bluuebunny/crossref_metadata_2025 huggingface dataset:
Tradisi Longkangan Sebagai Konvensi Budaya Lokal dan Agama Islam di Desa Binade Kecamatan Ngrayun Kabupaten Ponorogo
Authors: Prahara Erwin Yudi , Waris Waris , Saputro Eko
Published: January 2023

One of the traditions that includes local culture in Ponorogo is the Longkangan Tradition. The existence of the longkangan tradition has had various impacts on the lives of the people of Binade village, Ngrayun Ponorogo sub-district, mainly in the relationship between Islam and Javanese tradition which eventually formed a convention. This research uses a qualitative descriptive approach that explains the community's perceptions and the existence of local cultural and Islamic religious conventions in the Longkangan tradition. In this study, it was found that the people of Binade village as a whole are Muslim and come from Javanese tribes. Nearly all Binade villagers take water from the river or Belik. Therefore, the Longkangan tradition emerged, which aims to bring gratitude to God for the abundance of water sources for the community. In addition, the longkangan tradition also aims to commemorate services and pray for the spirits of the ancestors who have opened villages and water sources in Binade village. The conclusion of this research is that the conventions or agreements that exist in the longkangan tradition are still being obeyed by the Binade village community. In this case there is no written law regulating the longkangan tradition, but the existence of this convention has made the longkangan tradition still preserved until now. Until now the Longkangan tradition is still preserved as a convention of local culture and Islam.
Implementasi Moderasi Beragama di Madrasah Aliyah Tahdzibun Nufus Jakarta dalam Terbentuknya Nilai-Nilai Moderasi Beragama
Authors: Nurullah Akmal , Panggayuh Bina Prima , Shidiq Sapiudin
Published: January 2023

Religious moderation is a very important activity carried out by Indonesian people who have different beliefs and religious backgrounds. Religious leaders who are supported by the government are trying to prevent and anticipate radical and intolerance events in Indonesia. One of them is by holding interfaith religious moderation. The concept of moderate Islam is a religious perspective that is very relevant in the context of diversity in Indonesia. As a form of strengthening and strengthening the role of Madrasah Aliyah in countering radicalism and extremism, it is necessary to internalize religious moderation in the Madrasah Aliyah curriculum. Which aims to mediate these two extreme poles, by emphasizing the importance of substantively internalizing religious teachings on the one hand, and contextualizing religious texts on the other. To examine these problems, researchers used qualitative research methods. This type of research includes case study research, which is a qualitative research that seeks to find meaning, investigate processes, and gain deep understanding and understanding of individuals, groups, or situations. In analyzing the data, the researcher took the interactive model as the presentation. Activities in data analysis include data reduction, data presentation as well as drawing conclusions and, verification. The results of the study of religious moderation that were instilled in the students of MA Tahdzibun Nufus Jakarta were not in a formal atmosphere, inserted in every lesson. The factors that influence the religious moderation spirit of the students of MA Tahdzibun Nufus Jakarta are young people who think more modern according to their times, are involved in activities directly. The form of moderation practiced by the students of MA Tahdzibun Nufus Jakarta is giving each other advice between students, this practice raises concern among friends.
تحليل إحتياجات المواد التعليمية الإفتراضية لمهارة القراءة
Authors: Chusna Ali Ba'ul , Bahruddin Uril
Published: January 2023

AAbstractReading is one of the activities to improve human knowledge. And it is one of the four Arabic language skills wich must be learned by the students. Today, reading materials represent a wide range of knowledge. Before preparing the materials of reading skill, its important to appropriate it with the required teaching objectives and students need in the teaching process. This study aims to describe the reality of online reading learning at the university level and analyzing student needs for online teaching materials in online reading learning. This research was conducted at the Department of Arabic Language Education IAIN Ponorogo. Research data obtained through observation, interviews, and questionnaires. Data analysis was carried out using a quantitative descriptive approach. The results of the study show that online learning of reading skill at the Department of Arabic Language Education IAIN Ponorogo is currently carried out by using zoom media, google classroom, and google meet. However, the fact is that learning has not been able to meet the learning objectives that have been set. The students really need online teaching materials for learning reading skills. There are six things that must be considered by the compiler as needed by students, there are instructions for use, learning objectives, supporting pictures, vocabularies, various kinds of exercises, and easy access to teaching materials.   الملخصالقراءة هي احدى الأنشطة لترقية المعرفة والعلوم عند الناس وهي من المهارة اللغوية العربية الأربعة. تمثل المواد المقروءة بابا واسعا من أبواب المعرفة اليوم. فإعداد المواد التعليمية لمهارة القراءة المناسبة بأهداف التعليم المطلوبة أمر مهم عند المؤسسة التعليمية. والتعريف على الأمور التي يحتاجها الطلبة في عملية التعليم يكون شيئا ضروريا قبل إعداد المواد التعليمية. تهدف هذه الدراسة إلى كشف أمرين هامين. أولا، وصف واقع تعليم القراءة الإفتراضي بقسم تعليم اللغة العربية بجامعة فونوروجو الاسلامية الحكومية. و ثانيا، المواد التعليمية الإفتراضية لمادة القراءة التي يحتاجها طلبة قسم تعليم اللغة العربية بجامعة فونوروجو الاسلامية الحكومية. و الطريقة التي يستعملها الباحث للحصول على البيانات المطلوبة هي طريقة الملاحظة والمقابلة و الاستبانة. ويتم تحليل البيانات بالتحليل الوصفي الكمي. و من نتيجة هذه الدراسة هي أن تعليم القراءة بقسم تعليم اللغة العربية في عصر جائحة كوفيد-19 يكون إفتراضيا باستخدام الوسائل التعليمية الإفتراضية كجوجل كلاسروم و الزوم. ولكن الواقع يكون التعليم قليل الموافقة بأهداف التعليم المطلوبة يواجه المدرس والطلبة بعض المشكلات، منها المشكلة المتعلقة  بالمواد التعليمية. ثانيا، تكون المواد التعليمية الإفتراضية شيئا محتاجا ضروريا عند الطلبة و كذلك المدرس أثناء تعليم القراءة الإفتراضي في عصر جائحة كوفيد-19 اليوم. وهناك ستة أمور لابد أن تكون بهذه المواد التعليمية الافتراضية كما يحتاجها الطلبة، وهي دليل الاستخدام وأهداف التعليم والمفردات والصورة والتدريبات وسهولة الوصول نحو المادة
TUAN GURU ZAINUDIN ABDUL MAJID’S EPISTEMOLOGICAL VIEWS ON INTEGRATION OF ISLAMIC EDUCATION IN LOMBOK, WEST NUSA TENGGARA
Authors: Muhtar Fathurrahman
Published: January 2023

