bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive performance in DSWPD patients upon awakening from habitual sleep compared with forced conventional sleep
Authors: Solheim Brandy , Olsen Alexander , Kallestad Håvard , Langsrud Knut , Bjorvatn Bjørn , Gradisar Michael , Sand Trond 
Published: August 2018

AbstractDifficult early morning awakening is one of the defining symptoms of delayed sleep–wake phase disorder. It is accompanied by low cognitive arousal and drowsiness resulting in difficulty concentrating and focusing attention upon awakening. We designed the current study to quantitate cognitive performance (i.e. omissions, commissions, reaction time [average and variability]) and cognitive domains (i.e. focused attention, sustained attention, impulsivity and vigilance) with Conners’ Continuous Performance Test II during both habitual and conventional (00:00–07:00 hr) sleep–wake schedule in young adult patients with delayed sleep–wake phase disorder (n = 20, mean age = 24.8 years, SD = 3.0) and controls (n = 16, mean age = 24.4 years, SD = 3.4). Conners’ Continuous Performance Test II was administered after awakening and in the afternoon during both habitual and conventional conditions. In‐laboratory polysomnography was performed for 2 nights. We assessed sleep, tiredness, chronotype and depression using questionnaires. Saliva was sampled for dim light melatonin onset measurements. Repeated‐measures ANOVAs were applied for the Conners’ Continuous Performance Test II measures with group (patient/control), time (afternoon/morning) and condition (habitual/conventional schedule) as fixed factors. Patients with delayed sleep–wake phase disorder had reduced reaction times, especially in the morning, greater response speed variability, and made more omission and commission errors compared with controls. Patients with delayed sleep–wake phase disorder also had reduced focused attention, especially upon forced early awakening. The short total sleep time of patients with delayed sleep–wake phase disorder could not statistically explain this outcome. In conclusion, we observed a state‐dependent reduced ability to focus attention upon early morning awakening in patients with delayed sleep–wake phase disorder. Patients also had more omissions, longer reaction time and increased RT variability after habitual sleep, suggesting a possible small cognitive trait dysfunction in delayed sleep–wake phase disorder.
How to estimate kinship
Authors: Goudet Jérôme , Kay Tomas , Weir Bruce S. 
Published: August 2018

AbstractThe concept of kinship permeates many domains of fundamental and applied biology ranging from social evolution to conservation science to quantitative and human genetics. Until recently, pedigrees were the gold standard to infer kinship, but the advent of next‐generation sequencing and the availability of dense genetic markers in many species make it a good time to (re)evaluate the usefulness of genetic markers in this context. Using three published data sets where both pedigrees and markers are available, we evaluate two common and a new genetic estimator of kinship. We show discrepancies between pedigree values and marker estimates of kinship and explore via simulations the possible reasons for these. We find these discrepancies are attributable to two main sources: pedigree errors and heterogeneity in the origin of founders. We also show that our new marker‐based kinship estimator has very good statistical properties and behaviour and is particularly well suited for situations where the source population is of small size, as will often be the case in conservation biology, and where high levels of kinship are expected, as is typical in social evolution studies.
The single‐domain response regulator LerC functions as a connector protein in the Legionella pneumophila effectors regulatory network
Authors: Feldheim Yaron S. , Zusman Tal , Kapach Anya , Segal Gil 
Published: August 2018

SummaryThe intracellular pathogen Legionella pneumophila translocates more than 300 effector proteins into host cells during infection. The PmrAB two‐component system (TCS) has been shown to activate the expression of a large pool of these effector‐encoding genes (EEGs) and the LetAS TCS, as part of the LetAS‐RsmYZ‐CsrA cascade, has been shown to repress the expression of another pool of EEGs. We identified a single‐domain response regulator (SDRR), named LerC, which functions as a connector protein between the PmrAB and the LetAS TCSs. The lerC gene is strongly activated by the PmrAB TCS and the LerC protein inhibits the activity of the LetAS TCS. The LerC protein specifically interacts with the HPT (histidine‐phosphotransfer) domain of LetS, leading to reduced expression of the small RNAs RsmY and RsmZ, which leads to a reduced expression of the pool of EEGs regulated by the LetAS‐RsmYZ‐CsrA cascade. In addition, the conserved aspartic acid located in the LerC receiver domain is essential for its phosphorylation and function, suggesting that LerC functions as a phosphate‐sink of LetS. Our results demonstrate a new role for SDRRs as connector proteins in regulatory networks, suggesting that members of this widespread group of proteins might function as connector proteins in other bacterial regulatory networks.
MGL_3741 gene contributes to pathogenicity of Malassezia globosa in pityriasis versicolor
Authors: Aghaei Gharehbolagh Sanaz , Kordbacheh Parivash , Hashemi Seyed Jamal , Daie Ghazvini Roshanak , Asgari Yazdan , Agha Kuchak Afshari Setareh , Seyedmousavi Seyedmojtaba , Rezaie Sassan 
Published: August 2018

