bluuebunny/crossref_metadata_2025 huggingface dataset:
Estudio de modelos y/o herramientas para la Administración del Riesgo de Liquidez
Authors: Quizhpi-Sinchi AdPedro Martín , Idrovo-Armijos Grace Ivannova , Abril-Fajardo Ximena Catalina
Published: April 2021

En el presente estudio se analizó e identificó los modelos y herramientas para la administración del riesgo de liquidez en las Cooperativas de Ahorro y Crédito, para lo cual, se seleccionaron cinco entidades, aplicando en sus Unidades de Riesgo una entrevista, encuesta y revisión documental de los desarrollos y conseguidos en la materia. Se analizaron, también, datos necesarios para desarrollar un modelo de volatilidad en función al Valor en Riesgo (VaR), así como supuestos basados en modelos estadísticos requeridos para escenarios de brechas. Los resultados revelaron un importante fomento de la cultura de riesgo en los últimos cinco años; sin embargo, existe una brecha entre los estándares y la madurez alcanzada por sus similares del segmento 1. Tales aspectos, permitieron determinar áreas claves que requieren fortalecimiento, para las cuales, planteamos acciones de mejora que les permitan reducir la mencionada brecha y efectuar una gestión preventiva ante posibles eventos adversos.

Palabras Claves: Brechas de liquidez, Plan de contingencias, Valor en Riesgo, Volatilidad.
IMPLEMENTASI METODE HYBRID SAW-TOPSIS DALAM MULTI ATTRIBUTE DECISION MAKING PEMILIHAN LAPTOP
Authors: Hadikurniawati Wiwien , Nugraha Ivannofick Adha , Cahyono Taufiq Dwi
Published: April 2021

Abstract: Various specifications and prices for a laptop make potential buyers confused about choosing it. Information technology with its technological developments has produced a system that can provide alternative decisions for decision-making problems.This study aims to develop a system that can select the best laptop from several alternatives.                There are 5 parameters used in determining the priority of alternative laptops. They are hard disk drive, RAM, processor, operating system and price.The alternative of the decision making system also consists of 5 alternatives.The method used in the MultiAttribute Decision Making (MADM) research is a combination of 2 methods. These methods are SAW and TOPSIS methods.The SAW method is used to optimize the parameter weighting process and the specific TOPSIS method to complete the alternative ranking process.This hybrid method can produce a more precise MADM process because it uses two methods, each of which has characteristics in accordance with the process specifications. Keywords: laptop; multi attribute decision making; SAW; TOPSIS  Abstrak: Spesifikasi dan variasi harga yang beragam dari sebuah laptop membuat calon pembeli menjadi kebingungan dan ragu dalam memutuskan jenis atau tipe laptop mana yang akan dibeli. Teknologi informasi beserta dengan perkembangan teknologinya dapat menghasilkan suatu system untuk membantu memberikan alternative  keputusan untuk suatu permasalahan pengambilan keputusan. Pengembangan sistem yang dapat memilih laptop yang tepat dari beberapa alternatif  yang  ditawarkan merupakan tujuan dari penelitian ini. Ada 5 parameter yang digunakan dalam  menentukan prioritas alternatif  laptop, yaitu hard disk drive, RAM, prosesor, sistem operasi dan harga. Laptop yang ditawarkan sebagai alternatif juga sebanyak 5 jenis. Metode yang digunakan padaMulti Attribute Decision Making (MADM) adalah kombinasi dari 2 metode, yaitu metode SAW dan TOPSIS. Metode SAW digunakan untuk mengoptimalkan proses pembobotan parameter dan metode TOPSIS spesifik untuk menyelesaikan proses perangkingan alternatif. Metode hybrid ini dapat menghasilkan suatu proses MADM yang lebih tepat karena menggunakan dua metode yang masing-masing mempunyai karakteristik sesuai dengan proses yang dilakukannya. Kata kunci: laptop; multi-attribute decision making; SAW; TOPSIS
KORELASI TIME TO LIVE TERHADAP QUERY TIDAK NORMAL PADA DNS MENGGUNAKAN BINARY LOGISTIC REGRESSION
Authors: Aminudin Aminudin , Cahyono Eko Budi
Published: April 2021

Abstract: DNS plays a vital role in the operation of services on the internet. Almost all services on the internet are under DNS control, such as email, FTP, web apps, etc. So, it is not surprising that various malicious activities involve DNS services such as financial fraud, phishing, malware, and malicious activity, etc. Fortunately, in DNS there is a record with the name time to live which can be used to detect a query or the address accessed from the user is a normal query or an abnormal query. Therefore, the purpose of this study is to determine the correlation value between time to live and abnormal queries on passive DNS data using the Binary Logistic Regression model. The results showed that the Binary Logistic Regression method could model the correlation between TTL, elapsed, and bytes which have an optimal model F1 Score of 0.9997 and also have a condition close to the ideal state by using the Precision-Recall Curve (PRC) graph plot.            Keywords: Binary Logistic Regression; DNS Passive; Precision-Recall Curve (PRC); Query Abnormal  Abstrak: DNS memegang peranan yang vital di dalam berjalanya service di internet. Hampir seluruh layanan di internet berada di bawah kendali DNS seperti email, ftp, app web dll. Jadi, tidak mengherankan bahwa berbagai kegiatan jahat melibatkan layanan DNS seperti financial fraud, phising, malware dan aktivitas malicious dll. Untungnya, di dalam DNS tersimpan sebuah record dengan nama time to live yang dapat digunakan untuk mendeteksi sebuah query atau alamat yang diakses dari user tersebut bersifat query normal atau query tidak normal. Oleh karena itu, tujuan penelitian ini adalah untuk mengetahui nilai korelasi antara time to live dengan query tidak normal pada data passive DNS dengan menggunakan model Binary Logistic Regression. Hasil penelitian menunjukkan bahwa metode Binary Logistic Regression dapat memodelkan korelasi antara TTL, elapsed dan bytes yang memiliki model optimal F1 Score sebesar 0.9997 dan juga memiliki kondisi hampir mendekati keadaan ideal dengan menggunakan plot grafik Precision Recall Curve (PRC). Kata kunci: Binary Logistic Regression; DNS Passive; Precision-Recall Curve (PRC); Query Abnormal
Erään tieteenalan genealogiaa
Authors: Ikonen Risto
Published: April 2021

