bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ablation of phospholamban rescues reperfusion arrhythmias but exacerbates myocardium infarction in hearts with Ca2+/calmodulin kinase II constitutive phosphorylation of ryanodine receptors
Authors: Valverde Carlos A , Mazzocchi Gabriela , Di Carlo Mariano N , Ciocci Pardo Alejandro , Salas Nehuen , Ragone María Ines , Felice Juan I , Cely-Ortiz Alejandra , Consolini Alicia E , Portiansky Enrique , Mosca Susana , Kranias Evangelia G , Wehrens Xander H T , Mattiazzi Alicia 
Published: August 2018

Abstract

Aims
Abnormal Ca2+ release from the sarcoplasmic reticulum (SR), associated with Ca2+-calmodulin kinase II (CaMKII)-dependent phosphorylation of RyR2 at Ser2814, has consistently been linked to arrhythmogenesis and ischaemia/reperfusion (I/R)-induced cell death. In contrast, the role played by SR Ca2+ uptake under these stress conditions remains controversial. We tested the hypothesis that an increase in SR Ca2+ uptake is able to attenuate reperfusion arrhythmias and cardiac injury elicited by increased RyR2-Ser2814 phosphorylation.

Methods and results
We used WT mice, which have been previously shown to exhibit a transient increase in RyR2-Ser2814 phosphorylation at the onset of reperfusion; mice with constitutive pseudo-phosphorylation of RyR2 at Ser2814 (S2814D) to exacerbate CaMKII-dependent reperfusion arrhythmias and cardiac damage, and phospholamban (PLN)-deficient-S2814D knock-in (SDKO) mice resulting from crossbreeding S2814D with phospholamban knockout deficient (PLNKO) mice. At baseline, S2814D and SDKO mice had structurally normal hearts. Moreover none of the strains were arrhythmic before ischaemia. Upon cardiac I/R, WT, and S2814D hearts exhibited abundant arrhythmias that were prevented by PLN ablation. In contrast, PLN ablation increased infarct size compared with WT and S2814D hearts. Mechanistically, the enhanced SR Ca2+ sequestration evoked by PLN ablation in SDKO hearts prevented arrhythmogenic events upon reperfusion by fragmenting SR Ca2+ waves into non-propagated and non-arrhythmogenic events (mini-waves). Conversely, the increase in SR Ca2+ sequestration did not reduce but rather exacerbated I/R-induced SR Ca2+ leak, as well as mitochondrial alterations, which were greatly avoided by inhibition of RyR2. These results indicate that the increase in SR Ca2+ uptake is ineffective in preventing the enhanced SR Ca2+ leak of PLN ablated myocytes from either entering into nearby mitochondria and/or activating additional CaMKII pathways, contributing to cardiac damage.

Conclusion
Our results demonstrate that increasing SR Ca2+ uptake by PLN ablation can prevent the arrhythmic events triggered by CaMKII-dependent phosphorylation of RyR2-induced SR Ca2+ leak. These findings underscore the benefits of increasing SERCA2a activity in the face of SR Ca2+ triggered arrhythmias. However, enhanced SERCA2a cannot prevent but rather exacerbates I/R cardiac injury.
Fractalis: a scalable open-source service for platform-independent interactive visual analysis of biomedical data
Authors: Herzinger Sascha , Grouès Valentin , Gu Wei , Satagopam Venkata , Banda Peter , Trefois Christophe , Schneider Reinhard 
Published: August 2018

Abstract

Background
Translational research platforms share the aim of promoting a deeper understanding of stored data by providing visualization and analysis tools for data exploration and hypothesis generation. However, such tools are usually platform bound and are not easily reusable by other systems. Furthermore, they rarely address access restriction issues when direct data transfer is not permitted. In this article, we present an analytical service that works in tandem with a visualization library to address these problems.

Findings
Using a combination of existing technologies and a platform-specific data abstraction layer, we developed a service that is capable of providing existing web-based data warehouses and repositories with platform-independent visual analytical capabilities. The design of this service also allows for federated data analysis by eliminating the need to move the data directly to the researcher. Instead, all operations are based on statistics and interactive charts without direct access to the dataset.

