bluuebunny/crossref_metadata_2025 huggingface dataset:
THE COMMUNITY PROTECTION ON DISASTER MITIGATION PERSPECTIVE OF LOCAL GOVERNMENT LAW: AN EMPIRICAL STUDY
Authors: Pramono Joko , Kusumastuti Dora
Published: November 2022

According to mandate Act Number 23 the year 2014 on regional

government that local governments had one obligation of

community protection division for service. The role of community

protection one of them is disaster mitigation. The objective that

performs the functions of research is to know and how local

government efforts in carrying out on obligatory basic service of

disaster mitigation by community protection with the increasing

number of cases disasters is empirical research in Indonesia.

Method of juridical because use primary data obtained by

interviews, FGD, and observation. Data analyzed to use the

technique can draw interactive analysis to concluding. The local

government efforts in carrying out on obligatory basic service

disaster mitigation command regions conducted of disaster

training, members always involved in the disaster, and always

coordinate with an agency that has authority main of disaster

perform the functions.Not ideally of percentage members and

several people as well as the limited need to follow-up facilities

from local government to realize community protection division

for basic service.
CASTRATION PUNISHMENT FOR PERPETRATORS OF CRIMINAL OFFENSES OF SEXUAL VIOLENCE AGAINST CHILDREN
Authors: Susilawati Endang Yuliana
Published: November 2022

The castration sentence that has been imposed as an additional

punishment to provide a deterrent effect for perpetrators of

sexual violence against children in mid-2019 by judges at the

Sidoarjo District Court and the Surabaya District Court is

interesting to examine. The research objective was to determine

the effect of the nut on the perpetrator, as well as the effect of

its prevention on society. This type of juridical normative

research is descriptive in nature, with qualitative analysis. The

results of the research show that the judge's decision has only

had a panic effect on the perpetrator, it is not possible to see a

deterrent effect for the perpetrator because castration will only

be carried out when the convict has finished serving

imprisonment. While the preventive effect for the community

has not yet been seen, it is proven that currently the crime rate

is still high.
EXPLORING THE NOTARY LIABILITY IN TORTS (An Exclusive Interview with the Chairman of the Indonesian Notary Association of Batam City)
Authors: Seroja Triana Dewi , Nurlaily Nurlaily , Shahrullah Rina Shahriyani , Hadiyati Nur , Altison Kwariyon
Published: November 2022

In practice, it often occurs that a notary is summoned to the

court on the ground that he/she provides information on the

deeds or documents containing torts (an act against the law).

This study questions whether a notary is liablewhen the torts

occur. This study utilizes a socio-legal research method by

adopting qualitative juridical data analysis. It found thattorts

may occur due to 2 (two) factors, namely (1) lack of precaution

when drafting the deeds, and (2) deliberatelymaking the deeds

which do not meet the specified conditions. As the results, the

notary is liable to bear all losses arising from the issuing of the

deed, including a liability due to a criminal lawsuit. In order to

prevent torts, a notary mustdisclose all relevant information,

clarify documents, and have more legal awareness.
LAW ENFORCEMENT ON CAMPAIGN ACTIVITIES IN PLACES OF WORSHIP CASE STUDY OF DECISION NUMBER 56/PID.SUS/2019/PN SKH
Authors: Sukmadila Filadelfia Langit Ayu , Indrastuti Lusia , Aryani Esti
Published: November 2022

This study aims to find out the basis of Law Enforcement on campaign activities in places of worship that focuses on the Sukoharjo District Court Decision Number 56/Pid.Sus/2019/PN Skh, a case related to this research regarding campaign activities in places of worship.One of the characteristics of a democratic country is the existence of people's sovereignty within the country, and Indonesia is a country that adheres to the Pancasila Democracy system, as evidenced by the holding of General Elections, hereinafter referred to as General Elections. The implementation of elections is regulated in Law No. 7 of 2017 concerning General Elections, which also regulates election crimes, the legal basis is formed and enforced to maintain the dignity of democracy that applies in Indonesia.This research method in writing this thesis uses a normative type of research, which is carried out by reviewing secondary data, which includes primary legal materials, secondary legal materials, and tertiary legal materials. The nature of the research is descriptive, which is to describe the basis of the prosecutor's considerations in giving demands and the judge's considerations in making decisions as well. The duty of a Prosecutor as a Public Prosecutor is to prove his indictment. Where the decisions and demands of judges and prosecutors must uphold the value of justice, and not forget the value of humanity. As well as the judge's consideration in deciding this case, seeing from the indictment that the indictment was prepared on a subsidiary basis, it became the authority of the Panel of Judges to prove the indictment of Article 521 Jo. Article 280 paragraph (1) letter h of Law No. 7 of 2017 concerning General Elections.also pay attention to non-juridical elements.
THE ROLE OF CERTIFICATES AS EVIDENCE OF LAND RIGHTS TOWARDS THE ERA OF REVOLUTION 4.0
Authors: Maiyestati Maiyestati
Published: November 2022

