bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lyme Borreliosis Serology: Performance of Several Commonly Used Laboratory Diagnostic Tests and a Large Resource Panel of Well-Characterized Patient Samples
Authors: Molins Claudia R. , Delorey Mark J. , Sexton Christopher , Schriefer Martin E. 
Published: August 2016

ABSTRACTThe current recommendation for the laboratory confirmation of Lyme disease is serology-based diagnostics. Specifically, a standardized two-tiered testing (STTT) algorithm is applied that utilizes a first-tier immunofluorescence assay or enzyme immunoassay (EIA) that, if the result is positive or equivocal, is followed by second-tier immunoblotting. Despite the standardization and performance achievements, STTT is considered technically complex and subjective, as well as insensitive for early acute infection. These issues have prompted development of novel algorithms and testing platforms. In this study, we evaluated the performance of several commonly used assays for STTT. Several modified two-tiered testing (MTTT) algorithms, including a 2-EIA algorithm and modified criteria for second-tier IgG immunoblots, were also evaluated. All tests were performed on sera from a recently available, well-defined archive of positive- and negative-control patients. Our study demonstrates differences in the results between individual first- and second-tier tests, although the overall agreement of the different STTT algorithms used was strong. In addition, the MTTT algorithm utilizing 2-EIAs was found to be equivalent to all STTT algorithms tested, with agreement ranging from 94 to 97%. The 2-EIA MTTT algorithm slightly enhanced sensitivity in early disease compared to the STTT algorithms evaluated. Furthermore, these data add to the mounting evidence that a 2-EIA-based MTTT algorithm, where immunoblotting is replaced by the C6 EIA, performs as well or better than STTT.
Reduction of Neuraminidase Activity Exacerbates Disease in 2009 Pandemic Influenza Virus-Infected Mice
Authors: Ranadheera Charlene , Hagan Mable W. , Leung Anders , Collignon Brad , Cutts Todd , Theriault Steven , Embury-Hyatt Carissa , Kobasa Darwyn 
Published: August 2016

ABSTRACT
During the first wave of the 2009 pandemic, caused by a H1N1 influenza virus (pH1N1) of swine origin, antivirals were the only form of therapeutic available to control the proliferation of disease until the conventional strain-matched vaccine was produced. Oseltamivir is an antiviral that inhibits the sialidase activity of the viral neuraminidase (NA) protein and was shown to be effective against pH1N1 viruses in ferrets. Furthermore, it was used in humans to treat infections during the pandemic and is still used for current infections without reported complication or exacerbation of illness. However, in an evaluation of the effectiveness of oseltamivir against pH1N1 infection, we unexpectedly observed an exacerbation of disease in virus-infected mice treated with oseltamivir, transforming an otherwise mild illness into one with high morbidity and mortality. In contrast, an identical treatment regime alleviated all signs of illness in mice infected with the pathogenic mouse-adapted virus A/WSN/33 (H1N1). The worsened clinical outcome with pH1N1 viruses occurred over a range of oseltamivir doses and treatment schedules and was directly linked to a reduction in NA enzymatic activity. Our results suggest that the suppression of NA activity with antivirals may exacerbate disease in a host-dependent manner by increasing replicative fitness in viruses that are not optimally adapted for replication in that host.

IMPORTANCE
Here, we report that treatment of pH1N1-infected mice with oseltamivir enhanced disease progression, transforming a mild illness into a lethal infection. This raises a potential pitfall of using the mouse model for evaluation of the therapeutic efficacy of neuraminidase inhibitors. We show that antiviral efficacy determined in a single animal species may not represent treatment in humans and that caution should be used when interpreting the outcome. Furthermore, increased virulence due to oseltamivir treatment was the effect of a shift in the hemagglutinin (HA) and neuraminidase (NA) activity balance. This is the first study that has demonstrated that altering the HA/NA activity balance by reduction in NA activity can result in an increase in virulence in any animal model from nonpathogenic to lethal and the first to demonstrate a situation in which treatment with a NA activity inhibitor has an effect opposite to the intended therapeutic effect of ameliorating the infection.
Costs associated with functional gastrointestinal disorders and related signs and symptoms in infants: a systematic review protocol
Authors: Glanville Julie , Ludwig Thomas , Lifschitz Carlos , Mahon James , Miqdady Mohamad , Saps Miguel , Hock Quak Seng , Lenoir-Wijnkoop Irene , Edwards Mary , Wood Hannah , Szajewska Hania 
Published: August 2016

