bluuebunny/crossref_metadata_2025 huggingface dataset:
AKTIVITAS TAMPING KEBERSIHAN SEBAGAI BENTUK KOMUNIKASI ASERTIF DALAM PEMBINAAN WARGA DI RUTAN DEPOK KELAS I
Authors: Ono Dipo Krishyudi , Jayawinangun Roni , Handayani Prameswari
Published: June 2022

One of the important roles to keep the inmates from being aggressive and preventing behavior that causes riots requires an accurate communication pattern strategy approach, namely assertive communication. Assertive communication communicates what you think, feel, and want clearly and unequivocally to others without feeling intimidating, violating, and belittling the rights of yourself and others. Depok Class 1 Rutan has a cell block with a total of 400 inmates out of a total of 1100 inmates who are guarded by one officer by taking turns divided into three shifts in 1 day. Inmates who are employed at the detention center or called tamping, Impact experienced from experience their time serving as companion prisoners is an increase in personal, social and vocational. The study concluded that being a companion prisoner has an impact on change. Positive self-esteem and giving them the opportunity to become more skilled and productive people after They were released from prison one of them Named Joko is a resident of a special cell block for cleaning, he helps officers clean the detention center and maintains order and ensures that the condition of the detention center is clean and well-maintained every day. This research uses the rapid-ethnography Research method with participant observation and in depth interviews to find information on how the relationship between employees and tamping is related to uncover the motivations of the inmate's companion prisoners and the impact of the role  he changed himself during his stay in prison. in creating compliance, law compliance. to maintain security and order in the class 1 detention center Depok
STRUKTUR DAN PERAN MITOS DALAM NOVEL CIUNG WANARA KARYA AJIP ROSIDI
Authors: Meliasanti Ferina
Published: June 2022

ABSTRAKTujuan dari penelitian ini adalah untuk mendeskripsikan bagaimana struktur mitos yang terdapat dalam novel Ciung Wanara karya Ajip Rosidi dan bagaimana peran mitos cerita Ciung Wanara di novel tersebut dalam perkembangan budaya manusia. Sebagaimana diketahui, novel Ciung Wanara karya Ajip Rosidi merupakan saduran bebas ke dalam bentuk prosa berbahasa Indonesia berdasarkan cerita Ciung Wanara edisi teks C.M. Pleyte (1910) yang ditulis dengan bahasa Sunda. Novel Ciung Wanara karya Ajip Rosidi menceritakan kisah tentang tokoh Ciung Wanara yang merebut kembali kedudukannya sebagai salah satu penerus kekuasaan kerajaan Galuh dan memberikan hukuman kepada Dewi Pangrenyep yang telah memfitnah Pohaci Naganingrum, ibu dari Ciung Wanara. Terjadi pertarungan antara Hariang Banga dan Ciung Wanara, karena Hariang Banga murka setelah mendengar Dewi Pangrenyep dimasukan ke dalam penjara. Pada akhirnya, Hariang Banga pun menghentikan pertarungan dan mengakui bahwa Ciung Wanara benar-benar keturunan Galuh. Hariang Banga memerintah kerajaan Galuh bagian timur, sedangkan Ciung Wanara memerintah wilayah kekuasaan bagian barat. Metode penelitian ini menggunakan deskriptif analitis dengan pendekatan objektif (struktural). Hasil analisis struktur mitos menunjukkan bahwa novel Ciung Wanara karya Ajip Rosidi merupakan kondisi alamiah dari realitas hasrat manusia (individu) dalam memeroleh atau merebut kekuasaan, dan peran mitosnya sebagai Myth of freedom (mitos pembebasan) yang muncul dalam novel Ciung Wanara sebagai negasi atas mitos cerita Ciung Wanara. Kata kunci: novel, Ciung Wanara, struktur mitos, peran mitos.
KONFLIK BATIN TOKOH UTAMA PEREMPUAN DALAM ROMAN AROK DEDES KARYA PRAMOEDYA ANANTA TOER
Authors: Abdullah Muhammad Kamaludin
Published: June 2022

ABSTRAK Penelitian ini bertujuan mendeskripsikan unsur intrinsik, hasil psikoanalisis dan konflik batin tokoh utama perempuan dalam roman Arok Dedes karya Pramoedya Ananta Toer. Penelitian ini menggunakan metode deskriptif kualitatif. Objek penelitian ini adalah roman Arok Dedes karya Pramoedya Ananta Toer. Penelitian ini difokuskan pada permasalahan yang berkaitan dengan konflik batin tokoh utama perempuan, analisis struktural sebagai pijakan dan psikoanalisis Sigmund Freud untuk mengungkapkan konflik batin tersebut. Data diperoleh dengan teknik membaca dan mencatat. Hasil penelitian ini menunjukkan: (1) Struktur novel berupa unsur intrinsik yang difokuskan pada tema yaitu pemanfaatan perempuan dalam kekuasaan, plot yang terbagi  menjadi tahap awal, tahap tengah, dan tahap akhir, penokohan yaitu tokoh Dedes sebagai tokoh utama perempuan dalam cerita, dan latar yang terbagi menjadi latar tempat, latar waktu, latar sosial-budaya; (2) konflik batin yang disebabkan oleh tokoh utama laki-laki, perlakuan Tunggul Ametung dan perlakuan Arok; (3) pandangan masyarakat dalam roman Arok Dedes terhadap tokoh utama perempuan. Kata Kunci: Konflik, Psikoanalisis, Tokoh Utama Perempuan.
ANALISIS SEMIOTIKA PADA BACAAN SASTRA ANAK RADEN LEGOWO: PAHLAWAN DARI HUTAN PEREWANGAN KARYA SULISTIATI DENGAN PERSPEKTIF RELIGIUSITAS
Authors: Gunawan Ardi Rai , S. Putro Sasongko
Published: June 2022

