bluuebunny/crossref_metadata_2025 huggingface dataset:
Problems of Oral Health Protection of Disadvantaged Social Groups in the Chui Region
Authors: Yusupkhanov O. , Selpiev T. , Koshmuratov A.
Published: April 2021

In the Kyrgyz Republic, 22.4% of the population live below the poverty line. A sufficient number of problems related to improvement were identified. The problem of the availability of dental care is intractable for many states and often insoluble in many aspects of this issue. In his conclusions, the author proposes to solve or slightly alleviate this problem without attracting large financial flows. The problem of today is the insufficient funding of dentistry from the state to improve the state of the dental health of the population. Regardless of the patient’s social status, be it a child, an elderly patient, or a pregnant woman, the state allocates an average of ≈ 142 soms (about 1.5 US dollars).
POLICY AND IMPLEMENTATION OF EDUCATION MANAGEMENT BASED ON MADRASAH
Authors: Nurdiansyah Nana Meily , Hudriyah Hudriyah
Published: April 2021

This study aims to analyze policies from the socio-political scope as the basis for development in education in madrasah. Therefore, it goes on to say that this research was conducted through a descriptive qualitative approach to the type of library research, with the data source referring to literature data. The data analysis technique was carried out using content analysis, the scope of which consists of the depth of information content. The results showed that madrasah-based management is participatory management of madrasah by involving the principal, teachers, students, stakeholders, and the community to achieve the quality of education goals. The movement of education reform from centralization to decentralization abroad has been going on for 30 years, since 1960-1990. In Indonesia, constitutional reformation of education began to coincide with the reform era marked by the fall of the New Order in 1998. Education, which had been the matter of the central government, since the enactment of regional autonomy through Law number 22 of 1999 concerning Regional Government, was later amended by Law number 32 of the year. 2004, then the education affairs were handed over to the local government.
SCHOOL STRATEGY TO BUILD STUDENTS' SOCIAL SOLIDARITY DURING ONLINE LEARNING
Authors: Suwidiyanti Suwidiyanti , Anshori Isa
Published: April 2021

Teaching and learning in the school aim to enable students to gain knowledge and change behavior. Therefore, schools need to instil the values of social solidarity to respond to differences in society. Emile Durkheim's theories form the basis of the analysis of social facts about social solidarity. This study aims to describe the school's strategic steps in building social solidarity among students during online learning due to the impact of COVID-19 at SMA Muhammadiyah 2 Sidoarjo. This research uses a qualitative approach to the type of case study. Data collection was taken through interviews and documentation. The data were analyzed using the Miles and Huberman model with data collection, data reduction, data display, and conclusion/verification. The technique of data validity by triangulation. The results showed that strategic steps in building the social solidarity of students during online learning include: (1) The school uses Moodle application to support online learning, which can control the teacher's learning activities; (2) The principal determines by instructing all teachers to a) Each learning hour uses virtual face-to-face using zoom or google meet followed by Moodle application, b) Creating integrated learning tools in forming social solidarity values, c) Using learning methods and models that emphasize group learning; and (3) Schools facilitate infaq online.
ENGLISH LITERACY MANAGEMENT AT SMPI AL ABIDIN SURAKARTA
Authors: Hidayati Fithriyah Nurul
Published: April 2021

This study aims to analyze the implementation of school management to improve students' English literacy at SMP Islam Al Abidin Surakarta. This study uses a qualitative approach with a phenomenological method. The process of seeking and finding information related to English literacy improvement management is carried out through the 5W + 1H process. The study results showed that the implemented school management consisted of steps that supported English literacy starting from planning, organizing, implementing and evaluating activities. 1) The planning steps is related to determining goals, objectives, designing literacy activity programs, 2) organizing the resource, 3) implementing related to English literacy is through the following programs: (a) English Development Program, such as: English Camp, English Festival, Saturday Performance, Every day is English day, and Five Minutes Presentation (b) Literacy Programs, such as: Reading, Listening, Speaking Time and 4) controlling of implementing English literacy.
“ART AND CULTURE” LEARNING MANAGEMENT FOR STUDENTS’ INCREASED ACHIEVEMENT DURING THE COVID-19 PANDEMIC
Authors: Adham Anna Shopia , Mahmudah Fitri Nur
Published: April 2021

One of the keys to the success of learning is good management. During the Covid-19 pandemic, teachers need managerial skills for the learning process to take place. The purpose of this study is to determine the management of learning arts and culture to improve student achievement during the Covid-19 pandemic. The study employed the qualitative approach to research. Data collection techniques used were interviews, observation, and documentation. The results of this study indicate that the learning management that teachers need to do in Art and Culture is due to the characteristics, creation, communication, motivation, learning strategies, and discipline. The recommendations of this research can be used by teachers in developing culture and art learning during the Covid-19 pandemic. Hence, teachers will be able to provide learning to students, and students can attain improved skills and good learning outcomes.
ORGANIZATIONAL CULTURE IN THE ISLAMIC BOARDING SCHOOL : PHENOMENOLOGY REVIEW
Authors: Musaddad Ahmad
Published: April 2021

