bluuebunny/crossref_metadata_2025 huggingface dataset:
Keterampilan Guru Mengelola Kelas pada Proses Pembelajaran untuk Menumbuhkan Sikap Disiplin Belajar Siswa (Studi Deskriptif Kelas IVB SD Negeri 01 Kota Bengkulu)
Authors: Putra Eka Aryista , Djuwita Puspa , Juarsa Osa
Published: June 2021

Penelitian ini bertujuan untuk mendeskripsikan salah satu keterampilan guru untuk menumbuhkan sikapdisiplin yaitu, keterampilan guru dalam mengelola kelas pada pembelajaran di kelas IV SD Negeri 01 KotaBengkulu. Pendekatan dan jenis penelitian yang digunakan adalah deskriptif kualitatif. Subjek penelitianadalah guru kelas IV. Teknik pengumpulan data menggunakan teknik observasi, wawancara, dokumentasiserta dilengkapi dengan catatan lapangan. Teknik analisis data melalui tiga tahap yaitu reduksi data,penyajian data, dan penarikan kesimpulan. Uji kredibilitas data melalui perpanjangan pengamatan,peningkatan ketekunan, member check dan trianggulasi. Hasil penelitian menunjukkan bahwa subjekpenelitian dalam mengelola kelas pada proses pembelajaran telah sesuai dengan komponennya (Preventif)yaitu, 1) menunjukan sikap tanggap, 2) Memusatkan perhatian kelompok, dan 3) Memberi petunjuk yangjelas, 4) Penguatan serta komponen (Represif) yaitu, 1) memodifikasi tingkah laku 2) pengelolaan kelompokdan 3) menemukan dan mengatasi prilaku yang menimbulkan masalah. Berdasarkan hasil penelitiandisimpulkan bahwa guru kelas IV SD Negeri 01 Kota Bengkulu dalam pembelajaran melakukan pengelolankelas sesuai dengan komponen Preventif dan Represif.
Pembelajaran Pendidikan Kewarganegaraan Berbasis Pendidikan Nilai
Authors: Djuwita Puspa Djuwita
Published: June 2021

Pengembangan materi ajar merupakan hal yang sangat penting dalam aktivitas pendidikan. Tanpa adanya materi pembelajaran, kegiatan pendidikan tidak akan dapat terjadi. Oleh sebab itu materi ajar perkuliahan wajib diinovasi, karena kebutuhan akan keterbaharuan pengetahuan merupakan hal yang penting, apa lagi dengan pesatnya perkembangan kehidupan masyarakat global pada abad 21, di mana setiap saat terjadi perubahan pola kehidupan dalam hubungan berbangsa dan bernegara sesuai dengan perkembangan zaman, berdampak pada perkembangan ilmu pengetahuan disertai oleh kemajuan bidang informasi dan teknologi dalam pembelajaran, yang begitu pesat. Penelitian pengembangan materi ajar pembelajaran Sekolah Dasar (SD) bidang PKn bertujuan untuk; [a] melakukan pengembangan bahan ajar mata kuliah pengembangan pembelajaran SD bidang PKn berbasis pendidikan nilai, [b] terwujudnya bahan perkuliahan pengembangan pembelajaran PKn berbasis pendidikan nilai dengan konten yang kekinian, tanpa mengurangi esensi konten pembelejaran PKn selama ini, [c] tersedianya referensi pengembangan pembelajaran bidang PKn SD berbasis pendidikan nilai yang dapat digunakan sebagai acuan mahasiswa yang mengambil perkuliahan konsentrasi PKn, dan penyelesaian tugas akhir, [d] tersedianya variasi refrensi bahan ajar pengembangan pembelajaran bidang PKn yang pas bagi mahasiswa pasca sarjana. Penelitian ini dirancang dengan menggunakan pendekatan penelitian pengembangan (Resarch and Development), Teknik pengumpulan data, yaitu; wawancara, dokumentasi. Analisis menggunakan teknik analisis data kualitatif. Analisis dilakukan terhadap data kebutuhan mahasiswa terhadap konten bahan ajar pengembangan pembelajaran PKn SD, dan analisis terhadap pendekatan strategi, dan model penidikan nilai mana yang dapat diintegrasikan sebagai konten dalam bahan ajar pengembangan pembelajaran PKn. Hasil penelitian diperlukan penamabahan materi tentang pendidikan nilai dalam pembelajaran bidang PKn. Implikasi dari tersusunnya bahan ajar bidang PKn SD ini dapat menambah wawasan dan dapat dimanfaatkan maha siswa dalam melaksanakan kuliah konsentrasi PKn, dan menyelasaikan tugas akhir (tesis) bagi yang memilih kajian pembelajaran PKn Simpulan penelitian antara lain; bahan ajar pembelajaran PKn telah dapat disusun dalam bentuk draf yang akan dijadikan buku ajar.
Penerapan Model Delikan dan CTL untuk Meningkatkan Prestasi Belajar Pancasila dan Pengembangan Karakter Mahasiswa PGSD FKIP Unib
Authors: Juarsa Osa Juarsa , Djuwita Puspa Djuwita
Published: June 2021

