Miracle-dz/UniFAR-FTUs huggingface dataset:
New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) III: Endogenous Inhibition of Angiotensin Converting Enzyme (ACE) Provides Protection against Cardiovascular Diseases

ACE inhibitor drugs decrease mortality by up to one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors. Here we investigated the clinical significance of this potential endogenous ACE inhibition. ACE concentration and activity was measured in patient's serum samples (n = 151). ACE concentration was found to be in a wide range (47–288 ng/mL). ACE activity decreased with the increasing concentration of the serum albumin (HSA): ACE activity was 56±1 U/L in the presence of 2.4±0.3 mg/mL HSA, compared to 39±1 U/L in the presence of 12±1 mg/mL HSA (values are mean±SEM). Effects of the differences in ACE concentration were suppressed in human sera: patients with ACE DD genotype exhibited a 64% higher serum ACE concentration (range, 74–288 ng/mL, median, 155.2 ng/mL, n = 52) compared to patients with II genotype (range, 47–194 ng/mL, median, 94.5 ng/mL, n = 28) while the difference in ACE activities was only 32% (range, 27.3–59.8 U/L, median, 43.11 U/L, and range 15.6–55.4 U/L, median, 32.74 U/L, respectively) in the presence of 12±1 mg/mL HSA. No correlations were found between serum ACE concentration (or genotype) and cardiovascular diseases, in accordance with the proposed suppressed physiological ACE activities by HSA (concentration in the sera of these patients: 48.5±0.5 mg/mL) or other endogenous inhibitors. Main implications are that (1) physiological ACE activity can be stabilized at a low level by endogenous ACE inhibitors, such as HSA; (2) angiotensin II elimination may have a significant role in angiotensin II related pathologies.
Sharp decline in the food self-sufficiency ratio in Japan and its future prospects

Japan‘s food self-sufficiency ratio was 79% in 1960, and this ratio compares favorably with that of other advanced countries with similar farmland endowments. But it fell most rapidly of all major developed countries in the last 45 years, and became the lowest among countries with more than 100 million in population. In this paper, the mechanisms of the decline in the food self-sufficiency ratio in the last 45 years were examined, and it was pointed out that epoch making events such as drastic change of dietary habits under a rapid economic growth and drastic appreciation of the yen against the US dollar were major causes of the sharp decline in the food self-sufficiency ratio. Some preliminary examinations regarding the future food self-sufficiency ratio was carried out based on some assumptions. It was found that if the calorie supply from domestically produced food follows the trend of the period 1996 - 2006 the food self-sufficiency ratio will stay at 39% or decline slightly during the period 2005 - 2015. These projection results imply that calorie supply from domestically produced food has to be increased considerably in order to raise the food self-sufficiency ratio to 45% by 2015.
Disclosure of traumatic experiences, dissociation, and anxiety in group therapy for posttraumatic stress

Abstract This study examined the relationships among the symptoms of posttraumatic stress disorder (PTSD), anxiety, dissociation with self-disclosure among 72 male military veterans with PTSD who were attending an eight-week group therapy treatment program. At intake to the program, participants were administered a baseline demographics questionnaire, the Clinicians Administered PTSD Scale, a dissociation measure, and the Hospital Anxiety and Depression Scale (HADS). Participants completed the dissociation measure and the HADS again at discharge from the program and at a follow-up three months later. We found that the frequency and severity of dissociation reported by participants decreased over time. It was also found that high self-disclosers had higher levels of dissociation when compared to low self-disclosers at baseline and program end, but showed a greater decline in levels of dissociation at three-month follow-up. It was also found that, regardless of the level of disclosure, anxiety levels at follow-up were significantly lower than baseline levels of anxiety.
Landscape Genetics of Leaf-Toed Geckos in the Tropical Dry Forest of Northern Mexico

