bluuebunny/crossref_metadata_2025 huggingface dataset:
MENELISIK AKAR PENYEBAB KEKERASAN GENDER PADA MASYARAKAT PETANI PELADANG KECAMATAN GEDANGAN KABUPATEN MALANG
Authors: Asfiyak Khoirul
Published: February 2023

Gender-based violence often occurs in social life both in urban areas and in rural areas. The government has been trying to reduce the rate of this gender based crime. However, incidents like this have always been repeated in various places in Indonesia. In Malang regency, gender-based violence often occurs with all the contributing factors. This incident is interesting to study, especially in relation to the factors behind the incident and various forms of gender violence experienced by women in Malang regency. In order to answer these questions, this research was constructed using a descriptive qualitative approach. Research data obtained from the results of field studies or observations, interviews and documentation studies. The research data were condensed as suggested by Miles, Hubberman and Saldana to obtain maximum validity of meaning. The results of the study present data that the factors causing gender-based violence in Malang district are: Factors of Lack of Fulfillment of the Family Economy, Suspicion of Infidelity, Village Community Traditions for Early Marriage, Gender Bias Opinion or Interpretation of Religion and Misogyny Culture in Village Communities, The forms of gender violence that often occur in Malang Regency society are physical, symbolic, domestic, public and economic violence
MEMAHAMI MAQASHID ASY-SYARIAH PADA AYAT RADHAâ€™AH PERSPEKTIF KEADILAN GENDER
Authors: Ummah Siti Rohmatul
Published: February 2023

AbstrakÂ Perintah pemberian ASI merupakan salah satu bentuk pemeliharaan terhadap bayi. Dalam istilah fikih, pemberian ASI diatur dalam hukum radhaâ€™ah. Salah satu dasar pelaksanaan radhaâ€™ah adalah ayat 233 surat al-Baqarah (2). Selain menjelaskan perintah menyusui, ayat ini juga mengandung perintah pemberian nafkah bagi ibu menyusui. Dengan maksud mengungkap tujuan syariat yang tersirat dalam perintah di ayat ini dan hubungan tujuan tersebut dengan keadilan gender penelitian ini dilakukan dengan mengikuti kaidah penelitian kualitatif deskriptif yang menjabarkan konsep hasil pembacaan, pengumpulan dan analisis data yang bersumber pada data di perpustakaan. Hasil penelitian ini menjelaskan bahwa dalam ayat ini penggunaan panggilan umum bagi ayah, ibu dan anak bertujuan untuk menyatakan bahwa kewajiban memberi dan hak menerima ASI berlaku secara umum bagi semua orang tanpa membedakan gendernya. Hasil lain yang peneliti dapat disini adalah bahwa dalam kegiatan pemberian ASI terdapat kelima jaminan perlindungan yang disebut sebagai maqashid asy-syariâ€™ah paling penting. Dari kaca mata keadilan gender, kandungan ayat ini berhasil memberikan tugas yang sesuai dengan kemampuan dan kondisi masing-masing gender secara adil tanpa memihak salah satu di antara keduanya.Â Kata Kunci : Maqashid asy-syariâ€™ah, Ayat radhaâ€™ah, dan Keadilan gender.Â AbstractThe order for breastfeeding is a form of caring for the baby. In fiqh terms, breastfeeding is regulated in the law of radha'ah. One of the bases for implementing radha'ah is verse 233 surah al-Baqarah (2). Apart from explaining the commandment for breastfeeding, this verse also contains instructions for providing support for breastfeeding mothers. To reveal the objectives of the Shari'a implied in the commands in this verse and the relationship between these goals and gender justice, this research was conducted by following the principles of descriptive qualitative research which outlines the concept of reading, collecting, and analyzing data sourced from data in the library. The results of this study explain that in this verse the use of general calls for father, mother, and child aims to state that the obligation to give and the right to receive breastfeeding applies in general to all people regardless of gender. Another result that the researchers got here is that in the activity of breastfeeding there are five guarantees of protection which are called the most important objectives of the Shari'a. From the point of view of gender justice, the content of this verse succeeds in giving a task that is regarding the abilities and conditions of each gender fairly without taking sides with either of the two.Keywords: The objectives of the Shari'a, Verse of radhaâ€™ah, and Gender justice.
PERTIMBANGAN HAKIM PENGADILAN AGAMA DALAM PERKARA PUTUSAN DISPENSASI KAWIN PERSPEKTIF PERUNDANG-UNDANGAN DAN FILSAFAT HUKUM ISLAM Kajian Putusan Nomor 0026/Pdt.P/2019/PA.Mt
Authors: Iwannudin Iwannudin
Published: February 2023

The study aims to determine the judges basis consideration at the Religious Court of Metro City Lampung in the Case of Marriage Dispensation Decision in the perspective of Indonesian and Islamic Law Philosophy as a relief from obligations and prohibitions for men and women who have not met the age requirements for marriage. Men reach the 19 years and women 16 years which are allowed to marry under Law No.1 of 1974 concerning Marriage. What then happened was a renewal in Law Number 16 of 2019 concerning Amendments to Law Number 1 of 1974. Marriage is only permitted if the man and woman have reached the age of 19 years. While in Islam the purpose of these rules is found in the Maqashid Syari'ah theory that the purpose of the formation of laws is for the benefit of mankind. The panel of judges is guided by Law No.1 of 1974 on Marriage and Compilation of Islamic Law. The Panel of Judges did not pay attention to the values stated in Law No.4 of 1979 concerning Child Welfare, TAP. No. XVII/MPR/1998. on Human Rights, Law no. 39 of 1999 concerning Human Rights, Law No.23 of 2002 concerning Child Protection.
DAMPAK PANDEMI COVID-19 TERHADAP INTENSITAS PERCERAIAN, MASALAH DAN PENYELESAIANNYA
Authors: Saputra Megi
Published: February 2023

