bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporating Functional Genomic Information to Enhance Polygenic Signal and Identify Variants Involved in Gene‐by‐Environment Interaction for Young Adult Alcohol Problems
Authors: Salvatore Jessica E. , Savage Jeanne E. , Barr Peter , Wolen Aaron R. , Aliev Fazil , Vuoksimaa Eero , Latvala Antti , Pulkkinen Lea , Rose Richard J. , Kaprio Jaakko , Dick Danielle M. 
Published: November 2017

BackgroundCharacterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene‐by‐environment (G × E) interaction effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G × E effects.MethodsWe examined these questions in the young adult FinnTwin12 sample (n = 1,170). We used genomewide association estimates from an independent sample to derive 2 types of polygenic scores for alcohol problems in FinnTwin12. Genomewide polygenic scores included all SNPs surpassing a designated p‐value threshold. DNase polygenic scores were a subset of the genomewide polygenic scores including only variants in DNase I hypersensitive sites (DHSs), which are open chromatin marks likely to index regions with a regulatory function. We conducted parallel analyses using height as a nonpsychiatric model phenotype to evaluate the consistency of effects. For the G × E analyses, we examined whether SNPs in DHSs were overrepresented among SNPs demonstrating significant G × E effects in an interaction between romantic relationship status and intoxication frequency.ResultsContrary to our expectations, we found that DNase polygenic scores were not more strongly predictive of alcohol problems than conventional polygenic scores. However, variants in DNase polygenic scores had per‐SNP effects that were up to 1.4 times larger than variants in conventional polygenic scores. This same pattern of effects was also observed in supplementary analyses with height. In G × E models, SNPs in DHSs were modestly overrepresented among SNPs with significant interaction effects for intoxication frequency.ConclusionsThese findings highlight the potential utility of integrating functional genomic annotation information to increase the signal‐to‐noise ratio in polygenic scores and identify genetic variants that may be most susceptible to environmental modification.
THE RELATIONSHIP BETWEEN SOME DISORDERS OF THE UMBILICAL CORD AND INTRAUTERINE GROWTH RETARDATION
Authors: Rolschau John 
Published: November 2017

Some disorders of the umbilical cord—Single umbilical artery, oedema of the cord, battledore insertion and velamentous insertion—have been examined in a prospectively randomized material. The material consists of 447 placentae from liveborn, singleton infants, where 287 were from exemplary pregnancies, and 160 from births with a gestational age of less than 266 days and/or a birth weight of less than 2750 g.The placentae were examined macroscopically and microscopically, and the total amount of protein, RNA, and DNA were determined in a randomized sample.Single umbilical artery was found to coincide with circumvallate placenta, suggesting a common fault in the placentation. Oedema of the umbilical cord was found to have no significance for the infant, but their placentae were significantly heavier, without signs of generalized oedema. The birth weight and placental weight were slightly and equally reduced in battledore insertion of the cord. The RNA/DNA ratio was increased, indicating tissue stress. This anomaly contrasted to the placentae, in which the cords were inserted velamentously. These had significantly reduced birth weights, and the weights of the placentae were slightly reduced. The incidences of complications during labour and congenital anomalies were increased.
Phototherapy is commonly used for neonatal jaundice but greater control is needed to avoid toxicity in the most vulnerable infants
Authors: Mreihil Khalaf , Benth Jūratė Šaltytė , Stensvold Hans Jørgen , Nakstad Britt , Hansen Thor Willy Ruud ,   the Norwegian NICU Phototherapy Study Group,   the Norwegian Neonatal Network
Published: November 2017