AbstractCurrently, Muslims have a lack of understanding of epistemology, which results in the weak mastery of Muslim thought towards science and technology. In medieval times, Islamic thinkers with integrated thoughts were born from the mastery of epistemology sourced from the Qur'an and Sunnah.This study aims to explain Tuan Guru Kiai Zainuddin Abdul Majid's thinking in science development, making him a pioneer in Islamic education and a national hero in Lombok, West Nusa Tenggara. These paper methods are a historical approach and literature with content analysis. This study's results show that Tuan Guru Zainuddin Abdul Majid integrated his thoughts. His ideas are written in Tuhfatul Anfenaniyah Syarah Nahdlatuzzainiyah and his verse ya man yarum. His paper that religion and science are like buildings standing firmly. If religion and science are kept separate, so Muslims will fall behind. So, Islam people must comprehend Shari'a, Nahu, Shoref (grammar), Fiqh (Islamic law), astronomy, language, math, geometry, algebra, chemistry, and geography integrated to advance in this time and the future. His ideas were based on the scientific and dialectical foundations of Bayani, Burhani, and Irfani's epistemology, which is the basis for developing Islamic education. His thought was successful in developing Islamic education institutions based on Islamic integration. AbstrakLemahnya penguasaan epistemology menyebabkan lemahnya pemikiran umat Islam dalam penguasaan ilmu pengetahuan dan teknologi dewasa ini. Penguasaan epistemology yang bersumber dari al-Qur’an dan Sunnah telah melahirkan pemikir Islam yang memiliki pemikiran integral pada abad pertengahan. Penelitian ini bertujuan untuk menjelaskan pemikiran Tuan Guru Kiai Zainuddin Abdul Majid dalam pengembangan ilmu pengetahuan, yang menjadikannya sebagai pelopor pendidikan Islam dan pahlawan nasional di Lombok, Nusa Tenggara Barat. Pendekatan yang digunakan dalam penelitian ini adalah pendekatan historis dan literatur dengan analisis konten. Hasil penelitian ini menunjukkan bahwa Tuan Guru Zainuddin Abdul Majid telah mengintegrasikan pemikirannya. Ide-idenya ditulis dalam Tuhfatul Anfenaniyah Syarah Nahdlatuzzainiyah dan syairnya ya man yarum. Dalam karya tulisnya diyatakan bahwa agama dan sains ibarat bangunan yang berdiri kokoh. Jika agama dan sains dipisahkan, maka umat Islam akan tertinggal. Baginya, umat Islam harus memahami Syariat, Nahu, Shoref (tata bahasa), Fiqh (hukum Islam), astronomi, bahasa, matematika, geometri, aljabar, kimia, dan geografi yang terintegrasi untuk mencapai kemajuan di masa ini dan masa depan. Ide-idenya didasarkan pada fondasi ilmiah dan dialektis epistemologi Bayani, Burhani, dan Irfani, yang dijadikan sebagai dasar dalam mengembangkan pendidikan Islam. Pemikirannya telah menghasilkan lembaga pendidikan Islam berbasis integrasi Islam
KONTROL DIRI PADA REMAJA PENGGEMAR GAME ONLINE DI DESA SIDOHARJO PULUNG PONOROGO
Authors: Marista Elsa
Published: January 2023

Tujuan penelitian ini untuk mengetahui perilaku remaja penggemar game online, dampak game online pada remaja, dan kontrol diri pada remaja yang dilakukan di Desa Sidoharjo Pulung Ponorogo. Penelitian ini menggunakan pendekatan deskriptif kualitatif. . Hasil penelitian menunjukkan bahwa perilaku ketiga subjek remaja penggemar game online yaitu suka menunda pekerjaan, kurang berminat untuk bersosialisasi, pola hidup yang kurang sehat, dan sering membantah orang tua. Dampak game online pada ketiga subjek meliputi dampak negatif seperti mudah marah, perubahan pola makan dan istirahat, sering dimarahi orang tua dan nilai sekolah mengalami penurunan. Adapun dampak positif yaitu mereka dapat memahami beberapa istilah bahasa asing, merasa bahagia dan mengurangi stres. Jenis kontrol diri dari ketiga subjek menunjukkan kontrol diri yang sama yakni dengan appropriate control atau kontrol yang tepat. Aspek kontrol diri yang dilakukan ketiga subjek sama yakni kontrol kognitif dan kontrol perilaku. Kontrol kognitif yang dilakukan ketiga subjek dengan menyadari bahwa bermain game online sebenarnya kurang bermanfaat. Kontrol perilaku yang dilakukan ketiga subjek dengan menyibukkan diri untuk melakukan kegiatan yang lebih positif. Kata kunci: Kontrol Diri, Remaja, Penggemar Game Online
SELF MANAGEMENT DALAM MENGHADAPI STRES DI MASA PANDEMI PADA MAHASISWA YANG BEKERJA (Studi Kasus Mahasiswa Semester 7 Jurusan BPI IAIN Ponorogo)
Authors: Muthmainnah Shofiyatul Shofiyatul
Published: January 2023

