bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficits in Bone Architecture and Strength in Children Living With HIV on Antiretroviral Therapy
Authors: Shiau Stephanie , Yin Michael T. , Strehlau Renate , Burke Megan , Patel Faeezah , Kuhn Louise , Coovadia Ashraf , Norris Shane A. , Arpadi Stephen M. ,   Changes Bone Study Team
Published: March 2020

Background:
Reduced bone mineral mass by dual x-ray absorptiometry is reported in children living with HIV (CLWH), but few studies of bone microarchitecture, particularly in sub-Saharan Africa, have been conducted. Here, we compare bone architecture and strength in black South African CLWH and uninfected control children by peripheral quantitative computed tomography (pQCT).

Setting and Methods:
One hundred seventy-two CLWH on antiretroviral therapy (ART) and 98 controls in the CHANGES Bone Study in Johannesburg, South Africa received pQCT scans of the radius and tibia. Measurements included trabecular and cortical volumetric bone mineral density (vBMD) and bone strength, estimated by the polar strength strain index (SSI), a validated measure of fracture risk.

Results:
CLWH (51% boys) and controls (63% boys) were an average of age 10.4 years. Mean ART duration for CLWH was 9.5 years, with 70.9% on an efavirenz-based, 28.5% on a lopinavir/ritonavir-based, and 1 child on an atazanavir/ritonavir-based regimen. Male CLWH had lower trabecular vBMD at the radius than controls after adjustment for age, radial length, and Tanner stage (β = −17.3, standard error = 7.2, P = 0.018). Bone strength by polar SSI was lower in CLWH than controls (778 vs. 972 mm3, P < 0.01). CLWH on an LPV/r-based regimen had lower trabecular vBMD (199 vs. 222 mg/cm3, P < 0.001) and cortical vBMD (1074 vs. 1093 mg/cm3, P = 0.004) than those on an efavirenz-based regimen. No difference in bone strength by polar SSI was observed between treatment groups.

Conclusion:
CLWH initiated on ART early in life with well-controlled HIV have deficits in bone architecture and reductions in bone strength as detected by pQCT.
Cost-Effectiveness of HIV Pre-exposure Prophylaxis Among Heterosexual Men in South Africa: A Cost-Utility Modeling Analysis
Authors: Vogelzang Michelle , Terris-Prestholt Fern , Vickerman Peter , Delany-Moretlwe Sinead , Travill Danielle , Quaife Matthew 
Published: March 2020

Introduction:
Heterosexual men are not considered a key population in the HIV response and are mostly absent from pre-exposure prophylaxis (PrEP) studies to date. Yet, South African men face considerable HIV risk. We estimate the incremental cost-effectiveness of providing oral PrEP, injectable PrEP, or a combination of both to heterosexual South African men to assess whether providing PrEP would efficiently use resources.

Methods:
Epidemiological and costing models estimated the one-year costs and outcomes associated with PrEP use in 3 scenarios. PrEP uptake was estimated for younger (aged 18–24) and older (aged 25–49) men using a discrete choice experiment. Scenarios were compared with a baseline scenario of male condom use, while a health system perspective was used to estimate discounted lifetime costs averted per HIV infection. PrEP benefit was estimated in disability-adjusted life years (DALYs) averted. Uncertainty around the estimated incremental cost-effectiveness ratios (ICERs) was assessed using deterministic and probabilistic sensitivity analyses.

Results:
No PrEP intervention scenarios were cost-effective for both age groups at a willingness-to-pay threshold of $1175/DALY averted. The lowest ICER ($2873/DALY averted) was for the provision of oral PrEP to older men, although probability of cost-effectiveness was just 0.26%. Results found that ICERs were sensitive to HIV incidence and antiretroviral coverage.

