Miracle-dz/UniFAR-FTUs huggingface dataset:
Exosomes in Pathogen Infections: A Bridge to Deliver Molecules and Link Functions

Exosomes are extracellular vesicles derived from cell endocytosis which act as transmitters between cells. They are composed of proteins, lipids, and RNAs through which they participate in cellular crosstalk. Consequently, they play an important role in health and disease. Our view is that exosomes exert a bidirectional regulatory effect on pathogen infections by delivering their content. First, exosomes containing proteins and RNAs derived from pathogens can promote infections in three ways: (1) mediating further infection by transmitting pathogen-related molecules; (2) participating in the immune escape of pathogens; and (3) inhibiting immune responses by favoring immune cell apoptosis. Second, exosomes play anti-infection roles through: (1) inhibiting pathogen proliferation and infection directly; (2) inducing immune responses such as those related to the function of monocyte-macrophages, NK cells, T cells, and B cells. We believe that exosomes act as “bridges” during pathogen infections through the mechanisms mentioned above. The purpose of this review is to describe present findings regarding exosomes and pathogen infections, and highlight their enormous potential in clinical diagnosis and treatment. We discuss two opposite aspects: infection and anti-infection, and we hypothesize a balance between them. At the same time, we elaborate on the role of exosomes in immune regulation.
Bayesian analysis of twinning and ovulation rates using a multiple-trait threshold model and Gibbs sampling.

The Multiple-Trait Gibbs Sampler for Animal Models programs were extended to allow analysis of ordered categorical data using a Bayesian threshold model. The algorithm is based on data augmentation, where a value on the unobserved underlying normally distributed variable (liability) is generated in each round of iteration for each categorical observation. The programs allow analysis of several continuous and ordered categorical traits. Categorical traits can have any number of response levels. Models can be different for each trait. The programs were used to analyze twinning and ovulation rates from a herd of cattle selected for twinning rate at the U.S. Meat Animal Research Center. Data included number of calves born at each parturition for the lifetime of a cow and number of eggs ovulated for several estrous cycles before first breeding as heifers. A total of 6,411 calvings was recorded for 2,087 cows with 83.2% single and 16.8% multiple births. A total of 19,849 ovulations was recorded for 2,332 heifers with 85.2% single and 14.8% multiple ovulations. Mean posterior estimates of heritability and fraction of variance accounted for by permanent environmental effects (PE) were . 128 and . 103 for twinning rate and . 168 and . 079 for ovulation rate. Mean posterior estimate of genetic correlation was . 808, and correlation of PE effects was . 517. Use of a threshold model could allow for more rapid genetic improvement of the twinning herd through improved identification and selection of genetically superior animals because of higher heritability on the underlying scale.
A Rare-Event Simulation Algorithm for Periodic Single-Server Queues

An efficient algorithm is developed to calculate the periodic steady-state distribution and moments of the remaining workload Wy at time yc within a cycle of length c, 0 ≤ y b) is uniformly bounded in b. With the aid of a recent heavy-traffic limit theorem, the algorithm also applies to compute the periodic steady-state distribution of (i) reflected periodic Brownian motion (RPBM) by considering appropriately scaled GIt/GI/1 models .
Step count is associated with lower nighttime systolic blood pressure and increased dipping.

