bluuebunny/crossref_metadata_2025 huggingface dataset:
Capital social y expectativas profesionales en estudiantes universitarios
Authors: Orozco Sandoval Oscar Guillermo , Ruvalcaba Coyaso Francisco Javier , Maza Diaz Cortés Octavio Martin , Selva Olid Clara
Published: January 2021

El estudio de la etapa universitaria como momento clave de la formación personal y como antecedente de la vida laboral ha cobrado relevancia en los años recientes. El capital social y las expectativas profesionales son variables que guardan relación con el devenir de los estudiantes en actores del campo laboral. Sin embargo, poco se sabe de la relación de estas variables entre sí y de la forma en que inciden en la experiencia universitaria. En este estudio se propuso explorar la correlación entre capital social y expectativas profesionales positivas en estudiantes universitarios a través de un cuestionario autoadministrable entregado a 571 estudiantes de la Universidad Autónoma de Aguascalientes. El cuestionario contó con 43 preguntas que midieron capital social y expectativas profesionales positivas, incluyendo reactivos escalares y nominales, preguntas abiertas y descriptores libres. Se encontró que el capital social y las expectativas profesionales positivas guardan relación con variables como clase social percibida, promedio académico o situación laboral. A partir de estos resultados, se reflexiona entorno a distintas implicaciones y alcances del estudio.
Investigation of Different Laboratory Aging Methods of Bituminous Mixtures
Authors: Durmaz Cagla , Sengoz Burak , Kaya Ozdemir Derya , Topal Ali
Published: January 2021

The predicted performance and service life of the pavement depend largely on the properties of bitumen used in the mixtures. The most important feature of bitumen, which has profound effect on the performance of the road is durability. The durability of bitumen is expressed as the resistance to aging. In this study, the bituminous mixture aging was performed instead of bitumen aging in order to represent the aging in the field in the best possible way. The aim of this paper is to evaluate different proposed laboratory aging methods (NCHRP 09-52, NCHRP 09-54 and RILEM) in relation with the current Standard AASHTO R30 (Standard Practice For Mixture Conditioning of Hot Mix Asphalt standard) and to make comparison with the samples performance taken from the field in terms of Indirect Tensile Strength (ITS). The level of aging has also been compared with the samples taken from recently constructed pavement surface and from the five years old pavement surface. Results depicted that, laboratory aging methods revealed the field aging properties on the unaged bitumen. Based on the results, 2 hours forced draft oven aging at 135°C is recommended as short term aging condition because, 2 hours or 4 hours short term forced draft oven aging did not yield significant variation in terms of ITS values. Additionally, 120 hours (5 days) oven aging of compacted samples at 85°C can be recommended as long term aging condition.
Effect of Stirrup Spacing and Polypropylene Fiber Ratio on Behavior of Reinforced Concrete Beams
Authors: Ünal Alptuğ , Cengiz Salih , Kamanlı Mehmet
Published: January 2021

In this study, the effect of the change of stirrup ratio and polypropylene (PP) fiber ratio on the behavior of reinforced concrete beams was investigated. The variables of this study consisting of without stirrup, spacing up to 20 %, 40 % and 80 % of beam depth as stirrup spacing and 0.125 % and 0.500 % of the weight of reinforced concrete beam were used as PP fiber ratios. In the context of experimental study, 1/2 scaled 12 reinforced concrete beams were tested with 4-point bending mechanism. In the light of the obtained data, the load-displacement, stiffness and energy absorption graphs were plotted. The results were interpreted comparatively. According to the results, it is observed that the PP fiber additive significantly changed the behavior of the reinforced concrete beams, and the fiber effect decreased in proportion to the increase of the stirrup rate. It has been observed that the cracks spread more to the beam surfaces with the increase of PP fibers. In addition, the increase in the fiber ratio especially in the non-stirrup beams increases the bending capacity.
铝模板施工技术在高层建筑工程中的应用探讨
Authors: 方 伟东 , 张 琦
Published: January 2021

近年来，我国社会经济水平得到了快速的提升，从而为各个领域的发展壮大带来了诸多的机遇，有效的推动了建筑工程行业的不断进步。在建筑工程项目中，铝模板材料属于较为常用的一种施工材料，在整个建筑结构建造中起到了重要的影响作用。在当前新的历史时期中，大量的高层建筑的出现对施工技术和施工材料提出了更高的要求，因为铝模板材料自身整个规格较大，数量众多，适用范围较为广泛，所以受到了人们的一致青睐，可以说铝模板施工材料的质量与工程整体施工质量存在密切的关联，所以为了从根本上对建筑工程施工质量加以保证，那么施工单位就需要切实的对铝模板施工技术加以重点关注，充分结合各方面实际情况和需要，针对铝模板施工技术进行优化和创新，为建筑工程行业的未来良好发展打下坚实的基础。
EPC总承包管理模式中存在的问题与对策
Authors: 唐 明亮 , 路 海玉
Published: January 2021

工程总承包是工程总承包的简称，是对整个工程设计、材料设备采购、工程施工等环节进行的综合性管理活动。近几年来，CPE的总承包管理模式被广泛采用，给工程建设带来了许多效益。与此同时，EPC管理与传统的总分包、总分包管理有本质的区别，但也有其明显的优缺点。为此，本文对EPC管理模式存在的问题进行了分析，并提出了具体对策。
水工环地质勘查现状及改善策略研究
Authors: 伍 云仲
Published: January 2021

当前社会持续稳定进步和发展，经济持续发展对于能源需求量越来越大，为了可以将当前能源问题妥善的处理和解决，必须要重点关注地质勘查工作。开展水工环地质勘查活动时要重点关注的内容包括许多方面，只有充分重视起来才能够获得预期结果。当前阶段地质勘查还存在许多问题，这些问题的存在严重影响到勘查活动正常进行，因此文章就针对水工环地质勘查现状及改善策略展开，希望可以促进相关工作的进步和发展。
大跨度市政桥梁施工技术
Authors: 黄 节煜
Published: January 2021