Aikuiskasvatuksen tutkijat kiistelivät toista vuosikymmentä siitä, puhuako tieteenalasta ja sen käytännöistä sivistyksenä vai aikuiskasvatuksena. Aikuiskasvatus vakiintui ydinkäsitteeksi 1950-luvun puolivälissä. Termikiistan juurisyyt ovat yhä läsnä tavassa, jolla näemme aikuiskasvatustieteen tarkoituksen.
Pengaruh Kedisiplinan Belajar dan Motivasi Belajar terhadap Prestasi Belajar Siswa di SMA Muhammadiyah Maumere
Authors: Wahab Vicky , Rahman Nurdin , Fitri Mohammad
Published: April 2021

Tujuan penelitian ini untuk mengetahui pengaruh kedisiplinan belajar dan motivasi belajar terhadap prestasi belajar siswa di SMA Muhammadiyah Maumere, baik secara parsial maupun simultan. Penelitian ini menggunakan metode Ex-Post Facto. Subjek penelitian adalah siswa SMA Muhammadiyah Maumere berjumlah 250 siswa dengan sampel penelitian sebanyak 153 siswa. Data dikumpulkan melalui angket dan dokumentasi serta analisis adat menggunakan analisis regresi linear berganda. Kesimpulannya: 1) Kedisiplinan belajar tidak berpengaruh signifikan terhadap prestasi belajar siswa di SMA Muhammadiyah Maumere. 2) Motivasi belajar berpengaruh negatif dan signifikan terhadap prestasi belajar siswa di SMA Muhmmadiyah Maumere. 3) Kedisiplinan belajar dan motivasi belajar secara bersamaan berpengaruh signifikan terhadap prestasi belajar siswa di SMA Muhammadiyah Maumere.
Efektivitas Sistem Akuntabilitas Kinerja Instansi Pemerintah (SAKIP) pada Dinas Pertanian dan Pangan Kota Magelang
Authors: Mukaromah Ricky , Priyono Nuwun
Published: April 2021

Tujuan penelitian ini untuk mengetahui efektivitas Sistem Akuntabilitas Kinerja Instansi Pemerintah (SAKIP) dan untuk mengetahui faktor pendukung dan penghambatan penerapan efektivitas SAKIP di Dinas Pertanian dan Pangan Kota Magelang. Penelitian ini menggunakan pendekatan kualitatif deskriptif. Teknik pengumpulan data menggunakan wawancara, observasi, dan dokumentasi. Hasil penelitian ini menunjukkan bahwa SAKIP di Dinas Pertanian dan Pangan Kota Magelang telah berjalan efektif. Pelaksanaan SAKIP di lingkungan Dinas Pertanian dan Pangan Kota Magelang mengalami peningkatan setiap tahunnya yang dapat dilihat dari tingkat keberhasilan program kerja yang telah dilaksanakan.
Efisiensi dan Efektifitas Partisipasi Anggaran pada SKPD DISPERPA Kabupaten Magelang
Authors: Wati Lisna , Priyono Nuwun
Published: April 2021

Penelitian ini bertujuan untuk menganalisis efektifitas dan efisiensi pelaksanaan anggaran belanja Dinas Pertanian dan Pangan Kabupaten Magelang. Penelitian ini menggunakan jenis penelitian kualitatif dengan menggunakan pendekatan deskriptif. Tingkat dan kriteria efektifitas pelaksanaan anggaran belanja pada Dinas Pertanian dan Pangan Kabupaten Magelang tahun 2016-2019 sangat bervariasi, Tingkat efektifitas tertinggi terjadi pada tahun 2018 dan yang terendah pada tahun 2016. Pelaksanaan anggaran belanja tahun 2017, 2018 dan 2019 di katakan efektif, tetapi pada tahun 2016 tingkat efektifitasnya masih sangat kurang karena realisasi anggaran belanja memiliki perbedaan yang masih sangat jauh dengan target anggaran belanja. Perbedaan ini terjadi karena adanya kebijakan pada tahun 2016 bahwa Dinas tidak melaksanakan hibah. Dinas Pertanian dan Pangan Kabupaten Magelang menilai ketika kegiatan yang diprogramkan sudah terealisasi dan sesuai dengan yang diharapkan, maka kegiatan tersebut dikatakan efektif. Pelaksanaan anggaran belanja langsung Dinas Pertanian dan Pangan tahun 2016-2019 secara keseluruhan sudah diolah secara efisien. Pelaksanaan anggaran belanja langsung tahun 2017-2019 dikategorikan sangat efisien. Hanya pada tahun 2016 dikategorikan cukup efisien. Pengelolaan anggaran belanja langsung sudah memenuhi syarat efisiensi yaitu penggunaan dana yang minimum untuk mencapai hasil yang maksimum.
The ARGUE Mnemonic: A Strategy to Improve Argumentative Essay Writing with Students who have Visual Impairments
Authors: Dunn Michael William , Pogrund Rona
Published: April 2021