Mahasiswa yang bekerja memiliki beban yang lebih berat daripada mahasiswa yang tidak bekerja. Mahasiswa yang bekerja tentu pernah dihadapkan pada rintangan yang dapat mengakibatkan timbulnya stres. Mahasiswa yang bekerja yang menghadapi stres dengan baik maka dapat menyesuaikan diri dan menemukan solusi atas stres yang dihadapinya, sedangkan mahasiswa yang tidak mampu menghadapi stres dengan baik maka kesulitan untuk menemukan solusi. Salah satu cara untuk menghadapi stres yaitu dengan Self Management. Tujuan penelitian yaitu 1) Untuk mengetahui aspek self management pada mahasiswa yang bekerja selama pandemi, 2) Untuk mengetahui faktor pendukung self management pada mahasiswa yang bekerja selama pandemi. Dalam penelitian ini penulis menggunakan jenis penelitian deskriptif dengan pendekatan kualitatif. Hasil penelitian menunjukkan 1) Aspek self management yang dimiliki oleh mahasiswa yang bekerja adalah self motivation, self organization, self control dan self development, 2) Faktor pendukung self management yang dimiliki oleh mahasiswa yang bekerja meliputi kesehatan, keterampilan, aktivitas, dan identitas diri.
KONSEP DIRI PADA PEKERJA SEKS KOMERSIAL DI WARUNG REMANG-REMANG (Desa Kedung Banteng Kecamatan Kebonsari Kabupaten Ponorogo)
Authors: Zuhri Muhammad Syaifudin
Published: January 2023

Semenjak ditutupnya tempat lokalisasi bernama Janti pada 19 Februari 2015, nampaknya bukan menjadi solusi untuk menghentikan adanya prostitusi di Ponorogo. Hal ini terbukti dengan masih adanya warung remang-remang di sejumlah tempat salah satunya di Desa Kedungbanteng Kecamatan Sukorejo Kabupaten Ponorogo akibat adanya penutupan tempat lokalisasi. Kepala dinas sosial tenaga kerja dan transmigrasi ponorogo, Sumani mengatakan dari 176 PSK atau mucikari yang ada di Desa Kedungbanteng telah diberi uang kompensasi dari pemerintah. Namun hal ini juga masih belum bisa menguntaskan PSK dari pekerjaannya. Kurangnya skill dalam bidang pekerjaan sehingga membuat mereka kembali menjadi PSK.Penelitian ini bertujuan untuk mengetahui bagaimana konsep diri pada pekerja seks komersial (PSK) di warung remang-remang Desa Kedungbanteng Kecamatan Sukorejo Kabupaten Ponorogo dan untuk mengetahui cita-cita atau harapan hidup.pada pekerja seks komersial (PSK) di warung remang-remang Desa Kedungbanteng Kecamatan Sukorejo Kabupaten Ponorogo. Penelitian ini menggunakan metode kualitatif deskripstif yaitu metode penelitian yang berlandaskan pada filsafat postpositivisme , digunakan untuk meneliti pada kondisi yang alamiah, dimana peneliti adalah sebagai instrumen kunci, teknik pengumpulan data dilakukan secara triangulasi, analisis data bersifat induktif/kualitatif, dan hasil penelitian kualitatif lebih menekankan makna generalisasi.Hasil penelitian menunjukkan faktor yang mendorong seseorang menjadi PSK ialah faktor ekonomi atau kemiskinan, faktor pendidikan yang rendah dan keluarga yang kurang harmonis atau Broken Home. Konsep diri yang ada pada PSK cenderung buruk karena mereka ditolak oleh lingkungan dan juga keluarga sehingga merasa tidak ternilai.Kata Kunci: Konsep Diri, Pekerja Seks Komersial
Pengaruh Sosial Politik dan Budaya Terhadap Produk Hukum Keluarga di Malaysia
Authors: Nurhuda Rohmad
Published: January 2023

Tidak dapat dihindarkan bahwa sejarah Malaysia bertanggung jawab atas keberadaan dua kelompok etnis yang berbeda ini di negara ini. Sudah menjadi rahasia umum bahwa Malaysia (Melayu) berada di persimpangan strategis jalur perdagangan utama di Asia Tenggara. Karena di sinilah para pedagang dari India, Arab, dan Cina, selain penjajah Portugis, Belanda, dan Inggris, membawa ajaran Hindu, semenanjung Melayu menjadi pusat berkumpulnya berbagai pengaruh agama dan budaya. Selain itu, Malaysia adalah jajahan Portugis dan Belanda di masa lalu, dan kolonialisasi Inggris di wilayah tersebut dimulai pada kedua abad ke-18. Tentu saja hal ini akan berdampak pada produk hukum yang diproduksi di Malaysia karena kemungkinan besar hukum yang dibuat oleh para penakluk berakar di Malaysia. Menjadi pijakan penulis untuk membahas Hukum Keluarga Islam di Malaysia karena selain melihat kembali sejarah Malaysia tentunya juga harus melihat kondisi sosial politik yang berkembang di Malaysia yang kesemuanya merupakan faktor penentu bagi lahirnya hukum tersebut atau produk yang dihasilkan. Dalam tulisan ini penulis menggunakan metode diskriptif analisis agar nantinya penulis dapat mendiskripsikan dan menganalisis lebih mendalam terkait masalah diatas. Pada tulisan ini menghasilkan bahwasanya Sejarah perkembangan Hukum Keluarga Islam di Malaysia dimulai sejak zaman sebelum ekspansi atau penjajahan Inggris. Hukum Keluarga Islam di Malaysia di mulai dengan kombinasi hukum Islam dan adat. Kemudian, ketika Inggris datang Hukum Keluarga Islam di atur dalam Mohammedan Marriage Ordinance, No.V Tahun 1880, dan setelah merdeka hukum keluarga Islam yang diterapkan adalah Hukum Keluarga Islam Malaka 1983, Hukum Kelantan 1983, Hukum Negeri Sembilan 1983, Hukum Wilayah Federal 1984, Hukum Perak 1984 (No.1), Hukum Kedah 1979, Hukum Penang 1985, Hukum Trengganu 1985, Pahang Hukum 1987, Hukum Selangor 1989, Hukum Johor 1990, Hukum Sarawak 1991, Hukum Perlis 1992, dan Hukum Sabah 1992. Hukum Keluarga Islam di Malaysia masih belum terkodifikasi jadi satu kesatuan baik perkawinan, Batas usia Pernikahan, Perceraian, Poligami dan hukum keluarga lainnya dikarenakan tiap negara bagian memiliki aturan tersendiri terkait hukum keluarga. Secara esensial hukum keluarga Islam di Indonesia dan Malaysia tidak banyak perbedaan, akan tetapi rujukan hukum Indonesia bertumpu pada satu hukum untuk satu negara sedangkan di malaysia terpisah-pisah dan tidak ada penetapan satu hukum untuk satu negara.
Kontestasi Metodologi Legislasi Usia Perkawinan di Indonesia
Authors: Khaidarulloh Khaidarulloh
Published: January 2023

