bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Perspectives for Erectile Dysfunction Pharmacotherapy:
From Mechanism to Application
Authors: Zhang Haibao , Zhu Guodong , Ren Haomin , Song Wenbin , Yang Zhishang 
Published: June 2022

Abstract:
In recent years, the incidence of erectile dysfunction (ED) has continued to rise worldwide. Since pharmacotherapy is still the most common and effective method for the treatment of ED at present, many methods and drugs have been designed or developed for the treatment of ED. Oral phosphodiesterase-5 inhibitors and androgen supplement therapy are currently the common therapeutics for ED; however, some patients have poor response to these drugs because of the multiple pathogenic mechanisms of ED. Researchers are trying to find other treatment ways. On the one hand, many new strategies and concepts such as targeted therapy are also integrated into clinical or preclinical research; on the other hand, some combined therapies which have synergistic effects with reduced dose of single drug and less adverse effects are also developed. This review article summarized the efficacy of the latest first-line, second-line drugs and adjuvant therapies for the treatment of ED, as well as the application of comprehensive treatments, which will help doctors to not only deeply understand the mechanism of ED but select the suitable therapeutics for those patients.
Analysis of Pharmacological Activities and Mechanisms of Essential Oil in Leaves ofC. grandis‘Tomentosa’ by GC-MS/MS and Network Pharmacology
Authors: You Jie-Shu , He Sheng-Cai , Chen Liang , Guo Zhen-Hui , Gao Fei , Zhang Min-Yue , Dan Liu , Chen Wei 
Published: June 2022

Background:Citrus grandis ‘Tomentosa,’ a fruit epicarp of C. grandis ‘Tomentosa’ or C. grandis (L.) Osbeck is widely used in health food and medicine. Based on our survey results, there are also rich essential oils with bioactivities in leaves, but the chemical compounds in this part and relevant pharmacological activities have never been studied systematically. Therefore, this study was to preliminarily decipher the pharmacological activities and mechanisms of the essential oil in leaves of C. grandis ‘Tomentosa’ by an integrated network pharmacology approach.Methods:Essential oil compositions from leaves of C. grandis ‘Tomentosa’ were identified using GC-MS/MS. And then, the targets of these oil compositions were predicted and screened from TCMSP, SwissTargetPrediction, STITCH and SEA databases. STRING database was used to construct the protein-protein interaction networks, and the eligible protein targets were input into WebGestalt 2019 to carry out GO enrichment and KEGG pathway enrichment analysis. Based on the potential targets, disease enrichment information was obtained by TTD databases. Cytoscape software was used to construct the component-target-disease network diagrams.Results:Finally, 61 essential oil chemical components were identified by GC-MS/MS, which correspond to 679 potential targets. Biological function analysis showed 12, 19, and 12 GO entries related to biological processes, cell components and molecular functions, respectively. 43 KEGG pathways were identified, of which the most significant categories were terpenoid backbone biosynthesis, TNF signaling pathway and leishmaniasis. The component-target-disease network diagram revealed that the essential oil compositions in leaves of C. grandis ‘Tomentosa’ could treat tumors, immune diseases, neurodegenerative diseases and respiratory diseases, which were highly related to CHRM1, PTGS2, CASP3, MAP2K1 and CDC25B.Conclusion:This study may provide new insight into C. grandis ‘Tomentosa’ or C. grandis (L.) Osbeck and may provide useful information for future utilization and development.
Exosomes as Targeted Delivery Drug System: Advances in Exosome
Loading, Surface Functionalization and Potential for Clinical Application
Authors: Guo Zun Y. , Tang Yue , Cheng Yi C. 
Published: June 2022

Abstract:
Exosomes are subtypes of vesicles secreted by almost all cells and can play an important role
in intercellular communication. They contain various proteins, lipids, nucleic acids and other natural
substances from their metrocytes. Exosomes are expected to be a new generation of drug delivery systems
due to their low immunogenicity, high potential to transfer bioactive substances and biocompatibility.
However, exosomes themselves are not highly targeted, it is necessary to develop new surface
modification techniques and targeted drug delivery strategies, which are the focus of drug delivery research.
In this review, we introduced the biogenesis of exosomes and their role in intercellular communication.
We listed various advanced exosome drug-loading techniques. Emphatically, we summarized
different exosome surface modification techniques and targeted drug delivery strategies. In addition, we
discussed the application of exosomes in vaccines and briefly introduced milk exosomes. Finally, we
clarified the clinical application prospects and shortcomings of exosomes.
Heme Oxygenase-1 may Mediate Early Inflammatory Response of Intracerebral
Hemorrhage through Toll-like Receptor 4 Signaling Pathway
Authors: Qi Jiping , Song Yuejia , Li Ke , Zhang Zhen , Liu Qi , Wang Yu 
Published: June 2022