近些年来，随着国家经济水平快速发展，交通压力在汽车数量猛增的背景下，存在较大的压力。而桥梁施工可以帮助缩短路程，缓解交通存在的压力。另外，大跨度桥梁施工与常规桥梁相比较，施工复杂程度更高，需要投入更多的成本与精力。任何一道工序存在问题对于桥梁质量都会造成影响，因此需要控制好施工技术，保障施工质量。文章基于大跨度市政桥梁施工项目进行分析，阐述对应的施工技术。
Аналіз можливостей капсульних нейронних мереж для вирішення проблем, пов'язаних з розпізнаванням зображень
Authors: Арсенюк В.С. , Барбарук В.М.
Published: January 2021

У статті виконано огляд сьогочасних публікацій з досліджень щодо модифікацій базових алгоритмів маршрутизації, базової архітектури капсульної нейромережі та використовуваних даними мережами датасетів. На підставі аналізу та узагальнення зроблені висновки щодо принципів побудови таких мереж на сучасному етапі, вибору алгоритму маршрутизації та оптимізатора для складних наборів даних.

Розглянуто питання щодо можливості застосування капсульного підходу при побудові нейронної мережі з розпізнавання зображень для мобільних додатків.
Ipung Novel by Prie Gs and Sang Alkemis Novel by Paulo Coelho (Comparative Literature Study)
Authors: Pana Pramulia  , Nanda Saputra
Published: January 2021

Literary works in Indonesia, including novels, both in terms of ideas and content, are heavily influenced by works from abroad. This influence is caused by many things, for example Indonesian writers who idolize foreign writers, similarities in social situations and conditions, or even unplanned similarities because Indonesian writers unconsciously intensively read one of the works of foreign writers. This research attempts to compare the novel Ipung by Prie GS with the novel the Alchemist by Paulo Coelho. Comparisons are only limited to pouring out the ideas, genres, and motives contained in the two novels. This research is a descriptive qualitative research that describes a number of ideas, genres, and motives concerning the basic issues of creation, and the message can be expressed accuratel. Based on the research results, it was stated that the novel Sang Alkemis by Paulo Coelho influenced Prie GS novel Ipung, both in terms of ideas, genres, and motives.
Hutabolon Village Community Behavior in Overcoming Health Problems
Authors: Rholand Muary  , Agung Suharyanto  , Onggal Sihite  , Wiflihani  , Jamilah Nasution
Published: January 2021

The behavior of the Hutabolon Village community in overcoming the problem of diseases that occur or that they experience is still relatively moderate. The community is already aware of the importance of health, but because there are insufficient facilities or health facilities, it makes the community still have a little difficulty in getting treatment. The research method used is qualitative with a descriptive approach, through this research method researchers get information about the types of diseases that often occur, modern and traditional medicine carried out by the people in Hutabolon Village as a behavior in overcoming health problems. The results of the study concluded that the types of diseases that often occur in Hutabolon Village are eight such as flu or respiratory infections, fever, rheumatism, diarrhea, wounds or vulnus, cavities or toothache, acute respiratory infections, and stomach acid. Behavior of the people of Hutabolon Village To overcome the problem of the disease is to use modern medicine or medical services coupled with traditional medicine.
Language Acquisition of Children Age 4-5 Years Old in TK Dhinukum Zholtan Deli Serdang
Authors: Nurhasanah Purba  , Mukramah  , M. Wahyu Maulana  , Gustia Ningsi
Published: January 2021

This study aims to determine the language acquisition of children aged 4-5 years. This research was conducted at TK Dhinukum Zholtan Medan which was conducted on March 4, 2020 with 4 students, 2 students aged 4 years and 2 students aged 5 years. In this study, researchers used the method of observation and also a questionnaire to collect data. Based on the description above, it can be concluded that children aged 5 and 4 years have different mastery. In addition to clear pronunciation, 5 year olds have mastery of more vocabulary and are able to describe things. Meanwhile, children aged 4 years have less vocabulary, have not been able to describe something and are not able to pronounce it clearly. This difference occurs because 5 year olds have already taken part in learning compared to 4 year olds. So that children aged 5 years are better able to communicate well, because they often interact with teachers and peers at school.
Machines for intra-soil application of liquid organic fertiliz-ers
Authors:   Russian State Agrarian University – Moscow Timiryazev Agricultural Academy, Aldoshin N.V. , Manokhin A.A. ,   Russian State Agrarian University – Moscow Timiryazev Agricultural Academy, Semin V.V. ,   Russian State Agrarian University – Moscow Timiryazev Agricultural Academy
Published: January 2021

The article presents an analysis of tools for subsoil application of liquid or-ganic fertilizers using a hose system and a comparative assessment of technical means. Various types of working bodies for applying fertilizers deep into the soil layer are shown. Options of different depths of fertilization are described. Recommendations on the placement of the tie-down unit on the tool for attaching the towed hose are given.
Desenvolvimento de hambúrguer vegano adicionado da farinha de couve folha: avaliação físico-química, microbiológica e sensorial
Authors: Lima Segundo Jair Francisco de , Jerônimo Heloísa Maria Ângelo , Viera Vanessa Bordin , Nascimento Camila Maria Sousa de Andrade
Published: January 2021