IntroductionFunctional gastrointestinal disorders (FGIDs) and FGID-related signs and symptoms have a fundamental impact on the psychosocial, physical and mental well-being of infants and their parents alike. Recent reviews and studies have indicated that FGIDs and related signs and symptoms may also have a substantial impact on the budgets of third-party payers and/or parents. The objective of this systematic review is to investigate these costs.Methods and analysisThe population of interest is healthy term infants (under 12 months of age) with colic, regurgitation and/or functional constipation. Outcomes of interest will include the frequency and volume of reported treatments, the cost to third-party payers and/or parents for prescribed or over the counter treatments, visits to health professionals and changes in infant formula purchases, and the loss of income through time taken off work and out of pocket costs. Relevant studies will be identified by searching databases from 2005 onwards (including MEDLINE, EMBASE, PsycINFO, NEXIS, DARE, Health Technology Assessment database, National Health Service Economic Evaluation Database and others), conferences from the previous 3 years and scanning reference lists of eligible studies. Study selection, data extraction and quality assessment will be conducted by two independent reviewers and disagreements resolved in discussion with a third reviewer. Quality assessment will involve study design-specific checklists. Relevant studies will be summarised narratively and presented in tables. An overview of treatments and costs will be provided, with any geographical or other differences highlighted. An assessment of how the totals for cost differ across countries and elements that contribute to the differences will be generated.Ethics and disseminationThis is a systematic review of published studies that will be submitted for publication to a peer-reviewed journal. Ethical committee approval is not required.Trial registration numberCRD42016033119.
Drug-Driven Synthetic Lethality: Bypassing Tumor Cell Genetics with a Combination of AsiDNA and PARP Inhibitors
Authors: Jdey Wael , Thierry Sylvain , Russo Christophe , Devun Flavien , Al Abo Muthana , Noguiez-Hellin Patricia , Sun Jian-Sheng , Barillot Emmanuel , Zinovyev Andrei , Kuperstein Inna , Pommier Yves , Dutreix Marie 
Published: August 2016

Abstract
Purpose: Cancer treatments using tumor defects in DNA repair pathways have shown promising results but are restricted to small subpopulations of patients. The most advanced drugs in this field are PARP inhibitors (PARPi), which trigger synthetic lethality in tumors with homologous recombination (HR) deficiency. Using AsiDNA, an inhibitor of HR and nonhomologous end joining, together with PARPi should allow bypassing the genetic restriction for PARPi efficacy.
Experimental Design: We characterized the DNA repair inhibition activity of PARPi (olaparib) and AsiDNA by monitoring repair foci formation and DNA damage. We analyzed the cell survival to standalone and combined treatments of 21 tumor cells and three nontumor cells. In 12 breast cancer (BC) cell lines, correlation with sensitivity to each drug and transcriptome were statistically analyzed to identify resistance pathways.
Results: Molecular analyses demonstrate that olaparib and AsiDNA respectively prevent recruitment of XRCC1 and RAD51/53BP1 repair enzymes to damage sites. Combination of both drugs increases the accumulation of unrepaired damage resulting in an increase of cell death in all tumor cells. In contrast, nontumor cells do not show an increase of DNA damage nor lethality. Analysis of multilevel omics data from BC cells highlighted different DNA repair and cell-cycle molecular profiles associated with resistance to AsiDNA or olaparib, rationalizing combined treatment. Treatment synergy was also confirmed with six other PARPi in development.
Conclusions: Our results highlight the therapeutic interest of combining AsiDNA and PARPi to recapitulate synthetic lethality in all tumors independently of their HR status. Clin Cancer Res; 23(4); 1001–11. ©2016 AACR.
Sex Differences in Mental Stress‐Induced Myocardial Ischemia in Patients With Coronary Heart Disease
Authors: Vaccarino Viola , Wilmot Kobina , Mheid Ibhar Al , Ramadan Ronnie , Pimple Pratik , Shah Amit J. , Garcia Ernest V. , Nye Jonathon , Ward Laura , Hammadah Muhammad , Kutner Michael , Long Qi , Bremner J. Douglas , Esteves Fabio , Raggi Paolo , Quyyumi Arshed A. 
Published: August 2016

Background

Emerging data suggest that young women with coronary heart disease (
CHD
) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable
CHD
are more likely than their male peers to develop mental stress‐induced myocardial ischemia (
MSIMI
).