ABSTRAKÂ Tulisan ini bertujuan untuk mengekplorasi bagaimana Intesitas penceraian terjadi di Indonesia serta sebeb-sebab utamanya, karena sebagimana diketahui bahwa intesitas perceraian selama masa pandemi meningkat terutama di 3 provinsi teratas yakni Jawa Barat, Jawa Tengah dan Jawa Timur. Angka intesitas perceraian meninggkat hingga angka 5%. Kondisi ini memprihatinkan karena akan berdampak bagi kehidupan berbangsa, keluarga dan anak-anak. Oleh karena itu dalam artiket ini akan ditawarkan alternatif penyelesain masalah keluarga. Tulisan ini dilakukan dengan menggali informasi dan data dari sumber Pustaka, artikel dan sumber-sumber terkait pembahasan. bertujuan untuk mengekplorasi bagaimana solusi dan penyelesaian agar perceraian dapat diminimalisir atau dihindari. Sebagai hasil dari penelitian ini penulis menawarkan tiga alternatif solusi, sebagai upaya preventif terjadinya perceraian yakni 1). Melalui prinsip-prinsip perkawinan; 2). Melalui Tujuan Perkawinan; 3). Melalui Komunikasi Keluarga.Kata Kunci : Keluarga, dampaknya pada masa Pandemi Covid-19, alternatif Penyelesaian.Â
JAMINAN PERLINDUNGAN HUKUM DALAM PENCATATAN PERKAWINAN (PERSPEKTIF MAQASID ASY-SYARI'AH)
Authors: Ayu Mihardi Hutri Rahayu
Published: February 2023

Bahwa perkawinan selain memenuhi persyaratan dari hukum Islam, perkawinan juga harus memenuhi persyaratan dari negara berupa mencatatkan perkawinan kepada Petugas Pencatat Perkawinan. Hal tersebut bertujuan untuk mewujudkan kemaslahatan agama, jiwa, akal, keturunan, harta, dan kehormatan.
Gut Microbiota: Modulate its Complexity to Restore the Balance
Authors: Smithers Lucy
Published: February 2023

The importance of the gut microbiota to health is becoming more widely appreciated. The range of commensal microorganisms in healthy individuals and in patients with a variety of digestive diseases is under active investigation, and evidence is accumulating to suggest that both the diversity and balance of bacterial species are important for health. Disturbance of the balance of microorganisms – dysbiosis – is associated with obesity and a variety of diseases. Restoring the balance by modulating the microbiota through diet, probiotics, or drugs is now being developed as a potential treatment for digestive diseases. Rifaximin has been shown to increase levels of beneficial bacterial species without perturbing the overall composition of the microbiota in patients with a variety of digestive diseases, making it a ‘eubiotic’ rather than an antibiotic. Rifaximin has demonstrated clinical benefit in the treatment of symptomatic uncomplicated diverticular disease, where changes in the colonic microbiota contribute to the pathogenesis of this disease. Modulating the microbiota is also a promising treatment for some types of irritable bowel syndrome (IBS) that have been linked to an overgrowth of coliform and Aeromonas species in the small intestine. Rifaximin has demonstrated efficacy in relieving symptoms and reducing relapses in diarrhoeal IBS in the TARGET-1, 2, and 3 trials, without reducing microbial diversity or increasing antimicrobial resistance. While many aspects of the balance of gut microbiota in disease are not yet fully understood, the new understanding of rifaximin as a modulator of gut microbiota may open up new treatment options in digestive disease.
Why Biosimilars Matter: An Innovative Solution to Improve Patient Access
Authors: McEvoy Lynda
Published: February 2023

The meeting was introduced by Prof Robin Foà who spoke about the difficulties for patients accessing therapies in the context of rising healthcare costs and reduced budgets. Dr Mark McCamish then explained the biosimilar development process and the analytical techniques involved. Prof Felix Keil discussed the role of biosimilar medicines in haematology using the example of GP2013/rituximab (RTX), and Ms Karen Van Rassel of the Lymphoma Coalition presented the role a patient organisation can play when working with the physician to support a patient’s questions and concerns regarding lymphoma.
Narasi dan Representasi Kearifan Lokal dalam Video Promosi Pariwisata The Heartbeat Of Toba
Authors: Pamungkas Adi
Published: February 2023

