bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose IL-2 improved clinical symptoms by restoring reduced regulatory T cells in patients with refractory rheumatoid arthritis: A randomized controlled trial
Authors: Wang Jia , Zhang Sheng-Xiao , Chang Jia-Song , Cheng Ting , Jiang Xiao-Jing , Su Qin-Yi , Zhang Jia-Qi , Luo Jing , Li Xiao-Feng 
Published: November 2022

BackgroundRegulatory T cells (Tregs) have been found to play crucial roles in immune tolerance. However, the status of Tregs in refractory rheumatoid arthritis (RA) is still unclear. Moreover, low-dose interleukin-2 (IL-2) has been reported to selectively promote the expansion of Tregs. This study investigated the status of CD4+ Tregs and low-dose IL-2 therapy in patients with refractory RA.MethodsThe absolute number of CD4+CD25+FOXP3+ Treg (CD4 Treg), CD4+IL17+ T (Th17), and other subsets in peripheral blood (PB) from 41 patients with refractory RA and 40 healthy donors was characterized by flow cytometry combined with an internal microsphere counting standard. Twenty-six patients with refractory RA were treated with daily subcutaneous injections of 0.5 million IU of human IL-2 for five consecutive days. Then, its effects on CD4 Treg and Th17 cells in PB were analyzed.ResultsA decrease in the absolute number of PB CD4 Tregs rather than the increase in the number of Th17 was found to contribute to an imbalance between Th17 and CD4 Tregs in these patients, suggesting an essential role of CD4 Tregs in sustained high disease activity. Low-dose IL-2 selectively increased the number of CD4 Tregs and rebalanced the ratio of Th17 and CD4 Tregs, leading to increased clinical symptom remission without the observed side effects.ConclusionsAn absolute decrease of PB CD4 Tregs in patients with refractory RA was associated with continuing disease activation but not the increase of Th17 cells. Low-dose IL-2, a potential therapeutic candidate, restored decreased CD4 Tregs and promoted the rapid remission of patients with refractory RA without overtreatment and the observed side effects.Clinical trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=13909, identifier ChiCTR-INR-16009546.
Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer
Authors: Dai Yalan , Yang Liqiong , Sakandar Abass , Zhang Duoli , Du Fukuan , Zhang Xinyi , Zou Linglin , Zhao Yueshui , Wang Jigang , Zhang Zhenhua , Wu Xu , Li Mingxing , Ling Xiao , Yu Lei , Dong Lishu , Shen Jing , Xiao Zhangang , Wen Qinglian 
Published: November 2022

ObjectivesTo investigate the role of immune escape encoding genes on the prognosis of BC, and to predict the novel targeting agents.MethodsHuman immune genes and immune escape encoding genes were obtained from the IMMPORT database and the previous study. Sample information and clinical data on BC were obtained from the TCGA and GTEX databases. Obtaining differentially expressed protein data from cBioportal database. To construct a risk score model by lasso analysis, and nomogram was used to predict score core. GSCA, TIMER and CELLMINER databases were used for immune and drug susceptibility correlation analyses. Cell experiments were verified by MTT, Western blotting, and RT-qPCR.ResultsWe found prognostic models consisting of eleven immune escape related protein-coding genes with ROC curves that performed well in the ontology data (AUC for TCGA is 0.672) and the external data (AUC for GSE20685 is 0.663 and for GES42568 is 0.706). Five core prognostic models are related to survival (EIF4EBP1, BCL2A1, NDRG1, ERRFI1 and BRD4) were summarized, and a nomogram was constructed to validate a C-index of 0.695, which was superior to other prognostic models. Relevant drugs targeting core genes were identified based on drug sensitivity analysis, and found that Vemurafenib downregulates the PI3K-AKT pathway and BCL2A1 protein in BC, as confirmed by external data and cellular assays.ConclusionsBriefly, our work establishes and validates an 11-immune escape risk model, and five core prognostic factors that are mined deeply from this model, and elucidates in detail that Vemurafenib suppresses breast cancer by targeting the PI3K/AKT signaling pathway to inhibit the immune escape biomarker BCL2A1, confirms the validity of the prognostic model, and provides corresponding targeted agents to guide individualized treatment of BC patients.
Metabolome and transcriptome associated analysis of sesquiterpenoid metabolism in Nardostachys jatamansi
Authors: Feng Mingkang , Chen Chen , Qu-Bie Junzhang , Qu-Bie Axiang , Bao Xiaoming , Cui Qi , Yan Xinjia , Li Ying , Liu Yuan , Zhang Shaoshan 
Published: November 2022

