Miracle-dz/UniFAR-FTUs huggingface dataset:
Out-of-pocket health spending among Medicare beneficiaries: Which chronic diseases are most costly?

Background Little is known about the impact of different types of chronic diseases on older adults’ out-of-pocket healthcare spending and whether certain diseases trigger higher spending needs than others. Methods We use data from the 2014 Health and Retirement Study representing a weighted population of 35,939,270 Medicare beneficiaries aged 65+. Generalized linear models are applied to estimate the effect of different chronic diseases on total out-of-pocket expenditure, adjusted for demographics, socio-economic status, physical health, and other factors. We also decompose total spending by expenditure categories (inpatient, non-inpatient, and prescription drug spending). Sensitivity analysis is performed using a younger sample of older adults aged 50–64. Results Cardiovascular disease, diabetes, hypertension and cancer, induce significantly higher adjusted out-of-pocket spending among older adults than other conditions. These results hold regardless how the spending differences are assessed (absolute or percentage terms). For Medicare beneficiaries, cardiovascular disease is associated with an excess out-of-pocket spending of $317 per year, followed by diabetes ($237), hypertension ($150), and cancer ($144). Prescription drug spending is singularly the most important driver of additional expenses for cardiovascular disease, diabetes and hypertension, while non-inpatient services spending accounts for the bulk of increased spending among those with cancer. Conclusions Our finding that major noncommunicable diseases impact individuals’ out-of-pocket medical spending differentially–and that service drivers of increased spending may be heterogeneous across disease types–suggest that health professionals and policymakers should recognize that certain chronic diseases exert greater financial toll on the elderly. Interventions to promote more cost efficient healthcare services and consumer choices can help older adults better cope with these expensive long-lasting conditions and reduce the overall burden of noncommunicable diseases.
Electrochemical Polymerization of PEDOT–Graphene Oxide–Heparin Composite Coating for Anti-Fouling and Anti-Clotting of Cardiovascular Stents

In this study, a novel hemocompatible coating on stainless steel substrates was prepared by electrochemically copolymerizing 3,4-ethylenedioxythiophene (EDOT) with graphene oxide (GO), polystyrene sulfonate (PSS), or heparin (HEP) on SUS316L stainless steel, producing an anti-fouling (anti-protein adsorption and anti-platelet adhesion) surface to avoid the restenosis of blood vessels. The negative charges of GO, PSS, and HEP repel negatively charged proteins and platelets to achieve anti-fouling and anti-clotting. The results show that the anti-fouling capability of the poly(3,4-ethylenedioxythiophene) (PEDOT)/PSS coating is similar to that of the PEDOT/HEP coating. The anti-fouling capability of PEDOT/GO is higher than those of PEDOT/HEP and PEDOT/PSS. The reason for this is that GO exhibits negatively charged functional groups (COO−). The highest anti-fouling capability was found with the PEDOT/GO/HEP coating, indicating that electrochemical copolymerization of PEDOT with GO and HEP enhances the anti-fouling capability. Furthermore, the biocompatibility of the PEDOT coatings was tested with 3T3 cells for 1–5 days. The results show that all PEDOT composite coatings exhibited biocompatibility. The blood clotting time (APTT) of PEDOT/GO/HEP was prolonged to 225 s, much longer than the 40 s of pristine SUS316L stainless steel (the control), thus greatly improving the anti-blood-clotting capability of cardiovascular stents.
The Role of Supportive Food Environments to Enable Healthier Choices When Eating Meals Prepared Outside the Home: Findings from Focus Groups of 18 to 30-Year-Olds