Abstrak Sebagai materi audio visual, video sering digunakan sebagai alat promosi pariwisata karena kemampuannya dalam menyimulasikan citra dari sebuah destinasi wisata sehingga dapat mengenalkannya dengan baik kepada audiens. Tidak hanya menampilkan visual destinasi wisatanya saja, video promosi pariwisata juga dapat mengomunikasikan konten khusus lainnya guna memberikan perspektif yang lebih kaya, salah satunya tentang kearifan lokal. Penelitian ini bertujuan untuk mengetahui bagaimana video promosi The Heartbeat of Toba menarasikan konten kearifan lokal guna memperkaya storytelling sehingga dapat menjadi video promosi pariwisata yang tidak hanya menampilkan keindahan landscape destinasi tetapi juga menawarkan pengalaman berwisata yang lebih mendalam kepada audiensnya. Penelitian ini merupakan penelitian kualitatif dengan metode analisis isi teks media. Peneliti menggunakan teori paradigma naratif guna menganalisis narasi kearifan lokal dalam cerita yang disampaikan serta menggunakan teori semiotika guna mengetahui makna yang terkandung di dalamnya. Temuan penelitian memperlihatkan bahwa konten kearifan lokal dalam video disampaikan melalui narasi terstruktur yang rasional serta melalui representasi ikonik, indeksikal dan simbolik dalam teks yang digunakan. Penelitian lebih lanjut perlu dilakukan guna mengetahui efektivitas konten kearifan lokal dalam video promosi pariwisata terhadap persepsi audiens dalam menimbulkan niat untuk berwisata ke destinasi yang dipromosikan. Kata Kunci: analisis naratif, kearifan lokal, representasi, storytelling, video promosi AbstractAs audio visual material, videos are used as a tourism promotion tool refers to its ability to simulate the visual of the destination so they can introduce it well to the audience. Not only visualizing the destinations, but a tourism promotion video can also communicate particular content to provide richer perspectives, one of them is about local wisdom. This study aimed to find out how promotional video The Heartbeat of Toba narrates local wisdom to enrich their storytelling so the video not only visualizing the beauty of the landscape but also offers a fulfilling travel experience to the audience. This study was a qualitative content analysis refers to media texts. The author used the theory of the narrative paradigm to analyze the content of local wisdom in the stories also used the theory of semiotics to find out the meaning contained in it. The findings show that the content of local wisdom in the video was narrated through rational and structured narratives as well as through iconic, indexical, and symbolic representations texts. Further research is needed to determine the effectiveness of local wisdom content in tourism promotion videos on audience perceptions in generating intentions to travel to the promoted destinations. Keywords: local wisdom, narrative analysis, promotional video, representation, storytelling
Analisis Karakter “Si Korona” pada Buku Digital Kartun Edukasi Virus Corona untuk Anak-Anak di Tengah Pandemi
Authors: Handriyotopo Handriyotopo
Published: February 2023

AbstrakCovid-19 (Corona Virus Disease 2019) sangat mengkawatirkan bagi sendi umat manusia saat ini di dunia. Usaha untuk menyadarkan pentingnya protokol saat new normal telah banyak dilakukan. Menyadarkan pentingnya menjaga kesehatan tentang pengetahuan virus corona dibutuhkan oleh anak-anak yang juga rentan dengan virus ini. Edukasi pengetahuan tentang virus corona diperlukan bagi anak seperti yang dilakukan oleh HIMPSI (Himpunan Psikologi Indonesia) dengan membuat kartun secara online perlu diapresiasi. Penyadaran virus corona dengan pendekatan kartun pada anak sangat menarik untuk dikaji di tengah maraknya info virus corona dalam bentuk infografis dan motion graphic ataupun iklan layanan masyarakat tentang menjaga protokol kesehatan seperti patuh pada ibu dengan 3M. Penelitian ini menggunakan metode kualitatif untuk menemukan data-data penting dalam melakukan analisis deskriptif. Melalui pendekatan karakter kartun melalui proses mimikri dan retorika visual, untuk menemukan makna karakter Si Korona. Temuan penting untuk menciptakan karakter adalah melalui proses mimikri sebagai metode untuk membangun karakter tokoh utama kartun Si Korona. Watik Ideo dan Luluk N. secara reorika visual berhasil membuat karakter Si Korona yang sederhana agar anak-anak dapat memahami tentang virus corona untuk menyadarkan pemahaman covid-19 pada anak. Kata kunci: Edukasi Anak, Kartun, Si Korona, Virus Corona AbstractCovid-19 (Corona Virus Disease 2019) is very worrying for the joints of humanity today in the world. Many Covid-19 (Corona Virus Disease 2019) is very worrying for the joints of humanity today in the world. Many efforts have been made to make the protocols aware of the importance of the new normal. Awareness of the importance of maintaining health about knowledge of the coronavirus is needed by children who are also vulnerable to this virus. Education on knowledge about the coronavirus is needed for children, as done by HIMPSI (Indonesian Psychological Association) making cartoons online needs to be appreciated. Awareness of the coronavirus with a cartoon approach to children is very interesting to study amidst the rise of information on the coronavirus in the form of infographics and motion graphics or public service advertisements about maintaining health protocols such as obeying mothers with 3M. This study uses qualitative methods to find important data in conducting a descriptive analysis. Through a cartoon character approach through mimicry and visual rhetoric processes, to find the meaning of the character Si Corona. An essential finding for creating characters is through the process of mimicry as a method for building the character of the main character of the cartoon Si Corona. Watik Ideo and Luluk N. visually rhetorically succeeded in creating a simple Corona character so that children can understand the corona virus to awaken their children to an understanding of Covid-19. Keywords: Children Education, Cartoon, Corona Virus, Si Korona
The Correlation between Students’ Satisfaction with E-learning and Their English Achievement
Authors: Rellely Mercy Myshall , Sengkey Virginia Gabrella
Published: February 2023

