Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of primary care structures with polypharmacy and patient-reported indicators in patients with complex multimorbidity: a multicentre cross-sectional study in Japan

Objectives Evidence supporting the effects of primary care structures on the quality of care for patients with complex multimorbidity, which is one of the most important challenges facing primary care, is scarce internationally. This study aimed to examine the associations of the types of primary care facilities with polypharmacy and patient-reported indicators in patients with complex multimorbidity, with a focus on differences between community clinics and hospitals. Design Multicentre cross-sectional study. Setting A total of 25 primary care facilities (19 community clinics and 6 small- and medium-sized hospitals). Participants Adult outpatients with complex multimorbidity, which was defined as the co-occurrence of three or more chronic conditions affecting three or more different body systems within one person. Primary outcome measure Polypharmacy, the Patient-Reported Experience Measure using the Japanese version of Primary Care Assessment Tool Short Form (JPCAT-SF) and the Patient-Reported Outcome Measure using self-rated health status (SRH). Results Data were analysed for 492 patients with complex multimorbidity. After adjustment for possible confounders and clustering within facilities, clinic-based primary care practices were significantly associated with a lower prevalence of polypharmacy, higher JPCAT-SF scores in coordination and community orientation, and a lower prevalence of poor or fair SRH compared with hospital-based primary care practices. In contrast, the JPCAT-SF score in first contact was significantly lower in clinic-based practices. The associations between the types of primary care facilities and JPCAT-SF scores in longitudinality and comprehensiveness were not statistically significant. Conclusions Clinic-based primary care practices were associated with a lower prevalence of polypharmacy, better patient experience of coordination and community orientation, and better SRH in patients with complex multimorbidity compared with hospital-based primary care practices. In the primary care setting, small and tight teams may improve the quality of care for patients with complex multimorbidity.
Exocyst stimulates each step of exocytic SNARE complex assembly and vesicle fusion

The exocyst is a large multisubunit tethering complex essential for targeting and fusion of secretory vesicles in eukaryotic cells. Although the assembled exocyst complex is proposed to tether vesicles to the plasma membrane and activate the SNARE proteins for membrane fusion, only little is known about the key biochemical steps that exocyst stimulates in the course of SNARE complex assembly, a critical question defining the essential molecular role of the exocyst complex. Here, we use a combination of single molecule and bulk fluorescence assays with purified octameric yeast exocyst complexes to examine the role of exocyst in a reconstituted SNARE assembly and fusion system. We show that the exocyst complex simulates multiple steps spanning from SNARE protein activation to ternary complex assembly, rather than affecting only a specific subset of steps. We also observed that the exocyst has important downstream roles in driving membrane fusion, up to full content mixing of vesicle lumens. Our results suggest that the exocyst complex provides extensive chaperoning functions for the entire process of SNARE complex assembly, presumably using its multi-faceted structure provided by the eight subunits.
Novel ADAMTSL4 gene mutations in Chinese patients with isolated ectopia lentis

Background To characterise the phenotype and genetic defects of isolated ectopia lentis (IEL) and to determine the ADAMTSL4 gene mutation frequencies in a Chinese congenital ectopia lentis (CEL) cohort. Methods In total, 127 Chinese probands with a clinical CEL diagnosis were recruited for this study and underwent ocular and systemic examinations. Whole-exome sequencing was used to detect variants, and Sanger sequencing and bioinformatics analysis verified the pathogenic mutations. Results Overall, biallelic mutations in ADAMTSL4, involving 8 novel ADAMTSL4 mutations (c.21–2A>G, c.1174G>C, c.2169C>A, c.2236C>T, c.2263delG, c.2397C>A, c.2488dupC and c.2935T>C) were identified in 5 probands (5/127, 3.94%) with IEL. Additionally, four patients had combined congenital cataracts, and two patients had ectopia lentis et pupillae (ELP). One of eight mutations was a homozygous missense mutation, and the other seven mutations were compound heterozygous. These eight consisted of three missense (37.5%), three frameshift (37.5%), one stop-gain (12.5%) and one spicing mutation (12.5%). These mutations co-segregated with the IEL, and the substitution of amino acids greatly affected conserved residues. Most of the novel mutations were located in the thrombospondin type 1 (TSP1) domain, which ultimately alters the structure of the ADAMTSL4 protein. Conclusions This study reported five IEL probands with eight novel mutations in the ADAMTSL4 gene. The clinical IEL phenotypes caused by these mutations were variable and complex. This study thus establishes the ADAMTSL4 gene mutation frequency and expands the gene’s mutation spectrum to help recognise ADAMTSL4-related IEL clinical manifestations.
Glycemic outcomes among rural patients in the type 1 diabetes T1D Exchange registry, January 2016–March 2018: a cross-sectional cohort study

