bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGATURAN PHK EFISIENSI DALAM UNDANG-UNDANG NOMOR 13 TAHUN 2003 TENTANG KETENAGAKERJAAN DAN UNDANG-UNDANG NOMOR 11 TAHUN 2020 TENTANG CIPTA KERJA
Authors: Masrifatun Mahmudah  , Markus Dwi Pratiwi
Published: May 2023

Tujuan penelitian ini untuk mendeskripsikan pengaturan PHK dengan alasan efisiensi dalam UU No. 13 Tahun 2003 dan UU No. 11 Tahun 2020, serta menganalisis kedudukan hukum pengaturan PHK efisiensi dalam UU No. 11 Tahun 2020 terhadap Putusan Mahkamah Konstitusi No. 19/PUU-IX/2011. Penelitian normatif ini dilakukan dengan studi pustaka terhadap bahan hukum primer dan bahan hukum sekunder. Hasil penelitian ini didapatkan bahwa Pasal 154A ayat (1) huruf b UU No. 11 Tahun 2020 mengatur PHK dengan alasan efisiensi boleh dilakukan walaupun tanpa diikuti dengan tutupnya perusahaan secara permanen. Akan tetapi, Pasal 154A ayat (1) huruf b telah melanggar Putusan Mahkamah Konstitusi No. 19/PUU-IX/2011 yang menyatakan bahwa PHK efisiensi harus diikuti dengan tutupnya perusahaan secara permanen. Maka, Pasal 154A ayat (1) huruf b bertentangan dengan Putusan Mahkamah Konstitusi yang kedudukannya lebih tinggi daripada undang-undang sebab sumber validitas putusan Mahkamah Konstitusi adalah UUD 1945.
Konstitusionalitas Perlindungan Hukum Terhadap Kebebasan Beragama dan Beribadah di Indonesia
Authors: Razak Askari , A. Sakti R.S. Rakia  , A. Darmawansya
Published: May 2023

Dalam Penjelasan UU No. 1/PNPS/1965, disebutkan bahwa agama yang diakui di indonesia adalah Islam, Kristen, Khatolik, Hindu Budha, dan Khong Hu Chu. Dampaknya, kepercayaan yang tidak disebutkan kehilangan kedudukan hukum serta perlindungan hukum oleh negara. Masalah terhadap kebebasan beragama juga dipengaruhi oleh perbedaan penafsiran atas istilah “agama” dan “keyakinan” oleh masyarakat dan penegak hukum. Pertama, istilah “agama” dan “keyakinan” memiliki pengertian yang berbeda. “Agama” merujuk pada agama-agama yang dianut warga negara Indonesia, sesuai dengan Penjelasan dalam UU No. 1/PNPS/1965. Sedangkan istilah “keyakinan” tidak memiliki landasan hukum. Kedua, istilah “agama” dan “keyakinan” memiliki makna yang identik. Jika pendapat ini diakui maka terjadi generalisasi antara “agama wahyu”, dengan “agama budaya (kepercayaan). Disisi lain, Pasal 29 ayat (2) UUD NRI 1945 belum memiliki tafsir konstitusional yang memadai dalam menyelesaikan masalah ini.
PERTANGGUNGJAWABAN NOTARIS DALAM PENYIMPANAN PROTOKOL NOTARIS DI PROVINSI KEPULAUAN RIAU
Authors: Agustianto Agustianto
Published: May 2023

Notary is a protocol for public officials who have a fairly large responsibility, namely to keep the notary properly because the notary is a document belonging to the state. However, in practice, notaries in the Riau Islands region face various obstacles in keeping the notary protocol. The purpose of this study is to analyze the notary's accountability to the protocol he has made. Based on the results of the study that there are obstacles for notaries in storing notary protocols, namely the lack of facilities in the form of adequate and adequate storage places. Then, there are no regulations governing the storage of notary protocols, the regulations used are regarding the notary code of ethics and the Law on Notary Positions. based on the Legal Responsibility Theory by Hans Kelsen, a notary who violates the law should receive sanctions as stipulated in the Ethics and Laws concerning the Position of a Notary. Therefore, the recommendation in this study is the need for special regulations regarding the storage of notary protocols.
Perlindungan Hukum Kreditur Terhadap Meninggalnya Debitur Sebelum Pendaftaran Hak Tanggungan Elektronik
Authors: Wihandriati Wihandriati
Published: May 2023

The electronic mortgage system is expected to provide convenience for users of the system, but in its implementation it has not run optimally. One of the problems that arise is when the debtor dies after making the APHT and SKMHT which is then followed by the registration of mortgage rights. This study aims to find out how legal protection can be given to creditors against the death of the debtor before the electronic mortgage registration process is carried out. This research is a normative legal research. The data used in this study is secondary data. The collected data is then analyzed descriptively qualitatively by using a conceptual approach or concept approach. The results of this study indicate that there are two forms of legal protection for creditors against the death of the debtor prior to electronic registration of mortgage rights, namely preventive legal protection and repressive legal protection. The application of preventive legal protection is intended to prevent problems from arising in the future, while repressive legal protection is carried out with the aim of resolving disputes that arise between the parties.
Evaluating the appropriateness of risk-based approaches to assess the sustainability of fishery impacts on seabirds
Authors: Good SD , Gummery M , McLennan S , Dewar K , Votier SC , Phillips RA
Published: May 2023

