bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reassessment of hepatitis B virus window periods for two transcription‐mediated amplification assays using screening data of South African blood donors
Authors: Vermeulen Marion , van Drimmelen Harry , Coleman Charl , Sykes Wendy , Reddy Ravi , Busch Michael , Kleinman Steve , Lelie Nico 
Published: July 2019

BACKGROUNDTranscription‐mediated amplification assays for HBV DNA detection have transitioned from the Ultrio to the Ultrio Plus assay, which features increased analytic sensitivity due to inclusion of a target enhancer reagent. The impact on HBV detection for different categories of HBV infection has not been fully evaluated.STUDY DESIGN AND METHODSHepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) detection rates as well as viral load (VL) distributions in HBV nucleic acid test (NAT)‐yield samples were compared during 1 year of screening of South African blood donors with the Ultrio assay and the subsequent year by the Ultrio Plus version. HBV‐DNA concentration at the HBsAg seroconversion point was established by regression analysis using a set of antibody to hepatitis B core antigen–negative acute viremic samples.RESULTSUltrio Plus detected twofold more window‐period (WP) NAT yield donations and 1.7‐fold more occult HBV infections than Ultrio. The VL distribution data indicated that Ultrio not only missed samples of less than 100 copies/mL, but also a substantial number higher than this level. The VL at the HBsAg seroconversion point was estimated at 916 copies/mL, whereas the VL at the NAT‐conversion points was calculated at 63 and 4.1 copies/mL for Ultrio and Ultrio Plus. This reduced the infectious WP (compared to HBsAg testing) by 10.3 and 20.4 days, respectively.CONCLUSIONThe higher‐than‐expected increase in HBV‐NAT yields after introduction of the Ultrio Plus assay is likely attributable to variable sensitivity of the former Ultrio assay for different HBV samples. Therefore, previously published HBV WP reduction and residual risk estimates based on analytical sensitivity of the Ultrio assay need to be revised.
Arginine vasopressin improves cerebral perfusion following controlled haemorrhage in adult ewes
Authors: Berry Mary J. , Darby Jack R. T. , O'Byrne David M. , Dyson Rebecca M. , Sixtus Ryan , Holman Stacey L. , Abelentseva Alexandra , Bowler Paul , Stanbridge Kate , Morrison Janna L. 
Published: July 2019

Key points
Traumatic haemorrhagic shock carries significant morbidity and mortality related to the severity and duration of tissue hypoperfusion, much of which occurs in the pre‐hospital environment where therapy must be easy to use and would augment, not replace, local haemorrhage control measures.
Vasopressor therapy use in haemorrhagic shock remains controversial. Potential benefits from improved blood pressure and tissue perfusion need to be weighed against possible harm from increased blood loss if haemorrhage is uncontrolled.
We demonstrate that 20 IU I.M. vasopressin produces a progressive, sustained and clinically significant increase in blood pressure and carotid blood flow compared to 1 mg I.M. adrenaline or placebo in an animal model of controlled haemorrhagic shock.
I.M. vasopressin may play a role in the early management of haemorrhagic shock by improving cerebral perfusion and haemodynamic stability; however, further studies are required to establish the potential benefit against the risk of exacerbating haemorrhage, if it is uncontrolled.
AbstractHaemorrhagic shock causes significant morbidity and mortality. Novel pre‐hospital therapy to improve haemodynamic stability and cerebral perfusion may improve outcomes but remains controversial. In an ovine model of controlled haemorrhagic shock, the effects of early intramuscular arginine vasopressin (AVP), adrenaline or placebo on haemodynamic stability and cerebral perfusion were compared. Carotid pressure and flow catheters were placed in healthy, anaesthetized adult ewes. Frontal cortex cerebral oxygenation was measured using near infrared spectroscopy. Controlled, rapid, haemorrhage (∼30% estimated blood volume) was induced. Five minutes post‐bleed a 1 ml intramuscular dose of 0.9% saline, adrenaline 1 mg or AVP 20 IU was administered. Carotid blood pressure and flow improved significantly in the AVP group over the first 30 min post‐intervention. To emulate standard trauma care, 1 L of 0.9% saline was infused 30 min post‐bleed followed by re‐transfusion of the sheep's own blood at 60 min post‐bleed. Carotid blood pressure and flow in the AVP group remained significantly higher post‐crystalloid infusion, but this difference was lost post‐blood transfusion. Data were analysed by two‐way ANOVA with time, group as the main factors. When compared to saline or adrenaline, a single dose of intramuscular AVP resulted in a progressive and sustained increase in carotid artery blood pressure and flow with commensurate increase in cerebral oxygenation. Intramuscular AVP has potential as an emergency pre‐hospital therapy following exsanguinating haemorrhage; however, further studies are required to investigate whether the benefit of improved perfusion pressure outweighs the risks of exacerbating ongoing bleeding.
Estimated number of ophthalmologists worldwide (International Council of Ophthalmology update): will we meet the needs?
Authors: Resnikoff Serge , Lansingh Van Charles , Washburn Lindsey , Felch William , Gauthier Tina-Marie , Taylor Hugh R , Eckert Kristen , Parke David , Wiedemann Peter 
Published: July 2019