Objective:
The aim of this study was to investigate whether heme oxygenase-1 (HO-1)
promotes an early neuroinflammatory response after intracerebral hemorrhage (ICH) by regulating
the toll-like receptor 4 (TLR4) signaling pathway.

Methods:
We used a stereotaxic instrument to induce a mouse model of ICH through collagenase.
We divided the participants into a control group, an ICH group, and an ICH and zinc protoporphyrin
IX (ZnPP) group. The temporal expression pattern and cell localization of HO-1 and TLR4 after the
ICH were detected by immunofluorescence and western blot; after the expression of HO-1 was inhibited,
the expression levels of the TLR4 protein, the downstream molecule myeloid differentiation
factor 88 (MyD88), the Toll and interleukin-1 receptor (TIR) -domain-containing adapter-inducing
interferon-β (TRIF) and the inflammatory factors were measured by western blotting.

Results:
Immunofluorescence showed that HO-1 and TLR4 had similar temporal expression patterns
and cellular localization after ICH, and we found that inhibiting HO-1 reduces the expression
of TLR4 protein pathways, including TLR4, MyD88, TRIF, and related inflammatory factors, by
studying the inhibitor ZnPP.

Conclusion:
These results indicate that HO-1 may promote early neuroinflammation after ICH
through the TLR4/MyD88/TRIF signaling pathway.
An In-Silico Approach to Identify Therapeutic Target and Markers Associated with Diabetic Nephropathy
Authors: Rai Bhuvnesh , Maurya Pramod Kumar , Srivastava Medha , Mishra Prabhakar , Asif Mehar Hasan , Tiwari Swasti 
Published: June 2022

Background:
Renal disease in T2DM could arise independently of hyperglycemia, aka
non diabetic kidney disease. Its prevalence ranges from 33% to 72.5% among T2DM patients.
Specific molecular signatures that distinguish Diabetic Nephropathy from NDKD (FSGS) in
T2DM might provide new targets for CKD management.

Methods:
Five original GEO microarray DN and FSGS datasets were evaluated (GSE111154,
GSE96804, GSE125779, GSE129973 and GSE121233). Each of the three groups (DN, FSGS, and
Controls) had equal renal transcriptome data (n=32) included in the analysis to eliminate bias. The
DEGs were identified using TAC4.0. Pathway analysis was performed on the discovered genes
aligned to official gene symbols using Reactome, followed by functional gene enrichment analysis
using Funrich, Enrichr. STRING and Network analyst investigated PPI, followed by Webgestalt's
pathway erichment. Finally, using the Targetscan 7.0 and DIANA tools, filtered differential microRNAs
downregulated in DN were evaluated for target identification.

Result:
Between the three groups, DN, FSGS, and Control, a total of 194 DEGs with foldchange,>
2&<-2 and P-value0.01 were found in the renal transcriptome. In comparison to control,
45 genes were elevated, particularly in DN, whereas 43 were upregulated specifically in FSGS. DN
datasets were compared to FSGS in a separate analysis. FABP4, EBF1, ADIRF, and ART4 were
shown to be among the substantially up-regulated genes unique to DN in both analyses. The transcriptional
regulation of white adipocytes was discovered by pathway analysis.

Conclusion:
The molecular markers revealed might be employed as specific targets in the aetiology
of DN, as well as in T2DM patients' therapeutic care.
Docetaxel-induced Flagellate Erythema - Case Report and Brief Review
Authors: Asma Jerbi , Sarrah Kastalli , Ons Charfi , Riadh Dhaghfous , Sihem El Aidli 
Published: June 2022

Introduction:
Flagellate erythema is a distinctive morphologic reaction pattern, recognized by whiplash-like
pruritic erythematous eruption. Usually encountered in patients receiving bleomycin. Only one
case of docetaxel induced flagellate erythema was reported in the literature.

