bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mathematical model of HIV dynamics treated with a population of gene-edited haematopoietic progenitor cells exhibiting threshold phenomenon
Authors: Ratti Vardayani , Nanda Seema , Eszterhas Susan K , Howell Alexandra L , Wallace Dorothy I 
Published: May 2019

Abstract
The use of gene-editing technology has the potential to excise the CCR5 gene from haematopoietic progenitor cells, rendering their differentiated CD4-positive (CD4+) T cell descendants HIV resistant. In this manuscript, we describe the development of a mathematical model to mimic the therapeutic potential of gene editing of haematopoietic progenitor cells to produce a class of HIV-resistant CD4+ T cells. We define the requirements for the permanent suppression of viral infection using gene editing as a novel therapeutic approach. We develop non-linear ordinary differential equation models to replicate HIV production in an infected host, incorporating the most appropriate aspects found in the many existing clinical models of HIV infection, and extend this model to include compartments representing HIV-resistant immune cells. Through an analysis of model equilibria and stability and computation of $R_0$ for both treated and untreated infections, we show that the proposed therapy has the potential to suppress HIV infection indefinitely and return CD4+ T cell counts to normal levels. A computational study for this treatment shows the potential for a successful ‘functional cure’ of HIV. A sensitivity analysis illustrates the consistency of numerical results with theoretical results and highlights the parameters requiring better biological justification. Simulations of varying level production of HIV-resistant CD4+ T cells and varying immune enhancements as the result of these indicate a clear threshold response of the model and a range of treatment parameters resulting in a return to normal CD4+ T cell counts.
Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults
Authors: Halperin Scott A , Das Rituparna , Onorato Matthew T , Liu Kenneth , Martin Jason , Grant-Klein Rebecca J , Nichols Rick , Coller Beth-Ann , Helmond Frans A , Simon Jakub K 
Published: May 2019

Abstract

Background
This double-blind study assessed immunogenicity, lot consistency, and safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP).

Methods
Healthy adults (N = 1197) were randomized 2:2:2:2:1 to receive 1 of 3 consistency lots of rVSVΔG-ZEBOV-GP (2 × 107 plaque-forming units [pfu]), high-dose 1 × 108 pfu, or placebo. Antibody responses pre-/postvaccination (28 days, 6 months; in a subset [n = 566], months 12, 18, and 24) were measured. post hoc analysis of risk factors associated with arthritis following vaccination was performed.

Results
ZEBOV-GP enzyme-linked immunosorbent assay (ELISA) geometric mean titers (GMTs) increased postvaccination in all rVSVΔG-ZEBOV-GP groups by 28 days (>58-fold) and persisted through 24 months. The 3 manufacturing lots demonstrated equivalent immunogenicity at 28 days. Neutralizing antibody GMTs increased by 28 days in all rVSVΔG-ZEBOV-GP groups, peaking at 18 months with no decrease through 24 months. At 28 days, ≥94% of vaccine recipients seroresponded (ZEBOV-GP ELISA, ≥2-fold increase, titer ≥200 EU/mL), with responses persisting at 24 months in ≥91%. Female sex and a history of arthritis were identified as potential risk factors for the development of arthritis postvaccination.

Conclusions
Immune responses to rVSVΔG-ZEBOV-GP persisted to 24 months. Immunogenicity and safety results support continued rVSVΔG-ZEBOV-GP development.

Clinical Trials Registration
NCT02503202.
Serial monitoring of isavuconazole blood levels during prolonged antifungal therapy
Authors: Furfaro E , Signori A , Di Grazia C , Dominietto A , Raiola A M , Aquino S , Ghiggi C , Ghiso A , Ungaro R , Angelucci E , Viscoli C , Mikulska M 
Published: May 2019

Abstract

Background
Isavuconazole is the newest triazole antifungal approved for the treatment of invasive aspergillosis (IA) and invasive mucormycosis in adult patients.

Objectives
To characterize the assessment of the blood levels of isavuconazole and their association with efficacy and toxicity.