Introduction Does rural status influence glycemic outcomes among participants in the type 1 diabetes T1D Exchange clinic registry? Research design and methods Data from the T1D Exchange clinic registry between January 2016 and March 2018 were identified by rural–urban status and stratified by age and hemoglobin A1c (HbA1c). Multivariable regression modeling was performed to isolate HbA1c differences. A full model including all significant (p<0.05 via two-sided testing) differential factors was determined with an additional indicator for rural status, and adjusted for duration of diabetes, use of continuous glucose monitoring device, age, race/ethnicity, and private insurance status. The model was reduced using backwards elimination stepwise procedures until only significant factors remained. Results Mean HbA1c levels for all rural participants were significantly higher (8.71%; 72 mmol/mol) compared with the urban group (8.48%; 69 mmol/mol), p<0.001. For youth under 13 years of age, rural participants had a higher mean HbA1c (8.65%; 71 mmol/mol) compared with urban (8.45% 69 mmol/mol), p=0.022. Rural youth (13–<18 years) had a higher mean HbA1c (9.39%; 79 mmol/mol) than urban youth (9.14%; 76 mmol/mol), p<0.001. Rural young adults (18–<26 years) had a higher mean HbA1c (9.07%; 76 mmol/mol) than urban young adults (8.88%; 74 mmol/mol), p=0.042. Rural adults (≥26 years; n=589) were the only group that did not have a higher mean HbA1c (7.76%, 61.3 mmol) than urban adults (n=4770; 7.72%, 60.9 mmol/mol), p=0.503. Rural locale was highly significant (beta=0.175, p<0.001) despite controlling for potentially confounding differences between rural and urban groups. Conclusions Among this T1D Exchange cohort, there is a pattern of higher mean HbA1c being associated with rural status, even after adjustment for characteristic differences, most strikingly among those under 26 years of age. This disparity and contributing factors need to be more thoroughly studied to provide effective solutions.
Factors Affecting Online Chinese as a Foreign Language Learning Stickiness: A Study on International Students in China

This study explored international students’ online Chinese as a foreign language learning stickiness in a Chinese university context. A new theoretical model was designed and verified to serve the mixed-method investigation. Participants were a group of 194 international students learning CFL online in a Chinese university. Data were collected through an online questionnaire for all the students and semi-structural individual interviews with eight volunteer participants. The structural equation modeling was conducted to analyze the collected quantitative data, and content analysis was used for the qualitative interview. Findings revealed that the online learning stickiness was significantly impacted by students’ learning expectancy confirmation, which was closely correlated with three key factors: academic integration, social integration, and technological factors. Moreover, social integration was found to be a direct contributor to learning stickiness. These results highlighted the importance of the high quality of the curriculum, the harmonious learning atmosphere, and the need for technical preparations and training for online Chinese language teaching and learning. The study also emphasized the need of integrating social interaction into Chinese learning in an online context. Investigation of a wider range of Chinese learners was recommended for future studies on learning stickiness and the new online approach.
Platelet Mitochondrial DNA Methylation as Epigenetic Biomarker of Short-Term Air Pollution Exposure in Healthy Subjects