Conclusions
The software presented in this article has a potential to help translational researchers achieve a better understanding of a given dataset and quickly generate new hypotheses. Furthermore, it provides a framework that can be used to share and reuse explorative analysis tools within the community.
Pre-Strike Ballots and Collective Bargaining: The Impact of Quorum and Ballot Mode Requirements on Access to Lawful Industrial Action
Authors: Creighton Breen , Denvir Catrina , Johnstone Richard , McCrystal Shae , Orchiston Alice 
Published: August 2018

Abstract
In 2016, the UK Parliament passed the Trade Union Act 2016 (TU Act 2016), which introduced new quorum and approval requirements for pre-strike ballots. In Australia, mandatory pre-strike ballots, including a quorum requirement, were first introduced in 2006. This article explains the key features of the Australian pre-strike ballot system and reports on quantitative and qualitative empirical research findings on the operation of the ballots process to analyse the majority and quorum requirements, mode of ballot (postal, attendance or electronic) and choice of ballot agent. Quorum is the biggest obstacle to Australian unions authorising strike action under the pre-strike ballot rules, and postal ballots fail to reach quorum at significantly higher rates than do attendance ballots. By introducing quorums and retaining the requirement that all pre-strike ballots must be conducted by post, the TU Act 2016 endorsed the two factors under the Australian regime most likely to impede the authorisation of strike action in a pre-strike ballot.
Microtransplantation: clinical applications and mechanisms
Authors: Cai Bo , Guo Mei , Ai Huisheng 
Published: August 2018

Purpose of review
Microtransplantation (MST) has been successfully used to manage patients with hematological malignancies, especially older patients with acute myeloid leukemia (AML). Recent clinical applications and mechanistic studies of MST are reviewed.

Recent findings
MST improves complete remission rates which have no significant difference among age groups in older patients with AML. Sufficient courses of postremission therapy lead to prolonged overall survival and reduced relapse rate. MST also benefits young patients with low-risk or intermediate-risk AML who lack a human leukocyte antigen-identical donor and shows therapeutic potential extending to other malignancies. Both donor and recipient-derived T cells contribute to the antileukemic effect. Novel methods to monitor donor microchimerism and donor–recipient immune cell interaction may further unveil mechanisms of MST.

Summary
MST shows therapeutic efficacy to several hematological malignancies, whereas mechanistic studies still need to be promoted, and its combination with other targeted therapies is warranted to further reduce relapse rate.
Eviction From Renter-occupied Households and Rates of Sexually Transmitted Infections: A County-level Ecological Analysis
Authors: Niccolai Linda M. , Blankenship Kim M. , Keene Danya E. 
Published: August 2018

Background
Housing instability is linked to numerous health outcomes, but the specific impact of eviction from renter-occupied households, an event that has immediate implications for residential stability for low-income individuals, on sexually transmitted infections (STI) rates has not been adequately studied.

Methods
We examined county-level associations between eviction rates in 2014 and rates of chlamydia and gonorrhea in the following year using publicly available data sources (Eviction Lab National Database and AtlasPlus, respectively). Descriptive statistics compared medians and nonparametric distributions with Krusal-Wallis tests. Linear regression was used to compare tertile categories of eviction rates and STI rates while controlling for potential confounders.

Results
Median rates of chlamydia in counties with low, medium, and high rates of eviction were 229, 270, and 358 cases per 100,000 population, respectively (P < 0.001). The corresponding median rates of gonorrhea were 25, 37, and 75 cases per 100,000 population (P < 0.001). These associations remained statistically significant after controlling for all covariates in adjusted models. The beta coefficients and 95% confidence intervals (95% CI) for chlamydia and gonorrhea comparing high to low county-level eviction rates were 63.8 (95% CI, 45.1–82.5) and 20.4 (95% CI, 13.5–27.4), respectively. Similar associations were observed across levels of poverty and in both metropolitan and nonmetropolitan counties.

Conclusions
County-level eviction rates are associated with chlamydia and gonorrhea rates in a significant and robust way independent of other known predictors of STI. These results suggest that evictions result in residential instability in a way that may increase STI risk.
High Rates of Repeat Chlamydial Infections Among Young Women—Louisiana, 2000–2015
Authors: Cha Susan , Newman Daniel R. , Rahman Mohammad , Peterman Thomas A. 
Published: August 2018

Background
Chlamydial infections are common among young women and can lead to serious reproductive health complications. We assessed the risk of reported repeat chlamydial infection among young women in Louisiana and time interval between infections by age and race/ethnicity.

Methods
We analyzed surveillance data on chlamydial infections reported among women in Louisiana from January 1, 2000, to December 31, 2015. Multiple reports for the same person were matched using unique codes. Chlamydial infections reported more than 30 days after a previous positive test were considered new infections. Women aged 15 to 34 years at first infection during 2000 to 2012 were censored after 3 years or after they had a repeat infection. Cumulative incidence and incidence rate of repeat chlamydial infection among women were determined by year of first infection. Race- and age-specific results were obtained using stratified analyses.