Many seabird populations are declining, with fisheries bycatch as one of the greatest threats. Explicit risk criteria should be used to identify whether bycatch is a problem for particular species and fisheries, but these are often poorly defined. A variety of methods are used to determine the risk that a specific fishery is having an unsustainable impact on a seabird population. Up until October 2022, the Marine Stewardship Council (MSC) applied a general semi-quantitative productivity susceptibility analysis (PSA), a tool that has also been used widely by other management agencies for diverse taxa. Given the need to ensure fisheries risk assessments are robust and consistent, we examined how general PSAs perform when applied in 2 situations with good information on both the seabird population and fisheries bycatch rates and compare the outputs with those from 2 accessible and more quantitative tools: potential biological removal and population viability analysis. We found that risk scoring using the previous MSC version of the PSA was less robust and precautionary than using other approaches, given the steep declines observed in some seabird breeding populations. We make recommendations on how to select attributes for species-specific PSAs and, depending on the data available, identify the most appropriate risk assessment method to achieve a given objective. These should help ensure more consistent assessment and prioritisation of seabird bycatch issues, and improved ecosystem-based management of fisheries.
Integrating germline genetic testing into routine care of patients with breast or ovarian cancer
Authors:   , Bokkers Kyra
Published: May 2023

It is important to identify patients with breast or ovarian cancer who carry a hereditary predisposition for cancer. Identifying such a hereditary predisposition may impact treatment and surveillance options to prevent or identify a second cancer in an early stage. In addition, family members may also be eligible for surveillance options if they carry the same hereditary predisposition. Despite these important implications, not all patients with breast or ovarian cancer who are eligible for genetic testing are referred to a genetics department for counseling and testing. Therefore, we aimed to make genetic testing more accessible to patients with breast or ovarian cancer.
This thesis describes the development, implementation and evaluation of mainstream genetic testing. In these mainstream genetic testing pathways, non-genetic healthcare professionals (i.e., doctors and nurses who are already treating the patient) discuss the advantages and disadvantages of genetic testing and order genetic testing themselves for their patients after completing a concise online training. The results show that non-genetic healthcare professionals in both breast and ovarian cancer care have predominantly positive attitudes toward mainstream genetic testing and it is feasible for them to incorporate genetic testing into their routine care. Patients feel well-informed after counseling about genetic testing and mainstream genetic testing provides good quality of care. For patients with ovarian cancer, mainstream genetic testing led to higher testing rates and a reduction in genetics-related healthcare costs. Based on these results, we can conclude that mainstream genetic testing for patients with breast or ovarian cancer is acceptable and feasible for both healthcare professionals and patients to incorporate into routine care.
FUNGSI KOORDINASI DINAS LINGKUNGAN HIDUP DAN KEHUTANAN PROVINSI KEPULAUAN RIAU DAN DINAS LINGKUNGAN HIDUP KOTA TANJUNGPINANG DALAM PENGAWASAN HUTAN MANGROVE DI KOTA TANJUNGPINANG
Authors: Budiman Shahril , Prayoga Ilham Riady , Karim Zamzami A , Junriana Junriana
Published: May 2023

The purpose of the study was to determine the Coordination Function of the Environment and Forestry Service of the Riau Islands Province and the Tajungpinang City Environmental Service in Monitoring Mangrove Forests in Tanjungpinang City. In this study, the theory used by Hasibuan (2019:88). The population in the study amounted to 8 people, the data analysis used in this study was a qualitative descriptive data analysis technique. The conclusion obtained is that the Coordination Function of the Environment and Forestry Office of the Riau Islands Province in Supervision of Mangrove Forests in Tanjungpinang City is in accordance with their respective authorities although several things need to be improved. Then for the socialization that was carried out both to the community and to employees, it was found that the socialization was not comprehensive. Because the socialization carried out only in general terms, such as raising the theme of cleanliness and environmental protection, has not focused on monitoring mangroves. Before being able to implement a policy, the implementor must realize that a decision has been issued, there are often misunderstandings about the decisions that have been issued so that there are no misunderstandings, socialization must be carried out and that everything is coordinated even though it only occurs when the RTRW is drafted and problems are related to mangroves
GOOD VILLAGE GOVERNANCE DI DESA AYUMOLINGO
Authors: Junus Dikson , Nuna Muten , Hunawa Robby , Sahi Nirmala A , Tumuhulawa Arifin
Published: May 2023

The practice of good village governance has been pioneered and implemented since the outbreak of the reform era, during which the reformation of the government system led to a clean democratic process so that good governance is one of the reform tools that is absolutely necessary in the new government. However, if you look at the development of the implementation of good governance in Indonesia, especially in Ayumolingo Village, which has been running for about 15 years, it has not been fully successful in accordance with the aspirations of reform. This qualitative research by prioritizing primary data and secondary data, focuses on seeing how the application of the principle of transparency in governance towards good village governance in Ayumolingo Village and the factors that influence it? The conclusion is that the implementation of the principles of Good Village Governance in Ayumolingo Village, Gorontalo Regency, resulted in the application of the principle of transparency in Ayumolingo Village being good, but there is still a need for improvement from the aspect of community involvement in monitoring and supervising the governance of Ayumolingo Village. The factors that influence the application of the principle of transparency in the governance of Ayumolingo Village in realizing good village governance are coordination factors, physical factors and power factors.
Sistem Informasi Manajemen Kegiatan UKM English Club PSDKU Polinema Di Kediri Berbasis Framework Laravel
Authors: Arya Hafizh Tofani  , Fadelis Sukya
Published: May 2023