Case report:
Here in, we report a rare case of docetaxel induced flagellate erythema in a 53 years old woman with no particular medical history treated with docetaxel for metastatic adenocarcinoma of her right breast. Seven days after the third course, she developed multiple lineal and parallel pruritic erythematous streaks mainly on her chest and abdomen. The cutaneous erythema disappeared gradually over 10 days leaving hyper-pigmented post inflammatory linear scars lasting two
weeks. The same reaction reappeared after the fourth and the fifth docetaxel course.

Conclusion:
Flagellate erythema has been reported as an adverse drug reaction secondary to several
antineoplastic molecules including docetaxel. Further studies are needed to discover its
underlying mechanisms in order to figure out better treatment plans and prevention.
Hepatoprotective Effect of Myricetin following Lipopolysaccharide/DGalactosamine:
Involvement of Autophagy and Sirtuin 1
Authors: Roghani Mehrdad , Rostami Amir , Baluchnejadmojarad Tourandokht 
Published: June 2022

Background:
Acute liver injury (ALI) is a critical and fatal disorder associated with excessive
oxidative stress and inflammation, ultimately leading to the death of hepatocytes. Myricetin is a
bioflavonoid in some berries, including blueberries and strawberries, with anti-inflammatory, antioxidant
and anti-apoptotic properties.

Objective:
In the current research, the hepatoprotective potential of myricetin was studied in the
LPS/D-GalN model of ALI in C57BL/6 mice.

Methods:
For inducing liver injury, D-GalN (400 mg/kg) and LPS (50 g/kg) were injected via intraperitoneal
route and myricetin was orally administered (25 or 100 mg/kg/day) for two days before inducing
injury. Functional indices of liver dysfunction along with hepatic apoptotic, autophagic, oxidative
stress and inflammatory factors were measured.

Results:
Myricetin (100 mg/kg) reduced the fatality rate of animals and pathological liver changes and
suitably lowered serum levels of total bilirubin, 8-OH-dG, ALT, AST and ALP in addition to decreasing
apoptotic, oxidative and inflammatory factors, NOX, NLRP3, caspase 3, MPO and enhancing
some antioxidants. Besides, myricetin improved the hepatic level and activity of sirtuin 1 and reversed
inappropriate alterations of autophagic parameters, including LC3 II, Beclin 1, and P62. The beneficial
effects of myricetin were attenuated after co-treatment with the autophagy inhibitor 3-
methyladenine.

Conclusion:
This study indicates the hepatoprotective potential of myricetin that can be ascribed to its
down-regulation of oxidative, apoptotic, and inflammatory factors and upregulation of antioxidants
besides its partial regulation of sirtuin 1 and autophagic pathway.
Telepsicología para la adherencia al tratamiento en pacientes con diabetes mellitus tipo 2: una revisión sistemática
Authors: Pérez Ortiz Alejandro , Becerra Gálvez Ana Leticia , Mancilla Díaz Juan Manuel 
Published: June 2022

Objetivos: el artículo tiene dos objetivos, 1) reunir los estudios controlados y no controlados que den evidencia de la eficacia de la Telepsicología sobre índices y conductas de adherencia terapéutica: dieta, actividad física, consumo de medicamentos, monitoreo de glucosa capilar, cuidado del pie y HbA1C; en pacientes con diabetes mellitus tipo 2; 2) analizar las características metodológicas de los estudios.   Diseño metodológico:considerando los criterios PRISMA y la estrategia de búsqueda PIT, se consultaron seis bases de datos: Pubmed, OVID (PsycINFO y PsycArticles), Scopus, CINAHL y Web ofScience.   Resultados:se identificaron un total de 1,547 artículos, pero sólo cinco, ensayos controlados aleatorizados, cumplieron los criterios de inclusión. Las conductas e índices de adherencia terapéutica evaluadas fueron: HbA1C (n =3), actividad física (n = 2), consumo de medicamentos (n =1), monitoreo de glucosa capilar (n =1) y dieta (n =1). En dos estudios, la Telepsicología de tipo asincrónica (i.e. mediante páginas web y apps) mejoró la HbA1C, consumo de medicamentos, monitoreo de glucosa capilar y la dieta; los resultados en la actividad física difieren.   Limitaciones de la investigación:dado que sólo dos estudios describieron información sobre el tamaño del efecto y su intervalo de confianza, no es viable realizar un metaanálisis.   Hallazgos:la Telepsicología basada en la terapia cognitivo-conductual de tipo asincrónica muestra resultados alentadores para mejorar el control glucémico y conductas de adherencia terapéutica en personas con diabetes mellitus. Las investigaciones identificadas se realizaron en Estados Unidos, Europa y Oceanía.
Proses Pembelajaran Biologi Kelas XI Sekolah Menengah Atas Negeri 3 Kerinci
Authors: Nofriadi Nanang , Rohim Abd. 
Published: June 2022

