Miracle-dz/UniFAR-FTUs huggingface dataset:
Military Factors Associated with Smoking in Veterans.

Introduction Given the high prevalence of smoking among Veterans and the economic, social, and clinical implications, it is important to understand the factors that contribute to smoking in order to focus efforts to mitigate these factors and improve smoking cessation efforts among Veterans. The availability of research on smoking in Veterans compared with civilians is limited given the military-specific differences in their life course. We aimed to identify military-specific factors combined with sociodemographic factors for ever smoking and current smoking among Veterans to inform future interventions. Materials and Methods We used data from the 2010 National Survey of Veterans, the most current, to analyze the association of sociodemographic and military-specific factors with ever versus never smoking, and current versus past smoking using multiple variable logistic regression models (IRB#4125). Results Among 8,618 respondents, the proportions of current, past, and never smokers were 17%, 48%, and 34%, respectively. Sociodemographic factors associated with ever smoking were female gender, educational attainment of less than a bachelor's degree, and being divorced/separated/widowed. Military-specific factors associated with ever smoking were exposure to dead/dying/wounded soldiers during service, and past, current, and unsure enrollment in Veterans Affairs healthcare. Never smoking was associated with Hispanic ethnicity, income over $75,000, and reporting fair or poor health. Military factors associated with never smoking were presence of a service-connected disability and military service July 1964 or earlier (i.e., pre-Vietnam). Among 5,652 ever smokers, sociodemographic factors associated with current smoking were age less than 65, being non-Hispanic black, educational attainment of less than a bachelor's degree, being divorced/separated/widowed, never married, and having no insurance. Factors associated with reduced likelihood of current smoking compared with past smoking included income >$41,000 and reporting fair or poor health. Military-specific variables associated with reduced likelihood of current smoking were service era of May 1975 or later (i.e., post-Vietnam) and 5 or more years of service. Conclusion Military-specific variables are associated with smoking behaviors among Veterans. Findings from this study that exposure to dead/dying/wounded soldiers, service era, duration of service, service-connected disability status, and enrollment in VA care all influence smoking in Veterans, can inform prevention and cessation efforts in part by encouraging alternative healthy habits or cessation techniques in subgroups of Veterans with particular military backgrounds. By assessing risk factors in this unique population future research can leverage these findings to determine mechanisms that help explain these associations. Identifying factors associated with smoking offers insights for smoking cessation and prevention interventions given the military experiences and increased smoking incidence among Veterans.
Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with bioprosthetic valves

ABSTRACT Introduction: The non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, apixaban, edoxaban and rivaroxaban, are preferred over vitamin K antagonists for stoke prevention in most patients with non-valvular atrial fibrillation. The NOACs are contraindicated in atrial fibrillation patients with rheumatic mitral stenosis or mechanical heart valves. There is evidence that bioprosthetic heart valves are less thrombogenic than mechanical heart valves, but it is unknown whether the risk of thromboembolism in atrial fibrillation patients with bioprosthetic valves differs from that in patients without such valves. Areas covered: The authors present a review of the efficacy and safety evidence surrounding the use of NOACs for stroke prevention in atrial fibrillation patients with bioprosthetic heart valves. Expert commentary: While the data is limited, there is no significant difference in thromboembolic, and bleeding outcomes in patients with AF and bioprosthetic heart valves treated with NOAC therapy. Future studies are required before definitive conclusions can be drawn regarding the safety and efficacy of NOAC therapy in AF patients bioprosthetic heart valves.
Detection of Hepatozoon canis in the Brown Dog Tick and Domestic Dogs in Peninsular Malaysia

Abstract Hepatozoon canis has been widely reported in dogs. Its prevalence in ticks, however, has not been well-established. Here we determine the occurrence of Hepatozoon DNA in the brown dog tick Rhipicephalus sanguineus (Latreille) (Acari: Ixodidae) sensu lato (s.l.) and domestic dogs from Peninsular Malaysia using a polymerase chain reaction (PCR) assay based on amplification of the 18S ribosomal RNA coding sequence. Our results revealed a relatively low prevalence of H. canis DNA in both R. sanguineus s.l. (0.7%) and dogs (3.33%). This study represents the first report of H. canis DNA in R. sanguineus s.l. in Malaysia, highlighting the risk of this infection in dogs.
Nonlinear Adaptive Backstepping Controller Design for Islanded DC Microgrids