Methods and Results

We studied 686 patients (191 women) with stable coronary heart disease (
CHD
). Patients underwent
99m
Tc‐sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more‐adverse psychosocial profile than men whereas there were few differences in medical history and
CHD
risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction,
P
<0.001) and the incidence of
MSIMI
was 82.6% higher (interaction,
P
=0.004) in women than in men. Incidence of
MSIMI
in women ≤50 years was almost 4‐fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress.

Conclusions

Young women with stable
CHD
are susceptible to
MSIMI
, which could play a role in the prognosis of this group.
Different Combinations of Glucose Tolerance and Blood Pressure Status and Incident Diabetes, Hypertension, and Chronic Kidney Disease
Authors: Derakhshan Arash , Bagherzadeh‐Khiabani Farideh , Arshi Banafsheh , Ramezankhani Azra , Azizi Fereidoun , Hadaegh Farzad 
Published: August 2016

Background

The impact of different combinations of glucose tolerance and blood pressure status on the development of type 2 diabetes mellitus (T2
DM
), hypertension (
HTN
), and chronic kidney disease (
CKD
) still needs to be investigated.

Methods and Results

A total of 12 808 Iranian adults aged ≥20 years were included in 3 separate analyses to investigate incidence of T2
DM
,
HTN
, and
CKD
. Multivariate Cox proportional hazard models were used to calculate hazard ratios (95%
CI
). During a median follow‐up of >10 years, the overall incidence rate for T2
DM
,
HTN
, and
CKD
was 12.2, 29.8, and 24.8 per 1000 person‐years. For incident T2
DM
, considering normal glucose tolerance/normal blood pressure as reference, prediabetes (Pre
DM
)/
HTN
had the highest risk (hazard ratio: 7.22 [5.71–9.12]) while Pre
DM
/normal blood pressure also showed a significant risk (5.58 [4.41–7.05]). Furthermore, risk of Pre
DM
/
HTN
was higher than Pre
DM
/normal blood pressure (
P
<0.05). For incident
HTN
, normal glucose tolerance/prehypertension was a strong predictor (3.28 [2.91–3.69]); however, addition of Pre
DM
or T2
DM
did not increase the risk. For incident
CKD
, every category that included
HTN
and/or T2
DM
showed significant risk; this risk was marginally significant for the Pre
DM
/
HTN
group (1.19 [0.98–1.43],
P
=0.06). In addition, Pre
DM
/ normal blood pressure was a marginally significant risk factor for incident
HTN
while normal glucose tolerance/prehypertension was a significant predictor of T2
DM
.

Conclusions

Presence of
HTN
was associated with increased risk of T2
DM
among the Pre
DM
population; however, dysglycemia did not increase the risk of
HTN
among individuals with prehypertension. For incident
CKD
, intensive management of
HTN
and T2
DM
, rather than their predisease states, should be considered.
Prevalence of Low Cardiovascular Risk Profile Among Diverse Hispanic/Latino Adults in the United States by Age, Sex, and Level of Acculturation: The Hispanic Community Health Study/Study of Latinos
Authors: Daviglus Martha L. , Pirzada Amber , Durazo‐Arvizu Ramon , Chen Jinsong , Allison Matthew , Avilés‐Santa Larissa , Cai Jianwen , González Hector M. , Kaplan Robert C. , Schneiderman Neil , Sorlie Paul D. , Talavera Gregory A. , Wassertheil‐Smoller Sylvia , Stamler Jeremiah 
Published: August 2016

Background

Favorable levels of all readily measurable major cardiovascular disease risk factors (ie, low risk [
LR
]) are associated with lower risks of cardiovascular disease morbidity and mortality. Data are not available on
LR
prevalence among Hispanic/Latino adults of diverse ethnic backgrounds. This study aimed to describe the prevalence of a low cardiovascular disease risk profile among Hispanic/Latino adults in the United States and to examine cross‐sectional associations of
LR
with measures of acculturation.