ABSTRAKArtikel ini bertujuan menempatkan dongeng atau sastra anak memiliki fungsi yang sama dengan kritik sastra lainnya, dalam perkembangan sejarah dan kritik  sastra Indonesia. Metode yang digunakan dalam penelitian ini, adalah metode deskriptif kualitatif dengan meninjau berbagai sumber pustaka sebagai bahan referensi penulis. Struktur Greimas menjadi teori yang digunakan untuk analisis. Teori itu bertujuan menunjukkan fokus penulis pada tujuan penelitian, yaitu mengkaji semiotik yang berperspektif religiusitas Jawa. Hasil penelitian ini menunjukkan bahwa semua teori struktur Greimas, semiotik Bühler, dan perpektif religiusitas Jawa, saling berimplikasi, serta sesuai dengan misi pengarang dan Pusat Bahasa perihal menumbuhkan budaya literasi pada anak. Kata Kunci: Sastra Anak, Pusat Bahasa, Semiotik, Religiusitas.
MARGINALISASI PEREMPUAN DALAM CERPEN “INEM” KARYA PRAMOEDYA ANANTA TOER (SEBUAH KAJIAN FEMINISME)
Authors: Permana Tenu , Maulana Indra
Published: June 2022

ABSTRAKArtikel ini mendeskripsikan bentuk marginalisasi terhadap perempuan dalam cerpen “Inem” karya Pramoedya Ananta Toer. Artikel ini merupakan penelitian kualitatif deskriptif. Sumber data penelitian ini berupa novel Cerpen “Inem” Karya Pramoedya Ananta toer. Data dalam penelitiaan ini adalah berupa kalimat, paragraf, kutipan-kutipan dialog, dan wacana yang menggambarkan bentuk marginalisasi. Teknik analisis data yang digunakan dalam penelitian ini adalah teknik Intrinsik. Dari Hasil penelitian memperlihatkan bahwa marginalisasi pada kaum perempuan tidak hanya terjadi dalam masyarakat atau budaya, melainkan terjadi juga di rumah tangga, dan bahkan negara. Kesimpulannya, marginalisasi terhadap perempuan dalam Cerpen “Inem” Karya Pramoedya Ananta Toer terjadi bukan saja dari kemisikinan atau ketidaktahuan akan hak-haknya, melainkan dari peran dominan adat istiadat yang patriarkats dan tafsir keagamaan. Kata kunci: marginalisasi, perempuan, cerpen.
BAHAN AJAR SEBAGAI BAGIAN DALAM KAJIAN PROBLEMATIKA PEMBELAJARAN BAHASA INDONESIA
Authors: Aisyah Siti , Noviyanti Evih , Triyanto Triyanto
Published: June 2022

ABSTRAKMakalah ini menelaah problematika pembelajaran bahasa Indonesia dengan pendekatan unsur bahan ajar. Bahan  ajar yang  dikaji  dalam  penelitian  ini  adalah buku  ajar yang digunakan oleh guru sebagai bahan ajar yang dominan. Selain itu terdapat diktat dan modul sebagai bahan ajar lainnya untuk implementasi penyampaian materi. Berdasarkan penelaahan yang dilakukan, buku menjadi bahan ajar yang dominan digunakan oleh guru bahasa Indonesia. Kata kunci: bahan ajar, buku, problematika pembelajaran bahasa
MODEL KAJIAN SASTRA BANDINGAN BERPERSPEKTIF LINTAS BUDAYA (STUDI KASUS PENELITIAN SASTRA DI ASIA TENGGARA)
Authors: Anggradinata Langgeng Prima
Published: June 2022

Kajian sastra bandingan pernah menjadi kajian yang sangat berkembang dan memberi sumbangsih pada ilmu pengetahuan sastra. Namun, kini, kajian sastra bandingan berkurang peminat karena para peneliti lebih memilih metode, konsep, atau teori yang lebih mutakhir. Artikel ini bertujuan membahas metode kajian sastra bandingandan menemukan model kajian sastra bandingan, khususnya di Asia Tenggara. Artikel ini menggunakan metode kajian pustaka dengan membandingkan penelitian sastra bandingan yang telah dilakukan di Asia Tenggara. Artikel ini meninjau metode kajian sastra bandingan yang dilakukan oleh peneliti di Asia Tenggara. Hasilnya, kajian sastra bandingan cukup berkembangan jika diperkaya metode, konsep, perspektif, dan teori baru, misalnya kajian lintas budaya, teori-teori kritis, dll. Dalam menggunakan kajian sastra bandingan, pengkaji  dapat mencari persamaan satu karya sastra dengan karya sastra lain. Kemudian, pengkaji  dapat melihat perbedaan kedua karya sastra itu. Pada tahap terakhir, pengkaji  dapat menganalisis kedua karya sastra itu dengan pendekatan, konsep, atau teori tertentu, misalnya pendekatan lintas budaya. Kata kunci: Asia Tenggara; lintas budaya; sastra bandingan.
STRUKTUR NARATIF VLADIMIR PROPP (TINJAUAN KONSEPTUAL)
Authors: Trisari Agatha
Published: June 2022

