Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical congenital heart defects and abnormal levels of routinely collected first‐ and second‐trimester biomarkers

We examined the association between maternal characteristics, routinely collected first‐ and second‐trimester biomarkers and the risk of having an infant with a critical congenital heart defect (CCHD). Included were women who participated in the California Prenatal Screening Program who had nuchal translucency (NT) measurement and first‐ and second‐trimester serum screening. All pregnancies ended in a live birth of an infant without aneuploidy or a neural tube defect. Poisson regression analyses were used to estimate the relative risk and 95% confidence interval of a CCHD by maternal characteristics, first‐ and second‐trimester serum biomarkers or NT measurements. The sample included 118,194 mother–infant pairs; 284 infants had a CCHD. Women with preexisting diabetes were three‐times as likely to have an infant with a CCHD. After adjusting for preexisting diabetes, women with first‐trimester human chorionic gonatotropin (hCG) measurement <10th centile were 1.6‐times as likely to have an infant with a CCHD (P = 0.011). Women with a NT measurement ≥95th centile were at two‐ to threefold higher risk of having an infant with a CCHD (P's = 0.004–0.007). Pregnancies with two risk factors for an infant with a CCHD were 5.6‐times more likely to have an infant with a CCHD than women with no identified risk factors (P < 0.001). Despite the increased risk, performance testing demonstrated low sensitivity and specificity for screening use of these risk factors. Of the women with an infant with a CCHD, only 21.8% had an identified risk factor. © 2016 Wiley Periodicals, Inc.
Partial prevention of active Heymann nephritis by lα, 25 dihydroxyvitamin D3

The hormone lα, 25 dihydroxyvitamin D3 (1,25(OH)2DO3 has potent immunosuppressivc effects in vitro. Recent publications also described a protective effect of the hormone in various animal models of immune‐mediated diseases. To test its in vitro activity we induced active Heymann nephritis in Lewis rats that were either untreated or treated with 1,25(OH)2D3 or its synthetic 20‐epi analogue, KH1060. Treatment with cyclosporine A (CsA) was used as an immunosuppressive control. In this nephrotic model the administration of 1,25(OH)2D3 (0.5 μg/kg body weight) given on alternate days during the first 13 days after active immunization significantly reduced the proteinuria as measured by weeks 7–9. This reduction was comparable to the reduction observed in rats treated with CsA (20 mg/kg) on alternate days. A second series of experiments with 1,25(OH)2D3 confirmed these findings. The level of autoantibodies was found to be significantly suppressed during the treatment time in the CsA (20 mg/kg) group, whereas the limit of significance (P=0.06) was reached in the 1,25(OH)2D3 groups that developed less proteinuria. The administration of 1,25(OH)2D3 transiently increased the mean serum calcium Concentration with 2.5 mg/dl above the pretreatmcnt values, and the urinary calcium excretion by a factor of 3–5 during the short treatment time. Treatment with the analogue KH 1060 did not reduce the proteinuria significantly. Our experiments add evidence to the hypothesis that 1,25(OH)2D3 in pharmacological doses has immunosupprcssive potency.
Among 4 Diet Quality Indexes, Only the Alternate Mediterranean Diet Score Is Associated with Better Colorectal Cancer Survival and Only in African American Women in the Multiethnic Cohort.

