bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 in two patients with multiple sclerosis treated with beta interferons
Authors: Kania Karolina , Tokarz-Kupczyk Elżbieta , Kalinowska-Łyszczarz Alicja
Published: February 2021

Objectives. Treatment of multiple sclerosis (MS) in the era of the COVID-19 (coronavirus disease 2019) pandemic raises many questions for doctors.

Case reports. We are presenting two cases of patients suffering from multiple sclerosis (MS) treated with interferon beta-1b and interferon beta-1a, who suffered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with a benign course in one case and an asymptomatic one in another. None of the patients required hospitalisation.

Conclusions. MS treatment during coronavirus disease 2019 (COVID-19) pandemics poses several questions. Considering our own clinical experiences, we present a brief review of medical literature on the safety of MS immunotherapy. So far, the published data on MS and COVID-19 do not show increased risk associated with MS diagnosis or disease modifying therapy, even when associated with immunosuppression.
Food web approach for managing Arctic wildlife populations in an era of rapid environmental change
Authors: Mellard JP , Henden JA , Pedersen ÅØ , Marolla F , Hamel S , Yoccoz NG , Ims RA
Published: February 2021

Scientists and wildlife managers implementing adaptive monitoring and management schemes, are tasked with providing predictions of population responses to harvest and environmental changes. Such predictions are useful not only to forecast direct effects of climate, productivity, land use, or habitat degradation, but also changes in the food web, such as expanding/�increasing species that are predators, prey, and competitors of populations of concern. Explicit consideration of food webs and their dynamics in more complex models could provide better predictions of future changes, and allow us to better assess the influence of management actions. Here, we present our perspective on what we have learned from conducting a number of case studies using such a food web approach with a focus on climate and harvest impacts and their implications for management. We found empirical support for many of our hypothesized food web effects, and were able in some cases to obtain short-term forecasts with slightly lower prediction error using models that account for food web dynamics compared with simpler models. Predictions are the foundation of adaptive management because they allow quantitative assessment of the effects of management actions; however, evaluating predictions requires adequate and high-quality monitoring data. Results from our case studies show that a combination of long-term monitoring and different types of study designs coupled with models of adequate complexity are likely required to better understand populations’ responses to environmental changes and harvest, as well as the consequences for food webs.
Changes in wind erosion climatic erosivity in northern China from 1981-2016: a comparison of two climate/weather factors of wind erosion models
Authors: Zhang F , Wang J , Zou X , Mao R , Gong DY , Feng X , Zhu J
Published: February 2021

Wind erosion is largely determined by wind erosion climatic erosivity. In this study, we examined changes in wind erosion climatic erosivity during 4 seasons across northern China from 1981-2016 using 2 models: the wind erosion climatic erosivity of the Wind Erosion Equation (WEQ) model and the weather factor from the Revised Wind Erosion Equation (RWEQ) model. Results showed that wind erosion climatic erosivity derived from the 2 models was highest in spring and lowest in winter with high values over the Kumtag Desert, the Qaidam Basin, the boundary between Mongolia and China, and the Hulunbuir Sandy Land. In spring and summer, wind erosion climatic erosivity showed decreasing trends in whole of northern China from 1981-2016, whereas there was an increasing trend in wind erosion climatic erosivity over the Gobi Desert from 1992-2011. For the weather factor of the RWEQ model, the difference between northern Northwest China and the Gobi Desert and eastern-northern China was much larger than that of the wind erosion climatic erosivity of the WEQ model. In addition, in contrast to a decreasing trend in the weather factor of the RWEQ model over southern Northwest China during spring and summer from 1981-2016, the wind erosion climatic erosivity of the WEQ model showed a decreasing trend for 1981-1992 and an increasing trend for 1992-2011 over southern Northwest China. According to a comparison between dust emission and wind erosion climatic erosivity, the 2 models have the ability to project changes in future wind erosion in northern China.
EFEKTIFITAS LATIHAN TERHADAP KUALITAS HIDUP LANSIA DENGAN OSTEOARTRITIS LUTUT DI KOTA MALANG
Authors: Rosadi Rakhmad
Published: February 2021

ABSTRAK

Latar Belakang: Osteoartritis merupakan penyakit sendi yang memiliki ciri khas yaitu terjadinya degradasi tulang rawan sendi dan paling banyak menyerang pada individu dengan usia diatas 50 tahun. Osteoartritis menghasilkan rasa nyeri yang terjadi secara terus menerus, menurun hingga terbatasnya fungsi dan rendahnya kualitas hidup. Terapi non farmakologis yang disaran kan untuk penderita osteoartritis ialah exercise. Jenis exercise antara lain ROM Exercise, Strengthening Exercise, Aerobik exercise seperti forward walking atau retrowalking.

Metode: Penelitian ini menggunakan desain Quasy Experimental dengan rancangan Pre Test dan Post Test bertujuan untuk mengidentifikasi Perbandingan Efektifitas Quadriceps Strengthening Exercise dan Retrowalking Exercise terhadap Kualitas Hidup Lansia dengan Osteoartritis lutut. populasi penelitian ini adalah Lansia yang berada di Posyandu RW 9 Kendal Kerep dengan sampel sejumlah 30responden yang dibagi menjadi 15 responden sebagai kelompok intervensi Quadriceps Strengthening Exercise dan 15 responden sebagai kelompok retrowalking exercise.Kualitas hidup terkait kesehatan diukur menggunakan kuesioner Medical Outcome Study Short Form-36 (SF-36).Data yang diperoleh dianalisa menggunkan independent t test.