Em constante ascensão, o número de pessoas adeptas ao veganismo impõe ao mercado alternativas alimentares diversificadas, sendo assim, é de grande relevância o desenvolvimento de alimentos com formulações que visem a substituição da matéria cárnea animal pela de origem vegetal. Desta forma, a utilização da jaca como base para elaboração de um hambúrguer pode mostrar-se como potencial alimentício e socioeconômico. Objetivou-se elaborar e realizar análises físico-química, microbiológica, sensorial e de rendimento em hambúrgueres de “carne de jaca” adicionados de um mix de farinhas da semente do fruto e da couve folha. Foram selecionadas jacas, da variedade “dura”, imaturas. Após a higienização e sanitização, uma parte das frutas foi tratada termicamente ao forno para posterior separação da polpa e semente, que foi congelada e transformada em farinha, respectivamente, assim como na porção in natura. Em seguida, após elaboração, as duas formulações de hambúrguer foram submetidas às análises supracitadas, sendo que na avaliação sensorial as amostras foram submetidas a processo térmico e assim 60 provadores realizaram teste de aceitação em escala hedônica de 9 pontos e de intenção de compra. Ao final da pesquisa, o produto não apresentou diferenças físico-quimicas, mostrou boas características microbiológicas e obteve boas aceitação sensorial para a amostra HV01, demostrando potencial em ser uma boa colaboração com a indústria alimentícia, oferecendo assim uma mais opção mercadológica para o número crescente de indivíduos veganos.
Perfil agronômico, fermentativo e bromatológico da silagem obtida do consórcio entre milho e soja
Authors: Marques Karolyna Oliveira , Jakelaitis Adriano , Guimarães Kátia Cylene , Pereira Leandro Spíndola
Published: January 2021

O consórcio de milho com leguminosas pode aumentar a qualidade da silagem e resultar em maior produtividade animal. Objetivou-se nesta pesquisa avaliar aspectos agronômicos das culturas consorciadas entre milho e soja, perfil fermentativo e bromatológico da silagem produzida, em função do arranjo espacial das plantas e tipos de adubação. Foram realizados dois ensaios com dois arranjos espaciais: ensaio 1 – arranjo simples com uma linha de milho alternada com uma linha de soja; ensaio 2  - arranjo duplo com duas linhas de milho alternada com uma linha de soja. O delineamento foi em blocos ao acaso em esquema fatorial 2x2+1, com quatro repetições. O primeiro fator constou de duas modalidades de adubação de semeadura na linha: somente no milho e em área total. O segundo fator pelas doses de 100 e 70 kg ha-1 de P2O5 e K2O, respectivamente; e de 150 e 95 kg ha-1 de P2O5 e K2O, respectivamente. O monocultivo de milho foi a testemunha. Após a colheita, o material foi ensilado por 60 dias. Não houve diferença estatística no rendimento de silagem entre tratamentos, apenas aumentos na produção de vagens de soja e na qualidade da silagem nas doses maiores de adubação. Os resultados mostram que a adição de soja na silagem de milho ocasiona maiores perdas durante o processo de fermentação, mas em contrapartida eleva os teores de proteína, extrato etéreo e de digestibilidade. Ressalta-se que um volumoso com essas características pode vir a suprir a suplementação proteica em dietas de ruminantes.
PENERAPAN PENDEKATAN CONTEXTUAL TEACHING AND LEARNING (CTL) DALAM UPAYA MENINGKATKAN PEMAHAMAN KONSEP MATEMATIKA SISWA
Authors: Minarni Minarni
Published: January 2021

This research is motivated by the large number of students who find it difficult to understand the concept of mathematics because generally mathematics is an abstract subject so that the teacher must strive for learning to be concrete by applying learning that can relate the concept to the real life of students. One of the efforts is to apply a contextual teaching and learning approach to present learning that is full of abstract concepts to have a close relationship with students' daily lives. This type of research is a classroom action research conducted in class IV / A SDN 003 Sungai Salak. The number of research subjects was 24 students. The instrument used to analyze students' conceptual understanding used a multiple choice concept comprehension test. The results showed that students' understanding of mathematical concepts in the first cycle was 68.61 with 17 students who completed or 70.83%. In cycle II students' understanding of mathematical concepts increased to 71.11 with classical completeness of 83.33% where as many as 20 students were able to achieve the specified completeness. The conclusion based on the results of this study is that the application of the contextual teaching and learning approach can improve the understanding of the mathematical concepts of grade IV / A students of SDN 003 Sungai Salak on the subject of circumference and area of simple flat shapes.
Sequence Alignment Algorithms for Intrusion Detection in the Internet of Things
Authors: Kalinin M. , Krundyshev V.
Published: January 2021

The paper reviews the intrusion detection approach based on bioinformatics algorithms for alignment and comparing of the nucleotide sequences. Sequence alignment is a natureclose computational procedure for matching the coded strings by searching for the regions of individual characteristics that are located in the same order. A calculated rank of similarity is used instead of equity checking to estimate the distance between a sequence of the monitored operational acts and a generalized intrusion pattern. Multiple alignment schema is more effective and accurate than the Smith–Waterman local alignment due to ability to find few blocks of similarity. In comparison with a traditional signature-based IDS, it is found that the nature-inspired approach provides the better work characteristics. The experimental study have shown that new approach demonstrates high, 99 percent, level of accuracy.
Optimization of the Parameters of a Compact Laser Microchip Based on Nd:LSB with Cr:YAG Saturable Absorber
Authors: Burov L. I. , Krylova L. G.
Published: January 2021

Two models of Nd:LSB microchip laser with Cr:YAG saturable absorber have been compared: the travelling wave model and the point model which is deduced from the first one by averaging of all characteristics over the resonator length. It has been shown that the point model is applicable only for a narrow range of laser parameters, in other cases the results of simulations based on these two models differ significantly.
Cancer Radiation Therapy May Be Associated With Atrial Fibrillation
Authors: Apte Nachiket , Dherange Parinita , Mustafa Usman , Ya'qoub Lina , Dawson Desiree , Higginbotham Kathleen , Boerma Marjan , Morin Daniel P. , Gupta Dipti , McLarty Jerry , Mansour Richard , Dominic Paari
Published: January 2021

Background: The association of atrial fibrillation (AF) with cancer and cancer types is inconclusive. Similarly, data regarding the association of AF with different cancer therapies are controversial.