Methods
From January 2017 to May 2018, blood samples obtained from patients receiving isavuconazole were analysed for therapeutic drug monitoring. Factors influencing the blood concentrations of isavuconazole, such as weight, length of treatment, route of administration and results of selected liver function tests, were analysed in univariate and multivariate models. The receiver operating characteristic (ROC) curve was analysed to detect the best cut-off for isavuconazole toxicity.

Results
A total of 264 isavuconazole blood concentrations in 19 patients were analysed. The median value of isavuconazole concentration in all patients during the first 30 days of therapy was 3.69 mg/L (range 0.64–8.13 mg/L). A linear increase of 0.032 mg/L (range 0.023–0.041 mg/L) for each day of treatment (P = 0.002) was observed. In multivariate analysis the association between the length of treatment and higher levels of isavuconazole (P < 0.001) and higher serum GGT and lower isavuconazole levels (P = 0.001) was confirmed. Adverse events, mainly gastrointestinal, were reported in six patients (31.6%). Based on time-dependent and fixed-time ROC curve analysis, 4.87 mg/L and 5.13 mg/L, respectively, were the identified thresholds for toxicity.

Conclusions
Isavuconazole was efficacious and well tolerated. Side effects, mainly gastrointestinal, were associated with prolonged administration and high serum levels.
Identifying vulnerable older adult populations by contextualizing geriatric syndrome information in clinical notes of electronic health records
Authors: Chen Tao , Dredze Mark , Weiner Jonathan P , Kharrazi Hadi 
Published: May 2019

Abstract

Objective
Geriatric syndromes such as functional disability and lack of social support are often not encoded in electronic health records (EHRs), thus obscuring the identification of vulnerable older adults in need of additional medical and social services. In this study, we automatically identify vulnerable older adult patients with geriatric syndrome based on clinical notes extracted from an EHR system, and demonstrate how contextual information can improve the process.

Materials and Methods
We propose a novel end-to-end neural architecture to identify sentences that contain geriatric syndromes. Our model learns a representation of the sentence and augments it with contextual information: surrounding sentences, the entire clinical document, and the diagnosis codes associated with the document. We trained our system on annotated notes from 85 patients, tuned the model on another 50 patients, and evaluated its performance on the rest, 50 patients.

Results
Contextual information improved classification, with the most effective context coming from the surrounding sentences. At sentence level, our best performing model achieved a micro-F1 of 0.605, significantly outperforming context-free baselines. At patient level, our best model achieved a micro-F1 of 0.843.

Discussion
Our solution can be used to expand the identification of vulnerable older adults with geriatric syndromes. Since functional and social factors are often not captured by diagnosis codes in EHRs, the automatic identification of the geriatric syndrome can reduce disparities by ensuring consistent care across the older adult population.

Conclusion
EHR free-text can be used to identify vulnerable older adults with a range of geriatric syndromes.
Effect of Sex and Air Temperature on the Flight Capacity of Bradysia odoriphaga (Diptera: Sciaridae)
Authors: Hu Jing-rong , Xie Chao , Shi Cai-hua , Wang Shao-li , Wu Qing-jun , Li Chuan-ren , Zhang You-jun 
Published: May 2019

Abstract
Bradysia odoriphaga Yang & Zhang (Diptera: Sciaridae) is an important pest of Chinese chives. Information on the effects of biotic and abiotic factors on the flight performance of B. odoriphaga is crucial for understanding the pest’s ability to disperse and migrate. In this study, the effects of sex and air temperature on the flight performance of B. odoriphaga imagoes were assessed by tethering individual imagoes to computerized flight mills for a 10-h experiment. The results showed that the percentage of imagoes that flew a particular distance gradually decreased as flight distance increased. The percentage of imagoes was significantly higher for males than females when the flight distance was <300 m. Sex and air temperature significantly affected average flight time (which ranged from 14.6 to 68.3 min) and average flight distance (which ranged from 10.4 to 107.2 m), but did not significantly affect average flight speed (which ranged from 3.8 to 6.4 m/min). For both females and males, the average flight distance and flight time were shortest at 18°C and longest at 22°C; the interaction between air temperature and sex was not significant. The results suggest that B. odoriphaga has a poor potential for long-distance migration. These findings will be helpful for developing forecasting and management systems for B. odoriphaga.
The Interplay between ‘Abhyudaya’ and ‘Niḥśreyasa’ in Vaiśeṣika System
Authors: Moise Ionut 
Published: May 2019