BACKGROUND Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, with a 5-y survival rate of ∼65%. Therefore, the identification of modifiable health factors to improve CRC survival is crucial. OBJECTIVE We investigated the association of 4 prediagnostic a priori diet quality indexes with CRC-specific and all-cause mortality in the Multiethnic Cohort (MEC). METHODS The MEC included >215,000 African-American, Native Hawaiian, Japanese-American, Latino, and white adults living in Hawaii and California who completed a validated quantitative food-frequency questionnaire in 1993-1996. CRC cases and deaths were identified through linkages to cancer registries and to state and national vital registries. Sex-specific HRs and 95% CIs were estimated for the Healthy Eating Index (HEI) 2010, the Alternative HEI (AHEI) 2010, the alternate Mediterranean Diet (aMED) score, and the Dietary Approaches to Stop Hypertension (DASH) index with CRC-specific and overall mortality as the primary outcomes. Ethnicity-specific analyses were the secondary outcomes. RESULTS Among 4204 MEC participants diagnosed with invasive CRC through 2010, 1976 all-cause and 1095 CRC-specific deaths were identified. A higher aMED score was associated with lower CRC-specific mortality in women [HR continuous pattern score divided by its respective SD (HR1SD): 0.86; 95% CI: 0.77, 0.96] but not in men (HR1SD: 1.01; 95% CI: 0.92, 1.11). A higher aMED score was also associated with lower all-cause mortality in women (HR1SD: 0.88; 95% CI: 0.81, 0.96) but not in men (HR1SD: 1.00; 95% CI: 0.93, 1.07). The HEI-2010, AHEI-2010, and DASH index were not significantly associated with CRC-specific or with all-cause mortality. The inverse relation for the aMED score was limited to African Americans and to colon (compared with rectal) cancer. CONCLUSIONS The aMED score was related to lower mortality only in African-American women (1 of 5 ethnic groups studied). The results should be interpreted with caution due to the small numbers of cases within ethnic groups and the issue of multiple testing.
Service of Remembrance: A Comprehensive Cancer Center's Response to Bereaved Family Members

Comprehensive cancer centers that offer an array of clinical trials and treatment options often experience significant patient mortality rates. Bereavement resources may not be routinely incorporated into the service delivery model in these specialty hospitals. In response, an interdisciplinary team at one cancer center proposed, planned, and implemented an annual Service of Remembrance. The incorporation of music, poetry, and visual arts was important in designing a program that would provide a meaningful, spiritual experience. A community artist who designed an interactive memorial art piece played a pivotal role. This article outlines the process of institutional culture change and describes future challenges in the implementation of this type of bereavement service.
Potential Impacts of Antibiotic Use in Poultry Production

Abstract The ways in which antibiotics are used in poultry production have changed considerably during the past decade, mainly because of concerns about potential negative human health consequences caused by these uses. Human health improvements directly attributable to these antibiotic-use changes are difficult to demonstrate. Given that some antibiotics will continue to be used in the poultry industry, methods are needed for estimating the causal relationship between these antibiotic uses and actual animal and human health impacts. This is a challenging task because of the numerous factors that are able to select for the emergence, dissemination, and persistence of antibiotic resistance. Managing the potential impacts of antibiotic use in poultry requires more than a simple estimation of the risks that can be attributed to the use of antibiotics in poultry. Risk models and empirical studies that evaluate interventions that are capable of minimizing the negative consequences associated with specific antibiotic uses are desperately needed.
What is State Capacity?

Reform leaders who want to pursue technically sound policies are confronted with the problem of getting myriad government agencies, staffed by thousands of bureaucrats and state personnel, to deliver. This paper provides a framework for thinking about the problem as a series of interdependent principal-agent relationships in complex organizations, where one type of actor, the agent, takes actions on behalf of another, the principal. Using this framework to review and forge connections across a large literature, the paper shows how the crux of state capacity is the culture of bureaucracies -- the incentives, beliefs and expectations, or norms, shared among state personnel about how others are behaving. Although this characterization might apply generally to any complex organization, what distinguishes agencies of the state is the fundamental role of politics -- the processes by which the leaders who exercise power over bureaucracies, starting from the lowest village levels, are selected and sanctioned. Politics shapes not only the incentives of state personnel, but perhaps more importantly, it coordinates their beliefs and expectations, and thereby the performance of government agencies. Recognizing these roles of politics, the paper offers insights for what reform leaders can do to strengthen state capacity for public goods.
The mouse mammary tumour virus long terminal repeat encodes a type II transmembrane glycoprotein.