This research focuses on the facts and theories of organizational culture which include: 1) the formation of Salaf culture in modern Islamic boarding schools and 2) the maintenance of Salaf culture in the Modern Islamic boarding schools. This is a qualitative research with a phenomenological approach in the Salafiyah Syafi'iyah Islamic boarding school, Sukorejo, Situbondo. The results showed that organizational culture was formed by the founder's philosophy with the founder's education background and sourced from the salaf books known as four (4) elementary books. The maintenance of the organizational culture is manifested in the activities of the boarding school which include 1) Diniyah school obligations for all students; 2) Establishment of religious-based higher education institutions for mahasantri (Ma'had Aly organization); 3) Obligation to read the yellow book (kitab kuning) and the Koran properly for every student; 4) Obligation to pass basic Madrasah Diniyah; 5) Study of books at various places and times; 6) Wetonan, bandongan and Sorogan methods; 7) Method of muhafadloh or memorization; 8) curriculum system; and, 9) clothing and uniforms.
Four blessings and a funeral: Adomnán's theological map of Iona
Authors: Márkus Gilbert
Published: April 2021

Adomnán of Iona wrote a Life of Saint Columba, the founder of that monastery, but did not tell the story of Iona's foundation. Instead, the holiness of the monastery and its surrounding landscape, and their connection to the founder, were established by a narrative in the final chapter of Adomnán's work. In it we watch the final days of Columba's life and his movement across the island, blessing it and its inhabitants. The description is simple, but it is rich in references to scriptural, liturgical and sacramental themes, and it structures those themes spatially, revealing Adomnán's mental map of the island. Iona's various spaces and boundaries shape and express the lives of Columba's (and Adomnán's) monks, and so invite the reader to see how salvation is revealed in time and space, in movement, and in dwelling within the spatial order established by Columba's blessings.
Вулиці архаїчного Борисфена
Authors: Chistov Dmitriy
Published: April 2021

Стаття присвячена вивченню вуличної мережі Березанського поселення архаїчного періоду. Запропонована нова нумерація вулиць і житлових кварталів, яка може використовуватися у подальших дослідженнях. Робиться висновок про те, що планувальна сітка Борисфена ніколи не була ортогональною, але має ознаки організованого, одночасного планування з уніфікацією ширини вулиць та орієнтацією більшої їх частини за сторонами світу.
Виробництво скла чи його обробка? Ягорлицьке поселення у світлі нових досліджень
Authors: Kolesnychenko Anzhelika , Yatsuk Oleh
Published: April 2021

У статті висвітлено результати вивчення скляних намистин з Ягорлицького поселення та зразків піску довкола нього. У дослідженні використовувались методи природничих наук, а саме XRF, SEM-EDS та ICPMS. Хімічний склад намистин із золистого скла та піску свідчить про їх спорідненість за макроелементами та рідкісноземельними елементами. Отримані результати підтверджують гіпотезу А.С. Островерхова про місцеве виробництво скла.
Знаряддя рибальства, знайдені у приміських садибах Ольвії
Authors: Papanova Valentina , Lyashko Svitlana
Published: April 2021

Стаття присвячена аналізу та класифікації 41 рибальського грузила з приміських садиб Ольвії – Широка балка 6 другої третини V – початку III ст. до н.е. та Широка балка 7 кінця V – 30-х років IV ст. до н.е.

На сьогодні відсутня статистика і комплексна типологічна класифікація цих артефактів для всіх періодів існування Ольвії та її сільськогосподарської округи. Це ускладнює їх вивчення, визначення функціонального призначення, створення відповідної типології, а також не сприяє удосконаленню класифікації знарядь риболовлі, вивченню процесів, методів, особливостей рибальства у конкретних регіонах. Окрім того, функціональне призначення деяких видів грузил досі залишається дискусійним.

Відповідь на запитання щодо практичного використання грузил з садиб треба шукати у міждисциплінарному просторі й аналізі взаємозв’язку конкретних рибальських знарядь із особливостями відповідної акваторії та видового складу риби.
Теракотові статуетки із зображенням «п’яних Гераклів» з Північного Причорномор’я
Authors: Savelieva Kateryna
Published: April 2021

На античних пам’ятках Північного Причорномор’я у 1868 і 1988 рр. були виявлені теракотові статуетки із зображенням п’яного чоловіка, що сидить на скелі. Цей тип теракот є відомим у літературі під назвою «п’яний Геракл». У статті розглянуті різні варіанти інтерпретації цих статуеток. Акцентується увага на деяких деталях вбрання, які дозволяють стверджувати, що теракоти представляють зображення акторів давньої або середньої аттичної комедії. Запропоновано новий погляд на їхню інтерпретацію.
Декоративні елементи вбрання населення Степового Побужжя
Authors: Klochko Liubov
Published: April 2021

У статті йдеться про особливості іконографії та семантики образів, зображення яких вміщено на золотих ювелірних виробах – прикрасах костюмів соціальної верхівки суспільства. Розглянуто знакові функції головного убору модія, а також знімних прикрас у вбранні скіфів.
Пам’ятник невідомому алану поблизу озера Катлабух
Authors: Dobroliubskii Andrii , Smyrnov Ihor
Published: April 2021

Стаття присвячена вивченню захоронення аланського воїна зі скарбом візантійських монет ХІІ ст. Ці алани брали участь разом із кипчаками у болгаро-візантійській війні й у битві на Тревентському перевалі в 1190 р. на боці болгар і повернулися додому з багатою здобиччю.
Поселення «Городок» і перспективи дослідження середньовічної фортеці «Баликлей»
Authors: Gospodarenko Oksana
Published: April 2021

У статті подаються результати роботи експедиції Миколаївського державного педагогічного інституту під керівництвом Ю.С. Гребенникова у 1998 р. поблизу с. Городок Варюшинської сільради Веселинівського р-ну Миколаївської обл. Матеріали звіту друкуються вперше.