Artikel ini bertujuan menguraikan pokok pemikiran konseptual teori struktur naratif Vladimir Propp. Pokok pemikiran Propp dituangkan dalam bukunya yang berjudul Morfology of the Folktale. Analisis yang dilakukan menitikberatkan pada fungsi pelaku. Menurut Propp, suatu fungsi adalah tindakan seorang tokoh yang dibatasi dari segi maknanya. Dari teori Propp ini, diketahui terdapat unsur yang tetap dan unsur yang berubah.  Unsur yang tetap adalah perbuatan atau tindakan, sedangkan Unsur yang berubah adalah pelaku atau penderita.  Unsur yang tetap tersebut merupakan unsur yang penting dalam teori Propp.  Terdapat empat hal yang panting dalam teori ini.  Pertama, Fungsi Pelaku merupakan unsur-unsur yang tetap, Konstan dalam cerita, tanpa menghiraukan bagaimana dan oleh siapa fungsi-fungsi tersebut dipenuhi.   Kedua, jumlah fungsi dalam cerita adalah tetap (31 fungsi).   Ketiga, urutan fungsi pelaku senantiasa sama. Keempat, cerita dongeng  dipandang  dari  sudut  struktur  adalah  satu  tipe.   Melalui   analisis fungsi pelaku pada lima cerita  rakyat  Jambi  dapat  diketahui  beberapa  hal, (1)  Jumlah  fungsi  pelaku;  (2)  urutan  fungsi  pelaku  dan  kerangka  urutan  fungsi  pelaku;  (3) penyebaran  fungsi-fungsi  di antara  pelaku; (4)  skema  pergerakan  ceritaKata kunci: fungsi pelaku; penyebaran fungsi pelaku; Propp; skemapergerakan cerita; struktur naratif.
RAGAM BAHASA, PENGAYAAN, DAN IMPLIKASINYA
Authors: Suwarna Dadan
Published: June 2022

Ragam bahasa memberi pengayaan pada bahasa Indonesia karena munculnya variasi kebahasaa dan beragam istilah. Keberagaman istilah itu memperkaya kata atau ekspresi bahasa Indonesia. Namun, pengayaan memiliki masalah. Masalah itu adalah keberterimaan penggunanya, misalnya, pilihan dan tingkat ia diproses, sebut saja secara adopsi ataukah translasi. Pilihan itu kemudian memenpatkan hal sepele, tetapi memiliki beragam konsekuensi. Efek di baliknya adalah kesesuaian fonetis ataukah fonologis. Artikel ini lebih mendeskripsikan masalah dalam keragaman dan pengayaan bahasa Indonesia. Penelitian ini menggunakan metode kualitatif deskriptif. Hasil penelitian menunjukkan bahwa terdapat penyerapan dalam bentuk penerjemahan atau adopsi dalam bahasa Indonesia. Namun, penyerapan itu berimplikasi pada ketaksaan, keragaman, dan pengayaan bahasa Indonesia.Kata kunci: ragam bahasa; ragam istilah; serapan bahasa.
PENINGKATAN KETERAMPILAN MENULIS CERITA PENDEK SISWA KELAS IX DI SMP SWASTA HKBP SIDIKALANG MELALUI PENDEKATAN KONTEKSTUAL
Authors: Situmorang Ade Friska , Hutasoit Yanti , Sari Sartika
Published: June 2022

Penelitian ini bertujuan untuk mengetahui peningkatan keterampilan siswa dalam menulis cerita pendek dengan menggunakan pendekatan kontekstual. Penelitian ini dilakukan dengan penelitian tindakan kelas (PTK), yang menggunakan model penelitian Kemmis dan Taggart yang terdiri dari 4 tahap, yakni perencanaan, pelaksanaan, pengamatan, dan refleksi. Dalam pengamatan yang peneliti lakukan, ditemukan bahwa penyebab ketidakberhasilan siswa dalam menulis cerita pendek adalah pertama, motivasi belajar siswa yang sangat rendah. Kedua, kurangnya perhatian siswa pada saat guru mengajar. Ketiga, guru hanya menjelaskan teknis menulis cerpen yang tepat tanpa adanya sentuhan langsung dari lingkungan sekitar maupun kehidupan sosial. Pendekatan pembelajaran kontekstual dilaksanakan melalui pertanyaan, bertanya, dan diskusi. Kata Kunci: keterampilan menulis; pendekatan kontekstual.
The Relationship Between Professionalism of Christian Religious Education Teachers and Interest in Learning Christian Religious Education for Middle School Students in Donokerto Surabaya
Authors: Tarigan Apri , Wibowo Daniel Ari
Published: June 2022

The objectives of this research are: The author wants to know Is there a relationship between the professionalism of Christian Religious Education teachers and students' interest in learning Religious Christian education. Professional Relations of Religious Education Teachers Christian (X) with an interest in learning Christian Religious Education of SMP Donokerto Surabaya students (Y) there is a relationship. From the results of the simple regression statistical test between the variables of Professionalism of Christian Religious Education Teachers (X) with Interest in Learning Christian Religious Education of Donokerto Junior High School students Surabaya, the results obtained the finding of ryx value, is 0.701 and is positive. This means, that the magnitude of the relationship between the Professionalism of Christian Religious Education Teachers with interest in learning Christian Religious Education students of Junior High School students Donokerto Surabaya is 70.1%, then the relationship between variables X and Y is included in the category of high relationship.
Forebrain Organoids to Model the Cell Biology of Basal Radial Glia in Neurodevelopmental Disorders and Brain Evolution
Authors: Kaluthantrige Don Flaminia , Kalebic Nereo
Published: June 2022