UKM English Club PSDKU Polinema Di Kediri saat ini belum memiliki sistem  informasi untuk mengelola data kegiatan secara terintegrasi, pengelolaan data  kegiatan masih menggunakan cara manual, seperti pengarsipan dibuku catatan  masing-masing anggota organisasi, sehingga pengumpulan data kegiatan tidak  saling terintegrasi satu dengan lainnya. Data kegiatan yang tidak saling terintegrasi  akan menyebabkan kurangnya efisiensi dalam pengelolaan data kegiatan. Sehingga  perlu dirancang dan dibangun sistem informasi manajemen kegiatan untuk  mengelola data kegiatan UKM English Club PSDKU Polinema Di Kediri. Sistem  informasi manajemen kegiatan ini dibuat dalam framework Laravel dengan basis  bahasa pemrograman PHP dan menggunakan basis data PostgreSQL. Sistem  informasi manajemen kegiatan ini memiliki 4 user, yaitu DPK, ketua UKM,  sekretaris UKM dan admin kegiatan. Fitur aplikasi terdiri dari pengelolaan proker,  persetujuan proker, pengelolaan detail proker, pengelolaan proposal kegiatan,  pengelolaan LPJ kegiatan dan persetujuan proposal kegiatan telah diuji dan berhasil  sesuai dengan yang diharapkan.
Sistem Informasi Presensi Mahasiswa PKL Studi Kasus : Dinas Komunikasi dan Informatika Kabupaten Kediri
Authors: Ahmad Choirul Huda  , Agustono Heriadi  , Ratna Widyastuti
Published: May 2023

Abstrak— Di era perkembangan teknologi yang pesat sekarang, banyak sekali pemanfaatan teknologi yang mulai memasuki ke berbagai bidang yang ada mulai dari bidang sosial, bidang ekonomi dan khusunya pada bidang ilmu teknologi. Presensi adalah suatu kegiatan merekap kehadiran yang dilakukan bagi seseorang yang sedang melakukan sebuah pekerjaan. Penggunaan dari komputer sangat diperlukan dalam melakukan kegiatan presensi guna mendapatkan data yang lebih tepat dan akurat. Proses presensi mahasiswa pkl yang ada pada dinas komunikasi dan informatika kabupaten kediri masih menggunakanan presensi manual dimana proses ini masih mempunyai sisi negatif diantaranya terjadinya kerusakan pada buku absensi dikarenakan masih menggunakan kertas.
Pada penelitian ini menggunakan metode wawancara dan studi pustaka dari beberapa penelitian sebelumnya. Untuk menyelesaikan permasalahan yang ada, penulis akan memberikan alternatif penyelesaian pemecahan masalah dengan mengambangkan sebuah sistem informasi presensi yang terkomputerisasi berbasis android. Perancangan ini menggunakan bahasa pemrograman kotlin dan MySQL sebagai pengolahan database. Dengan sistem yang tekromputerisasi ini diharapkan dapat mengatasi permasalahn yang ada, sehingga mempermudahkan mahasiswa PKL dalam melakukan kegiatan presensi kehadiran yang akurat setiap harinya.
Peningkatan Strategi Pemasaran Ragam Olahan Susu Ronojoyo
Authors: Yanuarmawan Dion , Hamidah Fitria Nur
Published: May 2023

Permasalahan yang dihadapi oleh Usaha Mikro dan Kecil Menengah (UMKM) ragamcamilan olahan dari susu ronojoyo (RCOS)  adalah strategi atau cara bagaimana memasarkan produk yang dibuat agar masyarakat mengenal kemudian meminatinya terutama masyarakat di daerah nganjuk. RCOS berharap adanya strategi dalam memasarkan produknya untuk memudahkan usahanya dalam mengenalkan produk yang pada akhirnya akan peningkatan penjualan. Selain itu, permasalahan mengenai pembuatan laporan keuangan karena pembuatan laporan keuangan UMKM berbeda dengan laporan keuangan pada umumnya sehingga diperlukan laporan keuangan yang benar. Solusi yang dapat diberikan untuk memecahkan permasalahan di atas adalah menemukan strategi pemasaran yang tepat. “Tepat” maksudnya strategi pemasaran yang diterapkan sesuai dengan produk yang dihasilkan dan strategi bisnis yang dijalankan. Hasil yang didapat dalam pengabdian masyarakat adalah ditemukannya strategi pemasaran yang tepat yang dapat digunakan untuk memasarkan produknya dengan harapan dapat meningkatkan penjualan RCOS.
Akuntan(Si) Pitung: Mendobrak Mitos Abnormalitas Dan Rasialisme Praktik Akuntansi
Authors: Kamayanti Ari
Published: May 2023

Artikel ini bertujuan menjelaskan dan melakukan konstruksi atas aspek keadilan dalam praktik serta pemikiran akuntansi melalui birokrasi yang seringkali rasis dengan trah keilmuan. Konstruksi ini dilakukan melalui redefinisi (jika tidak mau menggunakan kata ‘dekonstruksi’) “normalitas”. Redefinisi ini sangat dibutuhkan untuk mencapai keadilan, sebagai sebuah konsep, yang berada pada tataran mitos atau wacana. Si Pitung, pahlawan Betawi, adalah metafora yang tepat untuk proses redefinisi ini karena dua alasan. Pertama, kajian tentang si Pitung banyak menempatkan tokoh ini sebagai sebuah mitos-urban legend yang aksinya dilakukan untuk mendapatkan keadilan. Kedua, aksi si Pitung pada esensinya merupakan konsekuensi logis atas redefinisi ‘normalitas’. Akhirnya, artikel ini mengusulkan sebuah perubahan asumsi atas normalitas akuntansi agar keadilan tidak menjadi sekadar mitos. Melalui akuntansi, menerima perubahan menuju perbaikan adalah hal yang normal, sedangkan mempertahankan kemapanan kuasa tertentu/status quo adalah hal yang abnormal.
Jenis Industri dan Ukuran KAP sebagai Pemoderasi Hubungan Auditor Internal dan Audit Delay
Authors: Putra Rediyanto , Sutrisno  , Mardiati Endang
Published: May 2023