Background/aimsTo estimate 2015 global ophthalmologist data and analyse their relationship to income groups, prevalence rates of blindness and visual impairment and gross domestic product (GDP) per capita.MethodsOnline surveys were emailed to presidents/chairpersons of national societies of ophthalmology and Ministry of Health representatives from all 194 countries to capture the number and density (per million population) of ophthalmologists, the number/density performing cataract surgery and refraction, and annual ophthalmologist population growth trends. Correlations between these data and income group, GDP per capita and prevalence rates of blindness and visual impairment were analysed.ResultsIn 2015, there were an estimated 232 866 ophthalmologists in 194 countries. Income was positively associated with ophthalmologist density (a mean 3.7 per million population in low-income countries vs a mean 76.2 in high-income countries). Most countries reported positive growth (94/156; 60.3%). There was a weak, inverse correlation between the prevalence of blindness and the ophthalmologist density. There were weak, positive correlations between the density of ophthalmologists performing cataract surgery and GDP per capita and the prevalence of blindness, as well as between GDP per capita and the density of ophthalmologists doing refractions.ConclusionsAlthough the estimated global ophthalmologist workforce appears to be growing, the appropriate distribution of the eye care workforce and the development of comprehensive eye care delivery systems are needed to ensure that eye care needs are universally met.
Risk factors and prognosis of seizures in adults with community-acquired bacterial meningitis in Denmark: observational cohort studies
Authors: Larsen Fredrikke Tove Birgitta Dam , Brandt Christian Thomas , larsen Lykke , Klastrup Vibeke , Wiese Lothar , Helweg-Larsen Jannik , Riber Mette , Hansen Birgitte Rønde , Østergaard Andersen Christian , Nielsen Henrik , Bodilsen Jacob 
Published: July 2019

ObjectiveTo examine predefined risk factors and outcome of seizures in community-acquired bacterial meningitis (CABM).DesignObservational cohort studiesSettingDenmarkParticipantsIn the derivation cohort, we retrospectively included all adults (>15 years of age) with CABM in North Denmark Region from 1998 to 2014 and at Hvidovre and Hillerød hospitals from 2003 to 2014. In the validation cohort, we prospectively included all adults (>18 years of age) with CABM treated at all departments of infectious diseases in Denmark from 2015 to 2017.Primary and secondary outcome measuresIn the derivation cohort, we used modified Poisson regression to compute adjusted relative risks (RRs) with 95% confidence intervals for predefined risk factors for seizures during CABM as well as for risks of death and unfavourable outcome assessed by the Glasgow Outcome Scale score (1-4). Next, results were validated in the validation cohort.ResultsIn the derivation cohort (n=358), risk factors for seizures at any time were pneumococcal aetiology (RR 1.69, 1.01–2.83) and abnormal cranial imaging (RR 2.27, 1.46–3.53), while the impact of age >65 years and immunocompromise was more uncertain. Examining seizures occurring after admission, risk factors were abnormal cranial imaging (RR 2.23, 1.40–3.54) and immunocompromise (RR 1.59, 1.01–2.50). Seizures at any time were associated with increased risks of in-hospital mortality (RR 1.45, 1.01–2.09) and unfavourable outcome at discharge (RR 1.27, 1.02–1.60). In the validation cohort (n=379), pneumococcal aetiology (RR 1.69, 1.10–2.59) and abnormal cranial imaging (RR 1.68, 1.09–2.59) were confirmed as risk factors for seizures at any time. For seizures occurring after admission, only pneumococcal meningitis (RR 1.92, 1.12–3.29) remained significant. Seizures at any time were also associated with in-hospital mortality (RR 3.26, 1.83–5.80) and unfavourable outcome (RR 1.23, 1.00–1.52) in this cohort.ConclusionsPneumococcal aetiology, immunocompromise and abnormal cranial imaging were risk factors for seizures in CABM. Seizures were strongly associated with mortality and unfavourable outcome.
Molecular epidemiological study of enterovirus D68 in hospitalised children in Hong Kong in 2014–2015 and their complete coding sequences
Authors: Wang Haichao , Tao Kinpong , Leung Cheuk Yin , Hon Kam Lun , Yeung C M Apple , Chen Zigui , Chan K S Paul , Leung Ting-Fan , Chan W Y Renee 
Published: July 2019