Superantigens are products of bacterial or viral origin which stimulate large numbers of T cells as a consequence of the interaction of particular V beta chains of the T cell receptor with class II major histocompatibility complex (MHC) molecules and superantigen on the stimulating cell. The Minor lymphocyte stimulatory (Mls) antigens, originally discovered as strong lymphocyte stimulatory determinants in vitro and subsequently shown to delete T cells expressing specific V beta chains during development, have recently been shown to be genetically linked to endogenous mouse mammary tumour viruses (MTVs). This stimulation is effectuated by an unidentified product encoded by an open reading frame (orf) present in the 3′ long terminal repeat (LTR) of MTVs. Using in vitro translation in the presence of rough microsomal vesicles, we show that (i) the orf of MTV encodes a type II transmembrane glycoprotein (N‐terminus intracellular, C‐terminus extracytoplasmic), and (ii) a cotranslationally secreted orf protein is not produced. We have also isolated and sequenced several endogenous MTV orfs (MTV‐1, MTV‐6 and MTV‐13) which are involved in the deletion of V beta‐bearing T cells; each of these sequences are nearly identical to each other. These observations, together with sequence comparisons of several orf genes, lead to a model of action of viral superantigens.
Facilitation of laryngeal mask insertion

The effects of pretreatment with lignocaine administered intravenously on the insertion of the laryngeal mask airway were investigated in 80 unpremedicated, ASA 1 or 2, adult day‐case patients in a randomised, double‐blind, placebo‐controlled trial. Patients received either intravenous lignocaine 1.5mg. kg‐1 or an equivalent volume of sodium chloride 0.9%. Induction of anaesthesia was achieved with propofol given via a syringe driver at a fixed rate of 600ml.h‐1 until the patient dropped a weighted syringe. No opioid or sedative drugs were given prior to induction. Pain on injection of propofol was recorded. Jaw opening, ease of insertion of the laryngeal mask, coughing, gagging and airway patency were all scored on three‐point scales immediately after mask insertion. If insertion failed, anaesthesia was deepened by gentle manual ventilation for 1 min with nitrous oxide/oxygen/2% enflurane and insertion re‐attempted. This cycle was continued until success was achieved and the number of such cycles recorded. There were no differences between the lignocaine and control groups with respect to induction dose of propofol, degree of jaw opening, or amount of gagging. Laryngeal mask insertion was facilitated by pretreatment with lignocaine administered intravenously, without an alteration in induction dose of propofol (p < 0.05). Coughing and airway obstruction were both significantly reduced by pretreatment with lignocaine, as was the incidence of failure of insertion requiring deepening of anaesthesia (p < 0.05).
Analysis of the mechanism of activation of cAMP-dependent protein kinase through the study of mutants of the yeast regulatory subunit.

Spontaneous mutations in the gene which encodes the regulatory subunit of cAMP-dependent protein kinase (PKA) of Saccharomyces cerevisiae (BCY1) have been isolated previously [Cannon, J. F. , Gibbs, J. B. & Tatchell, K. (1986) Genetics 113, 247-264] by selection of ras2::LEU2 revertants that grew on non-fermentable carbon sources. The revertants were placed into groups of increasing severity based on the number of PKA-dependent traits affected [Cannon, J. F. , Gitan, R. & Tatchell, K. (1990) J. Biol. Chem. 265, 11897-11904]. In this work the ras2 mutation has been crossed out in each bcy1 allele and the phenotypes of these mutants have been assessed. The order of severity of the mutants in both genetic backgrounds is maintained but the severity of each mutant in the normal background is higher than in the ras2::LEU2 background. Total catalytic-subunit and regulatory-subunit activities were measured in crude extracts of the bcy1 ras2::LEU2 mutants. With one exception (bcy1-6) the calculated regulatory subunit/catalytic subunit ratios of the bcy1 mutants relative to that of wild-type cells were greater than one. The dependence of PKA activity on cAMP was measured in permeabilized cells. The strains show an activity ratio in the absence and presence of cAMP in the range 0.5-1 for Kemptide phosphorylation. Overexpression of the high-affinity cAMP phosphodiesterase gene (PDE2) in the bcy1 ras2::LEU2 strains did not alter their PKA-dependent phenotypes. However, transformants were not observed from the parental ras2::LEU2 strain and the bcy1-6 ras2::LEU2 strain. The results are discussed with respect to a hypothesis for the molecular mechanism of the differential reversal of ras2 phenotypes by the bcy1 alleles. Mutations in the regulatory subunit are predicted to affect the structure of the holoenzyme such that the catalytic subunit is capable of maintaining an active catalytic state, without the need to dissociate from the regulatory subunit.
Reverse transcription of the HIV‐1 pandemic

