bluuebunny/crossref_metadata_2025 huggingface dataset:
AKTIVITAS ANTIBAKTERI SEDIAAN GEL ANTISEPTIK EKSTRAK ETANOL KULIT PISANG KEPOK MENTAH (Musa paradisiaca L.)TERHADAP BAKTERI Staphylococcus aureus DAN Staphylococcus epidermidis
Authors: Primadiamanti Annisa , Marcellia Selvi , Sukmawan Sigit
Published: August 2021

Kulit pisang kepok mengandung senyawa tanin, flavonoid, alkaloid, dan saponin yang berpotensi sebagai antibakteri. Penelitian ini bertujuan untuk mengetahui aktivitas antibakteri pada sediaan gel antiseptik ekstrak etanol kulit pisang kepok mentah (Musa paradisiaca L.) terhadap bakteri Staphylococcus aureus dan Staphylococcus epidermidisdengan berbagai konsentrasi ekstrak.Gel ekstrak etanol kulit pisang kepok mentah dibuat menjadi 3 formula dengan variasi konsentrasi (F1=0,5%; FII=1,0%; dan FIII=1,5%).Uji aktivitas antibakteri dilakukan dengan metode difusi sumuran. Hasil penelitian menunjukkan bahwa konsentrasi ekstrak kulit pisang kepok mentah (Musa paradisiaca L.) pada sediaan gel antiseptik yang efektif dalam menghambat pertumbuhan bakteri Staphylococcus aureus dan Staphylococcus epidermidis pada masing-masing bakteri yaitu pada konsentrasi 1,5%. Aktivitas antibakteri yang lebih baik dari gel ekstrak etanol kulit pisang kepok mentah (Musa paradisiaca L.) terdapat pada bakteri Staphylococcus aureus dilihat dari zona hambat yang terbentuk sebesar 14,21 mm.
The Legal Protection of Sea Ice Areas and the Triple Bottom Line Approach to Mining Management in the Arctic
Authors: Tkach Pavel
Published: August 2021

2020 is the year when 40% of the 4,000-year-old Milne Ice Shelf, located on the north-western edge of Ellesmere Island, caved into the sea. 2020 is the year when the Greenland Ice Sheet has already passed the point of no return. 2020 is the year when human presence in the Arctic Ocean fell dramatically due …
Entrepreneurship Competencies of School Principals: A Scale Development Study
Authors: DEMİRBİLEK  Mesut , ÇETİN Münevver
Published: August 2021

This research aims to produce a reliable and valid scale that includes the entrepreneurship competencies of school principals according to the perceptions of teachers working in state-owned schools. First, after the literature review, an item pool consisting of five-point Likert item type and seventy-four items was created, and then the relevant items were presented to eleven experts to determine the content validity. After the expert evaluations, the content validity rates of the relevant items were calculated with the Lawshe technique, the nineteen items below the criterion value were removed from the scale, and a scale draft form consisting of fifty-five items was created. To carry out the EFA of the scale, the first application was performed with 436 teachers working in Çekmeköy district of Istanbul province on an online platform in March-April 2020. In the EFA process carried out in line with the data obtained, observations revealed that the scale had a four-factor structure. Then, the Varimax technique was used to clarify the distribution of scale items to factors, and seventeen items that were found to have a load of .30 and above from more than one factor and that the load difference was less than .100 were removed from the scale. As a result of EFA, a scale consisting of 38 items and subdimensions of “Personal Competencies”, “Organizational Competencies”, “Relational Competencies”, and “Commitment Self-Confidence Competencies” which explain 73.32% of the total variance was obtained. Subsequently, reliability coefficients of the scale (Cronbach’s Alpha .98), discrimination indices, item-total – item-residual correlations, and correlations between scale total and subdimensions were calculated. Finally, to carry out the CFA, the second application was carried out online with a sample of 724 teachers in May-June 2020 and the obtained goodness of fit values confirmed the scale model. All these obtained values confirm the valid and reliable structure of the developed scale.
Isomorphism Problem in a Special Class of Banach Function Algebras and its Application
Authors: Takahası Sın-eı , Shirayanagi Kiyoshi , Tsukada Makoto
Published: August 2021

Given a weight function τ, we introduce a new class of Banach function algebras with respect to τ,
denoted by C_0b(X, τ ). We provide a complete solution to the isomorphism problem in this class. We further characterize the BSE-extension and the Inoue-Doss ideal associated with it. As an application of our results, we show the
equivalence of the four statements: (i) C_0b(X, τ) is of BSE, (ii) C_0b(X, τ) is of BED, (iii) C_0b(X, τ) is Tauberian and (iv)
τ is bounded.
Rancang Bangun Aplikasi Pengenalan Rukun Islam Sebagai Media Pembelajaran Menggunakan Teknologi Augmented Reality
Authors: Mulyani Asri , Kurniadi Dede , Akbar Musadad Mahendra
Published: August 2021