Results
One in 4 women diagnosed with a chlamydial infection at 15–34 years of age in Louisiana had a reported repeat infection in 3 years or less. Risk of repeat infection increased for younger women, racial/ethnic minorities, and women in more recent cohorts. Young black women aged 15 to 19 years in 2012 had the highest risk (44%). Black women also had shorter intervals between infections than white women.

Conclusions
Repeat chlamydial infections were common, especially among young black women. The true number is likely higher because surveillance data only count infections that were detected and reported. Comprehensive prevention strategies are needed to address high rates of repeat chlamydial infections among women.
The Effect of Hormonal Contraception and Menstrual Cycle Timing on Genital Herpes Simplex Virus-2 Shedding and Lesions
Authors: Micks Elizabeth , Son Hyunju , Magaret Amalia , Selke Stacy , Johnston Christine , Wald Anna 
Published: August 2018

Background
The effect of female sex hormones on herpes simplex virus (HSV)-2 shedding and lesion frequency is poorly understood. Previous studies suggest that hormonal contraception may increase the frequency of HSV-2 shedding.

Methods
We studied HSV-2 seropositive women who performed daily genital swabbing for HSV DNA and completed diaries for genital lesions and menses. We used Poisson mixed effects models to determine if HSV detection varied throughout the menstrual cycle, or in response to hormonal contraception. We used the Wilcoxon signed-rank test and rank-sum test to determine if lesion frequency differed by cycle phase or hormonal contraceptive use.

Results
In 189 women aged 19 to 46 years who collected swabs on 10,715 days and were not using hormonal contraception, HSV-2 DNA was detected on 20.9% of days in the follicular phase and 17.8% of days in the luteal phase (rate ratio, 1.19; 95% confidence interval, 1.03–1.37, P = 0.02). Genital lesions did not differ in the follicular versus luteal phase (12.8% vs. 10.7%, P = 0.07). In analyses of hormonal contraception, including 244 women, HSV-2 DNA was detected on 19.0% of days for women not using hormonal contraception and 18.3% of days for those using hormonal contraception (P = 0.50). Lesions were present on 11.1% of days for women not using hormonal contraception, and 8.7% of days for those using hormonal contraception (P = 0.66).

Conclusions
In women with genital HSV-2 infection who are not using hormonal contraception, the follicular phase of the cycle may be associated with a higher frequency of HSV-2 shedding compared to the luteal phase. Lesion frequency is similar during the 2 menstrual phases. Hormonal contraception use was not observed to affect genital HSV-2 DNA detection or lesions.
Neural Correlates of Giving Social Support: Differences Between Giving Targeted Versus Untargeted Support
Authors: Inagaki Tristen K. , Ross Lauren P. 
Published: August 2018

ABSTRACT

Objective
Giving support contributes to the link between social ties and health; however, the neural mechanisms are not known. Giving support in humans may rely on neural regions implicated in parental care in animals. The current studies, therefore, assess the contribution of parental care–related neural regions to giving support in humans and, as a further theoretical test, examine whether the benefits of giving targeted support to single, identifiable individuals in need extend to giving untargeted support to larger societal causes.

Methods
For study 1 (n = 45, M (SD) age = 21.98 (3.29), 69% females), participants completed a giving support task, followed by an emotional faces task in the functional magnetic resonance imaging scanner. For study 2 (n = 382, M (SD) age = 43.03 (7.28), 52% females), participants self-reported on their giving support behavior and completed an emotional faces task in the functional magnetic resonance imaging scanner.

Results
In study 1, giving targeted (versus untargeted) support resulted in greater feelings of social connection and support effectiveness. Furthermore, greater septal area activity, a region centrally involved in parental care in animals, to giving targeted support was associated with less right amygdala activity to an emotional faces task (r = −.297, 95% confidence interval = −.547 to −.043). Study 2 replicated and extended this association to show that self-reports of giving targeted support were associated with less amygdala activity to a different emotional faces task, even when adjusting for other social factors (r = −.105, 95% confidence interval = −.200 to −.011). Giving untargeted support was not related to amygdala activity in either study.