Air pollution exposure is now considered a growing concern for global public health. RNA or DNA methylation changes caused by air pollution may be related to the development of cardiovascular disease. To investigate the early biomarkers of air pollution exposure, a panel study of eight college students recorded after a business trip from Qingdao to Shijiazhuang and back to Qingdao was performed in this work. The concentration of PM2.5, PM10, SO2, NO2, and CO in Shijiazhuang was higher than that in Qingdao during the study period. The platelet count was positively correlated with air pollutants of 0–6 day moving averages (βPM2.5 = 88.90; βPM10 = 61.83; βSO2 = 41.13; βNO2 = 57.70; βCO = 62.99, respectively, for an IQR increased). Additionally, internal dose biomarkers 2-OHNa, 1-OHNa, 2-OHFlu, 2,3-OHPhe, and ∑PAHs were also significantly associated with platelet count in participants. Furthermore, PM2.5 and PM10 are positively linked with methylation of one CpG site at platelet mitochondrial gene CO2 (PM2.5 = 0.47; PM10 = 0.25, respectively, for an IQR increase). Both platelet counts and methylation levels returned to their pre-exposure levels after leaving the highly contaminated area. In short, this study investigated the relationship between platelet properties and air pollution exposure, revealing that short-term exposure to air pollution might increase the risk of thrombosis. Our research suggests that platelet count and mitochondrial DNA methylation of mtCO2 site 2 in platelets from healthy adults may be the novel biomarker for acute exposure to air pollution.
FangTianSim: High-Level Cycle-Accurate Resistive Random-Access Memory-Based Multi-Core Spiking Neural Network Processor Simulator

Realization of spiking neural network (SNN) hardware with high energy efficiency and high integration may provide a promising solution to data processing challenges in future internet of things (IoT) and artificial intelligence (AI). Recently, design of multi-core reconfigurable SNN chip based on resistive random-access memory (RRAM) is drawing great attention, owing to the unique properties of RRAM, e.g., high integration density, low power consumption, and processing-in-memory (PIM). Therefore, RRAM-based SNN chip may have further improvements in integration and energy efficiency. The design of such a chip will face the following problems: significant delay in pulse transmission due to complex logic control and inter-core communication; high risk of digital, analog, and RRAM hybrid design; and non-ideal characteristics of analog circuit and RRAM. In order to effectively bridge the gap between device, circuit, algorithm, and architecture, this paper proposes a simulation model—FangTianSim, which covers analog neuron circuit, RRAM model and multi-core architecture and its accuracy is at the clock level. This model can be used to verify the functionalities, delay, and power consumption of SNN chip. This information cannot only be used to verify the rationality of the architecture but also guide the chip design. In order to map different network topologies on the chip, SNN representation format, interpreter, and instruction generator are designed. Finally, the function of FangTianSim is verified on liquid state machine (LSM), fully connected neural network (FCNN), and convolutional neural network (CNN).
The Role of Brain-Derived Neurotrophic Factor in Obstructive Sleep Apnea and Endothelial Function in a Pediatric Population With Obesity

Background Childhood obesity has increased worldwide, becoming a significant public health concern. Brain-derived neurotrophic factor (BDNF) plays an important role in the central regulation of food intake and body weight, but little is known regarding its role in childhood obesity. Next to obesity, BDNF has been linked to obstructive sleep apnea (OSA) and endothelial dysfunction, two obesity-related comorbidities. The aim of this study is to investigate how BDNF, OSA and endothelial dysfunction interact in children with obesity and to determine the effect of weight loss on serum BDNF levels. Methods Children and adolescents with obesity aged 8–18 years who were enrolled in a multidisciplinary obesity treatment (MOT) in a tertiary hospital, were prospectively included. Several examinations were conducted during this MOT; at baseline, after 6 months and after 12 months, including the assessment of endothelial function, body composition measurements and a polysomnography. BDNF levels were measured on a serum sample by means of ELISA. Results A total of 103 patients with obesity was included, of which 20 had OSA (19.4%). BDNF levels were comparable in children with obesity and OSA and children with obesity but without OSA (26.75 vs. 27.87 ng/ml, p = 0.6). No correlations were found between BDNF and sleep-related variables or between BDNF and endothelial function parameters nor between BDNF and adiposity measures. To investigate if the interaction between OSA and endothelial dysfunction had an influence on BDNF levels, a general linear model was used. This model revealed that a diagnosis of OSA, as well as the interaction between OSA and maximal endothelial dilatation, contributed significantly (p = 0.03, p = 0.04, respectively) to BDNF levels. After 1 year of weight loss therapy, BDNF levels did not change (26.18 vs. 25.46 ng/ml, p = 0.7) in our population. Conclusion BDNF concentrations were comparable in children with obesity, both with and without OSA, indicating that BDNF levels are not affected by OSA. However, we did find an interaction effect of OSA and endothelial function on BDNF levels.
Human Umbilical Cord Mesenchymal Stem Cells Improve Locomotor Function in Parkinson’s Disease Mouse Model Through Regulating Intestinal Microorganisms