Hasil: Hasil penelitian denga Uji Independent T Testtest diperoleh nilai taraf signifikansi 0,000 sehingga diperoleh nilai (P<0,05), nilai sig. (2-tailed)< taraf nyata (α) sehingga hasil dari uji independent t test adalah Quadriceps strengthening exercise lebih efektif dibandingkan dengan retrowalking exercise terhadap peningkatan kualitas hidup lansia dengan osteoatritis lutut.

Diskusi: Dalam penelitian ini nilai kualitas hidup kelompok quadriceps strengthening exercise lebih tinggi dibandingkan kelompok retrowalking exercise. Penelitian ini dapat dijadikan sebagi acuan untuk penelitian yang akan dilakukan di masa yang akan datang dengan memodifikasi intervensi. Rekomendasi penelitian ini yaitu intervensi quadriceps strengthening exercise dan retrowlaking exercise dapat diterapkan di pelayanan kesehatan, khususnya fisioterapi pada pasien dengan osteoartritis lutut.
Еволюція питання Південно-Китайського моря у трикутнику інтересів Китай - держави АСЕАН - США
Authors: Тихоненко Ірина , Євтушенко Владислав
Published: February 2021

У статті розглянуто історичний розвиток ситуації у Південно-Китайському морі у ХХ – початку ХХІ ст. Питання Південно-Китайського моря висвітлено крізь призму взаємодії Китай – держави АСЕАН – США. Виявлено два рівня взаємодії: 1) територіальні суперечки між Китаєм і державами Південно-Східної Азії, насамперед, у форматі протистояння Китай-В’єтнам і Китай-Філіппіни; 2) активне залучення з 2009 р. до субрегіону США та формування нової осі протидії КНР-США.

Розглянуто хронологію загострень ситуації у Південно-Китайському морі, низку інцидентів і риторику між державами під впливом такої конфліктогенності. Автори дійшли висновку про циклічність ситуації у Південно-Китайському морі, яка проявляється у перманентному її загостренні через тиск Китаю та його непорушну позицію щодо одноосібного володіння цим простором, незважаючи на рішення Міжнародного суду відповідно до норм міжнародного права (новий цикл загострення у 2020 р.), а також переведення цього простору у сферу протистояння Китаю з США, в якому держави АСЕАН мають проводити більш гнучку політику – відстоювати свої інтереси, але не загострювати відносини з Китаєм, який є вагомим торговельним партнером й у 2020 р. все більше використовує політику тиску і «м’якої сили», зважаючи на світову пандемію.
Загострення протиріч у підготовці Угоди про асоціацію України з ЄС (липень-жовтень 2013 р.)
Authors: Денисенко Вадим
Published: February 2021

Розкривається поглиблення проблем навколо підписання Угоди про асоціацію України з Європейським Союзом. Детально відтворено збільшення економічного та дипломатичного тиску російської влади на Віктора Януковича з метою зірвати підписання угоди. Це включало в себе включення частини українських підприємств до «чорного списку» митниці РФ і прямий шантаж російської верхівки.

На основі даних періодики реконструйовано процес переговорів між українською владою та представниками Європарламенту щодо умов звільнення Юлії Тимошенко. Виокремлено основні плани вирішення проблеми Ю. Тимошенко: часткове помилування (зменшення строку покарання, виплата штрафу та позбавлення громадянських прав на три роки) та лікування за кордоном (зміна законодавства з метою зробити легальним залишення країни в’язнем у випадку необхідності лікування у зарубіжних закладах). Підкреслено, що В. Янукович віддавав перевагу першому варіанту, що гарантував неучасть Тимошенко у президентських виборах 2015 р. Однак у підсумку він використав проблему ув’язнення найбільш впливового опозиційного лідера задля затягування переговорів з ЄС, без бажання продовжувати рух до Європи на фоні зростання російського тиску та відвертих погроз керівництва РФ.

Проаналізовано роль європейських політиків у спробах вирішити переговорну кризу, зокрема ролі Пета Кокса, Александра Кваснєвського, Радослава Сікорського та Карла Більдта. Відтворено позицію Юлії Тимошенко та її оточення щодо планів звільнення з ув’язнення: намір боротися за відновленні громадянських прав у випадку часткового помилування, згода відкласти вирішення проблеми на більш пізній термін в обмін підписання угоди про асоціацію з ЄС. Доведено, що режим Януковича обрав шлях зближення з РФ як спосіб уникнути поразки на президентських виборах 2015 р. та через страх внаслідок погроз російської верхівки.
Зберігачі державної традиції
Authors: Шаповал Юрій
Published: February 2021

Рецензія на видання: Яблонський В.М. Державний центр УНР в екзилі: ідеї, боротьба, традиція (1921-1992 роки). Київ: КНТ, 2020. 648 с.
Investigation of Fracture Resistance of Zirconia Restorations After Different Surface Treatments
Authors: AKAR Türker , AKİN Hakan
Published: February 2021