Penelitian ini bertujuan menganalisis peningkatan prestasi belajar Pancasila serta ketertanaman karakter pada diri mahasiswa dan mendekripsikan strategi yang paling tepat dilakukan melalui pembelajaran model delikan, dan CTL. Metode pendekatan menggunakan kaji tindak latar kelas atau clasroon action reserch . Penelitian  ini dilaksanakan di kelas 1A PGSD FKIP UNIB TA 2019/2020 dengan menggunakan sistem siklus.  Setiap siklusnya terdiri atas beberapa tahapan yaitu: (1) Perencanaan (planning); (2)  Pelaksanaan tindakan (action); (3) Pengamatan (observation); dan (4) Refleksi (reflection), Metode pengumpulan data yang digunakan adalah Observasi ,Tes Hasil Belajar, Wawancara. Metode Analisis Data dengan penilaian acuan patokan (PAP), analisa data hasil sebelum dan sesudah perlakuan/treatment digunakan statistik mean serta data yang tidak bisa dianalisa dengan rumus statistik akan dinarasikan kemudian diberi argumen. Hasil penelitian menunjukkan bahwa prestasi belajar mahasiswa dapat ditingkatkan dari rata-rata hasil belajar kelas 66,60 menjadi 83 serta terjadi ketertanaman karakter kedalam diri mahasiswa. Rata-rata skor hasil ceklis pengamatan perubahan karakter mahasiswa atas nilai-nilai yang terkandung dalam materi pembelajaran pada siklus 2 jauh lebik daripada pada siklus 1, dimana rata-rata skor pada siklus 1 sebesar 66,25 dan rata-rata skor pada siklus 2 sebesar 80,06. Peningkatan ini terjadi setelah mahasiswa diajak menggali nilai yang terkandung dalam materi yang dipelajari juga diajak untuk mamantau keterbiasaan melakukan, dan mengkaji dengan cara mengemukakan pertanyaan apa, mengapa, bagaimana, siapa, dimana dan kapan dilakukan serta kemana harus dipertanggungjawabkan serta dilakukan secara terus menerus.
USE OF UBIQUITOUS COMPUTING TECHNOLOGY IN LEARNING ENGLISH FOR ACADEMIC PURPOSES
Authors: DAĞ Muhammet , YILDIZ Mine
Published: June 2021

This case study aims at revealing EAP (English for academic purposes) learners’ experiences in and perceptions about using ubiquitous computing technology. Data were collected through interviews carried out with eleven people being prepared for the foreign language (English) exams for academic purposes in a private language course in Turkey. Fifteen open-ended questions were involved in face-to-face interviews. Data were collected through the audio recordings of interviews and then examined by content analysis method, and afterwards, codes, categories and themes were obtained. The findings of this study revealed that all of the participants were continuously and actively using ubiquitous computing technologies, they thought ubiquitous computing technologies had several advantages in learning English for academic purposes such as continuous and permanent learning, quick access to information, preventing waste of time, and interacting with other learners. However, some disadvantages and limitations of ubiquitous computing technologies such as technical and infrastructural problems, information pollution, and inadequacies in translation of terms were also tackled.
Prof. Dr. M. Zeki Duman ve İlmi Çalışmaları
Authors: Kaya Mehmet
Published: June 2021

Bu çalışmada Erciyes Üniversitesi İlahiyat Fakültesi Öğretim Üyelerinden merhum Prof. Dr. M. Zeki Duman’ın hayatı ve eserleri ele alınacaktır. Duman, yaşadığı dönemde ülkemizdeki tefsir akademisyenlerinin duayenlerinden olmasının yanı sıra bir tefsir eseri kaleme alan ender ilim adamlarından biridir. Duman, mezun olduğu ve o dönemdeki ismi Kayseri Yüksek İslâm Enstitüsü olan Erciyes Üniversitesi İlahiyat Fakültesi’nde otuz yıldan fazla görev yapmış bu süre zarfında bugün bir kısmı çeşitli İlahiyat Fakültelerinde akademisyen olan çok sayıda öğrenci yetiştirmiştir. 2009-2012 yılları arasında dekanlık görevini de icra eden Duman, fakültenin fiziki ve akademik altyapısının güçlenmesine de önemli katkı sağlamıştır. Yazdığı eserlerde tefsir alanına ilişkin problemli konuları ve sosyal sorunları aydınlatmaya odaklanan Duman, kendisini Fakülte sınırlarına hapseden bir akademisyen olmamıştır. O, Beyânu’l-Hak tefsiri başta olmak üzere çeşitli eserleriyle toplumun sorunlarına ışık tutmaya çalışmış bir ilim adamıdır. Kendi adındaki internet sitesiyle isteyenlerin bu bilgilere kolay ve ücretsiz ulaşmalarını da sağlamıştır. Uzun yıllar boyunca haftanın dört günü çeşitli meslek gruplarıyla yaptığı derslerle ve yurt içi ve yurt dışında verdiği konferanslarla sahip olduğu birikimi halkla da paylaşmıştır. Naif bir kişiliğe sahip olmakla birlikte profesyonel olarak sporla da ilgilenen Duman yardımsever kişiliğiyle ve bu noktadaki girişimleriyle de tanınmaktadır. Duman 10 Temmuz 2013 tarihinde geçirdiği trafik kazası sonucunda hayatını kaybetmiştir. Duman’ın eserlerinin çoğu hayattayken yayımlanmakla birlikte bir kısmı vefatının ardından evlatlarının girişimiyle yayımlanmıştır. Duman’ın tamamlayamadığı eserleri de mevcuttur. Biz bu çalışmada tefsir alanına uzun yıllar boyunca hizmet eden ve çok sayıda eser kaleme alan Duman’ın hayatı ve eserleri hakkında bilgi vererek onun ve eserlerinin tanınmasına katkı sağlamayı hedeflemekteyiz.
La felicidad en tiempos de pandemia y educación virtual: un estudio en universitarios del Altiplano
Authors: Vargas Pacosonco Kleiber Rosendo , Callata Gallegos Zaida Esther
Published: June 2021