Writing can be a challenging task for many students. This study offered 10 ninth-grade students (8 females, 2 males) with visual impairments located in the Western United States the opportunity to learn a mnemonic strategy for argumentative-essay writing called ARGUE: Analyze data; Review keywords and create sentences; Generate a plan; Use your thoughts to say an oral draft; and Express your ideas in typed text. Action research methods were employed in the study from April through May over twenty-one 65-minute sessions. All students argumentative essay writing skills increased in content and quality by the end of the intervention’s timeline, except for one. Another student had an increase for content but not quality. Three participants had the highest end-of-intervention gains. They also had the largest gains in number of words written. From the results of repeated measures t-tests, there was a significant difference in the scores for content in baseline and application conditions. All student participants felt others would benefit from using ARGUE and that the mnemonic was effective as is. Limitations and future research are also discussed.
“İlkel” savaşın görünümleri: Claude Lévi-Strauss ve Pierre Clastres arasındaki irtibatlar ve ihtilaflar
Authors: TUNÇBİLEK Şeyda Sevde
Published: April 2021

“İlkel” toplumlarda savaşın anlamı ve işlevi konusunda 1971 yılındaki anlaşmazlığa kadar, 20. yüzyılın iki önemli antropoloğu Pierre Clastres ve tez danışmanı Claude Lévi-Strauss arasında oldukça yakın bir ilişki söz konusudur. Eserlerinde ilkel toplulukların mübadele üzerinden okunmasından ilkel şeflik kurumunun tanımı ve işlevine kadar pek çok konuda paralellik bulunmasına rağmen bu ikili, ilkel savaş hakkındaki pozisyon alışları itibariyle birbirlerinden ayrılarak antropolojik spektrumun farklı kutuplarına yerleşirler. Bu makale, Clastres ve Lévi-Strauss arasındaki irtibatları ve ihtilafları gayrişahsileştirerek makro düzeye taşımakta, 2. Dünya Savaşı sonrasında antropoloji disiplini içindeki dönüşümlerin ve cereyanların, bir altdisiplin olarak siyasal antropolojinin ortaya çıkışını dolayımlayan koşulların bütün özelliklerini haiz bir pars totalis olarak takdim etmektedir. Claude Lévi-Strauss ile Pierre Clastres arasındaki irtibatlar Paris’teki Labaratoire d’anthropologie sociale arşivlerinde yer alan yazışmalarından, ihtilaflar kısmı ise metinlerinden ve polemiklerinden hareketle kaleme alınmıştır.
DOES SELF-EFFICACY PLAY AN INTERVENING ROLE? STUDYING BETWEEN ORGANIZATIONAL CLIMATE AND JOB INVOLVEMENT
Authors: Yusnita Nancy
Published: April 2021

Many pieces of research on job involvement had generated findings that job involvement is considered to be one of the main ways to increase employees' performance. The objective of this study is to examine factors that have a relationship with job involvement namely organizational climate and self-efficacy. By finding the important factors that influence job involvement, it is expected that efforts to increase job involvement are useful for enhancing performance This study was conducted among lecturers at 4 private universities in Bogor, Indonesia. The sample for the study consisted of 252 lecturers derived randomly from its population. The study mainly utilized quantitative data (from questionnaires). The regression analysis was used to find out the relationship among variables. The findings revealed that organizational climate had a positive effect on job involvement. Similarly, self-efficacy had a positive effect on job involvement. The further organizational climate had a positive effect on job involvement through self-efficacy. The research result showed that self-efficacy as the intervening had significant a role in the effect of organizational climate on job involvement. Also, based on those findings, this study proposed some recommendations toward private universities to strengthening the self-efficacy of the lecturers to increasing their job involvement to increase performance
Egg Reintroduction Following Oral Food Challenge in Japanese Children
Authors: Masumi Hiroki , Takemura Yutaka , Arima Tomoyuki , Yamasaki Koji , Nagai Megumi , Inoue Norihiro , Sugimoto Keisuke
Published: April 2021

Background:Oral food challenge (OFC) is the most reliable method for diagnosing food allergies. However, the scarcity of long-term data on eating habits of people after a negative OFC poses a challenge for provisional medical care.

Objective:This study was performed to investigate the percentage of people who could reintroduce eggs into their diet several years after an OFC.

Methods:Study participants included 0–6-year-old children with negative results from an OFC using one egg as the food allergen, boiled for 20 min, from January 2012–March 2017, 1–3 years after the OFC.

Results:A total of 72 subjects were analyzed, out of which 52 were males (72.2%). The median age (range) was 20 months (16–32.3), and the median age (range) at the first OFC was 15 months (12.8–23.3). Eggs were reintroduced in 62 cases (86.1%), while 10 cases (13.9%) did not undergo any diet change. The adjusted odds ratio (OR, 95% CI), with post-OFC to pre-OFC anxiety ≥ 0.2, was 9.4 (1.0–86),p= 0.04; OR for allergic symptoms that occurred post-OFC was 2.2 (0.45–11),p= 0.34; OR for initial OFC at an age of ≥15 months was 3.2 (0.54–19),p= 0.2; and OR for the history of anaphylaxis from eggs was 0.17 (0.02–1.5),p= 0.11.