Considering the very importance of the use of land for people or business entities that demand legal certainty over the land, the formulation of the problem in this study is stated: how is the role of certificates as evidence of land rights in the era of revolution 4.0?. The type of research used to solve the problem in this study was juridical-normative, with qualitative analysis. The role of certificates as an evidence of land rights in the 4.0 revolution era in Indonesia is only a strong sign and is not an absolute evidence, with a negative system that contains positive elements. A certificate that has been legally issued in the name of a person or legal entity of another party who admit for the right may file a written objection to the certificate holder and to the Land Office.
The Implementation of Democracy in The Middle of The Application of Ite Law
Authors: Hermawan Ian Aji
Published: November 2022

Democracy in Indonesia has been running for quite a long time since Indonesia was founded until now, which is approximately 76 years. each order has its own characteristics in carrying out democracy in Indonesia according to the conditions and political interests at that time.So that each ruler has his own interpretation of democracy in the Sukarno era, in the guided democracy during the Suharto era, there was Pancasila democracy and in the reformation period, Pancasila democracy was implemented in accordance with the constitution. there is little difference in implementing Pancasila democracy during the New Order era and during the reformation period.This difference can be seen where during the new code of democracy Pancasila was implemented but not wholeheartedly because the authorities at that time implemented a subversion law, while during this reformation period, especially in the last 10 years, the government implemented a democratic system but also implemented a law on information and electronic transactions. considered by some legal and political observers to be a substitute for subversive laws.
THE LAXITY OF CRIMINAL LAW ENFORCEMENT IN INDONESIA AND EFFORTS TO OVERCOME IT
Authors: Kusumo Bambang Ali
Published: November 2022

The laxity of criminal law enforcement lied in the surveillance function in criminal justice management system and civil law culture. Effort needed to be done by empowering functions of broader Supreme Court surveillance, not only surveillance that

proceeding in the court but also surveillance from all criminal

law enforcement process. Beside that for the sake of actualizing

justice in the society, civil law culture required to be used broad

interpretation and always updated legal reform.
Keperawanan Maryam a.s dari perspektif Bible dan pandangan al-Quran terhadapnya.
Authors: Abu Hassan @ Abd Rahman Hamidah binti , Abd Aziz Md Yunus
Published: November 2022

Mary or Maryam is the greatest woman mentioned in Bible and Al-Quran. God chosen Mary to be a mother while she was yet a virgin. Mary was honored and highly regarded among the Muslims and Christians when she gave birth to Jesus or Isa a.s without any cohabitation with a male. Islam and Christian provide different perspectives on Maryam’s virginity based on the prophecies of their respective scriptures. This article discusses the virginity of Maryam according to the Christian and the Islamic perspectives. This article also aims to compare and analyze the differences of the viewpoints given by using comparative methods, analysis and criticism. Among the important findings of this study is that Christian’s teachings and beliefs about Mary ‘s virginity have a close relationship with Jesus divinity.From the Islamic perspective, the virginity of Maryam and the birth of Isa a.s is one of the great signs of Allah s.w.t. greatness and perfection.