Riset ini memiliki tujuan untuk membuktikan efek negatif auditor internal pada audit delay. Riset ini juga menganalisis efek moderasi dari jenis industri industri dan ukuran Kantor Akuntan Publik (KAP) pada pengaruh auditor internal pada audit delay. Populasi penelitian adalah perusahaan publik yang terdaftar di Bursa Efek Indonesia periode 2013 hingga 2015. Proses penentuan sampel penelitian dilakukan dengan metode purposive sampling. Penelitian ini menggunakan model persamaan struktural berbasis varians (SEMPLS). Proses pengujian hipotesis dilakukan dengan menggunakan dua metode yaitu uji direct impact dan analisis multigrup. Hasil penelitian menunjukkan bahwa waktu tunda audit yang dimiliki oleh perusahaan publik di Bursa Efek Indonesia tahun 2013 hingga 2015 adalah 6 hari hingga 194 hari. Hasil pengujian pengaruh langsung membuktikan adanya efek negatif dari auditor internal terhadap rentang waktu terjadinya audit delay. Hasil pengujian analisis multigrup membuktikan adanya efek moderasi dari jenis industri dan ukuran KAP pada pengaruh auditor internal terhadap audit delay.
Tantangan Pembelajaran Tematik dalam Jaringan dengan Model Website Berbasis Youtube di Sekolah Dasar
Authors: Yusuf Rendi Wibowo  , Andi Prastowo
Published: May 2023

Abstract: The purpose of this study is to reveal the challenges faced in online learning using a website model through Youtube. This is because during distance learning from home, students at the MI / SD level do a lot of online learning so that efforts are needed to make policies or solutions that can solve the challenges that occur. Qualitative is chosen as the approach that the researcher applies, while the method used is descriptive. The data collection technique used is by conducting interviews with class IV teachers and grade IV students of SD IT Baitul Muslim Way Jepara. The results of the study found that the challenges of learning the website model through Youtube were felt, namely: 1) Unstable internet network quality, 2) prices and quota usage, 3) infrastructure facilities were not supportive, 4) power outages that interfered with the quality of the internet network, 5) Difficulty of monitoring during the learning process. Some solutions that may be able to reduce these challenges are internet quota subsidies to educators and students by working with the provider, Youtube is used to deliver material only, for assignments it can be through Whatsapp or Google Classroom only, and the last solution if you don't want there to be challenges as explained, it is better to apply PTMT (limited face-to-face meetings).
Abstrak: Tujuan dilakukannya penelitian ini ialah untuk mengungkapkan tantangan-tantangan yang dihadapi dalam pembelajaran online menggunakan model website melalui youtube. Hal ini dikarenakan selama pembelajaran jarak jauh dari rumah, peserta didik dalam jenjang MI/SD banyak melakukan pembelajaran secara daring sehingga butuh upaya pengambilan kebijakan atau solusi yang bisa menyelesaikan tantangan yang terjadi. Kualitatif dipilih sebagai pendekatan yang peneliti terapkan, sedangkan metode yang diguanakan ialah deskriptif. Teknik pengambilan data yang digunakan yaitu dengan melakukan wawancara pada guru kelas IV dan murid kelas IV SD IT Baitul Muslim Way Jepara. Hasil dari penelitian didapatkan bahwa tantangan pembelajaran model website melalui youtube yang dirasakan yaitu: 1) Kualitas jaringan internet yang tidak stabil, 2) harga dan penggunaan kuota, 3) fasilitas sarana prasaran kurang mendukung, 4) pemadaman listrik yang mengganggu kualitas jaringan internet, 5) Sulitnya pemantaun saat proses pembelajaran dilakukan. Beberapa solusi yang mungkin bisa mengurangi tantangan tersebut ialah subsidi kuota internet ke pendidik dan peserta didik dengan cara bekerja sama dengan pihak provider, youtube digunakan untuk menyampaikan materi saja, untuk penugasan bisa melalui Whatsapp atau Google Classroom saja, dan solusi yang terakhir jika tidak ingin ada tantangan-tantangan seperti halnya yang sudah dijelaskan maka lebih baik terapkan PTMT (pertemuan tatap muka terbatas).
Developing Scrabble Wall for Students’ Vocabulary Learning
Authors: Sarah Fauziah  , Fitri Hilmiyati  , Siti Sa'diah
Published: May 2023

Mastering vocabulary could be one of the keys to be successful in learning English. Teaching by using a certain game could be an interesting way to increase students’ vocabulary.  The aim of this study is to create a scrabble wall to help students improve their vocabulary. This study employed the research and development method, as well as the ADDIE Model's theory, which is divided into five stages: analysis, design, development, implementation, and evaluation. Interviews, exams, and expert validation checklists were used as study instruments. This study used 25 students as a sample of product implementation among eleventh-grade students of SMA Putra Juang Cianjur. Data were gathered from student interviews, test results (Pre-test and Post-test), teacher replies, and expert validation results. The data analysis revealed that the product was both good and valid. The scrabble wall can be used as a means to teach English, particularly vocabulary. The scrabble wall is helpful for students as well. It may be concluded that the use of scrabble wall can enhance students’ vocabulary mastery.
Case report: Insulin desensitization as the only option for managing insulin allergy in a Sudanese patient
Authors: Said Rihan , Goda Rayan , Abdalrahman Ihab B. , Erwa Nahla H. H.
Published: May 2023

Introduction

Allergic reactions to insulin have become very rare with the introduction of human insulin. Anaphylaxis is a life-threatening condition that results from immediate IgE-mediated hypersensitivity. Desensitization to human insulin was reported to control immediate hypersensitivity reactions to insulin. Here, we describe the history and challenges of managing our patient and the development of an insulin desensitization protocol in a resource-limited setup.