Methods and Results

The multicenter, prospective, population‐based Hispanic Community Health Study/Study of Latinos examined 16 415 men and women aged 18 to 74 years at baseline (2008–2011) with diverse Hispanic/Latino backgrounds. Analyses involved 14 757 adults (mean age 41.3 years; 60.6% women).
LR
was defined using national guidelines for favorable levels of serum cholesterol, blood pressure, and body mass index and by not having diabetes mellitus and not currently smoking. Age‐adjusted
LR
prevalence was low (8.4% overall; 5.1% for men, 11.2% for women) and varied by background (4.2% in men of Mexican heritage versus 15.0% in women of Cuban heritage). Lower acculturation (assessed using proxy measures) was significantly associated with higher odds of a
LR
profile among women only: Age‐adjusted odds ratios of having LR were 1.64 (95% CI 1.24–2.17) for foreign‐born versus
US
‐born women and 1.96 (95% CI 1.49–2.58) for women residing in the United States <10 versus ≥10 years.

Conclusions

Among diverse
US
Hispanic/Latino adults, the prevalence of a
LR
profile is low. Lower acculturation is associated with higher odds of a
LR
profile among women but not men. Comprehensive public health strategies are needed to improve the cardiovascular health of
US
Hispanic/Latino adults.
A Seasonal Rainfall Performance Probability Tool for Famine Early Warning Systems
Authors: Novella Nicholas S. , Thiaw Wassila M. 
Published: August 2016

AbstractThis paper reports on the development of a new statistical tool that generates probabilistic outlooks of seasonal precipitation anomaly categories over Africa. Called the seasonal performance probability (SPP), it quantitatively evaluates the probability of precipitation to finish at predefined percent-of-normal anomaly categories corresponding to below-average (<80% of normal), average (80%–120% of normal), and above-average (>120% of normal) conditions. This is accomplished by applying methods for kernel density estimation (KDE), which compute smoothed, continuous density functions on the basis of more than 30 years of historical precipitation data from the Africa Rainfall Climatology, version 2, dataset (ARC2) for the remaining duration of a monsoon season. Discussion of various parameterizations of KDE and testing to determine optimality of density estimates (and thus performance of SPP for operational monitoring) are presented. Verification results from 2006 to 2015 show that SPP reliably provides probabilistic outcomes of seasonal rainfall anomaly categories by after the early to midstages of rain seasons for the major monsoon regions in East Africa, West Africa, and southern Africa. SPP has proven to be a useful tool by enhancing operational climate monitoring at CPC for its prognostic capability for famine early warning scenarios over Africa. These insights are anticipated to translate into better decision-making in food security, planning, and response objectives for the U.S. Agency for International Development/Famine Early Warning Systems Network (USAID/FEWS NET).
Connection between Anomalous Zonal Activities of the South Asian High and Eurasian Summer Climate Anomalies
Authors: Shi Jian , Qian Weihong 
Published: August 2016

Abstract
Using the daily mean anomalies of atmospheric variables from the NCEP Reanalysis-1 (NCEP R1), this study reveals the connection between anomalous zonal activities of the South Asian high (SAH) and Eurasian climate anomalies in boreal summer. An analysis of variance identifies two major domains with larger geopotential height variability located in the eastern and western flanks of the SAH at around 100 and 150 hPa, respectively. For both eastern and western domains, extreme events are selected during 1981–2014 when normalized height anomalies are greater than 1.0 (less than −1.0) standard deviation for at least 10 consecutive days. Based on these events, four SAH modes that include strong and weak Tibetan modes (STM and WTM, respectively) and strong and weak Iranian modes (SIM and WIM, respectively) are defined to depict the zonal SAH features. The positive composite in the eastern (western) domain indicates the STM (SIM) manifests a robust wavelike pattern with an anomalous low at 150 hPa, and surface cold and wet anomalies over Mongolia and northern China (Kazakhstan and western Siberia) are surrounded by three anomalous highs at 150 hPa and surface warm and dry anomalies over Eurasia. Opposite distributions are also evident in the negative composites of the two domains (WTM and WIM). The surface air temperature anomalies are the downward extension of an anomalous air column aloft while the precipitation anomalies are directly associated with the height anomalies above the air column.
The GPM Combined Algorithm
Authors: Grecu Mircea , Olson William S. , Munchak Stephen Joseph , Ringerud Sarah , Liao Liang , Haddad Ziad , Kelley Bartie L. , McLaughlin Steven F. 
Published: August 2016