Як середньовічна пам’ятка, поселення Городок серед археологів відоме також як фортеця Баликлей. Ймовірно, у часи Золотої Орди тут розміщувалася кочова ставка хана, а саме місто було торговим і ремісничим центром у Північно-Західному Причорномор’ї. Це підтверджується знахідками монет золотоординських ханів. Є припущення, що у XV ст. у фортеці знаходився монетний двір (тимчасовий або похідний) і карбували монети хана Менглі-Ґірея І (В. Пиворович).
Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling
Authors: Wang Feng , Wang Wenbo , Kong Lingchi , Shi Li , Wang Mengwei , Chai Yimin , Xu Jia , Kang Qinglin
Published: April 2021

Both osteogenic differentiation and the pro-angiogenic potential of bone marrow mesenchymal stem cells (BMSCs) contribute to bone regeneration during distraction osteogenesis (DO). Adrenomedullin 2 (ADM2), an endogenous bioactive peptide belonging to the calcitonin gene-related peptide family, exhibits various biological activities associated with the inhibition of inflammation and the attenuation of ischemic-hypoxic injury. However, the effects and underlying mechanisms of ADM2 in osteogenic differentiation and the pro-angiogenic potential of BMSCs, along with bone regeneration, remain poorly understood. In the present study, we found that osteogenic induction enhanced the pro-angiogenic potential of BMSCs, and ADM2 treatment further improved the osteogenic differentiation and pro-angiogenic potential of BMSCs. Moreover, the accumulation and activation of β-catenin, which is mediated by the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the activation of protein kinase B (AKT), have been shown to contribute to the effects of ADM2 on BMSCs. In vivo, ADM2 accelerated vessel expansion and bone regeneration, as revealed by improved radiological and histological manifestations and the biomechanical parameters in a rat DO model. Based on the present results, we concluded that ADM2 accelerates bone regeneration during DO by enhancing the osteogenic differentiation and pro-angiogenic potential of BMSCs, partly through the NF-κB/β-catenin and AKT/β-catenin pathways. Moreover, these findings imply that BMSC-mediated coupling of osteogenesis and angiogenesis may be a promising therapeutic strategy for DO patients.
Grain Configuration Effect on Pore Water Pressure in Debris Flow
Authors: Yang Taiqiang , Liu Daochuan , Li Yong , Guo Xiaojun , Zhang Jun , Jiang Yu
Published: April 2021

The generation and development of excess pore water pressure directly affects the grain interaction in debris flow, which can significantly reduce the friction strength and promote the movement of debris flow. It has been found that coarse grains favor the increase in excess pore water pressure, but the effect due to grain configuration is missing in studies. In order to study the influence of grain configuration, field investigations and laboratory tests were carried out for two typical cases, i.e., flow with coarse grains evenly mixed (case I) and flow with coarse grains floating on the surface (case II). The results show that case II generates much higher excess pore water pressure than case I. The variation of relative excess pore water pressure (Ur) with time (t) satisfies the power function relationship: Ur = mt–n. Case II often has a smaller n value, meaning a low dissipation rate of excess pore water pressure. This study is helpful for a better understanding of granular effects in debris flow.
The Semiotics of Test Design: Conceptual Framework on Optimal Item Features in Educational Assessment Across Cultural Groups, Countries, and Languages
Authors: Solano-Flores Guillermo
Published: April 2021

This paper offers a conceptual framework on test design from the perspective of social semiotics. Items are defined as arrangements of features intended to represent information, convey meaning, and capture information on the examinees’ knowledge or skills on a given content. The conceptual framework offers a typology of semiotic resources used to create items and discusses item representational complexity—the multiple ways in which the semiotic resources of an item are related to each other—and item semiotic alignment—the extent to which examinees share cultural experience encoded by items. Since the ability to make sense of items is shaped by the examinees’ level of familiarity with the social conventions underlying the ways in which information is represented, unnecessary representational complexity and limited semiotic alignment may increase extraneous item cognitive load and adversely impact the performance of examinees from certain populations. Semiotic test design allows specification of optimal pools of semiotic resources to be used in creating items with the intent to minimize representational complexity and maximize semiotic alignment for the maximum number of individuals in diverse populations of examinees. These pools of semiotic resources need to be specific to the content assessed, the characteristics of the populations of examinees, the languages involved, etc., and determined based on information produced by cross-cultural frequency analyses, cognitive interviews, focus groups, and expert panels.
From Caterpillars to Butterflies: Exploring Pre-service Teachers’ Transformations While Navigating Global Citizenship Education
Authors: Lourenço Mónica
Published: April 2021

Global citizenship education (GCE), which aims to empower learners to become proactive contributors to a more sustainable world, has recently emerged as one of the educational priorities of the 21st century. However, according to recent research, GCE is not yet embedded in teachers’ practice in a systematic manner, remaining an optional choice for willing and able teachers. Within this framework, this paper reports on a multiple case study conducted with a group of pre-service teachers (PSTs) in Portugal who were introduced to GCE in the third and final year of an undergraduate degree in Elementary Education. The study aimed to understand whether, how and to what extent the teacher education program contributed to PSTs’ professional development. Data consisted of individual reflections written by the PSTs throughout an academic year. These were analyzed thematically using grounded theory to formulate an original framework inspired by the butterfly’s metamorphosis. Results show that the experience with GCE was positive in developing PSTs’ professional knowledge and in helping them (re)construct their “becoming” teacher identities, albeit to different degrees. Implications of the results for teacher education programs are discussed.
Plasma Free Amino Acids and Risk of Cardiovascular Disease in Chinese Patients With Type 2 Diabetes
Authors: Li Tie , Luo Hui-Huan , Feng Xiao-Fei , Bai Yu , Fang Zhong-Ze , Wu Gui-Gang , Wu Jian-Lin
Published: April 2021

Objectives

This study aimed to explore associations between plasma free amino acids (PFAA) and risk of cardiovascular disease (CVD) in Chinese with Type 2 diabetes (T2D).