Conclusion:Most cases reintroduced eggs after an OFC. However, reintroduction did not occur in some cases, which was associated with greater anxiety among caregivers post-OFC. If the caregiver's anxiety is intense, it is necessary to provide psychological intervention and dietary guidance when reintroducing eggs at home after an OFC and to follow-up outpatient long-term progress.
Toward Predicting Motion Sickness Using Virtual Reality and a Moving Platform Assessing Brain, Muscles, and Heart Signals
Authors: Recenti Marco , Ricciardi Carlo , Aubonnet Romain , Picone Ilaria , Jacob Deborah , Svansson Halldór Á. R. , Agnarsdóttir Sólveig , Karlsson Gunnar H. , Baeringsdóttir Valdís , Petersen Hannes , Gargiulo Paolo
Published: April 2021

Motion sickness (MS) and postural control (PC) conditions are common complaints among those who passively travel. Many theories explaining a probable cause for MS have been proposed but the most prominent is the sensory conflict theory, stating that a mismatch between vestibular and visual signals causes MS. Few measurements have been made to understand and quantify the interplay between muscle activation, brain activity, and heart behavior during this condition. We introduce here a novel multimetric system called BioVRSea based on virtual reality (VR), a mechanical platform and several biomedical sensors to study the physiology associated with MS and seasickness. This study reports the results from 28 individuals: the subjects stand on the platform wearing VR goggles, a 64-channel EEG dry-electrode cap, two EMG sensors on the gastrocnemius muscles, and a sensor on the chest that captures the heart rate (HR). The virtual environment shows a boat surrounded by waves whose frequency and amplitude are synchronized with the platform movement. Three measurement protocols are performed by each subject, after each of which they answer the Motion Sickness Susceptibility Questionnaire. Nineteen parameters are extracted from the biomedical sensors (5 from EEG, 12 from EMG and, 2 from HR) and 13 from the questionnaire. Eight binary indexes are computed to quantify the symptoms combining all of them in the Motion Sickness Index (IMS). These parameters create the MS database composed of 83 measurements. All indexes undergo univariate statistical analysis, with EMG parameters being most significant, in contrast to EEG parameters. Machine learning (ML) gives good results in the classification of the binary indexes, finding random forest to be the best algorithm (accuracy of 74.7 for IMS). The feature importance analysis showed that muscle parameters are the most relevant, and for EEG analysis, beta wave results were the most important. The present work serves as the first step in identifying the key physiological factors that differentiate those who suffer from MS from those who do not using the novel BioVRSea system. Coupled with ML, BioVRSea is of value in the evaluation of PC disruptions, which are among the most disturbing and costly health conditions affecting humans.
Biomechanical Investigation Between Rigid and Semirigid Posterolateral Fixation During Daily Activities: Geometrically Parametric Poroelastic Finite Element Analyses
Authors: Nikkhoo Mohammad , Lu Meng-Ling , Chen Wen-Chien , Fu Chen-Ju , Niu Chi-Chien , Lin Yang-Hua , Cheng Chih-Hsiu
Published: April 2021

While spinal fusion using rigid rods remains the gold standard treatment modality for various lumbar degenerative conditions, its adverse effects, including accelerated adjacent segment disease (ASD), are well known. In order to better understand the performance of semirigid constructs using polyetheretherketone (PEEK) in fixation surgeries, the objective of this study was to analyze the biomechanical performance of PEEK versus Ti rods using a geometrically patient-specific poroelastic finite element (FE) analyses. Ten subject-specific preoperative models were developed, and the validity of the models was evaluated with previous studies. Furthermore, FE models of those lumbar spines were regenerated based on postoperation images for posterolateral fixation at the L4–L5 level. Biomechanical responses for instrumented and adjacent intervertebral discs (IVDs) were analyzed and compared subjected to static and cyclic loading. The preoperative model results were well comparable with previous FE studies. The PEEK construct demonstrated a slightly increased range of motion (ROM) at the instrumented level, but decreased ROM at adjacent levels, as compared with the Ti. However, no significant changes were detected during axial rotation. During cyclic loading, disc height loss, fluid loss, axial stress, and collagen fiber strain in the adjacent IVDs were higher for the Ti construct when compared with the intact and PEEK models. Increased ROM, experienced stress in AF, and fiber strain at adjacent levels were observed for the Ti rod group compared with the intact and PEEK rod group, which can indicate the risk of ASD for rigid fixation. Similar to the aforementioned pattern, disc height loss and fluid loss were significantly higher at adjacent levels in the Ti rod group after cycling loading which alter the fluid–solid interaction of the adjacent IVDs. This phenomenon debilitates the damping quality, which results in disc disability in absorbing stress. Such finding may suggest the advantage of using a semirigid fixation system to decrease the chance of ASD.
LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
Authors: Bozal-Basterra Laura , Gonzalez-Santamarta María , Muratore Veronica , Martín-Martín Natalia , Ercilla Amaia , Rodríguez Jose A. , Carracedo Arkaitz , Sutherland James D. , Barrio Rosa
Published: April 2021

LUZP1 is a centrosomal and actin cytoskeleton-localizing protein that regulates both ciliogenesis and actin filament bundling. As the cytoskeleton and cilia are implicated in metastasis and tumor suppression, we examined roles for LUZP1 in the context of cancer. Here we show that LUZP1 exhibits frequent genomic aberrations in cancer, with a predominance of gene deletions. Furthermore, we demonstrate that CRISPR/Cas9-mediated loss of Luzp1 in mouse fibroblasts promotes cell migration and invasion features, reduces cell viability, and increases cell apoptosis, centriole numbers, and nuclear size while altering the actin cytoskeleton. Loss of Luzp1 also induced changes to ACTR3 (Actin Related Protein 3, also known as ARP3) and phospho-cofilin ratios, suggesting regulatory roles in actin polymerization, beyond its role in filament bundling. Our results point to an unprecedented role for LUZP1 in the regulation of cancer features through the control of actin cytoskeleton.
Pkd2 Affects Cilia Length and Impacts LR Flow Dynamics and Dand5
Authors: Jacinto Raquel , Sampaio Pedro , Roxo-Rosa Mónica , Pestana Sara , Lopes Susana S.
Published: April 2021