SummaryDihydroxyacid dehydratase (DHAD) is a key enzyme in biosynthetic pathway of isoleucine and valine. This pathway is absent in human but exists in various organisms such as fungi. Using RNA‐seq analysis in this study, we identified MGL_3741gene which encodes DHAD protein in Malassezia globosa (M. globosa). Furthermore, we found that mentioned gene is homologous to the Ustilago maydis, Saccharomyces cerevisiae, Aspergillus flavus, and Aspergillus fumigatus ILV3P. For understanding the probable role of this gene in pathogenicity of M. globosa, we applied Real‐time PCR to investigate the differentially expressed of the MGL_3741 gene in healthy and pathogenic states. Our results indicate a significant difference between two mentioned stats. These results revealed that ILV3‐like gene in M. globosa can be related to the pathogenicity of this yeast.
Baby‐led weaning: Where are we now?
Authors: Rapley G. A. 
Published: August 2018

AbstractWhen baby‐led weaning (BLW) first emerged as a concept, in the early 2000s, it was seen as a new and different approach to complementary feeding, a challenge to the accepted way of doing things – which indeed it was. Since then, there has been a gradual reassessment of the perceived wisdom that guides how complementary feeding is approached, with the result that many of the features of BLW are now reflected in mainstream thinking. The publication of the report of the UK Scientific Advisory Committee on Nutrition, Feeding in the First Year of Life, which summarises and evaluates the existing evidence base for infant feeding as a benchmark for UK guidelines, provides a useful opportunity to look at how well the baby‐led approach fits with current evidence and which aspects of the introduction of solid foods remain to be investigated.
Isolated Schistosoma mansoni eggs prevent allergic airway inflammation
Authors: Obieglo Katja , Schuijs Martijn J. , Ozir‐Fazalalikhan Arifa , Otto Frank , van Wijck Yolanda , Boon Louis , Lambrecht Bart N. , Taube Christian , Smits Hermelijn H. 
Published: August 2018

SummaryChronic helminth infection with Schistosoma (S.) mansoni protects against allergic airway inflammation (AAI) in mice and is associated with reduced Th2 responses to inhaled allergens in humans, despite the presence of schistosome‐specific Th2 immunity. Schistosome eggs strongly induce type 2 immunity and allow to study the dynamics of Th2 versus regulatory responses in the absence of worms. Treatment with isolated S. mansoni eggs by i.p. injection prior to induction of AAI to ovalbumin (OVA)/alum led to significantly reduced AAI as assessed by less BAL and lung eosinophilia, less cellular influx into lung tissue, less OVA‐specific Th2 cytokines in lungs and lung‐draining mediastinal lymph nodes and less circulating allergen‐specific IgG1 and IgE antibodies. While OVA‐specific Th2 responses were inhibited, treatment induced a strong systemic Th2 response to the eggs. The protective effect of S. mansoni eggs was unaltered in μMT mice lacking mature (B2) B cells and unaffected by Treg cell depletion using anti‐CD25 blocking antibodies during egg treatment and allergic sensitization. Notably, prophylactic egg treatment resulted in a reduced influx of pro‐inflammatory, monocyte‐derived dendritic cells into lung tissue of allergic mice following challenge. Altogether, S. mansoni eggs can protect against the development of AAI, despite strong egg‐specific Th2 responses.
Microbiological findings in bronchoalveolar lavage fluid from lung transplant patients in Sweden
Authors: Stjärne Aspelund Anna , Hammarström Helena , Inghammar Malin , Larsson Hillevi , Hansson Lennart , Riise Gerdt C. , Friman Vanda , Christensson Bertil , Påhlman Lisa I. 
Published: August 2018