El artículo consideró como objetivo identificar el nivel de felicidad en estudiantes universitarios que atraviesan una coyuntura atípica ocasionada por la pandemia Covid-19, la misma que tuvo como una de sus consecuencias en el ámbito educativo el desarrollo de clases a partir de sistemas remotos y virtuales, sucesos nuevos en un país como el Perú, los cuales después de un periodo de implementación registran efectos peculiares que permiten su estudio, la investigación utilizó el método no experimental, de corte transversal, tipo descriptivo de carácter cuantitativo en una muestra estratificada y proporcional de 224 universitarios de la Facultad de Ciencias de la Educación de la UNA – Puno, la única variable de estudio se evaluó con la Escala de Felicidad de Lima que consta de 27 reactivos. Entre los resultados más resaltantes se tiene que el 33.9%, percibe la felicidad en un nivel bajo, el 38.8% en un nivel medio y un 27.2% en un nivel alto. Se concluye el estudio afirmando que el nivel de felicidad de los estudiantes no responde a niveles deseados, debido a situaciones nulas de socialización académica causada por la emergencia sanitaria.
Tensiones en la comprensión de la educación inclusiva: dilemas conceptuales y prácticos
Authors: Ocampo González Aldo
Published: June 2021

El presente trabajo analiza los bloques de construcción del sistema de racionalidad de la educación inclusiva, confirmando que su aplicación a la formación del profesorado y de las políticas públicas, establecen categorías a través de las cuales se colocan tácticamente al servicio del poder. Cada una de estas, se emplean para hablar con fines específicos, conduciéndonos a la legitimación de un fraude inocente en el que los planteamientos de la educación inclusiva se travestizan con la fuerza de lo especial, adjudicándose un rostro benigno y potencialmente nuevo que no deshace los problemas introducidos por la imaginación educativa neoliberal. Su objetivo consiste en analizar críticamente los impactos que se desprenden de la falta de claridad epistémico-conceptual y metodológica que enfrenta la educación inclusiva en la gestión las políticas públicas y de formación del profesorado y su transferencia a las comunidades educativas. La metodología empleada en este trabajo fue la de revisión documental crítica. Se concluye, afirmando que, la educación inclusiva aborda cuestiones relativas a la naturaleza de la exclusión, de la justicia y de la transformación educativa y, del problema que designan la titularidad de derechos humanos en la experiencia escolar ante la falta de responsabilidad ética y social de los sistemas educativos.
Detection of Fuchs’ Uveitis Syndrome From Slit-Lamp Images Using Deep Convolutional Neural Networks in a Chinese Population
Authors: Zhang Wanyun , Chen Zhijun , Zhang Han , Su Guannan , Chang Rui , Chen Lin , Zhu Ying , Cao Qingfeng , Zhou Chunjiang , Wang Yao , Yang Peizeng
Published: June 2021

Fuchs’ uveitis syndrome (FUS) is one of the most under- or misdiagnosed uveitis entities. Many undiagnosed FUS patients are unnecessarily overtreated with anti-inflammatory drugs, which may lead to serious complications. To offer assistance for ophthalmologists in the screening and diagnosis of FUS, we developed seven deep convolutional neural networks (DCNNs) to detect FUS using slit-lamp images. We also proposed a new optimized model with a mixed “attention” module to improve test accuracy. In the same independent set, we compared the performance between these DCNNs and ophthalmologists in detecting FUS. Seven different network models, including Xception, Resnet50, SE-Resnet50, ResNext50, SE-ResNext50, ST-ResNext50, and SET-ResNext50, were used to predict FUS automatically with the area under the receiver operating characteristic curves (AUCs) that ranged from 0.951 to 0.977. Our proposed SET-ResNext50 model (accuracy = 0.930; Precision = 0.918; Recall = 0.923; F1 measure = 0.920) with an AUC of 0.977 consistently outperformed the other networks and outperformed general ophthalmologists by a large margin. Heat-map visualizations of the SET-ResNext50 were provided to identify the target areas in the slit-lamp images. In conclusion, we confirmed that a trained classification method based on DCNNs achieved high effectiveness in distinguishing FUS from other forms of anterior uveitis. The performance of the DCNNs was better than that of general ophthalmologists and could be of value in the diagnosis of FUS.
Insights Into Chemical Reactions at the Beginning of the Universe: From HeH+ to H3+
Authors: Dash Soumya Ranjan , Das Tamal , Vanka Kumar
Published: June 2021

At the dawn of the Universe, the ions of the light elements produced in the Big Bang nucleosynthesis recombined with each other. In our present study, we have tried to mimic the conditions in the early Universe to show how the recombination process would have led to the formation of the first ever formed diatomic species of the Universe: HeH+, as well as the subsequent processes that would have led to the formation of the simplest triatomic species: H3+. We have also studied some special cases: higher positive charge with fewer number of hydrogen atoms in a dense atmosphere, and the formation of unusual and interesting linear, dicationic He chains beginning from light elements He and H in a positively charged atmosphere. For all the simulations, the ab initio nanoreactor (AINR) dynamics method has been employed.
Combining Metagenomic Sequencing With Whole Exome Sequencing to Optimize Clinical Strategies in Neonates With a Suspected Central Nervous System Infection
Authors: Ge Mengmeng , Gan Mingyu , Yan Kai , Xiao Feifan , Yang Lin , Wu Bingbing , Xiao Mili , Ba Yin , Zhang Rong , Wang Jin , Cheng Guoqiang , Wang Laishuan , Cao Yun , Zhou Wenhao , Hu Liyuan
Published: June 2021

Objectives

Central nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES).

Methods

We prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples.

Results

Eighty-eight neonatal patients were enrolled, and 101 CSF samples were collected. Fourty-three blood samples were collected for WES. mNGS showed a sample diagnostic yield of 19.8% (20/101) compared to 4.95% (5/101) for the conventional methods. In the empirical treatment group, the detection rate of mNGS was significantly higher than that of conventional methods [27% vs. 6.3%, p=0.002]. Among the 88 patients, 15 patients were etiologically diagnosed by mNGS alone, five patients were etiologically identified by WES alone, and one patient was diagnosed by both mNGS and WES. Twelve of 13 diagnoses based solely on mNGS had a likely clinical effect. Six patients diagnosed by WES also experienced clinical effect.