BACKGROUND Higher nighttime blood pressure (BP) and the loss of nocturnal dipping of BP are associated with an increased risk for cardiovascular events. However, the determinants of the loss of nocturnal BP dipping are only beginning to be understood. We investigated whether different indicators of physical activity were associated with the loss of nocturnal dipping of BP. METHODS We conducted a cross-sectional study of 103 patients referred for 24-hour ambulatory monitoring of BP. We measured these patients' step count (SC), active energy expenditure (AEE), and total energy expenditure simultaneously, using actigraphs. RESULTS In our study population of 103 patients, most of whom were hypertensive, SC and AEE were associated with nighttime systolic BP in univariate (SC, r = -0.28, P < 0.01; AEE, r = -0.20, P = 0.046) and multivariate linear regression analyses (SC, coefficient beta = -5.37, P < 0.001; AEE, coefficient beta = -0.24, P < 0.01). Step count was associated with both systolic (r = 0.23, P = 0.018) and diastolic (r = 0.20, P = 0.045) BP dipping. Nighttime systolic BP decreased progressively across the categories of sedentary, moderately active, and active participants (125mm Hg, 116mm Hg, 112mm Hg, respectively; P = 0.002). The degree of BP dipping of BP increased progressively across the same three categories of activity (respectively 8.9%, 14.6%, and 18.6%, P = 0.002, for systolic BP and respectively 12.8%, 18.1%, and 22.2%, P = 0.006, for diastolic BP). CONCLUSIONS Step count is continuously associated with nighttime systolic BP and with the degree of BP dipping independently of 24-hour mean BP. The combined use of an actigraph for measuring indicators of physical activity and a device for 24-hour measurement of ambulatory BP may help identify patients at increased risk for cardiovascular events in whom increased physical activity toward higher target levels may be recommended.
Updates of the ITRS design cost and power models

Design cost and power/energy have been major challenges for the semiconductor industry over the past decade or more. Increase in gate count, driven by scaling of physical dimensions per Moore's Law, has dramatically increased the diversity of integrated functions and overall design complexity. To control design cost and schedule in light of limited human and computing resources, design productivity must be continually improved. The International Technology Roadmap for Semiconductors (ITRS) Design Chapter [10], which provides a design technology roadmap to inform the electronic design automation (EDA) industry and internal CAD organizations, has since 2001 maintained a design cost model that tracks implications for SOC design cost of anticipated design productivity improvements. The power/energy challenge stems from a variety of causes, e.g., high-performance functional requirements, non-ideal scaling of supply voltages, interconnect capacitances, and leakage currents. The ITRS Design Chapter has since 2009 also roadmapped low-power design technologies that address the power challenge. This paper provides an updated overview of the ITRS design cost model, as well as the low-power design technology roadmap along with associated technology solutions. Potential design technology solutions to mitigate design cost and power/energy challenges in the coming decade are also noted.
Topographic heterogeneity and temperature amplitude explain species richness patterns of birds in the Qinghai–Tibetan Plateau

Abstract Large-scale patterns of species richness have gained much attention in recent years; however, the factors that drive high species richness are still controversial in local regions, especially in highly diversified montane regions. The Qinghai–Tibetan Plateau (QTP) and the surrounding mountains are biodiversity hot spots due to a high number of endemic montane species. Here, we explored the factors underlying this high level of diversity by studying the relationship between species richness and environmental variables. The richness patterns of 758 resident bird species were summarized at the scale of 1°×1° grid cell at different taxonomic levels (order, family, genus, and species) and in different taxonomic groups (Passeriformes, Galliformes, Falconiformes, and Columbiformes). These richness patterns were subsequently analyzed against habitat heterogeneity (topographical heterogeneity and land cover), temperature amplitude (annual temperature, annual precipitation, precipitation seasonality, and temperature seasonality) and a vegetation index (net primary productivity). Our results showed that the highest richness was found in the southeastern part of the QTP, the eastern Himalayas. The lowest richness was observed in the central plateau of the QTP. Topographical heterogeneity and temperature amplitude are the primary factors that explain overall patterns of species richness in the QTP, although the specific effect of each environmental variable varies between the different taxonomic groups depending on their own evolutionary histories and ecological requirements. High species richness in the southeastern QTP is mostly due to highly diversified habitat types and temperature zones along elevation gradients, whereas the low species richness in the central plateau of the QTP may be due to environmental and energetic constraints, as the central plateau is harsh environment.
Unrecognized Cardiovascular Emergencies Among Medicare Patients