Case Summary

A 42-year-old Sudanese woman with poorly controlled type 2 diabetes on maximum antidiabetic medications required insulin therapy to achieve reasonable glycemic control. She developed progressive and severe immediate hypersensitivity reactions to insulin, including anaphylaxis. Serum sample analysis demonstrated insulin-specific IgE antibodies. The patient's poor glycemic control and the need for breast surgery indicated insulin desensitization. A 4-day desensitization protocol was delivered in an ICU bed for close observation. Following successful desensitization and 24-h observation, our patient was discharged on pre-meal human insulin, which was tolerated well to the current date

Conclusions

Although insulin allergy is rare, once encountered, it is very challenging in patients who have no other treatment options available. Different protocols for insulin desensitization are described in the literature; the agreed protocol was implemented successfully in our patient despite the limited resources.
Senescence induces fundamental changes in the secretome of mesenchymal stromal cells (MSCs): implications for the therapeutic use of MSCs and their derivates
Authors: Siraj Yesuf , Galderisi Umberto , Alessio Nicola
Published: May 2023

Mesenchymal stromal cells (MSCs) are a heterogeneous population containing multipotent adult stem cells with a multi-lineage differentiation capacity, which differentiated into mesodermal derivatives. MSCs are employed for therapeutic purposes and several investigations have demonstrated that the positive effects of MSC transplants are due to the capacity of MSCs to modulate tissue homeostasis and repair via the activity of their secretome. Indeed, the MSC-derived secretomes are now an alternative strategy to cell transplantation due to their anti-inflammatory, anti-apoptotic, and regenerative effects. The cellular senescence is a dynamic process that leads to permanent cell cycle arrest, loss of healthy cells’ physiological functions and acquiring new activities, which are mainly accrued through the release of many factors, indicated as senescence-associated secretory phenotype (SASP). The senescence occurring in stem cells, such as those present in MSCs, may have detrimental effects on health since it can undermine tissue homeostasis and repair. The analysis of MSC secretome is important either for the MSC transplants and for the therapeutic use of secretome. Indeed, the secretome of MSCs, which is the main mechanism of their therapeutic activity, loses its beneficial functions and acquire negative pro-inflammatory and pro-aging activities when MSCs become senescent. When MSCs or their derivatives are planned to be used for therapeutic purposes, great attention must be paid to these changes. In this review, we analyzed changes occurring in MSC secretome following the switch from healthy to senescence status.
Biofabrication of nanoparticles: sources, synthesis, and biomedical applications
Authors: Kulkarni Deepak , Sherkar Rushikesh , Shirsathe Chaitali , Sonwane Rushikesh , Varpe Nikita , Shelke Santosh , More Mahesh P. , Pardeshi Sagar R. , Dhaneshwar Gargee , Junnuthula Vijayabhaskarreddy , Dyawanapelly Sathish
Published: May 2023

Graphical Abstract

Sources for biogenic synthesis: The synthesis sources include but are not limited to bacteria, fungi, algae, yeasts, marine and plant sources.
In silico biomechanical analysis of poller screw-assisted small-diameter intramedullary nail in the treatment of distal tibial fractures
Authors: Tan Jinchuan , Yang Yang , Wang Mian , Huang Xuecheng , Ouyang Hanbin , Zhao Dongliang , Huang Gang , Deng Yuping , Huang Wenhua
Published: May 2023

Objective: To evaluate the biomechanical effects of Poller screws (PS) combined with small-diameter intramedullary nails in the treatment of distal tibial fractures at different locations and on different planes.

Methods: Nine finite element (FE) models were used to simulate the placement of the intramedullary nail (IMN) and the PS for distal tibial fractures. Structural stiffness and interfragmentary motion (IFM) through the fracture were investigated to assess the biomechanical effects of the PS. The allowable stress method was used to evaluate the safety of the construct.

Results: With the axial load of 500 N, the mean axial stiffness of IMN group was 973.38 ± 95.65 N/mm, which was smaller than that at positions A and B of the coronal group and sagittal group (p < 0.05). The shear IFM of the IMN group was 2.10 ± 0.02 mm, which were smaller than that at positions A and B of the coronal group and sagittal group (p < 0.05). Under physiological load, the stresses of all internal fixation devices and the nail-bone interface were within a safe range.

Conclusion: In the treatment of distal tibial fractures, placing the PS in the proximal fracture block can obtain better biomechanical performance. The IMN fixation system can obtain higher structural stiffness and reduce the IFM of the fracture end by adding PS.
Nanoenhancer for improving naked DNA electrotransfection In vivo
Authors: Wang Yifei , Wang Chunxi , Sylvers Justin , Segura Tatiana , Yuan Fan
Published: May 2023

Introduction:Electrotransfection (ET) is a non-viral approach widely used for delivery of naked nucleic acids. Its efficiency can be increasedin vitroby treatment of cells with various small molecule enhancers. However, these enhancers often fail to improve ETin vivo, presumably due to rapid clearance in tissues after local injection, reducing their cellular uptake. To this end, we propose to develop a new type of ET enhancers, which we term nanoenhancer, that diffuse slowly in tissues and are poorly absorbed by blood and lymph microvessels.

Methods:Two nanoenhancers were synthesized with alginate (Alg) and chitosan (Chi) with or without poly (ethylene imine) (PEI). They were used to treat cellsin vitroor mouse muscle in the hind legin vivoprior to ET of plasmid DNA coding reporter genes. At 24 hours post ET, the efficiency of ET was quantified, and compared with that in the untreated controls. Changes in lysosomal size and acidity post nanoenhancer treatment were measured with fluorescence microscopy techniques.