The acquisition of higher intellectual abilities that distinguish humans from their closest relatives correlates greatly with the expansion of the cerebral cortex. This expansion is a consequence of an increase in neuronal cell production driven by the higher proliferative capacity of neural progenitor cells, in particular basal radial glia (bRG). Furthermore, when the proliferation of neural progenitor cells is impaired and the final neuronal output is altered, severe neurodevelopmental disorders can arise. To effectively study the cell biology of human bRG, genetically accessible human experimental models are needed. With the pioneering success to isolate and culture pluripotent stem cellsin vitro, we can now routinely investigate the developing human cerebral cortex in a dish using three-dimensional multicellular structures called organoids. Here, we will review the molecular and cell biological features of bRG that have recently been elucidated using brain organoids. We will further focus on the application of this simple model system to study in a mechanistically actionable way the molecular and cellular events in bRG that can lead to the onset of various neurodevelopmental diseases.
Fusobacterium necrophorum Promotes Apoptosis and Inflammatory Cytokine Production Through the Activation of NF-κB and Death Receptor Signaling Pathways
Authors: Wang Feng-Feng , Zhao Peng-Yu , He Xian-Jing , Jiang Kai , Wang Tian-Shuo , Xiao Jia-Wei , Sun Dong-Bo , Guo Dong-Hua
Published: June 2022

Fusobacterium necrophorum can cause liver abscess, foot rot in ruminants, and Lemire syndrome in humans, Also, its virulence factors can induce the apoptosis of macrophages and neutrophils. However, the detailed mechanism has not been fully clarified. This study investigated the mechanisms of apoptosis and inflammatory factor production in F. necrophorum–induced neutrophils and macrophages (RAW246.7). After infection of macrophages with F. necrophorum, 5-ethynyl-2’-deoxyuridine labeling assays indicated that F. necrophorum inhibited macrophage proliferation in a time- and dose-dependent manner. Hoechst staining and DNA ladder assays showed significant condensation of the nucleus and fragmentation of genomic DNA in F. necrophorum–infected macrophages, Annexin V (FITC) and propidium iodide (PI) assay confirmed the emergence of apoptosis in the macrophages and sheep neutrophils with F. necrophorum compared with the control. The group with significant apoptosis was subjected to RNA sequencing (RNA-Seq), and the sequencing results revealed 2581 up– and 2907 downregulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed genes showed that F. necrophorum drove apoptosis and production of inflammatory factors by activating genes related to the Nuclear Factor-κB (NF-κB) and death receptor pathways. Meanwhile, quantitative reverse transcription PCR and Western blot validation results were consistent with the results of transcriptome sequencing analysis. In conclusion, F. necrophorum induced apoptosis and production of pro-inflammatory factors through the NF-κB and death receptor signaling pathway, providing a theoretical basis for further mechanistic studies on the prevention and control of F. necrophorum disease treatment.
Mechanisms of SARS-CoV-2 Infection-Induced Kidney Injury: A Literature Review
Authors: He Weihang , Liu Xiaoqiang , Hu Bing , Li Dongshui , Chen Luyao , Li Yu , Tu Yechao , Xiong Situ , Wang Gongxian , Deng Jun , Fu Bin
Published: June 2022

The severe acute respiratory coronavirus 2 (SARS-CoV-2) has become a life-threatening pandemic. Clinical evidence suggests that kidney involvement is common and might lead to mild proteinuria and even advanced acute kidney injury (AKI). Moreover, AKI caused by coronavirus disease 2019 (COVID-19) has been reported in several countries and regions, resulting in high patient mortality. COVID-19‐induced kidney injury is affected by several factors including direct kidney injury mediated by the combination of virus and angiotensin-converting enzyme 2, immune response dysregulation, cytokine storm driven by SARS-CoV-2 infection, organ interactions, hypercoagulable state, and endothelial dysfunction. In this review, we summarized the mechanism of AKI caused by SARS-CoV-2 infection through literature search and analysis.
Inhibition of Porcine Epidemic Diarrhea Virus by Cinchonine via Inducing Cellular Autophagy
Authors: Ren Jingping , Zeng Wei , Jiang Changsheng , Li Chang , Zhang Chengjun , Cao Hua , Li Wentao , He Qigai
Published: June 2022

Porcine epidemic diarrhea virus (PEDV) could cause lethal diarrhea and dehydration in suckling piglets, which can adversely affect the development of the global swine industry. The lack of effective therapeutical and prophylactic treatment especially for PEDV variant strains underlines the importance of effective antiviral strategies, such as identification of novel antiviral agents. In the present study, the antiviral activity of cinchonine against PEDV was investigated in Vero CCL81 and LLC-PK1 cells at a non-cytotoxic concentration determined by Cell Counting Kit-8 assay in vitro. We found that cinchonine exhibited a significant suppression effect against PEDV infection and its inhibitory action was primarily focused on the early stage of PEDV replication. Moreover, we also observed that cinchonine could significantly induce autophagy by detecting the conversion of LC3-I to LC3-II by using western blot analysis. Cinchonine treatment could inhibit PEDV replication in a dose-dependent manner in Vero CCL81 cells, while this phenomenon disappeared when autophagy was attenuated by pre-treatment with autophagy inhibitor 3MA. Consequently, this study indicated that cinchonine can inhibit PEDV replication via inducing cellular autophagy and thus from the basis for successful antiviral strategies which potentially suggest the possibility of exploiting cinchonine as a novel antiviral agent.
Application of Light-Sheet Mesoscopy to Image Host-Pathogen Interactions in Intact Organs
Authors: Battistella Eliana , Quintana Juan F. , McConnell Gail
Published: June 2022