Poin utama dari ajaran islam adalah rukun islam dan juga merupakan pendoman seorang muslim seperti mengucapkan syahadat, sholat, zakat, puasa, dan naik haji. Pembelajaran mengenai rukun islam disekolah sering kali disampaikan melalui buku yang terkadang membuat menimbulkan efek bosan untuk menambah minat belajar pada anak disaat kegiatan pembelajaran tidak perbolehkan melakukan tatap muka dikarenakan situasi pandemi covid-19, maka dari itu pembelajaran tersebut dikemas lebih menarik dengan memasukan unsur multimedia. Penelitian ini bertujuan untuk membuat aplikasi pengenalan rukun islam menggunakan augmented reality yang menjadi variasi. manfaat dari penelitian ini yaitu dapat dijadikan media pembelajaran yang menarik minat anak dalam mempelajari rukun islam khususnya bacaan dan gerakan sholat dan sebagai alat bantu untuk pengajar dalam menyampaikan pembelajaran tentang rukun islam. Pembuatan aplikasi ini menggunakan metodologi  Research And Development dengan tahapan analisis, pengumpulan data, perancangan desain, implementasi desain, pengujian, validasi ahli, revisi, uji kelayakan, perbaikan media dan produk.Hasil dari penelitian ini berupa aplikasi pengenalan rukun islam sebagai media pembelajaran mengguanakan augmented reality dengan platform androidI untuk mengoprasikannya.
Correlation between Age and Body Mass Index (BMI) with Histopathological Features of Breast Cancer Patients in RSUP Haji Adam Malik Medan
Authors: Mardiah Harisa , Ginting Radita Nur Anggaeni , Rahmadhany Heru , Sitorus Esther Reny Deswani
Published: August 2021

Background: Breast cancer is influenced by various risk factors, including age and obesity. Older women who are overweighted and obese have a higher risk of developing breast cancer. This study aims to find the correlation between age and body mass index (BMI) with histopathological features of breast cancer patients in RSUP Haji Adam Malik Medan.Methods: This research is an analytical study using a cross-sectional design with 103 samples obtained from medical record data by random sampling. The data obtained were then adjusted to the research criteria and grouped based on predetermined variables.Results: The majority of the age group was 41-50 years (36.9%), obesity BMI (40.8%), histopathological subtype of invasive carcinoma of no special type (NST) (85.4%), and grade II (46.6%). Kruskal-Wallis test result between histopathological subtypes and breast cancer grading based on age, respectively, obtained p=0.503, r=.325; (α>0.05), and p=0.207, r=0.393; (α>0.05), while based on BMI obtained p=0.017, r=0.021; (α<0.05), and p=0.018, r=0.018; (α<0.05). The OR value (95% CI) obtained on overweight-obese BMI with invasive carcinoma NST subtype was 7.63 (7.27–14.90) and other subtypes were 2.40 (1.14–13.75), and for grades II and III, they were respectively 3.57 (1.32–8.09) and 3.27 (1.17–9.91).Conclusions:  There was a correlation between BMI with histopathological subtypes and breast cancer grading, but the correlation tended to be weak. Whereas, with age, there was no correlation. BMI overweight-obese were more likely to have invasive carcinoma NST subtype and higher-grade of breast cancer.
Potential Use of Biomarker γ-H2AX on Peripheral Blood Patient Who Underwent Radioiodine Ablation Treatment in Indonesia
Authors: HASAN BASRI IIN KURNIA
Published: August 2021

Thyroid cancer is one of the most common endocrine malignancies. Although the 10-year survival rate of differentiated thyroid cancer (DTC) is about 90% after conventional treatments, a small proportion of patients still suffer from tumor recurrence or drug resistance. DNA doublestrand breaks (DSBs) are important cellular lesions that can result from ionizing radiation exposure. The biomarker for DSB formation is the phosphorylated form of the histone H2 variant H2AX (γ-H2AX). We propose the use of γ-H2AX as a DNA DSB biomarker in thyroid cancer patients receiving radioiodine treatment as a possibility to detect the potential of instability genome after receiving the treatment. Evaluating DNA DSB damage with γ-H2AX biomarker might be important in managing thyroid cancer.
Radiotherapy in Inoperable Mucoepidermoid Parotid Cancer: A Case Report
Authors: Octavianus Steven , Kodrat Henry
Published: August 2021

Introduction: Salivary gland cancer is an uncommon malignancy in the head and neck. The most common histopathologic type in salivary gland malignancies is mucoepidermoid carcinoma (MEC). Radiotherapy has a role in salivary gland malignancy, especially in inoperable cases and postoperative settings. Definitive or postoperative radiotherapy with or without chemotherapy can improve locoregional control (LRC) in patients with parotid mucoepidermoid carcinoma. Case Presentation: We report a case of a 77-year-old male with inoperable MEC of the right parotid, who received definitive radiotherapy. From the three-month evaluation after radiation therapy, we found a significant reduction in the tumor mass. Conclusions: Surgery remains the treatment of choice for patients with salivary gland malignancies. Definitive radiotherapy can be a treatment modality in inoperable cases or patients who refuse surgery. Although the result is not satisfactory, radiotherapy can still give clinical benefits to patients.
Дискусія щодо поняття права публічної власності: аргументи “за” та “проти”
Authors: ПЕРВОМАЙСЬКИЙ ОЛЕГ
Published: August 2021