Conclusions:
This study estimates that providing PrEP to heterosexual South African men is not cost-effective at current cost-effectiveness thresholds. Given the ICERs' sensitivity to several variables, alongside the heterogeneity of HIV infection among South African men, PrEP may be cost-effective for older men with high incidence and other subgroups based on locality and race. We recommend further investigation to better identify and target these groups.
Exploring the evidence-practice gap in the use of plain radiography for acute abdominal pain and intestinal obstruction: a systematic review and meta-analysis
Authors: Denham Gary , Smith Tony , James Daphne , McKiernan Sharmaine , Evans Tiffany-Jane 
Published: March 2020

ABSTRACT

Aim:
Previous studies, some dating back several decades, have recommended that the use of plain abdominal radiography should be curbed, particularly with the growth of more accurate imaging modalities. However, evidence from referral data suggests that plain abdominal radiography continues to be a commonly requested examination. The aim of this review was to explore the gap between evidence and practice by re-examining the evidence using a robust methodology, investigating the diagnostic accuracy of plain abdominal radiography.

Methods:
Studies were identified from electronic databases and reference lists. Eligible studies provided data as to the sensitivity and specificity of plain abdominal radiography for either acute abdominal pain (Group A) or suspected intestinal obstruction (Group B). Version 2 of the Quality Assessment of Diagnostic Accuracy Studies was used to assess the quality of studies and hierarchical summary receiver operator characteristic curves and coupled forest plots were generated.

Results:
Four studies evaluated plain abdominal radiography for acute abdominal pain (Group A) and 10 for suspected intestinal obstruction (Group B). Two studies investigated both presentations and were included in both groups. Methodological quality of studies was moderately high, though incorporation bias was a common limitation. Sensitivity for Group A studies ranged from 30 to 46%, with specificity from 75 to 88%. For Group B, the range of sensitivity was 48 to 96% and specificity from 50 to 100%.

Conclusion:
The results suggest that use of plain abdominal radiography could be substantially reduced, particularly for patients with undifferentiated acute abdominal pain. While some guidelines exist, there is sound argument for clinical decision rules for abdominal imaging to inform evidence-based clinical decision-making and radiology referrals.
The involvement of HDAC3-mediated inhibition of microRNA cluster 17-92 in hyperoxia-mediated impairment of lung development in neonatal rats
Authors: Wang Di , Hong Hui , Li Xiao-Xia , Li Jing , Zhang Zhi-Qun 
Published: March 2020

AbstractBackgroundThe incidence of bronchopulmonary dysplasia (BPD), a chronic lung disease of newborns, has been paradoxically rising despite medical advances. Histone deacetylase 3 (HDAC3) has been reported to be a crucial regulator in alveologenesis. Hence, this study aims to investigate the mechanism of HDAC3 in the pulmonary angiogenesis and alveolarization of BPD.MethodsA hyperoxia-induced mouse model of BPD was constructed. The mean liner intercept (MLI) and alveolar volume were measured to evaluate the alveolarization in BPD mice. Immunofluorescence assay was performed to detect the microvessel density (MVD) of lung tissues. Next, the expression of HDAC3 and its enrichment in the promoter region of microRNA (miR)-17-92 cluster, as well as the enrichment of p65 in the placental growth factor (Pgf) promoter region were detected by Western blot analysis and chromatin immunoprecipitation (ChIP) assay. The effect of HDAC3 and p65 on the activity of miR-17-92 promoter and Pgf promoter were examined by dual-luciferase reporter gene assay, respectively. Finally, the role of HDAC3 in angiogenesis and alveolarization through miR-17 regulated EZH1-p65-Pgf axis was validated in BPD mouse models.ResultsHDAC3 was involved in the regulation of alveolarization and angiogenesis in BPD. Results demonstrated that the expression of the miR-17-92 cluster in BPD was regulated by HDAC3. miR-17 was related to the regulatory role of HDAC3 in regulating EZH1 expression and in lung fibroblasts of BPD. Besides, results showed that EZH1 could promote Pgf expression by recruiting p65 to regulate BPD. HDAC3 regulated the expression of EZH1 through miR-17 to promote the recruitment of p65 in the Pgf promoter region, thus enhancing the transcription and expression of Pgf. HDAC3 was demonstrated to regulate Pgf through the miR-17-EZH1-p65 axis to mediate angiogenesis and alveolarization of BPD mice.ConclusionAltogether, the present study revealed that HDAC3 could regulate the EZH1-p65-Pgf axis through miR-17 in the miR-17-92 cluster in the pulmonary angiogenesis and alveolarization of BPD mice.
Ontogenetic and static allometry of hind femur length in the cricketGryllus bimaculatus(Orthoptera: Gryllidae) with implications for evo-devo of morphological scaling
Authors: Neiro Jakke Sameli 
Published: March 2020