Importance The Institute of Medicine described diagnostic error as the next frontier in patient safety and highlighted a critical need for better measurement tools. Objectives To estimate the proportions of emergency department (ED) visits attributable to symptoms of imminent ruptured abdominal aortic aneurysm (AAA), acute myocardial infarction (AMI), stroke, aortic dissection, and subarachnoid hemorrhage (SAH) that end in discharge without diagnosis; to evaluate longitudinal trends; and to identify patient characteristics independently associated with missed diagnostic opportunities. Design, Setting, and Participants This was a retrospective cohort study of all Medicare claims for 2006 to 2014. The setting was hospital EDs in the United States. Participants included all fee-for-service Medicare patients admitted to the hospital during 2007 to 2014 for the conditions of interest. Hospice enrollees and patients with recent skilled nursing facility stays were excluded. Main Outcomes and Measures The proportion of potential diagnostic opportunities missed in the ED was estimated using the difference between observed and expected ED discharges within 45 days of the index hospital admissions as the numerator, basing expected discharges on ED use by the same patients in earlier months. The denominator was estimated as the number of recognized emergencies (index hospital admissions) plus unrecognized emergencies (excess discharges). Results There were 1 561 940 patients, including 17 963 hospitalized for ruptured AAA, 304 980 for AMI, 1 181 648 for stroke, 19 675 for aortic dissection, and 37 674 for SAH. The mean (SD) age was 77.9 (10.3) years; 8.9% were younger than 65 years, and 54.1% were female. The proportions of diagnostic opportunities missed in the ED were as follows: ruptured AAA (3.4%; 95% CI, 2.9%-4.0%), AMI (2.3%; 95% CI, 2.1%-2.4%), stroke (4.1%; 95% CI, 4.0%-4.2%), aortic dissection (4.5%; 95% CI, 3.9%-5.1%), and SAH (3.5%; 95% CI, 3.1%-3.9%). Longitudinal trends were either nonsignificant (AMI and aortic dissection) or increasing (ruptured AAA, stroke, and SAH). Patient characteristics associated with unrecognized emergencies included age younger than 65 years, dual eligibility for Medicare and Medicaid coverage, female sex, and each of the following chronic conditions: end-stage renal disease, dementia, depression, diabetes, cerebrovascular disease, hypertension, coronary artery disease, and chronic obstructive pulmonary disease. Conclusions and Relevance Among Medicare patients, opportunities to diagnose ruptured AAA, AMI, stroke, aortic dissection, and SAH are missed in less than 1 in 20 ED presentations. Further improvement may prove difficult.
Pure Endoscopic Management of Fourth Ventricle Arachnoid Cyst: Case Report and Literature Review

Arachnoid cysts (ACs) within the fourth ventricle are rare, and only a few cases have been reported in the literature. These are benign lesions within the arachnoid membrane, and they have been reported to occur in almost all locations where arachnoid is present. Different procedures have been performed to restore a normal cerebrospinal fluid dynamic and/or pressure, including shunting and partial or complete excision of the cyst by open microsurgery or endoscopic fenestration. We report the case of a fourth ventricle AC successfully treated using only endoscopic anterior trans-frontal cyst fenestration/marsupialization and standard third ventriculostomy. Clinical and technical features are discussed, along with the pertinent literature.
Potential Molecular Targets in the Treatment of Lung Cancer Using siRNA Technology

ABSTRACT Lung cancer is the leading cause of cancer-related mortality with about 1.6 million deaths every year worldwide. Gene mutations and overexpression of oncogenes play a central role in malignant transformation in NSCLC. Conventional approaches for treatments of NSCLC have shown low levels of success while showing severe side effects. Target therapy using siRNA has recently emerged as a new strategy for cancer treatment by specific targeting of genes involved in the development and metastasis of cancer. This article dedicated to an update review of molecular targets could potentially be used for target therapy of lung cancer using SiRNA technology.
Two novel variants of the PHEX gene in patients with X-linked dominant hypophosphatemic rickets and prenatal diagnosis for fetuses in these families

