Miracle-dz/UniFAR-FTUs huggingface dataset:
Barriers to a Timely Discharge From Short-Term Care in VA Community Living Centers

ABSTRACT This study aimed to identify the barriers to a timely discharge from short-term care in Veterans Health Administration (VHA) Community Living Centers (CLCs). Ninety-nine interviews were conducted with CLC staff in leadership and direct-care positions in eight varied CLCs. Major themes identified through qualitative analysis as barriers to a timely discharge were a lack of patients’ financial resources, low social support, and reluctance of some veterans and staff to view a timely veteran discharge as their goal. Staff also perceived that barriers were much more difficult to overcome in regions where community-based long-term services and supports were limited or nonexistent. Because VHA has lagged behind Medicaid more generally in terms of investment in these types of services, additional strategies are warranted to achieve the important policy goal of deinstitutionalizing VHA care and returning veterans to their homes in the community.
Injectable freeze‐dried chitosan‐platelet‐rich‐plasma implants improve marrow‐stimulated cartilage repair in a chronic‐defect rabbit model

Bone‐marrow stimulation (BMS) improves knee‐joint function but elicits incomplete repair. Liquid chitosan (CS)–glycerol phosphate/blood clots have been shown to improve BMS‐based cartilage repair. Platelet‐rich‐plasma (PRP)—a rich source of growth factors and cytokines—improves recruitment and chondrogenic potential of subchondral mesenchymal stem cells. We hypothesised that repair response in a rabbit chronic‐defect model will improve when freeze‐dried CS/PRP is used to augment BMS. Bilateral trochlear defects created in New Zealand white rabbits were allowed to progress to a chronic stage over 4 weeks. Chronic defects were debrided and treated by BMS in second surgery, then augmented with PRP (BMS + PRP) or freeze‐dried CS/PRP implants (BMS + CS/PRP). The quality of 8‐week repair tissue was assessed by macroscopic, histological, and micro computed tomography (Micro‐CT) analysis. ICRS macroscopic scores indicated fibrocartilaginous or fibrous repair in control defects that were improved in the BMS + CS/PRP group. An overall improvement in repair in BMS + CS/PRP group was further confirmed by higher O'Driscoll scores, %Saf‐O and %Coll‐II values. Micro‐CT analysis of subchondral bone indicated ongoing remodelling with repair still underway. Quality and quantity of cartilage repair was improved when freeze‐dried CS/PRP implants were used to augment BMS in a chronic defect model.
Quantifying between‐cohort and between‐sex genetic heterogeneity in major depressive disorder

Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between‐cohort and between‐sex heterogeneity. First, we used genome‐wide association study (GWAS) summary statistics to investigate between‐cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between‐sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD.
Disparities in the Global Burden of Age-Related Macular Degeneration: An Analysis of Trends from 1990 to 2015

ABSTRACT Purpose: The purpose of this study was to evaluate the disparities in burden of disease of age-related macular degeneration (AMD) in terms of disability-adjusted life years (DALYs). Method: This is an international, database observational study. The DALYs due to AMD were retrieved from the 2015 Global Burden of Disease study. The human development index (HDI) and gross domestic product (GDP) per capita across countries were obtained from the 2016 Human Development Report and the World Bank. Other related data were obtained from the World Health Organization and United Nations. Results: A total of 195 countries were included in this study. From 1990 to 2015, the AMD-related global DALY numbers, crude DALY rate, and age-standardized DALY rate increased by 147.66%, 78.13%, and 19.3%, respectively. Global DALY rates increased with age and females had higher DALY numbers and rates than males in each age group (all P < 0.01). The age-standardized DALY rate was positively associated with HDI and GDP per capita (P < 0.001). An analysis by HDI ordering showed substantial socioeconomic inequality, with a concentration index of 0.322 for DALY numbers, 0.472 for crude DALY rate, and 0.142 for age-standardized DALY rate, respectively. The country-wide mean body mass index (BMI), serum cholesterol concentration, alcohol consumption, physical inactivity, percent of cell phone subscribers, and urbanization rate were also significantly associated with age-standardized DALY rate. Four variables (GDP per capita, mean BMI, alcohol consumption, and urbanization rate) explained 36.48% of the variation of age-standardized DALY rate across countries. Conclusion: The global health burden of AMD is constantly increasing, implying more demand for AMD services in the coming decades. Older age, female gender, higher socioeconomic development, physical inactivity, and urbanization rate were related to higher AMD burden. These findings may raise the public concern and awareness of the global impact of AMD burden and are valuable for policy planning.
Acupuncture combined with Buyang Huanwu decoction in treatment of patients with ischemic stroke