ABSTRAK

Jesus Christ atau Isa a.s dilahirkan oleh seorang perawan suci iaitu Mary atau Maryam a.s. Kedua -dua agama Kristian dan Islam mengiktiraf hakikat tersebut. Namun begitu konsep keperawanan Maryam a.s telah mencetuskan pandangan yang berbeza dari perspektif kedua-dua agama. Justeru penulisan ini adalah untuk membentangkan konsep kelahiran perawan dan kedaraan selama-lamanya Maryam menurut pandangan Kristian dan Islam serta melakukan analisis terhadap asas-asas perbezaan antara kedua agama berpandukan dalil dan hujjah daripada kitab suci masing-masing. Kajian ini adalah berbentuk analisis kandungan yang menggunakan metod kajian perpustakaan. Hasil kajian mendapati bahawa keperawanan Maryam ketika mengandung dan melahirkan Jesus telah mengukuhkan doktrin ketuhanan Jesus Christ pada pandangan penganut Kristian sedangkan Islam melihat ia sebagai tanda kekuasaan dan kebesaran Allah S.W.t ke atas makhluk-Nya.
The Role of Quran and Sunnah in Solving Leadership Failure
Authors: Junaidi Juliyana , Abdul Majid Latifah , Nazri Mohd Arif
Published: November 2022

Social injustice issues that are skyrocketing in recent times have garnered attention from various parties. One of the issues includes leadership failure, which has caused an immense impact on the social structure. Strong leadership is essential in shaping society as it affects the growth of civilization. Unfortunately, the role of the Quran and Sunnah in guiding the leadership path has been abandoned by the leaders hence resulting in its crisis. Even though many scholars have provided the discussions of leadership’s crisis solutions, most of them are secular in essence due to the roles of revelations that have been continuously ignored and seen as irrelevant in the postmodern era. Therefore, this qualitative study aims to provide solutions to leadership failure through the exploration of the Quran and Sunnah. This study utilises the content analysis method to collect data whereby it combines descriptive and analytical approaches. First, the indicators of leadership incompetence are identified. Next, the solutions to these issues are analysed based on the Quran and Prophetic Sunnah. The result demonstrates that the Quran and Sunnah provide the best solution in solving leadership failure. Moreover, the divine revelations provide guidance to be a good leader for society so that a strong community will be built. The article unfolds five solutions, namely self-assessment before becoming a leader, selection of a strong and highly moral/ virtuous individual as a leader, fair distribution of wealth and opportunities, implementation of a just retribution system, and providing equal rights to different levels of people. Hence, the study is significant in emphasising the roles of revelation that should not be abandoned due to the timeless characteristics of the Quran and Sunnah.
The Potential Use of Anthocyanin in Butterfly Pea (Clinoteria ternatea) Petals as Colorimetric Indicator in Intelligent Food Packaging Article
Authors: Omar Siti Radhiah , NOH AHMAD ADHAM , ROHAIZAN AHMAD NAIM
Published: November 2022

Butterfly pea is a perennial leguminous twiner that lives within the tropical belt and certain warm areas. Butterfly pea contains anthocyanin that are highly sensitive towards any change of pH, making them suitable to be used as pH indicator. The mechanism of the pH sensing capabilities of anthocyanin from butterfly pea involves four reversible structure of anthocyanin that are present in different range of pH: flavylium cation, hemiketal, quinonoid base and chalcone. Colorimetric indicator is a tool that are used in an intelligent food packaging. Its purpose in intelligent food packaging is to provide information of the food contained inside through colour changes that are visible to naked eyes. This colorimetric indicator utilizes pH indicator to assess the freshness of the food by measuring the change of pH that the product undergoes. Anthocyanin from butterfly pea provides an option of natural and organic pH indicator as opposes to synthetic pH indicators that can cause health issues. Anthocyanin from butterfly pea is capable to react towards any change of pH both acidic and basic, stable at least up to 60 days and are organic, perfect to be used in intelligent food packaging and other food related purposes.
Synthesis of Graphene based nanocomposites and their application – A Review
Authors: Abdul Rashid Affa Rozana , Ahmad Tarmizi‬‬‬‬‬ Syaidatul Husna
Published: November 2022