AbstractIn this paper, the operational Global Precipitation Measurement (GPM) mission combined radar–radiometer algorithm is thoroughly described. The operational combined algorithm is designed to reduce uncertainties in GPM Core Observatory precipitation estimates by effectively integrating complementary information from the GPM Dual-Frequency Precipitation Radar (DPR) and the GPM Microwave Imager (GMI) into an optimal, physically consistent precipitation product. Although similar in many respects to previously developed combined algorithms, the GPM combined algorithm has several unique features that are specifically designed to meet the GPM objectives of deriving, based on GPM Core Observatory information, accurate and physically consistent precipitation estimates from multiple spaceborne instruments, and ancillary environmental data from reanalyses. The algorithm features an optimal estimation framework based on a statistical formulation of the Gauss–Newton method, a parameterization for the nonuniform distribution of precipitation within the radar fields of view, a methodology to detect and account for multiple scattering in Ka-band DPR observations, and a statistical deconvolution technique that allows for an efficient sequential incorporation of radiometer information into DPR precipitation retrievals.
Assessment of NOAA National Weather Service Methods to Warn for Extreme Heat Events
Authors: Hawkins Michelle D. , Brown Vankita , Ferrell Jannie 
Published: August 2016

Abstract
Recent climate studies have predicted a future with longer, more intense, and more frequent heat events. Evolving challenges presented by this paradigm necessitate an assessment of current efforts to warn for extreme heat events. NOAA’s National Weather Service (NWS) Weather Forecast Offices (WFOs) issue Excessive Heat Watch, Excessive Heat Warning, and Heat Advisory products as conditions warrant. In the fall of 2013 the NWS conducted an internal assessment with its WFOs to 1) document variations in the usage of heat-based watch, warning, and advisory hazard messages (products) across the country; 2) learn about the degree to which locally developed criteria are applied to forecaster decision-making processes in issuing these products; and 3) gather ideas for enhancing communication of expected excessive heat events in general. Survey responses indicate that WFOs selectively use one or a combination of products, and that various methodologies are used to develop criteria for issuing heat products. Given that forecasters use meteorological and nonmeteorological factors when deciding to issue heat products, forecaster judgment is a crucial element of the warning process. Results also revealed partner confusion due to inconsistent heat product issuance criteria. Suggestions were made for eliminating or revising existing products and policies, or creating new products, policies, or issuance criteria. Results of the survey led the NWS to investigate approaches for achieving higher levels of consistency in heat product issuance criteria, and to engage health partners to examine how heat product issuance criteria could incorporate the known health impacts of heat exposure.
The Conditional Nature of the Local Warming Effect
Authors: Druckman James N. , Shafranek Richard M. 
Published: August 2016

Abstract
The local warming effect occurs when perceived deviations in the day’s temperature affect individuals’ global warming beliefs. When people perceive the day to be warmer than usual, they tend to overestimate the number of warm days throughout the year, and to report increased belief in and worry about global warming. For many, this is normatively concerning because a single day’s perceived temperature fluctuation is not representative of longer-term, large-scale climate patterns. It thus makes for a poor basis for global warming judgments. Recent work shows that the local warming effect might disappear when people receive a reminder to think about weather patterns over the past year (i.e., a correction). This paper employs a survey experiment that extends past research by exploring the generalizability, conditionality, and durability of the corrective information. It identifies the conditions under which a local warming effect is more or less likely to occur.