AbstractBackgroundLung transplant patients experience a high risk of airway infections and microbial colonization of the lung due to constant exposure to the environment through inhaled microorganisms, denervation, reduced ciliary transport, and decreased cough.MethodsIn this nationwide prospective study on Swedish lung transplant patients, we evaluated the microbiological panorama of bacteria, fungi, and virus found in bronchoalveolar lavage fluid (BALF) obtained the first year after lung transplantation (LTx). Differences in microbiological findings depending of concomitant signs of infection and background factors were assessed.ResultsA total of 470 bronchoscopies from 126 patients were evaluated. Sixty‐two percent (n = 293) of BALF samples had positive microbiological finding(s). Forty‐six percent (n = 217) had bacterial growth, 29% (n = 137) fungal growth, and 9% (n = 43) were positive in viral PCR. In 38% of BALF samples (n = 181), a single microbe was found, whereas a combination of bacteria, fungi or virus was found in 24% (n = 112) of bronchoscopies. The most common microbiological findings were Candida albicans, Pseudomonas aeruginosa and coagulase negative Staphylococcus (in 42 (33%), 36 (29%), and 25 (20%) patients, respectively). Microbiological findings were similar in BALF from patients with and without signs of lung infection and the frequency of multidrug resistant (MDR) bacteria was low. No significant association was found between background factors and time to first lung infection.ConclusionThis study gives important epidemiologic insights and reinforces that microbiological findings have to be evaluated in the light of clinical symptoms and endobronchial appearance in the assessment of lung infections in lung transplant patients.
Racial differences and determinants of macular thickness profiles in multiethnic Asian population: the Singapore Epidemiology of Eye Diseases Study
Authors: Wong Kah Hie , Tham Yih-Chung , Nguyen Duc Quang , Dai Wei , Tan Nicholas Y Q , Mathijia Shivani , Neelam Kumari , Cheung Carol Yim-lui , Sabanayagam Charumathi , Schmetterer Leopold , Wong Tien Yin , Cheng Ching-Yu 
Published: August 2018

AimTo evaluate racial differences, and ocular and systemic determinants of macular thickness (MT), measured by spectral-domain optical coherence tomography (SD-OCT) in a normal multiethnic Asian population.MethodMT was measured from a 6×6 mm2 central macular area using the Cirrus high-definition OCT (HD-OCT) (Carl Zeiss Meditec, Dublin, CA). The associations between ocular and systemic factors with MT were evaluated using linear regression analyses with generalised estimating equation models to account for intereye correlation.Results7447 healthy eyes (2577 Chinese, 2072 Malays and 2798 Indians) of 4510 subjects were included. Multivariable analysis showed that older age (per decade, β=−4.39), female gender (β=−5.74), diabetes (β=−1.10), chronic kidney disease (CKD) (β=−3.21), longer axial length (per mm, β=−2.34), flatter corneal curvature (per mm, β=−1.79) and presence of cataract (β=−0.94) were associated with thinner overall average MT (OMT) (all p≤0.026); higher total cholesterol (β=0.44; p=0.010) was associated with thicker OMT. All these factors were also associated with thinner central subfield MT (CSMT) (all p≤0.001), except for cataract, total cholesterol and CKD. Meanwhile, longer axial length (β=2.51; p<0.001) was associated with thicker CSMT. OMT (mean±SD) was thickest in Chinese (279.9±12.5 µm), followed by Malays (276.5±13.7 µm) and Indians (272.4±13.1 µm), with p≤0.003 for all interethnic comparisons. Similar trend was observed for CSMT.ConclusionThere are interethnic differences in MT profile among Asians, particularly between Chinese and Indians. Ocular and systemic factors affect MT measurements as well. This Asian-specific information may be incorporated into existing clinical interpretation of macular OCT scans to aid in improving the diagnostic and monitoring accuracy of macular diseases among Asians.
Cardiac structure and function with and without metabolic syndrome: the Echocardiographic Study of Latinos (Echo-SOL)
Authors: Burroughs Peña Melissa , Swett Katrina , Schneiderman Neil , Spevack Daniel M , Ponce Sonia G , Talavera Gregory A , Kansal Mayank M , Daviglus Martha L , Cai Jianwen , Hurwitz Barry E , Llabre Maria M , Rodriguez Carlos J 
Published: August 2018