Methods

We retrieved 741 inpatients with T2D consecutively from tertiary hospital. Twenty-three PFAA were measured. CVD was defined as having coronary heart disease (CHD) or stroke. Principal component analysis was used to extract factors of PFAA. Factors and their components were introduced into binary logistic regressions as continuous and tertiles to obtain OR (odds ratio) and 95% confidence interval (CI) for CVD (or its components) risk.

Results

Of 741 inpatients, 282 (38.1%) had CVD (CHD alone: 122, stroke alone: 109, both: 51). Five factors were extracted, accounting for 65% of the total variance. Factor 3 composed of glutamate and tryptophan was associated with increased CVD risk (ORs, 95%CI of top vs. bottom tertiles: 1.60, 1.02–2.50 for CVD; 2.19, 1.17–4.07 for stroke, 1.51, 0.83–2.73 for CHD); the ORs (top vs. bottom tertiles) of glutamate were 2.62 (95%CI, 1.18–5.84) for stroke and 1.44 (0.80–2.61) for CHD; the ORs (top vs. bottom tertiles) of tryptophan were 1.50 (0.81–2.75) for stroke and 1.07 (0.58–1.97) for CHD. Comparable results were observed according to important confounders (all P for interaction >0.05).

Conclusions

Elevated factor 3 composed of glutamate and tryptophan was associated with increased CVD, especially stroke in T2D in China.
Relationship Between Vitamin D and Hormones Important for Human Fertility in Reproductive-Aged Women
Authors: Chu Chang , Tsuprykov Oleg , Chen Xin , Elitok Saban , Krämer Bernhard K. , Hocher Berthold
Published: April 2021

Vitamin D deficiency is very common in women of reproductive age. Studies in animals suggests a link between vitamin D and reproductive hormone biosynthesis. A systematic analysis of the correlation of reproductive hormones in reproductive-aged women with both total and free vitamin D was, however, not done so far. This cross-sectional study was performed in 351 healthy reproductive age Caucasian women (median age, 28.0 years; interquartile ranges, 24.7-31.0 years). We measured serum levels of both total and free 25(OH)D, endocrinological, hematological and biochemical parameters. Spearman’s rank correlations were performed to assess the correlation between 25(OH)D metabolites and selected parameters. Total vitamin D and free vitamin D measurements correlated well (rho=0.912, p < 0.0001). Both total 25(OH)D and free 25(OH)D showed significant negative correlation with FAI (rho=-0.229, p<0.0001 and rho=-0.195, p<0.0001 for total and free 25(OH)D, respectively); LH (rho=-0.177, p=0.001 and rho=-0.114, p=0.04 for total and free 25(OH)D, respectively), testosterone (rho=-0.174, p=0.001 and rho=-0.190, p<0.0001 for total and free 25(OH)D, respectively) and AMH (rho=-0.130, p=0.015 and rho=-0.107, p=0.047 for total and free 25(OH)D, respectively). Our study showed comparable correlations of both total and free 25(OH)D with endocrinological parameters, i.e. inverse correlations with free androgen index, luteinizing hormone, testosterone, LH/FSH ratio, androstenedione and anti-Müllerian hormone, and also with hematological and biochemical parameters, i.e. inverse correlations with erythrocytes, hsCRP and leukocytes count, and positive correlation with transferrin saturation, mean corpuscular hemoglobin and mean corpuscular volume in healthy reproductive age women.
Coming Out to Play: Privacy, Data Protection, Children’s Health, and COVID-19 Research
Authors: Beauvais Michael J. S. , Knoppers Bartha Maria
Published: April 2021

The COVID-19 pandemic has underscored the need for new ways of thinking about data protection. This is especially so in the case of health research with children. The responsible use of children’s data plays a key role in promoting children’s well-being and securing their right to health and to privacy. In this article, we contend that a contextual approach that appropriately balances children’s legal and moral rights and interests is needed when thinking about data protection issues with children. We examine three issues in health research through a child-focused lens: consent to data processing, data retention, and data protection impact assessments. We show that these issues present distinctive concerns for children and that theGeneral Data Protection Regulationprovides few bright-line rules. We contend that there is an opportunity for creative approaches to children’s data protection when child-specific principles, such as the best interests of the child and the child’s right to be heard, are put into dialogue with the structure and logic of data protection law.
Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer
Authors: Jia Sinong , Li Lei , Xie Li , Zhang Weituo , Zhu Tengteng , Qian Biyun
Published: April 2021

Background

Lung cancer is the tumor with the highest morbidity and mortality, and has become a global public health problem. The incidence of lung cancer in men has declined in some countries and regions, while the incidence of lung cancer in women has been slowly increasing. Therefore, the aim is to explore whether estrogen-related genes are associated with the incidence and prognosis of lung cancer.

