bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiretroviral Therapy Anchor-based Trends in Body Mass Index Following Treatment Initiation Among Military Personnel with HIV
Authors: Kline Maj David A , Daniels Colton , Xu Xiaohe , Sunil Thankam , Ganesan Anuradha , Agan Brian K , Colombo Rhonda E , Kronmann Karl C , Blaylock Jason M , Okulicz Jason F , Markelz A Elizabeth 
Published: October 2020

ABSTRACT

Introduction
Weight gain and obesity in people living with HIV have been associated with increased risk for non-AIDS-related comorbidities, and integrase strand transfer inhibitor (INSTI)-based regimens may lead to comparatively more weight gain than other regimens. We evaluated body mass index (BMI) following antiretroviral therapy (ART) initiation among participants in the U.S. Military HIV Natural History Study (NHS).

Materials and Methods
NHS participants with available baseline weight and height data initiating ART from 2006 to 2017 were considered for analysis. Antiretroviral therapy was categorized by anchor class to include INSTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Linear growth-curve modeling was used to predict BMI changes from ART initiation through 2 years of follow-up in participants stratified by baseline BMI (&lt;25 vs ≥25 kg/m2) at ART start and anchor drug class. These models were adjusted for demographic- and HIV-related characteristics.

Results
Of 961 NHS participants started on initial ART between 2006 and 2017, 491 men who had available baseline BMI data and were virally suppressed (&lt;200 c/mL) at 1 and 2 years of follow-up were included. Overall, the predicted BMI increased at each time point over 2 years regardless of baseline BMI. There was a trend toward less weight gain for non-INSTI regimens regardless of demographic- or HIV-related factors (−0.65 kg/m2/yr, P = .070). In participants with BMI &lt;25, all regimens were associated with BMI gains except in those with high viral load (≥100,000 copies/mL) started on PI regimens (−1.91 kg/m2/yr, P = .000; n = 13). For those participants with BMI ≥25, only INSTI- and PI-based regimens were significantly associated with increased BMI (INSTI 0.54 kg/m2/y, P = .000; PI 0.39 kg/m2/yr, P = .006). Non-nucleoside reverse transcriptase inhibitors were not associated with weight gain regardless of race- or HIV-related characteristics. African Americans with BMI ≥25 were more likely to gain weight as compared to Whites (0.99 kg/m2/yr, P = .016). Specific anchor drug-based predictions revealed that only INSTI use among African Americans was significantly associated with BMI gains (1.85 kg/m2/yr, P = .007); NNRTI- and PI-related weight change was not significant as compared to Whites.

Conclusions
In our cohort of young military members with HIV infection, those with BMI &lt;25 experienced BMI gains across all ART classes. Among those with BMI ≥25, African Americans on INSTI regimens had the greatest BMI gains. Further studies are needed to determine whether NNRTI regimens should be considered in certain individuals at risk for INSTI-associated weight gain.
Prevalence and Correlates of Cryptosporidium Infections in Kenyan Children With Diarrhea and Their Primary Caregivers
Authors: Deichsel Emily L , Hillesland Heidi K , Gilchrist Carol A , Naulikha Jaqueline M , McGrath Christine J , Van Voorhis Wesley C , Rwigi Doreen , Singa Benson O , Walson Judd L , Pavlinac Patricia B 
Published: October 2020

Abstract

Background
Cryptosporidium is a leading cause of diarrhea in Sub-Saharan Africa and is associated with substantial morbidity and mortality in young children.

Methods
We analyzed data from children aged 6–71 months presenting to 2 public hospitals in Western Kenya with acute diarrhea and their primary caregivers, including detection of Cryptosporidium by quantitative polymerase chain reaction (PCR) and immunoassay analysis in stool samples from both children and their caregivers. Associations between potential transmission sources and child/caregiver Cryptosporidium infection were evaluated using prevalence ratios (PRs). Secondary analyses evaluated host and clinical risk factors of child/caregiver Cryptosporidium infection.