Conclusions

For patients with a suspected CNS infections, mNGS combined with WES might significantly improve the diagnostic rate of the etiology and effectively guide clinical strategies.
Direct Flow Medical vs. Edwards Sapien 3 Prosthesis: A Propensity Matched Comparison on Intermediate Safety and Mortality
Authors: Edlinger Christoph , Bannehr Marwin , Wernly Bernhard , Kücken Tanja , Okamoto Maki , Lichtenauer Michael , Hähnel Valentin , Reiners David , Neuss Michael , Butter Christian
Published: June 2021

Aims: To compare intermediate performance and mortality rates in patients, who underwent transcatheter aortic valve implantation (TAVI) with two different types of prostheses: Edwards Sapien 3 (ES3) and Direct Flow Medical (DFM).

Methods and Results: 42 consecutive patients implanted with a DFM prosthesis for severe aortic stenosis were matched 1:1 with an equal number of patients, who received an ES3 during the same period. Primary endpoint was mortality. MACE, as a composite of all-cause death, stroke, and re-do-procedure (valve-in-valve), was defined as secondary endpoint. Moreover, we compared NYHA class, NT-proBNP-levels and the extent of restenosis. Patients were followed for 2 years. DFM patients showed echocardiographic elevated mean pressure gradients compared to ES3 patients before discharge (11.2 mmHg ± 5.3 vs. 3.5 mmHg ± 2.7; p < 0.001) and upon 6-months follow-up (20.3 mmHg ± 8.8 vs. 12.3 mmHg ± 4.4; p < 0.001). ES3 candidates showed superior NYHA class at follow-up (p = 0.001). Kaplan-Meier analysis revealed significantly worse survival in patients receiving a DFM prosthesis compared to ES3 (Breslow p = 0.020). MACE occurred more often in DFM patients compared to ES3 (Breslow p = 0.006).

Conclusions: Patients receiving DFM valve prostheses showed worse survival and higher rates in MACE compared to ES3. Prosthesis performance regarding mean pressure gradients and patients' NYHA class also favored ES3.
Clinical and Functional Genetic Characterization of the Role of Cardiac Calcium Channel Variants in the Early Repolarization Syndrome
Authors: Chen Xiu , Barajas-Martínez Hector , Xia Hao , Zhang Zhonghe , Chen Ganxiao , Yang Bo , Jiang Hong , Antzelevitch Charles , Hu Dan
Published: June 2021

Background: Early repolarization syndrome (ERS) is an inherited sudden cardiac death (SCD) syndrome. The present study investigates the role of genetic variants in cardiac calcium-channel genes in the pathogenesis of ERS and probes the underlying mechanisms.

Methods: Polymerase chain reaction–based next-generation sequencing was carried out using a targeted gene approach. Unrelated ERS probands carrying calcium-channel variants were evaluated clinically and compared with matched healthy controls. Wild-type (WT) and mutant CACNA1C genes were coexpressed with CACNB2b and CACNA2D1 in HEK293 cells and studied using whole-cell patch-clamp techniques and confocal fluorescence microscope.

Results: Among 104 ERS probands, 16 carried pathogenic variants in calcium-channel genes (32.2 ± 14.6 years old, 87.5% male). The symptoms at diagnosis included syncope (56.3%), ventricular tachycardia/fibrillation (62.5%), and SCD (56.3%). Three cases (18.8%) had a family history of SCD or syncope. Eight patients (50.0%) had a single calcium gene rare variant. The other half carried rare variants in other ERS-susceptible genes. Compared with controls, the heart rate was slower (72.7 ± 8.9 vs. 65.6 ± 16.1 beats/min, *p < 0.05), QTc interval was shorter (408.2 ± 21.4 vs. 386.8 ± 16.9 ms, **p < 0.01), and Tp-e/QT was longer (0.22 ± 0.05 vs. 0.28 ± 0.04, ***p < 0.001) in single calcium mutation carriers. Electrophysiological analysis of one mutation, CACNA1C-P817S (c.2449C>T), revealed that the density of whole-cell calcium current (ICa) was reduced by ~84.61% compared to WT (−3.17 ± 2.53 vs. −20.59 ± 3.60 pA/pF, n = 11 and 15, respectively, **p < 0.01). Heterozygous expression of mutant channels was associated with a 51.35% reduction of ICa. Steady-state inactivation was shifted to more negative potentials and significantly accelerated as well. Confocal microscopy revealed trafficking impairment of CACNA1C-P817S (peripheral/central intensity: 0.94 ± 0.10 in WT vs. 0.33 ± 0.12 in P817S, n = 10 and 9, respectively, **p < 0.01).

Conclusions: ERS associated with loss-of-function (LOF) genetic defects in genes encoding the cardiac calcium channel represents a unique clinical entity characterized by decreased heart rate and QTc, as well as increased transmural dispersion of repolarization. In the case of CACNA1C-P817S, impaired trafficking of the channel to the membrane contributes to the LOF.
Erosion Rate of Lateral Slope Deposit Under the Effects of Different Influencing Factors
Authors: Ge Yonggang , Guo Xiaojun , Zhan Meiqiang , Yan Hua
Published: June 2021

Lateral slope deposits along a channel represent an important source of material for initiation and development of debris flows/floods that are typically observed in many headwater tributaries. This study found that the failure process of such a deposit reflects combined interaction between external hydrodynamic factors (inflow discharge and channel slope) and internal factors (compactness and fine particle content). The erosion process comprises two stages: runoff erosion toward the toe of the deposit body and soil failure owing to gravity. Spatially, the erosion rate is distributed unevenly across the deposit; the highest value occurs at the section close to the middle of the deposit, on the upstream face. Temporally, the erosion rate decreases exponentially. Overall, the average erosion rate decreases (increases) with bulk density (inflow discharge and channel slope). However, a slope of 7 is a threshold at which the tendency of the erosion rate in relation to the fine particle content differs. In comparison with the other three influencing factors, the effect of the fine particle content is much smaller. Although the bulk density of the deposit imposes the most significant effect, it is of the same order as that of both inflow discharge and channel slope. As the failure process can be summarized as repeated runoff scouring of the toe of the deposit, deposit failure, and entrainment of the failure body by runoff, we proposed a calculation method for the total time required for a complete lateral erosion process, and validation of the calculation suggested its reasonability. The findings of this study enhance the understanding of the mechanism of lateral soil deposit failure, which could help improve runoff-induced debris flood forecasting in headwater regions of mountainous catchments.
Genomic Analysis Reveals Human-Mediated Introgression From European Commercial Pigs to Henan Indigenous Pigs
Authors: Wang Kejun , Zhang Lige , Duan Dongdong , Qiao Ruimin , Li Xiuling , Li Xinjian , Han Xuelei
Published: June 2021