AbstractThe evolution of morphological allometry or scaling is a long-standing enigma in biology. Three types of allometric relationships have been defined: static, ontogenetic and evolutionary allometry. However, the theory of the interrelationship between these three types of allometry have not been tested in Orthopterans and to a lesser extent in hemimetabolous insects. Here, the ontogenetic allometry of hind femur length in the cricketGryllus bimaculatuswas observed to be slightly positive as compared with a negative allometric relationship for Orthopterans in general, while the instar-specific static allometries were highly variable. The findings give support for the size-grain hypothesis in Orthoptera and indicate that ontogenetic allometries may not predict evolutionary allometries. The current model for the developmental basis of allometry derived from holometabolous insects is extended into a phylogenetic context and the potential ofG. bimaculatusand other Orthopterans for further experiments of evo-devo of morphological scaling is discussed.
Physical activity and Retirement: Original analysis of responses to the English Adult Active Lives Survey 2016/17
Authors: Brainard Julii , Cooke Rachel , Lane Kathleen , Salter Charlotte 
Published: March 2020

AbstractObjectivesOpportunities for older adults to do physical activity may depend on other commitments. To see if reported physical activity was higher or lower among older adults depending on work status: full time, part-time or retired.MethodsThe Active Lives Survey 2016/17 in England was used to see how active people were depending on employment or retirement status. Types of physical activity (PA) considered were: leisure, gardening, active travel and combined total, adjusted for age, sex, BMI, disability, rurality and deprivation in models using hurdle negative binomial regression.ResultsTotal PA was significantly greater for retired persons compared to both full- and part-time workers age 55-64, while being retired or working part-time at age 65-74 meant more PA. People did more leisure or gardening with less work, but active travel decreased with fewer work hours, at all ages. Retirement meant more leisure and gardening PA but less active travel.ConclusionsDemand for opportunities to engage in leisure and gardening PA appears to be high among retired people. Greater promotion of active travel in this cohort may be possible.
High dose-rate brachytherapy of localized prostate cancer converts tumors from cold to hot
Authors: Keam Simon P , Halse Heloise , Nguyen Thu , Wang Minyu , Van Kooten Losio Nicolas , Mitchell Catherine , Caramia Franco , Byrne David J , Haupt Sue , Ryland Georgina , Darcy Phillip K , Sandhu Shahneen , Blombery Piers , Haupt Ygal , Williams Scott G , Neeson Paul J 
Published: March 2020

AbstractProstate cancer (PCa) has a profoundly immunosuppressive microenvironment, we hypothesized that radiation therapy would break this immune suppression. To investigate this, we performed high-throughput immune cell subset analysis, and gene expression profiling of pre-versus post-radiation tissue in a cohort of patients with localized disease that received high dose-rate brachytherapy (HDRBT). We resolved tumor and non-tumor zones in our spatial analysis to explore what drives the immunological response. Nanostring immune profiling revealed numerous immune checkpoint molecules were stimulated in response to HDRBT (e.g. B7-H3, CTLA4, PDL1 and PDL2). A published 16-gene tumor inflammation signature (TIS) gene profiling of immune activation states (high:hot, intermediate and low:cold) showed that most tissues possessed a low TIS pre-HDRBT. Crucially, HDRBT converted 80% of these ‘cold’-phenotype tumors into an ‘intermediate’ or ‘hot’ class. We used digital spatial profiling to show these HDRBT-induced changes in prostate TIS scores were derived from the non-tumor regions. Furthermore, these changes in TIS were also associated with pervasive changes in immune cell density and spatial relationships – in particularly between T cell subsets and antigen presenting cells. We identified increased density of CD4+ FOXP3+ T cells, CD68+ macrophages and CD68+ CD11c+ dendritic cells in response to HDRBT. The only subset change in tumor zones was PDL1+ macrophages. While these immune responses were heterogeneous, HDRBT induced significant changes in immune cell associations, including a gained T cell and HMWCK+ PDL1+ interaction in tumor zones. In conclusion, we showed HDRBT has a clear impact in converting “cold” prostate tumors into more immunologically activated “hot” tissues, with accompanying spatially-organized immune infiltrates and signaling changes. Understanding and potentially harnessing these changes will have widespread implications for the future treatment of localized PCa and the possible use of combination immunotherapies.
Nonsense mediated RNA decay factor UPF1 is critical for post-transcriptional and translational gene regulation in Arabidopsis
Authors: Raxwal Vivek K. , Simpson Craig G. , Gloggnitzer Jiradet , Entinze Juan Carlos , Guo Wenbin , Zhang Runxuan , Brown John W.S. , Riha Karel 
Published: March 2020