The left-right (LR) field recognizes the importance of the mechanism involving the calcium permeable channel Polycystin-2. However, whether the early LR symmetry breaking mechanism is exclusively via Polycystin-2 has not been tested. For that purpose, we need to be able to isolate the effects of decreasing the levels of Pkd2 protein from any eventual effects on flow dynamics. Here we demonstrate that curly-up (cup) homozygous mutants have abnormal flow dynamics. In addition, we performed one cell stage Pkd2 knockdowns and LR organizer specific Pkd2 knockdowns and observed that both techniques resulted in shorter cilia length and abnormal flow dynamics. We conclude that Pkd2 reduction leads to LR defects that cannot be assigned exclusively to its putative role in mediating mechanosensation because indirectly, by modifying cell shape or decreasing cilia length, Pkd2 deficit affects LR flow dynamics.
A Non-canonical Wnt Signature Correlates With Lower Survival in Gastric Cancer
Authors: Astudillo Pablo
Published: April 2021

Genetic evidence suggests a role for the Wnt/β-catenin pathway in gastric cancer. However, Wnt5a, regarded as a prototypical non-canonical Wnt ligand, has also been extensively associated with this disease. Therefore, the roles of the Wnt signaling pathway in gastric cancer initiation and progression, and particularly the precise mechanisms by which the non-canonical Wnt pathway might promote the development and progression of gastric cancer, are not entirely well understood. This article analyzes publicly available gene and protein expression data and reveals the existence of a WNT5A/FZD2/FZD7/ROR2 signature, which correlates with tumor-infiltrating and mesenchymal cell marker expression. High expression of FZD7 and ROR2 correlates with a shared gene and protein expression profile, which in turn correlates with poor prognosis. In summary, the findings presented in this article provide an updated view of the relative contributions of the Wnt/β-catenin and non-canonical Wnt pathways in gastric cancer.
Semaphorin Regulation by the Chromatin Remodeler CHD7: An Emerging Genetic Interaction Shaping Neural Cells and Neural Crest in Development and Cancer
Authors: Lettieri Antonella , Oleari Roberto , Paganoni Alyssa J. J. , Gervasini Cristina , Massa Valentina , Fantin Alessandro , Cariboni Anna
Published: April 2021

CHD7 is a chromatin remodeler protein that controls gene expressionviathe formation of multi-protein complexes with specific transcription factors. During development, CHD7 controls several differentiation programs, mainly by acting on neural progenitors and neural crest (NC) cells. Thus, its roles range from the central nervous system to the peripheral nervous system and the organs colonized by NC cells, including the heart. Accordingly, mutatedCHD7is linked to CHARGE syndrome, which is characterized by several neuronal dysfunctions and by malformations of NC-derived/populated organs. Altered CHD7 has also been associated with different neoplastic transformations. Interestingly, recent evidence revealed that semaphorins, a class of molecules involved in developmental and pathological processes similar to those controlled by CHD7, are regulated by CHD7 in a context-specific manner. In this article, we will review the recent insights that support the existence of genetic interactions between these pathways, both during developmental processes and cancer progression.
Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis
Authors: Li Shenglong , Wang Wei
Published: April 2021

As one of the most common metastatic sites, bone has a unique microenvironment for the growth and prosperity of metastatic tumor cells. Bone metastasis is a common complication for tumor patients and accounts for 15–20% of systemic metastasis, which is only secondary to lung and liver metastasis. Cancers prone to bone metastasis include lung, breast, and prostate cancer. Extracellular vesicles (EVs) are lipid membrane vesicles released from different cell types. It is clear that EVs are associated with multiple biological phenomena and are crucial for intracellular communication by transporting intracellular substances. Recent studies have implicated EVs in the development of cancer. However, the potential roles of EVs in the pathological exchange of bone cells between tumors and the bone microenvironment remain an emerging area. This review is focused on the role of tumor-derived EVs in bone metastasis and possible regulatory mechanisms.
A Comparative Biology of Microglia Across Species
Authors: Sharma Kaushik , Bisht Kanchan , Eyo Ukpong B.
Published: April 2021

Microglia are unique brain-resident, myeloid cells. They have received growing interest for their implication in an increasing number of neurodevelopmental, acute injury, and neurodegenerative disorders of the central nervous system (CNS). Fate-mapping studies establish microglial ontogeny from the periphery during development, while recent transcriptomic studies highlight microglial identity as distinct from other CNS cells and peripheral myeloid cells. This evidence for a unique microglial ontogeny and identity raises questions regarding their identity and functions across species. This review will examine the available evidence for microglia in invertebrate and vertebrate species to clarify similarities and differences in microglial identity, ontogeny, and physiology across species. This discussion highlights conserved and divergent microglial properties through evolution. Finally, we suggest several interesting research directions from an evolutionary perspective to adequately understand the significance of microglia emergence. A proper appreciation of microglia from this perspective could inform the development of specific therapies geared at targeting microglia in various pathologies.
Hippo-Independent Regulation of Yki/Yap/Taz: A Non-canonical View
Authors: Cho Yong Suk , Jiang Jin
Published: April 2021