Objectives: To study the association of AF with cancer subtypes and cancer therapies.

Methods: We studied all patients aged 18–89 years who presented to the Feist Weiller Cancer Center, with or without a diagnosis of cancer, between January 2011 and February 2016. Electronic health records were systematically queried for baseline demographics and ICD-9 and ICD-10 codes for specific co-morbidities. Patients with a diagnosis of AF were tabulated based on cross-validation with the ECG database and/or by recorded history. We assessed the prevalence and risk of AF based on cancer diagnosis, specific cancer type, and cancer therapy.

Results: A total of 14,600 patients were analyzed. Compared to non-cancer patients (n = 6,801), cancer patients (n = 7,799) had a significantly higher prevalence of AF (4.3 vs. 3.1%; p < 0.001). However, following correction for covariates in a multivariable logistic regression model, malignancy was not found to be an independent risk factor for AF (p = 0.32). While patients with solid tumors had a numerically higher prevalence of AF than those with hematological malignancies (4.3 vs. 4.1%), tumor type was not independently associated with AF (p = 0.13). AF prevalence was higher in patients receiving chemotherapy (4.1%), radiation therapy (5.1%), or both (6.9%) when compared to patients not receiving any therapy (3.6%, p = 0.01). On multivariable logistic regression, radiation therapy remained an independent risk factor for AF for the entire study population (p = 0.03) as well as for the cancer population (p < 0.01).

Conclusions: Radiation therapy for cancer is an independent risk factor for AF. The known association between cancer and AF may be mediated, at least in part, by the effects of radiation therapy.
Novel Genetic Variants of PPARγ2 Promoter in Gestational Diabetes Mellitus and its Molecular Regulation in Adipogenesis
Authors: Wu Ling , Song Yi , Zhang Yuan , Liang Bo , Deng Yan , Tang Tao , Ye Yan Chou , Hou Hong Ying , Wang Chi Chiu
Published: January 2021

Peroxisome proliferator-activated receptor γ2 (PPARγ2) is a nuclear hormone receptor of ligand-dependent transcription factor with a key role in adipogenesis and insulin sensitization in diabetes mellitus. In this study, we investigated genetic variants in PPARγ2 promoter, its association with gestational diabetes mellitus (GDM), and its molecular regulation. PPARγ2 promoter and start codon (-2,091 to +82 bp) from 400 pregnancies with GDM and 400 gestational-age matched control pregnancies were sequenced. Association and linkage disequilibrium of the identified polymorphisms with GDM was determined. ChIP-seq, gene silencing, and dual-luciferase reporter assays were performed to confirm transcription factor binding sites and promoter activity of the variants. Transfection experiments were carried out to determine the effects of variants on gene expression and adipogenesis. Among 15 variants identified, 7 known variants were not significantly associated with the risk of GDM (odds ratio: 0.710–1.208, 95% confidence interval: 0.445–0.877 to 1.132–1.664, P > 0.05) while linkage disequilibrium was significant (D’ > 0.7, R2 > 0.9). However, T-A-A-T-G haplotype was not significantly associated with GDM (χ2 = 2.461, P = 0.117). Five rare variants and 3 novel variants (rs948820149, rs1553638909, and rs1553638903) were only found in GDM. Transcription factor glucocorticoid receptor β (GRβ) bound to -807A/C (rs948820149) and knockdown of GRβ suppressed PPARγ2 promoter activity. This mutation significantly down-regulated PPARγ2 expression and alleviated adipogenesis. In conclusion, a novel -807A/C in PPARγ2 promoter was identified in Chinese women with GDM and the mutation affected GRβ binding and transcription of PPARγ2 for adipogenesis.
The Contribution of Genetic Variants to the Risk of Papillary Thyroid Carcinoma in the Kazakh Population: Study of Common Single Nucleotide Polymorphisms and Their Clinicopathological Correlations
Authors: Mussazhanova Zhanna , Rogounovitch Tatiana I. , Saenko Vladimir A. , Krykpayeva Ainur , Espenbetova Maira , Azizov Bauyrzhan , Kondo Hisayoshi , Matsuda Katsuya , Kalmatayeva Zhanna , Issayeva Raushan , Yeleubayeva Zhanar , Madiyeva Madina , Mukanova Aray , Sandybayev Marat , Bolsynbekova Saltanat , Kozykenova Zhanna , Yamashita Shunichi , Nakashima Masahiro
Published: January 2021

Objective

Risk for developing papillary thyroid carcinoma (PTC), the most common endocrine malignancy, is thought to be mediated by lifestyle, environmental exposures and genetic factors. Recent progress in the genome-wide association studies of thyroid cancer leads to the identification of several genetic variants conferring risk to this malignancy across different ethnicities. We set out to elucidate the impact of selected single nucleotide polymorphisms (SNPs) on PTC risk and to evaluate clinicopathological correlations of these genetic variants in the Kazakh population for the first time.

Methods

Eight SNPs were genotyped in 485 patients with PTC and 1,008 healthy control Kazakh subjects. The association analysis and multivariable modeling of PTC risk by the genetic factors, supplemented with rigorous statistical validation, were performed.

Result

Five of the eight SNPs: rs965513 (FOXE1/PTCSC2, P = 1.3E-16), rs1867277 (FOXE1 5’UTR, P = 7.5E-06), rs2439302 (NRG1 intron 1, P = 4.0E-05), rs944289 (PTCSC3/NKX2-1, P = 4.5E-06) and rs10136427 (BATF upstream, P = 9.8E-03) were significantly associated with PTC. rs966423 (DIRC3, P = 0.07) showed a suggestive association. rs7267944 (DHX35) was associated with PTC risk in males (P = 0.02), rs1867277 (FOXE1) conferred the higher risk in subjects older than 55 years (P = 7.0E-05), and rs6983267 (POU5F1B/CCAT2) was associated with pT3–T4 tumors (P = 0.01). The contribution of genetic component (unidirectional independent effects of rs965513, rs944289, rs2439302 and rs10136427 adjusted for age and sex) to PTC risk in the analyzed series was estimated to be 30–40%.