Results and discussion:We observed that the pretreatment of cells with the nanoenhancers could enhance the ET efficiency and cell viability in both C2C12 and HCT116 cellsin vitro, and the nanoenhancer pretreatment had similar effects on the ET efficiencyin vivo. Mechanisms of the enhancement were related to transient inactivation of lysosomal functions triggered by the nanoenhancer treatment. The concept of nanoenhancer will lead to development of new enhancers that can be used to improve ET efficiencyin vivo, highlighting its potential in clinical applications.
Deficiency of Wdr60 and Wdr34 cause distinct neural tube malformation phenotypes in early embryos
Authors: Yan Lu , Yin Hailing , Mi Yiwei , Wu Yu , Zheng Yufang
Published: May 2023

Cilia are specialized organelles that extend from plasma membrane, functioning as antennas for signal transduction and are involved in embryonic morphogenesis. Dysfunction of cilia lead to many developmental defects, including neural tube defects (NTDs). Heterodimer WDR60-WDR34 (WD repeat domain 60 and 34) are intermediate chains of motor protein dynein-2, which play important roles in ciliary retrograde transport. It has been reported that disruption of Wdr34 in mouse model results in NTDs and defects of Sonic Hedgehog (SHH) signaling. However, no Wdr60 deficiency mouse model has been reported yet. In this study, piggyBac (PB) transposon is used to interfere Wdr60 and Wdr34 expression respectively to establish Wdr60PB/PB and Wdr34PB/PB mouse models. We found that the expression of Wdr60 or Wdr34 is significantly decreased in the homozygote mice. Wdr60 homozygote mice die around E13.5 to E14.5, while Wdr34 homozygote mice die around E10.5 to E11.5. WDR60 is highly expressed in the head region at E10.5 and Wdr60PB/PB embryos have head malformation. RNAseq and qRT-PCR experiments revealed that Sonic Hedgehog signaling is also downregulated in Wdr60PB/PB head tissue, demonstrating that WDR60 is also required for promoting SHH signaling. Further experiments on mouse embryos also revealed that the expression levels of planar cell polarity (PCP) components such as CELSR1 and downstream signal molecule c-Jun were downregulated in WDR34 homozygotes compared to wildtype littermates. Coincidently, we observed much higher ratio of open cranial and caudal neural tube in Wdr34PB/PB mice. CO-IP experiment showed that WDR60 and WDR34 both interact with IFT88, but only WDR34 interacts with IFT140. Taken together, WDR60 and WDR34 play overlapped and distinct functions in modulating neural tube development.
Role of miR-182 in cardiovascular and cerebrovascular diseases
Authors: Pei Gaiqin , Chen Li , Wang Yang , He Chengqi , Fu Chenying , Wei Quan
Published: May 2023

The treatment of cardiovascular and cerebrovascular diseases have undergone major advances in recent decades, allowing for a more effective prevention of cardiovascular and cerebrovascular events. However, cardiac and cerebral atherothrombotic complications still account for substantial morbidity and mortality worldwide. Novel therapeutic strategies are critical to improve patient outcomes following cardiovascular diseases. miRNAs are small non-coding RNAs, that regulate gene expression. Here, we discuss the role of miR-182 in regulating myocardial proliferation, migration, hypoxia, ischemia, apoptosis and hypertrophy in atherosclerosis, CAD, MI, I/R injury, organ transplant, cardiac hypertrophy, hypertension, heart failure, congenital heart disease and cardiotoxicity. Besides, we also summarize the current progress of miR-182 therapeutics in clinical development and discuss challenges that will need to be overcome to enter the clinic for patients with cardiac disease.
Attention-guided cascaded network with pixel-importance-balance loss for retinal vessel segmentation
Authors: Su Hexing , Gao Le , Lu Yichao , Jing Han , Hong Jin , Huang Li , Chen Zequn
Published: May 2023

Accurate retinal vessel segmentation from fundus images is essential for eye disease diagnosis. Many deep learning methods have shown great performance in this task but still struggle with limited annotated data. To alleviate this issue, we propose an Attention-Guided Cascaded Network (AGC-Net) that learns more valuable vessel features from a few fundus images. Attention-guided cascaded network consists of two stages: the coarse stage produces a rough vessel prediction map from the fundus image, and the fine stage refines the missing vessel details from this map. In attention-guided cascaded network, we incorporate an inter-stage attention module (ISAM) to cascade the backbone of these two stages, which helps the fine stage focus on vessel regions for better refinement. We also propose Pixel-Importance-Balance Loss (PIB Loss) to train the model, which avoids gradient domination by non-vascular pixels during backpropagation. We evaluate our methods on two mainstream fundus image datasets (i.e., DRIVE and CHASE-DB1) and achieve AUCs of 0.9882 and 0.9914, respectively. Experimental results show that our method outperforms other state-of-the-art methods in performance.
Resistance mechanisms of tigecycline in Acinetobacter baumannii
Authors: Sun Chunli , Yu Yunsong , Hua Xiaoting
Published: May 2023