Abstract. This research aimed to find out the correlation between students’ satisfaction with e-learning and their English achievement. This was a quantitative study that used descriptive and correlational research designs. The instruments used in this study were a questionnaire adopted from Liaw (2007) and the students’ final English class grades. Seventy-nine 11th-grade students enrolled at one of the private high schools in North Sulawesi in the first semester of the academic year 2020/2021 participated in this study. It was found that the students were satisfied with e-learning (M=3.48) and their English achievement was very good (M=91.62). Regarding the correlation between the two variables, a significant correlation was found between students’ satisfaction with e-learning and their English achievement with p=.000 < 0.005, r=.441. Thus, teachers should always ensure that students are satisfied with their e-learning so that their English achievement can also be maximized.Keywords: e-learning, English achievement, students’ satisfactionAbstrak. Penelitian ini bertujuan untuk mengetahui hubungan antara kepuasan siswa dengan e-learning dan pencapaian bahasa Inggris mereka. Penelitian ini merupakan penelitian kuantitatif dengan desain penelitian deskriptif dan korelasional. Instrumen yang digunakan dalam penelitian ini adalah angket yang diadopsi dari Liaw (2007) dan nilai akhir siswa di kelas Bahasa Inggris. Responden dari penelitian ini adalah 79 siswa kelas XI yang terdaftar di salah satu SMA Swasta di Sulawesi Utara pada semester I tahun ajaran 2020/2021. Hasil yang diperoleh adalah siswa puas dengan e-learning (M=3,48) dan prestasi bahasa Inggris mereka sangat baik (M=91,62). Berkenaan dengan korelasi antara kedua variabel, ditemukan korelasi yang signifikan antara kepuasan siswa dengan e-learning dan prestasi bahasa Inggris mereka dengan p=.000 < 0.005, r=.441. Oleh karena itu, guru perlu selalu memastikan bahwa siswa puas dengan e-learning mereka sehingga pencapaian bahasa Inggris mereka juga dapat maksimal.Kata kunci: e-learning, kepuasan siswa, pencapaian bahasa Inggris
МЕТОДИЧНІ ОСНОВИ НОВОГО ПОКОЛІННЯ БУДІВЕЛЬНИХ НОРМ З ЕНЕРГОЕФЕКТИВНОСТІ БУДІВЕЛЬ
Authors: Фаренюк Єгор , Фаренюк Генадій
Published: February 2023

На законодавчому рівні вимоги до енергетичноїефективності будівель встановлені у ЗаконіУкраїни «Про енергетичну ефективність будівель»,яким імплементовано в Україні Директивищодо енергоефективності будівель (EPBD)2010/31/ЄС. В Україні системна робота з норму-вання принципів проектування будівель за показ-никами енергоефективності ведеться з 2006 р.,коли були прийняті ДБН В.2.6-31:2006 «Тепловаізоляція будівель». У 2008 р. було введеноДБН В.1.2-11:2008 «Основні вимоги до будівельі споруд. Економія енергії», які розкривалиположення Директиви № 89/106/ЄС стосовнообов’язковості нормування показників безпе-ки будівельної продукції та будівельних об’єктівза їх енергоефективністю. У статті наводятьсяметодичні принципи, що покладені в основу ново-го покоління норм – ДБН В.2.6-31:2021 «Тепловаізоляція та енергоефективність будівель» таДБН В.1.2-11:2021 «Основні вимоги до будівель іспоруд. Енергозбереження та енергоефективність»,які встановлюють вимоги до показниківенергоефективності будівель, мінімальні вимоги допоказників енергоефективності теплоізоляційноїоболонки будівель та інженерних систем, методівоцінювання показників та правил проектуваннябудівель за характеристиками енергоефективності.Методологія нового покоління державнихбудівельних норм з енергоефективності реалізуєна технічному рівні положення Закону України«Про енергетичну ефективність будівель», ЗаконуУкраїни «Про надання будівельної продукціїна ринку», Закону України «Про будівельнінорми». В статті розглянуто методичні основита фізичний зміст критеріїв енергоефективностібудівель, особливості оцінювання показниківенергоефективності при проведенні енергетичнихобстежень будівель та їх енергетичної класифікаціїпід час проектування та в процесі експлуатації.Наведено перелік енергетичних потоків, якінеобхідно враховувати при оцінюванні енергетич-ного статусу будівлі. Проведено аналіз норматив-них актів та документів, які визначають методичніумови оцінювання будівель за показникамиенергоефективності. Визначено напрями подаль-шого розвитку та удосконалення методології оцінкита підвищення енергоефективності будівель.
The Effectiveness of Intersectional Political Science Pedagogy in an Introductory Course in American Public Policy
Authors: Fletcher Michelle , Hoffman Adam
Published: February 2023

The study seeks to confront the challenge of incorporating the role of inequality, identity, and intersectionality into political science teaching and learning. In this quasi-experimental design, we explore the variation in two introductory courses in public policy. The design and content were similar for both sections. For the experimental section, we integrated intersectional political science pedagogy. This section employed a flipped classroom, introducing innovative approaches to grading and assessment that were accessible, inclusive, and anti-racist. In the control group section, the course was traditionally taught without supplemental material on intersectionality or the more innovative and unconventional pedagogy. We hypothesize that students enrolled in the intersectional section will have more interest and knowledge in public policy, as well as a deeper understanding of racial progress as it relates to the policy process. Moreover, we predict that students will display some resistance and discomfort when it comes to participating in class discussions.
Creating Inclusive Classrooms with Faculty-Student Pedagogical Partnerships
Authors: Mered Milka , Nemacheck Christine
Published: February 2023