AbstractAimLimited information is available about how guidelines on phototherapy for neonatal jaundice are applied in practice and toxicity is a concern. We studied the use of phototherapy in relation to birthweight and gestational age (GA) in Norwegian neonatal intensive care units (NICUs).MethodsThe study population was all 5382 infants admitted to the 21 NICUs in Norway between September 1, 2013 and August 31, 2014. Data were recorded daily in the Norwegian Neonatal Network database and anonymised data on patient characteristics, diagnoses, duration, the ages at the start and discontinuation of phototherapy were analysed.ResultsMore than a quarter (26.6%) of all infants admitted to Norwegian NICUs during the study period received phototherapy. The use of phototherapy was inversely related to GA and birthweight. More than 80% of the preterm infants under 28 weeks of GA received phototherapy. The duration was significantly longer in the lowest birthweight and GA groups and decreased with increasing birthweight and GA.ConclusionPhototherapy is proved to be a strong candidate for the most common therapeutic modality in NICU infants. However, in the light of reported toxicity in the smallest, most vulnerable infants, we recommend increased emphasis on quality control.
Effect of follistatin on pre‐implantational development of pig parthenogenetic embryos
Authors: Li Yunsheng , Liu Xing , Chen Zhen , Song Dandan , Yang Jie , Zuo Xiaoyuan , Cao Zubing , Liu Ya , Zhang Yunhai 
Published: November 2017

AbstractThe present study was designed to explore effects of follistatin (FST) on pre‐implantational development of parthenogenetically activated embryos (PAEs) in pigs. First, we investigated the FST messenger RNA expression level and dynamic FST protein expression patterns in porcine oocytes and PAEs. Then, PAEs were placed in embryo culture medium supplemented with 10 ng/mL of FST‐288, FST‐300, and FST‐315. Next, PAEs were cultured with 0, 1, 10 and 100 ng/mL of FST‐315 protein throughout the in vitro culture (IVC) duration. Further, 10 ng/mL of FST‐300 was added from the start of IVC in which PAEs were treated for 30, 48 and 60 h. The results showed that 1 ng/mL FST‐315 could significantly increase the total cell numbers of blastocyst and trophectoderm cell number in PAEs. Exogenous FST‐300 supplementation could significantly promote the early cleavage divisions and improve the blastocyst formation rate of porcine embryos. FST‐300 appeared to affect early embryonic development before activation of the embryonic genome. In all, the study confirmed for the first time that FST plays a role in promoting early embryonic development in pigs, which differed with different FST subtypes. FST‐300 could facilitate the initial cleavage time and improve the blastocyst formation rate, and FST‐315 could improve the blastocyst quality.
Testing for Gene–Environment Interaction under Exposure Misspecification
Authors: Sun Ryan , Carroll Raymond J. , Christiani David C. , Lin Xihong 
Published: November 2017

Summary
Complex interplay between genetic and environmental factors characterizes the etiology of many diseases. Modeling gene–environment (GxE) interactions is often challenged by the unknown functional form of the environment term in the true data-generating mechanism. We study the impact of misspecification of the environmental exposure effect on inference for the GxE interaction term in linear and logistic regression models. We first examine the asymptotic bias of the GxE interaction regression coefficient, allowing for confounders as well as arbitrary misspecification of the exposure and confounder effects. For linear regression, we show that under gene–environment independence and some confounder-dependent conditions, when the environment effect is misspecified, the regression coefficient of the GxE interaction can be unbiased. However, inference on the GxE interaction is still often incorrect. In logistic regression, we show that the regression coefficient is generally biased if the genetic factor is associated with the outcome directly or indirectly. Further, we show that the standard robust sandwich variance estimator for the GxE interaction does not perform well in practical GxE studies, and we provide an alternative testing procedure that has better finite sample properties.
Tick attachment cement – reviewing the mysteries of a biological skin plug system
Authors: Suppan Johannes , Engel Benedikt , Marchetti‐Deschmann Martina , Nürnberger Sylvia 
Published: November 2017