BackgroundHuman enterovirus D68 (EV-D68) was first isolated in 1962 and has aroused public concern recently because of a nationwide outbreak among children in 2014–2015 in the USA. The symptoms include fever, runny nose, sneezing, cough and muscle pains. It might be associated with severe respiratory illness in individuals with pre-existing respiratory conditions and its potential association with acute flaccid myelitis is under investigation. In Asia, EV-D68 cases have been reported in several countries.The studyWe aimed to understand the EV-D68 prevalence and their genetic diversity in Hong Kong children.MethodsA total of 10 695 nasopharyngeal aspirate (NPA) samples from hospitalised patients aged <18 years were collected from September 2014 to December 2015 in two regional hospitals. NPAs tested positive for enterovirus/rhinovirus (EV/RV) were selected for genotyping. For those identified as EV-D68, their complete coding sequences (CDSs) were obtained by Sanger sequencing. A maximum-likelihood phylogeny was constructed using all EV-D68 complete coding sequences available in GenBank (n=482).Results2662/10 695 (24.9%) were tested positive with EV/RV and 882/2662 (33.1%) were selected randomly and subjected to molecular classification. EV-D68 was detected in 15 (1.70%) samples from patients with clinical presentations ranging from wheezing to pneumonia and belonged to subclade B3. Eight CDSs were successfully obtained. A total of 10 amino acid residue polymorphisms were detected in the viral capsid proteins, proteases, ATPase and RNA polymerase.ConclusionB3 subclade was the only subclade found locally. Surveillance of EV-D68 raises public awareness and provides the information to determine the most relevant genotypes for vaccine development.
Uncountable structures are not classifiable up to bi-embeddability
Authors: Calderoni Filippo , Mildenberger Heike , Motto Ros Luca 
Published: July 2019

Answering some of the main questions from [L. Motto Ros, The descriptive set-theoretical complexity of the embeddability relation on models of large size, Ann. Pure Appl. Logic 164(12) (2013) 1454–1492], we show that whenever [Formula: see text] is a cardinal satisfying [Formula: see text], then the embeddability relation between [Formula: see text]-sized structures is strongly invariantly universal, and hence complete for ([Formula: see text]-)analytic quasi-orders. We also prove that in the above result we can further restrict our attention to various natural classes of structures, including (generalized) trees, graphs, or groups. This fully generalizes to the uncountable case the main results of [A. Louveau and C. Rosendal, Complete analytic equivalence relations, Trans. Amer. Math. Soc. 357(12) (2005) 4839–4866; S.-D. Friedman and L. Motto Ros, Analytic equivalence relations and bi-embeddability, J. Symbolic Logic 76(1) (2011) 243–266; J. Williams, Universal countable Borel quasi-orders, J. Symbolic Logic 79(3) (2014) 928–954; F. Calderoni and L. Motto Ros, Universality of group embeddability, Proc. Amer. Math. Soc. 146 (2018) 1765–1780].
Third-order mock theta functions
Authors: Hu Qiuxia , Song Hanfei , Zhang Zhizheng 
Published: July 2019