Objective: The purpose of this study was to investigate the effects of the different surface treatments on fracture strength of the zirconia-based ceramic restorations.
Methods: Each of 120 dental implant abutments and analogs were used in the present study. Zirconia core materials were manufactured on dental implants by using CAD/CAM device and they were randomly divided into 6 groups (n=20) according to surface pretreatments; control group (Group C), airborne-particle abrasion (Group AA), silica-coating (Group SC), Nd:YAG laser (Group N), bur-cut from cervical region (Group BC), and bur-cut on the functional tubercule (Group BT). Cementation was succeeded with two different types of cements including a dual-cure resin-cement and a glass ionomer cement. The obtained data were evaluated statistically using one-way ANOVA and Tukey tests (p=0.05).
Results: No statistically significant difference was found between the groups (p>0.05). Similarly, no statistically significant difference was found between the resin cement and glass ionomer groups with respect to fracture strength values (p>0.05).
Conclusion: Within the limitations of the present study, surface treatments and cement have no effect on the flexural strength of zirconia ceramic crowns.
Laboratory Diagnostic Tools for Syphilis: Current Status and Future Prospects
Authors: Luo Yuting , Xie Yafeng , Xiao Yongjian
Published: February 2021

With the increasing number of patients infected with syphilis in the past 20 years, early diagnosis and early treatment are essential to decline syphilis prevalence. Owing to its diverse manifestations, which may occur in other infections, the disease often makes clinicians confused. Therefore, a sensitive method for detecting T. pallidum is fundamental for the prompt diagnosis of syphilis. Morphological observation, immunohistochemical assay, rabbit infectivity test, serologic tests, and nucleic acid amplification assays have been applied to the diagnosis of syphilis. Morphological observation, including dark-field microscopy, silver-staining, and direct fluorescent antibody staining for T. pallidum, can be used as a direct detection method for chancre specimens in primary syphilis. Immunohistochemistry is a highly sensitive and specific assay, especially in the lesion biopsies from secondary syphilis. Rabbit infectivity test is considered as a sensitive and reliable method for detecting T. pallidum in clinical samples and used as a historical standard for the diagnosis of syphilis. Serologic tests for syphilis are widely adopted using non-treponemal or treponemal tests by either the traditional or reverse algorithm and remain the gold standard in the diagnosis of syphilis patients. In addition, nucleic acid amplification assay is capable of detecting T. pallidum DNA in the samples from patients with syphilis. Notably, PCR is probably a promising method but remains to be further improved. All of the methods mentioned above play important roles in various stages of syphilis. This review aims to provide a summary of the performance characteristics of detection methods for syphilis.
The Macrophage Response to Mycobacterium tuberculosis and Opportunities for Autophagy Inducing Nanomedicines for Tuberculosis Therapy
Authors: Maphasa Retsepile E. , Meyer Mervin , Dube Admire
Published: February 2021

The major causative agent of tuberculosis (TB), i.e.,Mycobacterium tuberculosis (Mtb), has developed mechanisms to evade host defense responses and persist within host cells for prolonged periods of time.Mtbis also increasingly resistant to existing anti-TB drugs. There is therefore an urgent need to develop new therapeutics for TB and host directed therapies (HDTs) hold potential as effective therapeutics for TB. There is growing interest in the induction of autophagy inMtbhost cells using autophagy inducing compounds (AICs). Nanoparticles (NPs) can enhance the effect of AICs, thus improving stability, enabling cell targeting and providing opportunities for multimodal therapy. In this review, we focus on the macrophage responses toMtbinfection, in particular, the mechanistic aspects of autophagy and the evasion of autophagy by intracellularMtb. Due to the overlap between the onset of autophagy and apoptosis; we also focus on the relationship between apoptosis and autophagy. We will also review known AICs in the context ofMtbinfection. Finally, we discuss the applications of NPs in inducing autophagy with the intention of sharing insights to encourage further research and development of nanomedicine HDTs for TB therapy.
Estimating Watershed Subsurface Permeability From Stream Discharge Data Using Deep Neural Networks
Authors: Cromwell Erol , Shuai Pin , Jiang Peishi , Coon Ethan T. , Painter Scott L. , Moulton J. David , Lin Youzuo , Chen Xingyuan
Published: February 2021

Subsurface permeability is a key parameter in watershed models that controls the contribution from the subsurface flow to stream flows. Since the permeability is difficult and expensive to measure directly at the spatial extent and resolution required by fully distributed watershed models, estimation through inverse modeling has had a long history in subsurface hydrology. The wide availability of stream surface flow data, compared to groundwater monitoring data, provides a new data source to infer soil and geologic properties using integrated surface and subsurface hydrologic models. As most of the existing methods have shown difficulty in dealing with highly nonlinear inverse problems, we explore the use of deep neural networks for inversion owing to their successes in mapping complex, highly nonlinear relationships. We train various deep neural network (DNN) models with different architectures to predict subsurface permeability from stream discharge hydrograph at the watershed outlet. The training data are obtained from ensemble simulations of hydrographs corresponding to an permeability ensemble using a fully-distributed, integrated surface-subsurface hydrologic model. The trained model is then applied to estimate the permeability of the real watershed using its observed hydrograph at the outlet. Our study demonstrates that the permeabilities of the soil and geologic facies that make significant contributions to the outlet discharge can be more accurately estimated from the discharge data. Their estimations are also more robust with observation errors. Compared to the traditional ensemble smoother method, DNNs show stronger performance in capturing the nonlinear relationship between permeability and stream hydrograph to accurately estimate permeability. Our study sheds new light on the value of the emerging deep learning methods in assisting integrated watershed modeling by improving parameter estimation, which will eventually reduce the uncertainty in predictive watershed models.
Interventions for Keeping Adolescent Girls in School in Low- and Middle-Income Countries: A Scoping Review
Authors: Sampa Mutale , Musukuma Mwiche , Fisa Ronald , Musonda Patrick , Young Taryn
Published: February 2021

Background: Adolescent girls dropping out of school may lead to gender inequality, high illiteracy levels, single motherhood, unemployment, and many more undesirable outcomes that inhabit human capital development for girls. It is therefore important to put measures in place to support adolescent girls to stay in school. The objectives of the scoping review were to identify and describe the types of studies conducted to assess interventions for keeping adolescent girls in school and to describe these interventions in low- and middle-income countries.