There are two categories in the graphene preparations which are top-down and bottom-up methods. Top-down methods consist of mechanical exfoliation, chemical exfoliation and chemical synthesis reduction. Meanwhile, chemical vapor deposition (CVD), pyrolysis and epitaxial growth synthesis under bottom-up methods. Graphene has its own limitation and unsuitable for certain applications. Thus, functionalizing the graphene with selected molecules and nanomaterials may result in graphene functionalized nanomaterials that improve the feature of the graphene. Many methods can be done to synthesise graphene based on nanocomposites and cab be divided into two types which are in-situ methods and ex-situ methods. Hydrothermal methods, electrochemical deposition methods and reduction methods are categorized in in-situ methods, while covalent interaction and non-covalent interaction are categorized in ex-situ methods. Application of graphene based nanocomposite on biosensor and supercapacitor is discussed in this review paper.
Cold Bonded and Low Temperature Sintered Artificial Aggregate Production by Using Waste Materials
Authors: Ibrahim Mais Abdulrazzaq , Atmaca Nihat
Published: November 2022

The paper presented the possibility of manufacturing aggregates from industrial waste materials and their ecological benefits. The cold bonding process to create aggregates uses substantially less energy than the sintering technique. This study deals with the outcomes of an experimental assessment of the physical and strength properties of environment-friendly cold-bonded and sintered fly ash (FA), ground granulated blast furnace slag (GGBFS), and quartz (Q) lightweight aggregates. The waste materials were mixed with Portland cement at 20–50 percent by weight to make artificial lightweight aggregates. To investigate the impacts of temperature on the physical properties, such as crushing strength, density, and water absorption, the pellets were sintered at 300, 600, and 900 °C for an hour. The results show that all the produced aggregates might be categorized as lightweight aggregates due to the combinations' average densities being less than 2,000 kg/m3. The fly ash lightweight aggregates had higher density and crushing strength, as well as decreased water absorption. The density and crushing strength improved somewhat by raising the temperature, while the water absorption decreased with increased temperature. In this research, the most efficient mineral admixture concentration has been evaluated as 50 percent for both fly ash and ground granulated blast furnace slag and 30 percent for quartz for cold-bonded pellets. Furthermore, superior physical qualities have been reported at the 900 °C sintering temperature.
Penerapan Permainan Musical Chair Untuk Meningkatkan Kemampuan Motorik Kasar Anak Kelompok B
Authors: Fitria Fadilatul , Riswandi Fitta Nurisma
Published: November 2022

Penelitian ini berlatarbelakang dari masalah kemampuan motorik kasar anak kurang berkembang dengan baik. Hasil Berdasarkan observasi menunjukkan bahwa 70% kemampuan anak untuk mengikuti gerakan guru sederhana masih belum berkembang. Terlihat dari (1) anak ketika kurang bersemangat mengikuti gerak dan lagu senam, (2) minimnya kegiatan motorik kasar setiap hari, (3) anak jarang memanfaatkan alat permainan kasar. Penelitian ini menggunakan rancangan penelitian tindakan kelas (PTK) dengan subyek penelitian 19 anak kelompok B2 TK Negeri Pembina Kota Semarang. Pengumpulan data yang digunakan yaitu observasi dan dokumentasi. Penelitian ini menggunakan dua siklus dengan 4 perlakuan setiap siklusnya. Hasil penelitian menunjukkan aktivitas guru dalam permainan music chairmemperoleh rata-rata 82,64 dengan kriteria sangat baik dan aktivitas anak mencapai 82,80% dengan kualifikasi sangat baik. Tingkat keantusiasan anak dalam melakukan permainan music chair memperoleh 84,21%. Sehingga dapat dikatakan bahwa permainan kursi musik dapat menjadi salah satu alternatif guru untuk meningkatkan kemampuan motorik kasar anak.

Kata Kunci: Permainan Musical Chair , Motorik Kasar, Kelompok B

 

Latar belakang penelitian ini adalah masalah kemampuan motorik kasar anak yang belum berkembang dengan baik. Berdasarkan observasi menunjukkan bahwa 70% kemampuan anak mengikuti gerakan sederhana guru masih belum berkembang. Hal ini terlihat dari (1) anak kurang antusias mengikuti gerakan dan lagu saat berolahraga, (2) kurangnya aktivitas motorik kasar anak setiap hari, (3) anak jarang menggunakan alat permainan motorik kasar. Penelitian ini menggunakan desain penelitian tindakan kelas (PTK) dengan subjek penelitian 19 siswa kelompok B2 TK Negeri Pembina Kota Semarang. Pengumpulan data yang digunakan adalah observasi dan dokumentasi. Penelitian ini menggunakan dua siklus dengan 4 perlakuan pada setiap siklusnya. Hasil penelitian menunjukkan bahwa aktivitas guru dalam permainan Kursi Musik diperoleh rata-rata 82. 64 dengan kriteria sangat baik dan aktivitas anak mencapai 82,80% dengan kualifikasi sangat baik. Tingkat antusiasme anak dalam bermain kursi musik adalah 84,21%. Sehingga dapat disimpulkan bahwa permainan kursi musik dapat menjadi alternatif bagi guru untuk meningkatkan kemampuan motorik kasar anak.

