Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of two human leukocyte antigen-linked polymorphic heat shock protein 70 genes in patients with severe sepsis.

OBJECTIVE To determine whether the genotype and allelic frequencies of two human leukocyte antigen-linked bi-allelic 70-kilodalton heat shock protein (HSP70) gene polymorphisms are associated with susceptibility to and outcome of severe sepsis. Furthermore, we investigated a possible linkage between HSP70 gene polymorphisms and the previously reported and mortality-related tumor necrosis factor-beta (TNF-beta) NcoI gene polymorphism. DESIGN Consecutive entry study of patients with severe sepsis. SETTING Surgical intensive care unit in a university hospital. PATIENTS Eighty-seven patients with a diagnosis of severe sepsis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We studied two bi-allelic polymorphisms within the coding region of the constitutively expressed HSP70-HOM C/T, and the stress-inducible HSP70-2 G/A in patients with severe sepsis. The HSP70-HOM Ncol, HSP70-2 Pstl, and TNF-beta NcoI polymorphisms were identified by means of the polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. No significant differences in genotype and allelic frequencies were observed for both HSP70 gene polymorphisms between the 87 patients and the 110 healthy Caucasians serving as the control group. In addition, no differences in genotype and allelic frequencies between surviving and nonsurviving patients were detected. The allelic frequencies in the group of nonsurvivors were 0.8 for the HSP70-HOM C allele and 0.2 for the HSP70-HOM T allele vs. 0.87 and 0.13 for the survivors (p > .05). The frequency for the HSP70-2 G allele was 0.36 and 0.64 for the HSP70-2 A allele in the group of nonsurvivors vs. 0.41 and 0.59 for the survivors (p > .05). Analysis of a possible linkage between HSP70 and TNF-beta genotypes resulted in a significant association (odds ratio, 4.15; p < .01) of the HSP70-2 A/A homozygous genotype and the TNFB2/B2 homozygous genotype, which is reported to be a genomic marker for a poor prognosis in severe sepsis. CONCLUSIONS Our data show that the bi-allelic NcoI and PstI polymorphisms within the HSP70-HOM and HSP70-2 locus, respectively, are associated with neither susceptibility to nor outcome of severe sepsis. Moreover, we found a linkage between HSP70-2 A homozygotes and the previously reported and mortality-related homozygous genotype, TNFB2/B2, in patients suffering from severe sepsis.
Sirtuin-1 Targeting Promotes Foxp3+ T-Regulatory Cell Function and Prolongs Allograft Survival

ABSTRACT Sirtuin 1 (Sirt1), a class III histone/protein deacetylase, is central to cellular metabolism, stress responses, and aging, but its contributions to various host immune functions have been little investigated. To study the role of Sirt1 in T cell functions, we undertook targeted deletions by mating mice with a floxed Sirt1 gene to mice expressing CD4-cre or Foxp3-cre recombinase, respectively. We found that Sirt1 deletion left conventional T-effector cell activation, proliferation, and cytokine production largely unaltered. However, Sirt1 targeting promoted the expression of Foxp3, a key transcription factor in T-regulatory (Treg) cells, and increased Treg suppressive functions in vitro and in vivo. Consistent with these data, mice with targeted deletions of Sirt1 in either CD4+ T cells or Foxp3+ Treg cells exhibited prolonged survival of major histocompatibility complex (MHC)-mismatched cardiac allografts. Allografts in Sirt1-targeted recipients showed long-term preservation of myocardial histology and infiltration by Foxp3+ Treg cells. Comparable results were seen in wild-type allograft recipients treated with Sirt1 inhibitors, such as EX-527 and splitomicin. Hence, Sirt1 may inhibit Treg functions, and its targeting may have therapeutic value in autoimmunity and transplantation.
Public relations, society and culture : theoretical and empirical explorations

Historically, public relations research has been dominated by organisational interests, treating the profession as a function to help organisations achieve their goals, and focusing on practice and processes first and foremost. Such research is valuable in addressing how public relations can be used more effectively by organisations and institutions, but has tended to neglect the consequences of the practice on the social world in which those organisations operate.
The influence of mecamylamine on the action of certain other ganglionic blocking agents.