In this paper, a nonlinear adaptive backstepping controller is designed to control the common dc-bus voltage for different components in a dc microgrid under various operating conditions. The dc microgrid in this paper comprises a solar photovoltaic (PV) unit, a battery energy storage system (BESS), a backup diesel generator, and loads (both critical and noncritical). The controllers are designed for all components except loads where the main control objective for all controllers is to maintain a constant voltage at the dc-bus where all components are connected. This paper considers solar PV systems as the renewable energy source, whereas a diesel generator equipped with a rectifier is used as a backup supply to maintain the continuity of power supply in the case of emergency situations. The proposed controller is designed recursively based on the Lyapunov control theory, where all parameters within the model of different components are considered unknown. Adaptation laws are used to estimate these unknown parameters while the stability of the dc microgrid, with these adaptation laws, is ensured through the formulation of suitable control Lyapunov functions (CLFs) at different stages of the design process. The negative definiteness or semidefiniteness of these CLFs guarantees the stability of the dc microgrid. Finally, the performance of the proposed controllers is verified using both simulations and experiments on a test dc microgrid under different operating conditions. The proposed controller ensures the regulation of the dc-bus voltage within the acceptable limits under different operating conditions.
South Indian Isolates of the Fusarium solani Species Complex From Clinical and Environmental Samples: Identification, Antifungal Susceptibilities, and Virulence

Members of the Fusarium solani species complex (FSSC) are the most frequently isolated fusaria from soil. Moreover, this complex solely affects more than 100 plant genera, and is also one of the major opportunistic human pathogenic filamentous fungi, being responsible for approximately two-third of fusariosis cases. Mycotic keratitis due to Fusarium species is among the leading causes of visual impairment and blindness in South India, but its management is still challenging due to the poor susceptibility of the isolates to conventional antifungal drugs. Aims of the present study were to isolate South Indian clinical and environmental FSSC strains and identify them to species level, to determine the actual trends in their susceptibilities to antifungal therapeutic drugs and to compare the virulence of clinical and environmental FSSC members. Based on the partial sequences of the translation elongation factor 1α gene, the majority of the isolates—both from keratomycosis and environment—were confirmed as F. falciforme, followed by F. keratoplasticum and F. solani sensu stricto. In vitro antifungal susceptibilities to commonly used azole, allylamine and polyene antifungals were determined by the CLSI M38-A2 broth microdilution method. The first generation triazoles, fluconazole and itraconazole proved to be ineffective against all isolates tested. This phenomenon has already been described before, as fusaria are intrinsically resistant to them. However, our results indicated that despite the intensive agricultural use of azole compounds, fusaria have not developed resistance against the imidazole class of antifungals. In order to compare the virulence of different FSSC species from clinical and environmental sources, a Drosophila melanogaster model was used. MyD88 mutant flies having impaired immune responses were highly susceptible to all the examined fusaria. In wild-type flies, one F. falciforme and two F. keratoplasticum strains also reduced the survival significantly. Pathogenicity seemed to be independent from the origin of the isolates.
Chitosan Microsphere Used as an Effective System to Deliver a Linked Antigenic Peptides Vaccine Protect Mice Against Acute and Chronic Toxoplasmosis

Multiple antigenic peptide (MAP) vaccines have advantages over traditional Toxoplasma gondii vaccines, but are more susceptible to enzymatic degradation. As an effective delivery system, chitosan microspheres (CS) can overcome this obstacle and act as a natural adjuvant to promote T helper 1 (Th1) cellular immune responses. In this study, we use chitosan microparticles to deliver multiple antigenic epitopes from GRA10 (G10E), containing three dominant epitopes. When G10E was entrapped within chitosan microparticles (G10E-CS), adequate peptides for eliciting immune response were loaded in the microsphere core and this complex released G10E peptides stably. The efficiency of G10E-CS was detected both in vitro, via cell culture, and through in vivo mouse immunization. In vitro, G10E-CS activated Dendritic Cells (DC) and T lymphocytes by upregulating the secretion of costimulatory molecules (CD40 and CD86). In vivo, Th1 biased cellular and humoral immune responses were activated in mice vaccinated with G10E-CS, accompanied by significantly increased production of IFN-γ, IL-2, and IgG, and decreases in IL-4, IL-10, and IgG1. Immunization with G10E-CS conferred significant protection with prolonged survival in mice model of acute toxoplasmosis and statistically significant decreases in cyst burden in murine chronic toxoplasmosis. The results from this study indicate that chitosan microspheres used as an effective system to deliver a linked antigenic peptides is a promising strategy for the development of efficient vaccine against T. gondii.
Evolution of Gustatory Receptor Gene Family Provides Insights into Adaptation to Diverse Host Plants in Nymphalid Butterflies