Acinetobacter baumannii is widely distributed in nature and in hospital settings and is a common pathogen causing various infectious diseases. Currently, the drug resistance rate of A. baumannii has been persistently high, showing a worryingly high resistance rate to various antibiotics commonly used in clinical practice, which greatly limits antibiotic treatment options. Tigecycline and polymyxins show rapid and effective bactericidal activity against CRAB, and they are both widely considered to be the last clinical line of defense against multidrug resistant A. baumannii. This review focuses with interest on the mechanisms of tigecycline resistance in A. baumannii. With the explosive increase in the incidence of tigecycline-resistant A. baumannii, controlling and treating such resistance events has been considered a global challenge. Accordingly, there is a need to systematically investigate the mechanisms of tigecycline resistance in A. baumannii. Currently, the resistance mechanism of A. baumannii to tigecycline is complex and not completely clear. This article reviews the proposed resistance mechanisms of A. baumannii to tigecycline, with a view to providing references for the rational clinical application of tigecycline and the development of new candidate antibiotics.
A ParDE toxin–antitoxin system is responsible for the maintenance of the Yersinia virulence plasmid but not for type III secretion-associated growth inhibition
Authors: Schott Saskia , Scheuer Robina , Ermoli Francesca , Glatter Timo , Evguenieva-Hackenberg Elena , Diepold Andreas
Published: May 2023

Many Gram-negative pathogens utilize the type III secretion system (T3SS) to translocate virulence-promoting effector proteins into eukaryotic host cells. The activity of this system results in a severe reduction of bacterial growth and division, summarized as secretion-associated growth inhibition (SAGI). In Yersinia enterocolitica, the T3SS and related proteins are encoded on a virulence plasmid. We identified a ParDE-like toxin–antitoxin system on this virulence plasmid in genetic proximity to yopE, encoding a T3SS effector. Effectors are strongly upregulated upon activation of the T3SS, indicating a potential role of the ParDE system in the SAGI or maintenance of the virulence plasmid. Expression of the toxin ParE in trans resulted in reduced growth and elongated bacteria, highly reminiscent of the SAGI. Nevertheless, the activity of ParDE is not causal for the SAGI. T3SS activation did not influence ParDE activity; conversely, ParDE had no impact on T3SS assembly or activity itself. However, we found that ParDE ensures the presence of the T3SS across bacterial populations by reducing the loss of the virulence plasmid, especially under conditions relevant to infection. Despite this effect, a subset of bacteria lost the virulence plasmid and regained the ability to divide under secreting conditions, facilitating the possible emergence of T3SS-negative bacteria in late acute and persistent infections.
A review of malaria molecular markers for drug resistance in Plasmodium falciparum and Plasmodium vivax in China
Authors: Wang Siqi , Huang Fang , Yan He , Yin Jianhai , Xia Zhigui
Published: May 2023

China has now achieved the elimination of malaria, but it still faces severe challenges in the post-elimination stage. China continues to be plagued by imported malaria cases, and preventing re-transmission of imported malaria is critical. The effectiveness of antimalarial drugs for malaria control largely depends on the study of drug resistance markers in vitro. Monitoring molecular markers of parasite-associated drug resistance can help predict and manage drug resistance. There is currently a lack of systematic reviews of molecular markers for indigenous and imported malaria in China. Therefore, this review summarizes the published articles related to molecular marker polymorphism of indigenous and imported malaria cases in China in the past two decades, to study the mutation frequency and distribution of crt, mdr1, dhps, dhfr and K13 gene resistance-related loci. This can provide a whole picture of molecular markers and the resistance mutations of imported cases in China, which has certain significance for drug resistance surveillance planning, safe and effective treatment, and preventing the recurrence of local transmission by imported malaria in China in the future.
Comparative analysis of vaginal microbiota sampling using menstrual cups and high vaginal swabs in pregnant women living with HIV-1 infection
Authors: Short Charlotte-Eve S. , Quinlan Rachael , Lee Yun S. , Preda Veronica G. , Smith Ann , Marchesi Julian R. , Shattock Robin , Bennett Phillip R. , MacIntyre David A. , Taylor Graham P.
Published: May 2023

Background

Menstrual cups (MCs) are increasingly used to collect cervicovaginal secretions to characterise vaginal mucosal immunology, in conjunction with high vaginal swabs (HVS) for metataxonomics, particularly in HIV transmission studies. We hypothesised that both methods of collecting bacterial biomass are equivalent for 16S rRNA gene sequencing.

Material and Methods

Cervicovaginal fluid (CVF) samples from 16 pregnant women with HIV-1 (PWWH) were included to represent the major vaginal bacterial community state types (CST I-V). Women underwent sampling during the second trimester by liquid amies HVS followed by a MC (Soft disc™) and samples were stored at -80°C. Bacterial cell pellets obtained from swab elution and MC (500 µL, 1 in 10 dilution) were resuspended in 120 µL PBS for DNA extraction. Bacterial 16S rRNA gene sequencing was performed using V1-V2 primers and were analysed using MOTHUR. Paired total DNA, bacterial load, amplicon read counts, diversity matrices and bacterial taxa were compared by sampling method using MicrobiomeAnalyst, SPSS and R.

Results

The total DNA eluted from one aliquot of diluted CVF from an MC was similar to that of a HVS (993ng and 609ng, p=0.18); the mean bacterial loads were also comparable for both methods (MC: 8.0 log10 16S rRNA gene copies versus HVS: 7.9 log10 16S rRNA gene copies, p=0.27). The mean number of sequence reads generated from MC samples was lower than from HVS (MC: 12730; HVS:14830, p=0.05). The α-diversity metrices were similar for both techniques; MC Species Observed: 41 (range 12-96) versus HVS: 47 (range 16-96), p=0.15; MC Inverse Simpson Index: 1.98 (range 1.0-4.0) versus HVS: 0.48 (range 1.0-4.4), p=0.22). The three most abundant species observed were: Lactobacillus iners, Lactobacillus crispatus and Gardnerella vaginalis. Hierarchical clustering of relative abundance data showed that samples obtained using different techniques in an individual clustered in the same CST group.