Human African Trypanosomiasis (HAT) is a disease caused by the extracellular parasite Trypanosoma brucei that affects the central nervous system (CNS) during the chronic stage of the infection, inducing neuroinflammation, coma, and death if left untreated. However, little is known about the structural change happening in the brain as result of the infection. So far, infection-induced neuroinflammation has been observed with conventional methods, such as immunohistochemistry, electron microscopy, and 2-photon microscopy only in small portions of the brain, which may not be representative of the disease. In this paper, we have used a newly-developed light-sheet illuminator to image the level of neuroinflammation in chronically infected mice and compared it to naïve controls. This system was developed for imaging in combination with the Mesolens objective lens, providing fast sub-cellular resolution for tens of mm3-large imaging volumes. The mouse brain specimens were cleared using CUBIC+, followed by antibody staining to locate Glial Fibrillary Acid Protein (GFAP) expressing cells, primarily astrocytes and ependymocytes, used here as a proxy for cell reactivity and gliosis. The large capture volume allowed us to detect GFAP+ cells and spatially resolve the response to T. brucei infection. Based on morphometric analyses and spatial distribution of GFAP+ cells, our data demonstrates a significant increase in cell dendrite branching around the lateral ventricle, as well as dorsal and ventral third ventricles, that are negatively correlated with the branch extension in distal sites from the circumventricular spaces. To our knowledge, this is the first report highlighting the potential of light-sheet mesoscopy to characterise the inflammatory responses of the mouse brain to parasitic infection at the cellular level in intact cleared organs, opening new avenues for the development of new mesoscale imaging techniques for the study of host-pathogen interactions.
Re-repair vs. Replacement for Failed Mitral Valve Repair: A Systemic Review and Meta-Analysis
Authors: Zhong Zhaoji , Xu Hang , Song Wu , Liu Sheng
Published: June 2022

Objective

The objective of this study was to compare outcomes of re-repair with those of mitral valve replacement (MVR) for failed initial mitral valve repair (MVr).

Methods

We searched the Pubmed, Embase, and Cochrane Library databases for studies that compared mitral valve re-repair with MVR for the treatment of failed initial MVr. Data were extracted by two independent investigators and subjected to a meta-analysis. Odds ratio (OR), risk ratio (RR), hazard ratio (HR), ratio difference (RD), mean difference (MD), and 95% confidence interval (CI) were calculated with the Mantel-Haenszel and inverse-variance methods for mode of repair failure, perioperative outcomes, and follow-up outcomes.

Results

Eight retrospective cohort studies were included, with a total of 938 patients, and mean/median follow-up ranged from 1.8 to 8.9 years. Pooled incidence of technical failure was 41% (RD: 0.41; 95% CI: 0.32 to 0.5; P = 0.00; I2 = 86%; 6 studies, 846 patients). Pooled mitral valve re-repair rate was 36% (RD: 0.36; 95% CI: 0.26–0.46; P = 0; I2 = 91%; 8 studies, 938 patients). Pooled data showed significantly lower perioperative mortality (RR: 0.22; 95% CI: 07 to 0.66; I2 = 0%; P = 0.008; 6 studies, 824 patients) and significantly lower long-term mortality (HR:0.42; 95% CI: 0.3 to 0.58; I2 = 0%; P = 0; 7 studies, 903 patients) in the re-repair group compared with MVR.

Conclusions

Mitral valve re-repair was associated with better immediate and sustained outcomes for failed MVr and should be recommended if technically feasible.
VisU-HydRA: A Computational Toolbox for Groundwater Contaminant Transport to Support Risk-Based Decision Making
Authors: Morvillo Maria , Im Jinwoo , de Barros Felipe P. J.
Published: June 2022

Obtaining accurate and deterministic predictions of the risks associated with the presence of contaminants in aquifers is an illusive goal given the presence of heterogeneity in hydrological properties and limited site characterization data. For such reasons, a probabilistic framework is needed to quantify the risks in groundwater systems. In this work, we present a computational toolbox VisU-HydRA that aims to statistically characterize and visualize metrics that are relevant in risk analysis with the ultimate goal of supporting decision making. The VisU-HydRA computational toolbox is an open-source Python package that can be linked to a series of existing codes such as MODFLOW and PAR2, a GPU-accelerated transport simulator. To illustrate the capabilities of the computational toolbox, we simulate flow and transport in a heterogeneous aquifer within a Monte Carlo framework. The computational toolbox allows to compute the probability of a contaminant’s concentration exceeding a safe threshold value as well as the uncertainty associated with the loss of resilience of the aquifer. To ensure consistency and a reproducible workflow, a step-by-step tutorial is provided and available on a GitHub repository.
Circulating Irisin in Children and Adolescents With Prader-Willi Syndrome: Relation With Glucose Metabolism
Authors: Mai Stefania , Fintini Danilo , Mele Chiara , Convertino Alessio , Bocchini Sarah , Grugni Graziano , Aimaretti Gianluca , Vietti Roberta , Scacchi Massimo , Crinò Antonino , Marzullo Paolo
Published: June 2022

Irisin is a myokine involved in the browning of white adipose tissue and regulation of energy expenditure, glucose homeostasis and insulin sensitivity. Debated evidence exists on the metabolic role played by irisin in children with overweight or obesity, while few information exist in children with Prader Willi Syndrome (PWS), a condition genetically prone to obesity. Here we assessed serum irisin in relation to the metabolic profile and body composition in children and adolescents with and without PWS. In 25 PWS subjects [age 6.6-17.8y; body mass index standard deviation score (BMI SDS) 2.5 ± 0.3] and 25 age, and BMI-matched controls (age 6.8-18.0y; BMI SDS, 2.8 ± 0.1) we assessed irisin levels and metabolic profile inclusive of oral glucose tolerance test (OGTT), and body composition by dual-energy X-ray absorptiometry (DXA). In PWS, we recorded lower levels of fat-free mass (FFM) (p <0.05), fasting (p<0.0001) and 2h post-OGTT insulin (p<0.05) and lower insulin resistance as expressed by homeostatic model of insulin resistance (HOMA-IR) (p<0.0001). Irisin levels were significantly lower in PWS group than in controls with common obesity (p<0.05). In univariate correlation analysis, positive associations linked irisin to insulin OGTT0 (p<0.05), insulin OGTT120 (p<0.005), HOMA-IR (p<0.05) and fasting C-peptide (p<0.05). In stepwise multivariable regression analysis, irisin levels were independently predicted by insulin OGTT120. These results suggest a link between irisin levels and insulin sensitivity in two divergent models of obesity.
The Impact of Policy Orientation on Green Innovative Performance: The Role of Green Innovative Capacity and Absorptive Capacity
Authors: Li Bin , Lei Yongxin , Hu Minqi , Li Wenjing
Published: June 2022