Abstract The host plant range of herbivorous insects is a major aspect of insect–plant interaction, but the genetic basis of host range expansion in insects is poorly understood. In butterflies, gustatory receptor genes (GRs) play important roles in host plant selection by ovipositing females. Since several studies have shown associations between the repertoire sizes of chemosensory gene families and the diversity of resource use, we hypothesized that the increase in the number of genes in the GR family is associated with host range expansion in butterflies. Here, we analyzed the evolutionary dynamics of GRs among related species, including the host generalist Vanessa cardui and three specialists. Although the increase of the GR repertoire itself was not observed, we found that the gene birth rate of GRs was the highest in the lineage leading to V. cardui compared with other specialist lineages. We also identified two taxon-specific subfamilies of GRs, characterized by frequent lineage-specific duplications and higher non-synonymous substitution rates. Together, our results suggest that frequent gene duplications in GRs, which might be involved in the detection of plant secondary metabolites, were associated with host range expansion in the V. cardui lineage. These evolutionary patterns imply that the capability to perceive various compounds during host selection was favored during adaptation to diverse host plants.
The Anti-inflammatory Effects of Short Chain Fatty Acids on Lipopolysaccharide- or Tumor Necrosis Factor α-Stimulated Endothelial Cells via Activation of GPR41/43 and Inhibition of HDACs

Background and Aim: Previously, we found that short chain fatty acids (SCFA) inhibit LPS or TNFα-induced endothelial inflammatory responses and excessive vascular cell adhesion molecule-1 (VCAM-1) expression, two important steps in the development of atherosclerosis. However, the mechanisms involved are still unclear. We hypothesized that the effects of SCFA are associated with activation of G-protein coupled receptor 41/43 (GPR41/43) and/or inhibition of histone deacetylases (HDACs). Methods: The expression and location of GPR41/43 and HDAC3 in human umbilical vein endothelial cells (HUVEC) were confirmed. HUVEC were pre-incubated with acetate, butyrate or propionate alone or in combination with GLPG0974 (GLPG, antagonist of GPR43) or β-hydroxybutyrate (SHB, antagonist of GPR41) and then exposed to LPS or TNFα. Interleukin (IL)-6 and IL-8 levels and VCAM-1 expression were measured. HDAC activity was measured after treatment with butyrate, propionate and trichostatin A (TSA, HDAC inhibitor). The peripheral blood mononuclear cell (PBMC) adhesive level was also determined after TSA treatment. Results: GPR41/43 were expressed on the membrane of HUVEC and HDAC3 was located in cytoplasm and nucleus. The GLPG and/or SHB treatments restored the inhibitory effects of acetate on IL-6 and IL-8 production and the inhibitory effects of butyrate or propionate on IL-6 production, but not on IL-8. In contrast, GLPG and/or SHB treatments did not affect the inhibitory effects of butyrate or propionate on TNFα-induced VCAM-1 expression. TSA showed similar effects on IL-8 production and VCAM-1 expression as butyrate and propionate. In addition, TSA significantly inhibited the adhesion of PBMC to an endothelial monolayer. Conclusion: Activation of GPR41/43 mediates the effects of acetate on IL-6 and IL-8 production and the effects of butyrate and propionate on IL-6 production. Furthermore, inhibition of HDACs mediates the effects of butyrate and propionate on IL-8 production, VCAM-1 expression, and PBMC adhesion to an endothelial monolayer. These data indicate the beneficial roles of SCFA in preventing vascular inflammation and relevant diseases by activation of GPR41/43 and inhibition of HDACs.
Epidemiology of cutaneous lupus erythematosus and the associated risk of systemic lupus erythematosus: a nationwide cohort study in Denmark

Objectives The objectives of this paper are to describe the epidemiology of cutaneous lupus erythematosus (CLE) and its subtypes in Denmark, and to investigate the probability of receiving a subsequent diagnosis of systemic lupus erythematosus (SLE) and the related time course. Methods A nationwide registry-based cohort study was conducted in Denmark based on data from the Danish National Patient Registry from 1998 to 2013 using International Classification of Diseases, Revision 10. Results We identified 2380 patients with CLE. The annual incidence rate (IR) of CLE was 2.74/100,000 with a female:male ratio of 4:1. During 12,047 person-years of follow-up, 8% were diagnosed with SLE. The probability of receiving a subsequent diagnosis of SLE was 12.9% after 10 years taking death as a competing risk into consideration, and the probability was highest among women and patients diagnosed with subacute CLE. The median time until a diagnosis of SLE was 2.05 years. Conclusions This is the first nationwide study on CLE in Denmark. Although we found the annual IR of CLE and the risk of receiving an additional diagnosis of SLE to be lower than previously described, continued monitoring and thorough information for patients with CLE is important due to the inherent risk of SLE.
Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Frizzled receptors (FZDs) are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs) that serve as receptors for secreted Wingless-type (WNT) ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.
Anti-microbial Antibodies, Host Immunity, and Autoimmune Disease