As political science faculty, we often confront controversial topics in our classrooms. The general decline in respectful political discourse in the United States makes creating inclusive classrooms for all our students crucial, and perhaps, more difficult than it was five or ten years ago. One strategy we have found useful in our classrooms is creating pedagogical partnerships between faculty and students. There is substantial evidence that faculty-student partnerships with a pedagogical focus provide significant benefits to participating faculty and students (Cook-Sather, et. al. 2014). Further research finds that faculty-student partnerships involving students from historically underrepresented groups provide significant benefits for student partners (Cook-Sather 2018). In this paper, we explore the use of faculty-student partnerships focused on making classrooms more inclusive.
Data-to-Deal (D2D): Open Data and Modelling of Long Term Strategies to Financial Resource Mobilization - the case of Costa Rica
Authors: Jaramillo Marcella , Quirs-Torts Jairo , Vogt-Schilb Adrien , Money Alex , Howells Mark
Published: February 2023

Long Term Scenarios (LTSs) can be developed through an iterative process of codesigning with stakeholders and experts to form a joint vision of a development path. Once a roadmap is defined, governments can match financing sources and instruments to deliver the measures and projects defined in the LTS, providing signals to align broader finance flows toward the lower carbon economy. The exercise can increase access to and effectiveness of international climate finance. In the case of Costa Rica, a data-driven, stakeholder-codesigned National Decarbonization Plan (the country's LTS) was launched in 2019. It has been the foundation on which at least US$2.4 billion had been mobilized from international concessional finance sources by the end of 2022. An essential effort underpinning this was a carefully crafted and nationally owned LTS study that leveraged public-good open-models and associated: advanced-schools, communities, principles, and goals. The LTS study's direct cost was less than US$200k.
Optimal configuration for communication antenna along a railway line
Authors: Araújo Adérito , Cerdeira Jorge , Costa e Silva Eliana , Lopes Nuno , Moura Ana
Published: February 2023

Solvit’s main task is to provide and maintain stable signal coverage along railway tracks, ensuring quality communications. To do this, the company should design a suitable antenna network in order to guaran- tee good signal coverage while reducing the costs associated with the entire network. In this report we formulate the problem as 0/1 linear optimization models, and report computational results obtained using the models on real data provided by the company.
An assessment of bioinformatics tools for the detection of human endogenous retroviral insertions in short-read genome sequencing data
Authors: Bowles Harry , Kabiljo Renata , Al Khleifat Ahmad , Jones Ashley , Quinn John P. , Dobson Richard J. B. , Swanson Chad M. , Al-Chalabi Ammar , Iacoangeli Alfredo
Published: February 2023

There is a growing interest in the study of human endogenous retroviruses (HERVs) given the substantial body of evidence that implicates them in many human diseases. Although their genomic characterization presents numerous technical challenges, next-generation sequencing (NGS) has shown potential to detect HERV insertions and their polymorphisms in humans. Currently, a number of computational tools to detect them in short-read NGS data exist. In order to design optimal analysis pipelines, an independent evaluation of the available tools is required. We evaluated the performance of a set of such tools using a variety of experimental designs and datasets. These included 50 human short-read whole-genome sequencing samples, matching long and short-read sequencing data, and simulated short-read NGS data. Our results highlight a great performance variability of the tools across the datasets and suggest that different tools might be suitable for different study designs. However, specialized tools designed to detect exclusively human endogenous retroviruses consistently outperformed generalist tools that detect a wider range of transposable elements. We suggest that, if sufficient computing resources are available, using multiple HERV detection tools to obtain a consensus set of insertion loci may be ideal. Furthermore, given that the false positive discovery rate of the tools varied between 8% and 55% across tools and datasets, we recommend the wet lab validation of predicted insertions if DNA samples are available.
Regulation of biofilm formation in Zymomonas mobilis to enhance stress tolerance by heterologous expression of pfs and luxS
Authors: Cao Lian-Ying , Liu Chen-Guang , Yang Shi-Hui , Bai Feng-Wu
Published: February 2023

Zymomonas mobilis is a potential alternative of Saccharomyces cerevisiae to produce cellulosic ethanol with strengths in cofactor balance, but its lower tolerance to inhibitors in the lignocellulosic hydrolysate restricts the application. Although biofilm can improve bacteria stress tolerance, regulating biofilm formation in Z. mobilis is still a challenge. In this work, we constructed a pathway by heterologous expressing pfs and luxS from Escherichia coli in Z. mobilis to produce AI-2 (autoinducer 2), a universal quorum-sensing signal molecule, to control cell morphology for enhancing stress tolerance. Unexpectedly, the results suggested that neither endogenous AI-2 nor exogenous AI-2 promoted biofilm formation, while heterologous expression of pfs can significantly raise biofilm. Therefore, we proposed that the main factor in assisting biofilm formation was the product accumulated due to heterologous expression of pfs, like methylated DNA. Consequently, ZM4::pfs produced more biofilm, which presented an enhanced tolerance to acetic acid. All these findings provide a novel strategy to improve the stress tolerance of Z. mobilis by enhancing biofilm formation for efficient production of lignocellulosic ethanol and other value-added chemical products.
Micro RNA based MSC EV engineering: Targeting the BMP2 cascade for bone repair
Authors: Huang Chun-Chieh , Kang Miya , Leung Kasey , Lu Yu , Shirazi Sajjad , Gajendrareddy Praveen , Ravindran Sriram
Published: February 2023