Parkinson’s disease (PD) is a progressive neurological disorder characterized by loss of neurons that synthesize dopamine, and subsequent impaired movement. Umbilical cord mesenchymal stem cells (UC-MSCs) exerted neuroprotection effects in a rodent model of PD. However, the mechanism underlying UC-MSC-generated neuroprotection was not fully elucidated. In the present study, we found that intranasal administration of UC-MSCs significantly alleviated locomotor deficits and rescued dopaminergic neurons by inhibiting neuroinflammation in a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, a toxic agent which selectively destroys nigrostriatal neurons but does not affect dopaminergic neurons elsewhere). Furthermore, UC-MSC treatment altered gut microbiota composition characterized by decreased phylum Proteobacteria, class Gammaproteobacteria, family Enterobacteriaceae, and genus Escherichia-Shigella. In addition, the neurotransmitter dopamine in the striatum and 5-hydroxytryptamine in the colon were also modulated by UC-MSCs. Meanwhile, UC-MSCs significantly maintained intestinal goblet cells, which secrete mucus as a mechanical barrier against pathogens. Furthermore, UC-MSCs alleviate the level of TNF-α and IL-6 as well as the conversion of NF-κB expression in the colon, indicating that inflammatory responses were blocked by UC-MSCs. PICRUSt showed that some pathways including bacterial invasion of epithelial cells, fluorobenzoate degradation, and pathogenic Escherichia coli infection were significantly reversed by UC-MSCs. These data suggest that the beneficial effects were detected following UC-MSC intranasal transplantation in MPTP-treated mice. There is a possible neuroprotective role of UC-MSCs in MPTP-induced PD mice by cross talk between the brain and gut.
Initial Validation for the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) Hebrew Battery in Adolescents and Young Adults With Typical Development

Currently there is no validated battery to assess pragmatic abilities in Hebrew. The use of such battery has great importance, as it may provide norms to the assessment of impaired pragmatic skills across several populations, such as ASD, schizophrenia, specific learning disorders and intellectual disabilities. In order to validate the battery, the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) was translated to Hebrew. The APACS battery was previously validated and found high reliability and validity for ages 19–89 years. The battery includes six tasks, focusing on two main domains: pragmatic production and pragmatic comprehension. The assessment of pragmatic production will be conducted by the use of interview and description tasks, whereas pragmatic comprehension will be assessed by narratives, two figurative language, and humor tasks. The translated battery, APACS-Heb is currently the most comprehensive and the first validated battery for pragmatic tests in Hebrew. Forty Hebrew-speaking adolescents ages 16–20 participated in the study. All participants performed screening tests assessing vocabulary, Theory of Mind and social responsiveness. In addition, the validity and test-retest reliability of APACS-Heb were assessed. Furthermore, the effect of vocabulary, Theory of Mind and social responsiveness on performance was evaluated. High internal consistency, content validity and test-retest reliability was found for most APACS-Heb tasks and all composite scores. Furthermore, an effect of age and gender was found for most tasks with females outperformed males. In addition, a contribution of Theory of Mind to pragmatic production, pragmatic comprehension and APACS total scores was found. Lastly, a factor analysis revealed two factors, in which the first factor correlates with most tasks, and the second factor correlates only to humor. The results thus suggest that humor is a separate skill among the other pragmatic skills. In conclusion, normative data was collected for the APACS-Heb battery, and it was found that it is a valid and reliable measure of pragmatic skills. Since APACS is a comprehensive battery assessing the various aspects of figurative language, it can identify the specific deficits in figurative language and therefore may pinpoint the appropriate intervention program for each individual.
Different Rates of Bioprosthetic Aortic Valve Failure With Perimount™ and Trifecta™ Bioprostheses