Methods

We obtained all estrogen receptor genes and estrogen signaling pathway genes in The Cancer Genome Atlas (TCGA), and then compared the expression of each gene in tumor tissues and adjacent normal tissues for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) separately. Survival analysis was performed of the differentially expressed genes in LUAD and LUSC patients separately. The diagnostic and prognostic values of the candidate genes were validated in the Gene Expression Omnibus (GEO) datasets.

Results

We found 5 estrogen receptor genes and 66 estrogen pathway genes in TCGA. A total of 50 genes were differently expressed between tumor tissues and adjacent normal tissues and 6 of the 50 genes were related to the prognosis of LUAD in TCGA. 56 genes were differently expressed between tumor tissues and adjacent normal tissues and none of the 56 genes was related to the prognosis of LUSC in TCGA. GEO datasets validated that the 6 genes (SHC1, FKBP4, NRAS, PRKCD, KRAS, ADCY9) had different expression between tumor tissues and adjacent normal tissues in LUAD, and 3 genes (FKBP4, KRAS, ADCY9) were related to the prognosis of LUAD.

Conclusions

The expressions of FKBP4 and ADCY9 are related to the pathogenesis and prognosis of LUAD. FKBP4 and ADCY9 may serve as biomarkers in LUAD screening and prognosis prediction in clinical settings.
Immune Modulation Plus Tumor Ablation: Adjuvants and Antibodies to Prime and Boost Anti-Tumor Immunity In Situ
Authors: van den Bijgaart Renske J. E. , Schuurmans Fabian , Fütterer Jurgen J. , Verheij Marcel , Cornelissen Lenneke A. M. , Adema Gosse J.
Published: April 2021

In situtumor ablation techniques, like radiotherapy, cryo- and heat-based thermal ablation are successfully applied in oncology for local destruction of tumor masses. Although diverse in technology and mechanism of inducing cell death, ablative techniques share one key feature: they generate tumor debris which remainsin situ. This tumor debris functions as an unbiased source of tumor antigens available to the immune system and has led to the concept ofin situcancer vaccination. Most studies, however, report generally modest tumor-directed immune responses following local tumor ablation as stand-alone treatment. Tumors have evolved mechanisms to create an immunosuppressive tumor microenvironment (TME), parts of which may admix with the antigen depot. Provision of immune stimuli, as well as approaches that counteract the immunosuppressive TME, have shown to be key to boost ablation-induced anti-tumor immunity. Recent advances in protein engineering have yielded novel multifunctional antibody formats. These multifunctional antibodies can provide a combination of distinct effector functions or allow for delivery of immunomodulators specifically to the relevant locations, thereby mitigating potential toxic side effects. This review provides an update on immune activation strategies that have been tested to act in concert with tumor debris to achievein situcancer vaccination. We further provide a rationale for multifunctional antibody formats to be applied together within situablation to boost anti-tumor immunity for local and systemic tumor control.
Hydroxychloroquine Inhibits Macrophage Activation and Attenuates Renal Fibrosis After Ischemia-Reperfusion Injury
Authors: Zheng Haofeng , Zhang Yannan , He Jiannan , Yang Zhe , Zhang Rui , Li Lei , Luo Zihuan , Ye Yongrong , Sun Qiquan
Published: April 2021

Chronic kidney disease (CKD), which is associated with high morbidity, remains a worldwide health concern, while effective therapies remain limited. Hydroxychloroquine (HCQ), which mainly targets toll-like receptor-7 (TLR-7) and TLR-9, is associated with a lower risk of incident CKD. Taking into account that TLR-9 is involved in the development of renal fibrosis and serves as a potential therapy target for CKD, we investigated whether HCQ could attenuate CKD via TLR-9 signal pathway. The effects of HCQ on renal tubulointerstitial fibrosis were further explored using a mouse model of renal tubulointerstitial fibrosis after ischemia/reperfusion injury. Bone marrow-derived macrophages were isolated to explore the effects of HCQ in vitro. Judicious use of HCQ efficiently inhibited the activation of macrophages and MAPK signaling pathways, thereby attenuating renal fibrosis in vivo. In an in vitro model, results showed that HCQ promoted apoptosis of macrophages and inhibited activation of macrophages, especially M2 macrophages, in a dose-dependent manner. Because TLR-7 is not involved in the development of CKD post-injury, a TLR-9 knockout mouse was used to explore the mechanisms of HCQ. The effects of HCQ on renal fibrosis and macrophages decreased after depletion of TLR-9 in vivo and in vitro. Taken together, this study indicated that proper use of HCQ could be a new strategy for anti-fibrotic therapy and that TLR-9 could be a potential therapeutic target for CKD following acute kidney injury.
Case Report: Reversal of Long-Standing Refractory Diffuse Non-Scarring Alopecia Due to Systemic Lupus Erythematosus Following Treatment With Tofacitinib
Authors: Chen Yu-Lan , Liu Li-Xiong , Huang Qin , Li Xue-Ying , Hong Xiao-Ping , Liu Dong-Zhou
Published: April 2021