Mesenchymal stem cell derived extracellular vesicles (MSC EVs) possess excellent immunomodulatory and therapeutic properties. While beneficial, from a translational perspective, extracellular vesicles with consistent functionality and target specificity are required to achieve the goals of precision medicine and tissue engineering. Prior research has identified that the miRNA composition of mesenchymal stem cell derived extracellular vesicles contributes significantly towards extracellular vesicles functionality. In this study, we hypothesized that mesenchymal stem cell derived extracellular vesicle functionality can be rendered pathway-specific using a miRNA-based extracellular vesicles engineering approach. To test this hypothesis, we utilized bone repair as a model system and the BMP2 signaling cascade as the targeted pathway. We engineered mesenchymal stem cell extracellular vesicles to possess increased levels of miR-424, a potentiator of the BMP2 signaling cascade. We evaluated the physical and functional characteristics of these extracellular vesicles and their enhanced ability to trigger the osteogenic differentiation of naïve mesenchymal stem cell in vitro and facilitate bone repair in vivo. Results indicated that the engineered extracellular vesicles retained their extracellular vesicles characteristics and endocytic functionality and demonstrated enhanced osteoinductive function by activating SMAD1/5/8 phosphorylation and mesenchymal stem cell differentiation in vitro and enhanced bone repair in vivo. Furthermore, the inherent immunomodulatory properties of the mesenchymal stem cell derived extracellular vesicles remained unaltered. These results serve as a proof-of-concept for miRNA-based extracellular vesicles engineering approaches for regenerative medicine applications.
Research on named entity recognition method of marine natural products based on attention mechanism
Authors: Ma Xiaodong , Yu Rilei , Gao Chunxiao , Wei Zhiqiang , Xia Yimin , Wang Xiaowei , Liu Hao
Published: February 2023

Marine natural product (MNP) entity property information is the basis of marine drug development, and this entity property information can be obtained from the original literature. However, the traditional methods require several manual annotations, the accuracy of the model is low and slow, and the problem of inconsistent lexical contexts cannot be solved well. In order to solve the aforementioned problems, this study proposes a named entity recognition method based on the attention mechanism, inflated convolutional neural network (IDCNN), and conditional random field (CRF), combining the attention mechanism that can use the lexicality of words to make attention-weighted mentions of the extracted features, the ability of the inflated convolutional neural network to parallelize operations and long- and short-term memory, and the excellent learning ability. A named entity recognition algorithm model is developed for the automatic recognition of entity information in the MNP domain literature. Experiments demonstrate that the proposed model can properly identify entity information from the unstructured chapter-level literature and outperform the control model in several metrics. In addition, we construct an unstructured text dataset related to MNPs from an open-source dataset, which can be used for the research and development of resource scarcity scenarios.
PulseDB: A large, cleaned dataset based on MIMIC-III and VitalDB for benchmarking cuff-less blood pressure estimation methods
Authors: Wang Weinan , Mohseni Pedram , Kilgore Kevin L. , Najafizadeh Laleh
Published: February 2023

There has been a growing interest in developing cuff-less blood pressure (BP) estimation methods to enable continuous BP monitoring from electrocardiogram (ECG) and/or photoplethysmogram (PPG) signals. The majority of these methods have been evaluated using publicly-available datasets, however, there exist significant discrepancies across studies with respect to the size, the number of subjects, and the applied pre-processing steps for the data that is eventually used for training and testing the models. Such differences make conducting performance comparison across models largely unfair, and mask the generalization capability of various BP estimation methods. To fill this important gap, this paper presents “PulseDB,” the largest cleaned dataset to date, for benchmarking BP estimation models that also fulfills the requirements of standardized testing protocols. PulseDB contains 1) 5,245,454 high-quality 10-s segments of ECG, PPG, and arterial BP (ABP) waveforms from 5,361 subjects retrieved from the MIMIC-III waveform database matched subset and the VitalDB database; 2) subjects’ identification and demographic information, that can be utilized as additional input features to improve the performance of BP estimation models, or to evaluate the generalizability of the models to data from unseen subjects; and 3) positions of the characteristic points of the ECG/PPG signals, making PulseDB directly usable for training deep learning models with minimal data pre-processing. Additionally, using this dataset, we conduct the first study to provide insights about the performance gap between calibration-based and calibration-free testing approaches for evaluating generalizability of the BP estimation models. We expect PulseDB, as a user-friendly, large, comprehensive and multi-functional dataset, to be used as a reliable source for the evaluation of cuff-less BP estimation methods.
Evaluation of BISON metallic fuel performance modeling against experimental measurements within FIPD and IMIS databases
Authors: Paaren Kyle M. , Gale Micah , Medvedev Pavel , Porter Douglas
Published: February 2023