Objective This study was performed to investigate the effect of acupuncture combined with Buyang Huanwu decoction in patients with ischemic stroke. Methods In total, 115 patients with ischemic stroke were recruited and divided into 3 groups. The control group received normal treatment, the acupuncture group received additional acupuncture treatment, and the combined group received additional acupuncture combined with Buyang Huanwu decoction treatment. The National Institutes of Health Stroke Scale (NIHSS) and Chinese Stroke Scale (CSS) were used to evaluate the stroke condition, and the Barthel index (BI) was used to measure life quality. Blood lipids and recurrence were also analyzed. Results The CSS and NIHSS scores were significantly lower in the acupuncture group and combined group than in the control group; however, the BI score was significantly higher in the acupuncture group and combined group. Similarly, the levels of cholesterol, triglycerides, and low-density lipoprotein were all significantly increased, while the level of high-density lipoprotein showed no significant difference in all groups. The recurrence rate was significantly lower in the combined group than in the other two groups. Conclusion Acupuncture combined with Buyang Huanwu decoction could improve the clinical outcomes and reduce the recurrence rates in patients with ischemic stroke.
Back to the Future for Influenza Preimmunity—Looking Back at Influenza Virus History to Infer the Outcome of Future Infections

The influenza virus-host interaction is a classic arms race. The recurrent and evolving nature of the influenza virus family allows a single host to be infected several times. Locked in co-evolution, recurrent influenza virus infection elicits continual refinement of the host immune system. Here we give historical context of circulating influenza viruses to understand how the individual immune history is mirrored by the history of influenza virus circulation. Original Antigenic Sin was first proposed as the negative influence of the host’s first influenza virus infection on the next and Imprinting modernizes Antigenic Sin incorporating both positive and negative outcomes. Building on imprinting, we refer to preimmunity as the continual refinement of the host immune system with each influenza virus infection. We discuss imprinting and the interplay of influenza virus homology, vaccination, and host age establishing preimmunity. We outline host signatures and outcomes of tandem infection according to the sequence of virus and classify these relationships as monosubtypic homologous, monosubtypic heterologous, heterosubtypic, or heterotypic sequential infections. Finally, the preimmunity knowledge gaps are highlighted for future investigation. Understanding the effects of antigenic variable recurrent influenza virus infection on immune refinement will advance vaccination strategies, as well as pandemic preparedness.
Adaptive Sliding Mode Control of MEMS Gyroscope Based on Neural Network Approximation

An adaptive sliding controller using radial basis function (RBF) network to approximate the unknown system dynamics microelectromechanical systems (MEMS) gyroscope sensor is proposed. Neural controller is proposed to approximate the unknown system model and sliding controller is employed to eliminate the approximation error and attenuate the model uncertainties and external disturbances. Online neural network (NN) weight tuning algorithms, including correction terms, are designed based on Lyapunov stability theory, which can guarantee bounded tracking errors as well as bounded NN weights. The tracking error bound can be made arbitrarily small by increasing a certain feedback gain. Numerical simulation for a MEMS angular velocity sensor is investigated to verify the effectiveness of the proposed adaptive neural control scheme and demonstrate the satisfactory tracking performance and robustness.
Output Feedback Stabilization of Networked Control Systems Under a Stochastic Scheduling Protocol

This paper investigates the output feedback stabilization problem for networked control systems under a stochastic scheduling protocol. First, an independent and identically distributed (i.i.d) scheduling protocol is introduced to orchestrate the signal transmission via a communication network. Taking into account the i.i. d protocol, network-induced delay, and packet dropout, a stochastic impulsive delayed model is presented for the studied system. Second, by use of the Lyapunov–Krasovskii functional approach, sufficient conditions for guaranteeing the stability of the studied system in the mean-square sense are obtained in the form of matrix inequalities. Moreover, an optimization algorithm is investigated to obtain the suitable dynamic output feedback controller and optimal i.i. d protocol parameters simultaneously. Finally, two numerical examples are presented to show the validity of the proposed method.
Effects of micro/nano strontium-loaded surface implants on osseointegration in ovariectomized sheep.