Methods and Results: A comprehensive search was done in Epistemonikos, Social Science Citation index, Embase, OVID Medline, the Campbell Collaboration Library, and CENTRAL in March 2020. The search yielded 3,295 studies of which 18 studies were eligible for inclusion. All the 18 included studies were primary studies, and 12 out of these were randomized controlled studies. The other study designs of included studies were mixed-methods longitudinal design, random evaluation, cross section, etc. The interventions in the included studies were categorized as follows: provision of funding, school-based interventions for learners, community-based interventions, and education systems intervention. Provision of school fees, and other school supplies have shown evidence of reducing school dropouts, increasing enrolments and school attendance, while interventions like hygiene promotion and water treatment in a study done in Kenya found no significant evidence to support the observed effect on school attendance.

Conclusion: The scoping review found that several primary studies have been done on interventions to keep adolescent girls in school. However, there is need for more research to be done. Therefore, the authors propose to conduct a systematic review on the effect of provision of sanitary towels to adolescent girls on school retention in low- and middle-income countries.
Long Non-Coding RNAs as Key Modulators of Pancreatic β-Cell Mass and Function
Authors: López–Noriega Livia , Rutter Guy A.
Published: February 2021

Numerous studies have sought to decipher the genetic and other mechanisms contributing to β-cell loss and dysfunction in diabetes mellitus. However, we have yet to fully understand the etiology of the disease or to develop satisfactory treatments. Since the majority of diabetes susceptibility loci are mapped to non-coding regions within the genome, understanding the functions of non-coding RNAs in β-cell biology might provide crucial insights into the pathogenesis of type 1 (T1D) and type 2 (T2D) diabetes. During the past decade, numerous studies have indicated that long non-coding RNAs play important roles in the maintenance of β-cell mass and function. Indeed, lncRNAs have been shown to be involved in controlling β-cell proliferation during development and/or β-cell compensation in response to hyperglycaemia. LncRNAs such as TUG-1 and MEG3 play a role in both β-cell apoptosis and function, while others sensitize β-cells to apoptosis in response to stress signals. In addition, several long non-coding RNAs have been shown to regulate the expression of β-cell-enriched transcription factors in cis or in trans. In this review, we provide an overview of the roles of lncRNAs in maintaining β-function and mass, and discuss their relevance in the development of diabetes.
Identifying Differentially Expressed Genes of Zero Inflated Single Cell RNA Sequencing Data Using Mixed Model Score Tests
Authors: He Zhiqiang , Pan Yueyun , Shao Fang , Wang Hui
Published: February 2021

Single cell RNA sequencing (scRNA-seq) allows quantitative measurement and comparison of gene expression at the resolution of single cells. Ignoring the batch effects and zero inflation of scRNA-seq data, many proposed differentially expressed (DE) methods might generate bias. We propose a method, single cell mixed model score tests (scMMSTs), to efficiently identify DE genes of scRNA-seq data with batch effects using the generalized linear mixed model (GLMM). scMMSTs treat the batch effect as a random effect. For zero inflation, scMMSTs use a weighting strategy to calculate observational weights for counts independently under zero-inflated and zero-truncated distributions. Counts data with calculated weights were subsequently analyzed using weighted GLMMs. The theoretical null distributions of the score statistics were constructed by mixed Chi-square distributions. Intensive simulations and two real datasets were used to compare edgeR-zinbwave, DESeq2-zinbwave, and scMMSTs. Our study demonstrates that scMMSTs, as supplement to standard methods, are advantageous to define DE genes of zero-inflated scRNA-seq data with batch effects.
Mantle Modularity Underlies the Plasticity of the Molluscan Shell: Supporting Data From Cepaea nemoralis
Authors: Jackson Daniel J.
Published: February 2021

Molluscs have evolved the capacity to fabricate a wide variety of shells over their 540+ million-year history. While modern sequencing and proteomic technologies continue to expand the catalog of molluscan shell-forming proteins, a complete functional understanding of how any mollusc constructs its shell remains an ambitious goal. This lack of understanding also constrains our understanding of how evolution has generated a plethora of molluscan shell morphologies. Taking advantage of a previous expression atlas for shell-forming genes inLymnaea stagnalis, I have characterized the spatial expression patterns of seven shell-forming genes in the terrestrial gastropodCepaea nemoralis, with the aim of comparing and contrasting their expression patterns between the two species. Four of these genes were selected from a previous proteomic screen of theC. nemoralisshell, two were targeted by bioinformatics criteria designed to identify likely shell-forming gene products, and the final one was a clear homolog of a peroxidase sequence in theL. stagnalisdataset. While the spatial expression patterns of all sevenC. nemoralisgenes could be recognized as falling into distinct zones within the mantle tissue similar to those established inL. stagnalis, some zones have apparently been modified. These similarities and differences hint at a modularity to the molluscan mantle that may provide a mechanistic explanation as to how evolution has efficiently generated a diversity of molluscan shells.
Weaning Induces Stress-Dependent DNA Methylation and Transcriptional Changes in Piglet PBMCs
Authors: Corbett Ryan J. , Luttman Andrea M. , Wurtz Kaitlin E. , Siegford Janice M. , Raney Nancy E. , Ford Laura M. , Ernst Catherine W.
Published: February 2021