Conclusions
Results highlight the unique benefits of giving targeted support and elucidate neural pathways by which giving support may lead to health.
Platelet–lymphocyte Ratio After Granulocyte Colony Stimulating Factor Administration: an Early Prognostic Marker in Septic Shock Patients With Chemotherapy-Induced Febrile Neutropenia
Authors: Kim Youn-Jung , Kang Jihoon , Ryoo Seung Mok , Ahn Shin , Huh Jin Won , Kim Won Young 
Published: August 2018

ABSTRACT

Introduction:
Chemotherapy-induced febrile neutropenia (FN) causes life-threatening complications, but little is known in septic shock patients with FN. The aim of this study was to investigate the prognostic value of inflammatory markers, including C-reactive protein level, immature granulocyte count, white blood cell (WBC) count, absolute neutrophil count (ANC), neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR), in septic shock patients with FN at admission and after granulocyte colony-stimulating factor (G-CSF) administration.

Methods:
Data on consecutive adult septic shock patients with FN treated with G-CSF between June 2012 and June 2017 were extracted from a prospectively compiled septic shock registry. Clinical and serial laboratory data at admission and <24 h after G-CSF administration were compared between nonsurvivor and 1-month survivor groups.

Results:
Of 1,671 septic shock patients, 158 FN patients were treated with G-CSF and 114 (72.2%) survived for 1 month. At admission, no clinical and serial laboratory data were significant to predict survival. After G-CSF administration, PLR and APACHE II were independent predictors for 1-month survival. PLR after administration of G-CSF >100 (adjusted odds ratio [aOR], 9.394; 95% CI, 2.821–31.285, P < 0.001) showed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89.4%, 46.2%, 82.9%, and 60.0%, respectively, and APACHE II <28 (aOR, 6.944; 95% CI, 2.351–20.511, P < 0.001) showed sensitivity, specificity, PPV, and NPV of 86.8%, 63.6%, 86.1%, and 65.1%, respectively.

Conclusions:
After G-CSF administration in septic shock patients with chemotherapy-induced FN, PLR may be used as an early prognostic marker for mortality.
CIRP Induces Neutrophil Reverse Transendothelial Migration in Sepsis
Authors: Jin Hui , Aziz Monowar , Ode Yasumasa , Wang Ping 
Published: August 2018

ABSTRACT
Extracellular cold-inducible RNA-binding protein (CIRP) exaggerates inflammation in sepsis. Neutrophil reverse transendothelial migration (rTEM) allows neutrophils to migrate from tissues into the circulation. The phenotype of neutrophils after reverse migration is CD54hiCXCR1lo. We hypothesize that CIRP induces neutrophil rTEM in sepsis. Sepsis was induced in male C57BL/6 mice by cecal ligation and puncture (CLP), and at 5, 10, or 20 h after CLP the frequencies of reversely migrated (RM) neutrophils were assessed in the blood by flow cytometry. As 20 h of CLP showed highest increase in the frequency of RM neutrophils, we further assessed RM neutrophils in the blood of WT and CIRP−/− mice at this time point. The effect of CIRP on neutrophil rTEM was determined by injecting mice with recombinant mouse CIRP (rmCIRP) intratracheally (i.t.) and assessed the frequencies of RM neutrophils. The expression of neutrophil elastase (NE) and junctional adhesion molecule-C (JAM-C) in the lungs was measured by Western blot. The mean frequency of RM neutrophils in sham mice was 0.4%, whereas the frequencies were significantly increased to 1%, 3%, and 7% at 5, 10, and 20 h of CLP, respectively. The mean frequency of RM neutrophils in the blood of CIRP−/− mice was significantly lower than that of WT mice at 20 h of CLP. The RM neutrophils in the blood was significantly increased after administration of rmCIRP i.t. into mice in a time- and dose-dependent manners. NE expression was upregulated, whereas JAM-C expression was downregulated in the lungs after CLP or rmCIRP administration. For the first time, we have showed that CIRP induces neutrophil rTEM in sepsis by increasing NE and decreasing JAM-C.
DNMT inhibitors increase methylation at subset of CpGs in colon, bladder, lymphoma, breast, and ovarian, cancer genome
Authors: Giri Anil K , Aittokallio Tero 
Published: August 2018