In many cases, the issue of marriage age is often a symbol of state intervention in modernizing the law. In addition to being a tool for carrying out social change, it also represents the occurrence of negotiations between religious and state paradigms, where in essence, both want the same benefits, namely certainty and guarantee of citizen’s rights. The research is based on literature data on how the discourse on the modernization of Islamic family law in the scope of the issue of marriage age has evolved in the literature. In addition, secondary data is also based on the latest developments in the rate of marriage dispensation cases in some religious courts spread across Indonesia. The results showed that, historically, marriage age was an important issue in the concept of modernization of Islamic family law; it became evidence of the existence of ideological contestation between religion and the state. However, the rampant cases of marriage dispensation in parts of Indonesia are also proof that the country's big project to change people's culture cannot be said to be successful, considering that the marriage age bill since 1973 has been rolled out. For this reason, synergy between state institutions to reduce the high number of marriage dispensations needs to be reviewed, thus finding weak points for the enactment of existing rules.
Kolase Kapas: Skill Membangun Kemampuan Seni Bagi Anak Usia Dini
Authors: Binsa Ucik Hidayah , Solikhatin Muthik , Irbah Ariq Nurjannah
Published: January 2023

Abstract: Art ability is one of the main aspects that must be developed in improving children's skills. Art also has a very important influence in stimulating the development of a child's brain. The purpose of this study was to find out how the artistic abilities of group A1 students and how to improve the artistic abilities of group A1 students through cotton collage at RA Muslimat NU XIII Nawa Kartika Talok. This research includes Classroom Action Research. The subjects of this research were group A1 students of RA Muslimat NU XIII Nawa Kartika Talok, which consisted of 17 students. This research was conducted in two cycles, with several stages, namely action planning, action implementation, observation and reflection. The results showed that there was a significant increase with the completeness of the class target of at least 82.35% in cycle 2. Thus overall the artistic abilities of the children were in a very good stage of development (BSB) and through this cotton collage activity was able to improve artistic abilities in group students A1 RA Muslimat NU XIII Nawa Kartika Talok.
cpn60 metagenomic amplicon library preparation for the Illumina Miseq platform
Authors: Fernando Champika , Hill Janet E.
Published: January 2023

This protocol can be applied to determine the composition of a microbial community. The cpn60 gene (also known as groEL, hsp60) is present in almost all bacteria and a 552-558 bp region of the gene has been established as a barcode for species level identification of bacteria. The primer cocktail used in this protocol amplifies cpn60 barcode sequences from bacteria with a wide range of G+C content. Some species of Mycoplasma lack the cpn60 gene and therefore this method is not recommended to detect Mycoplasma. DNA sequences generated from this method could be compared to cpnDB, a public database of cpn60 sequences, for identification. Library preparation involves cpn60 amplicon generation, PCR clean-up, index PCR, index PCR clean-up, library quantification, normalization, pooling, library denaturation and loading. Time taken to complete depends on the number of samples included. If using 96 samples, the procedure takes 8 hours but there are several stages where the samples could be stored and continued the next day. Specific instructions are provided for the Illumina MiSeq platform, but the protocol could easily be adapted for other sequencing platforms.
A new rough PROMETHEE approach for the evaluation of potential failure modes and their effects in a general anesthesia process
Authors: Zafar Fariha , Saleem Muhammad Shoaib , Majeed Iqra Abdul , Javed Soha
Published: January 2023

Failure modes and effects analysis (FMEA) is a systematic framework that is broadly used to recognize and eliminate viable failures within objects, services, structures, designs, or organizations. In the general FMEA process, failure modes are assessed and ranked by the risk priority numbers which are attained through the product of crisp ratings of the risk elements such as detection, occurrence, and severity of each failure mode. But the traditional FMEA technique fails to deal with the uncertainty, present in complex systems. To enhance the effectiveness of conventional approaches, this paper presents a novel FMEA technique based on rough numbers and preference ranking organization method for enrichment evaluations (PROMETHEE) in the multi-criteria decision-making problems. Rough numbers are applied to handle ambiguous information in terms of rough intervals instead of single numerical ratings. In the proposed approach, an entropy weight technique is applied to determine the weights of risk factors. This presented approach uses the usual criteria preference function to show the preferences of failure modes. The risk priorities of the recognized failure modes are acquired by the rough PROMETHEE method. To illustrate its potential applications, the proposed method is applied to examine the risks of the general anesthesia process in the medical field. In the end, a comparison with the existing techniques is also described to show the efficiency of the proposed model.
CINC-2 and miR-199a-5p in exosomes secreted by transplanted Thy1+ cells activate hepatocytic progenitor cell growth in rat liver regeneration
Authors: Ichinohe Norihisa , Tanimizu Naoki , Ishigami Keisuke , Yoshioka Yusuke , Fujitani Naoki , Ochiya Takahiro , Takahashi Motoko , Mitaka Toshihiro
Published: January 2023