Conclusion

Genetic factors analyzed in the present work display significant association signals with PTC either on the whole group analysis or in particular clinicopathological groups and account for about one-third of the risk for PTC in the Kazakh population.
Genomic Engineering in Human Hematopoietic Stem Cells: Hype or Hope?
Authors: Klaver-Flores Stefanie , Zittersteijn Hidde A. , Canté-Barrett Kirsten , Lankester Arjan , Hoeben Rob C. , Gonçalves Manuel A. F. V. , Pike-Overzet Karin , Staal Frank J. T.
Published: January 2021

Many gene editing techniques are developed and tested, yet, most of these are optimized for transformed cell lines, which differ from their primary cell counterparts in terms of transfectability, cell death propensity, differentiation capability, and chromatin accessibility to gene editing tools. Researchers are working to overcome the challenges associated with gene editing of primary cells, namely, at the level of improving the gene editing tool components, e.g., the use of modified single guide RNAs, more efficient delivery of Cas9 and RNA in the ribonucleoprotein of these cells. Despite these efforts, the low efficiency of proper gene editing in true primary cells is an obstacle that needs to be overcome in order to generate sufficiently high numbers of corrected cells for therapeutic use. In addition, many of the therapeutic candidate genes for gene editing are expressed in more mature blood cell lineages but not in the hematopoietic stem cells (HSCs), where they are tightly packed in heterochromatin, making them less accessible to gene editing enzymes. Bringing HSCs in proliferation is sometimes seen as a solution to overcome lack of chromatin access, but the induction of proliferation in HSCs often is associated with loss of stemness. The documented occurrences of off-target effects and, importantly, on-target side effects also raise important safety issues. In conclusion, many obstacles still remain to be overcome before gene editing in HSCs for gene correction purposes can be applied clinically. In this review, in a perspective way, we will discuss the challenges of researching and developing a novel genetic engineering therapy for monogenic blood and immune system disorders.
A Review of Statistical Methods for Identifying Trait-Relevant Tissues and Cell Types
Authors: Zhu Huanhuan , Shang Lulu , Zhou Xiang
Published: January 2021

Genome-wide association studies (GWASs) have identified and replicated many genetic variants that are associated with diseases and disease-related complex traits. However, the biological mechanisms underlying these identified associations remain largely elusive. Exploring the biological mechanisms underlying these associations requires identifying trait-relevant tissues and cell types, as genetic variants likely influence complex traits in a tissue- and cell type-specific manner. Recently, several statistical methods have been developed to integrate genomic data with GWASs for identifying trait-relevant tissues and cell types. These methods often rely on different genomic information and use different statistical models for trait-tissue relevance inference. Here, we present a comprehensive technical review to summarize ten existing methods for trait-tissue relevance inference. These methods make use of different genomic information that include functional annotation information, expression quantitative trait loci information, genetically regulated gene expression information, as well as gene co-expression network information. These methods also use different statistical models that range from linear mixed models to covariance network models. We hope that this review can serve as a useful reference both for methodologists who develop methods and for applied analysts who apply these methods for identifying trait relevant tissues and cell types.
Genetic and Epigenetic Consequence of Early-Life Social Stress on Depression: Role of Serotonin-Associated Genes
Authors: Soga Tomoko , Teo Chuin Hau , Parhar Ishwar
Published: January 2021

Early-life adversity caused by poor social bonding and deprived maternal care is known to affect mental wellbeing and physical health. It is a form of chronic social stress that persists because of a negative environment, and the consequences are long-lasting on mental health. The presence of social stress during early life can have an epigenetic effect on the body, possibly resulting in many complex mental disorders, including depression in later life. Here, we review the evidence for early-life social stress-induced epigenetic changes that modulate juvenile and adult social behavior (depression and anxiety). This review has a particular emphasis on the interaction between early-life social stress and genetic variation of serotonin associate genes including the serotonin transporter gene (5-HTT; also known as SLC6A4), which are key molecules involved in depression.
QTL Mapping and Identification of Candidate Genes for Heat Tolerance at the Flowering Stage in Rice
Authors: Chen Lei , Wang Qiang , Tang Maoyan , Zhang Xiaoli , Pan Yinghua , Yang Xinghai , Gao Guoqing , Lv Ronghua , Tao Wei , Jiang Ligeng , Liang Tianfeng
Published: January 2021

High-temperature stress can cause serious abiotic damage that limits the yield and quality of rice. Heat tolerance (HT) during the flowering stage of rice is a key trait that can guarantee a high and stable yield under heat stress. HT is a complex trait that is regulated by multiple quantitative trait loci (QTLs); however, few underlying genes have been fine mapped and cloned. In this study, the F2:3 population derived from a cross between Huanghuazhan (HHZ), a heat-tolerant cultivar, and 9311, a heat-sensitive variety, was used to map HT QTLs during the flowering stage in rice. A new major QTL, qHTT8, controlling HT was identified on chromosome 8 using the bulked-segregant analysis (BSA)-seq method. The QTL qHTT8 was mapped into the 3,555,000–4,520,000 bp, which had a size of 0.965 Mb. The candidate region of qHTT8 on chromosome 8 contained 65 predicted genes, and 10 putative predicted genes were found to be associated with abiotic stress tolerance. Furthermore, qRT-PCR was performed to analyze the differential expression of these 10 genes between HHZ and 9311 under high temperature conditions. LOC_Os08g07010 and LOC_Os08g07440 were highly induced in HHZ compared with 9311 under heat stress. Orthologous genes of LOC_Os08g07010 and LOC_Os08g07440 in plants played a role in abiotic stress, suggesting that they may be the candidate genes of qHTT8. Generally, the results of this study will prove useful for future efforts to clone qHTT8 and breed heat-tolerant varieties of rice using marker-assisted selection.
Pivotal Role of Tenascin-W (-N) in Postnatal Incisor Growth and Periodontal Ligament Remodeling
Authors: Imhof Thomas , Balic Anamaria , Heilig Juliane , Chiquet-Ehrismann Ruth , Chiquet Matthias , Niehoff Anja , Brachvogel Bent , Thesleff Irma , Koch Manuel
Published: January 2021