Initially identified in Drosophila, the Hippo signaling pathway has emerged as an evolutionarily conserved tumor suppressor pathway that controls tissue growth and organ size by simultaneously inhibiting cell proliferation and promoting cell death. Deregulation of Hippo pathway activity has been implicated in a wide range of human cancers. The core Hippo pathway consists of a kinase cascade: an upstream kinase Hippo (Hpo)/MST1/2 phosphorylates and activates a downstream kinase Warts (Wts)/Lats1/2, leading to phosphorylation and inactivation of a transcriptional coactivator Yki/YAP/Taz. Many upstream signals, including cell adhesion, polarity, mechanical stress, and soluble factors, regulate Hippo signaling through the kinase cascade, leading to change in the cytoplasmic/nuclear localization of Yki/YAP/Taz. However, recent studies have uncovered other mechanisms that regulate Yki/YAP/Taz subcellular localization, stability, and activity independent of the Hpo kinase cascade. These mechanisms provide additional layers of pathway regulation, nodes for pathway crosstalk, and opportunities for pathway intervention in cancer treatment and regenerative medicine.
Targeting of CAT and VCAM1 as Novel Therapeutic Targets for DMD Cardiomyopathy
Authors: Li Bin , Xiong Weiyao , Liang Wen-Miin , Chiou Jian-Shiun , Lin Ying-Ju , Chang Alex C. Y.
Published: April 2021

Duchenne muscular dystrophy (DMD) related cardiomyopathy is the leading cause of early mortality in DMD patients. There is an urgent need to gain a better understanding of the disease molecular pathogenesis and develop effective therapies to prevent the onset of heart failure. In the present study, we used DMD human induced pluripotent stem cells (DMD-hiPSCs) derived cardiomyocytes (CMs) as a platform to explore the active compounds in commonly used Chinese herbal medicine (CHM) herbs. Single CHM herb (DaH, ZK, and CQZ) reduced cell beating rate, decreased cellular ROS accumulation, and improved structure of DMD hiPSC-CMs. Cross-comparison of transcriptomic profiling data and active compound library identified nine active chemicals targeting ROS neutralizing Catalase (CAT) and structural protein vascular cell adhesion molecule 1 (VCAM1). Treatment with Quecetin, Kaempferol, and Vitamin C, targeting CAT, conferred ROS protection and improved contraction; treatment with Hesperidin and Allicin, targeting VCAM1, induced structure enhancement via induction of focal adhesion. Lastly, overexpression of CAT or VCAM1 in DMD hiPSC-CMs reconstituted efficacious effects and conferred increase in cardiomyocyte function. Together, our results provide a new insight in treating DMD cardiomyopathy via targeting of CAT and VCAM1, and serves as an example of translating Bed to Bench back to Bed using a muti-omics approach.
Androgen Receptor-Related Non-coding RNAs in Prostate Cancer
Authors: Yang Yongyong , Liu Kilia Y. , Liu Qi , Cao Qi
Published: April 2021

Prostate cancer (PCa) is the second leading cause of cancer-related death among men in the United States. Androgen receptor (AR) signaling is the dominant oncogenic pathway in PCa and the main strategy of PCa treatment is to control the AR activity. A large number of patients acquire resistance to Androgen deprivation therapy (ADT) due to AR aberrant activation, resulting in castration-resistant prostate cancer (CRPC). Understanding the molecular mechanisms underlying AR signaling in the PCa is critical to identify new therapeutic targets for PCa patients. The recent advances in high-throughput RNA sequencing (RNA-seq) techniques identified an increasing number of non-coding RNAs (ncRNAs) that play critical roles through various mechanisms in different diseases. Some ncRNAs have shown great potentials as biomarkers and therapeutic targets. Many ncRNAs have been investigated to regulate PCa through direct association with AR. In this review, we aim to comprehensively summarize recent findings of the functional roles and molecular mechanisms of AR-related ncRNAs as AR regulators or targets in the progression of PCa.
Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis
Authors: Chen Qin , Liu Xingguang , Wang Dingyu , Zheng Jisi , Chen Lu , Xie Qianyang , Liu Xiaohan , Niu Sujuan , Qu Guanlin , Lan Jianfeng , Li Jing , Yang Chi , Zou Duohong
Published: April 2021

Periodontitis is an immune inflammatory disease that leads to progressive destruction of bone and connective tissue, accompanied by the dysfunction and even loss of periodontal ligament stem cells (PDLSCs). Pyroptosis mediated by gasdermin-D (GSDMD) participates in the pathogenesis of inflammatory diseases. However, whether pyroptosis mediates PDLSC loss, and inflammation triggered by pyroptosis is involved in the pathological progression of periodontitis remain unclear. Here, we found that PDLSCs suffered GSDMD-dependent pyroptosis to release interleukin-1β (IL-1β) during human periodontitis. Importantly, the increased IL-1β level in gingival crevicular fluid was significantly correlated with periodontitis severity. The caspase-4/GSDMD-mediated pyroptosis caused by periodontal bacteria and cytoplasmic lipopolysaccharide (LPS) dominantly contributed to PDLSC loss. By releasing IL-1β into the tissue microenvironment, pyroptotic PDLSCs inhibited osteoblastogenesis and promoted osteoclastogenesis, which exacerbated the pathological damage of periodontitis. Pharmacological inhibition of caspase-4 or IL-1β antibody blockade in a rat periodontitis model lead to the significantly reduced loss of alveolar bone and periodontal ligament damage. Furthermore, Gsdmd deficiency alleviated periodontal inflammation and bone loss in mouse experimental periodontitis. These findings indicate that GSDMD-driven PDLSC pyroptosis and loss plays a pivotal role in the pathogenesis of periodontitis by increasing IL-1β release, enhancing inflammation, and promoting osteoclastogenesis.
Telomere Replication: Solving Multiple End Replication Problems
Authors: Bonnell Erin , Pasquier Emeline , Wellinger Raymund J.
Published: April 2021