Background
Small hepatocyte-like progenitor cells (SHPCs) are hepatocytic progenitor cells that transiently form clusters in rat livers treated with retrorsine and with 70% partial hepatectomy (PH). We previously reported that transplantation of Thy1+ cells derived from d-galactosamine-treated livers promotes SHPC expansion, resulting in the acceleration of liver regeneration. Extracellular vesicles (EVs) produced by Thy1+ cells act on sinusoidal endothelial cells (SECs) and Kupffer cells to secrete IL17B and IL25, respectively, resulting in SHPC activation through IL17 receptor B (RB) signaling. Our aim is to identify factors in Thy1-EVs that activate IL17RB signaling.
Methods
Thy1+ cells isolated from rats with d-galactosamine-induced liver injury were cultured for one week. Although some liver stem/progenitor cells proliferated into colonies, others maintained as mesenchymal cells (MCs). Thy1-MCs or Thy1-liver stem/progenitor cells were transplanted into retrorsine/PH-treated livers to examine their effects on SHPCs. SHs isolated from adult rat livers were used to validate factors regulating growth induction.
Results
The number and size of SHPCs remarkably increased in livers transplanted with Thy1-MCs. Comprehensive analysis of Thy1-MC-EVs revealed that miR-199a-5p, CINC-2, and MCP-1 are candidates for stimulating SHPC growth. Administration of the miR-199a-5p mimic, and not CINC-2, promoted SH growth. SECs treated with CINC-2 induced IL17b expression and their conditioned medium promoted SH growth.
Conclusion
Thy1-MC transplantation may accelerate liver regeneration due to SHPCs expansion, which is stimulated by CINC-2/IL17RB signaling and miR-199a-5p.
Quality of life and clinical factors in women with endometriosis, the role of Dienogest vs EE/ Dienogest over time: a single-center study.
Authors: Maiorana Antonio , Alfano Pietro , Mercurio Antonella , Marcantonio Salvatore , Minneci Gabriella , Incandela Domenico , Audino Palma
Published: January 2023

Purpose: The aims of this observational study were: to assess the relationship between psychological variables, pain, Duration Untreated Endometriosis (DUE) in a sample of women with Endometriosis; and to assess the effect of Dienogest 2 mg/daily (DNG) and Dienogest/ethinylestradiol 0.03 mg/daily (EE/DNG) on Symptoms, QoL, HRQoL, pain and sexual satisfaction, over time.
Methods: 64 women constituted the study group; (56%) took DNG and (44%) took EE/DNG. VAS, SF-36, EHP-30 and ISS were used to assess endometriosis-associated pelvic pain, QoL, HRQoL and sexual satisfaction, respectively. The study included one follow-up at 18 months.
Results: At T0, a longer period of DUE was related both to worst HRQoL and Physical QoL. At T1, a correlation was found between longer DUE and worst HRQoL. At T0, a negative correlation was found between VAS and PCS and between VAS and EHP-30.
At T1, the same above correlation was found between VAS and PCS/MCS and VAS and EHP-30 scale. There was a correlation between ISS and VAS.
ANOVA showed a reduction in dysmenorrhea, in general pain level and an improvement in emotional wellbeing, relationship with medical profession, and PCS over time, regardless to type of treatment. Moreover, a significant time × treatment group interaction for dysmenorrhea was found.
Conclusion: DUE and pain are important variables related to psychological aspects of women with endometriosis. Treatment with both DNG and EE/DNG may have positive effects on the QoL, HRQoL and symptoms. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time.
Capecitabine Metronomic Chemotherapy for Metastatic Colorectal Cancer Patients Reaching NED Status: A Protocol for a Prospective, Randomized, Controlled Trial
Authors: Wu Jiaming , Dong Yu , WU Lexia , Meng Jincheng , Zhang Huatang , Li Luzhen , Fang Cantu
Published: January 2023

Background: A increasing number of patients with metastatic colorectal cancer (mCRC) have achieved no evidence of diseases (NED) status after surgery or other treatments. However, the latest guidelines for colorectal cancer do not recommend an appropriate treatment for patients with mCRC who achieve NED status. Capecitabine has the advantages of significant efficacy and minimal adverse reactions. Thus, capecitabine metronomic chemotherapy is a potential effective method for maintenance treatment for mCRC, but no relevant clinical studies have been reported. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of capecitabine metronomic chemotherapy as maintenance treatment for mCRC patients who achieve NED.
Methods/design: This study is a prospective, randomized controlled study that evaluates the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who achieve NED status. Sixty eligible participants will be randomly assigned to either a capecitabine metronomic chemotherapy group or a “watch and wait” group at a 1:1 allocation ratio. Eligible patients diagnosed with stage IV mCRC, both the primary tumor and the metastases, are those who have achieved R0 resection (or complete destruction by ablation) and reached NED. Participants who are enrolled in the capecitabine group will receive capecitabine 500 mg/m2 (bid) for 2 years. Meanwhile, those who are assigned to the control group will receive regular imaging examination and follow-up only. All participants will follow up for one year after receiving 2 years of intervention. The primary outcomes will be progression-free survival (PFS) and overall survival (OS) from randomization. Secondary outcomes will include 2-year and 1-year survival, adverse reactions and quality of life scores.
Discussion: As a potentially effective treatment, low-dose capecitabine metronomic chemotherapy has been explored in clinical practice. The results of this trial will provide evidence on the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who have reached NED status.
Trial registration: Chinese Clinical Trial Registry (ChiCTR2100047149, protocol version number F2.0)
Green extraction of phenolics and flavonoids from black mulberry fruit using natural deep eutectic solvents: optimization and surface morphology
Authors: Vo Tan Phat , Pham Thuy Vy , Weina Kasia , Tran Thi Ngoc Huyen , Vo Le Thao Vy , Nguyen Phuc Thanh , Bui Tran Linh Ha , Phan Thuy Han , Nguyen Dinh Quan
Published: January 2023