X-linked hypophosphatemic rickets (XLHR; OMIM 307800) is an X-linked dominant disorder caused by mutations in the phosphate-regulating neutral endopeptidase homolog X-linked (PHEX) gene, which is located at Xp22.11. In the present study, two novel variants of the PHEX gene were identified in two unrelated families with XLHR by directly sequencing all 22 exon regions and intron/exon boundaries of the PHEX gene. One missense variant, NM_000444. 5: c.1721T>A, was identified in exon 17 of the PHEX gene in Family 1, which led to an amino acid change in the p.Ile574Lys protein. The other splicing variant identified was NM_000444. 5: c.591A>G, in exon 5 in Family 2, resulting in a deletion of 77 bp in the 3′ site of exon 5 during splicing, which was verified by direct cDNA sequencing of the PHEX gene. According to the results of reverse transcription-quantitative polymerase chain reaction analysis, the affected male with the splicing variant c.591A>G showed normal gene expression of PHEX, whereas the affected female exhibited low gene expression, compared with normal females. Based on these findings, prenatal diagnoses were made for the fetuses with a family history of XLHR using the backup amniotic fluid samples. One fetus without the missense variant was confirmed to be a healthy girl in a follow-up visit 1 month following birth.
T-lymphokine-activated killer cell-originated protein kinase (TOPK) as a prognostic factor and a potential therapeutic target in glioma

TOPK is overexpressed in various types of cancer and associated with poor outcomes in different types of cancer. In this study, we first found that the expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was significantly higher in Grade III or Grade IV than that in Grade II in glioma (P = 0.007 and P < 0.001, respectively). Expression of TOPK was positively correlated with Ki67 (P < 0.001). Knockdown of TOPK significantly inhibited cell growth, colony formation and increased sensitivities to temozolomide (TMZ) in U-87 MG or U-251 cells, while TOPK overexpression promoted cell growth and colony formation in Hs 683 or A-172 cells. Glioma patients expressing high levels of TOPK have poor survival compared with those expressing low levels of TOPK in high-grade or low-grade gliomas (hazard ratio = 0.2995; 95% CI, 0.1262 to 0.7108; P = 0.0063 and hazard ratio = 0.1509; 95% CI, 0.05928 to 0.3842; P < 0.0001, respectively). The level of TOPK was low in TMZ-sensitive patients compared with TMZ-resistant patients (P = 0.0056). In TMZ-resistant population, patients expressing high TOPK have two months’ shorter survival time than those expressing low TOPK. Our findings demonstrated that TOPK might represent as a promising prognostic and predictive factor and potential therapeutic target for glioma.
Progranulin, a New Adipokine at the Crossroads of Metabolic Syndrome, Diabetes, Dyslipidemia and Hypertension.

BACKGROUND Progranulin is a multifunctional regulatory protein with growth-promoting, neuroprotective and antiinflammatory activities. Recent studies indicate that progranulin is one of the adipose tissue hormones (adipokines). Progranulin expression in visceral adipose tissue and circulating progranulin concentration are increased in obesity and hyperprogranulinemia is involved in the pathogenesis of obesity-associated insulin resistance. Progranulin impairs insulin signaling and reduces insulin-induced glucose uptake both in vitro and in vivo whereas progranulin deficiency protects from high fat diet-induced insulin resistance. Several studies, including some prospective ones, have demonstrated the association between high progranulin and type 2 diabetes and its complications such as nephro- and retinopathy as well as non-alcoholic fatty liver disease. It is quite well established that progranulin contributes to insulin resistance and resulting deterioration of carbohydrate metabolism. In addition, progranulin may be associated with the development of diabetic microangiopathy, fatty liver disease and possibly with the increased risk of cancer in subjects with the metabolic syndrome. On the other hand, progranulin augments vasorelaxation, inhibits inflammatory reaction, is neuroprotective and reduces ischemiareperfusion injury. CONCLUSION Progranulin has both detrimental and beneficial effects. More clinical studies including prospective ones are needed to clarify the role of progranulin in obesity-associated pathologies such as diabetes, hyperlipidemia, hypertension and atherosclerosis.
Neurophysiological Investigation of Spontaneous Correlated and Anticorrelated Fluctuations of the BOLD Signal

