bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Low-Dose rhGM-CSF Treatment in a Patient With Severe Congenital Neutropenia Due to CSF3R Deficiency: Case Report of a Novel Biallelic CSF3R Mutation and Literature Review
Authors: Zhou Junli , Sun Chengjun , Huang Honglin , Zhu Qiguo , Wen Fengyun , Dong Ying , Wang Hongsheng
Published: October 2021

This study reports the clinical manifestations, genetics, and efficacy of treatment with the efficacy of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-GSF) of a 2-year-old female patient with severe congenital neutropenia (SCN) type 7 (SCN7) caused by novel biallelic mutations in the colony-stimulating factor 3 receptor (CSF3R) gene. Genetic diagnosis of the patient was performed by whole-exome and Sanger sequencing. Expression of the CSF3R gene in the peripheral neutrophils of the patient was detected by real-time PCR and Western blotting. The patient presented with recurrent suppurative tonsillitis and decreased absolute neutrophil count <0.5 × 109/L. Novel heterozygous mutations were found to be inherited from each parent (maternal c.690delC [p.met231Cysfs*32] and paternal c.64+5G>A). The patient's neutrophils had lower CSF3R mRNA and protein levels than those of the parents. Low-dose rhGM-CSF (3 μg/kg/day once a week) prevented recurrent infection in the patient. These results demonstrate that the clinical manifestations of SCN7 with biallelic CSF3R mutations and downregulated CSF3R can be effectively treated with rhGM-CSF.
Prenatal and Early Childhood Exposure to Lead and Repeated Measures of Metabolic Syndrome Risk Indicators From Childhood to Preadolescence
Authors: Muciño-Sandoval Karla , Ariza Ana Carolina , Ortiz-Panozo Eduardo , Pizano-Zárate María Luisa , Mercado-García Adriana , Wright Robert , Maria Téllez-Rojo Martha , Sanders Alison P. , Tamayo-Ortiz Marcela
Published: October 2021

Background: Exposure to lead (Pb) during the early life stages has been associated with the development of metabolic syndrome (MetS). Longitudinal studies of Pb exposure in critical developmental windows in children are limited.

Methods: Our study included 601 mother–child dyads from the PROGRESS (Programming Research in Obesity, Growth, Environment and Social Stressors) birth cohort. Blood lead levels (BLLs) were assessed during the second and third gestational trimesters, in cord blood at delivery, and at ages 1, 2, and 4 years. Bone lead levels in the patella and tibia were assessed at 1 month postpartum and evaluated in separate models. To account for cumulative exposure (prenatal, postnatal, and cumulative), we dichotomized the BLLs at each stage visit and determined the following: “higher” if a BLL was at least once above the median (HPb) and “lower” if all BLLs were below the median (LPb). We analyzed fasting glucose, HbA1c, triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (cHDL), low-density lipoprotein cholesterol (cLDL), body mass index, waist circumference (WC), body fat percentage, and systolic (SBP) and diastolic blood pressure (DBP) at two study visits between 6 and 12 years of age and created cutoff points based on the clinical guidelines for each indicator. Mixed effects models were used to analyze each outcome longitudinally for each BLL score, adjusting for child's sex, size for gestational age, child's age, maternal parity, mother's age, and socioeconomic status.

Results: We observed associations for HPb exposure and TC in all stages (OR = 0.53, 95%CI = 0.32–0.86) and postnatally (OR = 0.59, 95%CI = 0.36–0.94) and for prenatal HPb and TGs (OR = 0.65, 95%CI = 0.44–0.95). HPb at all stages was associated with WC (OR = 0.27, 95%CI = 0.08–0.86), BMI (OR = 0.33, 95%CI = 0.11–0.99), SBP (OR = 0.53, 95%CI = 0.32–0.85), and DBP (OR = 0.57, 95%CI = 0.34–0.95). Pb levels in the patella were associated with cHDL (OR = 1.03, 95%CI = 1.00–1.07) and those in the tibia with TGs (OR = 0.95, 95%CI = 0.91–0.99).

Conclusion: Early life exposure to Pb may alter early indicators of MetS. A follow-up of these children will allow for more definition on the impact of longer-term exposures.
Transfusion-Associated Hyperkalemic Cardiac Arrest in Neonatal, Infant, and Pediatric Patients
Authors: Burke Morgan , Sinha Pranava , Luban Naomi L. C. , Posnack Nikki Gillum
Published: October 2021

Red blood cell (RBC) transfusions are a life-saving intervention, with nearly 14 million RBC units transfused in the United States each year. However, the safety and efficacy of this procedure can be influenced by variations in the collection, processing, and administration of RBCs. Procedures or manipulations that increase potassium (K+) levels in stored blood products can also predispose patients to hyperkalemia and transfusion-associated hyperkalemic cardiac arrest (TAHCA). In this mini review, we aimed to provide a brief overview of blood storage, the red cell storage lesion, and variables that increase extracellular [K+]. We also summarize cases of TAHCA and identify potential mitigation strategies. Hyperkalemia and cardiac arrhythmias can occur in pediatric patients when RBCs are transfused quickly, delivered directly to the heart without time for electrolyte equilibration, or accumulate extracellular K+due to storage time or irradiation. Advances in blood banking have improved the availability and quality of RBCs, yet, some patient populations are sensitive to transfusion-associated hyperkalemia. Future research studies should further investigate potential mitigation strategies to reduce the risk of TAHCA, which may include using fresh RBCs, reducing storage time after irradiation, transfusing at slower rates, implementing manipulations that wash or remove excess extracellular K+, and implementing restrictive transfusion strategies.
Machine Learning for Prediction of Stable Warfarin Dose in US Latinos and Latin Americans
Authors: Steiner Heidi E. , Giles Jason B. , Patterson Hayley Knight , Feng Jianglin , El Rouby Nihal , Claudio Karla , Marcatto Leiliane Rodrigues , Tavares Leticia Camargo , Galvez Jubby Marcela , Calderon-Ospina Carlos-Alberto , Sun Xiaoxiao , Hutz Mara H. , Scott Stuart A. , Cavallari Larisa H. , Fonseca-Mendoza Dora Janeth , Duconge Jorge , Botton Mariana Rodrigues , Santos Paulo Caleb Junior Lima , Karnes Jason H.
Published: October 2021