The continuously growing mouse incisor provides a fascinating model for studying stem cell regulation and organ renewal. In the incisor, epithelial and mesenchymal stem cells assure lifelong tooth growth. The epithelial stem cells reside in a niche known as the cervical loop. Mesenchymal stem cells are located in the nearby apical neurovascular bundle and in the neural plexus. So far, little is known about extracellular cues that are controlling incisor stem cell renewal and guidance. The extracellular matrix protein tenascin-W, also known as tenascin-N (TNN), is expressed in the mesenchyme of the pulp and of the periodontal ligament of the incisor, and is closely associated with collagen 3 fibers. Here, we report for the first time the phenotype of tenascin-W/TNN deficient mice, which in a C57BL/6N background exhibit a reduced body weight and lifespan. We found major defects in the alveolar bone and periodontal ligament of the growing rodent incisors, whereas molars were not affected. The alveolar bone around the incisor was replaced by a dense scar-like connective tissue, enriched with newly formed nerve fibers likely leading to periodontal pain, less food intake and reduced body weight. Using soft food to reduce mechanical load on the incisor partially rescued the phenotype.In situhybridization and Gli1 reporter mouse experiments revealed decreased hedgehog signaling in the incisor mesenchymal stem cell compartment, which coordinates the development of mesenchymal stem cell niche. These results indicate that TNN deficiency in mice affects periodontal remodeling and increases nerve fiber branching. Through periodontal pain the food intake is reduced and the incisor renewal and the neurovascular sonic hedgehog secretion rate are reduced. In conclusion, tenascin-W/TNN seems to have a primary function in rapid periodontal tissue remodeling and a secondary function in mechanosensation.
Dim Light at Night Impairs Daily Variation of Circulating Immune Cells and Renal Immune Homeostasis
Authors: Okuliarova Monika , Mazgutova Nikoleta , Majzunova Miroslava , Rumanova Valentina Sophia , Zeman Michal
Published: January 2021

Dim light at night (dLAN) has become a pervasive part of the modern world, and growing evidence shows its association with increased health risks. Though this link is attributed to a disturbed circadian clock, the underlying mechanisms that can explain how circadian disruption from dLAN causes negative health effects remain unclear. Here, we exposed rats to a light–dark cycle (12:12 h) with low-intensity light at night (~2 lx) for 2 and 5 weeks and explored the steady-state pattern of circulating immune cells and renal immune-related markers, which are well controlled by the circadian clock. After 5 weeks, dLAN impaired the daily variation in several types of white blood cells, especially monocytes and T cells. Two-week dLAN caused a reduction in blood monocytes and altered gene expression of macrophage marker Cd68 and monocyte-attracting chemokine Ccl2 in the kidney. Interestingly, dLAN decreased renal 3-nitrotyrosine levels and resulted in up-regulation of the main endogenous antioxidant pathways, indicating a disturbance in the renal redox balance and an activation of compensatory mechanisms. These effects paralleled the altered renal expression of the molecular clock components and increased plasma corticosterone levels. Together, our results show that chronic exposure to dLAN weakened the circadian control of daily variation of circulating immune cells and disturbed renal immune and redox homeostasis. Consequences of this dLAN-disturbed immune balance on the ability of the immune system to cope with other challenges should by clarified in further studies.
Single-Cell Analysis Reveals Characterization of Infiltrating T Cells in Moderately Differentiated Colorectal Cancer
Authors: Yang Xi , Qi Quan , Pan Yuefen , Zhou Qing , Wu Yinhang , Zhuang Jing , Xu Jiamin , Pan Mingyue , Han Shuwen
Published: January 2021

Objective

This study aimed to characterize the tumor-infiltrating T cells in moderately differentiated colorectal cancer.

Methods

Using single-cell RNA sequencing data of isolated 1632 T cells from tumor tissue and 1252 T cells from the peripheral blood of CRC patients, unsupervised clustering analysis was performed to identify functionally distinct T cell populations, followed by correlations and ligand-receptor interactions across cell types. Finally, differential analysis of the tumor-infiltrating T cells between colon cancer and rectal cancer were carried out.

Results

A total of eight distinct T cell populations were identified from tumor tissue. Tumor-Treg showed a strong correlation with Th17 cells. CD8+TRM was positively correlated with CD8+IEL. Seven distinct T cell populations were identified from peripheral blood. There was a strong correlation between CD4+TN and CD4+blood-TCM. Colon cancer and rectal cancer showed differences in the composition of tumor-infiltrating T cell populations. Tumor-infiltrating CD8+IEL cells were found in rectal cancer but not in colon cancer, while CD8+ TN cells were found in the peripheral blood of colon cancer but not in that of rectal cancer. A larger number of tumor-infiltrating CD8+ Tex (88.94%) cells were found in the colon cancer than in the rectal cancer (11.06%). The T cells of the colon and rectal cancers showed changes in gene expression pattern.