Analyses of intrinsic fMRI BOLD signal fluctuations reliably reveal correlated and anticorrelated functional networks in the brain. Because the BOLD signal is an indirect measure of neuronal activity and anticorrelations can be introduced by preprocessing steps, such as global signal regression, the neurophysiological significance of correlated and anticorrelated BOLD fluctuations is a source of debate. Here, we address this question by examining the correspondence between the spatial organization of correlated BOLD fluctuations and correlated fluctuations in electrophysiological high γ power signals recorded directly from the cortical surface of 5 patients. We demonstrate that both positive and negative BOLD correlations have neurophysiological correlates reflected in fluctuations of spontaneous neuronal activity. Although applying global signal regression to BOLD signals results in some BOLD anticorrelations that are not apparent in the ECoG data, it enhances the neuronal-hemodynamic correspondence overall. Together, these findings provide support for the neurophysiological fidelity of BOLD correlations and anticorrelations.
Enhancing Solubility and Bioavailability of Rosuvastatin into Self Nanoemulsifying Drug Delivery System.

OBJECTIVE The aim of this study was to develop new Rosuvastatin calcium (RCa) self nanoemulsifying drug delivery system (SNEDDS) and to evaluate the bioavailability and pharmacodynamic effect of RCa-SNEDDS in Yorkshire pigs. METHODS Firstly, SNEDDS was developed and prepared then RCa was incorporated into SNEDDS which was evaluated regarding their characterization, stability properties, drug release profiles, permeation and cytotoxicity studies. Finally, in vivo performance of RCa-SNEDDS (F1-RCa-SNEDDS) was examined by pharmacokinetic and pharmacodynamics studies. The average droplet size of RCa- SNEDDS ranged between 200 and 250 nm. RCa-SNEDDS that contained 12.8% Oleic acid, 11 % Labrafil M, 3.3 % Labrasol and 4.4 % Transcutol HP were found to be stable and exhibited approximately 4-fold higher permeation than commercial tablet (Crestor® 20 mg tablet). RESULTS In pharmacokinetic studies, when F1-RCa-SNEDDS and commercial tablet were administered orally, F1-RCa-SNEDDS showed higher bioavailability of RCa than commercial tablet. Respectively, in pharmacodynamic studies, triglyceride and total cholesterol levels were significantly reduced with F1- RCa-SNEDDS formulation by 37% and 19% when compared to baseline values. CONCLUSION However, these decreases with commercial formulation were only 6% and 2% respectively. According to these findings, development formulation could be potentially used to enhance the oral absorption of RCa.
Ethnocultural Gerontological Nursing

The aging population is growing increasingly more diverse, with one in four older adults from an ethnic minority group by 2050, while the nursing force will largely remain members of a single race White population. The purpose of this review is to appraise the state of nursing knowledge in relationship to meeting the needs of elders in unique racial/ethnic groups using two approaches: evaluating the efficacy of current knowledge and evaluating the state of nursing knowledge about ethnocultural gerontological nursing based on an integrative review of nursing literature. Thirty-four articles were reviewed. Most articles used qualitative methodology focused on a single ethnic group, with several articles focused on health promotion/prevention. Cultural perspectives were better addressed than aging concepts and few articles integrated ethnocultural and gerontological nursing concepts. This evaluation indicates many gaps in the knowledge base about ethnocultural gerontological nursing. Specific areas for future knowledge development are identified.
Doping of semiconductor nanowires

A cornerstone in the successful application of semiconductor nanowire devices is controlled impurity doping. In this review article, we discuss the key results in the field of semiconductor nanowire doping. Considerable development has recently taken place in this field, and half of the references in this review are less than 3 years old. We present a simple model for dopant incorporation during in situ doping of particle-assisted growth of nanowires. The effects of doping on nanowire growth are thoroughly discussed since many investigators have seen much stronger and more complex effects than those observed in thin-film growth. We also give an overview of methods of characterizing doping in nanowires since these in many ways define the boundaries of our current understanding.