Simulations were conducted using the BISON fuel performance code on an automated process to read initial and operating conditions from two databases—the Fuels Irradiation and Physics Database (FIPD) and Integral Fast Reactor Materials Information System (IMIS) database. These databases contain metallic fuel data from the Experimental Breeder Reactor-II (EBR-II) and the Fast Flux Test Facility (FFTF). The work demonstrates use of an integrated framework to access EBR-II fuel pin data for evaluating fuel performance models contained within BISON to predict fuel performance of next-generation metallic fuel systems. Between IMIS and FIPD, there is enough information to conduct 1,977 unique EBR-II metallic fuel pin histories from 29 different experiments, and 338 pins from FFTF MFF-3 and MFF-5 with varying levels of details between the two databases. Each of these fuel performance histories includes a high-resolution power history, flux history, coolant channel flow rates, and coolant channel temperatures, and new model developments in BISON since the initial demonstration of this integrated framework. Fission gas release (FGR), cumulative damage fraction, fuel axial swelling, FCCI wastage thickness, cladding profilometry, and burnup were all simulated in BISON and compared to post-irradiation examination (PIE) results to evaluate BISON fuel performance modeling. Implementation of new fuel performance models into a generic BISON input file coupled with IMIS and FIPD yielded results with a better representation of physics than the initial evaluation of the integrated framework. Cladding profilometry, FGR, and fuel axial swelling were found to be in good agreement with PIE measurements for most of the pins simulated. The chosen mechanical contact solver was found to significantly impact the axial fuel swelling and cladding strain predictions when used in conjunction with the U-Pu-Zr hot-pressing model since it bound the fuel to prevent further swelling and increased hydrostatic stresses. This work suggests that fuel performance modeling in BISON under steady-state conditions represents the PIE data well and should be reassessed when new PIE data become available in IMIS and FIPD databases and when improved physical models to better capture fuel performance are added to BISON.
Variations and possible causes of the December PM2.5 in Eastern China during 2000–2020
Authors: Bai Dongping , Liu Lin , Dong Zizhen , Ma Kangjie , Huo Yanfeng
Published: February 2023

High air pollutions of PM2.5 concentrations have become a serious environmental problem in China during recent decades, causing significant influences on urban air quality and human health. In the study, we investigate the variations of the December PM2.5 in Eastern China and the possible causes during 2000–2020. The empirical orthogonal function (EOF) analysis is employed to reveal the dominant patterns of PM2.5 variability in Eastern China. The EOF1 shows a consistent variability in the whole of the Eastern China, which reflects a consistent emission pattern in Eastern China in past two decades. The EOF2 exhibits a North-South dipole pattern, which is closely tied to the changes of atmospheric circulations. The increase of PM2.5 in the North Eastern China is mainly related to the decrease of wind speed, the decrease of boundary layer height and the increase of inversion temperature, while the decrease of PM2.5 in the South Eastern China is affected by the increase of local precipitation. Two atmospheric wave trains are identified that affect the dipole distribution of PM2.5 in Eastern China. The southern one is affected by ENSO, and the northern one is jointly affected by ENSO, sea surface temperature of Labrador Sea and sea ice concentration near Kara Sea. Finally, we reconstructed a comprehensive atmospheric external forcing index based on these factors. We find that the comprehensive index can well reproduce the North-South dipole distribution of PM2.5 in Eastern China, indicating the plausible effects of the atmospheric external forcings and the prediction potential for the variations of PM2.5 in Eastern China.
Characterization of the immune cell landscape in CRC: Clinical implications of tumour-infiltrating leukocytes in early- and late-stage CRC
Authors: Bazzi Zainab Ali , Sneddon Sophie , Zhang Peter G. Y. , Tai Isabella T.
Published: February 2023

Introduction

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally. Tumour-infiltrating leukocytes play an important role in cancers, including CRC. We therefore sought to characterize the impact of tumour-infiltrating leukocytes on CRC prognosis.

Methods

To determine whether the immune cell profile within CRC tissue could influence prognosis, we employed three computational methodologies (CIBERSORT, xCell and MCPcounter) to predict abundance of immune cell types, based on gene expression. This was done using two patient cohorts, TCGA and BC Cancer Personalized OncoGenomics (POG).

Results

We observed significant differences in immune cell composition between CRC and normal adjacent colon tissue, as well as differences in based on method of analysis. Evaluation of survival based on immune cell types revealed dendritic cells as a positive prognostic marker, consistently across methodologies. Mast cells were also found to be a positive prognostic marker, but in a stage-dependent manner. Unsupervised cluster analysis demonstrated that significant differences in immune cell composition has a more pronounced effect on prognosis in early-stage CRC, compared to late-stage CRC. This analysis revealed a distinct group of individuals with early-stage CRC which have an immune infiltration signature that indicates better survival probability.

Conclusions

Taken together, characterization of the immune landscape in CRC has provided a powerful tool to assess prognosis. We anticipate that further characterization of the immune landscape will facilitate use of immunotherapies in CRC.
Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature
Authors: Uhl Bernd , Haring Florian , Slotta-Huspenina Julia , Luft Joshua , Schneewind Vera , Hildinger Jonas , Wu Zhengquan , Steiger Katja , Smiljanov Bojan , Batcha Aarif M. N. , Keppler Oliver T. , Hellmuth Johannes C. , Lahmer Tobias , Stock Konrad , Weiss Bernhard G. , Canis Martin , Stark Konstantin , Bromberger Thomas , Moser Markus , Schulz Christian , Weichert Wilko , Zuchtriegel Gabriele , Reichel Christoph A.
Published: February 2023

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.
Systematic review and meta-analysis of the current literature on tocilizumab in patients with refractory Takayasu arteritis
Authors: Kang Limei , Liu Yang , Luo Zhongling , Zhou Yueyuan , Chen Bo , Yin Geng , Xie Qibing
Published: February 2023

Objective

To present the pooled quantitative evidence of baseline characteristics and clinical outcomes of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK).