Autoimmune diseases are a spectrum of clinical inflammatory syndromes with circulating autoantibodies. Autoimmune diseases affect millions of patients worldwide with enormous costs to patients and society. The diagnosis of autoimmune diseases relies on the presence of autoantibodies and the treatment strategy is to suppress the immune system using specific or non-specific immunosuppressive agents. The discovery of anti-microbial antibodies in the blood of patients with Crohn's disease and Sjogren's syndrome and cross-reactivity of anti-microbial antibodies to human tissue suggests a new molecular mechanism of pathogenesis, raising the possibility of designing a new therapeutic strategy for these patients. The presence of anti-microbial antibodies indicates the failure of the innate immunity system to clear the microbial agents from the blood and activation of adaptive immunity through B-lymphocytes/plasma cells. More importantly, the specific antibodies against the microbial proteins are directed toward the commensal microbes commonly present on the surface of the human host, and these commensal microbes are important in shaping the development of the immune system and in maintaining the interaction between the human host and the environment. Persistence of these anti-microbial antibodies in patients but not in normal healthy individuals suggests abnormal interaction between the human host and the commensal microbes in the body. Elimination of the organism/organisms that elicits the antibody response would be a new avenue of therapy to investigate in patients with autoimmune diseases.
Temporal and tissue-specific variability of SMN protein levels in mouse models of spinal muscular atrophy

Abstract Spinal muscular atrophy (SMA) is a progressive motor neuron disease caused by deleterious variants in SMN1 that lead to a marked decrease in survival motor neuron (SMN) protein expression. Humans have a second SMN gene (SMN2) that is almost identical to SMN1. However, due to alternative splicing the majority of SMN2 messenger ribonucleic acid (mRNA) is translated into a truncated, unstable protein that is quickly degraded. Because the presence of SMN2 provides a unique opportunity for therapy development in SMA patients, the mechanisms that regulate SMN2 splicing and mRNA expression have been elucidated in great detail. In contrast, how much SMN protein is produced at different developmental time points and in different tissues remains under-characterized. In this study, we addressed this issue by determining SMN protein expression levels at three developmental time points across six different mouse tissues and in two distinct mouse models of SMA (‘severe’ Taiwanese and ‘intermediate’ Smn2B/− mice). We found that, in healthy control mice, SMN protein expression was significantly influenced by both age and tissue type. When comparing mouse models of SMA, we found that, despite being transcribed from genetically different alleles, control SMN levels were relatively similar. In contrast, the degree of SMN depletion between tissues in SMA varied substantially over time and between the two models. These findings offer an explanation for the differential vulnerability of tissues and organs observed in SMA and further our understanding of the systemic and temporal requirements for SMN with direct relevance for developing effective therapies for SMA.
Fine-Grained Derandomization: From Problem-Centric to Resource-Centric Complexity

We show that popular hardness conjectures about problems from the field of fine-grained complexity theory imply structural results for resource-based complexity classes. Namely, we show that if either k-Orthogonal Vectors or k-CLIQUE requires n k time, for some constant > 1/2, to count (note that these conjectures are significantly weaker than the usual ones made on these problems) on randomized machines for all but finitely many input lengths, then we have the following derandomizations: • BPP can be decided in polynomial time using only n random bits on average over any efficient input distribution, for any constant α > 0 • BPP can be decided in polynomial time with no randomness on average over the uniform distribution This answers an open question of Ball et al. (STOC ’17) in the positive of whether derandomization can be achieved from conjectures from fine-grained complexity theory. More strongly, these derandomizations improve over all previous ones achieved from worst-case uniform assumptions by succeeding on all but finitely many input lengths, as is wanted for asymptotics. Previously, derandomizations from worst-case uniform assumptions were only know to succeed on infinitely many input lengths. It is specifically the structure and moderate hardness of the k-Orthogonal Vectors and k-CLIQUE problems that makes removing this restriction possible. Via this uniform derandomization, we connect the problem-centric and resource-centric views of complexity theory by showing that exact hardness assumptions about specific problems like k-CLIQUE imply quantitative and qualitative relationships between randomized and deterministic time. This can be either viewed as a barrier to proving some of the main conjectures of fine-grained complexity theory lest we achieve a major breakthrough in unconditional derandomization or, optimistically, as route to attain such derandomizations by working on very concrete and weak conjectures about specific problems