ABSTRACTThe majority of ticks in the family Ixodidae secrete a substance anchoring their mouthparts to the host skin. This substance is termed cement. It has adhesive properties and seals the lesion during feeding. The particular chemical composition and the curing process of the cement are unclear. This review summarizes the literature, starting with a historical overview, briefly introducing the different hypotheses on the origin of the adhesive and how the tick salivary glands have been identified as its source. Details on the sequence of cement deposition, the curing process and detachment are provided. Other possible functions of the cement, such as protection from the host immune system and antimicrobial properties, are presented. Histochemical and ultrastructural data of the intracellular granules in the salivary gland cells, as well as the secreted cement, suggest that proteins constitute the main material, with biochemical data revealing glycine to be the dominant amino acid. Applied methods and their restrictions are discussed. Tick cement is compared with adhesives of other animals such as barnacles, mussels and sea urchins. Finally, we address the potential of tick cement for the field of biomaterial research and in particular for medical applications in future.
From Sinks to Webs: Critical Social Science after the Fact‐Value Distinction
Authors: Gorski Philip S. 
Published: November 2017

AbstractThe fact‐value distinction is leaky. The problem is not just that values can color facts. The reverse is also true: facts are also entangled with values. Nor is that the end of the matter. The concepts of fact and value are not epistemologically or ethically neutral either. It is time to abandon the quest for axiological neutrality in favor of systematic attention to the complex relationship between the descriptive and the normative. Instead of attempting to be neutral, social scientists should strive to combine engagement with open‐mindedness.
Observing Facts and Values: A Brief Theory and History
Authors: Fuchs Stephan 
Published: November 2017

AbstractNot acknowledging the history and metaphysics of the fact/value distinction has led to confusion about the difference between the normative and the cognitive, and disputes on whether there are ways to move from one side, facts, to the other, values. One solution is to recognize values as more “objective” than facts, and thus blur the common way of drawing this distinction. The origin of the distinction between facts and values appears in the space between them, when and where it is uncertain whether an observation becomes fact or value. Once values turn into subjective beliefs, the entire distinction collapses, and modernity begins to end.
Investigating the hepatitis B virus life cycle using engineered reporter hepatitis B viruses
Authors: Nishitsuji Hironori , Harada Keisuke , Ujino Saneyuki , Zhang Jing , Kohara Michinori , Sugiyama Masaya , Mizokami Masashi , Shimotohno Kunitada 
Published: November 2017

Chronic infection with hepatitis B virus (HBV) increases the risk of developing fibrosis, cirrhosis or hepatocellular carcinoma. Current therapies are limited to type‐I interferons and/or nucleos(t)ide analogues; however, these are only partially effective. The development of novel anti‐HBV agents for new treatment strategies has been hampered by the lack of a suitable system that allows the in vitro replication of HBV. Studies of virus infection/replication at the molecular level using wild‐type HBV are labor‐intensive and time‐consuming. To overcome these problems, we previously constructed a recombinant reporter HBV bearing the NanoLuc gene and showed its usefulness in identifying factors that affect HBV proliferation. Because this system mimics the early stage of the HBV life cycle faithfully, we conducted a quantitative analysis of HBV infectivity to several human hepatocyte cell lines as well as the effect of dimethyl sulfoxide and HBV protein X on the early stage of HBV proliferation using this system. Furthermore, we developed a system to produce a reporter HBV expressing a pol gene. These reporter HBV may provide an opportunity to enhance our understanding of the HBV life cycle and aid strategies for the development of new anti‐HBV agents.
Altered intracellular signaling by imatinib increases the anti‐cancer effects of tyrosine kinase inhibitors in chronic myelogenous leukemia cells
Authors: Hirao Takuya , Yamaguchi Masashi , Kikuya Megumi , Chibana Hiroji , Ito Kousei , Aoki Shigeki 
Published: November 2017