Results
Among 243 child–caregiver pairs enrolled, 77 children (32%) and 57 caregivers (23%) had Cryptosporidium identified by either immunoassay or PCR. Twenty-six of the 243 child–caregiver pairs (11%) had concordant detection of Cryptosporidium. Cryptosporidium infection in children was associated with detection of Cryptosporidium in caregivers (adjusted PR [aPR], 1.8; 95% CI, 1.2 to 2.6; P = .002) and unprotected water source (aPR, 2.0; 95% CI, 1.3 to 3.2; P = .003). Risk factors for Cryptosporidium detection in caregivers included child Cryptosporidium infection (aPR, 2.0; 95% CI, 1.3 to 3.0; P = .002) as well as cow (aPR, 3.1; 95% CI, 1.4 to 7.0; P = .02) and other livestock ownership (aPR, 2.6; 95% CI, 1.1 to 6.3; P = .03) vs no livestock ownership. Recent diarrhea in caregivers and children was independently associated with child and caregiver Cryptosporidium infections, respectively.

Conclusions
Our results are consistent with the hypothesis that Cryptosporidium transmission can occur directly between child–caregiver dyads as well as through other pathways involving water and livestock. Additional research into caregivers as a source of childhood Cryptosporidium infection is warranted.
A qualitative exploration of 14 to 17-year old adolescents’ views of early and preventative mental health support in schools
Authors: Spencer Liam , McGovern Ruth , Kaner Eileen 
Published: October 2020

Abstract

Background
Preventative interventions may be effective in reducing and preventing symptoms of mental ill health in children and young people. However, there is a paucity of research in this area that explores the views of young people. This paper reports on a qualitative study to inform the future development of attractive and appropriate early and preventative school-based mental health interventions.

Methods
Semi-structured interviews were conducted with a purposive sample of 12 young people aged 14–17 in North East England. Interviews were audio-recorded, transcribed, anonymised and analysed following a thematic approach.

Results
Four key themes were identified, relevant to those providing, designing and commissioning early and preventative mental health interventions in schools: ‘mental health literacy’, ‘risk factors for wellbeing decline’, ‘experience of school-based support’ and ‘recommendations for future support’.

Conclusions
Young people have varying levels of mental health literacy, but are able to identify academic stress, bullying and the transition from primary to secondary school as leading causes of worry. Young people want more regular and in-depth mental health education, tailored levels of support in school and improved training for teachers.
Evaluation of the pharmacokinetics and efficacy of transdermal flunixin for pain mitigation following castration in goats
Authors: Graves Meggan T , Schneider Liesel , Cox Sherry , Caldwell Marc , Krawczel Peter , Lee Amanda , Lear Andrea 
Published: October 2020

Abstract
The mitigation of pain associated with common management procedures is a rising concern among veterinarians, producers and consumers. Nonsteroidal anti-inflammatory drugs are vital compounds for this purpose due to their cost, convenience, and efficacy. A transdermal formulation of flunixin meglumine (FM) was approved for the treatment of pain in cattle; however, the efficacy has yet to be determined for small ruminants. The current study had two aims: 1) to determine the pharmacokinetics of transdermal flunixin meglumine (TD FM) in bucklings and 2) to evaluate pain mitigation by TD FM following castration. To evaluate pharmacokinetics, 12 male goats (mean age = 6 mo) received 2.2 mg/kg of FM IV (n = 6) or 3.3 mg/kg TD FM (n = 6). Plasma FM concentrations were measured. The mean Cmax, Tmax, and harmonic mean half-life for TD FM were 1.09 ± 0.65 μg/mL, 5.50 ± 2.95 h, and 7.16 ± 2.06 h, respectively. To evaluate the efficacy of pain mitigation, 18 goats were randomly assigned to three treatment groups: 1) TD FM and castration (FM CAST) (n = 6); 2) transdermal placebo and castration (PL CAST) (n = 6); and 3) TD FM and sham castration (SHAM) (n = 6). Plasma samples were collected at 0, 12, 24, 36, 48, 72, and 96 h to assess cortisol and prostaglandin E2 (PGE2). Daily dry matter intake (DMI) was recorded and body weight was measured at the beginning and end of the study. Thermography (IRT) images of the scrotum, as well as heart rate (HR), respiratory rate (RR), and rectal temperature, were taken twice daily. Separate mixed analysis of variance models were used to test the effects of treatment, time, and their interaction on mean body temperature, IRT, HR, and RR. Autoregressive covariance structure was utilized to account for repeated measures and individual goat DMI prior to the study was added as a covariate. There were no differences in vital parameters, IRT measurements, cortisol, or PGE2 in animals receiving either TD FM or placebo following castration (P &gt; 0.05). DMI had a treatment by hour interaction and was significantly higher in FM CAST and SHAM groups than the PL CAST group (P = 0.04). Goats in the SHAM group gained weight throughout the study, whereas goats in all other groups lost weight (P = 0.02). Results indicate that TD FM may mitigate pain as demonstrated by increased DMI; however, a single dose may not be sufficient to reduce physiological indicators of pain associated with castration in goats.
Impact of beef carcass size on chilling rate, pH decline, display color, and tenderness of top round subprimals
Authors: Lancaster Jessica M , Buseman Brianna J , Weber Tanya M , Nasados James A , Richard Ron P , Murdoch Gordon K , Price William J , Colle Michael J , Bass Phillip D 
Published: October 2020

