Miracle-dz/UniFAR-FTUs huggingface dataset:
National Expansion of Sleep Telemedicine for Veterans: The TeleSleep Program.

STUDY OBJECTIVES (1) Review the prevalence and comorbidity of sleep disorders among United States military personnel and veterans. (2) Describe the status of sleep care services at Veterans Health Administration (VHA) facilities. (3) Characterize the demand for sleep care among veterans and the availability of sleep care across the VHA. (4) Describe the VA TeleSleep Program that was developed to address this demand. METHODS PubMed and Medline databases (National Center for Biotechnology Information, United States National Library of Medicine) were searched for terms related to sleep disorders and sleep care in United States military and veteran populations. Information related to the status of sleep care services at VHA facilities was provided by clinical staff members at each location. Additional data were obtained from the VA Corporate Data Warehouse. RESULTS Among United States military personnel, medical encounters for insomnia increased 372% between 2005-2014; encounters for obstructive sleep apnea (OSA) increased 517% during the same period. The age-adjusted prevalence of sleep disorder diagnoses among veterans increased nearly 6-fold between 2000-2010; the prevalence of OSA more than doubled in this population from 2005-2014. CONCLUSIONS Most VA sleep programs are understaffed for their workload and have lengthy wait times for appointments. The VA Office of Rural Health determined that the dilemma of limited VHA sleep health care availability and accessibility might be solved, at least in part, by implementing a comprehensive telehealth program in VA medical facilities. The VA TeleSleep Program is an expansion of telemedicine services to address this need, especially for veterans in rural or remote regions.
Multi-Sensor Fusion Approach for Improving Map-Based Indoor Pedestrian Localization

The interior space of large-scale buildings, such as hospitals, with a variety of departments, is so complicated that people may easily lose their way while visiting. Difficulties in wayfinding can cause stress, anxiety, frustration and safety issues to patients and families. An indoor navigation system including route planning and localization is utilized to guide people from one place to another. The localization of moving subjects is a critical-function component in an indoor navigation system. Pedestrian dead reckoning (PDR) is a technology that is widely employed for localization due to the advantage of being independent of infrastructure. To improve the accuracy of the localization system, combining different technologies is one of the solutions. In this study, a multi-sensor fusion approach is proposed to improve the accuracy of the PDR system by utilizing a light sensor, Bluetooth and map information. These simple mechanisms are applied to deal with the issue of accumulative error by identifying edge and sub-edge information from both Bluetooth and the light sensor. Overall, the accumulative error of the proposed multi-sensor fusion approach is below 65 cm in different cases of light arrangement. Compared to inertial sensor-based PDR system, the proposed multi-sensor fusion approach can improve 90% of the localization accuracy in an environment with an appropriate density of ceiling-mounted lamps. The results demonstrate that the proposed approach can improve the localization accuracy by utilizing multi-sensor data and fulfill the feasibility requirements of localization in an indoor navigation system.
HSP-Target of Therapeutic Agents in Sepsis Treatment

Sepsis is a syndrome characterized by a dysregulated inflammatory response, cellular stress, and organ injury. Sepsis is the main cause of death in intensive care units worldwide, creating need for research and new therapeutic strategies. Heat shock protein (HSP) analyses have recently been developed in the context of sepsis. HSPs have a cytoprotection role in stress conditions, signal to immune cells, and activate the inflammatory response. Hence, HSP analyses have become an important focus in sepsis research, including the investigation of HSPs targeted by therapeutic agents used in sepsis treatment. Many therapeutic agents have been tested, and their HSP modulation showed promising results. Nonetheless, the heterogeneity in experimental designs and the diversity in therapeutic agents used make it difficult to understand their efficacy in sepsis treatment. Therefore, future investigations should include the analysis of parameters related to the early and late immune response in sepsis, HSP localization (intra or extracellular), and time to the onset of treatment after sepsis. They also should consider the differences in experimental sepsis models. In this review, we present the main results of studies on therapeutic agents in targeting HSPs in sepsis treatment. We also discuss limitations and possibilities for future investigations regarding HSP modulators.
Mirrors Can Affect Growth Rate, Blood Profile, Carcass and Meat Traits and Caecal Microbial Activity of Rabbits Reared in a “Small Group” Free-Range System