BackgroundNardostachys jatamansi, an extremely endangered valuable plant of the alpine Himalayas, can synthesize specific sesquiterpenoids with multiple effective therapies and is widely exploited for the preparation of drugs, cosmetics and even religious functions (e.g., well-known spikenard). However, how accumulation trend of the sesquiterpenoids in tissues and the molecular mechanisms underlying the production of the active ingredients are not well understood.MethodsThe single-molecule real-time (SMRT) and RNA-seq transcriptome sequencing were combined to analyse the roots, rhizomes, leaves, flowers and anthocaulus of N. jatamansi. The phytochemical analysis was performed by gas chromatography‒mass spectrometry (GC‒MS) and ultrahigh-performance liquid chromatography (UPLC).ResultsA high-quality full-length reference transcriptome with 26,503 unigenes was generated for the first time. For volatile components, a total of sixty-five compounds were successfully identified, including fifty sesquiterpenoids. Their accumulation levels in five tissues were significantly varied, and most of the sesquiterpenoids were mainly enriched in roots and rhizomes. In addition, five aromatic compounds were only detected in flowers, which may help the plant attract insects for pollination. For nonvolatile ingredients, nardosinone-type sesquiterpenoids (nardosinone, kanshone C, and isonardosinone) were detected almost exclusively in roots and rhizomes. The candidate genes associated with sesquiterpenoid biosynthesis were identified by transcriptome analysis. Consistently, it was found that most biosynthesis genes were abundantly expressed in the roots and rhizomes according to the functional enrichment and expression patterns results. There was a positive correlation between the expression profile of genes related to the biosynthesis and the accumulation level of sesquiterpenoids in tissues. Gene family function analysis identified 28 NjTPSs and 43 NjCYPs that may be involved in the biosynthesis of the corresponding sesquiterpenoids. Furthermore, gene family functional analysis and gene coexpression network analysis revealed 28 NjTPSs and 43 NjCYPs associated with nardosinone-type sesquiterpenoid biosynthesis.ConclusionOur research results reveal the framework of sesquiterpenoids accumulation and biosynthesis in plant tissues and provide valuable support for further studies to elucidate the molecular mechanisms of sesquiterpenoid regulation and accumulation in N. jatamansi and will also contribute to the comprehensive utilization of this alpine plant.
Relationships among nursing students’ self-concept clarity, meaning in life, emotion regulation ability and depression: Testing a moderated mediation model
Authors: Hong Youjuan , Zhang Xuan , Wu Weiwei , Chen Jingjing , Lin Yan , Zhao Junyu , Xiao Huimin 
Published: November 2022

ObjectiveSelf-concept clarity as an inducing factor of depressive symptoms has been confirmed in previous studies. However, little is known about how and when it induces depressive symptoms in nursing students. The study is to examine the potential mediating role of meaning in life and the moderation of emotion regulation ability in the association between self-concept clarity and depressive symptoms among college nursing students.Materials and MethodsA sample of 488 college nursing students participated in this study Southeast China. The Chinese adaptations of Self-concept clarity Scale, Sense of life Scale, Depression scale, Emotion regulation scale were used. Mediation and moderation analyses were carried out in the SPSS macro PROCESS.ResultsSelf-concept clarity was significantly and negatively associated with depression in nursing students, meaning in life had a partial mediating effect on the relationship between self-concept clarity and depression. Furthermore, emotion regulation ability moderated the direct effect of self-concept clarity on depression.ConclusionThe findings enrich the knowledge of the mediating and moderating mechanisms to explain the association between self-concept clarity and depression in nursing students. There have been proposed interventions concerning increasing self-concept clarity, meaning in life and emotion regulation ability training which could help help reduce the depression among nursing students.
O processo de cultivo de horta em caixotes de madeira em uma escola da cidade de Manaus
Authors: Dos Santos Selma Israel , Dos Santos Géssica Aline Nogueira , Da Silva Andreia Ferreira , Pinheiro Erika Cristina Nogueira Marques , Mata Rafaela Rodrigues 
Published: November 2022

