results Of 4893 patients with HCM, 3126 (63.9%) were male, and the mean (SD) age at presentation was 49.2 (16.4) years. During a median follow-up of 6.2 years (interquartile range, 3.1-9.8 years), 721 patients (14.7%) reached the composite end point. Compared with the general population, patients with HCM had excess mortality throughout the age spectrum (SMR, 2.0, 95% CI, 1.48-2.63). Excess mortality was highest among patients presenting prior to the year 2000 but persisted in the cohort presenting between 2006 and 2013 (SMR, 1.84; 95% CI, 1.55-2.18). Women had higher excess mortality than men (SMR, 2.66; 95% CI, 2.38-2.97; vs SMR, 1.68; 95% CI, 1.52-1.85; P < .001). Conclusions and Relevance Among patients referred to European specialty centers, HCM was associated with significant excess mortality through the life course. Although there have been improvements in survival with time, potentially reflecting improved treatments for HCM, these findings highlight the need for more research into the causes of excess mortality among patients with HCM and for better risk stratification.
The Burden of Fungal Infections in Ethiopia

The burden of severe fungal infections (FIs) is not well addressed in Ethiopia. We have estimated the burden of FIs from multiple demographic sources and by searching articles from PubMed. Opportunistic FIs were estimated using modelling and 2017 national HIV data. The burdens of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA) were estimated by using the prevalence of asthma, chronic obstructive pulmonary disease, and annual the incidence of tuberculosis. Of the 105,000,000 estimated Ethiopian population, 610,000 are thought to have HIV infection. Our estimation of HIV-related FIs were: 9900 cryptococcal meningitis (CM), 12,700 Pneumocystis jirovecii pneumonia (PCP), 76,300 oral and 56,000 oesophageal candidiasis cases. A remarkable 7,051,700 4–14-year-olds probably have tinea capitis and 1,469,000 women probably have recurrent Candida vaginitis. There were 15,200 estimated CPA cases (prevalence) and 11,500 invasive aspergillosis (IA) cases (incidence). Data are scant, but we estimated 5300 candidaemia and 800 Candida peritonitis cases. In conclusion, approximately 8% of Ethiopians suffer from FIs annually, mostly schoolchildren with tinea capitis. IA, CM and PCP are the major causes of fungal deaths. The absence of CD4 count is challenging the identification of HIV patients at risk of opportunistic FIs. There is a pressing need to improve FI diagnosis, probably including national surveillance.
Maturation of the Oral Microbiome in Caries-Free Toddlers: A Longitudinal Study

Understanding the development of the oral microbiota in healthy children is of great importance to oral and general health. However, limited data exist on a healthy maturation of the oral microbial ecosystem in children. Moreover, the data are biased by mislabeling “caries-free” populations. Therefore, we aimed to characterize the healthy salivary and dental plaque microbiome in young children. Caries-free (ICDAS [International Caries Detection and Assessment System] score 0) children (n = 119) and their primary caregivers were followed from 1 until 4 y of child age. Salivary and dental plaque samples were collected from the children at 3 time points (T1, ~1 y old; T2, ~2.5 y old; and T3, ~4 y old). Only saliva samples were collected from the caregivers. Bacterial V4 16S ribosomal DNA amplicons were sequenced using Illumina MiSeq. The reads were denoised and mapped to the zero-radius operational taxonomic units (zOTUs). Taxonomy was assigned using HOMD. The microbial profiles of children showed significant differences (P = 0.0001) over time. Various taxa increased, including Fusobacterium, Actinomyces, and Corynebacterium, while others showed significant decreases (e.g., Alloprevotella and Capnocytophaga) in their relative abundances over time. Microbial diversity and child-caregiver similarity increased most between 1 and 2.5 y of age while still not reaching the complexity of the caregivers at 4 y of age. The microbiome at 1 y of age differed the most from those at later time points. A single zOTU (Streptococcus) was present in all samples (n = 925) of the study. A large variation in the proportion of shared zOTUs was observed within an individual child over time (2% to 42% of zOTUs in saliva; 2.5% to 38% in dental plaque). These findings indicate that the oral ecosystem of caries-free toddlers is highly heterogeneous and dynamic with substantial changes in microbial composition over time and only few taxa persisting across the 3 y of the study. The salivary microbiome of 4-y-old children is still distinct from that of their caregivers.
The use of blended learning to facilitate critical thinking in entry level occupational therapy students

The popularity of using online instruction (both in blended and complete distance learning) in higher education settings is increasing (Appana, 2008; Newton, 2006; Oh, 2006). Occupational therapy educators are using blended learning methods under the assumption that this learning platform will facilitate in their students the required level of clinical reasoning skills necessary for optimum health care delivery. Since the use of a blended learning model is becoming popular as a method to teach occupational therapy students, it is very important to evaluate its efficacy in supporting clinical reasoning skills. The purpose of this mixed methods study design was to determine how and to what extent the uses of blended learning formats facilitate clinical reasoning skills in occupational therapy students. A total of 48 occupational therapy students participated in the blended learning course, with only 24 of them completing preand post survey of the California Critical Thinking Test and the Health Sciences Reasoning Test. Results indicate that the blended learning model does facilitate clinical reasoning skills; however, further research is needed to determine if the students are able to generalize their learning to a clinic setting.