Simple Summary The rabbit farming sector is going through a difficult period. The reduction in the consumption of rabbit meat and the increased attention paid by consumers to the welfare of farmed animals require the adoption of farming methods that are as “natural” as possible and at the same time may ensure the maintenance of good growth performance. In this sense, free-range breeding on the ground and in colonies allows the rabbits to express more natural behaviour, but it also presents some negative aspects such as decreased growth performance, higher energy expenditure of subjects due to a higher locomotion activity, and the need for a larger rearing space. Mirrors can represent a valid solution by improving the rabbits welfare and at the same time ensuring good growth performance and carcass quality traits. Abstract The aim of this work was to propose a model of free-range raising for rabbit able to maximize the animal welfare and at the same time the productive performances through the use of mirrors. A total of 81 rabbits were allocated into free-range areas and divided into three groups (nine replicates per group): in the first group (face to face, F2F), the rabbits of each replicate could see each other. In the second group (blind) each replicate was isolated from the others; in the third group (mirrors), the replicates were divided as for the Blind group but two mirrors were placed in a corner of the perimeter. The blind group rabbits showed the lowest final weight (p < 0.05), while rabbits from the mirrors groups showed the best FCR and net dressing out values. The blind group showed the highest production of total short chain fatty acids, acetate (p < 0.05) and propionate (p < 0.01). The F2F rabbits showed higher levels of creatine phosphokinase and lactate dehydrogenase and lower values of blood glucose than those of the other groups, due to the higher locomotion activity. The use of mirrors can improve rabbit’s growth performance and carcass traits by lowering the rabbit’s locomotion activity in comparison to the other tested systems.
Prognostic Value of Variant Histology in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Systematic Review and Meta-Analysis.

PURPOSE This systematic review and meta-analysis aimed to assess the prognostic value of variant histology in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy. MATERIAL AND METHODS The PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in May 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Studies were deemed eligible if they compared overall, cancer-specific, and recurrence-free survival in UTUC patients with and without variant histology. Formal meta-analyses were performed for these outcomes. RESULTS The review identified 32 studies with 16,052 patients, including 26 studies and 12,865 patients that were eligible for the meta-analysis. Variant histology was associated with poor outcomes in terms of cancer-specific survival (pooled hazard ratio [HR]: 2.00, 95% confidence interval [CI]: 1.57-2.56), overall survival (pooled HR: 1.76, 95% CI: 1.51-2.04), and recurrence-free survival (pooled HR: 1.64, 95% CI: 1.42-1.89). Subgroup analyses revealed that 'micropapillary' and 'squamous and/or glandular' variant histology were also associated with poor cancer-specific survival (pooled HR: 3.02, 95% CI: 1.71-5.34, and pooled HR: 1.48, 95% CI: 1.14-1.92, respectively). CONCLUSIONS Variant histology in patients with UTUC is associated with an increased risk of cancer-specific mortality, overall mortality, and disease recurrence. Furthermore, variant histology was independently associated with cancer-specific survival in the 'micropapillary' and 'squamous and/or glandular' variant histology subgroups. It might be useful to incorporate variant histology into prognostic tools that help guide patients and physicians in selecting appropriate treatment strategies for UTUC.
Automatic Regularization of TomoSAR Point Clouds for Buildings Using Neural Networks

Tomographic SAR (TomoSAR) is a remote sensing technique that extends the conventional two-dimensional (2-D) synthetic aperture radar (SAR) imaging principle to three-dimensional (3-D) imaging. It produces 3-D point clouds with unavoidable noise that seriously deteriorates the quality of 3-D imaging and the reconstruction of buildings over urban areas. However, existing methods for TomoSAR point cloud processing notably rely on data segmentation, which influences the processing efficiency and denoising performance to a large extent. Inspired by regression analysis, in this paper, we propose an automatic method using neural networks to regularize the 3-D building structures from TomoSAR point clouds. By changing the point heights, the surface points of a building are refined. The method has commendable performance on smoothening the building surface, and keeps a precise preservation of the building structure. Due to the regression mechanism, the method works in a high automation level, which avoids data segmentation and complex parameter adjustment. The experimental results demonstrate the effectiveness of our method to denoise and regularize TomoSAR point clouds for urban buildings.
Heparanase accelerates obesity-associated breast cancer progression.