Tyrosine kinase inhibitors (TKI), including imatinib (IM), improve the outcome of CML therapy. However, TKI treatment is long‐term and can induce resistance to TKI, which often leads to a poor clinical outcome in CML patients. Here, we examined the effect of continuous IM exposure on intracellular energy metabolism in K562 cells, a human Philadelphia chromosome‐positive CML cell line, and its subsequent sensitivity to anti‐cancer agents. Contrary to our expectations, we found that continuous IM exposure increased sensitivity to TKI. Cancer energy metabolism, characterized by abnormal glycolysis, is linked to cancer cell survival. Interestingly, glycolytic activity was suppressed by continuous exposure to IM, and autophagy increased to maintain cell viability by compensating for glycolytic suppression. Notably, increased sensitivity to TKI was not caused by glycolytic inhibition but by altered intracellular signaling, causing glycolytic suppression and increased autophagy, as evidenced by suppression of p70 S6 kinase 1 (S6K1) and activation of AMP‐activated protein kinase (AMPK). Using another human CML cell line (KCL22 cells) and BCR/ABL+ Ba/F3 cells (mimicking Philadelphia chromosome‐positive CML cells) confirmed that suppressing S6K1 and activating AMPK increased sensitivity to TKI. Furthermore, suppressing S6K1 and activating AMPK had a synergistic anti‐cancer effect by inhibiting autophagy in the presence of TKI. The present study provides new insight into the importance of signaling pathways that affect cellular energy metabolism, and suggests that co‐treatment with agents that disrupt energy metabolic signaling (using S6K1 suppressors and AMPK activators) plus blockade of autophagy may be strategies for TKI‐based CML therapy.
Noise‐induced hearing loss — An examination of the methods of assessment in a cross‐sectional study of 87 industrial workers
Authors: Das S. , Mulheran M. , Brewster M. , Banerjee A.R. 
Published: November 2017

ObjectivesThe surveillance of noise‐induced hearing loss (NIHL) according to the Health and Safety Executive (HSE) differs from the medico‐legal criteria used to assess NIHL. Our study compares the two systems and proposes a novel method of simplifying the medico‐legal criteria and applying it to ascertain noise‐induced hearing loss.DesignThe anonymised audiograms of a group of 87 industrial workers from a single site were analysed with both methods.ResultsThe comparison showed approximately one‐third of the workers assessed in this study had their noise‐induced hearing loss underestimated by the HSE criteria. The majority of these individuals were over 40 years of age.ConclusionsThe HSE criteria for noise‐induced hearing loss need review and re‐alignment with the medico‐legal criteria to address the discrepancy between the two systems.
Renal transplant outcomes in primary FSGS compared with other recipients and risk factors for recurrence: A national review of the Irish Transplant Registry
Authors: Cormican Sarah , Kennedy Claire , O'Kelly Patrick , Doyle Brendan , Dorman Anthony , Awan Atif , Conlon Peter 
Published: November 2017

AbstractIntroductionPrimary focal segmental glomerular sclerosis (p‐FSGS) is commonly complicated by recurrence (r‐FSGS) post‐transplantation. Our objective was to describe Irish outcomes for transplantation after end‐stage renal disease (ESRD) due to p‐FSGS, specifically rates of, and treatments for, r‐FSGS.Patients and MethodsIrish patients with biopsy‐proven FSGS were identified from the Irish National Kidney Transplant database (1982‐2015). Medical record review was performed to identify predictors of r‐FSGS and treatments for r‐FSGS. Transplant outcomes were compared to outcomes in all renal transplants performed during the same time period using registry data. Demographic and clinical predictors of r‐FSGS were identified. Statistical analysis was performed using Stata (version 13, College Station, TX, USA).ResultsThirty‐eight transplant recipients had biopsy‐proven p‐FSGS, 16 received a second transplant. A total of 3846 transplants formed the comparator group. r‐FSGS complicated 60.5% (23/38) of first transplants. Eighty‐six percent (10/12) of patients with previous r‐FSGS developed recurrent disease after further transplantation.Patients with p‐FSGS receiving a first renal transplant had higher rate of graft failure than those with another cause of ESRD (HR 1.9, 95% CI 1.152‐3.139).Sixteen patients received immunotherapy for r‐FSGS; 12 (86%) had at least partial response, but two (14%) developed significant complications.DiscussionWe demonstrate high rates of r‐FSGS and describe modest success from with treatments for r‐FSGS.
Development of the ability to combine visual and acoustic information in working memory
Authors: Cowan Nelson , Li Yu , Glass Bret A. , Scott Saults J. 
Published: November 2017