Habitat fragmentation due to both natural and anthropogenic forces continues to threaten the evolution and maintenance of biological diversity. This is of particular concern in tropical regions that are experiencing elevated rates of habitat loss. Although less well-studied than tropical rain forests, tropical dry forests (TDF) contain an enormous diversity of species and continue to be threatened by anthropogenic activities including grazing and agriculture. However, little is known about the processes that shape genetic connectivity in species inhabiting TDF ecosystems. We adopt a landscape genetic approach to understanding functional connectivity for leaf-toed geckos (Phyllodactylus tuberculosus) at multiple sites near the northernmost limit of this ecosystem at Alamos, Sonora, Mexico. Traditional analyses of population genetics are combined with multivariate GIS-based landscape analyses to test hypotheses on the potential drivers of spatial genetic variation. Moderate levels of within-population diversity and substantial levels of population differentiation are revealed by F ST and D est. Analyses using structure suggest the occurrence of from 2 to 9 genetic clusters depending on the model used. Landscape genetic analysis suggests that forest cover, stream connectivity, undisturbed habitat, slope, and minimum temperature of the coldest period explain more genetic variation than do simple Euclidean distances. Additional landscape genetic studies throughout TDF habitat are required to understand species-specific responses to landscape and climate change and to identify common drivers. We urge researchers interested in using multivariate distance methods to test for, and report, significant correlations among predictor matrices that can impact results, particularly when adopting least-cost path approaches. Further investigation into the use of information theoretic approaches for model selection is also warranted.
Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence

CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva. Thus, IL-10+CD4+ T cells suppress antiviral immune responses against CMV. Expansion of this T-cell population in the periphery was promoted by IL-27 whereas mucosal IL-10+ T cell responses were ICOS-dependent. Infected Il27rα-deficient mice with reduced peripheral IL-10+CD4+ T cell accumulation displayed robust T cell responses and restricted MCMV persistence and shedding. Temporal inhibition experiments revealed that IL-27R signaling during initial infection was required for the suppression of T cell immunity and control of virus shedding during MCMV persistence. IL-27 production was promoted by type-I IFN, suggesting that β-herpesviridae exploit the immune-regulatory properties of this antiviral pathway to establish chronicity. Further, our data reveal that cytokine signaling events during initial infection profoundly influence virus chronicity.
Design and evaluation of a probe for simultaneous EEG and near-infrared imaging of cortical activation

We present a novel probe design which enables simultaneous electroencephalography (EEG) and near-infrared (NIR) optical imaging to be performed in a manner which is easy to apply, allows for optimum co-registration of the two forms of data and maximizes the number of sensors which can be applied to a given area. Our probe design is evaluated using a dual-modality, tissue-mimicking phantom and by performing a simple functional activation study of the human motor cortex. We successfully acquired NIR optical and EEG data simultaneously for both our phantom and our human motor cortex experiments, clearly demonstrating the effectiveness and suitability of our ‘opto-electrode’.
Modulation of Ambient Temperature-Dependent Flowering in Arabidopsis thaliana by Natural Variation of FLOWERING LOCUS M

Plants integrate seasonal cues such as temperature and day length to optimally adjust their flowering time to the environment. Compared to the control of flowering before and after winter by the vernalization and day length pathways, mechanisms that delay or promote flowering during a transient cool or warm period, especially during spring, are less well understood. Due to global warming, understanding this ambient temperature pathway has gained increasing importance. In Arabidopsis thaliana, FLOWERING LOCUS M (FLM) is a critical flowering regulator of the ambient temperature pathway. FLM is alternatively spliced in a temperature-dependent manner and the two predominant splice variants, FLM-ß and FLM-δ, can repress and activate flowering in the genetic background of the A. thaliana reference accession Columbia-0. The relevance of this regulatory mechanism for the environmental adaptation across the entire range of the species is, however, unknown. Here, we identify insertion polymorphisms in the first intron of FLM as causative for accelerated flowering in many natural A. thaliana accessions, especially in cool (15°C) temperatures. We present evidence for a potential adaptive role of this structural variation and link it specifically to changes in the abundance of FLM-ß. Our results may allow predicting flowering in response to ambient temperatures in the Brassicaceae.
Inwardly rectifying whole cell potassium current in human blood eosinophils

1 Membrane currents were studied in single human blood eosinophils using the whole cell voltage clamp technique. The whole cell current‐voltage relationship exhibited rectification about the membrane potential which followed the potassium equilibrium potential when [K+]o was raised. Elevation of [K+]o considerably potentiated inward current amplitude, and in some cells channel activity was discernible in the whole cell membrane current recordings. The single channel conductance was 24 ± 1 pS ([K+]o, 100 mM; [K+]i, 140 mM), and eosinophils were found to have as few as three, and on average twenty, inward rectifier channels each. 2 The inward current was inhibited in a voltage‐dependent manner by extracellular cations in order of potency Ba2+ > Cs+ > Na+. Intracellular acidification inhibited while alkalization augmented the inward current. Mg2+ contributed to rectification as dialysis with nominally Mg2+‐free pipette solution was associated with an increase in the outward current during membrane polarization. 3 By reverse transcription‐polymerase chain reaction (RT‐PCR) using suitable primers on human eosinophil mRNA, an inward rectifier channel, Kir2.1, was identified, which is known from expression studies to have very similar properties to those found in this study. 4 Superoxide anion production or its stimulation by phorbol 12‐myristate 13‐acetate (PMA) was not significantly affected by depolarization with 140 mM [K+]o, or by 1 mM BaCl2. 5 It is concluded that the single channel currents and the whole cell current rectification observed in human blood eosinophils resulted from the presence of an inwardly rectifying potassium channel, probably Kir2.1.
Simulated Electronic Health Record (Sim-EHR) Curriculum: Teaching EHR Skills and Use of the EHR for Disease Management and Prevention