Introgression of genetic features from European pigs into Chinese pigs was reported possibly contributing to improvements in productivity traits, such as feed conversion efficiency and body size. However, the genomic differences from European pigs and the potential role of introgression in Henan indigenous pigs remains unclear. In this study, we found significant introgression from European pigs into the genome of Chinese indigenous pigs, especially in Henan indigenous pigs. The introgression in Henan indigenous pigs, particularly in the Nanyang black pig, was mainly derived from Duroc pigs. Most importantly, we found that the NR6A1, GPD2, and CSRNP3 genes were introgressed and reshaped by artificial selection, and these may have contributed to increases in pig body size and feed conversion efficiency. Our results suggest that human-mediated introgression and selection have reshaped the genome of Henan pigs and improved several of their desired traits. These findings contribute to our understanding of the history of Henan indigenous pigs and provide insights into the genetic mechanisms affecting economically important traits in pig populations.
Genetic Variants in KIR/HLA-C Genes Are Associated With the Susceptibility to HCV Infection in a High-Risk Chinese Population
Authors: Shen Chao , Ge Zhijun , Dong Chen , Wang Chunhui , Shao Jianguo , Cai Weihua , Huang Peng , Fan Haozhi , Li Jun , Zhang Yun , Yue Ming
Published: June 2021

Background

KIR/HLA-C signaling pathway influences the innate immune response which is the first defense to hepatitis C virus (HCV) infection. The aim of this study was to determine the association between the genetic polymorphisms of KIR/HLA-C genes and the outcomes of HCV infection in a high-risk Chinese population.

Methods

In this case-control study, four single nucleotide polymorphisms (SNPs) of KIR/HLA-C genes (KIR2DS4/KIR2DS1/KIR2DL1 rs35440472, HLA-C rs2308557, HLA-C rs1130838, and HLA-C rs2524094) were genotyped by TaqMan assay among drug users and hemodialysis (HD) patients including 1,378 uninfected control cases, 307 subjects with spontaneous viral clearance, and 217 patients with persistent HCV infection. Bioinformatics analysis was used to functionally annotate the SNPs.

Results

After logistic regression analysis, the rs35440472-A and rs1130838-A alleles were found to be associated with a significantly elevated risk of HCV infection (OR = 1.562, 95% CI: 1.229–1.987, P < 0.001; OR = 2.134, 95% CI: 1.180–3.858, P = 0.012, respectively), which remained significant after Bonferroni correction (0.05/4). The combined effect of their risk alleles and risk genotypes (rs35440472-AA and rs1130838-AA) were linked to the increased risk of HCV infection in a locus-dosage manner (all Ptrend < 0.001). Based on the SNPinfo web server, rs35440472 was predicted to be a transcription factor binding site (TFBS) while rs1130838 was predicted to have a splicing (ESE or ESS) function.

Conclusion

KIR2DS4/KIR2DS1/KIR2DL1 rs35440472-A and HLA-C rs1130838-A variants are associated with increased susceptibility to HCV infection in a high-risk Chinese population.
Lipoprotein-Associated Phospholipase A2: A Novel Contributor in Sjögren’s Syndrome-Related Lymphoma?
Authors: Nezos Adrianos , Skarlis Charalampos , Psarrou Anna , Markakis Konstantinos , Garantziotis Panagiotis , Papanikolaou Asimina , Gravani Fotini , Voulgarelis Michael , Tzioufas Athanasios G. , Koutsilieris Michael , Moutsopoulos Haralampos M. , Kotsifaki Eleni , Mavragani Clio P.
Published: June 2021

Background

B-cell non-Hodgkin’s lymphoma (B-NHL) is one of the major complications of primary Sjögren’s syndrome (SS). Chronic inflammation and macrophages in SS minor salivary glands have been previously suggested as significant predictors for lymphoma development among SS patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2)—a product mainly of tissue macrophages—is found in the circulation associated with lipoproteins and has been previously involved in cardiovascular, autoimmune, and malignant diseases, including lymphoma.

Objective

The purpose of the current study was to investigate the contributory role of Lp-PLA2 in B-NHL development in the setting of primary SS.

Methods

Lp-PLA2 activity in serum samples collected from 50 primary SS patients with no lymphoma (SS-nL), 9 primary SS patients with lymphoma (SS-L), and 42 healthy controls (HC) was determined by detection of [3H]PAF degradation products by liquid scintillation counter. Moreover, additional sera from 50 SS-nL, 28 SS-L, and 32 HC were tested for Lp-PLA2 activity using a commercially available ELISA kit. Lp-PLA2 mRNA, and protein expression in minor salivary gland (MSG) tissue samples derived from SS-nL, SS-L patients, and sicca controls (SC) were analyzed by real-time PCR, Western blot, and immunohistochemistry.