AbstractPresentation of two kinds of materials in working memory (visual and acoustic), with the requirement to attend to one or both modalities, poses an interesting case for working memory development because competing predictions can be formulated. In two experiments, we assessed such predictions with children 7–13 years old and adults. With development, the ability to hold more information in the focus of attention could lead to an increase in the size of the trade‐off between modalities; if attention can hold A items during unimodal‐attention trials, then on average attention should hold A/2 of those same items during bimodal‐attention trials. If A increases with age, so would the dual‐task cost, A/2. The results clearly ruled out that possibility. It was the modality‐ or code‐specific components of working memory that improved with age and not the central component. We discuss various mechanisms that could have produced these results, including alternative attention‐based mechanisms. The findings point to a rich field for continued research.
Great walls over African rivers: Chinese engagement in African hydropower projects
Authors: Brautigam Deborah , Hwang Jyhjong 
Published: November 2017

AbstractRecent acceleration of Chinese engagement in African hydropower is attracting increasing attention and concern. Yet there is scant research and little reliable data on this engagement. This article analyses Chinese hydropower engagement based on a new, verified dataset. We examined over 100 projects reported by the media and lists compiled by other organizations, amassing case studies for each project using desk research, interviews and field visits. We demonstrate that Chinese engagement in African hydropower is often overestimated in both numbers and value. Further, misunderstanding and myths abound regarding Chinese financing and construction practices. This evidence‐based understanding provides a firmer foundation for advocacy, research and efforts by other companies and funding agencies to co‐operate with Chinese actors in this controversial sector.
Land grabbing: A gendered understanding of perceptions and reactions from affected communities in Nguti Subdivision of South West Cameroon
Authors: Ndi Frankline A. 
Published: November 2017

AbstractThis article examines the political economic processes and gendered consequences involved in large‐scale land acquisition (LSLA) in rural South West Cameroon. The study adopts a gender‐disaggregated approach to data collection to understand local perceptions and reactions toLSLAin the region. It shows how traditional cultural prescriptions have combined with contemporary land laws to masculinize power over land to the detriment of women. It argues that although men and women are both affected byLSLAprojects, the impacts are much greater for women because what the state considers “empty land”is used by them to secure household food security. Second, it argues that amid societal discrimination over land‐ownership rights, perceived gender differences between men and women appear “rational” in the event ofLSLA—men follow their ascribed roles in overt reactions, women being more covert and much less vocal in land‐related contests. New policies that promote rural women's land rights will not only empower them during land struggles, they will also provide communities with greater security to sustain ecologically viable livelihoods.
The neural representation of social status in the extended face‐processing network
Authors: Koski Jessica E. , Collins Jessica A. , Olson Ingrid R. 
Published: November 2017

AbstractSocial status is a salient cue that shapes our perceptions of other people and ultimately guides our social interactions. Despite the pervasive influence of status on social behavior, how information about the status of others is represented in the brain remains unclear. Here, we tested the hypothesis that social status information is embedded in our neural representations of other individuals. Participants learned to associate faces with names, job titles that varied in associated status, and explicit markers of reputational status (star ratings). Trained stimuli were presented in an functional magnetic resonance imaging experiment where participants performed a target detection task orthogonal to the variable of interest. A network of face‐selective brain regions extending from the occipital lobe to the orbitofrontal cortex was localized and served as regions of interest. Using multivoxel pattern analysis, we found that face‐selective voxels in the lateral orbitofrontal cortex – a region involved in social and nonsocial valuation, could decode faces based on their status. Similar effects were observed with two different status manipulations – one based on stored semantic knowledge (e.g., different careers) and one based on learned reputation (e.g., star ranking). These data suggest that a face‐selective region of the lateral orbitofrontal cortex may contribute to the perception of social status, potentially underlying the preferential attention and favorable biases humans display toward high‐status individuals.