Eukaryotic genomes are highly complex and divided into linear chromosomes that require end protection from unwarranted fusions, recombination, and degradation in order to maintain genomic stability. This is accomplished through the conserved specialized nucleoprotein structure of telomeres. Due to the repetitive nature of telomeric DNA, and the unusual terminal structure, namely a protruding single stranded 3′ DNA end, completing telomeric DNA replication in a timely and efficient manner is a challenge. For example, the end replication problem causes a progressive shortening of telomeric DNA at each round of DNA replication, thus telomeres eventually lose their protective capacity. This phenomenon is counteracted by the recruitment and the activation at telomeres of the specialized reverse transcriptase telomerase. Despite the importance of telomerase in providing a mechanism for complete replication of telomeric ends, the majority of telomere replication is in fact carried out by the conventional DNA replication machinery. There is significant evidence demonstrating that progression of replication forks is hampered at chromosomal ends due to telomeric sequences prone to form secondary structures, tightly DNA-bound proteins, and the heterochromatic nature of telomeres. The telomeric loop (t-loop) formed by invasion of the 3′-end into telomeric duplex sequences may also impede the passage of replication fork. Replication fork stalling can lead to fork collapse and DNA breaks, a major cause of genomic instability triggered notably by unwanted repair events. Moreover, at chromosomal ends, unreplicated DNA distal to a stalled fork cannot be rescued by a fork coming from the opposite direction. This highlights the importance of the multiple mechanisms involved in overcoming fork progression obstacles at telomeres. Consequently, numerous factors participate in efficient telomeric DNA duplication by preventing replication fork stalling or promoting the restart of a stalled replication fork at telomeres. In this review, we will discuss difficulties associated with the passage of the replication fork through telomeres in both fission and budding yeasts as well as mammals, highlighting conserved mechanisms implicated in maintaining telomere integrity during replication, thus preserving a stable genome.
Satisfaction With the Collaboration Between Families and Schools – The Parent’s View
Authors: Paccaud Ariane , Keller Roger , Luder Reto , Pastore Giuliana , Kunz André
Published: April 2021

Families and schools are two of the central living environments of children. Their collaboration is therefore seen as an important factor in education, having a high impact on learning outcomes, motivation, and children’s health. Nevertheless, current research also shows potential tensions in the educational partnership of families and schools, as different opinions and expectations about goals, competences and roles in education can result in conflicts. Based on a nationwide survey of Swiss parents who assessed the school situation of their children (N= 1275), this study examined parent’s experiences, needs and expectations regarding collaboration with schools, with a focus on important issues such as involvement in educational decisions, inclusion, and health. Results show a generally high level of satisfaction among parents, which is particularly related to the emotional well-being of their children at school, the quality of collaboration, and the trust in schools and teachers, both for parents of children with and without special educational needs (SEN). Nevertheless, involvement in educational decisions is perceived as rather marginal. Furthermore, the results indicate that parents of children with SEN are less confident about their children’s future. They are also less optimistic about their children’s academic self-concept and slightly more dissatisfied with their children’s school. Parents’ attitudes toward inclusion showed a wide range of opinions: on the one hand, inclusion is seen positively in terms of developing students’ social skills or promoting a more inclusive society. On the other hand, however, the resources of the school and the skills of the teachers were sometimes considered as insufficient. Our findings provide important insights regarding the further development of the educational partnership between schools and families. Good collaboration between schools and families can create an environment that promotes students’ emotional well-being as well as their academic skills. The positive impact of this partnership has been demonstrated in numerous studies and contributes to the implementation of an inclusive healthy school.
Mechanisms That Underly T Cell Immunity in Graves’ Orbitopathy
Authors: Fang Sijie , Lu Yi , Huang Yazhuo , Zhou Huifang , Fan Xianqun
Published: April 2021

Graves’ orbitopathy (GO), also known as thyroid-associated ophthalmopathy, is the most common ocular abnormality of Graves’ disease. It is a disfiguring, invalidating, and potentially blinding orbital disease mediated by an interlocking and complicated immune network. Self-reactive T cells directly against thyroid-stimulating hormone receptor-bearing orbital fibroblasts contribute to autoimmune inflammation and tissue remodeling in GO orbital connective tissues. To date, T helper (Th) 1 (cytotoxic leaning) and Th2 (antibody leaning) cell subsets and an emerging role of Th17 (fibrotic leaning) cells have been implicated in GO pathogenesis. The potential feedback loops between orbital native residential CD34-fibroblasts, CD34+infiltrating fibrocytes, and effector T cells may affect the T cell subset bias and the skewed pattern of cytokine production in the orbit, thereby determining the outcomes of GO autoimmune reactions. Characterization of the T cell subsets that drive GO and the cytokines they express may significantly advance our understanding of orbital autoimmunity and the development of promising therapeutic strategies against pathological T cells.
Four Novel Prognostic Genes Related to Prostate Cancer Identified Using Co-expression Structure Network Analysis
Authors: Feng Tao , Wei Dechao , Li Qiankun , Yang Xiaobing , Han Yili , Luo Yong , Jiang Yongguang
Published: April 2021