The Janus kinases (JAKs) are intracellular tyrosine kinases involved in a broad variety of inflammatory cascades participating in the pathogenesis of systemic lupus erythematosus (SLE). Diffuse non-scarring alopecia is one of the most frequent cutaneous manifestations in SLE, resulting in devastating psychosocial consequences. Although recent studies have shown promising outcomes of the JAK inhibitors in SLE treatment, the efficacy of tofacitinib in diffuse non-scarring alopecia due to SLE has never been reported. Here we present a 29-year-old SLE patient with a 10-year history of refractory severe diffuse non-scarring alopecia who experienced dramatic hair regrowth with tofacitinib. Furthermore, we have made a systematic review regarding the potential effectiveness of tofacitinib in systemic and cutaneous lupus erythematosus. To the best of our knowledge, this is the first case study depicting an SLE patient with refractory alopecia who experienced impressive hair regrowth with the JAK1/3 inhibitor tofacitinib therapy, which contributes to expanding the field of possible uses of tofacitinib in SLE patients with difficult-to-treat cutaneous involvement, including severe alopecia.
ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer
Authors: Liu Jiazhou , Wei Yuxian , Wu Yushen , Li Jie , Sun Jiazheng , Ren Guosheng , Li Hongzhong
Published: April 2021

Tumor microenvironment (TME) is vital for the occurrence and development of breast cancer (BRCA). However, it remains challenging to understand the dynamic modulation of the stromal and immune components comprehensively in TME. Herein, we used ESTIMATE and CIBERSORT algorithm to estimate the number of stromal and immune components and the abundance of tumor-infiltrating immune cells (TICs) in 582 BRCA cases from gene expression omnibus (GEO) database. We employed three regression models including univariable Cox proportion, LASSO regression model and multivariate Cox regression, and identified 7 immune-specific genes related to BRCA survival. Of 7 genes, ATPase Secretory Pathway Ca2+ Transporting 2 (ATP2C2) attracts our attention for significantly predicting prognosis of BRCA patients. Further analysis indicated that ATP2C2 expression was closely related to the clinicopathological features (age, T- and N-staging) and negatively correlated with patients’ survival in BRCA. Gene Set Enrichment Analysis (GSEA) was performed to reveal pathway enrichment between ATP2C2high and ATP2C2low groups. The low ATP2C2 expression groups’ genes were mainly enriched for immune-related activities, while those in the ATP2C2 high-expression group were largely enriched in metabolic-related pathways. Notably, Pearson’s correlation analysis identified that ATP2C2 expression was positively correlated with T follicular helper (Tfh) cells, and negatively correlated with gamma delta (γδ) T cell, suggesting that ATP2C2 might be accountable for the maintenance of immune-dominant status for TME. To sum up, this study comprehensively analyzed the TME and shed light on prognostic immune-related biomarkers for BRCA. In particular, ATP2C2 might be helpful for predicting the prognosis of BRCA patients, which provided an extra insight for BRCA treatment.
Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge
Authors: Sahu Rajnish , Dixit Saurabh , Verma Richa , Duncan Skyla A. , Smith Lula , Giambartolomei Guillermo H. , Singh Shree R. , Dennis Vida A.
Published: April 2021

Recently we reported the immune-potentiating capacity of aChlamydiananovaccine (PLGA-rMOMP) comprising rMOMP (recombinant major outer membrane protein) encapsulated in extended-releasing PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. Here we hypothesized that PLGA-rMOMP would bolster immune-effector mechanisms to confer protective efficacy in mice against aChlamydia muridarumgenital challenge and re-challenge. Female BALB/c mice received three immunizations, either subcutaneously (SC) or intranasally (IN), before receiving an intravaginal challenge withC. muridarumon day 49 and a re-challenge on day 170. Both the SC and IN immunization routes protected mice against genital challenge with enhanced protection after a re-challenge, especially in the SC mice. The nanovaccine induced robust antigen-specific Th1 (IFN-γ, IL-2) and IL-17 cytokines plus CD4+proliferating T-cells and memory (CD44highCD62Lhigh) and effector (CD44highCD62Llow) phenotypes in immunized mice. Parallel induction of antigen-specific systemic and mucosal Th1 (IgG2a, IgG2b), Th2 (IgG1), and IgA antibodies were also noted. Importantly, immunized mice produced highly functional Th1 avidity and serum antibodies that neutralizedC. muridaruminfectivity of McCoy fibroblastsin-vitrothat correlated with their respective protection levels. The SC, rather than the IN immunization route, triggered higher cellular and humoral immune effectors that improved mice protection against genitalC. muridarum.We report for the first time that the extended-releasing PLGA 85:15 encapsulated rMOMP nanovaccine confers protective immunity in mice against genitalChlamydiaand advances the potential towards acquiring a nano-basedChlamydiavaccine.
Analysis of LncRNA-mRNA Co-Expression Profiles in Patients With Polycystic Ovary Syndrome: A Pilot Study
Authors: Sun Xiuhong , Liu Yishan , Gao Xinyu , Du Mengxuan , Gao Mengge , Zhong Xingming , Wei Xiangcai
Published: April 2021

Purpose

This study aimed to investigate the profiles of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in peripheral blood samples collected from polycystic ovary syndrome (PCOS) patients. In addition, an in-depth bioinformatics analysis regarding the lncRNA-mRNA co-expression network was performed.

Methods

High-throughput sequencing was used to measure the profiles of mRNAs and lncRNAs expressed in the peripheral blood samples isolated from six patients (three patients with PCOS and three normal women). In addition, five differentially expressed lncRNAs were chosen to validate the results of high-throughput sequencing by quantitative RT-PCR (qRT-PCR). Furthermore, a lncRNA-mRNA co-expression network was constructed using the Cytoscape software.