Populations used to create warfarin dose prediction algorithms largely lacked participants reporting Hispanic or Latino ethnicity. While previous research suggests nonlinear modeling improves warfarin dose prediction, this research has mainly focused on populations with primarily European ancestry. We compare the accuracy of stable warfarin dose prediction using linear and nonlinear machine learning models in a large cohort enriched for US Latinos and Latin Americans (ULLA). Each model was tested using the same variables as published by the International Warfarin Pharmacogenetics Consortium (IWPC) and using an expanded set of variables including ethnicity and warfarin indication. We utilized a multiple linear regression model and three nonlinear regression models: Bayesian Additive Regression Trees, Multivariate Adaptive Regression Splines, and Support Vector Regression. We compared each model’s ability to predict stable warfarin dose within 20% of actual stable dose, confirming trained models in a 30% testing dataset with 100 rounds of resampling. In all patients (n = 7,030), inclusion of additional predictor variables led to a small but significant improvement in prediction of dose relative to the IWPC algorithm (47.8 versus 46.7% in IWPC, p = 1.43 × 10−15). Nonlinear models using IWPC variables did not significantly improve prediction of dose over the linear IWPC algorithm. In ULLA patients alone (n = 1,734), IWPC performed similarly to all other linear and nonlinear pharmacogenetic algorithms. Our results reinforce the validity of IWPC in a large, ethnically diverse population and suggest that additional variables that capture warfarin dose variability may improve warfarin dose prediction algorithms.
Asymmetric Interplay Between K+ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K+ Channel Blocker Release
Authors: Gabriel Tobias S. , Hansen Ulf-Peter , Urban Martin , Drexler Nils , Winterstein Tobias , Rauh Oliver , Thiel Gerhard , Kast Stefan M. , Schroeder Indra
Published: October 2021

Modulating the activity of ion channels by blockers yields information on both the mode of drug action and on the biophysics of ion transport. Here we investigate the interplay between ions in the selectivity filter (SF) of K+ channels and the release kinetics of the blocker tetrapropylammonium in the model channel KcvNTS. A quantitative expression calculates blocker release rate constants directly from voltage-dependent ion occupation probabilities in the SF. The latter are obtained by a kinetic model of single-channel currents recorded in the absence of the blocker. The resulting model contains only two adjustable parameters of ion-blocker interaction and holds for both symmetric and asymmetric ionic conditions. This data-derived model is corroborated by 3D reference interaction site model (3D RISM) calculations on several model systems, which show that the K+ occupation probability is unaffected by the blocker, a direct consequence of the strength of the ion-carbonyl attraction in the SF, independent of the specific protein background. Hence, KcvNTS channel blocker release kinetics can be reduced to a small number of system-specific parameters. The pore-independent asymmetric interplay between K+ and blocker ions potentially allows for generalizing these results to similar potassium channels.
Salt Stress Affects Plastid Ultrastructure and Photosynthetic Activity but Not the Essential Oil Composition in Spearmint (Mentha spicata L. var. crispa “Moroccan”)
Authors: Ounoki Roumaissa , Ágh Ferenc , Hembrom Richard , Ünnep Renáta , Szögi-Tatár Bernadett , Böszörményi Andrea , Solymosi Katalin
Published: October 2021

High levels of soil salinity affect plant growth, reproduction, water and ion uptake, and plant metabolism in a complex manner. In this work, the effect of salt stress on vegetative growth, photosynthetic activity, and chloroplast ultrastructure of spearmint (Mentha spicataL. var.crispa“Moroccan”) was investigated. After 2 weeks of low concentration treatments (5, 25, and 50 mM NaCl) of freshly cut shoots, we observed that the stem-derived adventitious root formation, which is a major mean for vegetative reproduction among mints, was completely inhibited at 50 mM NaCl concentration. One-week-long, high concentration (150 mM NaCl) salt stress, and isosmotic polyethylene glycol (PEG) 6000 treatments were compared in intact (rooted) plants and freshly cut, i.e., rootless shoots. Our data showed that roots have an important role in mitigating the deleterious effects of both the osmotic (PEG treatment) and specific ionic components of high salinity stress. At 50 mM NaCl or above, the ionic component of salt stress caused strong and irreversible physiological alterations. The effects include a decrease in relative water content, the maximal and actual quantum efficiency of photosystem II, relative chlorophyll content, as well as disorganization of the native chlorophyll-protein complexes as revealed by 77 K fluorescence spectroscopy. In addition, important ultrastructural damage was observed by transmission electron microscopy such as the swelling of the thylakoid lumen at 50 mM NaCl treatment. Interestingly, in almost fully dry leaf regions and leaves, granum structure was relatively well retained, however, their disorganization occurred in leaf chloroplasts of rooted spearmint treated with 150 mM NaCl. This loss of granum regularity was also confirmed in the leaves of these plants using small-angle neutron scattering measurements of intact leaves of 150 mM NaCl-stressed rooted plants. At the same time, solid-phase microextraction of spearmint leaves followed by gas chromatography and mass spectrometry (GC/MS) analyses revealed that the essential oil composition of spearmint was unaffected by the treatments applied in this work. Taken together, the used spearmint cultivar tolerates low salinity levels. However, at 50 mM NaCl concentration and above, the ionic components of the stress strongly inhibit adventitious root formation and thus their clonal propagation, and severely damage the photosynthetic apparatus.
Identification of Promising Genotypes Through Systematic Evaluation for Arsenic Tolerance and Exclusion in Rice (Oryza sativa L.)
Authors: Murugaiyan Varunseelan , Ali Jauhar , Frei Michael , Zeibig Frederike , Pandey Ambika , Wairich Andriele , Wu Lin-Bo , Murugaiyan Jayaseelan , Li Zhikang
Published: October 2021