Trabalhar com a horta na escola também é um recurso pedagógico que estimula o desenvolvimento de diversas habilidades importantes para a formação dos alunos. O objetivo desse estudo é mostrar o processo de cultivo de horta em caixotes de madeira em uma escola da cidade de Manaus-AM. A metodologia desse estudo deu-se a partir da realização das pesquisas bibliográficas relacionadas ao tema de pesquisa, quanto aos fins, a pesquisa é exploratória que tem como objetivo principal desenvolver, esclarecer e modificar conceitos e ideias, tendo em vista a formulação de problemas mais precisos ou hipóteses pesquisáveis para estudos posteriores. Conclui-se que cultivar uma horta na escola promove a conscientização socioecológica dos alunos o que exige um comportamento humano responsável em relação à natureza com o objetivo de reduzir a poluição e melhorar as condições de vida no planeta. Os alimentos produzidos também podem ser aplicados no preparo da merenda escolar, o que gera economia nas compras e garante a qualidade do que é consumido.
Pengaruh Lingkungan Kerja terhadap Disiplin Kerja dan Semangat Kerja Pegawai pada Dinas Perikanan dan Kelautan Provinsi Sumatera Utara
Authors: Putri Intan Diana 
Published: November 2022

The purpose of this study was to determine and analyze the effect of the work environment on work discipline, the influence of the work environment on work morale and the indirect effect of the work environment on work morale through work discipline at the Department of Fisheries and Maritime Affairs of North Sumatra Province. The method used in this study is a quantitative method with multiple linear regression analysis and sobel. The sample used in this study were 130 employees of the Department of Fisheries and Maritime Affairs of North Sumatra Province.
The results of this study indicate that the Work environment has no effect on the Work Discipline of the employees of the Department of Fisheries and Maritime Affairs of North Sumatra Province. The Work Environment has a positive and significant influence on the Work Enthusiasm of the employees of the Department of Fisheries and Maritime Affairs of the Province of North Sumatra and there is an indirect influence between the Work Environment on the Work Enthusiasm through Work Discipline.
Analisis Yuridis Atas Peralihan Hak Atas Tanah yang Tidak Dilakukan Dihadapan Ppat (Pejabat Pembuat Akta Tanah) (Studi Pada Perumahan Bumi Berngam Baru Di Kota Binjai)
Authors: Harahap Siti Melisa 
Published: November 2022

Peralihan hak atas tanah adalah berpindahnya hak atas tanah dari pemegang hak yang lama kepada pemegang hak yang baru. Menurut Hukum Adat, peralihan hak atas tanah adalah suatu perbuatan jual beli yang bersifat terang dan tunai. Terang berarti perbuatan pemindahan hak tersebut harus dilakukan dihadapan Kepala Adat atau Pejabat yang berwenang yakni Pejabat Pembuat Akta Tanah (PPAT). Tunai berarti bahwa perbuatan pemindahan hak dan pembayaran harganya dilakukan secara serentak. Namun, tidak dapat dipungkiri bahwa dewasa ini peralihan hak atas tanah tidak dilakukan dihadapan PPAT. Permasalahan yang diangkat pada penelitian ini, yakni bagaimana pengaturan hukum peralihan hak atas tanah menurut ketentuan yang berlaku, proses peralihan hak atas tanah yang tidak dilakukan dihadapan PPAT, dan akibat hukum atas peralihan hak atas tanah yang tidak dilakukan dihadapan PPAT.
Untuk menemukan jawaban dari permasalahan tersebut maka penelitian ini menggunakan jenis penelitian hukum normatif yang bersifat deskriptif, dimana penelitian ini menggunakan pendekatan yuridis empiris dan menggunakan wawancara sebagai data primer dan studi kepustakaan sebagai data sekunder, serta analisis data menggunakan metode analisis data kualitatif. Analisis data ini dimaksudkan berdasarkan gambaran, fakta yang diperoleh akan dilakukan analisis untuk menjawab permasalahan.
Pengaturan hukum peralihan hak atas tanah menurut ketentuan yang berlaku diatur dalam Kitab Undang-Undang Hukum Perdata yakni Pasal 1457 dan 1458, kemudian Hukum Adat secara terang dan tunai, dan Hukum Tanah Nasional (Agraria) yang menggunakan Hukum Adat sebagai dasar hukumnya. Proses peralihan hak atas tanah yang tidak dilakukan dihadapan PPAT tidak memenuhi ketentuan Pasal 37 Peraturan Pemerintah Nomor 24 Tahun 1997 Tentang Pendaftaran Tanah seperti yang terjadi di Perumahan Bumi Berngam Baru di Kota Binjai. Proses peralihan hak atas tanah yang tidak dilakukan dihadapan PPAT seperti Perjanjian Pengikatan Jual Beli dapat dijadikan dasar untuk proses balik nama dan apabila hanya dilakukan dibawah tangan apalagi hanya dengan selembar kwitansi tidak dapat memberikan kepastian hukum dan perlindungan hukum bagi pembeli. Akibat hukum atas peralihan hak atas tanah yang tidak dilakukan dihadapan PPAT adalah jual beli tanah tersebut tidak memiliki kepastian hukum.
Analisis Yuridis Atas Praktek Pinjam Meminjam Uang Tanpa Jaminan di Kalangan Masyarakat Pasar Tradisional Horas Kota Pematang Siantar
Authors: Saragih Trinitaty 
Published: November 2022