In [G. E. Andrews and B. C. Berndt, Ramanujan’s Lost Notebook, Part II (Springer, New York, 2009), Entry 3.4.7, p. 67; Y.-S. Choi, The basic bilateral hypergeometric series and the mock theta functions, Ramanujan J. 24(3) (2011) 345–386; B. Chen, Mock theta functions and Appell–Lerch sums, J. Inequal Appl. 2018(1) (2018) 156; E. Mortenson, Ramanujan’s radial limits and mixed mock modular bilateral [Formula: see text]-hypergeometric series, Proc. Edinb. Math. Soc. 59(3) (2016) 1–13; W. Zudilin, On three theorems of Folsom, Ono and Rhoades, Proc. Amer. Math. Soc. 143(4) (2015) 1471–1476], the authors found the bilateral series for the universal mock theta function [Formula: see text]. In [Choi, 2011], the author presented the bilateral series connected with the odd-order mock theta functions in terms of Appell–Lerch sums. However, the author only derived the associated bilateral series for the fifth-order mock theta functions. The purpose of this paper is to further derive different types of bilateral series for the third-order mock theta functions. As applications, the identities between the two-group bilateral series are obtained and the bilateral series associated to the third-order mock theta functions are in fact modular forms. Then, we consider duals of the second type in terms of Appell–Lerch sums and duals in terms of partial theta functions defined by Hickerson and Mortenson of duals of the second type in terms of Appell–Lerch sums of such bilateral series associated to some third-order mock theta functions that Chen did not discuss in [On the dual nature theory of bilateral series associated to mock theta functions, Int. J. Number Theory 14 (2018) 63–94].
Cutting Edge of Reproductive Medicine
Authors: Wiweko Budi 
Published: July 2019

Background: Louise Brown’s delivery in 1978 was the mark of a successful IVF program that has now been in practice for more than 40 years. The technology has delivered more than 8 million babies. Many breakthrough innovations were established to answer the problem in ART services. Optimizing ART biomarkers and cross border reproductive care have become a rising issue in ART services. Disruptive innovation disrupts the existing condition and takes the lead in the new market, including to change our patient behavior in health services. National health services addressed new issues about the impact of 4.0 industrial revolution on health workforce and our daily practices. Every disruptive innovation today is enhanced by a combination of physical, digital, and biological domain. The advancement in the area of the internet of things, artificial intelligence, virtual reality, nanotechnology, cloud computing, big data, deep learning, machine learning, robotics, and gene editing could potentially support us to innovate. And to improve the quality and outcome of ART, the introduction of the latest technology, such as robotics and artificial intelligence, has become an essential approach. A recent study discovered that the use of artificial intelligence would remove the embryologist’s subjectivity and improve the way we choose the best embryo for implantation. The next challenging issue in ART is improving the success rate through optimizing noninvasive biomarkers development. Many biological products such as blood, tissue, organ fluid can be assessed and considered to be used as IVF biomarkers. Proteomic tools were used and are needed to analyze a sample from subjects before it was created as a biomarker for improving the IVF services quality. Conclusion: The development of IVF over 40 years has brought about many distinct achievements in the laboratory and in clinic. Industrial revolution 4.0 has generated many innovations that have helped improve the quality of ART services, including AUGMENT social egg freezing, artificial intelligence, and genome editing. In this era, precision medicine looks very promising for bridging the gap and increasing the accuracy and efficacy of promotive, preventive, diagnostic, and treatment approaches in reproductive medicine.
PYE
Authors: Thakur Manas , Nandivada V. Krishna 
Published: July 2019

Languages like Java and C# follow a two-step process of compilation: static compilation and just-in-time (JIT) compilation. As the time spent in JIT compilation gets added to the execution-time of the application, JIT compilers typically sacrifice the precision of program analyses for efficiency. The alternative of performing the analysis for the whole program statically ignores the analysis of libraries (available only at runtime), and thereby generates imprecise results. To address these issues, in this article, we propose a two-step (static+JIT) analysis framework called precise-yet-efficient (PYE) that helps generate precise analysis-results at runtime at a very low cost.