Hexamethonium is shown to produce neuromuscular block in cats previously given mecamylamine. Trimetaphan camphorsulphonate is shown to have a similar but less marked action at the motor endplate under the same conditions. The mechanism by which mecamylamine modifies the action of these ganglion blocking agents is discussed. Attention is drawn to the potential risk if similar influences prevail in man.
Evidence that two main bottleneck events shaped modern human genetic diversity

There is a strong consensus that modern humans originated in Africa and moved out to colonize the world approximately 50 000 years ago. During the process of expansion, variability was lost, creating a linear gradient of decreasing diversity with increasing distance from Africa. However, the exact way in which this loss occurred remains somewhat unclear: did it involve one, a few or a continuous series of population bottlenecks? We addressed this by analysing a large published dataset of 783 microsatellite loci genotyped in 53 worldwide populations, using the program ‘Bottleneck’. Immediately following a sharp population decline, rare alleles are lost faster than heterozygosity, creating a transient excess of heterozygosity relative to allele number, a feature that is used by Bottleneck to infer historical events. We find evidence of two primary events, one ‘out of Africa’ and one placed around the Bering Strait, where an ancient land bridge allowed passage into the Americas. These findings agree well with the regions of the world where the largest founder events might have been expected, but contrast with the apparently smooth gradient of variability that is revealed when current heterozygosity is plotted against distance from Africa.
A Randomized, Placebo-Controlled Trial of the Bivalent Killed, Whole-Cell, Oral Cholera Vaccine in Adults and Children in a Cholera Endemic Area in Kolkata, India

Objectives An effective vaccine against cholera has been used for public health purposes in Vietnam since the 1990s. This vaccine was reformulated to meet WHO requirements. We assessed the safety and immunogenicity of the reformulated bivalent (Vibrio cholerae 01 and 0139) killed whole cell oral vaccine in a cholera endemic area in Kolkata, India. Design Double-blind, randomized, placebo controlled trial Setting The trial was conducted in the clinical trial ward of the Infectious Diseases Hospital in Kolkata, India Participants The participants were 101 healthy adults (males and non-pregnant females) aged 18–40 years and 100 healthy children (males and non-pregnant females) aged 1–17 years. Interventions Participants were randomized to receive either the bivalent killed whole cell oral cholera vaccine or placebo (killed oral Escherichia coli K12) Outcome Measures For safety: proportion of subjects with adverse events during the duration of study participation. For immunogenicity: Proportion of subjects who had a ≥4-fold rise in serum vibriocidal antibody titers 14 days after the second dose of vaccine or placebo. Results Adverse reactions were observed with similar frequency among vaccine and placebo recipients in both age groups. Among adults 4% of vaccine and 8% of placebo recipients and among children 4% of vaccine and 2% of placebo recipients had at least one adverse event within 28 days of the first dose of the vaccine. Following immunization, 53% of adult and 80% of children vaccinees showed a ≥4 fold rise in serum V. cholerae O1 vibriocidal antibody titers. A less pronounced response to V. cholerae O139 vibriocidal antibody titers post-immunization was noted among vaccinees. Conclusions We found the vaccine to be safe and immunogenic in a cholera-endemic area in India. Trial Registration ClinicalTrials.gov NCT00119197
Experiences of working with induced abortion: focus group discussions with gynaecologists and midwives/nurses.

BACKGROUND While there exists an extensive amount of research regarding the medical aspects of abortion, there is a great lack of studies investigating staff's views and experiences of working in abortion services. AIMS To elucidate gynaecologists' and midwives'/nurses' experiences, perceptions and interactions working in abortion services, their experiences of medical abortions and abortions performed at the woman's home. An additional aim was to illustrate gynaecologists', midwives' and nurses' visions of their future professional roles within the abortion services. METHOD Three focus group discussions within each profession were carried out in 1-hour sessions with a total of 25 gynaecologists and 15 midwives/nurses from three different hospitals. RESULTS The content analysis reflected that gynaecologists and midwives/nurses had no doubts about participating in abortions despite the fact that they had experienced complex and difficult situations, such as repeat and late-term abortions. They experienced their work as paradoxical and frustrating but also as challenging and rewarding. However, they were rarely offered ongoing guidance and continuously professional development education. For gynaecologists, as well as midwives/nurses, their experiences and perceptions were strongly linked to the concurrent development of abortion methods. The interaction between the professions was found to be based on great trust in each other's skills. CONCLUSIONS In order to promote women's health, gynaecologists' and midwives'/nurses' need for a forum for reflection and ongoing guidance should be acted on. With a higher number of abortions done medically and a higher proportion of home abortions, midwives/nurses will get increased, responsibilities in the abortion services in the future.
Development of a multicomponent Staphylococcus aureus vaccine designed to counter multiple bacterial virulence factors

Staphylococcus aureus is a major cause of healthcare-associated infections and is responsible for a substantial burden of disease in hospitalized patients. Despite increasingly rigorous infection control guidelines, the prevalence and corresponding negative impact of S. aureus infections remain considerable. Difficulties in controlling S. aureus infections as well as the associated treatment costs are exacerbated by increasing rates of resistance to available antibiotics. Despite ongoing efforts over the past 20 years, no licensed S. aureus vaccine is currently available. However, learnings from past clinical failures of vaccine candidates and a better understanding of the immunopathology of S. aureus colonization and infection have aided in the design of new vaccine candidates based on multiple important bacterial pathogenesis mechanisms. This review outlines important considerations in designing a vaccine for the prevention of S. aureus disease in healthcare settings.
Reactive astrocytes as neural stem or progenitor cells: In vivo lineage, In vitro potential, and Genome‐wide expression analysis