Green innovation has been recognized as a key factor for balancing environmental sustainability and financial growth. Although the literature has examined the impacts of policy orientation on green innovation, there are still outstanding issues to be addressed. On the one hand, existing studies have focused on the direct impact of environmental regulation or institutional pressure on green innovation, but fail to account for the issue of intermediate mechanisms between policy orientation and green innovations. On the other hand, there are inconsistent findings in the current empirical evidence on the impact of environmental policies on green innovation. Therefore, this study tries to address these research gaps by clarifying the internal mechanisms and boundary conditions between policy orientation and green innovation. Based on Porter’s hypothesis and absorptive capacity perspective, this study explores the mediation effect of green innovative capability and the moderation effect of absorptive capacity in the relationship between policy orientation and green innovative capacity. To test the research model, we collected data from 359 Chinese green manufacturing companies. Our findings suggest that whether policy orientation has a significant positive effect on a firm’s green innovation performance depends on the firm’s absorptive capacity. In addition, green innovative capacity mediated the effect of policy orientation on green innovation performance. Furthermore, absorptive capacity strengthens this mediation effect. Therefore, we identified the mediating role of green innovative capacity and the moderating role of absorptive capacity between policy orientation and green innovation performance. Our findings theoretically enrich the literature on Porter’s hypothesis and absorptive capacity perspectives and provide a reference for green innovation practices.
Research on the Impact of Rural Population Structure Changes on the Net Carbon Sink of Agricultural Production-Take Huan County in the Loess Hilly Region of China as an Example
Authors: Ma Libang , Zhang Wenbo , Wu Shanshan , Shi Zhihao
Published: June 2022

People are the fundamental purpose and driving force of agricultural development. The changes in population structure can directly affect social and economic development of rural areas and the entire process of agricultural production. This paper takes Huan County in the Loess Hilly Region of China as the evaluation object, the townships as the evaluation unit, the change of rural population structure as the key point, and the agricultural production as the mediating factor, to study the mechanism of agricultural net carbon sinks. The results show: 1) From 2009 to 2018, the number of rural labor force in Huan County was seriously lost, the quality of the labor force was steadily improved, and the age of the labor force was increased. The number of agricultural employees dropped from 72.6 to 49.4%. The number of people with high school education or above increased from 9.7 to 15.1%. Those over working age who participated in the labor force rose from 5.2 to 8.3%. 2) The Loess Hilly Region in the northwest of Huan County was “grain-trending,” and the River Valley and Plain Area in the southeast was “grain-removing.” The input structure index both increased first and then decreased. and the Loess Hilly Region was more dependent on the fertilizer. 3) The rural population structure affects the agricultural net carbon sink by affecting the planting structure index and the input structure index. The rural population quantity and quality structure have a significant positive effect on the agricultural net carbon sink, while the population age structure has a significant negative effect on the agricultural net carbon sink. 4) From the mediating effect, the loss of population can cause fluctuations in the agricultural net carbon sink. The improvement of population quality will promote the growth of the agricultural net carbon sink, and the aging of the population will cause the decline of the agricultural net carbon sink. 5) The return of the labor force, the improvement of labor force quality, the improvement of production methods, technological innovation, and skill training are the main ways to increase agricultural net carbon sinks and reduce emissions. This paper can lay a solid foundation for realizing the overall emission reduction target of agricultural production in the Loess Hilly Region.
Modeling the Impact of Foreign Direct Investment on China’s Carbon Emissions: An Economic and Environmental Paradigm
Authors: Xiao Yuanzhi , Gao Ke , Sun Ruiqi
Published: June 2022

Under the background of high-quality development, the impact of foreign direct investment on carbon emissions has attracted increasing attention. This research studies the impact of foreign direct investment on carbon emissions under the effect of institutional quality regulation. Specifically, this study uses China’s provincial panel data from 2010 to 2019, taking political system quality, economic system quality, and legal system quality as the external environment of system quality, this research studies the threshold effect of foreign direct investment on carbon emissions. The results show that foreign direct investment can effectively restrain the increase in carbon emissions. The impact of FDI on China’s carbon emissions has an obvious economic threshold effect: with the increase of regional corruption, the political quality is gradually declining, and the inhibition effect of foreign direct investment on carbon emissions is declining. With the increase of marketization and intellectual property protection, the regional economic system and legal system have gradually improved, and the role of foreign direct investment in carbon emissions has been further increased. Therefore, China should create a good institutional environment for FDI technology spillovers.
Case Report: Recurrent Deposition in Renal Allografts: A Rare Case of Fibronectin Glomerulopathy Overlooked in Native Kidneys
Authors: Wei Xiaona , Wang Xiangdong , Zhang Rui , Liang Peifen , Liu Bo , Wang Lin , Yue Shuling , Li Xiaojuan , Chen Wenfang , Yang Qiongqiong
Published: June 2022