Право власності, будучи поняттям і юридичним інститутом, може та має бути досліджено не лише як винятково цілісне утворення, а й у своїх розумно виокремлених складових, видах, аспектах, ознаках тощо. Застосування подібної дослідницької методології не руйнує ідею цілісності права власності, а навпаки – у разі виваженого та збалансованого застосування надає підґрунтя для більш якісного розуміння самого права власності та відносин, у межах яких воно здійснюється. Враховуючи зазначені міркування, безпосереднім об’єктом дослідження у межах цієї праці обрано поняття “право публічної власності”.
Метою статті є, по-перше, виявлення змісту поняття “право публічної власності”, по-друге, встановлення подальших перспектив застосування цього поняття e теоретичній і практичній юриспруденції.
Встановлено, що у Конституції та законах України термін “право публічної власності” не використовується, а його зміст не визначається. Водночас більшість сучасних науковців або підтверджують можливість і доречність використання у науко вих дослідженнях терміна та поняття “право публічної власності” з певними обмеженнями, або обґрунтовують шлях подальшого розвитку та еволюції цього поняття з метою його застосування у законодавстві, правозастосовній діяльності тощо. При цьому “право публічної власності” переважно розглядаються як родове поняття, що охоплює своїм обсягом такі поняття, як “право власності Українського народу”, “право державної власності”, “право комунальної власності”.
У статті аргументується теза про відсутність підстав для тлумачення змісту й обсягу поняття “права публічної власності” через види права власності, що належать різним суб’єктам публічного права, констатовано відсутність теоретичної та практичної потреби у понятті “право публічної власності”. Натомість запропоновано підтримати ідею поділу державної власності на приватну (використовується для задоволення приватного інтересу з отримання прибутку від свого майна) та публічну (не підлягає відчуженню, приватизації, оскільки вона задовольняє публічні інтереси). Унаслідок цього під правом державної публічної власності слід розуміти насамперед право власності Українського народу. Зі свого боку, під правом приватної державної власності слід розуміти право власності на те державне майно, що може бути відчужене на користь приватних власників.
Частка у статутному капіталі товариства як об’єкт права власності: окремі аспекти
Authors: КІБЕНКО ОЛЕНА , ПЕЛИПЕНКО ОЛЕНА
Published: August 2021

Що являє собою частка у статутному капіталі товариства з обмеженою відповідальністю? Чи є достатнім укладення договору купівлі-продажу для переходу права власності на частку як на звичайне рухоме майно? Або чи достатньо державної реєстрації змін складу учасників товариства для набуття права власності на частку? Ці та безліч інших подібних запитань постійно виникають на практиці. Одна із причин таких дискусій – законодавча невизначеність чіткого механізму переходу права власності на частку та, відповідно, захисту таких прав, зокрема й у судовому порядку.
Метою статті є висвітлення особливостей правової природи частки у статутному капіталі товариств з обмеженою та додатковою відповідальністю як об’єкта права власності. У статті розкриваються належні способи захисту права власності на частку крізь призму сформованої судової практики. Авторки публікації підкреслюють, що частку як об’єкт цивільного права вже не раз досліджували науковці у своїх працях і, в принципі, є доктринальне розуміння того, що частка у статутному капіталі є не майном у класичному розумінні цього терміна, а являє собою сукупність майнових і немайнових прав учасника товариства, на яку для зручності цивільного обігу (передачі такої сукупності прав від однієї особи до іншої) законодавець фактично поширив режим рухомого майна.
Встановлено, що відступлення частки та вихід учасника із товариства не можна ототожнювати. Крім того, відступлення частки не є спеціальним механізмом відчуження частки або окремим видом договору та відбувається у межах вже існуючих правових механізмів відчуження майна (купівля-продаж, міна, дарування). З’ясовано, що відсутність правочину, який може бути підставою для переходу права власності на частку в статутному капіталі до третьої особи та, відповідно, припинення права власності в учасника товариства, свідчить про те, що переходу права власності на частку не відбулося.
У статті порушується проблема виконання судових рішень у справах про захист прав на частку. Авторки наголошують, що у деяких справах не є достатнім звернення особи до суду без усвідомлення нею порядку виконання судового рішення, у разі задоволення позову, наслідків впливу такого рішення на законні права та інтереси інших осіб (учасників) товариства. Ця публікація присвячена впливу судової практики на доктринальне розуміння частки як об’єкта цивільного обігу та, відповідно, доктринальної трансформації правового уявлення щодо природи володіння часткою порівняно із володінням майном у класичному розумінні. У статті розглядаються належні та ефективні способи судового захисту прав на частку.
The Study of The Architectural Characteristics of Rumah Godong of The Anak Dalam Tribe in Sumatra
Authors: Khamdevi Muhammar
Published: August 2021

The Anak Dalam tribe (Suku Anak Dalam or Suku Kubu or Orang Rimba) is one of the tribes in Central Sumatra. This tribe still lives simply and depends on nature in the forest. This tribe has its own very simple traditional house, which indicates the earliest vernacular houses in Sumatra, especially in the "Malay" or Malayic-speaking areas of Central Sumatra. However, a comprehensive study of the architectural characteristics of Rumah Godong is still not well available. What are the characteristics of Rumah Godong? Suku Anak Dalam This research uses a qualitative method approach to descriptively analyze case objects in the field. The results of this study provide a description of the architectural characteristics of Rumah Godong.
How Islamic is an Islamic State: A Theoretical Debate on Islamic Political Order
Authors: Stanizai Zaman
Published: August 2021

The Muslim world is at the bottom rung of participatory democracy, representative governance, and political stability in comparison to the rest of the world. Prevalent and perpetual social disintegration, economic stagnation, and resistance to modernity are all problems in search of answers whose validity and relevance are constantly questioned. Some have vested hopes in the ideal of an ‘Islamic state,’ but very few have defined such a loosely defined state, and even fewer have critically analyzed or offered its theoretical parameters. In this regard, Islamist political activism suffers from a theoretical disconnect with the present political reality. They pursue two divergent paths: regression to a largely irrelevant political past or digression from historical models that the reformists claim to champion. In this writing, we delineate the inconsistencies between these arguments and offer solutions.
Application of Surgical Decision Model for Patients With Childhood Cataract: A Study Based on Real World Data
Authors: Chen Jingjing , Xiang Yifan , Li Longhui , Xu Andi , Hu Weiling , Lin Zhuoling , Xu Fabao , Lin Duoru , Chen Weirong , Lin Haotian
Published: August 2021