Abstract
Beef carcass weights in the United States have continued to increase over the past 30 yr. As reported by the United States Department of Agriculture, grid-based carcass weight discounts begin when carcasses exceed 408 kg. Despite weight discounts, beef carcass weights continue to increase. At the same time, an increased prevalence of discoloration and color variability in top round subprimals has been observed throughout the industry which may be influenced by the increases in carcass weights. The objectives of this study were to assess the effects of beef carcass size and its relationship to chill time, color, pH, and tenderness of the beef top round. In the current study, eight industry average weight beef carcasses (AW, 341–397 kg) and eight oversized beef carcasses (OW, exceeding 432 kg) were evaluated. Temperatures and pH measurements were observed on both sides of all carcasses for the initial 48 h postharvest at a consistent superficial and deep anatomical location of the respective top rounds. Carcasses were fabricated into subprimals at 48 h and top rounds were aged at 2 °C for an additional 12 d. The superficial location of both AW and OW carcasses cooled at a faster rate (P &lt; 0.01) than the deep locations. The deep location of OW carcasses had a lower pH and a more rapid (P &lt; 0.01) initial pH decline. Quantitative color of steaks from OW carcasses had greater mean L* (lightness; P = 0.01) and initial b* (yellowness; P &lt; 0.01) values. The delayed temperature decline and the accelerated pH decline of the deep location of the top round of OW carcasses occur at different rates than AW carcasses. Delayed rate of cooling leads to irreversible impacts on steak appearance of top round steaks fabricated from OW beef carcasses when compared with AW carcasses.
Expression and localization of SWEETs inPopulusand the effect ofSWEET7overexpression in secondary growth
Authors: Zhang Li , Wang Lijuan , Zhang Jin , Song Cai , Li Yu , Li Jianbo , Lu Mengzhu 
Published: October 2020

AbstractIn trees, wood formation needs carbon import from the photosynthetic source tissues. Sugar transporters play important roles in carbohydrate transport into wood-forming cells. Sugars will eventually be exported transporters (SWEETs) play essential roles in many physiological processes. However, the roles of this family in the growth and development of woody plants have not been systematically investigated. In this study, 27 SWEET genes were identified in the Populus trichocarpa genome. These SWEET genes were classified into four clades based on their phylogenetic relationships, gene structures, conserved motifs and chromosomal locations. Representative SWEET members from each clade were selected for further studies. The PagSWEETs of Populus alba × Populus glandulosa were localized to plasma membrane, vacuolar, endoplasmic reticulum or Golgi. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis showed that PagSWEETs have distinct expression patterns in various tissues, and PagSWEET5, 7, 10b, 10c, 15b, 17a and 17c exhibited high expression levels in stems. PagSWEET7 is localized to the cytoplasmic membrane and specifically expressed in the phloem as detected by histochemical GUS ($\beta $ - glucuronidase) assays. Xylem production and xylem sugar content were greater in developing wood of PagSWEET7 overexpression than wild-type lines. Collectively, these results provide valuable information for further investigating functions of PagSWEET genes, and identify PagSWEET7 as a candidate gene for using biotechnology to modify the wood formation in poplar.
Global DNA Methylation in Cord Blood and Neurodevelopmental Outcome at 18 Months of Age among Intrauterine Growth Restricted and Appropriate for Gestational Age Infants
Authors: Gurugubelli Krishna Rao , Ballambattu Vishnu Bhat , Bobby Zacheriah 
Published: October 2020

Abstract

Background
Intrauterine growth restriction (IUGR) is associated with faltered growth and development later in life. Alteration in DNA methylation may occur among IUGR babies and it can have bearing on the outcome.