Results

Serum Lp-PLA2 activity was significantly increased in SS-L compared to both SS-nL and HC by two independent methods implemented [mean ± SD (nmol/min/ml): 62.0 ± 13.4 vs 47.6 ± 14.4 vs 50.7 ± 16.6, p-values: 0.003 and 0.04, respectively, and 19.4 ± 4.5 vs 15.2 ± 3.3 vs 14.5 ± 3.0, p-values: <0.0001, in both comparisons]. ROC analysis revealed that the serum Lp-PLA2 activity measured either by radioimmunoassay or ELISA has the potential to distinguish between SS-L and SS-nL patients (area under the curve [AUC]: 0.8022, CI [95%]: 0.64–0.96, p-value: 0.004 for radioimmunoassay, and AUC: 0.7696, CI [95%]: 0.66–0.88, p-value: <0.0001, for ELISA). Lp-PLA2 expression in MSG tissues was also increased in SS-L compared to SS-nL and SC at both mRNA and protein level. ROC analysis revealed that both MSG mRNA and protein Lp-PLA2 have the potential to distinguish between SS-nL and SS-L patients (area under the curve [AUC] values of 0.8490, CI [95%]: 0.71–0.99, p-value: 0.0019 and 0.9444, CI [95%]: 0.79–1.00, p- value: 0.0389 respectively). No significant difference in either serum Lp-PLA2 activity or MSG tissue expression was observed between SS-nL and HC.

Conclusions

Lp-PLA2 serum activity and MSG tissue mRNA/protein expression could be a new biomarker and possibly a novel therapeutic target for B-cell lymphoproliferation in the setting of SS.
ILC2 Cells Promote Th2 Cell Differentiation in AECOPD Through Activated Notch-GATA3 Signaling Pathway
Authors: Jiang Min , Cai Ren , Wang Jing , Li Zheng , Xu Dan , Jing Jing , Zhang Fengbo , Li Fengsen , Ding Jianbing
Published: June 2021

This study is to investigate the capacity of type 2 innate lymphoid cells (ILC2s) in regulating the Th2 type adaptive immune response of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The study enrolled healthy people, stable chronic obstructive pulmonary disease (COPD) patients, and AECOPD patients. Flow cytometry was used to detect Th2 and ILC2 cells in the peripheral blood. In addition, ILC2s from the peripheral blood of AECOPD patients were stimulated with PBS, IL-33, Jagged1, DAPT, IL-33+Jagged1, IL-33+DAPT, and IL-33+Jagged-1+DAP in vitro. The levels of cytokines in the culture supernatant were detected by ELISA and the culture supernatant was used to culture CD4 + T cells. The mRNA and protein levels of Notch1, hes1, GATA3, RORα, and NF-κB of ILC2s were detected by real-time PCR and Western blot. The proportion of Th2 and ILC2s was significantly increased in the peripheral blood of AECOPD patients, alone with the increased Notch1, hes1, and GATA3 mRNA levels. In vitro results showed that the mRNA and protein levels of Notch1, hes1, GATA3 and NF-κB were significantly increased after stimulation with Notch agonist, meanwhile, the level of type 2 cytokines were increased in the supernatant of cells stimulated with Notch agonist, and significantly promoted differentiation of Th2 cells in vitro. Disruption of Notch pathway weakened GATA3 expression and cytokine production, and ultimately affected the differentiation of Th2 cells. In conclusion, our results suggest that ILC2s can promote Th2 cell differentiation in AECOPD via activated Notch-GATA3 signal pathway.
Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes
Authors: Ardighieri Laura , Missale Francesco , Bugatti Mattia , Gatta Luisa Benerini , Pezzali Irene , Monti Matilde , Gottardi Stefano , Zanotti Laura , Bignotti Eliana , Ravaggi Antonella , Tognon Germana , Odicino Franco , Calza Stefano , Missolo-Koussou Yoann , Ries Carola Hermine , Helft Julie , Vermi William
Published: June 2021

Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3+ T-cells and CD163+ tumor-associated macrophages (TAMs) densities identify a subgroup of immune infiltrated high-grade serous carcinomas (HGSCs) with better outcomes and superior response to platinum-based therapies. On the contrary, in most clear cell carcinomas (CCCs) showing poor prognosis and refractory to platinum, a high TAM density is associated with low T cell frequency. Immune infiltrated HGSC are characterized by the 30-genes signature (OC-IS30) covering immune activation and IFNγ polarization and predicting good prognosis (n = 312, TCGA). Immune infiltrated HGSC contain CXCL10 producing M1-type TAM (IRF1+pSTAT1Y701+) in close proximity to T-cells. A fraction of these M1-type TAM also co-expresses TREM2. M1-polarized TAM were barely detectable in T-cell poor CCC, but identifiable across various immunogenic human cancers. Single cell RNA sequencing data confirm the existence of a tumor-infiltrating CXCL10+IRF1+STAT1+ M1-type TAM overexpressing antigen processing and presentation gene programs. Overall, this study highlights the clinical relevance of the CXCL10+IRF1+STAT1+ macrophage subset as biomarker for intratumoral T-cell activation and therefore offers a new tool to select patients more likely to respond to T-cell or macrophage-targeted immunotherapies.
Myeloid-Derived Suppressor Cells as a Potential Biomarker and Therapeutic Target in COVID-19
Authors: Rowlands Marianna , Segal Florencia , Hartl Dominik
Published: June 2021

Clinical presentations of COVID-19 are highly variable, yet the precise mechanisms that govern the pathophysiology of different disease courses remain poorly defined. Across the spectrum of disease severity, COVID-19 impairs both innate and adaptive host immune responses by activating innate immune cell recruitment, while resulting in low lymphocyte counts. Recently, several reports have shown that patients with severe COVID-19 exhibit a dysregulated myeloid cell compartment, with increased myeloid-derived suppressor cells (MDSCs) correlating with disease severity. MDSCs, in turn, promote virus survival by suppressing T-cell responses and driving a highly pro-inflammatory state through the secretion of various mediators of immune activation. Here, we summarize the evidence on MDSCs and myeloid cell dysregulation in COVID-19 infection and discuss the potential of MDSCs as biomarkers and therapeutic targets in COVID-19 pneumonia and associated disease.
Analyzing 13 Years of Cetacean Strandings: Multiple Stressors to Cetaceans in Taiwanese Waters and Their Implications for Conservation and Future Research
Authors: Li Wen-Ta , Chou Lien-Siang , Chiou Hue-Ying , Chen I-Hua , Yang Wei-Cheng
Published: June 2021