Reliable validated methods are necessary to verify the performance of diagnosis and therapy-assisted models in clinical practice. However, some validated results have research bias and may not reflect the results of real-world application. In addition, the conduct of clinical trials has executive risks for the indeterminate effectiveness of models and it is challenging to finish validated clinical trials of rare diseases. Real world data (RWD) can probably solve this problem. In our study, we collected RWD from 251 patients with a rare disease, childhood cataract (CC) and conducted a retrospective study to validate the CC surgical decision model. The consistency of the real surgical type and recommended surgical type was 94.16%. In the cataract extraction (CE) group, the model recommended the same surgical type for 84.48% of eyes, but the model advised conducting cataract extraction and primary intraocular lens implantation (CE + IOL) surgery in 15.52% of eyes, which was different from the real-world choices. In the CE + IOL group, the model recommended the same surgical type for 100% of eyes. The real-recommended matched rates were 94.22% in the eyes of bilateral patients and 90.38% in the eyes of unilateral patients. Our study is the first to apply RWD to complete a retrospective study evaluating a clinical model, and the results indicate the availability and feasibility of applying RWD in model validation and serve guidance for intelligent model evaluation for rare diseases.
LncRNA OIP5-AS1 Regulates the Warburg Effect Through miR-124-5p/IDH2/HIF-1α Pathway in Cervical Cancer
Authors: Li Li , Ma Yan , Maerkeya Kamalibaike , Reyanguly Davuti , Han Lili
Published: August 2021

Hypoxia reprogrammed glucose metabolism affects the Warburg effect of tumor cells, but the mechanism is still unclear. Long-chain non-coding RNA (lncRNA) has been found by many studies to be involved in the Warburg effect of tumor cells under hypoxic condition. Herein, we find that lncRNA OIP5-AS1 is up-regulated in cervical cancer tissues and predicts poor 5-years overall survival in cervical cancer patients, and it promotes cell proliferation of cervical cancer cells in vitro and in vivo. Moreover, OIP5-AS1 is a hypoxia-responsive lncRNA and is essential for hypoxia-enhanced glycolysis which is IDH2 or hypoxia inducible factor-1α (HIF-1α) dependent. In cervical cancer cells, OIP5-AS1 promotes IDH2 expression by inhibiting miR-124-5p, and IDH2 promotes the Warburg effect of cervical under hypoxic condition through regulating HIF-1α expression. In conclusion, hypoxia induced OIP5-AS1 promotes the Warburg effect through miR-124-5p/IDH2/HIF-1α pathway in cervical cancer.
Flubendazole Elicits Antitumor Effects by Inhibiting STAT3 and Activating Autophagy in Non-small Cell Lung Cancer
Authors: Xie Xiaona , Cai Xueding , Tang Yemeng , Jiang Chunhui , Zhou Feng , Yang Lehe , Liu Zhiguo , Wang Liangxing , Zhao Haiyang , Zhao Chengguang , Huang Xiaoying
Published: August 2021

Non-small cell lung carcinoma (NSCLC) is a major neoplastic disease with a high mortality worldwide; however, effective treatment of this disease remains a challenge. Flubendazole, a traditional anthelmintic drug, possesses potent antitumor properties; however, the detailed molecular mechanism of flubendazole activity in NSCLC needs to be further explored. In the present study, flubendazole was found to exhibit valid antitumor activity in vitro as well as in vivo. Flubendazole blocked phosphorylation of STAT3 in a dose- and time-dependent manner and regulated the transcription of STAT3 target genes encoding apoptotic proteins. Further, flubendazole inhibited STAT3 activation by inhibiting its phosphorylation and nuclear localization induced by interleukin-6 (IL-6). Notably, the autophagic flux of NSCLC cell lines was increased after flubendazole treatment. Furthermore, flubendazole downregulated the expression of BCL2, P62, and phosphorylated-mTOR, but it upregulated LC3-I/II and Beclin-1 expression, which are the main genes associated with autophagy. Collectively, these data contribute to elucidating the efficacy of flubendazole as an anticancer drug, demonstrating its potential as a therapeutic agent via its suppression of STAT3 activity and the activation of autophagy in NSCLC.
Differentiation Between Glioblastoma Multiforme and Metastasis From the Lungs and Other Sites Using Combined Clinical/Routine MRI Radiomics
Authors: Han Yuqi , Zhang Lingling , Niu Shuzi , Chen Shuguang , Yang Bo , Chen Hongyan , Zheng Fei , Zang Yuying , Zhang Hongbo , Xin Yu , Chen Xuzhu
Published: August 2021

Background

Differentiation between cerebral glioblastoma multiforme (GBM) and solitary brain metastasis (MET) is important. The existing radiomic differentiation method ignores the clinical and routine magnetic resonance imaging (MRI) features.

Purpose

To differentiate between GBM and MET and between METs from the lungs (MET-lung) and other sites (MET-other) through clinical and routine MRI, and radiomics analyses.

Methods and Materials

A total of 350 patients were collected from two institutions, including 182 patients with GBM and 168 patients with MET, which were all proven by pathology. The ROI of the tumor was obtained on axial postcontrast MRI which was performed before operation. Seven radiomic feature selection methods and four classification algorithms constituted 28 classifiers in two classification strategies, with the best classifier serving as the final radiomics model. The clinical and combination models were constructed using the nomograms developed. The performance of the nomograms was evaluated in terms of calibration, discrimination, and clinical usefulness. Student’s t-test or the chi-square test was used to assess the differences in the clinical and radiological characteristics between the training and internal validation cohorts. Receiver operating characteristic curve analysis was performed to assess the performance of developed models with the area under the curve (AUC).