Objectives The use of bioprostheses in surgical aortic valve replacement (SAVR) has increased in younger patients. Comparative analysis of different types of bioprostheses is lacking. We aimed to compare two proprietary bioprostheses with different designs, i.e., internally and externally mounted leaflets, focusing on the long-term durability and survival. Methods We conducted a large single-center retrospective analysis of all consecutive patients who underwent SAVR with either Perimount™ or Trifecta™ bioprostheses between 2001 and 2019. The patient groups were further subdivided by age <65 and >65. Endpoints of the study were all-cause mortality and reoperation due to bioprosthetic valve failure (BVF). Results Selection criteria resulted in a total sample of 5,053 patients; 2,630 received a Perimount prosthesis (internally mounted leaflets) and 2,423 received a Trifecta prosthesis (externally mounted leaflets). The mean age at surgery was similar (69 ± 11 y, PM, and 68 ± 10 y, TF, p = 0.9), as was estimated survival at 8 years (76.1 ± 1.3%, PM, and 63.7 ± 1.9% TF; p=0.133). Patients in the Trifecta group had a significantly higher cumulative reoperation rate at 8 years compared to those in the Perimount group (16.9 ± 1.9% vs. 3.8 ± 0.4%; p < 0.01). This difference persisted across age groups (<65 y, 13.3% TF vs. 8.6% PM; >65 y, 12% TF vs. 7% PM). Conclusion Bioprostheses for SAVR with externally mounted leaflets (Trifecta) showed significantly higher long-term reoperation rates compared to those with internally mounted leaflets (Perimount), regardless of the patient's age at SAVR. Survival was similar with both bioprostheses.
Association Between Korean-Style Balanced Diet and Risk of Abdominal Obesity in Korean Adults: An Analysis Using KNHANES-VI (2013–2016)

Abdominal obesity is a critical factor for metabolic diseases, and specific eating patterns such as the Mediterranean diet help prevent metabolic diseases. This study aimed to investigate the association between the modified Korean health eating index (MKHEI), including a Korean-balanced diet, and abdominal obesity risk according to genders in adults aged 20–64 years (4,886 males and 7,431 females), using the Korea National Health and Nutrition Examination Survey VI (2013–2016). Adjusted means and 95% confidence intervals of MKHEI scores and nutrient intake estimated using the 24-h recall method were calculated according to abdominal obesity (waist circumference ≥90 cm for men and ≥85 cm for women) after adjusting for age, residence area, region, education, income, drinking status, smoking status, marital status, and exercise. Adjusted odds ratios (ORs) for abdominal obesity were measured according to MKHEI tertiles using logistic regression analysis while controlling for covariates. Individuals aged >50 years, married, below high school, lower-income, heavy alcohol drinkers, past and current smokers, and males living in the southern areas had a higher risk of abdominal obesity. In both genders, the scores of all MKHEI components were lower in the abdominal obesity group (n = 2,895) than in the control group (n = 9,422). Further, the scores of fruits with and without fruit juice and those of beans, including fermented beans, were lower in the abdominal obesity group only in females but not in males. Further, the scores of fast foods were higher in the abdominal obesity group than in the control group only in females. After adjusting for covariates, the adjusted OR for abdominal obesity was inversely associated with Korean balanced diet (KBD) related to KHEI scores. Unlike KBD, MKHEI of Western-style diet was not associated with abdominal obesity in either gender. In conclusion, KBD can lower the risk of abdominal obesity in females and should thus be recommended to prevent abdominal obesity.
Development of a double gaussian wake model

Understanding the intra wind farm flow has historically been driven by the need for estimating the annual energy production. The task was addressed with a combination of simplified, static engineering wake [1] and embedding background flow models [2]. Due to its low computational cost this bottom-up concept has been widely adopted and especially the individual description of the wake allowed for continuous development and improvement of its modeling [3]. One of the most popular wake models is the Gaussian model, developed by [4].