Abstract
In the second half of the first millennium AD, Vaiśeṣika system undergoes a process of synthesis, articulated by the development of the doctrine of dharma under which umbrella, two contrasting views on ‘salvation’ abhyudaya (possibly Vedic) and niḥśreyasa (Upaniṣadic) come to be explained as implying each other. The doctrine of salvation in Vaiśeṣika is a static state, devoid of change, and is indeed defined with niḥśreyasa (mokṣa), but because it is determined by a particular dharma as Candrānanda says [Vaiśeṣikasūtras with Candrānanda’s Vṛtti (VSc) 6.2.11; VSc 1.1.2], it comes to be seen as not exclusively removed from the necessity of action, be it ethical or karmic, which are so much the domain of abhyudaya (VSc 1.1.2; 1.1.6). It seems that the system’s soteriology expands as to include not only the renouncer’s acts, but also worldly ones, hence abhyudaya becomes preliminary to niḥśreyasa.
The First Molecular and Phenotypic Characterization of the Invasive Population of Aedes albopictus (Diptera: Culicidae) from the Central Balkans
Authors: Gojković Nemanja , Ludoški Jasmina , Krtinić Bosiljka , Milankov Vesna 
Published: May 2019

AbstractAedes (Stegomya) albopictus (Skuse 1984), the Asian tiger mosquito, represents the most invasive and one of the medically most important mosquito vectors. Although native to South East Asia, the species has recently spread globally, and was registered in the city of Novi Sad (Serbia, Central Balkans) in August 2018. We characterized the invasive population using phenotypic (wing size and shape) and molecular (nuclear, internal transcribed spacer 2- ITS2, and mitochondrial, cytochrome c oxidase subunit I- COI) markers. The results of phenotypic analyses indicated that the Serbian population could be differentiated from the native (Thailand) and invasive (Hawaii and Florida) populations due to restricted gene flow, founder effect, and supposed different strain origin. The Serbian population showed genetic homogeneity, indicative of a small founder number (bottleneck invasion model). Despite the incorporation of ITS2 GenBank sequences into the data set, neither spatial (Geneland) nor nonspatial (BAPS) genetic structuring analyses helped infer the Serbian population origin. However, the comparison of the retrieved COI haplotype with previously characterized mitogenomes indicated a temperate strain origin, capable of overwintering. Such findings suggest that the newly registered Ae. albopictus population could be able to establish itself since previous studies outlined Novi Sad as a suitable area.
Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies
Authors: McGee Emma E , Jackson Sarah S , Petrick Jessica L , Van Dyke Alison L , Adami Hans-Olov , Albanes Demetrius , Andreotti Gabriella , Beane-Freeman Laura E , Berrington de Gonzalez Amy , Buring Julie E , Chan Andrew T , Chen Yu , Fraser Gary E , Freedman Neal D , Gao Yu-Tang , Gapstur Susan M , Gaziano J Michael , Giles Graham G , Grant Eric J , Grodstein Francine , Hartge Patricia , Jenab Mazda , Kitahara Cari M , Knutsen Synnove F , Koh Woon-Puay , Larsson Susanna C , Lee I-Min , Liao Linda M , Luo Juhua , Milne Roger L , Monroe Kristine R , Neuhouser Marian L , O’Brien Katie M , Peters Ulrike , Poynter Jenny N , Purdue Mark P , Robien Kim , Sandler Dale P , Sawada Norie , Schairer Catherine , Sesso Howard D , Simon Tracey G , Sinha Rashmi , Stolzenberg-Solomon Rachael , Tsugane Shoichiro , Wang Renwei , Weiderpass Elisabete , Weinstein Stephanie J , White Emily , Wolk Alicja , Yuan Jian-Min , Zeleniuch-Jacquotte Anne , Zhang Xuehong , Zhu Bin , McGlynn Katherine A , Campbell Peter T , Koshiol Jill 
Published: May 2019

Abstract

Background
Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear.