ObjectiveWe assessed the hypothesis that metabolic syndrome is associated with adverse changes in cardiac structure and function in participants of the Echocardiographic Study of Latinos (Echo-SOL).MethodsNon-diabetic Echo-SOL participants were included in this cross-sectional analysis. Metabolic syndrome was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Survey multivariable linear regression analyses using sampling weights were used adjusting for multiple potential confounding variables. Additional analysis was stratified according to the presence/absence of obesity (body mass index (BMI) ≥25 kg/m2) and the presence/absence of metabolic syndrome.ResultsWithin Echo-SOL, 1260 individuals met inclusion criteria (59% female; mean age 55.2 years). Compared with individuals without metabolic syndrome, those with metabolic syndrome had lower medial and lateral E′ velocities (−0.4 cm/s, (SE 0.1), p=0.0002; −0.5 cm/s (0.2), p=0.02, respectively), greater E/E′ (0.5(0.2), p=0.01) and worse two-chamber left ventricular longitudinal strain (0.9%(0.3), p=0.009), after adjusting for potential confounding variables. Increased left ventricular mass index (9.8 g/m2(1.9), p<0.0001 and 7.5 g/m2(1.7), p<0.0001), left ventricular end-diastolic volume (11.1 mL (3.0), p=0.0003 and 13.3 mL (2.7), p<0.0001), left ventricular end-systolic volume (5.0 mL (1.4), p=0.0004 and 5.7 mL (1.3) p<0.0001) and left ventricular stroke volume (10.2 mL (1.8), p<0.0001 and 13.0 mL (2.0), p<0.0001) were observed in obese individuals with and without metabolic syndrome compared with individuals with normal weight without metabolic syndrome. In sensitivity analyses, individuals with normal weight (BMI <25 kg/m2) and metabolic syndrome had worse left ventricular global longitudinal strain (2.1%(0.7), p=0.002) and reduced left ventricular ejection fraction (−3.5%(1.4), p=0.007) compared with normal-weight individuals without metabolic syndrome.ConclusionsIn a sample of US Hispanics/Latinos metabolic syndrome was associated with worse left ventricular systolic and diastolic function. Adverse changes in left ventricular size and function were observed in obese individuals with and without metabolic syndrome but decreased left ventricular function was also present in normal-weight individuals with metabolic syndrome.
Data-driven approach to Early Warning Score-based alert management
Authors: Capan Muge , Hoover Stephen , Miller Kristen E , Pal Carmen , Glasgow Justin M , Jackson Eric V , Arnold Ryan C 
Published: August 2018

BackgroundIncreasing adoption of electronic health records (EHRs) with integrated alerting systems is a key initiative for improving patient safety. Considering the variety of dynamically changing clinical information, it remains a challenge to design EHR-driven alerting systems that notify the right providers for the right patient at the right time while managing alert burden. The objective of this study is to proactively develop and evaluate a systematic alert-generating approach as part of the implementation of an Early Warning Score (EWS) at the study hospitals.MethodsWe quantified the impact of an EWS-based clinical alert system on quantity and frequency of alerts using three different alert algorithms consisting of a set of criteria for triggering and muting alerts when certain criteria are satisfied. We used retrospectively collected EHRs data from December 2015 to July 2016 in three units at the study hospitals including general medical, acute care for the elderly and patients with heart failure.ResultsWe compared the alert-generating algorithms by opportunity of early recognition of clinical deterioration while proactively estimating alert burden at a unit and patient level. Results highlighted the dependency of the number and frequency of alerts generated on the care location severity and patient characteristics.ConclusionEWS-based alert algorithms have the potential to facilitate appropriate alert management prior to integration into clinical practice. By comparing different algorithms with regard to the alert frequency and potential early detection of physiological deterioration as key patient safety opportunities, findings from this study highlight the need for alert systems tailored to patient and care location needs, and inform alternative EWS-based alert deployment strategies to enhance patient safety.
PTEN inhibitor VO-OHpic attenuates inflammatory M1 macrophages and cardiac remodeling in doxorubicin-induced cardiomyopathy
Authors: Johnson Taylor A. , Singla Dinender K. 
Published: August 2018