PYE achieves the twin objectives of precision and performance during JIT compilation by using a two-pronged approach: (i) It performs expensive analyses during static compilation, while accounting for the unavailability of the runtime libraries by generating partial results, in terms of
conditional values
, for the input application. (ii) During JIT compilation, PYE resolves the conditions associated with these values, using the pre-computed conditional values for the libraries, to generate the final results. We have implemented the static and the runtime components of PYE in the Soot optimization framework and the OpenJDK HotSpot Server Compiler (C2), respectively. We demonstrate the usability of PYE by instantiating it to perform two context-, flow-, and field-sensitive heap-based analyses: (i) points-to analysis for null-dereference-check elimination; and (ii) escape analysis for synchronization elimination. We evaluate these instantiations against their corresponding state-of-the-art implementations in C2 over a wide range of benchmarks. The extensive evaluation results show that our strategy works quite well and fulfills both the promises it makes: enhanced precision while maintaining efficiency during JIT compilation.
MYCRegulates theHIF2αStemness Pathway viaNanogandSox2to Maintain Self-Renewal in Cancer Stem Cells versus Non-Stem Cancer Cells
Authors: Das Bikul , Pal Bidisha , Bhuyan Rashmi , Li Hong , Sarma Anupam , Gayan Sukanya , Talukdar Joyeeta , Sandhya Sorra , Bhuyan Seema , Gogoi Gayatri , Gouw Arvin M. , Baishya Debabrat , Gotlib Jason R. , Kataki Amal C. , Felsher Dean W. 
Published: July 2019

AbstractCancer stem cells (CSC) maintain both undifferentiated self-renewing CSCs and differentiated, non-self-renewing non-CSCs through cellular division. However, molecular mechanisms that maintain self-renewal in CSCs versus non-CSCs are not yet clear. Here, we report that in a transgenic mouse model of MYC-induced T-cell leukemia, MYC, maintains self-renewal in Sca1+ CSCs versus Sca-1− non-CSCs. MYC preferentially bound to the promoter and activated hypoxia-inducible factor-2α (HIF2α) in Sca-1+ cells only. Furthermore, the reprogramming factors, Nanog and Sox2, facilitated MYC regulation of HIF2α in Sca-1+ versus Sca-1− cells. Reduced expression of HIF2α inhibited the self-renewal of Sca-1+ cells; this effect was blocked through suppression of ROS by N-acetyl cysteine or the knockdown of p53, Nanog, or Sox2. Similar results were seen in ABCG2+ CSCs versus ABCG2− non-CSCs from primary human T-cell lymphoma. Thus, MYC maintains self-renewal exclusively in CSCs by selectively binding to the promoter and activating the HIF2α stemness pathway. Identification of this stemness pathway as a unique CSC determinant may have significant therapeutic implications.Significance:These findings show that the HIF2α stemness pathway maintains leukemic stem cells downstream of MYC in human and mouse T-cell leukemias.
DNA-Dependent Protein Kinase Drives Prostate Cancer Progression through Transcriptional Regulation of the Wnt Signaling Pathway
Authors: Kothari Vishal , Goodwin Jonathan F. , Zhao Shuang G. , Drake Justin M. , Yin Yi , Chang S. Laura , Evans Joseph R. , Wilder-Romans Kari , Gabbara Kristina , Dylgjeri Emanuela , Chou Jonathan , Sun Grace , Tomlins Scott A. , Mehra Rohit , Hege Kristen , Filvaroff Ellen H. , Schaeffer Edward M. , Karnes R. Jeffrey , Quigley David A. , Rathkopf Dana E. , He Housheng H. , Speers Corey , Spratt Daniel E. , Gilbert Luke A. , Ashworth Alan , Chinnaiyan Arul M. , Raj Ganesh V. , Knudsen Karen E. , Feng Felix Y. 
Published: July 2019

Abstract

Purpose:
Protein kinases are known to play a prominent role in oncogenic progression across multiple cancer subtypes, yet their role in prostate cancer progression remains underexplored. The purpose of this study was to identify kinases that drive prostate cancer progression.
Experimental Design: To discover kinases that drive prostate cancer progression, we investigated the association between gene expression of all known kinases and long-term clinical outcomes in tumor samples from 545 patients with high-risk disease. We evaluated the impact of genetic and pharmacologic inhibition of the most significant kinase associated with metastatic progression in vitro and in vivo.

Results:
DNA-dependent protein kinase (DNAPK) was identified as the most significant kinase associated with metastatic progression in high-risk prostate cancer. Inhibition of DNAPK suppressed the growth of both AR-dependent and AR-independent prostate cancer cells. Gene set enrichment analysis nominated Wnt as the top pathway associated with DNAPK. We found that DNAPK interacts with the Wnt transcription factor LEF1 and is critical for LEF1-mediated transcription.

Conclusions:
Our data show that DNAPK drives prostate cancer progression through transcriptional regulation of Wnt signaling and is an attractive therapeutic target in aggressive prostate cancer.