This study deployed ultrasonic-assisted extraction (UAE), combined with natural deep eutectic solvents (NADES), to extract phenolics and flavonoids from the black mulberry fruit, and the antioxidant activity was examined. The extraction yields of NADES-based UAE were assessed based on total phenolic and flavonoid contents (TPC and TFC, respectively). NADES produced from choline chloride-lactic acid at a 1:2 molar ratio had the highest extraction yield. One-factor experiments evaluated the effect of UAE conditions (liquid-to-solid ratio, water content in NADES, temperature, and time) on TPC, TFC, and antioxidant activity. Response surface methodology with the Box-Behnken design model optimized the NADES-based UAE process based on response (TPC, TFC, ABTS, OH, and DPPH). The optimal conditions for the NADES-based UAE process were 70 ml/g of LSR, 38.9% water content in NADES, 67.9°C, and 24.2 min of retention time. The predicted values of the Box-Behnken design were compatible with the experimental results. Moreover, scanning electron microscopy was used to survey the surface of black mulberry fruit with and without sonication. This study proposes an efficient and green method for extracting bioactive compounds from black mulberry fruits.
A multicenter, open-label, multiple-dose Phase Ib/II study evaluating the safety and tolerability of CS3008 (BLU-554) in combination with CS1001 in subjects with locally advanced or metastatic hepatocellular carcinoma (HCC) Research
Authors: Zhou Mingzhen , Zhu Sihui , Xu Chen , Liu Baorui , Shen Jie
Published: January 2023

Objective: The treatment model of targeted therapy combined with immunotherapy has become the treatment modality for hepatocellular carcinoma due to problems such as single drug resistance. This trial was designed to evaluate the safety and tolerability of the fibroblast growth factor receptor 4 inhibitor CS3008 (BLU-554) in combination with the anti-PD-L1 monoclonal antibody CS1001 in patients with locally advanced or metastatic hepatocellular carcinoma (HCC).
patients and methods: This multicenter, open-label, multidose Phase Ib/II trial enrolled patients with locally advanced or metastatic hepatocellular carcinoma (HCC). Patients received CS1001 1200 mg intravenously every three weeks and BLU-554 600 mg orally daily. The primary endpoint was objective response rate (ORR) as assessed according to RECISTv1.1.
Result: A total of 18 patients were screened, of which 8 patients were FGF19 positive. And only four patients ultimately received the combination of treatment CS3008 (BLU-554) and CS1001 after entry row review, with ORR of 50% and DCR of 100%, and only one patient had an immune-related adverse reaction.
Conclusion: Preliminary confirmation that CS3008 (BLU-554) in combination with CS1001 is safe and effective in the treatment of patients with locally advanced or metastatic hepatocellular carcinoma.
Registration number: NCT04194801
Efficacy of a stretching exercise versus transcranial direct current stimulation(tDCS) on task performance, kinematic and electroencephalography (EEG) spectrum in subjects with slump posture: A study protocol
Authors: Abdollahzade zahra , Rasanani Mohammad-Reza Hadian , Kahnmohammadi Roya , Talebian saeed
Published: January 2023

Background

Slumped sitting is a common poor posture which may cause mental fatigue and some disturbances in social activity. The management of slump posture often focuses on some biomechanical recommendations. To date, almost limited studies have explored the non-biomechanical factors such as the central component including mental fatigue of poor posture. Therefore, utilizing the quantitative electroencephalography (QEEG) to find out the changes after a prolonged repetitive task might be considered as a tool for tracking the central part in poor posture individuals. Accordingly, this study was designed to find out the differences of EEG parameters between normal and poor posture individuals; also, in the second step, to explore the effect of stretching exercises and tDCS to monitor the mentioned parameters during a continuous activity of typing in subjects with slump posture.

Methods

A sample of 60 volunteers will participate in this study and they will be assigned to two equal groups of people with normal and slump postures. In the first and last 3 minutes of 60 minutes of continuous typing, these people will be assessed for outcome measures of mental fatigue through QEEG and visual analog fatigue scale, the typing performances (i.e. speed and errors of typing), musculoskeletal discomfort and kinematic behavior of neck. Furthermore, the effects of stretching exercises and transcortical stimulation on the outcome measures in slump posture group will be evaluated.

Discussion

With the assumption of providing individuals' differences in terms of outcome measures in normal and slump posture and also by showing the possible changes of the measures, due to either tDCS as a central modality or stretching exercises as a peripheral modality; we might conclude that first, a central component is critical for evaluation in poor posture and second, may provide evidence to introduce the effective method to overcome mental fatigue and promote work productivity.

Trial registration

Registered on the Iranian Registry of Clinical Trials on 21 September 2022, IRCT Identifier: IRCT20161026030516N2
Prone versus lateral position in acute hypoxemic respiratory failure patients with HFNO therapy: study protocol for a multicentre randomised controlled open-label trial
Authors: Zhou Xixin , Luo Xiaoqing , Chen Guihua , Li Qin , Tong Jin , Deng Wang
Published: January 2023