Obese women have higher risk of bearing breast tumors which are highly aggressive and resistant to therapies. Tumor-promoting effects of obesity occur locally via adipose inflammation and related alterations to the extracellular matrix (ECM) as well as systemically via circulating metabolic mediators (e.g. free fatty acids, FFA) associated with excess adiposity and implicated in toll-like receptor-mediated activation of macrophages - key cellular players in obesity-related cancer progression. While the contribution of macrophages to pro-neoplastic effects of obesity is well-documented, the role of ECM components and their enzymatic degradation is less appreciated. We show that heparanase, the sole mammalian endoglucuronidase that cleaves heparan sulfate in ECM, is preferentially expressed in clinical/experimental obesity-associated breast tumors. Heparanase deficiency abolished obesity-accelerated tumor progression in vivo. Heparanase orchestrated a complex molecular program which occurred concurrently in adipose and tumor tissue, and sustained the cancer-promoting action of obesity. Heparanase was required for adipose tissue macrophages (atM) to produce inflammatory mediators responsible for local induction of aromatase, a rate-limiting enzyme in estrogen biosynthesis. Estrogen upregulated heparanase in hormone-responsive breast tumors. In subsequent stages, elevated levels of heparanase induced acquisition of pro-cancerous phenotype by tumor-associated macrophages (TAM), resulting in activation of tumor-promoting signaling and acceleration of breast tumor growth under obese conditions. As techniques to screen for heparanase expression in tumors become available, these findings provide rational and a mechanistic basis for designing anti-heparanase approaches to uncouple obesity and breast cancer in a rapidly growing population of obese patients.
Selenium Nanoparticles as an Efficient Nanomedicine for the Therapy of Huntington's Disease.

Huntington's disease (HD) is an incurable disease with progressive loss of neural function, which is influenced by epigenetic, oxidative stress, metabolic, and nutritional factors. Targeting inhibition of huntingtin protein aggregation is a strategy for HD therapy, but the efficacy is unsatisfactory. Studies found that selenium (Se) levels in the brain is insufficient for HD disease, while improvement in Se homeostasis in the brain may attenuate neuronal loss and dysfunction. In this study, we applied selenium nanoparticles (NPs) (Nano-Se) for the HD disease therapy by regulating HD-related neurodegeneration and cognitive decline based on transgenic HD models of Caenorhabditis elegans (C. elegans). At low dosages, Nano-Se NPs significantly reduced neuronal death, relieved behavioral dysfunction, and protected C. elegans from damages in stress conditions. Molecular mechanism also revealed that Nano-Se attenuated oxidative stress, inhibited the aggregation of huntingtin proteins, and down regulated the expression of histone deacetylase family members at mRNA levels. The results suggested that Nano-Se has great potential for Huntington's disease therapy. In conclusion, mechanism about how Nano-Se NPs protect from damages in stress conditions and repair neural functions will benefit to HD disease therapy. This study will also guide rational design of Nano-Se NPs or other selenium compounds to improve HD therapy in the future.
Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications

Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of CYP4 genes cause inter-individual variations in metabolism and disease susceptibility. Genetic variants of CYP4A11, 4F2 genes are associated with cardiovascular diseases. Mutations of CYP4B1, CYP4Z1, and other CYP4 genes that generate 20-HETE are a potential risk for cancer. CYP4V2 gene variants are associated with ocular disease, while those of CYP4F22 are linked to skin disease and CYP4F3B is associated with the inflammatory response. The present study comprehensively collected research to provide an updated view of the molecular functionality of CYP4 genes and their associations with human diseases. Functional analysis of CYP4 genes with clinical implications is necessary to understand inter-individual variations in disease susceptibility and for the development of alternative treatment strategies.
Production Strategies for Pentamer-Positive Subviral Dense Bodies as a Safe Human Cytomegalovirus Vaccine