Results

The classifier fisher_decision tree (fisher_DT) showed the best performance (AUC: 0.696, 95% CI:0.608-0.783) for distinguishing between GBM and MET in internal validation cohorts; the classifier reliefF_random forest (reliefF_RF) showed the best performance (AUC: 0.759, 95% CI: 0.613-0.904) for distinguishing between MET-lung and MET-other in internal validation cohorts. The combination models incorporating the radiomics signature and clinical-radiological characteristics were superior to the clinical-radiological models in the two classification strategies (AUC: 0.764 for differentiation between GBM in internal validation cohorts and MET and 0.759 or differentiation between MET-lung and MET-other in internal validation cohorts). The nomograms showed satisfactory performance and calibration and were considered clinically useful, as revealed in the decision curve analysis.

Data Conclusion

The combination of radiomic and non-radiomic features is helpful for the differentiation among GBM, MET-lung, and MET-other.
Copy Number Signatures and Clinical Outcomes in Upper Tract Urothelial Carcinoma
Authors: Guan Bao , Liang Yuan , Lu Huan , Xu Zhengzheng , Shi Yue , Li Juan , Kong Wenwen , Tian Chuanyu , Tan Yezhen , Gong Yanqing , Liu Jin , Fang Dong , Shen Qi , He Shiming , Shakeel Muhammad , Zhang Zhongyuan , He Qun , Li Xuesong , Ci Weimin , Zhou Liqun
Published: August 2021

Tumor staging of upper tract urothelial carcinomas (UTUCs) is relatively difficult to assert accurately before surgery. Here, we used copy number (CN) signatures as a tool to explore their clinical significance of molecular stratification in UTUC. CN signatures were extracted by non-negative matrix factorization from the whole-genome sequencing (WGS) data of 90 Chinese UTUC primary tumor samples. A validation UTUC cohort (n = 56) and a cohort from urinary cell-free DNA (cfDNA) of urothelial cancer patients (n = 94) and matched primary tumors were also examined. Survival analyses were measured using the Kaplan–Meier, and Cox regression was used for multivariate analysis. Here, we identified six CN signatures (Sig1–6). Patients with a high contribution of Sig6 (Sig6high) were associated with higher microsatellite instability level and papillary architecture and had a favorable outcome. Patients with a low weighted genome integrity index were associated with positive lymph node and showed the worst outcome. Sig6high was identified to be an independently prognostic factor. The predictive significance of CN signature was identified by a validation UTUC cohort. CN signatures retained great concordance between primary tumor and urinary cfDNA. In conclusion, our results reveal that CN signature assessment for risk stratification is feasible and provides a basis for clinical studies that evaluate therapeutic interventions and prognosis.
Identification of Immune Cell Infiltration Landscape and Their Prognostic Significance in Uveal Melanoma
Authors: Zhao Han , Chen Yun , Shen Peijun , Gong Lan
Published: August 2021

Uveal melanoma (UVM) is the most common primary intraocular cancer in adults. Increasing evidence has demonstrated that immune cell infiltration (ICI) is crucial in predicting patient outcomes and therapeutic efficacy. Thus, describing the immune cell infiltrative landscape of UVM tumors may yield a novel prognostic marker and provide direction for immunotherapeutic selection. In this study, the gene expression data and clinical information of UVM patients were obtained from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. The ICI landscape of UVM was analyzed using the CIBERSORT and ESTIMATE algorithms. Two ICI phenotypes were defined, and the ICI scores were calculated by using principal component analysis algorithms. We found that a subtype with high ICI scores had poorer prognosis and increased expression levels of immune checkpoint-related genes. This study demonstrates that ICI scores are an independent prognostic biomarker and highlights their value in predicting immunotherapeutic outcomes.
Impact of Chronobiological Variation in Takotsubo Syndrome: Prognosis and Outcome
Authors: El-Battrawy Ibrahim , Aweimer Assem , Lang Siegfried , Ansari Uzair , Gietzen Thorsten , Ullrich Niklas , Mügge Andreas , Zhou Xiaobo , Borggrefe Martin , Akin Ibrahim
Published: August 2021

Background: A considerable amount of evidence has shown that acute cardiovascular diseases exhibit specific temporal patterns in their onset.

Aim: This study was performed to determine if takotsubo syndrome (TTS) shows chronobiological variations with short and long-term impacts on adverse events.

Design: Our institutional database constituted a collective of 114 consecutive TTS patients between 2003 and 2015.

Methods: Patients were divided into groups defined by the onset of TTS as per time of the day, day of the week, month and quarter of year.

Results: TTS events were most common afternoon and least common in the night, indicating a wave-like pattern (p = 0.001) of manifestation. The occurrence of TTS events was similar among days of the week and weeks of the month. TTS patients diagnosed in the month of November and subsequently in the fourth quarter showed a significantly longer QTc interval. These patients also revealed a significantly lower event-free-survival over a 1-year follow-up. In a multivariate Cox regression analysis, TTS events occurring in the fourth quarter of year (HR 6.8, 95%CI: 1.3–35.9; p = 0.02) proved to be an independent predictor of lower event-free-survival.