Prostate cancer (PCa) is one of the most common malignancies for males, but very little is known about its pathogenesis. This study aimed to identify novel biomarkers associated with PCa prognosis and elucidate the underlying molecular mechanism. First, The Cancer Genome Atlas (TCGA) RNA-sequencing data were utilized to identify differentially expressed genes (DEGs) between tumor and normal samples. The DEGs were then applied to construct a co-expression and mined using structure network analysis. The magenta module that was highly related to the Gleason score (r = 0.46, p = 3e–26) and tumor stage (r = 0.38, p = 2e–17) was screened. Subsequently, all genes of the magenta module underwent function annotation. From the key module, CCNA2, CKAP2L, NCAPG, and NUSAP1 were chosen as the four candidate genes. Finally, internal (TCGA) and external data sets (GSE32571, GSE70770, and GSE141551) were combined to validate and predict the value of real hub genes. The results show that the above genes are up-regulated in PCa samples, and higher expression levels show significant association with higher Gleason scores and tumor T stage. Moreover, receiver operating characteristic curve and survival analysis validate the excellent value of hub genes in PCa progression and prognosis. In addition, the protein levels of these four genes also remain higher in tumor tissues when compared with normal tissues. Gene set enrichment analysis and gene set variation analysis for a single gene reveal the close relation with cell proliferation. Meanwhile, 11 small molecular drugs that have the potential to treat PCa were also screened. In conclusion, our research identified four potential prognostic genes and several candidate molecular drugs for treating PCa.
Multigenerational Epigenetic Regulation of Allergic Diseases: Utilizing an Experimental Dust Mite-Induced Asthma Model
Authors: Pulczinski Jairus C. , Shang Yan , Dao Tyna , Limjunyawong Nathachit , Sun Qinying , Mitzner Wayne , Cheng Robert YS , Tang Wan-yee
Published: April 2021

Environmental exposures have been linked to increased asthma risk, particularly during pregnancy and in early life. Here we use a mouse model of allergic lung disease to examine the effects of pre- and perinatal house dust mite (HDM) allergen exposure on offspring phenotypic and transcriptional outcomes in three generations. We show that maternal HDM exposure (F0) acts synergistically with adult HDM exposure, leading to enhanced airway hyperresponsiveness (AHR) and lung inflammation when compared to mice exposed solely in adulthood. Additionally, a subset of F1 males were not challenged in adulthood, and used to generate F2 progeny, which was then used to generate F3 progeny. Upon adult challenge to HDM, F2, and F3 males generated from the maternal HDM (F0) exposure lineage displayed increased airway reactivity and inflammation when compared to mice exposed solely in adulthood. These findings indicate that maternal allergen exposure is capable of enhancing either susceptibly to or severity of allergic airway disease. To examine the role of epigenetic inheritance of asthma susceptibility induced by maternal HDM exposure, we utilized a genome-wide MeDIP-seq and hMeDIP-seq analysis to identify genes differentially methylated (DMG) and hydroxymethylated (DHG), and their association with the enhanced AHR. In addition, we validated the relationship between DNA methylation and mRNA expression of the DMGs and DHGs in the male sub-generations (F1-F3). We found the expression of Kchn1, Nron, and Spag17 to be differentially hydroxymethylated and upregulated in the F1 exposed to HDM both in early life and in adulthood when compared to F1 mice exposed solely in adulthood. Kcnh1 remained upregulated in the F2 and F3 from the maternal HDM (F0) exposure lineage, when compared to F1 mice exposed solely in adulthood. In summary, we demonstrated that maternal HDM exposure in early life can alter the gene expression and phenotype of offspring upon adult HDM exposure, resulting in more severe disease. These effects persist at least two generations past the initial insult, transmitted along the paternal line.
Interplay Between Thiamine and p53/p21 Axes Affects Antiproliferative Action of Cisplatin in Lung Adenocarcinoma Cells by Changing Metabolism of 2-Oxoglutarate/Glutamate
Authors: Aleshin Vasily A. , Zhou Xiaoshan , Krishnan Shuba , Karlsson Anna , Bunik Victoria I.
Published: April 2021

Thiamine (vitamin B1) is often deficient in oncopatients, particularly those undergoing chemotherapy. However, interaction between the thiamine deficiency and anticancer action of drugs has not been characterized. A major natural thiamine derivative, thiamine diphosphate (ThDP), is a coenzyme of central metabolism, also known to affect transcriptional activity of the master metabolic regulator and genome guardian p53. A direct transcriptional target of p53, p21, regulates cell cycle dynamics and DNA damage response. Our work focuses on dependence of the action of the DNA damaging anticancer drug cisplatin on metabolic regulation through p53/p21 axes and cellular thiamine status in human lung adenocarcinoma cells A549. These cells are used as a model of a hardly curable cancer, known to develop chemoresistance to platinum drugs, such as cisplatin. Compared to wild type (A549WT), a stable line with a 60% knockdown of p21 (A549p21–) is less sensitive to antiproliferative action of cisplatin. In contrast, in the thiamine-deficient medium, cisplatin impairs the viability of A549p21– cells more than that of A549WT cells. Analysis of the associated metabolic changes in the cells indicates that (i) p21 knockdown restricts the production of 2-oxoglutarate via glutamate oxidation, stimulating that within the tricarboxylic acid (TCA) cycle; (ii) cellular cisplatin sensitivity is associated with a 4-fold upregulation of glutamic-oxaloacetic transaminase (GOT2) by cisplatin; (iii) cellular cisplatin resistance is associated with a 2-fold upregulation of p53 by cisplatin. Correlation analysis of the p53 expression and enzymatic activities upon variations in cellular thiamine/ThDP levels indicates that p21 knockdown substitutes positive correlation of the p53 expression with the activity of 2-oxoglutarate dehydrogenase complex (OGDHC) for that with the activity of glutamate dehydrogenase (GDH). The knockdown also changes correlations of the levels of OGDHC, GDH and GOT2 with those of the malate and isocitrate dehydrogenases. Thus, a p53/p21-dependent change in partitioning of the glutamate conversion to 2-oxoglutarate through GOT2 or GDH, linked to NAD(P)-dependent metabolism of 2-oxoglutarate in affiliated pathways, adapts A549 cells to thiamine deficiency or cisplatin treatment. Cellular thiamine deficiency may interfere with antiproliferative action of cisplatin due to their common modulation of the p53/p21-dependent metabolic switch between the glutamate oxidation and transamination.