Here, we review the stem cell hallmarks of endogenous neural stem cells (NSCs) during development and in some niches of the adult mammalian brain to then compare these with reactive astrocytes acquiring stem cell hallmarks after traumatic and ischemic brain injury. Notably, even endogenous NSCs including the earliest NSCs, the neuroepithelial cells, generate in most cases only a single type of progeny and self‐renew only for a rather short time in vivo. In vitro, however, especially cells cultured under neurosphere conditions reveal a larger potential and long‐term self‐renewal under the influence of growth factors. This is rather well comparable to reactive astrocytes in the traumatic or ischemic brain some of which acquire neurosphere‐forming capacity including multipotency and long‐term self‐renewal in vitro, while they remain within their astrocyte lineage in vivo. Both reactive astrocytes and endogenous NSCs exhibit stem cell hallmarks largely in vitro, but their lineage differs in vivo. Both populations generate largely a single cell type in vivo, but endogenous NSCs generate neurons and reactive astrocytes remain in the astrocyte lineage. However, at some early postnatal stages or in some brain regions reactive astrocytes can be released from this fate restriction, demonstrating that they can also enact neurogenesis. Thus, reactive astrocytes and NSCs share many characteristic hallmarks, but also exhibit key differences. This conclusion is further substantiated by genome‐wide expression analysis comparing NSCs at different stages with astrocytes from the intact and injured brain parenchyma. GLIA 2015;63:1452–1468
Parkinson's disease mortality and the industrial use of heavy metals in Michigan

Parkinson's disease (PD) mortality rates in Michigan counties for 1986–1988 were calculated with respect to potential heavey metal exposure (iron, zinc, copper, mercury, magnesium, and manganese) from industry based on recent census data. Individuals were counted as a PD death if the diagnosis was listed as an “underlying” or “related” cause of death on the death certificate. Counties with an industry in the paper, chemical, iron, or copper related‐industrial categories (ICs) had statiscally significantly (p < 0.05) higher PD death rates than counties without these industries. Significant correlations of chemical (rs =0.22;p = 0.05), paper (rs =0.22;p = 0.05) and iron (rs =0.29;p = 0.008) industry densities with PD death rates were also present. Counties were divided into high (>15/100,000 individuals 45 years old and over) and low (< = 15/100.000) PD death rate counties by cluster analysis. Geographically, counties with high PD mortality were located mainly in the southern half of the lower peninsula and eastern half of the upper peninsula; low PD death rate counties formed two distinct clusters in the western edge of the upper peninsula and the north‐central portion of the lower peninsula. Other possible risk factors that may explain the varied distribution of PD death rates in Michigan were examined. Those significantly correlated with PD mortality included population density (rs =0.31;p= 0.005), farming density (rs= 0.25;p =0.02), and well water use (rs =−0.24;p =0.03). These ecologic findings suggest a geographic association between PD mortality and the industrial use of heavy metals.
Effects of Arm Crossing on Spatial Perspective-Taking

Human social interactions often require people to take a different perspective than their own. Although much research has been done on egocentric spatial representation in a solo context, little is known about how space is mapped in relation to other bodies. Here we used a spatial perspective-taking paradigm to investigate whether observing a person holding his arms crossed over the body midline has an impact on the encoding of left/right and front/back spatial relations from that person’s perspective. In three experiments, we compared performance in a task in which spatial judgments were made from the perspective of the participant or from that of a co-experimenter. Depending on the experimental condition, the participant’s and the co-experimenter’s arms were either crossed or not crossed over the midline. Our results showed that crossing the arms had a specific effect on spatial judgments based on a first-person perspective. More specifically, the responses corresponding to the dominant hand side were slower in the crossed than in the uncrossed arms condition. Crucially, a similar effect was also found when the participants adopted the perspective of a person holding his arms crossed, but not when the other person’s arms were held in an unusual but uncrossed posture. Taken together these findings indicate that egocentric space and altercentric space are similarly coded in neurocognitive maps structured with respect to specific body segments.
A Treatment Validation Protocol for Cyber-Physical-Human Medical Systems

In cyber-physical-human medical environments, coordinating supervisory medical systems and medical staff to perform treatments in in accordance with best practice is essential for patient safety. However, the dynamics of patient conditions and the non-deterministic nature of potential side effects of treatments pose significant challenges. In this paper, we propose a validation protocol to enforce the correct execution sequence of performing treatment, regarding preconditions validation, side effects monitoring, and expected responses checking based on the path physiological models. The proposed protocol organizes the medical information concisely and comprehensively to help medical staff validate treatments. Unlike traditional validation mechanism for cyber systems, the medical system cannot lock or rollback the states of physical components, such as patient conditions. Therefore, the proposed protocol dynamically adapts to the patient conditions and side effects of treatments. Moreover, a cardiac arrest scenario is used as a case study to verify the safety and correctness properties of the proposed protocol.
Analytical performance and clinical utility of the INNOTEST® PHOSPHO-TAU(181P) assay for discrimination between Alzheimer's disease and dementia with Lewy bodies