Methods

A comprehensive systematic review and meta-analysis was performed on all available studies retrieved from the MEDLINE, Embase, and Cochrane databases, using TCZ in patients with refractory TAK. We applied the commands metan and metaprop_one in Stata Software to pool overall estimates of continuous data and binomial data, respectively. A random-effects model was recruited for analysis.

Results

Nineteen studies with 466 patients were included in this meta-analysis. The mean age at implementation of TCZ was 34.32 years. Female sex and Numano Type V were the most prominent baseline characteristics. During the 12-month follow-up when receiving TCZ treatment, pooled CRP was 1.17 mg/L (95% confidence interval [CI] -0.18-2.52), pooled ESR was 3.54 mm/h (95% CI 0.51-6.58), and pooled glucocorticoid dose was 6.26 mg/d (95% CI 4.24-8.27). Approximately 76% (95% CI 58-87%) of patients achieved a decrease in glucocorticoid dosage. Meanwhile, patients with TAK had a remission rate of 79% (95% CI 69-86%), a relapse rate of 17% (95% CI 5-45%), an imaging progress rate of 16% (95% CI 9-27%), and a retention rate of 68% (95% CI 50-82%). Adverse events occurred in 16% (95% CI 5-39%) of patients, and infection was the most common adverse event, with a rate of 12% (95% CI 5-28%).

Conclusion

TCZ treatment can provide favorable outcomes in terms of inflammatory markers, steroid-sparing effects, clinical response, drug retention and minimizing adverse effects for patients with refractory TAK.
Dual stimulation by autoantigen and CpG fosters the proliferation of exhausted rheumatoid factor-specific CD21low B cells in hepatitis C virus-cured mixed cryoglobulinemia
Authors: Del Padre Martina , Marrapodi Ramona , Minafò Ylenia A. , Piano Mortari Eva , Radicchio Giovanna , Bocci Chiara , Gragnani Laura , Camponeschi Alessandro , Colantuono Stefania , Stefanini Lucia , Basili Stefania , Carsetti Rita , Fiorilli Massimo , Casato Milvia , Visentini Marcella
Published: February 2023

Introduction

Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV specificity. These cells display an atypical CD21low phenotype and functional exhaustion evidenced by unresponsiveness to BCR and Toll-like receptor 9 (TLR9) stimuli. Although antiviral therapy is effective on MC vasculitis, pathogenic B cell clones persist long thereafter and can cause virus-independent disease relapses.

Methods

Clonal B cells from patients with HCV-associated type 2 MC or healthy donors were stimulated with CpG or heath-aggregated IgG (as surrogate immune complexes) alone or in combination; proliferation and differentiation were then evaluated by flow cytometry. Phosphorylation of AKT and of the p65 NF-kB subunit were measured by flow cytometry. TLR9 was quantified by qPCR and by intracellular flow cytometry, and MyD88 isoforms were analyzed using RT-PCR.

Discussion

We found that dual triggering with autoantigen and CpG restored the capacity of exhausted VH1-69pos B cells to proliferate. The signaling mechanism for this BCR/TLR9 crosstalk remains elusive, since TLR9 mRNA and protein as well as MyD88 mRNA were normally expressed and CpG-induced phosphorylation of p65 NF-kB was intact in MC clonal B cells, whereas BCR-induced p65 NF-kB phosphorylation was impaired and PI3K/Akt signaling was intact. Our findings indicate that autoantigen and CpG of microbial or cellular origin may unite to foster persistence of pathogenic RF B cells in HCV-cured MC patients. BCR/TLR9 crosstalk might represent a more general mechanism enhancing systemic autoimmunity by the rescue of exhausted autoreactive CD21low B cells.
Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis
Authors: Sedney Colleen J. , Caulfield Amanda , Dewan Kaylan K. , Blas-Machado Uriel , Callender Maiya , Manley Nancy R. , Harvill Eric T.
Published: February 2023

The increased susceptibility of neonates to specific pathogens has previously been attributed to an underdeveloped immune system. More recent data suggest neonates have effective protection against most pathogens but are particularly susceptible to those that target immune functions specific to neonates. Bordetella pertussis (Bp), the causative agent of “whooping cough”, causes more serious disease in infants attributed to its production of pertussis toxin (PTx), although the neonate-specific immune functions it targets remain unknown. Problematically, the rapid development of adult immunity in mice has confounded our ability to study interactions of the neonatal immune system and its components, such as virtual memory T cells which are prominent prior to the maturation of the thymus. Here, we examine the rapid change in susceptibility of young mice and define a period from five- to eight-days-old during which mice are much more susceptible to Bp than mice even a couple days older. These more narrowly defined “neonatal” mice display significantly increased susceptibility to wild type Bp but very rapidly and effectively respond to and control Bp lacking PTx, more rapidly even than adult mice. Thus, PTx efficiently blocks some very effective form(s) of neonatal protective immunity, potentially providing a tool to better understand the neonatal immune system. The rapid clearance of the PTx mutant correlates with the early accumulation of neutrophils and T cells and suggests a role for PTx in disrupting their accumulation. These results demonstrate a striking age-dependent response to Bp, define an early age of extreme susceptibility to Bp, and demonstrate that the neonatal response can be more efficient than the adult response in eliminating bacteria from the lungs, but these neonatal functions are substantially blocked by PTx. This refined definition of “neonatal” mice may be useful in the study of other pathogens that primarily infect neonates, and PTx may prove a particularly valuable tool for probing the poorly understood neonatal immune system.