The HIV/AIDS pandemic has existed for >25 years. Extensive work globally has provided avenues to combat viral infection, but the disease continues to rage on in the human population and infected ~4 million people in 2006 alone. In this review, we provide a brief history of HIV/AIDS, followed by analysis of one therapeutic target of HIV‐1: its reverse transcriptase (RT). We discuss the biochemical characterization of RT in order to place emphasis on possible avenues of inhibition, which now includes both nucleoside and non‐nucleoside modalities. Therapies against RT remain a cornerstone of anti‐HIV treatment, but the virus eventually resists inhibition through the selection of drug‐resistant RT mutations. Current inhibitors and associated resistance are discussed, with the hopes that new therapeutics can be developed against RT. — Basavapathruni, A. , Anderson, K. S. Reverse transcription of the HIV‐1 pandemic. FASEB J. 21, 3795–3808 (2007)
Spliced mRNA Encoding the Murine Cytomegalovirus Chemokine Homolog Predicts a β Chemokine of Novel Structure

ABSTRACT A viral mRNA of the late kinetic class expressed by murine cytomegalovirus (MCMV) contains an open reading frame (ORF) whose predicted protein, designated MCK-1, has homology to β chemokines (M. R. MacDonald, X.-Y. Li, and H. W. Virgin IV, J. Virol. 71:1671–1678, 1997). The present study analyzed further the structure of the transcript in infected fibroblast cells. A splicing event removed the MCK-1 stop codon, bringing a downstream ORF into frame with the chemokine homolog and demonstrating that the MCK-1 ORF was an exon of a larger gene. The predicted 31.4-kDa protein, designated MCK-2, contains a putative amino-terminal signal sequence and a β chemokine domain, followed by a carboxyl-terminal domain without significant homology to known proteins. Quantitative analysis of mRNA forms in MCMV-infected fibroblast cells at late times after infection indicated that the viral chemokine RNA was predominantly spliced. There was no evidence for expression of RNA encoding either MCK-1 or MCK-2 at immediate early or early times after infection with MCMV. Monoclonal antibodies generated against bacterially expressed MCK-2 recognized multiple proteins in the range of ∼30 to ∼45 kDa in Western blot analysis of MCK-2 expressed in transfected COS cells. The monoclonal antibodies immunoprecipitated a similar group of proteins in transfected COS cells metabolically labeled with radioactive cysteine. Radiolabelled protein of apparent higher molecular mass was immunoprecipitated from culture medium overlying the transfected cells, suggesting that posttranslationally modified MCK-2 can be secreted. Two proteins with apparent molecular mass suggestive of posttranslational modification were detected by Western blot analysis of cells harvested at late times after infection with MCMV. These studies show that MCMV encodes and expresses a β chemokine homolog with a novel predicted structure.
Structure and function of Norrin in assembly and activation of a Frizzled 4–Lrp5/6 complex

Norrin is an important growth factor and Wnt ligand required for angiogenesis in the eye, ear, brain, and female reproductive organs. Structural and functional studies by Ke et al. now reveal that Norrin forms a unique dimer required for binding and activation of the Frizzled 4 (Fz4) receptor. Interestingly, Norrin contains separate binding sites for Wnt ligand coreceptors Lrp5/6 and induces the formation of a ternary complex with Fz4 and Lrp5/6 extracellular domains. This study provides critical new insight into the Wnt and Norrin signaling pathways.
Health-related quality of life in children and adolescents with juvenile localized scleroderma.