AbstractBackgroundDNA methyltransferase inhibitors (DNMTi) decitabine and azacytidine are approved therapies for acute myeloid leukemia and myelodysplastic syndrome. Identification of CpGs violating demethylaion due to DNMTi treatment may help to understand their resistance mechanisms.Materials and MethodsTo identify such CpGs, we analysed publicly available 450K methylation data of multiple cancer type cell lines.ResultsWe identified 637 CpGs corresponding to genes enriched for p53 and olfactory receptor pathways with a transient increase in methylation (median Δβ = 0.12) after decitabine treatment in HCT116 cells. Azacytidine treatment also increased methylation of identified CpGs in 9 colon, 9 ovarian, 3 breast, and 1 lymphoma cancer cell lines.ConclusionDNMTi treatment increases methylation of subset of CpGs in cancer genome.
Laminar Segregation of Sensory Coding and Behavioral Readout in Macaque V4
Authors: Pettine Warren W. , Steinmetz Nicholas A. , Moore Tirin 
Published: August 2018

SummaryNeurons in sensory areas of the neocortex are known to represent information both about sensory stimuli and behavioral state, but how these two disparate signals are integrated across cortical layers is poorly understood. To study this issue, we measured the coding of visual stimulus orientation and of behavioral state by neurons within superficial and deep layers of area V4 in monkeys while they covertly attended or prepared eye movements to visual stimuli. We show that single neurons and neuronal populations in superficial layers convey more information about the orientation of visual stimuli, whereas single neurons and neuronal populations in deep layers convey greater information about the behavioral relevance of those stimuli. In particular, deep layer neurons encode greater information about the direction of prepared eye movements. These results reveal a division of labor between laminae in the coding of visual input and visually guided behavior.
Perceptual inference employs intrinsic alpha frequency to resolve perceptual ambiguity
Authors: Shen Lu , Han Biao , Chen Lihan , Chen Qi 
Published: August 2018

AbstractThe brain uses its intrinsic dynamics to actively predict observed sensory inputs, especially under perceptual ambiguity. However, it remains unclear how this inference process is neurally implemented in biasing perception of ambiguous inputs towards the predicted percepts. Using electroencephalography and intracranial recordings, we first show that the alpha-band frequency defines a unified time window for perceptual grouping across both space and time: information segments, either spatially or temporally segregated, will be integrated if they fall within the same alpha cycle. Moreover, predictions employ this prior knowledge on intrinsic alpha frequency to shift perceptual inference towards the most possibly observed percepts. Multivariate decoding analysis showed that perceptual inference, based on variance in prestimulus alpha frequency (PAF), biases post-stimulus neural representations by inducing preactivation of the predicted percepts. fMRI results additionally showed that prestimulus activity and intrinsic organization status in the frontoparietal attentional network predict perceptual outcomes, probably by modulating occipitoparietal PAFs.
Evaluation of tuberculosis treatment response with serial C-reactive protein measurements
Authors: Wilson Douglas , S Moosa Mahomed-Yunus , Cohen Ted , Cudahy Patrick , Aldous Collen , Maartens Gary 
Published: August 2018

AbstractBackgroundNovel biomarkers are needed to assess response to antituberculosis therapy in smear-negative patients.MethodsTo evaluate the utility of CRP in monitoring response to antituberculosis therapy we conducted a post-hoc analysis on a cohort of adults with symptoms of tuberculosis and negative sputum smears in a high tuberculosis and HIV prevalence setting in KwaZulu-Natal, South Africa. Serial changes in CRP, weight, and haemoglobin were evaluated over 8 weeks.Results421 participants with suspected smear-negative tuberculosis were enrolled and 33 excluded. 295 were treated for tuberculosis (137 confirmed, 158 possible), and 93 did not have tuberculosis. 185 of 215 (86%) participants who agreed to HIV testing were HIV-positive. At week 8, the on-treatment median CRP reduction in the tuberculosis group was 79.5% (IQR 25.4; 91.7), median weight gain 2.3% (IQR −1.0; 5.6), and median haemoglobin increase 7.0% (IQR 0.8; 18.9) (p-value <0.0001 for baseline to week 8 comparison of absolute median values). Only CRP changed significantly at week 2 (median reduction of 75.1% (IQR 46.9; 89.2) in the group with confirmed tuberculosis and 49.0% (IQR −0.4; 80.9) in the possible tuberculosis group. Failure of CRP to reduce to ≤55% of the baseline value at week 2 predicted hospitalization or death in both tuberculosis groups, with 99% negative predictive value.ConclusionChange in CRP may have utility in early evaluation of response to antituberculosis treatment and to identify those at increased risk of adverse outcomes.Key pointsC-reactive protein (CRP) falls by 80% after eight weeks of antituberculosis treatment. At two weeks sustained CRP elevation is associated with death or hospitalization.