Results

A total of 14,276 differentially expressed mRNAs and 4,048 differentially expressed lncRNAs were obtained from the RNA-seq analysis of PCOS patients and healthy controls (adjusted q-value < 0.05, Fold change >2.0).The qRT-PCR results were consistent with the data obtained through high-throughput sequencing. Gene ontology (GO) and KEGG pathway analyses showed that the differentially expressed mRNAs were enriched in the chemokine signaling pathway. In addition, the analysis of the lncRNA-mRNA co-expression network of the chemokine signaling pathway showed the involvement of 6 mRNAs and 42 lncRNAs.

Conclusion

Clusters of mRNAs and lncRNAs were aberrantly expressed in the peripheral blood of PCOS patients compared with the controls. In addition, several pairs of lncRNA-mRNAs in the chemokine signaling pathway may be related to PCOS genetically.
Computed Tomography-Guided Methylene Blue Localization: Single vs. Multiple Lung Nodules
Authors: Lin Chia-Ying , Chang Chao-Chun , Huang Li-Ting , Chung Ta-Jung , Liu Yi-Sheng , Yen Yi-Ting , Tseng Yau-Lin
Published: April 2021

Background: Preoperative localization for small invisible and impalpable pulmonary nodules is important in single-port video-assisted thoracoscopic surgery (VATS). Localization of multiple pulmonary nodules during VATS resection remains challenging. The aim of our study is to elucidate the efficacy of preoperative CT-guided methylene blue localization of both single and multiple pulmonary nodules.

Methods: Consecutive patients undergoing preoperative CT-guided methylene blue dye localization for lung nodules, followed by VATS resection, were retrospectively analyzed between January 2014 and November 2019. Chi-square tests, Fisher's exact test and independent T-test were used to compare variables between the groups. Logistic regression was used to identify risk factors for procedure-related complications.

Results: A total of 388 patients, including 337 with single nodule and 51 with multiple nodules, were analyzed. The success rate of preoperative CT-guided methylene blue localization for both single and multiple pulmonary nodules were comparable as 98.8% (333/337) vs. 100% (108/108). The procedure time was longer (23.2 ± 9.4 vs. 7.6 ± 4.8 min, p < 0.001) and risk of pneumothorax was higher (47.1 vs. 25.5%, p = 0.002) in the multiple nodule group. The procedure time (OR 1.079; 95% CI = 1.041–1.118; p < 0.001) was an independent risk factor for pneumothorax. Nodule depth (OR 2.829; 95% CI = 1.259–6.356; p = 0.011) was an independent risk factor for pulmonary hemorrhage.

Conclusions: Preoperative CT-guided methylene blue localization for both single and multiple pulmonary nodules is safe, feasible, and effective.
The Succession of the Gut Microbiota in Insects: A Dynamic Alteration of the Gut Microbiota During the Whole Life Cycle of Honey Bees (Apis cerana)
Authors: Dong Zhi-Xiang , Chen Yi-Fei , Li Huan-Yuan , Tang Qi-He , Guo Jun
Published: April 2021

The Asian honey bee Apis cerana is a valuable biological resource insect that plays an important role in the ecological environment and agricultural economy. The composition of the gut microbiota has a great influence on the health and development of the host. However, studies on the insect gut microbiota are rarely reported, especially studies on the dynamic succession of the insect gut microbiota. Therefore, this study used high-throughput sequencing technology to sequence the gut microbiota of A. cerana at different developmental stages (0 days post emergence (0 dpe), 1 dpe, 3 dpe, 7 dpe, 12 dpe, 19 dpe, 25 dpe, 30 dpe, and 35 dpe). The results of this study indicated that the diversity of the gut microbiota varied significantly at different developmental stages (ACE, P = 0.045; Chao1, P = 0.031; Shannon, P = 0.0019; Simpson, P = 0.041). In addition, at the phylum and genus taxonomic levels, the dominant constituents in the gut microbiota changed significantly at different developmental stages. Our results also suggest that environmental exposure in the early stages of development has the greatest impact on the gut microbiota. The results of this study reveal the general rule of gut microbiota succession in the A. cerana life cycle. This study not only deepens our understanding of the colonization pattern of the gut microbiota in workers but also provides more comprehensive information for exploring the colonization of the gut microbiota in insects and other animals.
RNA-Mediated Control in Listeria monocytogenes: Insights Into Regulatory Mechanisms and Roles in Metabolism and Virulence
Authors: Krawczyk-Balska Agata , Ładziak Magdalena , Burmistrz Michał , Ścibek Katarzyna , Kallipolitis Birgitte H.
Published: April 2021

Listeria monocytogenes is an intracellular pathogen that is well known for its adaptability to life in a broad spectrum of different niches. RNA-mediated regulatory mechanisms in L. monocytogenes play important roles in successful adaptation providing fast and versatile responses to a changing environment. Recent findings indicate that non-coding RNAs (ncRNAs) regulate a variety of processes in this bacterium, such as environmental sensing, metabolism and virulence, as well as immune responses in eukaryotic cells. In this review, the current knowledge on RNA-mediated regulation in L. monocytogenes is presented, with special focus on the roles and mechanisms underlying modulation of metabolism and virulence. Collectively, these findings point to ncRNAs as important gene regulatory elements in L. monocytogenes, both outside and inside an infected host. However, the involvement of regulatory ncRNAs in bacterial physiology and virulence is still underestimated and probably will be better assessed in the coming years, especially in relation to discovering the regulatory functions of 5′ and 3′ untranslated regions and excludons, and by exploring the role of ncRNAs in interaction with both bacterial and host proteins.
Congenital Human Cytomegalovirus Infection Inducing Sensorineural Hearing Loss
Authors: Xia Wenwen , Yan Hui , Zhang Yiyuan , Wang Congcong , Gao Wei , Lv Changning , Wang Wentao , Liu Zhijun
Published: April 2021