Fibronectin glomerulopathy (FNG) is a rare inherited kidney disease characterized by extensive deposition of fibronectin in the glomeruli, especially in the mesangial and subendothelial regions. The disease progresses slowly and eventually leads to kidney failure in 15–20 years. Here, we report an interesting case. The patient presented with proteinuria and was diagnosed with immune complex–mediated glomerulonephritis, and lupus nephritis was suspected. This patient progressed to end-stage renal disease after 18 years and received an allogeneic kidney transplant. However, proteinuria recurred 27 months after kidney transplantation. The renal biopsy found extensive deposition in glomeruli, and the patient was diagnosed with FNG using mass spectrometry analysis and confirmed by immunohistochemistry in both the native and transplanted kidneys. Gene sequencing revealed that a missense mutation in the fibronectin 1 (FN1) gene caused reduced binding to heparin, endothelial cells, and podocytes and impaired stress fiber formation. The patient had stable renal function but persistent nephrotic proteinuria after 6 months of follow-up. Given the persistence of abnormal circulating fibronectin levels, FNG can relapse following renal transplantation. The circulating fibronectin deposits on grafts, and renal function progressively deteriorates after recurrence. Therefore, whether renal transplantation is an acceptable treatment for FNG is still debatable.
A Pan-Cancer Analysis Revealing the Dual Roles of Lysine (K)-Specific Demethylase 6B in Tumorigenesis and Immunity
Authors: Ding Jia-Tong , Yu Xiao-Ting , He Jin-Hao , Chen De-Zhi , Guo Fei
Published: June 2022

Introduction: Epigenetic-targeted therapy has been increasingly applied in the treatment of cancers. Lysine (K)-specific demethylase 6B (KDM6B) is an epigenetic enzyme involved in the coordinated control between cellular intrinsic regulators and the tissue microenvironment whereas the pan-cancer analysis of KDM6B remains unavailable.

Methods: The dual role of KDM6B in 33 cancers was investigated based on the GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) databases. TIMER2 and GEPIA2 were applied to investigate the KDM6B levels in different subtypes or stages of tumors. Besides, the Human Protein Atlas database allowed us to conduct a pan-cancer study of the KDM6B protein levels. GEPIA2 and Kaplan–Meier plotter were used for the prognosis analysis in different cancers. Characterization of genetic modifications of the KDM6B gene was analyzed by the cBioPortal. DNA methylation levels of different KDM6B probes in different TCGA tumors were analyzed by MEXPRESS. TIMER2 was applied to determine the association of the KDM6B expression and immune infiltration and DNA methyltransferases. Spearman correlation analysis was used to assess the association of the KDM6B expression with TMB (tumor mutation burden) and MSI (microsatellite instability). The KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis and GO (Gene ontology) enrichment analysis were used to further investigate the potential mechanism of KDM6B in tumor pathophysiology.

Results: KDM6B was downregulated in 11 cancer types and upregulated across five types. In KIRC (kidney renal clear cell carcinoma) and OV (ovarian serous cystadenocarcinoma), the KDM6B level was significantly associated with the pathological stage. A high level of KDM6B was related to poor OS (overall survival) outcomes for THCA (thyroid carcinoma), while a low level was correlated with poor OS and DFS (disease-free survival) prognosis of KIRC. The KDM6B expression level was associated with TMB, MSI, and immune cell infiltration, particularly cancer-associated fibroblasts, across various cancer types with different correlations. Furthermore, the enrichment analysis revealed the relationship between H3K4 and H3K27 methylation and KDM6B function.

Conclusion: Dysregulation of the DNA methyltransferase activity and methylation levels of H3K4 and H3K27 may involve in the dual role of KDM6B in tumorigenesis and development. Our study offered a relatively comprehensive understanding of KDM6B’s dual role in cancer development and response to immunotherapy.
Cytokine TGFβ Gene Polymorphism in Asthma: TGF-Related SNP Analysis Enhances the Prediction of Disease Diagnosis (A Case-Control Study With Multivariable Data-Mining Model Development)
Authors: Panek Michał , Stawiski Konrad , Kaszkowiak Marcin , Kuna Piotr
Published: June 2022

Introduction

TGF-β and its receptors play a crucial role in asthma pathogenesis and bronchial remodeling in the course of the disease. TGF-β1, TGF-β2, and TGF-β3 isoforms are responsible for chronic inflammation, bronchial hyperreactivity, myofibroblast activation, fibrosis, bronchial remodeling, and change the expression of approximately 1000 genes in asthma. TGF-β SNPs are associated with the elevated plasma level of TGF-β1, an increased level of total IgE, and an increased risk of remodeling of bronchi.

Methods

The analysis of selected TGF-β1, TGF-β2, TGF-β3-related single-nucleotide polymorphisms (SNP) was conducted on 652 DNA samples with an application of the MassARRAY® using the mass spectrometry (MALDI-TOF MS). Dataset was randomly split into training (80%) and validation sets (20%). For both asthma diagnosis and severity prediction, the C5.0 modelling with hyperparameter optimization was conducted on: clinical and SNP data (Clinical+TGF), only clinical (OnlyClinical) and minimum redundancy feature selection set (MRMR). Area under ROC (AUCROC) curves were compared using DeLong’s test.

Results

Minor allele carriers (MACs) in SNP rs2009112 [OR=1.85 (95%CI:1.11-3.1), p=0.016], rs2796821 [OR=1.72 (95%CI:1.1-2.69), p=0.017] and rs2796822 [OR=1.71 (95%CI:1.07-2.71), p=0.022] demonstrated an increased odds of severe asthma. Clinical+TGF model presented better diagnostic potential than OnlyClinical model in both training (p=0.0009) and validation (AUCROC=0.87 vs. 0.80,p=0.0052). At the same time, the MRMR model was not worse than the Clinical+TGF model (p=0.3607 on the training set, p=0.1590 on the validation set), while it was better in comparison with the Only Clinical model (p=0.0010 on the training set, p=0.0235 on validation set, AUCROC=0.85 vs. 0.87). On validation set Clinical+TGF model allowed for asthma diagnosis prediction with 88.4% sensitivity and 73.8% specificity.