Changes to the epigenome, including those to DNA methylation, have been proposed as mechanisms by which stress can induce long-term physiological changes in livestock species. Pig weaning is associated with dietary and social stress, both of which elicit an immune response and changes to the hypothalamic–pituitary–adrenal (HPA) axis. While differential methylation following stress has been assessed in model organisms, it remains poorly understood how the pig methylome is altered by stressors in production settings. We quantified changes in CpG methylation and transcript abundance in piglet peripheral blood mononuclear cells (PBMCs) following weaning and also assessed differential patterns in pigs exhibiting high and low stress response as measured by cortisol concentration and lesion scores. Blood was collected from nine gilt piglets 24 h before and after weaning, and whole-genome bisulfite sequencing (WGBS) and RNA-sequencing were performed on six and nine animals, respectively, at both time points. We identified 2,674 differentially methylated regions (DMRs) that were enriched within promoters of genes associated with lymphocyte stimulation and transcriptional regulation. Stress groups displayed unique differential methylation and expression patterns associated with activation and suppression of T cell immunity in low and high stress animals, respectively. Differential methylation was strongly associated with differential expression; specifically, upregulated genes were enriched among hypomethylated genes. We observed post-weaning hypermethylation of the glucocorticoid receptor (NR3C1) promoter and a significant decrease in NR3C1 expression (n = 9, p = 6.1 × 10–3). Our results indicate that weaning-associated stress elicits genome-wide methylation changes associated with differential gene expression, reduced T cell activation, and an altered HPA axis response.
Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cells and Extracellular Vesicles: Therapeutic Outlook for Inflammatory and Degenerative Diseases
Authors: Dabrowska Sylwia , Andrzejewska Anna , Janowski Miroslaw , Lukomska Barbara
Published: February 2021

Mesenchymal stem cells (MSCs) are non-hematopoietic, multipotent stem cells derived from mesoderm, which can be easily isolated from many sources such as bone marrow, umbilical cord or adipose tissue. MSCs provide support for hematopoietic stem cells and have an ability to differentiate into multiple cell lines. Moreover, they have proangiogenic, protective and immunomodulatory properties. MSCs have the capacity to modulate both innate and adaptive immune responses, which accompany many diseases, by inhibiting pro-inflammatory reactions and stimulating anti-inflammatory activity. Recent findings revealed that the positive effect of MSCs is at least partly associated with the production of extracellular vesicles (EVs). EVs are small membrane structures, containing proteins, lipids and nuclei acids, which take part in intra-cellular communication. Many studies indicate that EVs contain protective and pro-regenerative properties and can modulate an immune response that is activated in various diseases such as CNS diseases, myocardial infarction, liver injury, lung diseases, ulcerative colitis or kidney injury. Thus, EVs have similar functions as their cells of origin and since they do not carry the risk of cell transplantation, such as tumor formation or small vessel blockage, they can be considered a potential therapeutic tool for cell-free therapy.
Comparative Cell Surface Proteomic Analysis of the Primary Human T Cell and Monocyte Responses to Type I Interferon
Authors: Soday Lior , Potts Martin , Hunter Leah M. , Ravenhill Benjamin J. , Houghton Jack W. , Williamson James C. , Antrobus Robin , Wills Mark R. , Matheson Nicholas J. , Weekes Michael P.
Published: February 2021

The cellular response to interferon (IFN) is essential for antiviral immunity, IFN-based therapy and IFN-related disease. The plasma membrane (PM) provides a critical interface between the cell and its environment, and is the initial portal of entry for viruses. Nonetheless, the effect of IFN on PM proteins is surprisingly poorly understood, and has not been systematically investigated in primary immune cells. Here, we use multiplexed proteomics to quantify IFNα2a-stimulated PM protein changes in primary human CD14+ monocytes and CD4+ T cells from five donors, quantifying 606 and 482 PM proteins respectively. Comparison of cell surface proteomes revealed a remarkable invariance between donors in the overall composition of the cell surface from each cell type, but a marked donor-to-donor variability in the effects of IFNα2a. Furthermore, whereas only 2.7% of quantified proteins were consistently upregulated by IFNα2a at the surface of CD4+ T cells, 6.8% of proteins were consistently upregulated in primary monocytes, suggesting that the magnitude of the IFNα2a response varies according to cell type. Among these differentially regulated proteins, we found the viral target Endothelin-converting enzyme 1 (ECE1) to be an IFNα2a-stimulated protein exclusively upregulated at the surface of CD4+ T cells. We therefore provide a comprehensive map of the cell surface of IFNα2a-stimulated primary human immune cells, including previously uncharacterized interferon stimulated genes (ISGs) and candidate antiviral factors.
How Do Marine Mammals Manage and Usually Avoid Gas Emboli Formation and Gas Embolic Pathology? Critical Clues From Studies of Wild Dolphins
Authors: Fahlman Andreas , Moore Michael J. , Wells Randall S.
Published: February 2021