Kata kunci: Permainan Kursi Musik, Motorik Kotor, Grup B
Pola Asuh Orangtua Generasi Milenial terhadap Perkembangan Sosial Emosional Anak Usia Dini
Authors: Siti Khumaeroh  , Widjayatri RR. Deni
Published: November 2022

Penelitian ini memaparkan tentang bagaimana perilaku sosial emosional anak dengan orangtua yang berasal dari generasi milenial dimana generasi milenial ini lahir bersamaan dengan mulainya teknologi. Subjek penelitian ini yaitu anak usia dini. Pengumpulan data dilakukan menggunakan metode studi literatur dengan melakukan telaah dari berbagai sumber ilmiah. Telaah ini bertujuan untuk mengetahui pola asuh yang diterapkan oleh orangtua dari generasi milenial dan dampaknya terhadap perilaku sosial emosioanl anak usia dini. Berdasarkan telaah studi literatur ini, orangtua di generasi milenial harus memiliki kesadaran tentang penerapan pola asuh di era tekonologi yang memiliki pengaruh besar terhadap perkembangan sosial emosional anak usia dini.

Kata Kunci: Pola Asuh, Generasi Milenial, Sosial Emosional, Anak Usia Dini
PENERAPAN PEMBELAJARAN KOOPERATIF TIPE TWO STAY TWO STRAY UNTUK MENINGKATKAN HASIL BELAJAR SISWA KELAS VII SMP NEGERI 11 KOTA BENGKULU
Authors: Efrialinda Aisyah , Yensy Nurul Astuty , Rahimah Dewi
Published: November 2022

Penelitian bertujuan untuk mengetahui cara meningkatkan hasil belajar dengan penerapan pembelajaran kooperatif tipe two stay two stray. Penelitian ini merupakan tindakan penelitian terhadap suatu  Kelas dengan tehnik pengumpulan data melalui tes hasil belajar siswa. Subjek dalam penelitian adalah Kelas VII F SMP N 11 Kota Bengkulu tahun ajaran 2017/2018 berjumlah 20 siswa. Hasil belajar peserta didik dapat ditingkatkan dengan cara memberikan motivasi kepada peserta didik agar lebih baik lagi dalam melaksanakan pembelajaran dan menekankan peserta didik agar lebih teliti dalam mengerjakan soal, dan menanyakan kesulitan belajar yang peserta didik alami. Peningkatan hasil belajar dilihat dari nilai rata-rata peserta didik pada siklus I sampai siklus III yaitu 67,01; 75,75; 86,72 dengan persentase ketuntasan belajar yaitu 35%; 70%; 90%.
Switching off Inflammation with Diet: A Review of Exclusive Enteral Nutrition in Children with Crohn’s Disease
Authors: Day Andrew S.
Published: November 2022

The specific dietary intervention known as exclusive enteral nutrition (EEN) is well-established as the preferred treatment to induce remission in children with active Crohn’s disease. The majority of children managed with EEN respond well to this intervention, with high rates of mucosal healing, improved nutrition, and enhanced bone health, with few side effects. This dietary therapy, utilising a complete nutritional liquid product, is generally well-tolerated over the short period of induction of remission, but does require substantial changes to routine oral intake and daily patterns. After a period of exclusive use of this therapy, ongoing use of the same formulae (as maintenance enteral nutrition) may prolong remission and prevent relapse. Over the last few years, new reports have advanced our understanding of the mechanisms by which EEN acts: these include modulation of the intestinal microbiota and direct anti-inflammatory effects upon the epithelium. This review highlights key outcomes of EEN in children with Crohn’s disease and highlights the current understanding of the mechanisms of action.
Finding the Limits of Machine Learning in Optimization
Authors: Edwards David A , Gu Binan , Johnston Katherine , Wichman Maia , Zyskin Maxim
Published: November 2022