Young adults are the highest consumers of food prepared outside home, which has been linked to weight gain. The aim of this qualitative research was to gather opinions from young adults about what influences their food choice when eating out and if they so desired, what might enable healthy choices. Thirty-one adults aged 18 to 30 years participated in four focus groups (females = 24). Predetermined questions were used to guide discussions which were audiotaped then transcribed. The content was organized into themes and sub-themes using NVivo software. Two broad groupings arose—personal behaviors and changes to physical and social food environments. For many, eating out was viewed as a special occasion so that healthy food was not a priority and despite understanding health consequences of poor diets this was not an immediate concern. Price discounts and menu-labelling were suggested and trust in credible organizations and peers’ endorsement of meals and venues expressed. The role of smartphones in the modern food environment emerged as a tool to enable immediate access to many restaurants to order food and access reviews and social media as a source of persuasive food imagery. Current menu-labelling initiatives should continue, food pricing be explored and influence of smartphones on diet further researched. However, these findings may be limited by the high proportion of women and higher socioeconomic status and urban residence of many participants.
Analysis of Orthologous SECONDARY WALL-ASSOCIATED NAC DOMAIN1 (SND1) Promotor Activity in Herbaceous and Woody Angiosperms

SECONDARY WALL-ASSOCIATED NAC DOMAIN1 (SND1) is a master regulator of fibre secondary wall deposition in Arabidopsis thaliana (Arabidopsis), with homologs in other angiosperms and gymnosperms. However, it is poorly understood to what extent the fibre-specific regulation of the SND1 promoter, and that of its orthologs, is conserved between diverged herbaceous and woody lineages. We performed a reciprocal reporter gene analysis of orthologous SND1 promoters from Arabidopsis (AthSND1), Eucalyptus grandis (EgrNAC61) and Populus alba × P. grandidentata (PagWND1A) relative to secondary cell wall-specific Cellulose Synthase4 (CesA4) and CesA7 promoters, in both a non-woody (Arabidopsis) and a woody (poplar) system. β-glucuronidase (GUS) reporter analysis in Arabidopsis showed that the SND1 promoter was active in vascular tissues as previously reported and showed interfascicular and xylary fibre-specific expression in inflorescence stems, while reporter constructs of the woody plant-derived promoters were partial to the (pro)cambium-phloem and protoxylem. In transgenic P. tremula × P. alba plants, all three orthologous SND1 promoters expressed the GUS reporter similarly and preferentially in developing secondary xylem, ray parenchyma and cork cambium. Ours is the first study to reciprocally test orthologous SND1 promoter specificity in herbaceous and woody species, revealing diverged regulatory functions in the herbaceous system.
Deployment, suicide, and overdose among comorbidity phenotypes following mild traumatic brain injury: A retrospective cohort study from the Chronic Effects of Neurotrauma Consortium

Mild traumatic brain injury in the Veteran population is frequently comorbid with pain, post-traumatic stress disorder, and/or depression. However, not everyone exposed to mild traumatic brain injury experiences these comorbidities and it is unclear what factors contribute to this variability. The objective of this study was to identify comorbidity phenotypes among Post-9/11 deployed Veterans with no or mild traumatic brain injury and examine the association of comorbidity phenotypes with adverse outcomes. We found that Veterans with mild traumatic brain injury (n = 93,003) and no brain injury (n = 434,378) were mean age of 32.0 (SD 9.21) on entering Department of Veterans Health Administration care, were predominantly Caucasian non-Hispanic (64.69%), and served in the Army (61.31%). Latent class analysis revealed five phenotypes in each subcohort; Moderately Healthy and Mental Health phenotypes were common to both. The Healthy phenotype was found only in no brain injury. Unique phenotypes in mild traumatic brain injury included Moderately Healthy+Decline, Polytrauma, and Polytrauma+Improvement. There was substantial variation in adverse outcomes. The Polytrauma+Improvement phenotype had the lowest likelihood of adverse outcomes. There were no differences between Moderately Healthy+Decline and Polytrauma phenotypes. Phenotypes of comorbidity vary significantly by traumatic brain injury status including divergence in phenotypes (and outcomes) over time in the mild traumatic brain injury subcohort. Understanding risk factors for the divergence between Polytrauma vs. Polytrauma+Improvement and Moderately Healthy vs. Moderately Healthy+Decline, will improve our ability to proactively mitigate risk, better understand the early patterns of comorbidity that are associated with neurodegenerative sequelae following mild traumatic brain injury, and plan more patient-centered care.
Molecular Characterization of Equine Staphylococcus aureus Isolates Exhibiting Reduced Oxacillin Susceptibility