Objectives
To compare the DNA methylation in the cord blood among IUGR and appropriate for gestational age (AGA) babies and find it is association with their neurodevelopmental outcome at 18 months of age.

Methodology
Genomic DNA methylation among 40 IUGR and equal number of AGA neonates was estimated by using 5-mC ELISA kit in the cord blood. Infants were assessed at birth and their anthropometric measurements were taken. They were regularly followed up and assessed for neurodevelopment outcome till 18 months of age using DASII (Developmental Assessment Scale for Indian Infants). DNA methylation was correlated with neurodevelopmental outcome. Numbers and percentages were used for categorical data. Mean and SD were used for continuous variables. The significant mean difference between IUGR and AGA was determined by independent Student t-test. To study the association between the DNA methylation and outcome, Spearman correlation was used. A p &lt; 0.05 was considered as statistically significant.

Results
Significant difference in DNA methylation was observed between IUGR and AGA infants (IUGR: 3.12 ± 1.24; AGA: 4.40 ± 2.03; p &lt; 0.001). Anthropometry (weight, length and head circumference) at birth was significantly decreased among IUGR infants. Hospital stay was significantly longer for IUGR infants. Motor (IUGR: 89.98 ± 18.77; AGA: 101.75 ± 9.62; p &lt; 0.001), and mental (IUGR: 90.81 ± 11.13; AGA: 105.71 ± 7.20; p &lt; 0.001) scores were significantly decreased among IUGR compared with AGA neonates at 18 months of follow-up. Global DNA methylation had a significant positive correlation with mental score but not with motor developmental score.

Conclusion
IUGR babies had lower motor and mental score compared with AGA babies. Cord blood global DNA methylation significantly correlated with mental development score but not with motor development at 18 months of age.
Using a betting game to reveal the rich nature of visual working memories
Authors: Jabar Syaheed B. , Sreenivasan Kartik K. , Lentzou Stergiani , Kanabar Anish , Brady Timothy F. , Fougnie Daryl 
Published: October 2020

AbstractWhen we ask people to hold a color in working memory, what do they store? Do they remember colors as point estimates (e.g. a particular shade of red) or are memory representations richer, such as uncertainty distributions over feature space? We developed a novel paradigm (a betting game) to measure the nature of working memory representations. Participants were shown a set of colored circles and, after a brief memory delay, asked about one of the objects. Rather than reporting a single color, participants placed multiple bets to create distributions in color space. The dispersion of bets was correlated with performance, indicating that participants’ internal uncertainty guided bet placement. Furthermore, relative to the first response, memory performance improved when averaging across multiple bets, showing that memories contain more information than can be conveyed in a single response. Finally, information about the item in memory was present in subsequent responses even when the first response would generally be classified as a guess or report of an incorrect item, suggesting that such failures are not all-or-none. Thus, memory representations are more than noisy point estimates; they are surprisingly rich and probabilistic.
Evidence for adaptive evolution in the receptor-binding domain of seasonal coronaviruses OC43 and 229E
Authors: Kistler Kathryn E. , Bedford Trevor 
Published: October 2020

AbstractSeasonal coronaviruses (OC43, 229E, NL63 and HKU1) are endemic to the human population, regularly infecting and reinfecting humans while typically causing asymptomatic to mild respiratory infections. It is not known to what extent reinfection by these viruses is due to waning immune memory or antigenic drift of the viruses. Here, we address the influence of antigenic drift on immune evasion of seasonal coronaviruses. We provide evidence that at least two of these viruses, OC43 and 229E, are undergoing adaptive evolution in regions of the viral spike protein that are exposed to human humoral immunity. This suggests that reinfection may be due, in part, to positively-selected genetic changes in these viruses that enable them to escape recognition by the immune system. It is possible that, as with seasonal influenza, these adaptive changes in antigenic regions of the virus would necessitate continual reformulation of a vaccine made against them.
The evolution of social learning as phenotypic cue integration
Authors: Kuijper Bram , Leimar Olof , Hammerstein Peter , McNamara John M. , Dall Sasha R. X. 
Published: October 2020