Background: High flow nasal oxygen (HFNO) therapy is a leading treatment technique for acute hypoxemic respiratory failure (AHRF), but its treatment failure rate remains high. The awake prone position（APP） has been proven to inease oxygenation and reduce the endotracheal intubation rate in patients with COVID-19-induced AHRF. However, because the APP is poorly tolerated in patients, its performance in improving prognoses is controversial. The lateral position has a similar mechanism and effect to the prone position, but it is more tolerable than the prone position. Thus, it is worth exploring whether the lateral position is better for awake patients with acute respiratory failure.
Methods: This is a protocol for a three-arm parallel group multicentre randomised controlled open-label exploratory trial. A total of 220 patients from two teaching hospitals in Chongqing, China, will be randomised to take the semirecumbent position, lateral position, or prone position at a ratio of 1:1:1. Patients are all diagnosed with AHRF secondary to non-COVID-19-related pneumonia or lung infection and receiving HFNO therapy. The primary outcome is 28-day all-cause mortality. The secondary outcomes are the 28-day intubation rate, total position change time, the incidence of adverse events, number of days using HFNO therapy, length of hospital and intensive care unit (ICU) stay, and others. We will conduct subgroup analyses on the arterial partial pressure of oxygen to the fraction of inspiration oxygen（PaO2/FiO2）ratio (>200 mmHg or ≤200 mmHg), time from hospitalisation to implementation (<24 h or ≥24 h), position changing time, and different diagnoses.
Discussion: Thistrial will explore the prognostic effects of the APP with that of the lateral position in awake patients with non-COVID-19 induced AHRF, and compare the differences between them. To provide evidence for clinical decision-making and further research on position management.
Trial registration: This trial was registered in the Chinese Clinical Trial Registry. The registration number is ChiCTR2200055822. Registered on January 20, 2022 ，https://www.chictr.org.cn/showproj.aspx?proj=130563
The electrophysiological signature of dorsal hippocampus-basolateral amygdala circuit in anxiety-like behavior in the intrahippocampal kainic acid mice model of temporal lobe epilepsy: With emphasis on the impact of glycolysis inhibition
Authors: Khatibi Vahid Ahli , Salimi Morteza , Rahdar Mona , Rezaei Mahmoud , Nazari Milad , Dehghan Samaneh , Davoudi Shima , Raoufy Mohammad Reza , Mirnajafi-Zadeh Javad , Javan Mohammad , Hosseinmardi Narges , Behzadi Gila , Janahmadi Mahyar
Published: January 2023

Pharmacoresistant temporal lobe epilepsy affects millions of people around the world with uncontrolled seizures and comorbidities, like anxiety, being the most problematic aspects calling for novel therapeutic procedures. The intrahippocampal kainic acid model of temporal lobe epilepsy is an appropriate rodent model to evaluate the effects of novel interventions, including glycolysis inhibition, on epilepsy-induced alterations. Here, we investigated kainic acid-induced changes in the dorsal hippocampus (dHPC) and basolateral amygdala (BLA) circuit and the efficiency of a glycolysis inhibitor, 2-deoxy D-glucose (2-DG), in resetting such alterations using simultaneous LFP recording and elevated zero-maze test. dHPC theta and gamma powers were lower in epileptic groups, both in the baseline and anxiogenic conditions. BLA theta power was higher in baseline condition while it was lower in anxiogenic condition in epileptic animals and 2-DG could reverse it. dHPC-BLA coherence was altered only in anxiogenic condition and 2-DG could reverse it only in gamma frequency. This coherence was significantly correlated with the time in which the animals exposed themselves to the anxiogenic condition. Further, theta-gamma phase-locking was lower in epileptic groups in the dHPC-BLA circuit and 2-DG could considerably increase it.
Focused ultrasound-mediated brain genome editing
Authors: Leong Kam , Lao Yeh-Hsing , Ji Robin , Zhou Joyce , Snow Kathy , Kwon Nancy , Saville Ethan , He Siyu , Chauhan Shradha , Chi Chun-Wei , Datta Malika , Zhang Hairong , Quek Chai Hoon , Cai Sarah , Li Mingqiang , Gaitan Yaned , Bechtel Lawrence , Wu Shih-Ying , Lutz Cathleen , Tomer Raju , Murray Stephen , Chavez Alejandro , Konofagou Elisa
Published: January 2023

Gene editing in the mammalian brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain. We demonstrate a safe and effective gene editing technique by using focused ultrasound (FUS) to transiently open the BBB for the transport of intravenously delivered CRISPR/Cas9 machinery to the brain.
Monitoring for micronutrient deficiency after bariatric surgery - what is the risk?
Authors: Lewis Carrie-Anne , Osland Emma , de Jersey Susan , Hopkins George , Seymour Matthew , Webb Lindsey , Chatfield Mark , Hickman Ingrid
Published: January 2023

Background: Bariatric surgery may increase the risk of micronutrient deficiencies; however, confounders including preoperative deficiency, supplementation and inflammation are rarely considered.
Objective: To examine the impact of bariatric surgeries, supplementation and inflammation on micronutrient deficiency.
Setting: Two public hospitals, Australia.
Methods: Participants were recruited to an observational study monitoring biochemical micronutrient outcomes, supplementation dose, inflammation and glycemic control, pre-operatively and at 1-3, 6 and 12 months after gastric bypass (GB; Roux-en-Y Gastric Bypass and Single Anastomosis Gastric Bypass; N=66) or sleeve gastrectomy (SG; N=144). Participant retention at 12 months was 81%.
Results: Pre-operative micronutrient deficiency was common, for vitamin D (29-30%), iron (13-22%) and selenium (39% GB cohort). Supplement intake increased after surgery; however, dose was <50% of target for most nutrients. After SG, folate was vulnerable to deficiency at 6-months (OR 13 [95% CI 2, 84]; p=0.007), with folic acid supplementation being independently associated with reduced risk. Within 1-3 months of GB, three nutrients had higher deficiency rates compared to pre-operative levels; vitamin B1 (21% vs. 6%, p<0.01), vitamin A (21% vs. 3%, p<0.01) and selenium (59% vs. 39%, p<0.05). Vitamin B1 deficiency was independently associated with surgery and inflammation, selenium deficiency with improved glycemic control after surgery and inflammation, whilst vitamin A deficiency was associated with inflammation only.
Conclusion: In the setting of prophylactic post-surgical micronutrient prescription, few nutrients are at risk of de novo deficiency. Although micronutrient supplementation and monitoring remains important, rationalising high frequency biochemical testing protocols in the first year after surgery may be warranted.
WONDER-01: immediate necrosectomy vs. drainage-oriented step-up approach after endoscopic ultrasound-guided drainage of walled-off necrosis—study protocol for a multicentre randomised controlled trial
Authors: Sato Tatsuya , Saito Tomotaka , Takenaka Mamoru , Iwashita Takuji , Shiomi Hideyuki , Fujisawa Toshio , Hayashi Nobuhiko , Iwata Keisuke , Maruta Akinori , Mukai Tsuyoshi , Masuda Atsuhiro , Matsubara Saburo , Hamada Tsuyoshi , Inoue Tadahisa , Ohyama Hiroshi , Kuwatani Masaki , Kamada Hideki , Hashimoto Shinichi , Shiratori Toshiyasu , Yamada Reiko , Kogure Hirofumi , Ogura Takeshi , Nakahara Kazunari , Doi Shinpei , Chinen Kenji , Isayama Hiroyuki , Yasuda Ichiro , Nakai Yousuke
Published: January 2023