Human cytomegalovirus (HCMV) is the primary cause of congenital infections. Despite its clinical significance, congenital HCMV infection is frequently overlooked clinically since most affected infants are asymptomatic. Sensorineural hearing loss (SNHL) is one of the most widely known disorders caused by congenital HCMV infection. The potential mechanism, however, remains unknown to date. The mechanism by which congenital HCMV infection induces sensorineural deafness has been partly characterized, leading to advancements in diagnosis, therapy, and prevention strategies. HCMV-induced hearing loss primarily involves immune responses, the release of inflammatory factors by natural killer (NK) cells, apoptosis of cochlear spiral ganglion, and potential changes due to vascular dysfunction. The diagnosis of HCMV induced SNHL includes serological examination to mothers, imaging, and amniotic fluid examination. Ganciclovir, mainly used for antiviral therapy and behavioral prevention, can, to some degree, prevent congenital HCMV infection. The role of HCMV infection in hearing loss needs further investigation since the mechanism of hearing loss caused by cytomegalovirus infection is not well understood. Although some advancement has been made in diagnosing and treating SNHL, more improvement is needed. A comprehensive understanding of cytomegalovirus’s pathogenesis is of key importance for preventing, diagnosing, and treating SNHL.
Frozen Mother’s Own Milk Can Be Used Effectively to Personalize Donor Human Milk
Authors: Torrez Lamberti Monica F. , Harrison Natalie A. , Bendixen Marion M. , DeBose-Scarlett Evon M. , Thompson Sharon C. , Neu Josef , Parker Leslie Ann , Lorca Graciela L.
Published: April 2021

Feeding preterm infants mother’s own milk (MOM) lowers rates of sepsis, decreases necrotizing enterocolitis, and shortens hospital stay. In the absence of freshly expressed MOM, frozen MOM (FMOM) is provided. When MOM is unavailable, preterm infants are often fed pasteurized donor human milk (DHM), rendering it devoid of beneficial bacteria. We have previously reported that when MOM is inoculated into DHM to restore the live microbiota [restored milk (RM)], a similar microbial diversity to MOM can be achieved. Yet, it is unknown if a similar diversity to MOM can be obtained when FMOM is inoculated into DHM. The goal of this study was to determine whether a similar microbial composition to MOM could be obtained when FMOM is used to personalize DHM. To this end, a fresh sample of MOM was obtained and divided into fresh and frozen fractions. MOM and FMOM were inoculated into DHM at different dilutions: MOM/FMOM 10% (RM/FRM10) and MOM/FMOM 30% (RM/FRM30) and incubated at 37°C. At different timepoints, culture-dependent and culture-independent techniques were performed. Similar microbiota expansion and alpha diversity were observed in MOM, RM10, and RM30 whether fresh or frozen milk was used as the inoculum. To evaluate if microbial expansion would result in an abnormal activation on the innate immune system, Caco-2 epithelial cells were exposed to RM/FRM to compare interleukin 8 levels with Caco-2 cells exposed to MOM or DHM. It was found that RM samples did not elicit a significant increase in IL-8 levels when compared to MOM or FMOM. These results suggest that FMOM can be used to inoculate DHM if fresh MOM is unavailable or limited in supply, allowing both fresh MOM and FMOM to be viable options in a microbial restoration strategy.
Slow Protein Turnover Explains Limited Protein-Level Response to Diurnal Transcriptional Oscillations in Cyanobacteria
Authors: Karlsen Jan , Asplund-Samuelsson Johannes , Jahn Michael , Vitay Dóra , Hudson Elton P.
Published: April 2021

Metabolically engineered cyanobacteria have the potential to mitigate anthropogenic CO2 emissions by converting CO2 into renewable fuels and chemicals. Yet, better understanding of metabolic regulation in cyanobacteria is required to develop more productive strains that can make industrial scale-up economically feasible. The aim of this study was to find the cause for the previously reported inconsistency between oscillating transcription and constant protein levels under day-night growth conditions. To determine whether translational regulation counteracts transcriptional changes, Synechocystis sp. PCC 6803 was cultivated in an artificial day-night setting and the level of transcription, translation and protein was measured across the genome at different time points using mRNA sequencing, ribosome profiling and quantitative proteomics. Furthermore, the effect of protein turnover on the amplitude of protein oscillations was investigated through in silico simulations using a protein mass balance model. Our experimental analysis revealed that protein oscillations were not dampened by translational regulation, as evidenced by high correlation between translational and transcriptional oscillations (r = 0.88) and unchanged protein levels. Instead, model simulations showed that these observations can be attributed to a slow protein turnover, which reduces the effect of protein synthesis oscillations on the protein level. In conclusion, these results suggest that cyanobacteria have evolved to govern diurnal metabolic shifts through allosteric regulatory mechanisms in order to avoid the energy burden of replacing the proteome on a daily basis. Identification and manipulation of such mechanisms could be part of a metabolic engineering strategy for overproduction of chemicals.