Electronic health records (EHRs) can improve many aspects of patient care, yet few formal EHR curricula exist to teach optimal use to students and other trainees. The Simulated EHR (Sim-EHR) curriculum was introduced in January 2011 at Oregon Health & Science University (OHSU) to provide learners with a safe hands-on environment in which to apply evidence-based guidelines while learning EHR skills. Using an EHR training platform identical to the OHSU EHR system, learners review and correct a simulated medical chart for a complex virtual patient with chronic diseases and years of fragmented care. They write orders and prescriptions, create an evidence-based plan of care for indicated disease prevention and management, and review their work in a small-group setting. Third-year students complete the Sim-EHR curriculum as part of the required family medicine clerkship; their chart work is assessed using a rubric tied to the curriculum’s general and specific objectives. As of January 2014, 406 third-year OHSU medical students, on campus or at remote clerkship sites, and 21 OHSU internal medicine interns had completed simulated charts. In this article, the authors describe the development and implementation of the Sim-EHR curriculum, with a focus on use of the curriculum in the family medicine clerkship. They also share preliminary findings and lessons learned. They suggest that the Sim-EHR curriculum is an effective, interactive method for providing learners with EHR skills education while demonstrating how a well-organized chart helps ensure safe, efficient, and quality patient care.
Altered sciatic nerve fiber morphology and endoneural microvessels in mouse models relevant for obesity, peripheral diabetic polyneuropathy, and the metabolic syndrome

The morphology of sciatic nerves from leptin‐deficient ob/ob mice and leptin receptor‐deficient db/db mice, both models for obesity, peripheral diabetic neuropathy, and the metabolic syndrome, has yet to be examined for changes in nerve fibers and in endoneural microvessels. Sciatic nerves from three groups of 4‐month‐old mice (WT C57BL6, ob/ob, and db/db) were investigated. In ultrathin sections, the thickness of myelin sheaths was significantly reduced in small, medium‐sized, and large axons of db/db mice compared with WT mice. In ob/ob mice, only large fibers showed a decrease in myelin sheath thickness. The number of nonmyelinated nerve fibers was lower in ob/ob mice than in the db/db group. A thickened basal lamina of Schwann cells occurred in the ob/ob group only. In contrast, the basement membrane of endoneural microvessels was thickened in both obese groups. For this reason, laminin expression in Western blot analysis was lower in the db/db group than in the ob/ob one. Endoneural microvessels, which had been injected with fluorescein isothiocyanate, depicted signs of vasodilatation in the ob/ob and vasoconstriction in db/db mice. Endoneural vessels displayed two receptors of oxLDL. LOX‐1 was strongly expressed in db/db mice, whereas TLR4 was at its maximum in the ob/ob group. We conclude that changes in nerve fibers and in endoneural microvessels are present in sciatic nerve of both mouse models of type 2 diabetes. Upregulation of oxLDL‐dependent receptors in endoneural microvessels might be connected to different degrees of oxidative stress in severe diabetic db/db mice and in the mild diabetic ob/ob group. © 2011 Wiley Periodicals, Inc.
Microbes and the Inflammatory Response in Necrotising Enterocolitis