The ineffectiveness of the learning process is part of the problems experienced by the world of education, to optimize it so that it is in accordance with the goals set, the government has set a standard process contained in the Minister of National Education Regulation No. 41 of 2007. This study aims to see the quality of biology learning in class XI high school ( SMA) Negeri 3 Kerinci consists of a Learning Process Plan (RPP), implementation and assessment of learning achievement. Methods The research uses a mixed method that combines quantitative and qualitative approaches. Data were taken by means of observation, interviews, documentation, IPKG 2008. The data analysis technique used was triangulation. The results of the study revealed that the Assessment of the Biology Learning Process Plan (RPP) Class XI SMA Negeri 3 Kerinci according to the 2008 GPA regarding the Learning Process Plan (RPP) reached a score of 3 (50 - 75 % implemented) in the Good category (76 - 90). Assessment of the Biology learning implementation process for Class XI SMA Negeri 3 Kerinci according to the 2008 GPA regarding the Implementation of the Learning Process In class XI A2 it was 2.82 (25-50% accomplished) in the Enough category (61 - 75). While the value of Learning Implementation in Class XI A4 is 2.71 (25-50% accomplished) in the Enough category (50 - 75). -50% done) with category Enough (61 - 75).

Key words: Learning, Biology, SMA

Abstrak

Kurang efektifnya proses belajar bagian dari persoalan yang dialami dunia pendidikan, untuk mengoptimalkan agar hal tersebut sesuai dengan tujuan yang ditetapkan, pemerintah telah menetapkan standar proses yang dimuat dalam Permendiknas No 41 tahun 2007. Penelitian ini bertujuan melihat kualitas pembelajaran Biologi kelas XI Sekolah Menengah Atas (SMA) Negeri 3 Kerinci terdiri dari Rencana Proses Pembelajaran (RPP), Pelaksanaan serta penilaian prestasi belajar. Metode Penelitian menggunakan mixed method yang menggabungkan pendekatan secara kuantitatif dan kualitatif. Data diambil dengan cara observasi, interview, dokumenasi, IPKG Tahun 2008. Teknik analisis data yang dipakai yaitu secara triangulasi. Hasil dari penelitian diketahui bahwa Penilaian Rencana Proses Pembelajaran (RPP) biologi Kelas XI SMA Negeri 3 Kerinci menurut IPKG tahun 2008 tentang rencana Proses Pembelajaran (RPP) mencapai nilai 3 (50 - 75 % terlaksana) dengan kategori Baik (76-90). Penilaian Proses Pelaksanaan pembelajaran Biologi Kelas XI SMA Negeri 3 Kerinci menurut IPKG tahun 2008 tentang Pelaksanaan Proses pembelajaran Pada kelas XI A2 adalah 2,82 (25-50% terlaksana) dengan kategori Cukup (61 - 75). Sedangkan nilai Pelaksanaan Pembelajaran di Kelas XI A4 adalah 2,71 (25-50 % terlaksana) dengan kategori Cukup (50 - 75) Penilaian proses pembelajaran (evaluasi) biologi Kelas XI SMA Negeri 3 Kerinci menurut IPKG tahun 2008 tentang 2,90 (25-50% terlaksana) dengan kategori Cukup (61 - 75).

Kata kunci: Pembelajaran, Biologi, SMA
Perlindungan Hukum Pemegang Obligasi Terhadap Resiko Emiten Yang Gagal Bayar (Default)
Authors: Clasrissa Sasqia Putri Nabilla , Hasan Umar 
Published: June 2022

The objectives of this study are (1) to identify and analyze the responsibility of the issuer of the bonds to issuers who default on after the enactment of the Financial Services Authority Law No. 21 of 2011 (2) to determine and analyze the form of legal protection of bondholders against issuers who default on after the enactment of the Financial Services Authority Law No. 21 of 2011. The research method used is juridical normative, which is research that aims to study legal materials, both primary and secondary legal materials. The data source in this research and writing is using secondary data in the form of library research. The approaches used in the research are the normative approach, the conceptual approach, and the historical approach. The result of this research is that the responsibility of the issuer to default (default), the issuer has an important role in the issuance of bonds, the issuer has the main responsibility of paying the bond interest on time. In addition, the protection needed by bond investors to protect their capital from the possibility of default risk can consist of three things, namely information disclosure, collateral included in bond issuance, and sinking fund (reserve fund). provided in the context of providing funds for the payment of loan principal along with the agreed interest in bonds.