This study summarizes the postmortem investigations of 73 cetaceans stranded on the coast of Taiwan between 2001 and 2013, including 51 Delphinidae, 17 Kogiidae, 3 Ziphiidae, 1 Physeteridae, and 1 Balaenopteridae. Of these, eight (11%) were categorized into direct human-related strandings, including fisheries interaction (bycatch), vessel collision and other anthropogenic-related pathology. Gastrointestinal foreign bodies were found in eight individuals (11%). Most of the bacteria isolated from stranded dolphins were zoonotic pathogens including extended-spectrum β-lactamasesEscherichia coli, which indicates waste pollution from land. Severe parasite infestation was found in 36 of the cases (49%), which suggests that the immune function could be compromised. Thirty-eight cases (52%) were diagnosed with myocardial patchy fibrosis or dilated cardiomyopathy. The evidence shown here indicates that cetaceans around Taiwanese waters may suffer from multiple stressors. This study provides baseline data for the health assessment of cetacean populations in Taiwan, which may ultimately provide recommendations for future cetacean conservation and research throughout the western Pacific.
Field Monitoring of Tritia mutabilis (Linnaeus, 1758) Egg Capsule Deposition and Intracapsular Embryonic Patterns Using Artificial Substrates and Machine Learning-Based Approaches
Authors: Cocci Paolo , Troli Emanuele , Angeletti Mauro , Palermo Francesco Alessandro
Published: June 2021

Tritia mutabilis (Linnaeus, 1758) represents a marine gastropod species of ecological and economical importance especially in coastal areas of the central Adriatic Sea (Italy). T. mutabilis encloses its fertilized eggs within capsules which play a protective role in the embryo defense against adverse environmental factors. Egg capsules are attached to any hard substrates and the availability of adequate substrates for oviposition represents therefore a major determinant of reproductive output of this species. The aim of the present study was to provide the first comprehensive monitoring of T. mutabilis egg capsule deposition and intracapsular embryonic patterns using specific artificial substrates and innovative analytical approaches. Square-based pyramid structures were placed within an area subjected to small-scale fishing activity along the Italian coastal waters of the central Adriatic Sea and monitored from March to June 2019. In addition, a machine learning-based approach was developed in order to speed up and automate time-consuming counting procedures of egg capsules attached on each pyramid. Overall, egg capsules were deposited on the almost totality of the artificial substrates reaching values of the surface coverage per site ranging from 31 to 97%. These findings lead to a quantitative estimation of egg number per site included between 27,060 and 62,940 capsules. Our results demonstrate that using these artificial substrates together with monitoring of both egg capsule deposition patterns and intracapsular developmental stages may be useful to improve the T. mutabilis stock management.
Diagnostic Value of the Fimbriae Distribution Pattern in Localization of Urinary Tract Infection
Authors: Li Xiao , Zhou Kaichen , Wang Jingyu , Guo Jiahe , Cao Yang , Ren Jie , Guan Tao , Sheng Wenchao , Zhang Mingyao , Yao Zhi , Wang Quan
Published: June 2021

Urinary tract infections (UTIs) are one of the most common infectious diseases. UTIs are mainly caused by uropathogenic Escherichia coli (UPEC), and are either upper or lower according to the infection site. Fimbriae are necessary for UPEC to adhere to the host uroepithelium, and are abundant and diverse in UPEC strains. Although great progress has been made in determining the roles of different types of fimbriae in UPEC colonization, the contributions of multiple fimbriae to site-specific attachment also need to be considered. Therefore, the distribution patterns of 22 fimbrial genes in 90 UPEC strains from patients diagnosed with upper or lower UTIs were analyzed using PCR. The distribution patterns correlated with the infection sites, an XGBoost model with a mean accuracy of 83.33% and a mean area under the curve (AUC) of the receiver operating characteristic (ROC) of 0.92 demonstrated that fimbrial gene distribution patterns could predict the localization of upper and lower UTIs.
Glomerular Endothelial Cells Are the Coordinator in the Development of Diabetic Nephropathy
Authors: Li Tingting , Shen Kaiyuan , Li Jiawei , Leung Susan W. S. , Zhu Tongyu , Shi Yi
Published: June 2021

The prevalence of diabetes is consistently rising worldwide. Diabetic nephropathy is a leading cause of chronic renal failure. The present study aimed to explore the crosstalk among the different cell types inside diabetic glomeruli, including glomerular endothelial cells, mesangial cells, podocytes, and immune cells, by analyzing an online single-cell RNA profile (GSE131882) of patients with diabetic nephropathy. Differentially expressed genes in the glomeruli were processed by gene enrichment and protein-protein interactions analysis. Glomerular endothelial cells, as well as podocytes, play a critical role in diabetic nephropathy. A subgroup of glomerular endothelial cells possesses characteristic angiogenesis genes, indicating that angiogenesis takes place in the progress of diabetic nephropathy. Immune cells such as macrophages, T lymphocytes, B lymphocytes, and plasma cells also contribute to the disease progression. By using iTALK, the present study reports complicated cellular crosstalk inside glomeruli. Dysfunction of glomerular endothelial cells and immature angiogenesis result from the activation of both paracrine and autocrine signals. The present study reinforces the importance of glomerular endothelial cells in the development of diabetic nephropathy. The exploration of the signaling pathways involved in aberrant angiogenesis reported in the present study shed light on potential therapeutic target(s) for diabetic nephropathy.
A Systematic Study of the Stability, Safety, and Efficacy of the de novo Designed Antimicrobial Peptide PepD2 and Its Modified Derivatives Against Acinetobacter baumannii
Authors: Chen Sung-Pang , Chen Eric H-L , Yang Sheng-Yung , Kuo Pin-Shin , Jan Hau-Ming , Yang Tsai-Chen , Hsieh Ming-Yen , Lee Kung-Ta , Lin Chun-Hung , Chen Rita P-Y
Published: June 2021