BACKGROUND Poor osseointegration of dental implants often occurs in osteoporotic patients and processed implant surfaces could help to improve the dilemma. PURPOSE This study aimed to compare the effects of different titanium (Ti) surfaces on bone-implant osseointegration in ovariectomized (OVX) sheep. MATERIALS AND METHODS Four groups were included: smooth titanium (ST) was merely polished Ti; micro titanium (MT) was treated with hydrofluoric acid (HF) for 30 minutes; strontium-loaded nano titanium (NT-Sr) was formed by magnetron sputtering; strontium-loaded micro/nano titanium (MNT-Sr) was fabricated by HF etching combined with magnetron sputtering. The biological responses were evaluated by human bone marrow-derived mesenchymal stem cells (hBMMSCs) experiments in vitro. Osseointegration was evaluated in vivo after each surface implant was inserted into OVX sheep' mandibles. RESULTS The numbers of adhered and mineralized hBMMSCs increased significantly in the MNT-Sr group. The bone-implant contact and the maximal pull-out force increased significantly with MNT-Sr surface. The bone volume ratio and trabecular number of the MNT-Sr group were significantly higher than others, whereas trabecular separation decreased. CONCLUSIONS These results indicated that an MNT-Sr surface promotes the differentiation of hBMMSCs in vitro and enhances bone-implant osseointegration in vivo, which may be a promising option for clinical implants in osteoporotic patients.
The development and prevalidation of an in vitro mutagenicity assay based on MutaMouse primary hepatocytes, Part II: Assay performance for the identification of mutagenic chemicals

As demonstrated in Part I, cultured MutaMouse primary hepatocytes (PHs) are suitable cells for use in an in vitro gene mutation assay due to their metabolic competence, their “normal” phenotype, and the presence of the MutaMouse transgene for reliable mutation scoring. The performance of these cells in an in vitro gene mutation assay is evaluated in this study, Part II. A panel of 13 mutagenic and nonmutagenic compounds was selected to investigate the performance of the MutaMouse PH in vitro gene mutation assay. The nine mutagens represent a range of classes of chemicals and include mutagens that are both direct‐acting and requiring metabolic activation. All the mutagens tested, except for ICR 191, elicited significant, concentration‐dependent increases in mutant frequency (MF) ranging from 2.6‐ to 14.4‐fold over the control. None of the four nonmutagens, including two misleading, or “false,” positives (i.e., tertiary butylhydroquinone [TBHQ] and eugenol), yielded any significant increases in MF. The benchmark dose covariate approach facilitated ranking of the positive chemicals from most (i.e., 3‐nitrobenzanthrone [3‐NBA], benzo[a]pyrene [BaP], and aflatoxin B1 [AFB1]) to least (i.e., N‐ethyl‐N‐nitrosourea [ENU]) potent. Overall, the results of this preliminary validation study suggest that this assay may serve as a complimentary tool alongside the standard genotoxicity test battery. This study, alongside Part I, illustrates the promise of MutaMouse PHs for use in an in vitro gene mutation assay, particularly for chemicals requiring metabolic activation. Environ. Mol. Mutagen. 60:348–360, 2019. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.
Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study

Abstract Background (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand. Methods In this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients. Results Of 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= −0.74, standard error [SE] = 0.16, P = 3.44 ×10–6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10–6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele. Conclusions Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies. Clinical Trials Registation NCT01401400.
Apomorphine‐Induced Immune Hemolytic Anemia

Since the first description of drug-induced immune hemolytic anemia (DIIHA), more than 130 drugs have been reported to cause this adverse hematologic effect. L-dopa was the first dopaminergic drug to be directly related to DIIHA. The involvement of other dopaminergic drugs has been suggested, including the dopamine agonists cabergoline and apomorphine, although very few confirmed cases have been published.
Ethanol-Mediated Compaction and Crosslinking Enhance Mechanical Properties and Degradation Resistance While Maintaining Cytocompatibility of a Nucleus Pulposus Scaffold