The people at the Horas traditional market, Siantar Barat Sub-district, Pematang Sianar, re allowed to pay their loan by installment, and the loan is without collateral such as land certificate or other valuable devices. Some debtors usually do not pay off their installment to creditors. Loan agreement such as this will have a potential risk for money lenders, but it seems that they have never learned their lesson so that it is necessary for either the debtors or the creditors (money lenders) to get legal protection.
The research used juridical empirical method through which the gathered data were analyzed descriptively and qualitatively.
The loan agreement without any collateral in the people at Pematang Siantar is the same as used-up loan as it is specified in Article 1754 and Article 1765 of the Civil Code which is not contrary to Article 46, paragraph 1 of Law on Banking. If a debtor does not want or is not able to pay his debt after he has been warned, the creditor can file his complaint about a default to the court, based on Article 1243 of the Civil Code for compensation, interest, or cost. Request for debt relief or the length of term should have creditor’s approval. If the request for interest relief is rejected, a debtor can file it to the Court based on the request of “Wocker-ordinantie 1938”. A debtor who is charged with offensive criminal case can sue the creditor based on Article 335, paragraph 1 and Article 368 of the Penal Code if there is blackmailing in dunning.
Special law which regulates the implementation of loan agreement between individuals should always pay attention to the balance in legal and economic position between a creditor and a debtor and not contrary to laws. A creditor should keep the balance in a loan agreement, and a debtor should consider the amount of money he will borrow by comparing it with the profit he will get from it.
Peranan Pemerintah Dalam Meningkatkan Produk Indikasi Geografis di Indonesia
Authors: Pratitis Sugih Ayu 
Published: November 2022

In addition to the role of government entrepreneurs optimally, proper preparation of human resources is needed. The right human resources will greatly assist in the development of potential geographic indications in Indonesia. As a field of law that is not yet popular among practitioners, academics, and the public, counseling about geographical indications is very important. Academics do not understand and understand about IPR and moreover about geographical indications. Because geographical indication is a new thing in Indonesia. Understanding of geographical indications is new in Indonesia. Understanding of geographical indications requires socialization to prevent violations of these geographical indications.
The government's role in increasing geographical indication products in Indonesia is through the government's efforts to increase the utilization of geographical indication products in Indonesia, namely by maximizing the utilization of geographical indications where in this case the government is represented by the Ministry of Industry and Trade (Depperindag), namely by providing guidance and conducting searches and collecting data and forming cross-departmental collaborations that are relevant nationally and internationally.
To resolve the unlawful abuse of geographical indications in Indonesia, the government can make its own provisions in the Geographical Indication Law or add articles in the trademark law which explicitly regulates the legal protection of geographical indications which refers to the Monopoly and competition Law. unhealthy business, for fake and misleading goods.
Aspek kepastian hukum terkait restitusi dalam perkara perlindungan anak
Authors: Siregar Erry Fendy 
Published: November 2022

THE ASPECT OF LEGAL CERTAINTY IN RELATION TO RESTITUTION IN THE CASES OF CHILD PROTECTION (A CASE STUDY OF LUBUK PAKAM’S STATE COURT’S VERDICT NUMBER 975/Pid.Sus/2019/PN.Lbp)