Rice remains a major staple food source for the rapidly growing world population. However, regular occurrences of carcinogenic arsenic (As) minerals in waterlogged paddy topsoil pose a great threat to rice production and consumers across the globe. Although As contamination in rice has been well recognized over the past two decades, no suitable rice germplasm had been identified to exploit in adaptive breeding programs. Therefore, this current study identified suitable rice germplasm for As tolerance and exclusion based on a variety of traits and investigated the interlinkages of favorable traits during different growth stages. Fifty-three different genotypes were systematically evaluated for As tolerance and accumulation. A germination screening assay was carried out to identify the ability of individual germplasm to germinate under varying As stress. Seedling-stage screening was conducted in hydroponics under varying As stress to identify tolerant and excluder genotypes, and a field experiment was carried out to identify genotypes accumulating less As in grain. Irrespective of the rice genotypes, plant health declined significantly with increasing As in the treatment. However, genotype-dependent variation in germination, tolerance, and As accumulation was observed among the genotypes. Some genotypes (WTR1-BRRI dhan69, NPT-IR68552-55-3-2, OM997, and GSR IR1-5-Y4-S1-Y1) showed high tolerance by excluding As in the shoot system. Arsenic content in grain ranged from 0.12 mg kg−1in Huang-Hua-Zhan (indica) from China to 0.48 mg kg−1in IRAT 109 (japonica) from Brazil. This current study provides novel insights into the performance of rice genotypes under varying As stress during different growth stages for further use in ongoing breeding programs for the development of As-excluding rice varieties for As-polluted environments.
SEVEN IN ABSENTIA Ubiquitin Ligases Positively Regulate Defense Against Verticillium dahliae in Gossypium hirsutum
Authors: Ren Zhongying , Liu Wei , Wang Xingxing , Chen Mingjiang , Zhao Junjie , Zhang Fei , Feng Hongjie , Liu Ji , Yang Daigang , Ma Xiongfeng , Li Wei
Published: October 2021

Ubiquitination is a post-translational regulatory mechanism that controls a variety of biological processes in plants. The E3 ligases confer specificity by recognizing target proteins for ubiquitination. Here, we identified SEVEN IN ABSENTIA (SINA) ubiquitin ligases, which belong to the RING-type E3 ligase family, in upland cotton (Gossypium hirsutum). Twenty-fourGhSINAs were characterized, and the expression levels ofGhSINA7,GhSINA8, andGhSINA9were upregulated at 24 h after inoculation withVerticillium dahliae.In vitroubiquitination assays indicated that the three GhSINAs possessed E3 ubiquitin ligase activities. Transient expression inNicotiana benthamianaleaves showed that they localized to the nucleus. And yeast two-hybrid (Y2H) screening revealed that they could interact with each other. The ectopic overexpression ofGhSINA7,GhSINA8, andGhSINA9independently inArabidopsis thalianaresulted in increased tolerance toV. dahliae, while individual knockdowns ofGhSINA7,GhSINA8, andGhSINA9compromised cotton resistance to the pathogen. Thus,GhSINA7,GhSINA8, andGhSINA9act as positive regulators of defense responses againstV. dahliaein cotton plants.
Taking the Wheel – de novo DNA Methylation as a Driving Force of Plant Embryonic Development
Authors: Markulin Lucija , Škiljaica Andreja , Tokić Mirta , Jagić Mateja , Vuk Tamara , Bauer Nataša , Leljak Levanić Dunja
Published: October 2021