Necrotising enterocolitis (NEC) is a progressive disease of the neonatal intestine beginning in the distal ileum and proximal colon and characterised by inflammatory necrosis [1,2]. It typically affects low birth-weight, preterm infants who account for the majority (70–90%) of cases [3–5]. Since the 1960s, advances in medical care have raised the survival rate for preterm infants with increasingly shortened gestation periods, resulting in a concomitant surge in NEC cases. The overall incidence of NEC is generally accepted as ranging from <1% to 5% of neonatal intensive care unit (NICU) admissions, or up to 5 cases per 1,000 live births [4– 6]. There is an inverse relationship between NEC and birth-weight, so that very low birthweight infants (VLBW; <1500 g) carry the greatest burden of disease [4,5,7]. Caplan report‐ ed NEC rates for VLBW infants vary greatly across countries, ranging from 1.5% in Japan to 28% in Hong Kong, with racial disparity apparent in VLBW black infants who have an increased risk and greater associated mortality [5,8]. Despite advances in neonatal care, the overall mortality remains high at around 20–30% [3,8-10]. An estimated 20-40% of infants with NEC require surgery, which has a case fatality rate of up to 50%, the smallest, least mature infants having the worst prognosis [5]. Most cases of NEC are sporadic with no clear seasonal distribution, but outbreaks have been documented [5]. Treatment of NEC is mainly supportive with the administration of broad-spectrum antibiotics while surgery is indicat‐ ed for intestinal perforation or removal of necrotic bowel segments. NEC complications and sequelae include serious neurodevelopmental delay, poor growth, intestinal obstruction due to scarring, short bowel syndrome, and liver failure due to prolonged hyperalimentation [6, 9]. The annual financial cost of NEC is considerable and in the USA has been estimated at $500 million to $1 billion [9].
MicroRNA-190 regulates FOXP2 genes in human gastric cancer

Objective To investigate how microRNA-190 (miR-190) regulates FOXP2 genes in gastric cancer (GC) cell line SGC7901. Methods We identified that miR-190 could target FOXP2 genes by using dual luciferase enzyme assay. Precursor fragment transfection of miR-190 was performed with GC cell line SGC7901 and human gastric mucosal cell line GES-1. miR-190 expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and FOXP2 protein expression was measured by Western blotting. Results FOXP2-3′-untranslated region (UTR) in miR-190 transfection group was significantly decreased as compared with other groups. There were no significant differences in fluorescence signals of FOXP2mut-3′-UTR in each group. Therefore, it was assumed that miR-190 can target FOXP2 genes. Through RT-PCR verification, it was observed that the expression level of miR-190 was significantly higher in GC cell line SGC7901 than in human gastric mucosa cell line GES-1 after transfection with miR-190 mimics. The expression level of miR-190 was significantly higher in GES-1 cells than in SGC7901 cells after transfection with miR-190 inhibitors. Western blotting results showed the expression level of FOXP2 was significantly lower in GC cell line SGC7901 than in GES-1 cells. Compared with blank, mimics control, and inhibitors control groups, the miR-190 mimics group showed significantly enhanced proliferation, migration, and invasion abilities, while miR-190 inhibitors group showed decreased abilities toward proliferation, migration, and invasion (P<0.05). The transcription level of miR-190 and the expression level of FOXP2 in tumor tissues and adjacent normal tissues in GC patients were verified to be consistent with those of cell line experiments. Conclusion Upregulation of miR-190 can lead to downregulation of FOXP2 protein expression. miR-190 may serve as a potential target for GC diagnosis.
Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery.

BACKGROUND Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. METHODS We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. CONCLUSIONS Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.
Learning discriminative dictionaries with partially labeled data

While recent techniques for discriminative dictionary learning have demonstrated tremendous success in image analysis applications, their performance is often limited by the amount of labeled data available for training. Even though labeling images is difficult, it is relatively easy to collect unlabeled images either by querying the web or from public datasets. In this paper, we propose a discriminative dictionary learning technique which utilizes both labeled and unlabeled data for learning dictionaries. Extensive evaluation on existing datasets demonstrate that the proposed method performs significantly better than state of the art dictionary learning approaches when unlabeled images are available for training.
Japanese Guideline for the Management of Hyperuricemia and Gout: Second Edition

Gout is a urate deposition disease caused by persistent hyperuricemia. Because gout patients present with a variety of clinical symptoms, it is necessary to have a guideline for the standard management and care of gout and hyperuricemia. The Japanese Society of Gout and Nucleic Acid Metabolism, a scientific society committed to study nucleic acid metabolism and related diseases, established the first edition of the “Guideline for the Management of Hyperuricemia and Gout” in 2002, and published the revised version in January 2010. This second edition is not only evidence based on a search of systemic literature, but also includes consensus levels by a Delphi exercise to determine the strength of the recommendations. A draft version of this guideline was reviewed by internal and external reviewers as well as a patient. In this guideline, key messages from each chapter are listed as statements together with the evidence level, consensus level, and strength of the recommendation. In this proceeding, several selected chapters on the clinical management of gout and hyperuricemia are described. We hope this guideline is appropriately used for the standard management and care of patients with hyperuricemia and gout in daily practice.