Decompression theory has been mainly based on studies on terrestrial mammals, and may not translate well to marine mammals. However, evidence that marine mammals experience gas bubbles during diving is growing, causing concern that these bubbles may cause gas emboli pathology (GEP) under unusual circumstances. Marine mammal management, and usual avoidance, of gas emboli and GEP, or the bends, became a topic of intense scientific interest after sonar-exposed, mass-stranded deep-diving whales were observed with gas bubbles. Theoretical models, based on our current understanding of diving physiology in cetaceans, predict that the tissue and blood N2levels in the bottlenose dolphin (Tursiops truncatus) are at levels that would result in severe DCS symptoms in similar sized terrestrial mammals. However, the dolphins appear to have physiological or behavioral mechanisms to avoid excessive blood N2levels, or may be more resistant to circulating bubbles through immunological/biochemical adaptations. Studies on behavior, anatomy and physiology of marine mammals have enhanced our understanding of the mechanisms that are thought to prevent excessive uptake of N2. This has led to theselective gas exchangehypothesis, which provides a mechanism how stress-induced behavioral change may cause failure of the normal physiology, which results in excessive uptake of N2, and in extreme cases may cause formation of symptomatic gas emboli. Studies on cardiorespiratory function have been integral to the development of this hypothesis, with work initially being conducted on excised tissues and cadavers, followed by studies on anesthetized animals or trained animals under human care. These studies enabled research on free-ranging common bottlenose dolphins in Sarasota Bay, FL, and off Bermuda, and have included work on the metabolic and cardiorespiratory physiology of both shallow- and deep-diving dolphins and have been integral to better understand how cetaceans can dive to extreme depths, for long durations.
In situ Growth Rate Assessment of the Hexactinellid Sponge Asconema setubalense Using 3D Photogrammetric Reconstruction
Authors: Prado Elena , Cristobo Javier , Rodríguez-Basalo Augusto , Ríos Pilar , Rodríguez-Cabello Cristina , Sánchez Francisco
Published: February 2021

We describe the first application of a non-invasive and novel approach to estimate the growth rate of Asconema setubalense (Porifera, Hexactinellida) through the use of 3D photogrammetric methodology. Structure-from-Motion techniques (SfM) were applied to videos acquired with the Politolana ROTV in the El Cachucho Marine Protected Area (MPA) (Cantabrian Sea) on three different dates (2014, 2017, and 2019) over six years. With these data, a multi-temporal study was conducted within the framework of MPA monitoring. A complete 3D reconstruction of the deep-sea floor was achieved with Pix4D Mapper Pro software for each date. Having 3D point clouds of the study area enabled a series of measurements that were impossible to obtain in 2D images. In 3D space, the sizes (height, diameter, cup-perimeter, and cup-surface area) of several A. setubalense specimens were measured each year. The annual growth rates recorded ranged from zero (“no growth”) for a large size specimen, to an average of 2.2 cm year–1 in cup-diameter, and 2.5 cm year–1 in height for developing specimens. Von Bertalanffy growth parameters were estimated. Taking into account the size indicators used in this study and based on the von Bertalanffy growth model, this sponge reaches 95% maximum size at 98 years of age. During the MPA monitoring program, a high number of specimens disappeared. This raised suspicions of a phenomenon affecting the survival of this species in the area. This type of image-based methodology does not cause damage or alterations to benthic communities and should be employed in vulnerable ecosystem studies and MPA monitoring.
Genetic Diversity of Astrovirus in Children From a Birth Cohort in Nepal
Authors: Shrestha Sanjaya Kumar , Shrestha Jasmin , Andreassen Ashild K. , Strand Tor A. , Dudman Susanne , Dembinski Jennifer L.
Published: February 2021

Objective: This study describes the types of Human astroviruses detected in stool samples collected from a birth cohort of children in Nepal.

Methods: Using a commercial kit (ProSpecT), a total of 5,224 diarrheal and non-diarrheal stool samples were screened for Human astrovirus by ELISA. RT-PCR was performed on ELISA positive samples (2.8%) for further confirmation. The primary RT-PCR assay used targets the ORF2 region and detects human astrovirus type 1–8. Samples that were negative in this assay were further analyzed using primers that target the ORF1b region of human astrovirus which detect both classical type (HAstV 1–8) and novel types (MLB1–5, VA 1–5). PCR positive samples were analyzed by Sanger sequencing to determine the genotype.

Results: A total of 148 available ELISA positive stool samples were analyzed by RT-PCR and further genotyped. RT-PCR analysis of these samples using the ORF2 and ORF1b assay revealed that 124 (84%) were positive for classical human types (HAstV 1–8). Seven different classical HAstV genotypes based on ORF2 and ORF1a were identified (HAstV 1- HAstV 8) with the greatest prevalence of HAstV 5 genotype (42.2%), followed by HAstV 1 (34.7%), HAstV 2 and HAstV 8 (7.4%), HAstV 4 (4.1%), HAstV 3 (3.3%), and HAstV 6 (0.8%). Non-classical types were not detected in our study.