Abstrak
Tujuan dari penelitian ini adalah (1) untuk mengetahui dan menganalisis tanggung jawab pihak penerbit obligasi terhadap emiten yang gagal bayar (default) pasca berlakuknya Undang-Undang Otoritas Jasa Keuangan No. 21 Tahun 2011 (2) untuk mengetahui dan menganalisis bentuk perlindungan hukum pemegang obligasi terhadap emiten yang gagal bayar (default) pasca berlakuknya Undang-Undang Otoritas Jasa Keuangan No. 21 Tahun 2011. Metode penelitian yang digunakan adalah Yuridis Normatif, yaitu penelitian yang bertujuan untuk pengkajian terhadap bahan-bahan hukum, baik bahan hukum primer maupun bahan hukum sekunder. Sumber data dalam penelitian dan penulisan ini adalah menggunakan data sekunder berupa penelusuran kepustakaan (library research).Pendekatan yang digunakan dalam penelitian adalah pendekatan Perundang-Undangan (normatif approach), Pendekatan Konseptual (conceptual approach), Pendekatan Historis (Historical Approach). Hasil penelitian ini adalah bahwa tanggung jawab pihak penerbit terhadap gagal bayar (default), emiten memiliki peran penting dalam penerbitan obligasi, emiten memiliki tanggung jawab pokok yaitu melakukan pembayaran bunga obligasi dengan tepat waktu. Selain itu, perlindungan yang dibutuhkan oleh investor obligasi untuk melindungi modalnya dari kemungkinan terjadinya risiko gagal bayar (default) dapat terdiri dari tiga hal, yaitu keterbukaan informasi, adanya jaminan (collateral) yang disertakan dalam penerbitan obligasi, dan adanya sinking fund (dana cadangan) yang disediakan dalam rangka penyediaan dana untuk pembayaran pokok pinjaman beserta bunga yang diperjanjikan dalam obligasi
BARRIERS IN THE PEDAGOGICAL SUPPORT OF ELECTRONIC LEARNING IN A HIGHER EDUCATION INSTITUTION
Authors: Яковлева Кристина Игоревна 
Published: June 2022

Представлен анализ трудностей преподавателей и студентов в высшем учебном заведении при взаимодействии в электронном формате, а также анализ результатов социологических исследований, проведенных в Томском государственном университете и Томском политехническом университете в 2016 г., и результатов фокус-группы «Сопровождение онлайн-курсов», организованной в Томском государственном университете в 2018/2019 гг. В результате исследования выделены и систематизированы педагогические, организационные, технические и экономические дефициты субъектов образовательного процесса при педагогическом сопровождении электронного обучения и сформулированы рекомендации по преодолению этих дефицитов. Полученные результаты будут полезны специалистам, занимающимся организацией электронного обучения в вузах, и преподавателям для создания эффективной системы педагогического сопровождения.E-learning is becoming an integral part of the educational process in universities. Online interaction between students, students and teachers remains significant in e-learning. It affects the involvement of students in the educational process. The article deals with the analysis of the interaction difficulties in e-learning which teachers and students face in universities. The author looks for the difficulties in the results of sociological research conducted at Tomsk State University and Tomsk Polytechnic University in 2016, and the results of the focus group «Online course support» organized at Tomsk State University in 2018. The article highlights social, organizational, technical and economic difficulties for the educational process subjects in the pedagogical support of e-learning. Also, recommendations were formulated to overcome these difficulties. The main difficulties for teachers and students in quantitative research are the lack of time, the lack of ICT competencies necessary to work in an electronic campus environment. In addition, students note failures in the work of the portal. The focus group participants agree on the weak communication of teachers with students and fellow students among themselves, as well as technical difficulties when working with platforms and their technical services. Quantitative studies showed more technical and organizational difficulties, and qualitative research showed social and technical difficulties. The results will be useful for specialists and teachers involved in the organization of e-learning in universities to create an effective system of pedagogical support.