Infections with the human cytomegalovirus (HCMV) are associated with severe clinical manifestations in children following prenatal transmission and after viral reactivation in immunosuppressed individuals. The development of an HCMV vaccine has long been requested but there is still no licensed product available. Subviral dense bodies (DB) are immunogenic in pre-clinical models and are thus a promising HCMV vaccine candidate. Recently, we established a virus based on the laboratory strain Towne that synthesizes large numbers of DB containing the pentameric protein complex gH/gL/UL128-131 (Towne-UL130repΔGFP). The work presented here focuses on providing strategies for the production of a safe vaccine based on that strain. A GMP-compliant protocol for DB production was established. Furthermore, the DB producer strain Towne-UL130rep was attenuated by deleting the UL25 open reading frame. Additional genetic modifications aim to abrogate its capacity to replicate in vivo by conditionally expressing pUL51 using the Shield-1/FKBP destabilization system. We further show that the terminase inhibitor letermovir can be used to reduce infectious virus contamination of a DB vaccine by more than two orders of magnitude. Taken together, strategies are provided here that allow for the production of a safe and immunogenic DB vaccine for clinical testing.
Effects of replacement of para-grass with oil palm compounds on body weight, food intake, nutrient digestibility, rumen functions and blood parameters in goats

Objective The aim of the present study was to investigate the beneficial effects of dietary supplementation with oil palm frond (leaf) (OPF) with and without oil palm meal (OPM) on nutrient intake and digestibility, ruminal fermentation and growth performance in goats. Methods Six female crossbred goats were fed for 28 days of 3 diet treatments; 100% para-grass (T1); 50% para-grass + 50% OPF (T2), and 30% para-grass + 50% OPF + 20% OPM (T3). Body weight, rectal temperature, respiratory rate, and urine volume, food intake, dry matter intake and water intake were measured daily. Nutrient digestibility was determined from five consecutive days of last week in each diet. Ruminal fluid, urine and blood were collected at the end for determination of rumen protozoa and volatile fatty acid contents, urinary allantoin excretion, blood cell count and chemistry profiles. Results Goats fed T2 and T3 showed higher dry matter and nutrients intakes while protein digestibility was suppressed compared with those for T1. Crude fat digestibility declined in T2 but maintained after adding the OPM (T3). High fat intake by giving OPF and OPM corresponded to a higher ruminal acetate/propionate ratio (C2/C3) and serum cholesterol level. An increased urinary allantoin/creatinine ratio was found in T2 and T3 compared with T1, implying an increased number of ruminal microbes. Conclusion Increased dry matter intake in T2 and T3 suggested that oil palm by-products are partly useful as a replacement for para-grass in goats. Replacement with the by-products increased plasma cholesterol level, which suggested that these products are a useful energy source. Changes in rumen parameters suggested an increased microbial number and activity suitable for acetate production. However, the limited digestibility of protein implies that addition of high protein feeds may be recommended to increase body weight gain of goats.
Structural Insights into the Interaction of Cytochrome P450 3A4 with Suicide Substrates: Mibefradil, Azamulin and 6′,7′-Dihydroxybergamottin

Human cytochrome P450 3A4 (CYP3A4) is the most important drug-metabolizing enzyme. Some drugs and natural compounds can act as suicide (mechanism-based) inactivators of CYP3A4, leading to unanticipated drug-drug interactions, toxicity and therapeutic failures. Despite significant clinical and toxicological implications, the mechanism-based inactivation remains incompletely understood. This study provides the first direct insights into the interaction of CYP3A4 with three suicide substrates: mibefradil, an antihypertensive drug quickly withdrawn from the market; a semi-synthetic antibiotic azamulin; and a natural furanocoumarin, 6′,7′-dihydroxybergamottin. Novel structural findings help better understand the suicide substrate binding and inhibitory mechanism, and can be used to improve the predictability of the binding ability, metabolic sites and inhibitory/inactivation potential of newly developed drugs and other chemicals relevant to public health.
TeoNAM: A Nested Association Mapping Population for Domestication and Agronomic Trait Analysis in Maize