Intervertebral disc degeneration is a complex, cell-mediated process originating in the nucleus pulposus (NP) and is associated with extracellular matrix catabolism leading to disc height loss and impaired spine kinematics. Previously, we developed an acellular bovine NP (ABNP) for NP replacement that emulated human NP matrix composition and supported cell seeding; however, its mechanical properties were lower than those reported for human NP. To address this, we investigated ethanol-mediated compaction and crosslinking to enhance the ABNP’s dynamic mechanical properties and degradation resistance while maintaining its cytocompatibility. First, volumetric and mechanical effects of compaction only were confirmed by evaluating scaffolds after various immersion times in buffered 28% ethanol. It was found that compaction reached equilibrium at ∼30% compaction after 45 min, and dynamic mechanical properties significantly increased 2-6x after 120 min of submersion. This was incorporated into a crosslinking treatment, through which scaffolds were subjected to 120 min pre-compaction in buffered 28% ethanol prior to carbodiimide crosslinking. Their dynamic mechanical properties were evaluated before and after accelerated degradation by ADAMTS-5 or MMP-13. Cytocompatibility was determined by seeding stem cells onto scaffolds and evaluating viability through metabolic activity and fluorescent staining. Compacted and crosslinked scaffolds showed significant increases in DMA properties without detrimentally altering their cytocompatibility, and these mechanical gains were maintained following enzymatic exposure.
An Insect Counteradaptation against Host Plant Defenses Evolved through Concerted Neofunctionalization

Abstract Antagonistic chemical interactions between herbivorous insects and their host plants are often thought to coevolve in a stepwise process, with an evolutionary innovation on one side being countered by a corresponding advance on the other. Glucosinolate sulfatase (GSS) enzyme activity is essential for the Diamondback moth, Plutella xylostella, to overcome a highly diversified secondary metabolite-based host defense system in the Brassicales. GSS genes are located in an ancient cluster of arylsulfataselike genes, but the exact roles of gene copies and their evolutionary trajectories are unknown. Here, we combine a functional investigation of duplicated insect arylsulfatases with an analysis of associated nucleotide substitution patterns. We show that the Diamondback moth genome encodes three GSSs with distinct substrate spectra and distinct expression patterns in response to glucosinolates. Contrary to our expectations, early functional diversification of gene copies was not indicative of a coevolutionary arms race between host and herbivore. Instead, both copies of a duplicated arylsulfatase gene evolved concertedly in the context of an insect host shift to acquire novel detoxifying functions under positive selection, a pattern of duplicate gene retention that we call “concerted neofunctionalization. ”
Providing a parent-implemented language intervention to a young male with fragile X syndrome: Brief Report

Abstract Purpose: Although fragile X syndrome (FXS) is the leading inherited cause of intellectual disability, there are no published intervention studies focused on improving communication and language outcomes for affected children. The current study utilized a collaborative coaching approach incorporating strategies from speech-language pathology and applied behavior analysis to examine the efficacy of a naturalistic parent-implemented language intervention for a young boy with FXS. Methods: The mother was taught the language and behavioral support strategies and submitted weekly video recordings of a caregiving routine. Written feedback was provided. Results: Results indicated moderate increases in maternal use of targeted language support strategies and variable performance in maternal use of behavior support strategies. Child use of appropriate requests increased while challenging behaviors decreased. Conclusions: This collaborative approach model should be used to guide future larger scale replications and develop new intervention models.
A Geographic Cline of Skull and Brain Morphology among Individuals of European Ancestry

Background: Human skull and brain morphology are strongly influenced by genetic factors, and skull size and shape vary worldwide. However, the relationship between specific brain morphology and genetically-determined ancestry is largely unknown. Methods: We used two independent data sets to characterize variation in skull and brain morphology among individuals of European ancestry. The first data set is a historical sample of 1,170 male skulls with 37 shape measurements drawn from 27 European populations. The second data set includes 626 North American individuals of European ancestry participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with magnetic resonance imaging, height and weight, neurological diagnosis, and genome-wide single nucleotide polymorphism (SNP) data. Results: We found that both skull and brain morphological variation exhibit a population-genetic fingerprint among individuals of European ancestry. This fingerprint shows a Northwest to Southeast gradient, is independent of body size, and involves frontotemporal cortical regions. Conclusion: Our findings are consistent with prior evidence for gene flow in Europe due to historical population movements and indicate that genetic background should be considered in studies seeking to identify genes involved in human cortical development and neuropsychiatric disease.