Article 71 D section (1) of the Act Number 35 Year 2014 on the amendment of the Act Number 23 Year 2002 concerning child protection guarantees that a child who has been a sex crime victim is permitted to lay claim to restitution from the criminal, which is intended to compensate for the loss of wealth, suffering from the crime, and/or medical fees, and/or psychological damage as a form of the criminal’s recompense. Besides, restitution is also intended to soothe the sex crime victim’s distress and enforce justice for them.
This study is normative legal research which fostered the descriptive analytic method based on constitutional interpretation, especially that in connection with child protection, and the case interpretation of Lubuk Pakam’s State Court’s verdict number 975/Pid.Sus/2019/Pn.Lbp. This research employed the data collection technique of library review and qualitative data analysis.
The verdict number 975/Pid.Sus/2019/PN.Lbp of Lubuk Pakam’s State Court’s judicial panel ordered the convict to pay a restitution of Rp. 1,200,000 (one million two hundred thousand rupiahs) to the victim. The verdict was not apart from the consideration of the fact that it was proven the convict had done the crime referred to by Article 81 section (2) in association with Article 76 D of the Act of Child Protection and the misdeed has caused the victim embarrassment. Moreover, in meting out the sentence, the judicial panel had to take into account the convict’s and social senses of justice. However, in this case, the convict did not pay the specified restitution. From the verdict, it is obvious that there is no guarantee restitution can be paid to the victim soon. What commonly happens is that the convict is not willing or able to pay it. In anticipation of the problem, the prosecutors as the verdict executors can apply Article 38 in association with Article 40 of the Act of Witness and Victim Protection to ensnare the criminal/convict who does not pay restitution to establish the legal certainty of restitution payment to the victim.
Penyerahan Tanah Yang Terikat Dalam Perjanjian Dondon Di Desa Aeklung Kecamatan Doloksanggul Kabupaten Humbang Hasundutan
Authors: Simamora Silvia Agustina 
Published: November 2022

ABSTRACT
The Dondon Agreement is to pawn a plot of rice field land to another party with an agreement that one day the land will be redeemed by the owner and when the land is pawned the land owner will receive the amount of money that the land owner needs from the dondon recipient. Dondon agreements according to customary law have a minimum time limit of 2 years, but in reality what happened in Aeklung village, Doloksanggul district, Humbang Hasundutan district, especially in hamlet I, the people still use the dondon agreement not using the time limit as it should be. The formulation of the problem from this research is how is the mechanism for transferring the dondon agreement in Aeklung village, Doloksanggul district, Humbang Hasundutan district, what are the rights and obligations of the parties who make the dondon agreement, how are the legal protections for the parties who make the dondon agreement. This study uses empirical legal research that is descriptive analytical. The mechanism for the transfer of the dondon agreement in Aeklung village, Doloksanggul sub-district, Humbang Hasundutan Regency, namely party I (dondon giver) and party II (dondon recipient) meet together to make a dondon agreement under sufficient stamp duty witnessed by each party. Based on the agreement, the rights and obligations of the parties arise.
Pelatihan Penggunaan Table Of Contents (TOC) dan Heading Style untuk Membuat Daftar Isi Makalah secara Otomatis di SMK Pab 8 Sampali
Authors: Alfina Ommi , Siregar Elida Tuti , Rahmadani Suci 
Published: November 2022

Penggunaan teknologi perangkat lunak dengan aplikasi pengolah data seperti Microsoft Word sangat dibutuhkan di dunia pembelajaran, terlebih aplikasi ini sudah mulai digunakan secara merata di kalangan sekolah menengah atas. Di SMK PAB 8 Sampali contohnya, di sekolah ini sudah menggunakan aplikasi komputer untuk menyelesaikan beberapa tugas yang diberikan oleh guru mereka. Misalnya dalam pembuatan makalah. Makalah adalah sebuah karya yang ditulis, memiliki sifat ilmiah dan di dalamnya berisi pembahasan mengenai suatu topik tertentu. Namun, tidak sedikit siswa yang salah dalam membuat makalah. Faktornya beragam seperti kerangka pembahasan dan penyusunan daftar isi yang kurang tepat, tata bahasa yang kurang baik, format penulisan yang salah, dan masih banyak lagi. Dalam sebuah makalah, daftar isi adalah salah satu komponen yang wajib ada. Fungsi dari daftar isi itu sendiri antara lain adalah untuk memudahkan kita ataupun pembaca mencari dengan mudah apa yang dituju. Oleh karena itu, semua penulis wajib mencantumkan daftar isi dalam makalahnya. Table Of Contents (TOC) dan Heading Style adalah perintah yang digunakan untuk membuat daftar isi dan mengatur format penulisan judul dan sub judul pada makalah yang sedang dikerjakan secara otomatis. Melalui pelatihan kepada para siswa SMK PAB 8 Sampali diharapkan mereka dapat memanfaatkan Table Of Contents (TOC) dan Heading Style untuk membuat daftar isi dan mengatur format penulisan makalah secara otomatis dan efisien sebagai penunjang dalam proses belajar mengajar.