Conclusion: A high diversity of circulating Astrovirus strains were detected in young children, both with and without symptoms of gastroenteritis. HAstV 5 and HAstV 1 were the most common genotypes in young children in Nepal.
Evaluation of an O2-Substituted (1–3)-β-D-Glucan, Produced by Pediococcus parvulus 2.6, in ex vivo Models of Crohn’s Disease
Authors: Notararigo Sara , Varela Encarnación , Otal Anna , Cristobo Iván , Antolín María , Guarner Francisco , Prieto Alicia , López Paloma
Published: February 2021

1,3-β-glucans are extracellular polysaccharides synthesized by microorganisms and plants, with therapeutic potential. Among them, the O2-substituted-(1–3)-β-D-glucan, synthesized by some lactic acid bacteria (LAB), has a prebiotic effect on probiotic strains, an immunomodulatory effect on monocyte-derived macrophages, and potentiates the ability of the producer strain to adhere to Caco-2 cells differentiated to enterocytes. In this work, the O2-substituted-(1–3)-β-D-glucan polymers produced by GTF glycoyltransferase in the natural host Pediococcus parvulus 2.6 and in the recombinant strain Lactococcus lactis NZ9000[pNGTF] were tested. Their immunomodulatory activity was investigated in an ex vivo model using human biopsies from patients affected by Crohn’s disease (CD). Both polymers had an anti-inflammatory effect including, a reduction of Interleukine 8 both at the level of its gene expression and its secreted levels. The overall data indicate that the O2-substituted-(1–3)-β-D-glucan have a potential role in ameliorating inflammation via the gut immune system cell modulation.
Case Report: Neoadjuvant PD-1 Blockade Plus Concurrent Chemoradiotherapy in Unresectable Locally Advanced Gastric Cancer Patients
Authors: Wei Jia , Lu Xiaofeng , Liu Qin , Li Lin , Liu Song , Liu Fangcen , Fu Yao , Fan Xiangshan , Yang Yang , Qi Chuang , Yu Yangyang , Guan Wenxian , Liu Baorui
Published: February 2021

Programmed death 1(PD-1) blockade has shown promising efficacy in advanced gastric cancer. Here, we performed a retrospective analysis of three patients with locally advanced gastric cancer who received adjuvant PD-1 plus chemoradiotherapy as neoadjuvant treatment. Neoadjuvant sintilimab plus concurrent chemoradiotherapy had an acceptable side-effect profile. All three patients underwent surgical gastrectomy after a median of 3.9 months. A major pathological response occurred in two resected tumors and a pathologic complete response was observed in one patient. Our results suggest that PD-1 blockade combined with chemoradiotherapy is a promising strategy as a neoadjuvant therapy in patients with unresectable locally advanced gastric cancer.
Heterozygous P32/C1QBP/HABP1 Polymorphism rs56014026 Reduces Mitochondrial Oxidative Phosphorylation and Is Expressed in Low-grade Colorectal Carcinomas
Authors: Raschdorf Annika , Sünderhauf Annika , Skibbe Kerstin , Ghebrehiwet Berhane , Peerschke Ellinor I. , Sina Christian , Derer Stefanie
Published: February 2021

Rapid proliferation of cancer cells is enabled by favoring aerobic glycolysis over mitochondrial oxidative phosphorylation (OXPHOS). P32 (C1QBP/gC1qR) is essential for mitochondrial protein translation and thus indispensable for OXPHOS activity. It is ubiquitously expressed and directed to the mitochondrial matrix in almost all cell types with an excessive up-regulation of p32 expression reported for tumor tissues. We recently demonstrated high levels of non-mitochondrial p32 to be associated with high-grade colorectal carcinoma. Mutations in human p32 are likely to disrupt proper mitochondrial function giving rise to various diseases including cancer. Hence, we aimed to investigate the impact of the most common single nucleotide polymorphism (SNP)rs56014026in the coding sequence ofp32on tumor cell metabolism.In silicohomology modeling of the resulting p.Thr130Met mutated p32 revealed that the single amino acid substitution potentially induces a strong conformational change in the protein, mainly affecting the mitochondrial targeting sequence (MTS).In vitroexperiments confirmed an impaired mitochondrial import of mutated p32-T130M, resulting in reduced OXPHOS activity and a shift towards a low metabolic phenotype. Overexpression of p32-T130M maintained terminal differentiation of a goblet cell-like colorectal cancer cell line compared to p32-wt without affecting cell proliferation. Sanger sequencing of tumor samples from 128 CRC patients identified the heterozygous SNPrs56014026in two well-differentiated, low proliferating adenocarcinomas, supporting ourin vitrodata. Together, the SNPrs56014026reduces metabolic activity and proliferation while promoting differentiation in tumor cells.
Measuring the Impact of Nuclear Interaction in Particle Therapy and in Radio Protection in Space: the FOOT Experiment
Authors: Battistoni Giuseppe , Toppi Marco , Patera Vincenzo , The FOOT Collaboration
Published: February 2021

In Charged Particle Therapy (PT) proton or 12C beams are used to treat deep-seated solid tumors exploiting the advantageous characteristics of charged particles energy deposition in matter. For such projectiles, the maximum of the dose is released at the end of the beam range, in the Bragg peak region, where the tumour is located. However, the nuclear interactions of the beam nuclei with the patient tissues can induce the fragmentation of projectiles and/or target nuclei and needs to be carefully taken into account when planning the treatment. In proton treatments, the target fragmentation produces low energy, short range fragments along all the beam path, that deposit a non-negligible dose especially in the first crossed tissues. On the other hand, in treatments performed using 12C, or other (4He or 16O) ions of interest, the main concern is related to the production of long range fragments that can release their dose in the healthy tissues beyond the Bragg peak. Understanding nuclear fragmentation processes is of interest also for radiation protection in human space flight applications, in view of deep space missions. In particular 4He and high-energy charged particles, mainly 12C, 16O, 28Si and 56Fe, provide the main source of absorbed dose in astronauts outside the atmosphere. The nuclear fragmentation properties of the materials used to build the spacecrafts need to be known with high accuracy in order to optimise the shielding against the space radiation. The study of the impact of these processes, which is of interest both for PT and space radioprotection applications, suffers at present from the limited experimental precision achieved on the relevant nuclear cross sections that compromise the reliability of the available computational models. The FOOT (FragmentatiOn Of Target) collaboration, composed of researchers from France, Germany, Italy and Japan, designed an experiment to study these nuclear processes and measure the corresponding fragmentation cross sections. In this work we discuss the physics motivations of FOOT, describing in detail the present detector design and the expected performances, coming from the optimization studies based on accurate FLUKA MC simulations and preliminary beam test results. The measurements planned will be also presented.
Electrocardiographic Risk Markers of Cardiac Death: Gender Differences in the General Population
Authors: Haukilahti Mira Anette E. , Kenttä Tuomas V. , Tikkanen Jani T. , Anttonen Olli , Aro Aapo L. , Kerola Tuomas , Eranti Antti , Holkeri Arttu , Rissanen Harri , Heliövaara Markku , Knekt Paul , Junttila M. Juhani , Huikuri Heikki V.
Published: February 2021