AbstractNonsense mediated RNA decay (NMD) is an evolutionary conserved RNA control mechanism that has also been implicated in the broader regulation of gene expression. Nevertheless, a role for NMD in genome regulation has not been fully assessed, partially because NMD inactivation is lethal in many organisms. Here, we performed in depth comparative analysis of Arabidopsis mutants lacking key proteins involved in different steps of NMD. We observed that UPF3, UPF1, and SMG7 have different impacts on NMD and the Arabidopsis transcriptome, with UPF1 having the biggest effect. Transcriptome assembly using stringent pipeline in UPF1-null plants revealed genome wide changes in alternative splicing, including switches in mRNA variants, suggesting a role for UPF1 in splicing. We further found that UPF1 inactivation leads to translational repression, manifested by a global shift in mRNAs from polysomes to monosomes and a downregulation of genes involved in translation and ribosome biogenesis. Despite this global change, NMD targets and low-expressed mRNAs with short half-lives were enriched in polysomes, indicating that UPF1 specifically suppresses the translation of aberrant RNAs. Particularly striking was an increase in the translation of TIR domain-containing, nucleotide-binding, leucine-rich repeat (TNL) immune receptors. The regulation of TNLs via UPF1/NMD-mediated mRNA stability and translational de-repression offers a dynamic mechanism for the rapid activation of TNLs in response to pathogen attack.
Assessing the effects of thinning on stem growth allocation of individual Scots pine trees
Authors: Saarinen Ninni , Kankare Ville , Yrttimaa Tuomas , Viljanen Niko , Honkavaara Eija , Holopainen Markus , Hyyppä Juha , Huuskonen Saija , Hynynen Jari , Vastaranta Mikko 
Published: March 2020

AbstractForest management alters the growing conditions and thus further development of trees. However, quantitative assessment of forest management on tree growth has been demanding as methodologies for capturing changes comprehensively in space and time have been lacking. Terrestrial laser scanning (TLS) has shown to be capable of providing three-dimensional (3D) tree stem reconstructions required for revealing differences between stem shapes and sizes. In this study, we used 3D reconstructions of tree stems from TLS and an unmanned aerial vehicle (UAV) to investigate how varying thinning treatments and the following growth effects affected stem shape and size of Scots pine (Pinus sylvestrisL.) trees. The results showed that intensive thinning resulted in more stem volume and therefore total biomass allocation and carbon uptake compared to the moderate thinning. Relationship between tree height and diameter at breast height (i.e. slenderness) varied between both thinning intensity and type (i.e. from below and above) indicating differing response to thinning and allocation of stem growth of Scots pine trees. Furthermore, intensive thinning, especially from below, produced less variation in relative stem attributes characterizing stem shape and size. Thus, it can be concluded that thinning intensity, type, and the following growth effects have an impact on post-thinning stem shape and size of Scots pine trees. Our study presented detailed measurements on post-thinning stem growth of Scots pines that have been laborious or impracticable before the emergence of detailed 3D technologies. Moreover, the stem reconstructions from TLS and UAV provided variety of attributes characterizing stem shape and size that have not traditionally been feasible to obtain. The study demonstrated that detailed 3D technologies, such as TLS and UAV, provide information that can be used to generate new knowledge for supporting forest management and silviculture as well as improving ecological understanding of boreal forests.
Optimization of data-independent acquisition using predicted libraries for deep and accurate proteome profiling
Authors: Doellinger Joerg , Blumenscheit Christian , Schneider Andy , Lasch Peter 
Published: March 2020