Searching for new antimicrobials is a pressing issue to conquer the emergence of multidrug-resistant (MDR) bacteria and fungi. Antimicrobial peptides (AMPs) usually have antimicrobial mechanisms different from those of traditional antibiotics and bring new hope in the discovery of new antimicrobials. In addition to antimicrobial activity, stability and target selectivity are important concerns to decide whether an antimicrobial peptide can be applied in vivo. Here, we used a simple de novo designed peptide, pepD2, which contains only three kinds of amino acid residues (W, K, L), as an example to evaluate how the residues and modifications affect the antimicrobial activity against Acinetobacter baumannii, stability in plasma, and toxicity to human HEK293 cells. We found that pepI2 with a Leu→Ile substitution can decrease the minimum bactericidal concentrations (MBC) against A. baumannii by one half (4 μg/mL). A D-form peptide, pepdD2, in which the D-enantiomers replaced the L-enantiomers of the Lys(K) and Leu(L) residues, extended the peptide half-life in plasma by more than 12-fold. PepD3 is 3-residue shorter than pepD2. Decreasing peptide length did not affect antimicrobial activity but increased the IC50 to HEK293 cells, thus increased the selectivity index (SI) between A. baumannii and HEK293 cells from 4.7 to 8.5. The chain length increase of the N-terminal acyl group and the Lys→Arg substitution greatly enhanced the hemolytic activity, hence those modifications are not good for clinical application. Unlike colistin, the action mechanism of our peptides relies on negatively charged lipids rather than lipopolysaccharides. Therefore, not only gram-negative bacteria but also gram-positive bacteria can be killed by our peptides.
Poly (ADP-ribose) Interacts With Phosphorylated α-Synuclein in Post Mortem PD Samples
Authors: Puentes Laura N. , Lengyel-Zhand Zsofia , Lee Ji Youn , Hsieh Chia-Ju , Schneider Mark E. , Edwards Kimberly J. , Luk Kelvin C. , Lee Virginia M.-Y. , Trojanowski John Q. , Mach Robert H.
Published: June 2021

Poly (ADP-ribose) (PAR) is a negatively charged polymer that is biosynthesized by Poly (ADP-ribose) Polymerase-1 (PARP-1) and regulates various cellular processes. Alpha-synuclein (αSyn) is an intrinsically disordered protein (IDP) that has been directly implicated with driving the onset and progression of Parkinson’s disease (PD). The mechanisms by which α-synuclein (αSyn) elicits its neurotoxic effects remain unclear, though it is well established that the main components of Lewy bodies (LBs) and Lewy neurites (LNs) in PD patients are aggregated hyperphosphorylated (S129) forms of αSyn (pαSyn). In the present study, we used immunofluorescence-based assays to explore if PARP-1 enzymatic product (PAR) promotes the aberrant cytoplasmic accumulation of pαSyn. We also performed quantitative measurements using in situ proximity ligation assays (PLA) on a transgenic murine model of α-synucleinopathy (M83-SNCA∗A53T) and post mortem PD/PDD patient samples to characterize PAR–pαSyn interactions. Additionally, we used bioinformatic approaches and site-directed mutagenesis to identify PAR-binding regions on αSyn. In summary, our studies show that PAR–pαSyn interactions are predominantly observed in PD-relevant transgenic murine models of αSyn pathology and post mortem PD/PDD patient samples. Moreover, we confirm that the interactions between PAR and αSyn involve electrostatic forces between negatively charged PAR and lysine residues on the N-terminal region of αSyn.
Training-of-Trainers Neuroscience and Mental Health Teacher Education in Liberia Improves Self-Reported Support for Students
Authors: Brick Kara , Cooper Janice L. , Mason Leona , Faeflen Sangay , Monmia Josiah , Dubinsky Janet M.
Published: June 2021

Education programs have been central to reestablishing social norms, rebuilding public educational institutions, and addressing public attitudes toward mental illness in Liberia following a protracted civil war and the Ebola epidemic. The aim of this study was to determine if a program combining an understanding of neuroscience with mental health literacy content could increase teachers’ awareness of students’ mental health issues and produce changes in teacher attitudes and classroom practices. A tiered Training-of-Trainers approach was employed. The first workshop trained 24 Liberian secondary science teachers in the neurobiology of learning, memory, emotions, stress and adolescent brain development. A Leadership Team formed from eight of the Tier I participants then adapted the curriculum, added in more mental health literacy content and led four Tier II workshops and four follow-up Refresher sessions. Participants completed a neuroscience knowledge test and surveys assessing stigma, general perceptions of people with mental illness, and burnout. A subset of Tier II teachers participated in a structured interview at the Refresher time point. Teachers in both tiers acquired basic neuroscience knowledge. Tier I, but not Tier II teachers significantly improved their surveyed attitudes toward people with mental illness. No changes were found in overall teacher burnout. Despite these survey results, the interviewed Tier II teachers self-reported behavioral changes in how they approached their teaching and students in their classrooms. Interviewees described how they now understood social and emotional challenges students might be experiencing and recognized abnormal behaviors as having a biopsychosocial basis. Teachers reported reduced use of verbal and corporal punishment and increased positive rewards systems, such as social and emotional support for students through building relationships. Refresher discussions concurred with the interviewees. In contrast to previous teacher mental health literacy programs which did not bring about a change in helping behaviors, this pilot program may have been successful in changing teacher knowledge and self-reported behaviors, improving teacher–student relationships and decreasing harsh discipline. The combination of basic neuroscience concepts with training on how to recognize mental health issues and refer students should be investigated further as a strategy to promote teacher mental health literacy.