Background: With the increasing popularity of endoscopic ultrasound (EUS)-guided transmural interventions, walled-off necrosis (WON)of the pancreas is increasingly managed via non-surgical endoscopic interventions. However, there has been an ongoing debate over the appropriate treatment strategy following the initial EUS-guided drainage. Endoscopic necrosectomy (EN) directly removes intracavity necrotic tissue, potentially facilitating early resolution of the WON, but may associate with a high rate of adverse events. Given the increasing safety of EN, this trial aims to assess the superiority of immediate EN over the step-up approach in terms of time required for WON resolution.
Methods: The WONDER-01 trial is a multicentre, open-label, superiority, randomised controlled trial, which will enrol WON patients aged ≥ 18 years requiring EUS-guided treatment in 23 centres in Japan. This trial plans to enrol 70 patients who will be randomised at a 1:1 ratio to receive either the immediate EN or drainage-oriented step-up approach (35 patients per arm). In the immediate EN group, EN will be initiated during (or within 72 hours of) the EUS-guided drainage session. In the step-up approach group, drainage-based step-up treatment with on-demand EN will be considered after 72-96 hours observation. The primary endpoint is time to clinical success, which is defined as a decrease in a WON size to ≤ 3 cm and an improvement of inflammatory markers (i.e., body temperature, white blood cell count, and C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, and recurrence of the WON.
Discussion: The WONDER-01 trial will investigate the efficacy and safety of immediate EN compared to the step-up approach for WON patients receiving EUS-guided treatment. The findings will help us to establish new treatment standards for patients with symptomatic WON.
Trial registration: ClinicalTrials.gov NCT05451901, registered on 11 July 2022. UMIN000048310, registered on 7 July 2022. jRCT1032220055, registered on 1 May 2022.
The research status, potential hazards and toxicological mechanisms of fluoroquinolone antibiotics in the environment
Authors: Du Jia , Liu Qinghua , Fu Li , Pan Ying , Yao Meng , Xu Shaodan , Li Huanxuan , Wang Chunhui , Tang Junhong
Published: January 2023

Fluoroquinolone antibioticsare widely used in pharmaceuticals and personal care products due to their disease treatment, growth promotion, and prophylaxis, which lead to increasing biological exposure to fluoroquinolones in the global environment. This paper recapitulates the occurrence, fate, and ecotoxicity of fluoroquinolone antibiotics in various environmental media. The toxicity effect and mechanism are also reviewed based on in vitro and in vivo experiments, referring to many organisms, such as microorganisms, cells, higher plants, land and aquatic animals. The combined toxicity effect and coexisting characteristics of fluoroquinolone antibiotics absorbed with other chemicals to organisms in various environmental matrices are also summarized. The current knowledge gaps, further research interests and toxicity mechanisms of fluoroquinolone antibiotics in the environment have been discussed in this research.
APOEε4 potentiates Aβ effects on longitudinal tangle accumulation via tau phosphorylation
Authors: Ferrari-Souza João Pedro , Bellaver Bruna , Ferreira Pâmela , Benedet Andrea , Povala Guilherme , Lussier Firoza , Leffa Douglas , Therriault Joseph , Tissot Cécile , Soares Carolina , Wang Yi-Ting , Chamoun Mira , Servaes Stijn , Macedo Arthur , Vermeiren Marie , Bezgin Gleb , Kang Min Su , Stevenson Jenna , Rahmouni Nesrine , Pallen Vanessa , Poltronetti Nina , Cohen Ann , Lopez Oscar , Klunk William , Soucy Jean-Paul , Gauthier Serge , Souza Diogo , Triana-Baltzer Gallen , Saad Ziad , Kolb Hartmuth , Karikari Thomas , Villemagne Victor , Tudorascu Dana , Ashton Nicholas , Zetterberg Henrik , Blennow Kaj , Zimmer Eduardo , Rosa-Neto Pedro , Pascoal Tharick
Published: January 2023

The mechanisms by which the apolipoprotein E ε4 (APOEε4) allele influences Alzheimer’s disease (AD) pathophysiological progression are poorly understood. Here, we tested the association of APOEε4 carriership and amyloid-β (Aβ) burden with longitudinal tau pathology progression. We studied 104 individuals across the aging and AD spectrum who underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for Aβ ([18F]AZD4694) and tau ([18F]MK-6240) at baseline, as well as a follow-up tau-PET scan (mean follow-up, 2.4 years). We further assessed longitudinal changes in tau phosphorylation (plasma phosphorylated tau at threonine 217 [p-tau217+]), brain atrophy (gray matter density), and clinical function (clinical dementia rating scale sum of boxes). We found that APOEε4 carriership potentiates Aβ effects on longitudinal tau tangle accumulation over two years. The APOEε4-potentiated Aβ effects on tangles were mediated by longitudinal plasma p-tau217+ increase. This longitudinal tau accumulation as measured by PET was accompanied by brain atrophy and clinical decline. Our results support a model in which the APOEε4 allele plays a key role in Aβ downstream effects on the aggregation of phosphorylated tau in the form of neurofibrillary tangles in the living human brain.