OBJECTIVES To examine the health-related quality of life (HRQOL) of children with juvenile localized scleroderma (JLS) and to compare them with patients with atopic dermatitis (AD) and healthy controls. METHODS The cohorts were identified through a diagnostic index and were seen between January 1996 and December 2006. We identified 81 JLS patients to whom we age- and sex-matched 75 AD patients and 75 healthy controls. All patients were mailed a survey containing the English-language version of the German Revised Children's Quality of Life Questionnaire (KINDL) and the Children's Dermatology Life Quality Index (CDLQI). Linear regression models, adjusted for age and sex, examined differences in the KINDL and CDLQI scores. RESULTS Survey completion rates in the JLS, AD and healthy control groups were 40, 28 and 44%, respectively. There was no difference in KINDL scores between JLS vs AD (73 vs 74, P = 0.3) and JLS vs healthy controls (73 vs 74, P = 0.8). However, CDLQI scores showed some impairment in HRQOL in JLS patients as compared with a healthy reference population, but not to the degree seen in AD (2 vs 4, P = 0.05). An exploratory analysis showed that HRQOL did not differ among the types of JLS with either measure. CONCLUSION JLS patients have some impairment in skin disease-specific HRQOL when compared with a healthy reference population, but not as severe as that seen in AD patients. Overall HRQOL in this JLS cohort was as good as healthy controls, a reassuring finding for patients, families and healthcare providers.
Probiotics for the prevention of pediatric upper respiratory tract infections: a systematic review

Background: Acute upper respiratory tract infections (URTIs) contribute substantially to pediatric morbidity and mortality worldwide. Prevention of these infections in childhood is a very important public health challenge. Previous systematic reviews, including both adult and childhood populations, have reported that probiotics seem promising, but with modest evidence. This study aimed to focus on prophylactic probiotic use in the prevention of URTIs in childhood. Methods: Relevant trials on two databases were identified in a systematic review, from inception to June 2014. Study selection, data extraction and quality assessment were carried out by two reviewers. In this review, the effects of probiotics, particularly the Lactobacillus and Bifidobacterium strains, on the incidence and symptom scores of URTI in otherwise healthy children were evaluated for the first time. This review comprises 14 randomized controlled trials (RCTs) applied to a pediatric population with high-quality methodology. Results: This systematic review suggests that probiotics in immunocompetent children have a modest effect both in diminishing the incidence of URTIs and the severity of the infection symptoms. Conclusions: At least one beneficial effect of prophylactic probiotic was observed in the majority of RCTs. Even a minimal reduction of 5 – 10% in the incidence of URTIs would have an important clinical and economic mpact on societies. Furthermore, the long-term administration of probiotics appeared to have a good safety profile in childhood and none of the studies reported any serious adverse events related to the probiotic strain.
16S rDNA analysis of periodontal plaque in chronic obstructive pulmonary disease and periodontitis patients

ABSTRACT This study investigated if chronic obstructive pulmonary disease (COPD) is correlated with periodontitis via periodontal microbiota and if certain bacteria affect periodontitis as well as COPD. Moreover, the study investigated whether suffering from COPD is associated with a decrease in the richness and diversity of periodontal microbiota. Subgingival plaque was obtained from 105 patients. Bacterial DNA was isolated from 55 COPD and 50 non-COPD participants (either with or without periodontitis). 16S rRNA gene metagenomic sequencing was used to characterize the microbiota and to determine taxonomic classification. In the non-periodontitis patients, suffering from COPD resulted in a decrease in bacteria richness and diversity in the periodontal microenvironment. An increase in the genera Dysgonomonas, Desulfobulbus, and Catonella and in four species (Porphyromonas endodontalis, Dysgonomonas wimpennyi, Catonella morbi, and Prevotella intermedia) in both COPD and periodontitis patients suggests that an increase in these periodontitis-associated microbiota may be related to COPD. Three genera (Johnsonella, Campylobacter, and Oribacterium) were associated with COPD but not with periodontitis. The decrease in the genera Arcanobacterium, Oribacterium, and Streptomyces in COPD patients implies that these genera may be health-associated genera, and the decrease in these genera may be related to disease. These data support the hypothesis that COPD is correlated with periodontitis via these significantly changed specific bacteria.