Conclusions

We characterized the T cell populations in the CRC tumor tissue and peripheral blood.
Semi-Automated Cell and Tissue Analyses Reveal Regionally Specific Morphological Alterations of Immune and Neural Cells in a Porcine Middle Cerebral Artery Occlusion Model of Stroke
Authors: Spellicy Samantha E. , Scheulin Kelly M. , Baker Emily W. , Jurgielewicz Brian J. , Kinder Holly A. , Waters Elizabeth S. , Grimes Janet A. , Stice Steven L. , West Franklin D.
Published: January 2021

Histopathological analysis of cellular changes in the stroked brain provides critical information pertaining to inflammation, cell death, glial scarring, and other dynamic injury and recovery responses. However, commonly used manual approaches are hindered by limitations in speed, accuracy, bias, and the breadth of morphological information that can be obtained. Here, a semi-automated high-content imaging (HCI) and CellProfiler histological analysis method was developed and used in a Yucatan miniature pig permanent middle cerebral artery occlusion (pMCAO) model of ischemic stroke to overcome these limitations. Evaluation of 19 morphological parameters in IBA1+ microglia/macrophages, GFAP+ astrocytes, NeuN+ neuronal, FactorVIII+ vascular endothelial, and DCX+ neuroblast cell areas was conducted on porcine brain tissue 4 weeks post pMCAO. Out of 19 morphological parameters assessed in the stroke perilesional and ipsilateral hemisphere regions (38 parameters), a significant change in 3838 measured IBA1+ parameters, 3438 GFAP+ parameters, 3238 NeuN+ parameters, 3138 FactorVIII+ parameters, and 2838 DCX+ parameters were observed in stroked vs. non-stroked animals. Principal component analysis (PCA) and correlation analyses demonstrated that stroke-induced significant and predictable morphological changes that demonstrated strong relationships between IBA1+, GFAP+, and NeuN+ areas. Ultimately, this unbiased, semi-automated HCI and CellProfiler histopathological analysis approach revealed regional and cell specific morphological signatures of immune and neural cells after stroke in a highly translational porcine model. These identified features can provide information of disease pathogenesis and evolution with high resolution, as well as be used in therapeutic screening applications.
QT Interval Dispersion as a Predictor of Clinical Outcome in Acute Ischemic Stroke
Authors: Tang Hefei , Sun Jiayao , Wang Yu , Jie Xu , Ma Yan , Wang Anxin , Zhang Yijun , Wang Xingao , Wang Yongjun
Published: January 2021

Background and Purpose: QT dispersion (QTd) abnormalities are widely documented in stroke patients. This study aims to investigate the association between QTd and clinical outcomes in IS patients.

Methods: IS patients registered in the Blood Pressure and Clinical Outcome in transient ischemic attack (TIA) or IS (BOSS) registry between 2012 and 2014 within 24 h of onset were analyzed. In this prospective observational study, we identified 1,522 IS cases with adequate electrocardiographic evaluations to assess QTd after the index stroke. Patients were classified into four groups based on the quartile of QTd, with the lowest group as the reference. The primary stroke outcome was defined as a modified Rankin Scale score ≥3 at 1-year. Multiple logistic regressions were utilized to investigate the association between QTd and outcome events.

Results: The mean QTd across all cases was 57 ms (40–83). Functional dependency or death was documented in 214 (14.98%) cases at 1 year. After adjusting for confounders, the prevalence of death and major disability (mRS ≥ 3) showed significant differences according to the quartile of QTd, with the risk of death and major disability (mRS ≥ 3) at 1 year being significantly higher for patients in Q4 than for those in Q1 (adjusted OR = 1.626, 95% CI:1.033–2.560). However, there were no significant correlation between QTd and the event outcomes at 1 year.

Conclusions: QTd was associated with poor functional outcomes at 1 year. QTd is a useful surrogate marker for adverse functional prognosis, which might help to stratify risk in patients with acute IS.
Evaluation of Changes in Preoperative Cortical Excitability by Navigated Transcranial Magnetic Stimulation in Patients With Brain Tumor
Authors: Neville Iuri Santana , Gomes dos Santos Alexandra , Almeida Cesar Cimonari , Hayashi Cintya Yukie , Solla Davi Jorge Fontoura , Galhardoni Ricardo , de Andrade Daniel Ciampi , Brunoni Andre Russowsky , Teixeira Manoel Jacobsen , Paiva Wellingson Silva
Published: January 2021

Background: This prospective study aimed to evaluate the cortical excitability (CE) of patients with brain tumors surrounding or directly involving the corticospinal tract (CST) using navigated transcranial magnetic stimulation (nTMS).

Methods: We recruited 40 patients with a single brain tumor surrounding or directly involving the CST as well as 82 age- and sex-matched healthy controls. The patients underwent standard nTMS and CE evaluations. Single and paired pulses were applied to the primary motor area (M1) of both affected and unaffected cerebral hemispheres 1 week before surgery. The CE parameters included resting motor threshold (RMT), motor evoked potential (MEP) ratio for 140 and 120% stimulus (MEP 140/120 ratio), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Motor outcome was evaluated on hospital discharge and on 30-day and 90-day postoperative follow-up.

Results: In the affected hemispheres of patients, SICI and ICF were significantly higher than in the unaffected hemispheres (p=0.002 and p=0.009, respectively). The 140/120 MEP ratio of patients' unaffected hemispheres was lower than that in controls (p=0.001). Patients with glioblastomas (GBM) had a higher interhemispheric RMT ratio than patients with grade II and III gliomas (p = 0.018). A weak correlation was observed among the RMT ratio and the preoperative motor score (R2 = 0.118, p = 0.017) and the 90-day follow-up (R2 = 0.227, p = 0.016).