Recombinant inbred lines (RILs) are an important resource for mapping genes controlling complex traits in many species. While RIL populations have been developed for maize, a maize RIL population with multiple teosinte inbred lines as parents has been lacking. Here, we report a teosinte nested association mapping (TeoNAM) population, derived from crossing five teosinte inbreds to the maize inbred line W22. The resulting 1257 BC1S4 RILs were genotyped with 51,544 SNPs, providing a high-density genetic map with a length of 1540 cM. On average, each RIL is 15% homozygous teosinte and 8% heterozygous. We performed joint linkage mapping (JLM) and a genome-wide association study (GWAS) for 22 domestication and agronomic traits. A total of 255 QTL from JLM were identified, with many of these mapping near known genes or novel candidate genes. TeoNAM is a useful resource for QTL mapping for the discovery of novel allelic variation from teosinte. TeoNAM provides the first report that PROSTRATE GROWTH1, a rice domestication gene, is also a QTL associated with tillering in teosinte and maize. We detected multiple QTL for flowering time and other traits for which the teosinte allele contributes to a more maize-like phenotype. Such QTL could be valuable in maize improvement.
Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer

Purpose: Androgen receptor (AR)-targeting prostate cancer drugs, which are predominantly competitive ligand-binding domain (LBD)-binding antagonists, are inactivated by common resistance mechanisms. It is important to develop next-generation mechanistically distinct drugs to treat castration- and drug-resistant prostate cancers. Experimental Design: Second-generation AR pan antagonist UT-34 was selected from a library of compounds and tested in competitive AR binding and transactivation assays. UT-34 was tested using biophysical methods for binding to the AR activation function-1 (AF-1) domain. Western blot, gene expression, and proliferation assays were performed in various AR-positive enzalutamide-sensitive and -resistant prostate cancer cell lines. Pharmacokinetic and xenograft studies were performed in immunocompromised rats and mice. Results: UT-34 inhibits the wild-type and LBD-mutant ARs comparably and inhibits the in vitro proliferation and in vivo growth of enzalutamide-sensitive and -resistant prostate cancer xenografts. In preclinical models, UT-34 induced the regression of enzalutamide-resistant tumors at doses when the AR is degraded; but, at lower doses, when the AR is just antagonized, it inhibits, without shrinking, the tumors. This indicates that degradation might be a prerequisite for tumor regression. Mechanistically, UT-34 promotes a conformation that is distinct from the LBD-binding competitive antagonist enzalutamide and degrades the AR through the ubiquitin proteasome mechanism. UT-34 has a broad safety margin and exhibits no cross-reactivity with G-protein–coupled receptor kinase and nuclear receptor family members. Conclusions: Collectively, UT-34 exhibits the properties necessary for a next-generation prostate cancer drug.
Endophytic bacteria as contributors to theanine production in Camellia sinensis.

Theanine is the most abundant non-protein amino acid in Camellia sinensis, but it is not known how tea plant accumulates such high levels of theanine. The endophyte isolated from in vitro grown plantlets of C. sinensis cultivars were identified as Luteibacter spp. , showing strong biocatalytic activity for converting both glutamine and ethylamine to theanine. The theanine was secreted outside of the bacterial. Endophyte isolated from in vitro plantlets of Camellia oleifera cultivar were identified as Bacillus safensis, not converting glutamine and ethylamine to theanine. Enzymatic assays in vitro indicated that γ-glutamyl transpeptidases rCsEGGTs from the endophyte Luteibacter strains converted glutamine and ethylamine into theanine at higher rates than rCsGGTs from C. sinensis. This is the first report on theanine biosynthesis by an endophyte from C. sinensis, which provide a new pathway to explore the mechanism of theanine biosynthesis in C. sinensis and the interactions between endophyte and tea plants.