Background

Cardiac death is one of the leading causes of death and sudden cardiac death (SCD) is estimated to cause approximately 50% of cardiac deaths. Men have a higher cardiac mortality than women. Consequently, the mechanisms and risk markers of cardiac mortality are not as well defined in women as they are in men.

Aim

The aim of the study was to assess the prognostic value and possible gender differences of SCD risk markers of standard 12-lead electrocardiogram in three large general population samples.

Methods

The standard 12-lead electrocardiographic (ECG) markers were analyzed from three different Finnish general population samples including total of 20,310 subjects (49.9% women, mean age 44.8 ± 8.7 years). The primary endpoint was cardiac death, and SCD and all-cause mortality were secondary endpoints. The interaction effect between women and men was assessed for each ECG variable.

Results

During the follow-up (7.7 ± 1.2 years), a total of 883 deaths occurred (24.5% women, p < 0.001). There were 296 cardiac deaths (13.9% women, p < 0.001) and 149 SCDs (14.8% women, p < 0.001). Among those who had died due to cardiac cause, women had more often a normal electrocardiogram compared to men (39.0 vs. 27.5%, p = 0.132). After adjustments with common cardiovascular risk factors and the population sample, the following ECG variables predicted the primary endpoint in men: left ventricular hypertrophy (LVH) with strain pattern (p < 0.001), QRS duration > 110 ms (p < 0.001), inferior or lateral T-wave inversion (p < 0.001) and inferolateral early repolarization (p = 0.033). In women none of the variables remained significant predictors of cardiac death in multivariable analysis, but LVH, QTc ≥ 490 ms and T-wave inversions predicted SCD (p < 0.047 and 0.033, respectively). In the interaction analysis, LVH (HR: 2.4; 95% CI: 1.2–4.9; p = 0.014) was stronger predictor of primary endpoint in women than in men.

Conclusion

Several standard ECG variables provide independent information on the risk of cardiac mortality in men but not in women. LVH and T-wave inversions predict SCD also in women.
How Refugees’ Stereotypes Toward Host Society Members Predict Acculturation Orientations: The Role of Perceived Discrimination
Authors: Lutterbach Sebastian , Beelmann Andreas
Published: February 2021

Refugee migration leads to increased diversity in host societies and refugees have to face many stereotyped attitudes in the host society. However, there has been little research on minority group stereotypes toward host society members and how these stereotypes relate to the acculturation-relevant attitudes of refugees in their first phase of acculturation. This study surveyed 783 refugees in Germany who had migrated mostly in the so-called “refugee crisis” between 2015 and 2016. At the time of the survey in 2018, they had been in Germany for an average of 27 months (SD = 15 months). These refugees reported their positive and negative sociability stereotypes toward German host society members, acculturation-related orientations, shared reality values, and perceived discrimination. Results showed that positive sociability stereotypes toward host society members were associated with increased cultural adoption and shared reality. In contrast, negative sociability stereotypes negatively affected cultural adoption and shared reality. However, stereotypes showed no association at all with cultural maintenance. Interactions between sociability stereotypes and discrimination experiences highlighted a disillusion effect, in the sense that discrimination reduced the motivation to adopt the host culture more strongly among refugees who held strongly positive sociability stereotypes. The study extends knowledge on the significance of minority group stereotypes in the context of refugee migration and reveals the maladaptive consequences of discriminatory behavior against refugees by host society members.
Modelo holístico de planificación curricular para institutos y colegios universitarios de tecnología
Authors: Bastidas Terán Felipe Antonio
Published: February 2021

El presente trabajo tuvo como objetivo desarrollar un modelo de planificación curricular, basado en los principios de la holística y en los aportes de la hologogía. Se hizo una investigación proyectiva, con un diseño de fuente mixta (documentos y fuentes vivas), en el Instituto Universitario de Tecnología de Caripito, en el estado Monagas, Venezuela. Se aplicaron entrevistas a los profesores, un cuestionario estructurado a los estudiantes, y se revisaron los diseños curriculares de los programas vigentes para el momento. Para determinar los requerimientos del sector laboral de la región, se estudió la oferta laboral de la zona y se hizo un estadio predictivo a fin de anticipar tendencias futuras de demanda laboral. El resultado fue la construcción del Modelo holístico de planificación curricular (Mhoplan), que presenta un proceso continuo y organizado, con énfasis en la investigación, e incorpora seis etapas en un bucle recurrente: Diagnóstico, Viabilidad, (Re) Diseño, Aplicación, Evaluación y Fortalecimiento.