The detection of borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a challenge to both, veterinary and human laboratories. Between 2015 and 2017, 19 equine S. aureus with elevated minimal inhibitory concentrations for oxacillin were detected in routine diagnostics. The aim of this study was to characterize these isolates to identify factors possibly associated with the BORSA phenotype. All S. aureus were subjected to antimicrobial susceptibility testing and whole genome sequencing (WGS). A quantifiable β-lactamase activity assay was performed for a representative subset of 13 isolates. The WGS data analysis of the 19 BORSA isolates identified two different genomic lineages, sequence type (ST) 1 and ST1660. The core genome multilocus sequence typing (cgMLST) revealed a close relatedness of all isolates belonging to either ST1 or ST1660. The WGS analysis identified the resistance genes aadD, dfrG, tet(L), and/or blaZ and aacA-aphD. Phenotypic resistance to penicillins, aminoglycosides, tetracyclines, fluoroquinolones and sulfamethoxazole/trimethoprim was observed in the respective isolates. For the penicillin-binding proteins 1–4, amino acid substitutions were predicted using WGS data. Since neither transglycosylase nor transpeptidase domains were affected, these alterations might not explain the BORSA phenotype. Moreover, β-lactamase activity was found to be associated with an inducible blaZ gene. Lineage-specific differences regarding the expression profiles were noted.
Exploration of icariin analog structure space reveals key features driving potent inhibition of human phosphodiesterase-5

The natural product icariin inhibits human phosphodiesterase-5 (PDE5) and represents a unique pharmacophore for treating erectile dysfunction, pulmonary hypertension, and other diseases. In this study, we explore the available icariin-derived chemical scaffolds through medicinal chemistry to develop novel icariin PDE5 inhibitors with improved potency and specificity. We synthesized six novel semi-synthetic icariin analogs as well as three naturally occurring icariin analogs, and characterized the structure-activity relationship in the context of human PDE5 inhibition using in vitro enzyme inhibition and kinetics assays and molecular modeling. Mammalian-cell-based assays and in vitro enzyme inhibition assays against human PDE6C further helped to identify the most potent and selective icariin analogs. Our results reveal the synergistic contribution of functional groups at the C3 and C7 positions of the icariin backbone towards PDE5 inhibition. Whereas a hydrophobic and flexible alkanol group at the C7 position is sufficient to enhance icariin analog potency, combining this group with a hydrophilic sugar group at the C3 position leads to further enhancement of potency and promotes specificity towards PDE5 versus PDE6C. In particular, compounds 3 and 7 exhibit Ki values of 0.036 ± 0.005 μM and 0.036 ± 0.007 μM towards PDE5 respectively, which are approaching those of commercial PDE5 inhibitors, and can effectively reduce GMP levels in cultured human BJ-hTERT cells. This study identifies novel icariin analogs as potent and selective PDE5 inhibitors poised to become lead compounds for further pharmaceutical development.
Tick Bites Induce Anti-α-Gal Antibodies in Dogs

Due to the functional inactivation of the gene encoding for the enzyme that is involved in the oligosaccharide galactose-α-1,3-galactose (α-Gal) synthesis, humans and Old-World primates are able to produce a large amount of antibodies against the glycan epitope. Apart from being involved in the hyperacute organ rejection in humans, anti-α-Gal antibodies have shown a protective effect against some pathogenic agents and an implication in the recently recognized tick-induced mammalian meat allergy. Conversely, non-primate mammals, including dogs, have the ability to synthetize α-Gal and, thus, their immune system is not expected to naturally generate the antibodies toward this self-antigen molecule. However, in the current study, we detected specific IgG, IgM, and IgE antibodies to α-Gal in sera of clinically healthy dogs by an indirect enzyme-linked immunosorbent assay (ELISA) for the first time. Furthermore, in a tick infestation experiment, we showed that bites of Ixodes ricinus induce the immune response to α-Gal in dogs and that the resulting antibodies (IgM) might be protective against Anaplasma phagocytophilum. These findings may help lead to a better understanding of the underlying mechanisms involved in mammalian meat allergy and tick-host-pathogen interactions, but they also open up the question about the possibility that dogs could develop an allergy to mammalian meat after tick bites, similar to that in humans.
The Evaluation of Glioblastoma Cell Dissociation and Its Influence on Its Behavior