During plant embryogenesis, regardless of whether it begins with a fertilized egg cell (zygotic embryogenesis) or an induced somatic cell (somatic embryogenesis), significant epigenetic reprogramming occurs with the purpose of parental or vegetative transcript silencing and establishment of a next-generation epigenetic patterning. To ensure genome stability of a developing embryo, large-scale transposon silencing occurs by an RNA-directed DNA methylation (RdDM) pathway, which introduces methylation patterns de novo and as such potentially serves as a global mechanism of transcription control during developmental transitions. RdDM is controlled by a two-armed mechanism based around the activity of two RNA polymerases. While PolIV produces siRNAs accompanied by protein complexes comprising the methylation machinery, PolV produces lncRNA which guides the methylation machinery toward specific genomic locations. Recently, RdDM has been proposed as a dominant methylation mechanism during gamete formation and early embryo development in Arabidopsis thaliana, overshadowing all other methylation mechanisms. Here, we bring an overview of current knowledge about different roles of DNA methylation with emphasis on RdDM during plant zygotic and somatic embryogenesis. Based on published chromatin immunoprecipitation data on PolV binding sites within the A. thaliana genome, we uncover groups of auxin metabolism, reproductive development and embryogenesis-related genes, and discuss possible roles of RdDM at the onset of early embryonic development via targeted methylation at sites involved in different embryogenesis-related developmental mechanisms.
PsEND1 Is a Key Player in Pea Pollen Development Through the Modulation of Redox Homeostasis
Authors: Hamza Rim , Roque Edelín , Gómez-Mena Concepción , Madueño Francisco , Beltrán José Pío , Cañas Luis A.
Published: October 2021

Redox homeostasis has been linked to proper anther and pollen development. Accordingly, plant cells have developed several Reactive Oxygen Species (ROS)-scavenging mechanisms to maintain the redox balance. Hemopexins constitute one of these mechanisms preventing heme-associated oxidative stress in animals, fungi, and plants. Pisum sativum ENDOTHECIUM 1 (PsEND1) is a pea anther-specific gene that encodes a protein containing four hemopexin domains. We report the functional characterization of PsEND1 and the identification in its promoter region of cis-regulatory elements that are essential for the specific expression in anthers. PsEND1 promoter deletion analysis revealed that a putative CArG-like regulatory motif is necessary to confer promoter activity in developing anthers. Our data suggest that PsEND1 might be a hemopexin regulated by a MADS-box protein. PsEND1 gene silencing in pea, and its overexpression in heterologous systems, result in similar defects in the anthers consisting of precocious tapetum degradation and the impairment of pollen development. Such alterations were associated to the production of superoxide anion and altered activity of ROS-scavenging enzymes. Our findings demonstrate that PsEND1 is essential for pollen development by modulating ROS levels during the differentiation of the anther tissues surrounding the microsporocytes.
Suspension of Criminal Proceedings for Perpetrators of Intimate Partner Violence Against Women: Impact on Re-Entries
Authors: Vieira-Pinto Paulo , Muñoz-Barús José Ignacio , Taveira-Gomes Tiago , Vidal-Alves Maria João , Magalhães Teresa
Published: October 2021

Intimate partner violence (IPV) is one of the most prevalent crimes in our society, but the legal mechanisms to oppose it are recent. The Portuguese Provisional Suspension of Criminal Proceedings (PSCP) as a criminal justice system (CJS) response proposes an integrated consensual solution with the involved parties, to reduce offenders’ recidivism. This article analyses the effect of PSCP on re-entries into the CJS. We examined 1,662 IPV police reports, exploring cases that underwent PSCP and re-entries of the same offender in the CJS. Results show that PSCP is applied in 17% of the cases. From all analyzed determinants, with a possible relation to the PSCP implementation, it was found that social violence and the age of both victims and defendants emerge as significantly associated with the request or acceptance of this legal mechanism. No variables tested moderated the relationship between PSCP and re-entry over 96months following the first police report. The article also examined variables that might moderate the decision to request this legal mechanism among victims and defendants.
Representation of Different Types of Adjectival Polysemy in the Mental Lexicon
Authors: Apresjan Valentina , Lopukhina Anastasiya , Zarifyan Maria
Published: October 2021

We studied mental representations of literal, metonymically different, and metaphorical senses in Russian adjectives. Previous studies suggested that in polysemous words, metonymic senses, being more sense-related, were stored together with literal senses, whereas more distant metaphorical senses had separate representations. We hypothesized that metonymy may be heterogeneous with respect to its mental storage. “Whole-part” metonymy (“sad person” – “sad eyes”), which is cognitively closer to the literal sense and more regular, should be stored differently from temporal, causal or resultative metonymy (“sad person” – “sad time;” “sad person” – “sad news;” “lead.ADJ ball” – “lead.ADJ poisoning”), which is irregular and semantically distant from the literal sense. We conducted an online experiment with semantic clustering task in which the participants were asked to classify sentences with a literal, proximal metonymic, distal metonymic, or metaphorical sense of an adjective into virtual baskets so that sentences with the same perceived sense were put in the same basket. Our results showed that proximal metonymies were grouped together with the literal sense and with each other more often than with distal metonymies and metaphors. Distal metonymies, in turn, were grouped with literal senses more often than with metaphors. Overall, we concluded that literal senses and proximal metonymies were stored in single representations, distal metonymies formed hybrid representations with literal senses, and metaphors were stored separately from literal senses. Additionally, we discovered that perception of semantic differences is affected by the surrounding senses: distal metonymies were more discernible from literal senses when presented with proximal metonymies, and less so when presented with metaphors.
Bayesian and Maximum-Likelihood Modeling and Higher-Level Scores of Interpersonal Problems With Circumplex Structure
Authors: Weide Anneke C. , Scheuble Vera , Beauducel André
Published: October 2021