The initial position and velocity of a robot is given, and the problem posed is to make it stop at the origin in the shortest possible time, given a maximum acceleration and speed. The robot can control its acceleration vector, and hence the full optimization problem can be specified as a Hamiltonian system where the solution will minimize the transit time. This problem is discussed in both the one- and two-dimensional cases. The key control parameter is the acceleration direction; reducing the problem to a one-dimensional optimization opens up several areas of exploration. The direction can be optimized using a global search algorithm, or can be updated periodically using a local search algorithm with a penalty function. Numerical solutions are presented in these cases, including when physical obstacles are included in the penalty function. The one-dimensional optimization also allows the use of reinforced learning to minimize the transit time.
The roles of ING5 in cancer: A tumor suppressor
Authors: Zheng Hua-chuan , Xue Hang , Jiang Hua-mao
Published: November 2022

As a Class II tumor suppressor, ING5 contains nuclear localization signal, plant homeodomain, novel conserved region, and leucine zipper-like domains. ING5 proteins form homodimer into a coil-coil structure, and heterodimers with ING4, histone H3K4me3, histone acetyltransferase (HAT) complex, Tip60, Cyclin A1/CDK2, INCA1 and EBNA3C for the transcription of target genes. The acetylated proteins up-regulated by ING5 are preferentially located in nucleus and act as transcription cofactors, chromatin and DNA binding functions, while those down-regulated by ING5 mostly in cytoplasm and contribute to metabolism. ING5 promotes the autoacetylation of HAT p300, p53, histone H3 and H4 for the transcription of downstream genes (Bax, GADD45, p21, p27 and so forth). Transcriptionally, YY1 and SRF up-regulate ING5 mRNA expression by the interaction of YY1-SRF-p53-ING5 complex with ING5 promoter. Translationally, ING5 is targeted by miR-196, miR-196a, miR-196b-5p, miR-193a-3p, miR-27-3p, miR-200b/200a/429, miR-1307, miR-193, miR-222, miR-331-3p, miR-181b, miR-543 and miR-196-b. ING5 suppresses proliferation, migration, invasion and tumor growth of various cancer cells via the suppression of EGFR/PI3K/Akt, IL-6/STAT3, Akt/NF-κB/NF-κB/MMP-9 or IL-6/CXCL12 pathway. ING5-mediated chemoresistance is closely linked to anti-apoptosis, overexpression of chemoresistant genes, the activation of PI3K/Akt/NF-κB and Wnt/β-catenin signal pathways. Histologically, ING5 abrogation in gastric stem-like and pdx1-positive cells causes gastric dysplasia and cancer, and conditional ING5 knockout in pdx1-positive and gastric chief cells increases MNU-induced gastric carcinogenesis. Intestinal ING5 deletion increases AOM/DSS- induced colorectal carcinogenesis and decreases high-fat-diet weight. The overexpression and nucleocytoplasmic translocation of ING5 are seen during carcinogenesis, and ING5 expression was inversely associated with aggressive behaviors and poor prognosis in a variety of cancers. These findings indicated that ING5 might be used for a molecular marker for carcinogenesis and following progression, and as a target for gene therapy if its chemoresistant function might be ameliorated.
Highly sensitive and specific responses of shrimp gill cells to high pH stress based on single cell RNA-seq analysis
Authors: Ge Qianqian , Wang Jiajia , Li Jitao , Li Jian
Published: November 2022