Purpose: Primary cell lines are a valuable tool for evaluation of tumor behavior or sensitivity to anticancer treatment and appropriate dissociation of cells could preserve genomic profile of the original tissue. The main aim of our study was to compare the influence of two methods of glioblastoma multiforme (GBM) cell derivation (mechanic—MD; enzymatic—ED) on basic biological properties of thus derived cells and correlate them to the ones obtained from stabilized GBM cell line A-172. Methods: Cell proliferation and migration (xCELLigence Real-Time Cell Analysis), expression of microRNAs and protein markers (RT-PCR and Western blotting), morphology (phase contrast and fluorescent microscopy), and accumulation of temozolomide (TMZ) and its metabolite 5-aminoimidazole-4-carboxamide (AIC) inside the cells (LC-MS analysis) were carried out in five different samples of GBM (GBM1, GBM2, GBM32, GBM33, GBM34), with each of them processed by MD and ED types of isolations. The same analyses were done in the A-172 cell line too. Results: Primary GBM cells obtained by ED or MD approaches significantly differ in biological behavior and properties of these cells. Unlike in primary MD GBM cells, higher proliferation, as well as migration, was observed in primary ED GBM cells, which were also associated with the acquired mesenchymal phenotype and higher sensitivity to TMZ. Finally, the same analyses of stabilized GBM cell line A-172 revealed several important differences in measured parameters. Conclusions: GBM cells obtained by MD and ED dissociation show considerable heterogeneity, but based on our results, MD approach should be the preferred method of primary GBM cell isolation
Subjective Health Literacy among School-Aged Children: First Evidence from Lithuania

Health literacy as a set of competencies to promote and sustain health has received significant research attention, particularly in studies on adults. Improving health literacy at an early age is crucial to personal health and development, so there is a need to investigate the health literacy of school-aged children. The aims of this study were to determine the level of subjective health literacy among adolescents in Lithuania and to examine the association between health literacy, school achievement, health education in schools, and family affluence. Health literacy was assessed using a brief Health Literacy for School-Aged Children instrument on a representative sample of 2369 subjects (from the 7th to 10th grades). Overall, 12.1% of all respondents had low, 70.5% moderate, and 17.4% a high level of health literacy. School achievements were found to be a significant predictor of health literacy, as were the number of school-based health promotion events. Family affluence also predicted an increased level of health literacy. This study was the first nationally representative examination of this topic in Lithuania and it highlighted the alarming finding that less than one-fifth of adolescents had high health literacy.
Geographical Patterning of Physical Activity Prevalence in Iran: Spatial Analysis of 4 Pooled National Health Surveys Among 119,560 Adults.

BACKGROUND To investigate the geographical distribution of physical activity (PA) prevalence among adults aged 15-64 years old across Iran provinces using geographic maps. METHODS Data from 4 consecutive national surveys conducted between 2007 and 2010 were pooled to determine the geographical distribution. Prevalence of low PA with 95% confidence interval was estimated by sociodemographic subpopulations over provinces using complex survey design. RESULTS In total, 119,560 participants (49.9% females) were included in the analyses. The mean (SD) age of participants was 39.5 (14.3) years. The prevalence of the low PA in the pooled 2007-2010 was 35.8% (95% confidence interval, 34.1-37.6). The 3 provinces with the highest prevalence of low PA were Sistan and Baluchestan, Yazd, and Hormozgan. The results of hot spot analysis showed that the Kerman province was a hot spot, and Ilam, Kermanshah, Hamedan, and Markazi were cold spots for low PA. Ilam, Kohgiluyeh and Boyer-Ahmad, and Mazandaran had the highest total PA volume (metabolic equivalent minutes per week). Hot spot analysis showed that Ilam and Khuzestan provinces were hot spots for the total PA volume. CONCLUSIONS The regions with low and high PA are predominately situated in the near center/southeast and west, respectively.
Exogenous Expression of an Alternative Splicing Variant of Myostatin Prompts Leg Muscle Fiber Hyperplasia in Japanese Quail