Abstract Background: Total tau (T-tau) and β-amyloid(1-42) (Aβ1-42) levels in cerebrospinal fluid (CSF) can differentiate Alzheimer's disease (AD) from normal aging or depressive pseudo-dementia. Differential diagnosis from dementia with Lewy bodies (DLB) in clinical settings is difficult. Methods: The analytical performance of the INNOTEST® PHOSPHO-TAU(181P) assay was validated in terms of selectivity, sensitivity, specificity, precision, robustness, and stability. Clinical utility of the assay alone, or combined with T-tau and Aβ1-42, for discrimination of AD (n=94) from patients suffering from DLB (n=60) or from age-matched control subjects (CS) (n=60) was assessed in a multicenter study. Results: CSF concentrations of tau phosphorylated at threonine 181 (P-tau181P) in AD was significantly higher than in DLB and CS. Discriminant analysis, a classification tree, and logistic regression showed that P-tau181P was the most statistically significant single variable of the three biomarkers for discrimination between AD and DLB. Conclusions: P-tau181P quantification is a robust and reliable assay that may be useful in discriminating AD from DLB. Clin Chem Lab Med 2006;44:1472–80.
Temporal Data Modeling and Reasoning for Information Systems

Temporal knowledge representation and reasoning is a major research field in Artificial Intelligence, in Database Systems, and in Web and Semantic Web research. The ability to model and process time and calendar data is essential for many applications like appointment scheduling, planning, Web services, temporal and active database systems, adaptive Web applications, and mobile computing applications. This article aims at three complementary goals. First, to provide with a general background in temporal data modeling and reasoning approaches. Second, to serve as an orientation guide for further specific reading. Third, to point to new application fields and research perspectives on temporal knowledge representation and reasoning in the Web and Semantic Web.
Endogenous Monocarboxylates Sustain Hippocampal Synaptic Function and Morphological Integrity during Energy Deprivation

The ability to fuel neurons via glycogenolysis is believed to be an important function of glia. Indeed, the slow, rather than immediate, depression of synaptic transmission in hippocampal slices during exogenous glucose deprivation suggests that intrinsic energy reservoirs help to sustain neurotransmission. It is believed that glia fuel neighboring neurons via diffusible monocarboxylates such as pyruvate and lactate, although a role for glucose has been proposed also. Using α-cyano-4-hydroxycinnamate (4-CIN) to inhibit monocarboxylate transport and cytochalasin B (CCB) to inhibit glucose transport, we examined the role of glucose and monocarboxylates in supporting the functional and morphological integrity of hippocampal neurons during glucose deprivation. Although 200 μm 4-CIN failed to depress EPSPs supported by 10 mm glucose, pretreatment with 4-CIN accelerated the depression of EPSPs during glucose deprivation. 4-CIN also accelerated the decline in glucose-supported EPSPs after administration of 50 μm CCB, whereas CCB failed to alter the slow decay of pyruvate-supported EPSPs during pyruvate deprivation. 4-CIN did not alter the morphology of pyramidal neurons in the presence of 10 mm glucose but produced significant damage during glucose deprivation or CCB administration. These results suggest that endogenous monocarboxylates rather than glucose maintain neuronal integrity during energy deprivation. Furthermore, EPSPs supported by 2–3.3 mm glucose were sensitive to 4-CIN, suggesting that endogenous monocarboxylates are involved in maintaining neuronal function even under conditions of mild glucose deprivation.
Does the Decision to Issue Public Debt Affect Firm Valuation? Russian Evidence

This paper examines the association between firm valuation and the sources of debt financing. In particular, using a sample of 353 firms, we test whether the decision to issue bonds affects the firm's stock market performance in the emerging Russian markets. Our results indicate that public debt financing may have a negative effect on the firm's market valuation. After controlling for the differences in firm-specific characteristics and addressing potential endogeneity issues, we document that the firms which rely on public debt underperform relative to firms with other sources of debt financing in terms of stock market valuation.
Welfare Policy and the Distribution of Hours of Work

We examine the distribution of hours of work across industrial sectors in OECD countries. We find large disparities when sectors are divided into three groups: one that produces goods without home substitutes and two others that have home substitutes — health and social work, and all others. We attribute the disparities to the countries’ tax and subsidy policies. High taxation substantially reduces hours in sectors that have close home substitutes but less so in other sectors. Health and social care subsidies increase hours in that sector. We compute these effects for nineteen OECD countries.