Conclusions: TTS seems to exhibit temporal preference in its onset, but nevertheless this possibly coincidental result needs to be analyzed in a large multicenter registry.
Variation of Organic Pore Structure With Maceral Types in the Longmaxi Shale, Sichuan Basin
Authors: Pang Qian , Hu Guang , Hu Chaowei , Zhang Cong
Published: August 2021

Organic matter (OM), composed of various macerals, has a strong influence on the enrichment of shale gas. Nevertheless, the connection between OM-hosted pore structure and maceral type is not yet fully understood because of the difficulty to identify the maceral types by traditional scanning electron microscope (SEM). Using a combination of the reflected light microscopy, focused ion beam SEM (FIB-SEM), and Raman spectrum, three maceral types, including alginite, graptolite, and solid bitumen, are identified in the Longmaxi Shale of the Sichuan Basin. The alginate is characterized by the linear arrangement of OM-hosted pores due to the inherited biological structure of benthic algae. Pores in the structureless solid bitumen are randomly distributed with the highest abundance. The graptolite containing pore rarely is unfavorable for the pore generation but can be a good proxy for thermal maturity. Variation in thermal maturity levels accounts for the change of total pore volume in a given marcel type in the Longmaxi Shale obtained from different shale gas fields.
How to Use Challenge-Based Learning for the Acquisition of Learning to Learn Competence in Early Childhood Preservice Teachers: A Virtual Archaeological Museum Tour in Spain
Authors: Abril-López Daniel , López Carrillo Dolores , González-Moreno Pedro Miguel , Delgado-Algarra Emilio José
Published: August 2021

This article presents the research results in relation to an interdisciplinary teaching innovation project—Teaching and Learning of Social Sciences and Teaching and Learning of Natural Sciences—with Early Childhood Preservice Teachers (ECPT) at the University of Alcalá (Spain) in the pandemic context by COVID-19 during 2020–2021 (N = 55): 52 women (94.55%) and 3 men (5.45%) from 20 to 22 years of age. The main research problem is to know if the ECPT improves the learning to learn competence after a challenge-based learning (CBL) linked to virtual tour in a museum. The main objective was to improve the learning to learn competence, during a virtual tour at the Community of Madrid Regional Archaeological Museum (MAR) (Alcalá de Henares, Spain) for a reflective training of students to understand problems of the past and present and future global challenges, promote collaborative and multidisciplinary work, and defend ethics and leadership. In order to ascertain the level of acquisition of this competence in those teachers who were being trained, their self-perception—pretest–posttest—of the experience was assessed through a system of categories adapted from the European Commission. ECPT worked, in small groups and using e/m-learning tools, ten challenges and one storytelling cooperatively with university teachers to solve prehistoric questions related to current situations and problems. Subsequently, two Early Childhood Education teachers from a school in Alcalá de Henares reviewed the proposals and adapted them for application in the classroom of 5-year-old boys and girls. The results show an improvement in this competence in Early Childhood Preservice Teachers: total score pre-post comparison paired-samples Wilcoxon test result shows a statistically significant difference (p> 0.001); an evaluation rubric verified the results of self-perception. Second, we highlight the importance of carrying out virtual museum tours from a challenge-based learning for the development of big ideas, essential questions, challenges, and activities on socioeconomic, environmental, and emotional knowledge, skills, and attitudes. Third, this experience shows the insufficient educational adaptation of the virtual museum tour to the Early Childhood Education stage from a technological and didactic workshops point of view, but there is a diversity of paleontological and archaeological materials and a significant sociocritical discourse.
Effects of Age Dependency and Urbanization on Energy Demand in BRICS: Evidence From the Machine Learning Estimator
Authors: Lu Zhou , Mahalik Mantu Kumar , Padhan Hemachandra , Gupta Monika , Gozgor Giray
Published: August 2021

This paper examines the effects of age dependency ratio (the young age, old-age and overall age) and urbanization on renewable and non-renewable energy consumption in Brazil, India, China, and South Africa, considering the panel data from 1990 to 2019. We control economic growth and foreign direct investment inflows as key factors in the energy demand function using the Stochastic Impacts by Regression on Population, Affluence and Technology approach. Empirical analysis has been implemented using the Kernel Regularized Least Squares machine learning method to solve possible classification problems in the traditional regressions without relying on the linearity assumption. It is observed that the young age dependency, overall age dependency, and urbanization negatively affect both renewable and non-renewable energy demand. On the contrary, old-age dependency and economic growth are positively associated with renewable and non-renewable energy demand. The mixed effects of foreign direct investment inflows on renewable and non-renewable energy demand patterns are also found. Thus, the findings suggest that environment policymakers in the BRICS economies should prioritize urbanization, young age, and overall age population to improve energy efficiency.
A Central Role for Atg5 in Microbiota-Dependent Foxp3+ RORγt+ Treg Cell Preservation to Maintain Intestinal Immune Homeostasis
Authors: Plaza-Sirvent Carlos , Zhao Bei , Bronietzki Alisha W. , Pils Marina C. , Tafrishi Neda , Schuster Marc , Strowig Till , Schmitz Ingo
Published: August 2021

Autophagy is an evolutionary conserved catabolic pathway that ensures the degradation of intracellular components. The autophagic pathway is regulated by autophagy-related (Atg) proteins that govern formation of double-membraned vesicles called autophagosomes. Autophagy deficiency in regulatory T (Treg) cells leads to increased apoptosis of these cells and to the development of autoimmune disorders, predominantly characterized by intestinal inflammation. Recently, RORγt-expressing Treg cells have been identified as key regulators of gut homeostasis, preventing intestinal immunopathology. To study the role of autophagy in RORγt+ Foxp3+ Treg cells, we generated mice lacking the essential component of the core autophagy machinery Atg5 in Foxp3+ cells. Atg5 deficiency in Treg cells led to a predominant intestinal inflammation. While Atg5-deficient Treg cells were reduced in peripheral lymphoid organs, the intestinal RORγt+ Foxp3+ subpopulation of Treg cells was most severely affected. Our data indicated that autophagy is essential to maintain the intestinal RORγt+ Foxp3+ Treg population, thereby protecting the mice from gut inflammatory disorders.
The E3 Ubiquitin Ligase TRIM65 Negatively Regulates Inflammasome Activation Through Promoting Ubiquitination of NLRP3
Authors: Tang Tiantian , Li Ping , Zhou Xinhui , Wang Rui , Fan Xiuqin , Yang Mengyi , Qi Kemin
Published: August 2021