Doxorubicin (Doxo) is an effective agent commonly used in cancer therapeutics. Unfortunately, Doxo treatment can stimulate cardiomyopathy and subsequent heart failure, limiting the use of this drug. The role of phosphatase and tensin homolog (PTEN) in apoptosis has been documented in Doxo-induced cardiomyopathy (DIC) and heart failure models. However, whether direct inhibition of PTEN attenuates apoptosis, cardiac remodeling, and inflammatory M1 macrophages in the DIC model remains elusive. Therefore, the present study was designed to understand the effects of VO-OHpic (VO), a potent inhibitor of PTEN, in reducing apoptosis and cardiac remodeling. At day 56, echocardiography was performed, which showed that VO treatment significantly ( P < 0.05) improved heart function. Immunohistochemistry, TUNEL, and histological staining were used to determine apoptosis, proinflammatory M1 macrophages, anti-inflammatory M2 macrophages, and cardiac remodeling. Our data show a significant increase in apoptosis, hypertrophy, fibrosis, and proinflammatory M1 macrophages with Doxo treatment, whereas VO treatment significantly reduced apoptosis, adverse cardiac remodeling, and proinflammatory M1 macrophages significantly ( P < 0.05) compared with the Doxo-treated group. Western blot analysis confirmed the reduction of phosphorylated PTEN and increase in phosphorylated AKT protein expression in the Doxo + VO-treated group. Moreover, VO administration increased anti-inflammatory M2 macrophages. Collectively, our data suggest that VO treatment attenuates apoptosis and adverse cardiac remodeling, a process that is mediated through the PTEN/AKT pathway, resulting in improved heart function in DIC. NEW & NOTEWORTHY Doxorubicin-induced cardiomyopathy (DIC) is still a major issue in patients with cancer. These novel findings on the phosphatase and tensin homolog inhibitor VO-OHpic in DIC is the first report, as per the best of our knowledge, that VO-OHpic significantly decreases apoptosis, fibrosis, hypertrophy, adverse cardiac remodeling, and proinflammatory M1 macrophages and increases anti-inflammatory M2 macrophages along with significantly improved cardiac function. VO-OHpic could be a future therapeutic agent for patients with DIC.
Pulmonary endothelial cells exhibit sexual dimorphism in their response to hyperoxia
Authors: Zhang Yuhao , Dong Xiaoyu , Shirazi Jasmine , Gleghorn Jason P. , Lingappan Krithika 
Published: August 2018

Abnormal pulmonary vascular development is a critical factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Despite the well-established sex-specific differences in the incidence of BPD, the molecular mechanism(s) behind these are not completely understood. Exposure to a high concentration of oxygen (hyperoxia) contributes to BPD and creates a profibrotic environment in the lung. Our objective was to elucidate the sex-specific differences in neonatal human pulmonary microvascular endothelial cells (HPMECs) in normoxic and hyperoxic conditions, including the propensity for endothelial-to-mesenchymal transition. HPMECs (18- to 24-wk gestation donors, 6 male donors and 5 female donors) were subjected to hyperoxia (95% O2 and 5% CO2) or normoxia (air and 5% CO2) up to 72 h. We assessed cell migration and angiogenesis at baseline. Cell proliferation, viability, and expression of endothelial (CD31) and fibroblast markers (α-smooth muscle actin) were measured upon exposure to hyperoxia. Female HPMECs had significantly higher cell migration when assessed by the wound healing assay (40.99 ± 4.4%) compared with male HPMECs (14.76 ± 3.7%) and showed greater sprouting (1710 ± 962 μm in female cells vs. 789 ± 324 in male cells) compared with male endothelial cells in normoxia. Hyperoxia exposure decreased cell viability (by 9.8% at 48 h and 11.7% at 72 h) and proliferation (by 26.7% at 72 h) markedly in male HPMECs, whereas viability was sustained in female endothelial cells. There was greater expression of α-smooth muscle actin (2.5-fold) and decreased expression (5-fold) of CD31 in male HPMECs upon exposure to hyperoxia. The results indicate that cellular sex affects response in HPMECs in normoxia and hyperoxia. NEW & NOTEWORTHY Cellular sex affects response in human neonatal pulmonary microvascular endothelial cells in normoxia and hyperoxia. Under normoxic conditions, female human neonatal pulmonary microvascular endothelial cells display greater migration and angiogenic sprouting compared with male endothelial cells. Compared with female endothelial cells, hyperoxia exposure decreased cell viability and proliferation and increased α-smooth muscle actin and decreased CD31 expression in male endothelial cells, indicating an increased endothelial-mesenchymal transition.