Conclusion

These data demonstrate that despite sampling slightly different areas of the lower genital tract, there was no difference in bacterial load or composition between methods. Both are suitable for characterisation of vaginal microbiota in PWWH. The MC offers advantages, including a higher volume of sample available for DNA extraction and complimentary assays.
Building the case for mitochondrial transplantation as an anti-aging cardiovascular therapy
Authors: Headley Colwyn A. , Tsao Philip S.
Published: May 2023

Mitochondrial dysfunction is a common denominator in both biological aging and cardiovascular disease (CVD) pathology. Understanding the protagonist role of mitochondria in the respective and independent progressions of CVD and biological aging will unravel the synergistic relationship between biological aging and CVD. Moreover, the successful development and implementation of therapies that can simultaneously benefit mitochondria of multiple cell types, will be transformational in curtailing pathologies and mortality in the elderly, including CVD. Several works have compared the status of mitochondria in vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in CVD dependent context. However, fewer studies have cataloged the aging-associated changes in vascular mitochondria, independent of CVD. This mini review will focus on the present evidence related to mitochondrial dysfunction in vascular aging independent of CVD. Additionally, we discuss the feasibility of restoring mitochondrial function in the aged cardiovascular system through mitochondrial transfer.
Prognostication of treatment non-compliance among patients with multidrug-resistant tuberculosis in the course of their follow-up: a logistic regression–based machine learning algorithm
Authors: Anley Denekew Tenaw , Akalu Temesgen Yihunie , Dessie Anteneh Mengist , Anteneh Rahel Mulatie , Zemene Melkamu Aderajew , Bayih Wubet Alebachew , Solomon Yenealem , Gebeyehu Natnael Atnafu , Kassie Gizachew Ambaw , Mengstie Misganaw Asmamaw , Abebe Endeshaw Chekol , Seid Mohammed Abdu , Gesese Molalegn Mesele , Moges Natnael , Bantie Berihun , Feleke Sefineh Fenta , Dejenie Tadesse Asmamaw , Adella Getachew Asmare , Muche Achenef Asmamaw
Published: May 2023

Introduction

Drug compliance is the act of taking medication on schedule or taking medication as prescribed and obeying other medical instructions. It is the most crucial aspect in the treatment of chronic diseases particularly for patients with multidrug-resistant tuberculosis (MDR-TB). Drug non-compliance is the main reason for causing drug resistance and poor treatment outcomes. Hence, developing a risk prediction model by using early obtainable prognostic determinants of non-compliance is vital in averting the existing, unacceptably high level of poor treatment outcomes and reducing drug resistance among MDR-TB patients.

Materials and methods

A retrospective follow-up study was conducted on a total of 517 MDR-TB patients in Northwest Ethiopia. A logistic regression–based machine learning algorithm was used to develop a risk score for the prediction of treatment non-compliance among MDR-TB patients in selected referral hospitals of Northwest Ethiopia. The data were incorporated in EpiData version 3.1 and exported to STATA version 16 and R version 4.0.5 software for analysis. A simplified risk prediction model was developed, and its performance was reported. It was also internally validated by using a bootstrapping method.

Results

Educational status, registration group (previously treated/new), treatment support, model of care, and khat use were significant prognostic features of treatment non-compliance. The model has a discriminatory power of area under curve (AUC) = 0.79 with a 95% CI of 0.74–0.85 and a calibration test of p-value = 0.5. It was internally validated by using a bootstrapping method, and it has a relatively corrected discriminatory performance of AUC = 0.78 with a 95% CI of 0.73–0.86 and an optimism coefficient of 0.013.

Conclusion

Educational status, registration group, treatment supporter, model of care, and khat use are important features that can predict treatment non-compliance of MDR-TB patients. The risk score developed has a satisfactory level of accuracy and good calibration. In addition, it is clinically interpretable and easy to use in clinical practice, because its features are easily ascertainable even at the initial stage of patient enrolment. Hence, it becomes important to reduce poor treatment outcomes and drug resistance.
Soil gas CO2 emissions from active faults: a case study from the Anninghe—Zemuhe fault, Southeastern Tibetan Plateau, China
Authors: Liu Fengli , Zhou Xiaocheng , Dong Jinyuan , Yan Yucong , Tian Jiao , Li Jingchao , Ouyang Shupei , He Miao , Liu Kaiyi , Yao Bingyu , Wang Yuwen , Zeng Zhaojun , Zhang Yongxian
Published: May 2023

Introduction: Carbon dioxide emissions from non-volcanic areas are undervalued in the carbon cycle.

Methods: First estimates of diffuse CO2 flux from the Anninghe—Zemuhe fault (AZF), Southeastern Tibetan Plateau, China, which suggests this could equal 15% emissions from all volcanoes in China. Following the accumulation chamber method, CO2 flux was investigated at 1,483 points, and along 67 profiles crossing the AZF.

Results and discussion: Total CO2 emissions from the AZF were estimated 1.2 Mt yr-1. The relationship between soil gas CO2 fluxes, earthquakes, and fault activity was discussed. The intense fault activity in the southern part of the Zemuhe fault (ZMHF) and the northern part of the Anninghe fault (ANH) was inferred, which could have enhanced the porosity of the soil, and accelerated the water-rock interactions and soil gas emission within the fault zone. The chemical and isotopic data indicated that biogenic CO2 was the primary source of CO2 from the AZF. Produced by interactions between groundwaters and carbonates, soil gas CO2 could migrate to the near surface through cracks. Spatial variations of CO2 flux in soil gas indicate that seismic activity could be responsible for the jumpy variations of CO2 flux. The diffuse CO2 from deep faults may contribute considerably to the greenhouse gas cycles.