The dysregulation of NLRP3 inflammasome plays a critical role in pathogenesis of various human inflammatory diseases, thus NLRP3 inflammasome activation must be tightly controlled at multiple levels. However, the underlying mechanism regulating NLRP3 inflammasome activation remains unclear. Herein, the effects of Tripartite motif-containing protein 65 (TRIM65) on NLRP3 inflammasome activation and the underlying molecular mechanism were investigated in vitro and in vivo. Inhibition or deletion of Trim65 could significantly strengthen agonist induced NLRP3 inflammasome activation in THP-1 cells and BMDMs, indicated by increased caspase-1 activation and interleukin-1β secretion. However, TRIM65 had no effect on poly (dA: dT)-induced AIM2 inflammasome activation or flagellin-induced IPAF inflammasome activation. Mechanistically, immunoprecipitation assays demonstrated that TRIM65 binds to NACHT domain of NLRP3, promotes lys48- and lys63- linked ubiquitination of NLRP3 and restrains the NEK7-NLRP3 interaction, thereby inhibiting NLRP3 inflammasome assembly, caspase-1 activation, and IL-1β secretion. In vivo, three models of inflammatory diseases were used to confirm the suppression role of TRIM65 in NLRP3 inflammasome activation. TRIM65-deficient mice had a higher production of IL-1β induced by lipopolysaccharide in sera, and more IL-1β secretion and neutrophil migration in the ascites, and more severity of joint swelling and associated IL-1β production induced by monosodium urate, suggesting that TRIM65 deficiency was susceptible to inflammation. Therefore, the data elucidate a TRIM65-dependent negative regulation mechanism of NLRP3 inflammasome activation and provide potential therapeutic strategies for the treatment of NLRP3 inflammasome-related diseases.
Molecular Characteristics of Novel Phage vB_ShiP-A7 Infecting Multidrug-Resistant Shigella flexneri and Escherichia coli, and Its Bactericidal Effect in vitro and in vivo
Authors: Xu Jing , Zhang Ruiyang , Yu Xinyan , Zhang Xuesen , Liu Genyan , Liu Xiaoqiu
Published: August 2021

In recent years, increasing evidence has shown that bacteriophages (phages) can inhibit infection caused by multidrug-resistant (MDR) bacteria. Here, we isolated a new phage, named vB_ShiP-A7, using MDR Shigella flexneri as the host. vB_ShiP-A7 is a novel member of Podoviridae, with a latency period of approximately 35 min and a burst size of approximately 100 phage particles/cell. The adsorption rate constant of phage vB_ShiP-A7 to its host S. flexneri was 1.405 × 10–8 mL/min. The vB_ShiP-A7 genome is a linear double-stranded DNA composed of 40,058 bp with 177 bp terminal repeats, encoding 43 putative open reading frames. Comparative genomic analysis demonstrated that the genome sequence of vB_ShiP-A7 is closely related to 15 different phages, which can infect different strains. Mass spectrometry analysis revealed that 12 known proteins and 6 hypothetical proteins exist in the particles of phage vB_ShiP-A7. Our results confirmed that the genome of vB_ShiP-A7 is free of lysogen-related genes, bacterial virulence genes, and antibiotic resistance genes. vB_ShiP-A7 can significantly disrupt the growth of some MDR clinical strains of S. flexneri and Escherichia coli in liquid culture and biofilms in vitro. In addition, vB_ShiP-A7 can reduce the load of S. flexneri by approximately 3–10 folds in an infection model of mice. Therefore, vB_ShiP-A7 is a stable novel phage with the potential to treat infections caused by MDR strains of S. flexneri and E. coli.
The Molecular Mechanism of Hemocyte Immune Response in Marsupenaeus japonicus Infected With Decapod Iridescent Virus 1
Authors: He Zihao , Zhao Jichen , Chen Xieyan , Liao Minze , Xue Yuan , Zhou Jianing , Chen Haozhen , Chen Guoliang , Zhang Shuang , Sun Chengbo
Published: August 2021

As a new type of shrimp lethal virus, decapod iridescent virus 1 (DIV1) has caused huge economic losses to shrimp farmers in China. Up to now, DIV1 has been detected in a variety of shrimps, but there is no report in Marsupenaeus japonicus. In the current study, we calculated the LC50 to evaluate the toxicity of DIV1 to M. japonicus and determined through nested PCR that M. japonicus can be the host of DIV1. Through enzyme activity study, it was found that DIV1 can inhibit the activities of superoxide dismutase, catalase, lysozyme, and phenoloxidase, which could be a way for DIV1 to achieve immune evasion. In a comprehensive study on the transcriptomic changes of M. japonicus in response to DIV1 infection, a total of 52,287 unigenes were de novo assembled, and 20,342 SSR markers associated with these unigenes were obtained. Through a comparative transcriptomic analysis, 6,900 differentially expressed genes were identified, including 3,882 upregulated genes and 3,018 downregulated genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that some GO terms related to virus invasion, replication, and host antiviral infection were promoted under DIV1 infection, such as carbohydrate binding, chitin binding, chitin metabolic process, and DNA replication initiation, and some KEGG pathways related to immune response were significantly influenced by DIV1 infection, including Toll and IMD signaling pathway, JAK-STAT signaling pathway, IL-17 signaling pathway, C-type lectin receptor signaling pathway, complement and coagulation cascades, antigen processing and presentation, necroptosis, apoptosis, NOD-like receptor signaling pathway, apoptosis—multiple species, and TNF signaling pathway. Further analysis showed that STAT, Dorsal, Relish, heat shock protein 70 (HSP70), C-type lectins, and caspase play an important role in DIV1 infection. This is the first detailed study of DIV1 infection in M. japonicus, which initially reveals the molecular mechanism of DIV1 infection in M. japonicus by using the transcriptome analysis of hemocytes combined with enzyme activity study.
Exploring Ligand Binding to Calcitonin Gene-Related Peptide Receptors
Authors: Deganutti Giuseppe , Atanasio Silvia , Rujan Roxana-Maria , Sexton Patrick M. , Wootten Denise , Reynolds Christopher A.
Published: August 2021