Methods
We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided.

Results
Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend &lt; .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, &gt;40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers.

Conclusions
Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.
Plugging the holes—new Canadian and US regulations to reduce upstream methane emissions
Authors: Ingelson Allan 
Published: May 2019

Abstract
In the USA and Canada where most of global shale oil and gas development has occurred, due to concerns about climate change the national governments have adopted new regulations to further significantly reduce national methane emissions from the upstream oil and gas industry. The 2016 US Environmental Protection Agency emissions standards and 2018 Canadian methane regulations build on decades old oil and gas conservation schemes to further reduce the volume of methane that is released from facility equipment leaks and venting. In Canada, venting methane at new oil and gas well sites is now prohibited. Operators are required to capture and use a much larger volume of natural gas than in the past. A negotiated settlement of the first US emissions reduction enforcement action was reached in April 2018. The facility operator agreed to pay a civil penalty of US $610,000 and spend a minimum of $2 million to install new technology at its facilities to further reduce methane emissions. The creative settlement agreement contains a comprehensive set of conditions to provide for a reduction in upstream industry emissions.
Current approaches to measure nitric oxide in plants
Authors: Vishwakarma Abhaypratap , Wany Aakanksha , Pandey Sonika , Bulle Mallesham , Kumari Aprajita , Kishorekumar Reddy , Igamberdiev Abir U , Mur Luis A J , Gupta Kapuganti Jagadis 
Published: May 2019

AbstractNitric oxide (NO) is now established as an important signalling molecule in plants where it influences growth, development, and responses to stress. Despite extensive research, the most appropriate methods to measure and localize these signalling radicals are debated and still need investigation. Many confounding factors such as the presence of other reactive intermediates, scavenging enzymes, and compartmentation influence how accurately each can be measured. Further, these signalling radicals have short half-lives ranging from seconds to minutes based on the cellular redox condition. Hence, it is necessary to use sensitive and specific methods in order to understand the contribution of each signalling molecule to various biological processes. In this review, we summarize the current knowledge on NO measurement in plant samples, via various methods. We also discuss advantages, limitations, and wider applications of each method.
S-Alk(en)ylcysteine sulfoxides in the genus Allium: proposed biosynthesis, chemical conversion, and bioactivities
Authors: Yoshimoto Naoko , Saito Kazuki 
Published: May 2019

AbstractS-Alk(en)ylcysteine sulfoxides are sulfur-containing natural products characteristic of the genus Allium. Both the flavor and medicinal properties of Allium plants are attributed to a wide variety of sulfur-containing compounds that are generated from S-alk(en)ylcysteine sulfoxides. Previous radiotracer experiments proposed that S-alk(en)ylcysteine sulfoxides are biosynthesized from glutathione. The recent identification of γ-glutamyl transpeptidases and a flavin-containing S-oxygenase involved in the biosynthesis of S-allylcysteine sulfoxide (alliin) in garlic (Allium sativum) provided insights into the reaction order of deglutamylation and S-oxygenation together with the localization of the biosynthesis, although the rest of the enzymes in the pathway still await discovery. In intact plants, S-alk(en)ylcysteine sulfoxides are stored in the cytosol of storage mesophyll cells. During tissue damage, the vacuolar enzyme alliinase contacts and hydrolyzes S-alk(en)ylcysteine sulfoxides to produce the corresponding sulfenic acids, which are further converted into various sulfur-containing bioactive compounds mainly via spontaneous reactions. The formed sulfur-containing compounds exhibit bioactivities related to pathogen defense, the prevention and alleviation of cancer and cardiovascular diseases, and neuroprotection. This review summarizes the current understanding of the occurrence, biosynthesis, and alliinase-triggered chemical conversion of S-alk(en)ylcysteine sulfoxides in Allium plants as well as the impact of S-alk(en)ylcysteine sulfoxides and their derivatives on medicinal, food, and agricultural sciences.
Gene expression changes in human bronchial epithelial cells (BEAS-2B) and human pulmonary alveolar epithelial cells (HPAEpiC) after interaction with Cladosporium sphaerospermum
Authors: Lo Sing Gee , Wong Shew Fung , Mak Joon Wah , Choo Khi Khi , Ng Kee Peng 
Published: May 2019