Difficulties in interpersonal behavior are often measured by the circumplex-based Inventory of Interpersonal Problems. Its eight scales can be represented by a three-factor structure with two circumplex factors, Dominance and Love, and a general problem factor, Distress. Bayesian confirmatory factor analysis is well-suited to evaluate the higher-level structure of interpersonal problems because circumplex loading priors allow for data-driven adjustments and a more flexible investigation of the ideal circumplex pattern than conventional maximum likelihood confirmatory factor analysis. Using a non-clinical sample from an online questionnaire study (N = 822), we replicated the three-factor structure of the IIP by maximum likelihood and Bayesian confirmatory factor analysis and found great proximity of the Bayesian loadings to perfect circumplexity. We found additional support for the validity of the three-factor model of the IIP by including external criteria-Agreeableness, Extraversion, and Neuroticism from the Big Five and subclinical grandiose narcissism-in the analysis. We also investigated higher-level scores for Dominance, Love, and Distress using traditional regression factor scores and weighted sum scores. We found excellent reliability (with Rtt ≥ 0.90) for Dominance, Love, and Distress for the two scoring methods. We found high congruence of the higher-level scores with the underlying factors and good circumplex properties of the scoring models. The correlational pattern with the external measures was in line with theoretical expectations and similar to the results from the factor analysis. We encourage the use of Bayesian modeling when dealing with circumplex structure and recommend the use of higher-level scores for interpersonal problems as parsimonious, reliable, and valid measures.
Confounding Factors Affecting the Emotional Intelligence Amongst Jordanian Nursing and Midwifery Undergraduate Students During the COVID-19 Pandemic's Outbreak: A Cross-Sectional Study Using USMEQ-i
Authors: Alnjadat Rafi , Al-Rawashdeh Ahmad
Published: October 2021

Objective: This aim of this study was to determine which variables from the demographic data most affect the EI regarding the COVID-19 outbreak and the lockdown amongst the nursing and midwifery students in Jordan.

Background: Emotional intelligence (EI) is the ability to recognize, express, comprehend, motivate, influence and regulate emotions proposed the first EI model, which includes three constructs: emotion assessment and expression, emotion consumption and emotion control. During the COVID-19 outbreak and lockdown, face-to-face study methods have been replaced by online teaching, which has caused many psychological effects.

Method: A cross-sectional approach was used to measure EI for nursing and midwifery students. The tool was completed online by nursing and midwifery students using Google Forms. All of the findings were received online and then analyzed accordingly. In this study, USMEQ-i was used to gather data from the participants.

Results: The general EI score for the student respondents falls into the average score (M = 39.6). Regarding the difference between males and females, the results showed no significant difference. Moreover, the general linear regressions analysis of independent variables on EI score showed four significant factors. Nursing students who study in Years 1 and 4 had significantly higher EI scores than those in Years 2 and 3. EI ability decreased when a student's economic status changed from luxurious to middle income. Moreover, an increase in age significantly decreased the value of EI. This study indicates that all nursing and midwifery students who enrolled in general nursing program tended to have higher EI scores than others (p = 0.006).

Conclusion: Year of study, age, average lifestyle and enrollment in a nursing program were found to be the most significant factors associated with EI amongst Jordanian nursing and midwifery students. This issue needs to be researched further, such that appropriate steps can be taken to address it.
Adapting the Surveillance Platform for Enteric and Respiratory Infectious Organisms at United States Veterans Affairs Medical Centers (SUPERNOVA) for COVID-19 Among Hospitalized Adults: Surveillance Protocol
Authors: Meites Elissa , Bajema Kristina L. , Kambhampati Anita , Prill Mila , Marconi Vincent C. , Brown Sheldon T. , Rodriguez-Barradas Maria C. , Beenhouwer David O. , Holodniy Mark , Lucero-Obusan Cynthia , Cardemil Cristina , Cates Jordan , Surie Diya
Published: October 2021

Introduction: Early in the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) rapidly initiated COVID-19 surveillance by leveraging existing hospital networks to assess disease burden among hospitalized inpatients and inform prevention efforts.

Materials and Methods: The Surveillance Platform for Enteric and Respiratory Infectious Organisms at Veterans Affairs Medical Centers (SUPERNOVA) is a network of five United States Veterans Affairs Medical Centers which serves nearly 400,000 Veterans annually and conducts laboratory-based passive and active monitoring for pathogens associated with acute gastroenteritis and acute respiratory illness among hospitalized Veterans. This paper presents surveillance methods for adapting the SUPERNOVA surveillance platform to prospectively evaluate COVID-19 epidemiology during a public health emergency, including detecting, characterizing, and monitoring patients with and without COVID-19 beginning in March 2020. To allow for case-control analyses, patients with COVID-19 and patients with non-COVID-19 acute respiratory illness were included.

Results: SUPERNOVA included 1,235 participants with COVID-19 and 707 participants with other acute respiratory illnesses hospitalized during February through December 2020. Most participants were male (93.1%), with a median age of 70 years, and 45.8% non-Hispanic Black and 32.6% non-Hispanic White. Among those with COVID-19, 28.2% were transferred to an intensive care unit, 9.4% received invasive mechanical ventilation, and 13.9% died. Compared with controls, after adjusting for age, sex, and race/ethnicity, COVID-19 case-patients had significantly higher risk of mortality, respiratory failure, and invasive mechanical ventilation, and longer hospital stays.