AbstractMost analyses of the origins of cultural evolution focus on when and where social learning prevails over individual learning, overlooking the fact that there are other developmental inputs that influence phenotypic fit to the selective environment. This raises the question how the presence of other cue ‘channels’ affects the scope for social learning. Here, we present a model that considers the simultaneous evolution of (i) multiple forms of social learning (involving vertical or horizontal learning based on either prestige or conformity biases) within the broader context of other evolving inputs on phenotype determination, including (ii) heritable epigenetic factors, (iii) individual learning, (iv) environmental and cascading maternal effects, (v) conservative bet-hedging and (vi) genetic cues. In fluctuating environments that are autocorrelated (and hence predictable), we find that social learning from members of the same generation (horizontal social learning) explains the large majority of phenotypic variation, whereas other cues are much less important. Moreover, social learning based on prestige biases typically prevails in positively autocorrelated environments, whereas conformity biases prevail in negatively autocorrelated environments. Only when environments are unpredictable or horizontal social learning is characterised by an intrinsically low information content, other cues such as conservative bet-hedging or vertical prestige biases prevail.
A Network Medicine Approach to Drug Repurposing for Chronic Pancreatitis
Authors: Golden Megan , Wilson Jabe 
Published: October 2020

AbstractDespite decades of clinical investigations, there is currently no effective treatment for patients diagnosed with Chronic Pancreatitis (CP). Computational drug repurposing holds promise to rapidly identify therapeutics which may prove efficacious against the disease. Using a literature-derived knowledge graph, we train multiple machine learning models using embeddings based on i) the network topology of regulation bipartite networks, ii) protein primary structures and iii) molecule substructures. Using these models, we predict approved drugs that down-regulate the disease, and assess their proposed respective drug targets and mechanism of actions. We analyse the highest predicted drugs and find a diverse range of regulatory mechanisms including inhibition of fibrosis, inflammation, immmune response, oxidative stress and calcium homeostasis. Notably, we identify resiniferatoxin, a potent analogue of capsaicin, as a promising repurposable candidate due to its antiinflammatory properties, nociceptive pain suppression, and regulation of calcium homeostatis (through potentiation of mutant cystic fibrosis transmembrane conductance regulator (CFTR)). Resiniferatoxin may also regulate intracellular acinar Ca2+ via agonism of transient receptor potential vanilloid subfamily member 6 (TRPV6). We believe the potential of this repurposable drug warrants furtherin silicoandin vitrotesting, particularly the affect of the TRPV6 agonism on disease pathogenesis.
Binding of regulatory proteins to nucleosomes is modulated by dynamic histone tails
Authors: Peng Yunhui , Li Shuxiang , Onufriev Alexey , Landsman David , Panchenko Anna R. 
Published: October 2020

AbstractDespite histone tails’ critical roles in epigenetic regulation, little is known about mechanisms of how histone tails modulate the nucleosomal DNA solvent accessibility and recognition of nucleosomes by other macromolecules. Here we generate extensive atomic level conformational ensembles of histone tails in the context of the full human nucleosome, totaling 26 microseconds of molecular dynamics simulations. We explore the histone tail binding with the nucleosomal and linker DNA and observe rapid conformational transitions between bound and unbound states allowing us to estimate kinetic and thermodynamic properties of the histone tail-DNA interactions. Different histone types exhibit distinct, although conformationally heterogeneous, binding modes and each histone type occludes specific DNA regions from the solvent. Using a comprehensive set of experimental data on nucleosome structural complexes, we find that majority of the studied nucleosome-binding proteins and histone tails target mutually exclusive regions on nucleosomal or linker DNA around the super-helical locations ±1, ±2, and ±7. This finding is explained within the generalized competitive binding and tail displacement models of partners recruitment to nucleosomes. Finally, we demonstrate the crosstalk between different histone post-translational modifications, where charge-altering modifications and mutations typically suppress tail-DNA interactions and enhance histone tail dynamics.