ABSTRACTIn silicospectral library prediction of all possible peptides from whole organisms has a great potential for improving proteome profiling by data-independent acquisition (DIA) and extending its scope of application. In combination with other recent improvements in the field of mass spectrometry (MS)-based proteomics, including sample preparation, peptide separation and data analysis, we aimed to uncover the full potential of such an advanced DIA strategy by optimization of the data acquisition. The results demonstrate that the combination of high-qualityin silicolibraries, reproducible and high-resolution peptide separation using micro-pillar array columns as well as neural network supported data analysis enables the use of long MS scan cycles without impairing the quantification performance. The study demonstrates that mean coefficient of variations of 4 % were obtained even at only 1.5 data points per peak (full width at half maximum) across different gradient lengths, which in turn improved proteome coverage up to more than 8000 proteins from HeLa cells using empirically-corrected libraries and more than 7000 proteins using a whole humanin silicopredicted library. These data were obtained using a Q Exactive orbitrap mass spectrometer with moderate scanning speed (12 Hz) and perform very well in comparison to recent studies using more advanced MS instruments, which underline the high potential of this optimization strategy for various applications in clinical proteomics, microbiology and molecular biology.
Comprehensive analysis of fungal G1 cyclin docking motif sequences that control CDK regulatory potency in vivo
Authors: Bandyopadhyay Sushobhana , Bhaduri Samyabrata , Örd Mihkel , Davey Norman E. , Loog Mart , Pryciak Peter M. 
Published: March 2020

SUMMARYCyclin-dependent kinases (CDKs) control the ordered series of events during eukaryotic cell division. The stage at which individual CDK substrates are phosphorylated can be dictated by cyclin-specific docking motifs. In budding yeast, substrates with Leu/Pro-rich (LP) docking motifs are recognized by Cln1/2 cyclins in late G1 phase, yet the key sequence features of these motifs and the conservation of this mechanism were unknown. Here we comprehensively analyzed LP motif requirements in vivo by combining a competitive growth assay with mutational scanning and deep sequencing. We quantified the impact of all single-residue replacements in five different LP motifs, using six distinct G1 cyclins from diverse fungi including medical and agricultural pathogens. The results reveal the basis for variations in potency among wild-type motifs, and allow derivation of a quantitative matrix that predicts the potency of other candidate motifs. In one protein, Whi5, we found overlapping LP and phosphorylation motifs with partly redundant effects. In another protein, the CDK inhibitor Sic1, we found that its LP motif is inherently weak due to unfavorable residues at key positions, and this imposes a beneficial delay in its phosphorylation and degradation. The overall results provide a general method for surveying viable docking motif sequences and quantifying their potency in vivo, and they reveal how variations in LP motif potency can tune the strength and timing of CDK regulation.
Quantitative fluxomics of circulating metabolites
Authors: Hui Sheng , Cowan Alexis J. , Zeng Xianfeng , Yang Lifeng , TeSlaa Tara , Li Xiaoxuan , Bartman Caroline , Zhang Zhaoyue , Jang Cholsoon , Wang Lin , Lu Wenyun , Rojas Jennifer , Baur Joseph , Rabinowitz Joshua D. 
Published: March 2020

SUMMARYMammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting both for circulatory metabolic cycles and tissue TCA inputs, across fed and fasted mice on either high carbohydrate or ketogenic diet. We find that a majority of circulating carbon flux is carried by two major cycles: glucose-lactate and triglyceride-glycerol-fatty acid. Futile cycling through these pathways is prominent when dietary content of the associated nutrients is low, rendering internal metabolic activity robust to food choice. The presented in vivo flux quantification methods are broadly applicable to different physiological and disease states.