Discussion: Strengths of the SUPERNOVA platform for COVID-19 surveillance include the ability to collect and integrate multiple types of data, including clinical and illness outcome information, and SARS-CoV-2 laboratory test results from respiratory and serum specimens. Analysis of data from this platform also enables formal comparisons of participants with and without COVID-19. Surveillance data collected during a public health emergency from this key U.S. population of Veterans will be useful for epidemiologic investigations of COVID-19 spectrum of disease, underlying medical conditions, virus variants, and vaccine effectiveness, according to public health priorities and needs.
The Status Quo and Attribution of Wildlife Crimes: A Study of Cases in China From the Perspective of Ecological Economic Ethics
Authors: Zhang Zhongmin , Zeng Yuting , Xie Danqi
Published: October 2021

The COVID-19 pandemic, which has ravaged the world, has led to a rethinking of the relationship between humans and nature and the clichés of the economic-centered model. Thus, the ecological economy has been reviewed, especially from an ethical worldview. This paper uses statistical methods to retrieve and categorize 3,646 wildlife crime cases for analysis and quantitative research. It adopts legal and ethical perspectives to analyze the subject and the subjective, incidence, and sentencing factors of wildlife crimes and uses the ecological economic ethical model to measure wildlife crimes. We argue that the existing judicial system fails to answer the difficulties of the economic ethics of wildlife crimes. It is recommended that ecological and economic ethical awareness be internalized. We suggest calling for comprehensive legislation on wildlife crimes from the perspective of ecological economic ethics to effectively prevent and reduce wildlife crime and eventually promote public health.
Atezolizumab Plus Chemotherapy vs. Chemotherapy in Advanced or Metastatic Triple-Negative Breast Cancer: A Cost-Effectiveness Analysis
Authors: Liu Xiaoyan , Lang Yitian , Liao Yahui , Zhu Yizhun
Published: October 2021

Purpose: The IMpassion130 trial demonstrated the efficacy of adding atezolizumab to paclitaxel for advanced or metastatic triple-negative breast cancer (TNBC). The current study evaluated the cost-effectiveness of adding atezolizumab to nab-paclitaxel for TNBC from the perspective of Chinese health sector.

Methods: A partitioned survival model was implemented for patients with TNBC. The survival data were derived from IMpassion130 trial. Direct costs and utility values were collected from the Chinese Drug Bidding Database and published literatures. The primary analysis outcomes were quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed to observe model stability.

Results: In the base-case analysis, the ICER of atezolizumab plus nab-paclitaxel vs. nab-paclitaxel is respectively, $176,056/QALY, $118,146/QALY, and $323,077/QALY in the ITT, PD-L1(+) and PD-L1(–) group.

Conclusion: Adding atezolizumab to nab-paclitaxel could improve survival time significantly in the PD-L1-positive group, but it is not a cost-effective strategy compared to nab-paclitaxel monotherapy for Chinese patients with advanced or metastatic triple-negative breast cancer in the current economic context of China.
Diagnosis and Treatment of Hypertension Among People Aged 45 Years and Over in India: A Sub-national Analysis of the Variation in Performance of Indian States
Authors: Bhatia Mrigesh , Kumar Manish , Dixit Priyanka , Dwivedi Laxmi Kant
Published: October 2021

Introduction: Cardiovascular disease (CVD) is the single largest contributor to non-communicable disease (NCD) deaths, with hypertension contributing to a significant proportion of these deaths. This study aims to provide estimates of the prevalence, awareness, treatment and control of hypertension at sub-national levels in India and identifies well and under-performing states with respect to the diagnosis and treatment of hypertension.

Methods: The study utilises data from the Longitudinal Study of Ageing in India (LASI), a nationally representative survey of more than 72,000 individuals. Age-sex adjusted prevalence rates of self-reported hypertension was calculated using the direct standardisation method. Multivariable logistic regression was performed to assess the association of self-reported hypertension with the various individual co-morbidity, lifestyle, and household factors. Self-reported prevalence was compared with an objective measure of hypertension for each state, and funnel plots were constructed to assess the performance of states.

Results: Our findings suggest that the overall prevalence of age-sex adjusted self-reported hypertension was 25.8% in India with significant variation among states. Results based on logistic regression confirm that those individuals who are elderly, obese, belong to a higher socio-economic group and have associated co-morbidities are at increased odds of reporting hypertension. Overall, 4 out of 10 adults over 45 years of age in India are not aware of their hypertensive condition, and of those who are aware, 73% are currently taking medication, and only 10% of these have their hypertension under control. Based on the performance, states were classified into high and low performing categories. States with an increased proportion of population below the poverty line had significantly lower performance with respect to the diagnosis of hypertension, whereas states with higher literacy rates and greater availability of specialist doctors at community health centres (CHCs) had significantly better performance with respect to treatment-seeking behaviour.

Conclusion: The findings of this study and its policy implications are discussed. Based on state performance, strategies are proposed in terms selective targeting vs. population-based strategies. High impact states and sub-groups are identified where intense efforts are needed to tackle the growing menace of hypertension in India.
Veillonellae: Beyond Bridging Species in Oral Biofilm Ecology
Authors: Zhou Peng , Manoil Daniel , Belibasakis Georgios N. , Kotsakis Georgios A.
Published: October 2021