Myostatin (MSTN) negatively regulates muscle growth and development through inhibiting myoblast proliferation and differentiation. Five alternative splicing isoforms of MSTN (MSTN-A to MSTN-E) have been discovered in domestic avian species. MSTN-A has high expression in skeletal muscle and encodes the full-length peptide with anti-myogenic activity. Another isoform, MSTN-B, is also highly expressed in skeletal muscle and encodes a truncated peptide that has pro-myogenic capabilities in vitro, which include promoting the proliferation and differentiation of quail muscle precursor cells. The objective of this study was to investigate overexpression of MSTN-B in vivo by using two independent lines of transgenic Japanese quail with expression directed in the skeletal muscle. Unexpectedly, the chicken skeletal muscle alpha actin 1 (cACTA1) promoter resulted in restricted exogenous MSTN-B protein expression to certain skeletal muscles, such as the gastrocnemius and tibialis anterior, but not the pectoralis major muscle. Gastrocnemius weight as a percentage of body weight in transgenic quail was increased compared to non-transgenic quail at posthatch day 21 (D21) and posthatch D42. An increase in the size of the gastrocnemius in transgenic quail was attributed to an increase in fiber number but not fiber cross-sectional area (CSA). During embryonic development, paired box 7 (PAX7) expression was prolonged in the transgenic embryos, but other myogenic regulatory factors (MRFs) were unchanged after MSTN-B overexpression. Taken together, these data provide novel insights into the regulation of skeletal muscle development by alternative splicing mechanisms in avians.
Single-Cell Analysis of CD4 T Cells in Type 1 Diabetes: From Mouse to Man, How to Perform Mechanistic Studies

Type 1 diabetes is the prototypical CD4 T cell–mediated autoimmune disease. Its genetic linkage to a single polymorphism at position 57 of the HLA class II DQβ chain makes it unique to study the molecular link between HLA and disease. However, investigating this relationship has been limited by a series of anatomical barriers, the small size and dispersion of the insulin-producing organ, and the scarcity of appropriate techniques and reagents to interrogate antigen-specific CD4 T cells both in man and rodent models. Over the past few years, single-cell technologies, paired with new biostatistical methods, have changed this landscape. Using these tools, we have identified the first molecular link between MHC class II and the onset of type 1 diabetes. The translation of these observations to man is within reach using similar approaches and the lessons learned from rodent models.
GSK-3 modulates SHH-driven proliferation in postnatal cerebellar neurogenesis and medulloblastoma

ABSTRACT Cerebellar development requires regulated proliferation of cerebellar granule neuron progenitors (CGNPs). Inadequate CGNP proliferation causes cerebellar hypoplasia whereas excessive CGNP proliferation can cause medulloblastoma, the most common malignant pediatric brain tumor. Although sonic hedgehog (SHH) signaling is known to activate CGNP proliferation, the mechanisms downregulating proliferation are less defined. We investigated CGNP regulation by GSK-3, which downregulates proliferation in the forebrain, gut and breast by suppressing mitogenic WNT signaling in mouse. In striking contrast to these systems, we found that co-deleting Gsk3a and Gsk3b blocked CGNP proliferation, causing severe cerebellar hypoplasia. The GSK-3 inhibitor CHIR-98014 similarly downregulated SHH-driven proliferation. Transcriptomic analysis showed activated WNT signaling and upregulated Cdkn1a in Gsk3a/b-deleted CGNPs. Ctnnb co-deletion increased CGNP proliferation and rescued cerebellar hypoproliferation in Gsk3a/b mutants, demonstrating physiological control of CGNPs by GSK-3, mediated through WNT. SHH-driven medulloblastomas similarly required GSK-3, as co-deleting Gsk3a/b blocked tumor growth in medulloblastoma-prone SmoM2 mice. These data show that a GSK-3/WNT axis modulates the developmental proliferation of CGNPs and the pathological growth of SHH-driven medulloblastoma. The requirement for GSK-3 in SHH-driven proliferation suggests that GSK-3 may be targeted for SHH-driven medulloblastoma therapy. Summary: WNT signaling must be suppressed by GSK-3 to permit SHH-driven postnatal cerebellar neurogenesis and medulloblastoma tumor growth, indicating that GSK-3 may be targeted as a novel therapy for SHH-driven medulloblastoma.