Conclusion: Using preoperative nTMS, we found that brain hemispheres affected by tumors had abnormal CE and that patients with GBM had a distinct pattern of CE. These findings suggest that tumor biological behavior might play a role in CE changes.
Quantifying a Learning Curve for Video Head Impulse Test: Pitfalls and Pearls
Authors: Korda Athanasia , Sauter Thomas C. , Caversaccio Marco Domenico , Mantokoudis Georgios
Published: January 2021

Objective: The video head impulse test (vHIT) is nowadays a fast and objective method to measure vestibular function. However, its usability is controversial and often considered as a test performed by experts only. We sought to study the learning curve of novices and to document all possible mistakes and pitfalls in the process of learning.

Methods: In a prospective cohort observational study, we included 10 novices. We tested their ability to perform correctly horizontal head impulses recorded with vHIT. We assessed vHITs in 10 sessions with 20 impulses per session giving a video instruction after the first session (S1) and individual feedback from an expert for session 2 (S2) up to session 10 (S10). We compared VOR gain, the HIT acceptance rate by the device algorithm, mean head velocity, acceleration, excursion, and overshoot between sessions.

Results: A satisfying number of accepted HITs (80%) was reached after an experience of 160 vHITs. Mean head velocity between sessions was always in accepted limits. Head acceleration was too low at the beginning (S1) but improved significantly after the video instruction (p = 0.001). Mean head excursion and overshoot showed a significant improvement after 200 head impulses (p < 0.001 each).

Conclusions: We showed that novices can learn to perform head impulses invHIT very fast provided that they receive instructions and feedback from an experienced examiner. Video instructions alone were not sufficient. The most common pitfall was a low head acceleration.
Does Impairment of Adult Neurogenesis Contribute to Pathophysiology of Alzheimer's Disease? A Still Open Question
Authors: Li Puma Domenica Donatella , Piacentini Roberto , Grassi Claudio
Published: January 2021

Adult hippocampal neurogenesis is a physiological mechanism contributing to hippocampal memory formation. Several studies associated altered hippocampal neurogenesis with aging and Alzheimer's disease (AD). However, whether amyloid-β protein (Aβ)/tau accumulation impairs adult hippocampal neurogenesis and, consequently, the hippocampal circuitry, involved in memory formation, or altered neurogenesis is an epiphenomenon of AD neuropathology contributing negligibly to the AD phenotype, is, especially in humans, still debated. The detrimental effects of Aβ/tau on synaptic function and neuronal viability have been clearly addressed both in in vitro and in vivo experimental models. Until some years ago, studies carried out on in vitro models investigating the action of Aβ/tau on proliferation and differentiation of hippocampal neural stem cells led to contrasting results, mainly due to discrepancies arising from different experimental conditions (e.g., different cellular/animal models, different Aβ and/or tau isoforms, concentrations, and/or aggregation profiles). To date, studies investigating in situ adult hippocampal neurogenesis indicate severe impairment in most of transgenic AD mice; this impairment precedes by several months cognitive dysfunction. Using experimental tools, which only became available in the last few years, research in humans indicated that hippocampal neurogenesis is altered in cognitive declined individuals affected by either mild cognitive impairment or AD as well as in normal cognitive elderly with a significant inverse relationship between the number of newly formed neurons and cognitive impairment. However, despite that such information is available, the question whether impaired neurogenesis contributes to AD pathogenesis or is a mere consequence of Aβ/pTau accumulation is not definitively answered. Herein, we attempted to shed light on this complex and very intriguing topic by reviewing relevant literature on impairment of adult neurogenesis in mouse models of AD and in AD patients analyzing the temporal relationship between the occurrence of altered neurogenesis and the appearance of AD hallmarks and cognitive dysfunctions.
Research on the Role of Combined Chemotherapy and Radiotherapy in Patients With N+ Non-Metastatic Metaplastic Breast Carcinoma: A Competing Risk Analysis Model Based on the SEER database, 2000 to 2015
Authors: Ma Yifei , Yang Zejian , Gao Yihan , Li Kunlong , Qiu Pei , Chen Heyan , Pu Shengyu , Wang Bo , Zhou Can
Published: January 2021

Purpose

Due to the rarity of metaplastic breast carcinoma (MpBC), no randomized trials have investigated the role of combined chemotherapy and radiotherapy (CCRP) in this condition. We aimed to explore and identify the effectiveness of CCRP in patients with regional lymph node metastasis (N+) non-metastatic MpBC.

Materials and Methods

Data were obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program database. We assessed the effects of CCRP on overall survival (OS), breast cancer-specific survival (BCSS), and breast cancer-specific death (BCSD) using Kaplan-Meier analysis, competing risk model analysis, and competing risk regression mode analysis.

Results

A total of 707 women and 361 death cases were included in the unmatched cohort, of which 76.45% (276/361) were BCSD, and 23.55% (85/361) were non-breast cancer-specific deaths (non-BCSD). Both the ChemT and CCRP groups had better OS (ChemT group: HR: 0.59, 95% CI: 0.45–0.78, P<0.001; CCRP group: HR: 0.31, 95% CI: 0.23–0.41, P<0.001) and BCSS (ChemT group: HR: 0.63, 95% CI: 0.45–0.87, P<0.001; CCRP group: HR: 0.32, 95%CI: 0.22–0.46, P<0.001) than the non-therapy group. Subjects in the CCRP group tended to have significantly lower cumulative BCSD (Gray’s test, P=0.001) and non-BCSD (Gray’s test, P<0.001) than the non-therapy group or ChemT group. In competing risk regression model analysis, subjects in the CCRP group had a better prognosis in BCSD (HR: 0.710, 95% CI: 0.508–0.993, P=0.045) rather than the ChemT group (HR: 1.081, 95% CI: 0.761–1.535, P=0.660) than the non-therapy group.

Conclusion

Our study demonstrated that CCRP could significantly decrease the risk of death for both BCSD and non-BCSD and provided a valid therapeutic strategy for patients with N+ non-metastatic MpBC.