The genus Veillonella comprises 16 characterized species, among which eight are commonly found in the human oral cavity. The high abundance of Veillonella species in the microbiome of both supra- and sub-gingival biofilms, and their interdependent relationship with a multitude of other bacterial species, suggest veillonellae to play an important role in oral biofilm ecology. Development of oral biofilms relies on an incremental coaggregation process between early, bridging and later bacterial colonizers, ultimately forming multispecies communities. As early colonizer and bridging species, veillonellae are critical in guiding the development of multispecies communities in the human oral microenvironment. Their ability to establish mutualistic relationships with other members of the oral microbiome has emerged as a crucial factor that may contribute to health equilibrium. Here, we review the general characteristics, taxonomy, physiology, genomic and genetics of veillonellae, as well as their bridging role in the development of oral biofilms. We further discuss the role of Veillonella spp. as potential “accessory pathogens” in the human oral cavity, capable of supporting colonization by other, more pathogenic species. The relationship between Veillonella spp. and dental caries, periodontitis, and peri-implantitis is also recapitulated in this review. We finally highlight areas of future research required to better understand the intergeneric signaling employed by veillonellae during their bridging activities and interspecies mutualism. With the recent discoveries of large species and strain-specific variation within the genus in biological and virulence characteristics, the study of Veillonella as an example of highly adaptive microorganisms that indirectly participates in dysbiosis holds great promise for broadening our understanding of polymicrobial disease pathogenesis.
High Prevalence and Factors Associated With the Distribution of the Integron intI1 and intI2 Genes in Scottish Cattle Herds
Authors: Fernández Rivas Cristina , Porphyre Thibaud , Chase-Topping Margo E. , Knapp Charles W. , Williamson Helen , Barraud Olivier , Tongue Sue C. , Silva Nuno , Currie Carol , Elsby Derek T. , Hoyle Deborah V.
Published: October 2021

Integrons are genetic elements that capture and express antimicrobial resistance genes within arrays, facilitating horizontal spread of multiple drug resistance in a range of bacterial species. The aim of this study was to estimate prevalence for class 1, 2, and 3 integrons in Scottish cattle and examine whether spatial, seasonal or herd management factors influenced integron herd status. We used fecal samples collected from 108 Scottish cattle herds in a national, cross-sectional survey between 2014 and 2015, and screened fecal DNA extracts by multiplex PCR for the integrase genes intI1, intI2, and intI3. Herd-level prevalence was estimated [95% confidence interval (CI)] for intI1 as 76.9% (67.8–84.0%) and intI2 as 82.4% (73.9–88.6%). We did not detect intI3 in any of the herd samples tested. A regional effect was observed for intI1, highest in the North East (OR 11.5, 95% CI: 1.0–130.9, P = 0.05) and South East (OR 8.7, 95% CI: 1.1–20.9, P = 0.04), lowest in the Highlands. A generalized linear mixed model was used to test for potential associations between herd status and cattle management, soil type and regional livestock density variables. Within the final multivariable model, factors associated with herd positivity for intI1 included spring season of the year (OR 6.3, 95% CI: 1.1–36.4, P = 0.04) and watering cattle from a natural spring source (OR 4.4, 95% CI: 1.3–14.8, P = 0.017), and cattle being housed at the time of sampling for intI2 (OR 75.0, 95% CI: 10.4–540.5, P < 0.001). This study provides baseline estimates for integron prevalence in Scottish cattle and identifies factors that may be associated with carriage that warrant future investigation.
Influence of GlycoGag on the Incorporation of Host Membrane Proteins Into the Envelope of the Moloney Murine Leukemia Virus
Authors: Maltseva Mariam , Langlois Marc-André
Published: October 2021

Analysis of viral particle heterogeneity produced from infected cells has been limited by the inefficiency of traditional analytical methods to characterize large populations of viruses at an individual particle level. Flow virometry (FVM) is an emerging technique based on flow cytometry principles that enables a high throughput, multiparametric, and phenotypic characterization of viruses at a single particle resolution. Here, we performed FVM to analyze surface markers found on Murine Leukemia Virus (MLV) and glycosylated Gag-deficient (glycoGag) MLV. The glycoGag viral accessory protein has several roles in the MLV viral infection cycle including directing retroviral assembly and particle release at lipid rafts. Based on previous studies, we hypothesize that glycoGag modulates host protein incorporation into the viral envelope during viral assembly and budding. Here, by using FVM, we reveal that glycoGag is associated with an increased incorporation of the host-derived tetraspanins CD81 and CD63 along with the lipid raft marker and immune antigen Thy1.2 during the assembly and release of viral particles from infected NIH 3T3, EL4, and primary CD4+ T cells. Moreover, we show differences in the uptake of host proteins by viruses that are released from the two cell lines and primary T lymphocytes. Additionally, at the individual viral particle level, we observed a degree of expression heterogeneity of host-derived antigens within the viral population. Finally, certain cellular antigens can show either enrichment or exclusion from the viral envelope depending on whether glycoGag is expressed by the virus. This suggests that glycoGag is involved in a mechanism of selective host protein incorporation into the viral envelope.
Overweight and Obesity are Potential Risk Factors for Disrupted Nocturnal Sleep in Iranian Adults: A Cross-Sectional Study
Authors: Darroudi Susan , Sharifan Payam , Sadeghzadeh Parastoo , Namjou Negin , Zamiri Bidary Mohammad , Zamani Parvin , Esmaily Habibollah , Ferns Gordon A. , Moohebati Mohsen , Ghayour-Mobarhan Majid
Published: October 2021

Objectives: Obesity is a risk factor for several chronic conditions, including sleep disorders. We aimed to analyze the relationship between BMI, body fat percentage (FAT%), hip and waist circumference, and weight on the duration of nocturnal sleep.