AbstractCladosporium is one of the most abundant spore. Fungi of this genus can cause respiratory allergy and intrabronchial lesion. We studied the differential expression of host genes after the interaction of Cladosporium sphaerospermum conidia with Human Bronchial Epithelial Cells (BEAS-2B) and Human Pulmonary Alveolar Epithelial Cells (HPAEpiC). C. sphaerospermum conidia were harvested and co-cultured with BEAS-2B cells or HPAEpiC cells for 48 hours respectively. This culture duration was chosen as it was associated with high germination rate. RNA was extracted from two biological replicates per treatment. RNA of BEAS-2B cells was used to assess changes in gene expression using AffymetrixGeneChip® Human Transcriptome Array 2.0. After co-culture with Cladosporium spores, 68 individual genes were found differentially expressed (P ≤ 0.05) and up-regulated ≥ 1.5 folds while 75 genes were found differentially expressed at ≤ −1.5 folds compared with controls. Reverse transcription and qPCR were performed on the RNA collected from both BEAS-2B cells and HPAEpiC cells to validate the microarray results with 7 genes. Based on the findings, infected pulmonary epithelial cells exhibited an increase in cell death-related genes and genes associated with innate immunity.
Characterizing stellar parameters from high-resolution spectra of main sequence cool stars. I. The G2V–K2V stars
Authors: Kulenthirarajah Logithan , Donati Jean-François , Hussain Gaitee , Morin Julien , Allard France 
Published: May 2019

Abstract
The goal of the present study is to construct, test, and validate a high-resolution synthetic spectral library using PHOENIX model atmospheres and develop a reliable tool to estimate stellar parameters from high-resolution optical and/or near-infrared spectra of M dwarfs. We report here the preliminary results of tests characterizing main sequence G–K stars from high-resolution spectra. We anchored the atomic line-list using the stellar standards Sun, ξ Boo A, and ϵ Eri to ensure the synthetic spectra computed with PHOENIX reproduce their observed counterparts. These stars were chosen because their parameters are very well characterized, and on which the absolute accuracy of our method depends on.
We successfully estimated the stellar parameters with associated error bars for 17 stars. Using a pseudo Monte Carlo statistical analysis, we present overall improved uncertainties on the stellar parameters compared to those in the literature (on average 9 K, 0.014 dex, and 0.008 dex for the effective temperature, the surface gravity, and the metallicity, respectively). Our estimated stellar parameters are also in good agreement with values found in the literature.
Solving the γ-ray radiative transfer equation for supernovae
Authors: Wilk Kevin D , Hillier D John , Dessart Luc 
Published: May 2019

ABSTRACT
We present a new relativistic radiative transfer code for γ-rays of energy less than 5 MeV in supernova (SN) ejecta. This code computes the opacities, the prompt emissivity (i.e. decay), and the scattering emissivity, and solves for the intensity in the co-moving frame. Because of the large expansion velocities of SN ejecta, we ignore redistribution effects associated with thermal motions. The energy deposition is calculated from the energy removed from the radiation field by scattering or photoelectric absorption. This new code yields comparable results to an independent Monte Carlo code. However, both yield non-trivial differences with the results from a pure absorption treatment of γ-ray transport. A synthetic observer’s frame spectrum is also produced from the co-moving frame intensity. At early times when the optical depth to γ-rays is large, the synthetic spectrum shows asymmetric line profiles with redshifted absorption as seen in SN 2014J. This new code is integrated within cmfgen and allows for an accurate and fast computation of the decay energy deposition in SN ejecta.