Class B1 G protein-coupled receptors (GPCRs) are important targets for many diseases, including cancer, diabetes, and heart disease. All the approved drugs for this receptor family are peptides that mimic the endogenous activating hormones. An understanding of how agonists bind and activate class B1 GPCRs is fundamental for the development of therapeutic small molecules. We combined supervised molecular dynamics (SuMD) and classic molecular dynamics (cMD) simulations to study the binding of the calcitonin gene-related peptide (CGRP) to the CGRP receptor (CGRPR). We also evaluated the association and dissociation of the antagonist telcagepant from the extracellular domain (ECD) of CGRPR and the water network perturbation upon binding. This study, which represents the first example of dynamic docking of a class B1 GPCR peptide, delivers insights on several aspects of ligand binding to CGRPR, expanding understanding of the role of the ECD and the receptor-activity modifying protein 1 (RAMP1) on agonist selectivity.
Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration
Authors: Zhang Yuan , Dou Shengqian , Qi Xia , Zhang Zhenzhen , Qiao Yujie , Wang Yani , Xie Jin , Jiang Hui , Zhang Bin , Zhou Qingjun , Wang Qun , Xie Lixin
Published: August 2021

Diabetes mellitus (DM) is a complex metabolic disorder. Long-term hyperglycemia may induce diabetic keratopathy (DK), which is mainly characterized by delayed corneal epithelial regeneration. MicroRNAs (miRNAs) have been reported to play regulatory roles during tissue regeneration. However, the molecular mechanism by which miRNAs influence epithelial regeneration in DK is largely unknown. In this study, we performed miRNA and mRNA sequencing of regenerative corneal epithelium tissue from streptozotocin-induced type 1 diabetic (T1DM) and wild-type mice to screen for differentially expressed miRNAs and mRNAs. Based on regulatory network analysis, miR-223-5p was selected for subsequent experiments and Hpgds was then identified as a direct target gene. MiR-223-5p downregulation significantly promoted diabetic corneal epithelial wound healing and nerve regeneration. However, the beneficial effects of miR-223-5p inhibition were abolished by an Hpgds inhibitor. Furthermore, mechanistic studies demonstrated that miR-223-5p suppression ameliorated inflammation and enhanced cell proliferation signaling in DK. Taken together, our findings revealed that the regulatory role of miR-223-5p in diabetic corneal epithelial and nerve regeneration by mediating inflammatory processes and cell proliferation signaling. And silencing miR-223-5p may contribute to the development of potential therapeutic strategies for DK.
Effectiveness of Telerehabilitation on Motor Impairments, Non-motor Symptoms and Compliance in Patients With Parkinson's Disease: A Systematic Review
Authors: Vellata Chiara , Belli Stefano , Balsamo Francesca , Giordano Andrea , Colombo Roberto , Maggioni Giorgio
Published: August 2021

Introduction: Parkinson's disease (PD) is a chronic neurodegenerative disease involving a progressive alteration of the motor and non-motor function. PD influences the patient's daily living and reduces participation and quality of life in all phases of the disease. Early physical exercise can mitigate the effects of symptoms but access to specialist care is difficult. With current technological progress, telemedicine, and telerehabilitation is now a viable option for managing patients, although few studies have investigated the use of telerehabilitation in PD. In this systematic review, was investigated whether telerehabilitation leads to improvements in global or specific motor tasks (gait and balance, hand function) and non-motor dysfunction (motor speech disorder, dysphagia). The impact of TR on quality of life and patient satisfaction, were also assessed. The usage of telerehabilitation technologies in the management of cognitive impairment was not addressed.

Method: An electronic database search was performed using the following databases: PubMed/MEDLINE, COCHRANE Library, PEDro, and SCOPUS for data published between January 2005 and December 2019 on the effects of telerehabilitation systems in managing motor and non-motor symptoms. This systematic review was conducted in accordance with the PRISMA guideline and was registered in the PROSPERO database (CRD42020141300).

Results: A total of 15 articles involving 421 patients affected by PD were analyzed. The articles were divided into two categories based on their topic of interest or outcome. The first category consisted of the effects of telerehabilitation on gait and balance (3), dexterity of the upper limbs (3), and bradykinesia (0); the second category regarded non-motor symptoms such as speech disorders (8) and dysphagia (0). Quality of life (7) and patient satisfaction (8) following telerehabilitation programs were also analyzed, as well as feasibility and costs.

Conclusion: Telerehabilitation is feasible in people affected by PD. Our analysis of the available data highlighted that telerehabilitation systems are effective in maintaining and/or improving some clinical and non-clinical aspects of PD (balance and gait, speech and voice, quality of life, patient satisfaction).

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier: CRD42020141300.