Methods: This study was part of the MASHAD cohort study. In all participants BMI and FAT% were measured. BMI was used to categorize individuals as obese, overweight, and normal subjects. FAT% was used to categorize individuals into tertile: tertile 1 (low) < 27.5, tertile 2 (medium) 27.5–41, and tertile 3 (high) > 41. The level of nightly sleep duration was categorized into three groups: <6, 6–8 (reference group), and >8 h.

Results: There was a significant inverse association between body weight and duration of sleep (p < 0.05). Obese and overweight participants had 1.152 OR (CI:1.083–1.225) and 1.126 OR (CI:1.063–1.194) for a short duration of nocturnal sleep, respectively, relative to those with a normal BMI.

Conclusion: BMI was an independent determinant of nocturnal sleep duration; obesity and overweight may have negative consequences on sleep duration. Weight control should be considered as a factor in adjusting sleep quality.
Development of Aircraft Spoiler Demonstrators for Cost-Efficient Investigations of SHM Technologies under Quasi-Realistic Loading Conditions
Authors: Winklberger Markus , Kralovec Christoph , Schagerl Martin
Published: October 2021

An idealized 1:2 scale demonstrator and a numerical parameter optimization algorithm are proposed to closely reproduce the deformation shape and, thus, spatial strain directions of a real aerodynamically loaded civil aircraft spoiler using only four concentrated loads. Cost-efficient experimental studies on demonstrators of increasing complexity are required to transfer knowledge from coupons to full-scale structures and to build up confidence in novel structural health monitoring (SHM) technologies. Especially for testing novel sensor systems that depend on or are affected by mechanical strains, e.g., strain-based SHM methods, it is essential that the considered lab-scale structures reflect the strain states of the real structure at operational loading conditions. Finite element simulations with detailed models were performed for static strength analysis and for comparison to experimental measurements. The simulated and measured deformations and spatial strain directions of the idealized demonstrator correlated well with the numerical results of the real aircraft spoiler. Thus, using the developed idealized demonstrator, strain-based SHM systems can be tested under conditions that reflect operational aerodynamic pressure loads, while the test effort and costs are significantly reduced. Furthermore, the presented loading optimization algorithm can be easily adapted to mimic other pressure loads in plate-like structures to reproduce specific structural conditions.
Affordable Use of Satellite Imagery in Agriculture and Development Projects: Assessing the Spatial Distribution of Invasive Weeds in the UNESCO-Protected Areas of Cuba
Authors: Moreno Eduardo , Zabalo Alberto , Gonzalez Encarnacion , Alvarez Reinaldo , Jimenez Victor Manuel , Menendez Julio
Published: October 2021

The effective and regular remote monitoring of agricultural activity is not always possible in developing countries because the access to cloud-based geospatial analysis platforms or expensive high-resolution satellite images are not always available. Herein, using paid high-resolution satellite images first and then free medium-resolution satellite images, we aimed to develop a cost-free, affordable method for regularly mapping the spatial distribution of sicklebush (Dichrostachys cinerea), an archetypal allochthonous invasive plant in Cuba that is becoming impossible to control owing to its rapid growth in areas planted with sugar cane in the Trinidad-Valle de los Ingenios area (Cuba), a UNESCO World Heritage Site. Two types of images were used (WorldView-2 and Landsat-8); these were subjected to supervised classification, with accuracy values of 88.7% and 93.7%, respectively. Vegetation cover was first derived from the purchased WorldView-2 image, and this information was then used as the training field to obtain spectral signatures from the Landsat-8 free image so that Landsat images may be regularly used to monitor D. cinerea infestations. The results obtained in the spatial distribution map for sicklebush in the Landsat-8 images had an overall reliability of 93.7% and a Kappa coefficient reliability of 91.9%. These values indicate high confidence in the results, which suggests that sicklebush has invaded 52.7% of the total 46,807.26-ha area of the Trinidad-Valle de los Ingenios. This process proved extremely effective and demonstrated the benefits of using high-resolution spatial images from which information can be transferred to free satellite images with a larger pixel size.
Combined Therapy of Probiotic Supplementation and Rehydration Improves Blood Dehydration Parameters and Decreases Mortality of Neonatal Piglets Naturally Infected with Porcine Epidemic Diarrhea Virus: A Clinical Trial
Authors: Inatomi Takio , Tsukahara Takamitsu , Romero-Pérez Gustavo A. , Inoue Ryo
Published: October 2021

Although rehydration therapy (RT) has been used to treat animals suffering from viral diarrhea, mortality among farm animals still remains high, as RT alone neither significantly minimizes the duration of the illness nor reduces the looseness of stools. As porcine epidemic diarrhea (PED) is a viral disease and PED treatments are still very limited, vaccination is the common strategy to prevent it. Thus, the aim of the present study was to test whether a combination of RT and probiotics supplementation could help to improve the mortality of suckling piglets kept in a commercial farm and naturally infected with PED virus. Piglets receiving a combination of probiotic supplementation and RT showed improved (p < 0.01) blood parameters such as base excess and bicarbonate ion concentration when compared with untreated control piglets and piglets administered with RT alone. When compared with that of control piglets, mortality during the suckling period was the lowest (p < 0.05) in piglets receiving the combined therapy, but statistically unchanged between piglets receiving either RT or RT and probiotics. Our preliminary results should motivate further research on the use of a combined rehydration and probiotics therapy to reduce mortality in piglets suffering from acute diarrhea.