Discussion

Derived predictive models suggest the analysis of selected SNPs in TGF-β genes in combination with clinical factors could predict asthma diagnosis with high sensitivity and specificity, however, the benefit of SNP analysis in severity prediction was not shown.
Comprehensive Urinomic Identification of Protein Alternatives to Creatinine Normalization for Diagnostic Assessment of Lupus Nephritis
Authors: Soomro Sanam , Stanley Samantha , Lei Rongwei , Saxena Ramesh , Petri Michelle , Mohan Chandra
Published: June 2022

Introduction

The current gold standard used for urine biomarker normalization, creatinine, poses a challenge to translate to the point of care because antibodies to creatinine are difficult to develop and currently available ligands to creatinine are sub-optimal for this purpose. Hence, protein alternatives to creatinine are clearly needed. To address this need, lupus nephritis was selected as a model disease where urine protein assessment is required for diagnosis.

Methods

A comprehensive proteomic screen of 1129 proteins in healthy and lupus nephritis urine was executed to identify protein alternatives to creatinine for the normalization of urine biomarkers. Urinary proteins that correlated well with creatinine but did not vary with disease were further validated by ELISA in an independent cohort of lupus nephritis subjects.

Results

The comprehensive proteomic screen identified 14 urine proteins that correlated significantly with urine creatinine but did not differ significantly between SLE and controls. Of the top five proteins selected for ELISA validation, urine HVEM and RELT once again showed significant correlation with urine creatinine in independent cohorts. Normalizing a lupus nephritis biomarker candidate ALCAM using urinary HVEM demonstrated comparable diagnostic ability to creatinine normalization when distinguishing active lupus nephritis from inactive SLE patients.

Conclusions

The discovery of urine HVEM as a protein alternative to creatinine for biomarker normalization has applications in the engineering of antibody-based point of care diagnostics for monitoring lupus nephritis progression.
PD-1 Immune Checkpoint Blockade and PSGL-1 Inhibition Synergize to Reinvigorate Exhausted T Cells
Authors: Viramontes Karla M. , Neubert Emily N. , DeRogatis Julia M. , Tinoco Roberto
Published: June 2022

Chronic viral infections where the antigen persists long-term, induces an exhaustion phenotype in responding T cells. It is now evident that immune checkpoints on T cells including PD-1, CTLA-4, and PSGL-1 (Selplg) are linked with the differentiation of exhausted cells. Chronic T cell receptor signaling induces transcriptional signatures that result in the development of various exhausted T cell subsets, including the stem-like T cell precursor exhausted (Tpex) cells, which can be reinvigorated by immune checkpoint inhibitors (ICIs). While PSGL-1 has been shown to inhibit T cell responses in various disease models, the cell-intrinsic function of PSGL-1 in the differentiation, maintenance, and reinvigoration of exhausted T cells is unknown. We found Selplg-/- T cells had increased expansion in melanoma tumors and in early stages of chronic viral infection. Despite their increase, both WT and Selplg-/- T cells eventually became phenotypically and functionally exhausted. Even though virus-specific Selplg-/- CD4+ and CD8+ T cells were increased at the peak of T cell expansion, they decreased to lower levels than WT T cells at later stages of chronic infection. We found that Selplg-/- CD8+ Tpex (SLAMF6hiTIM3lo, PD-1+TIM3+, TOX+, TCF-1+) cell frequencies and numbers were decreased compared to WT T cells. Importantly, even though virus-specific Selplg-/- CD4+ and CD8+ T cells were lower, they were reinvigorated more effectively than WT T cells after anti-PD-L1 treatment. We found increased SELPLG expression in Hepatitis C-specific CD8+ T cells in patients with chronic infection, whereas these levels were decreased in patients that resolved the infection. Together, our findings showed multiple PSGL-1 regulatory functions in exhausted T cells. We found that PSGL-1 is a cell-intrinsic inhibitor that limits T cells in tumors and in persistently infected hosts. Additionally, while PSGL-1 is linked with T cell exhaustion, its expression was required for their long-term maintenance and optimal differentiation into Tpex cells. Finally, PSGL-1 restrained the reinvigoration potential of exhausted CD4+ and CD8+ T cells during ICI therapy. Our findings highlight that targeting PSGL-1 may have therapeutic potential alone or in combination with other ICIs to reinvigorate exhausted T cells in patients with chronic infections or cancer.
Human Disseminated Protothecosis: The Skin is the “Window”?
Authors: Wang Xue , Ran Yuanshuai , Jia Songgan , Ahmed Sarah , Long Xuemei , Jiang Yinhui , Jiang Yanping
Published: June 2022

Human disseminated protothecosis is a rare infection caused by members of the genus Prototheca, an achlorophyllic algae always associated with debilitated hosts. The presence of non-budding cells and large, spherical cells (sporangia) with endosporulation (morula) in histology is proof of Prototheca infection. Regrettably, due to the lack of specificity of clinical features and low awareness among clinicians, protothecosis is always underestimated and misdiagnosed. The available data on a species-specific analysis of this infection are limited. In this review, we summarize the etiological, epidemiological, and clinical aspects of disseminated protothecosis. The potential pathogenicity and clinical differences between P. zopfii and P. wickerhamii were observed. Additionally, the skin not only became the main invasion site but also the most involved organ by the pathogen. With the increasing numbers of immunocompromised individuals throughout the world, the incidence of disseminated infection caused by Prototheca is bound to increase, and disseminated protothecosis that accompanies skin symptoms should be taken into account by clinicians.