High pH is one of the main stressors affecting the shrimp survival, growth, and physiology in aquaculture ponds, but the cellular and molecular mechanism responsible for high pH stress has not been elucidated in shrimp. In this study, the shrimp acid-base disturbance and gill cell alterations were significantly observed and then single cell RNA-sequencing (scRNA-seq) was performed to study the sensitive and specific responses of gill cells to high pH stress. Three main gill cell types, including pillar cells, hemocytes and septal cells were identified. By comparative scRNA-seq analysis between control and pH group, the pillar cell was regarded as the target cell type in response to high pH stress with the down-regulation of ammonia excretion and H+ transport related genes and up-regulation of immune related genes. Notedly, high pH resulted in the emergence of a new immune cell subcluster in pillar cells, with immune activation and stress defense states. Pseudotime analysis also showed that the pillar cells could transform into the functionally inhibited ion cell subclusters and functionally activated immune cell subclusters after high pH stress. Further, the regulatory network of pillar cell population was predicted by WGCNA and two transcription factors were identified. In conclusion, these results provide key insights into the shrimp gill cell-type-specific mechanisms underlying high pH stress response at a single-cell resolution.
Clinician's guide to trustworthy and responsible artificial intelligence in cardiovascular imaging
Authors: Szabo Liliana , Raisi-Estabragh Zahra , Salih Ahmed , McCracken Celeste , Ruiz Pujadas Esmeralda , Gkontra Polyxeni , Kiss Mate , Maurovich-Horvath Pal , Vago Hajnalka , Merkely Bela , Lee Aaron M. , Lekadir Karim , Petersen Steffen E.
Published: November 2022

A growing number of artificial intelligence (AI)-based systems are being proposed and developed in cardiology, driven by the increasing need to deal with the vast amount of clinical and imaging data with the ultimate aim of advancing patient care, diagnosis and prognostication. However, there is a critical gap between the development and clinical deployment of AI tools. A key consideration for implementing AI tools into real-life clinical practice is their “trustworthiness” by end-users. Namely, we must ensure that AI systems can be trusted and adopted by all parties involved, including clinicians and patients. Here we provide a summary of the concepts involved in developing a “trustworthy AI system.” We describe the main risks of AI applications and potential mitigation techniques for the wider application of these promising techniques in the context of cardiovascular imaging. Finally, we show why trustworthy AI concepts are important governing forces of AI development.
Comprehensive functional and anatomic assessment of myocardial bridging: Unlocking the Gordian Knot
Authors: Ciliberti Giuseppe , Laborante Renzo , Di Francesco Marco , Restivo Attilio , Rizzo Gaetano , Galli Mattia , Canonico Francesco , Zito Andrea , Princi Giuseppe , Vergallo Rocco , Leone Antonio Maria , Burzotta Francesco , Trani Carlo , Palmieri Vincenzo , Zeppilli Paolo , Crea Filippo , D’Amario Domenico
Published: November 2022

Myocardial bridging (MB) is the most frequent congenital coronary anomaly in which a segment of an epicardial coronary artery takes a tunneled course under a bridge of the myocardium. This segment is compressed during systole, resulting in the so-called “milking effect” at coronary angiography. As coronary blood flow occurs primarily during diastole, the clinical relevance of MB is heterogeneous, being usually considered an asymptomatic bystander. However, many studies have suggested its association with myocardial ischemia, anginal symptoms, and adverse cardiac events. The advent of contemporary non-invasive and invasive imaging modalities and the standardization of intracoronary functional assessment tools have remarkably improved our understanding of MB-related ischemia, suggesting the role of atherosclerotic lesions proximal to MB, vasomotor disorders and microvascular dysfunction as possible pathophysiological substrates. The aim of this review is to provide a contemporary overview of the pathophysiology and of the non-invasive and invasive assessment of MB, in the attempt to implement a case-by-case therapeutic approach according to the specific endotype of MB-related ischemia.
Temporal trends in cardiovascular care: Insights from the COVID-19 pandemic
Authors: Kodsi Matthew , Bhat Aditya
Published: November 2022

In response to the ongoing COVID-19 pandemic, public health care measures have been implemented to limit spread of the contagion and ensure adequate healthcare resource allocation. Correlating with these measures are observed changes in the incidence and outcomes of cardiovascular conditions in the absence of COVID-19 infection. The pandemic has resulted in a reduction in acute coronary syndrome, heart failure and arrhythmia admissions but with worsened outcomes in those diagnosed with these conditions. This is concerning of an underdiagnosis of cardiovascular diseases during the pandemic. Furthermore, cardiovascular services and investigations have decreased to provide healthcare allocation to COVID-19 related services. This threatens an increasing future prevalence of cardiovascular morbidity in healthcare systems that are still adapting to the challenges of a continuing pandemic. Adaption of virtual training and patient care delivery platforms have been shown to be useful, but adequate resources allocation is needed to ensure effectiveness in vulnerable populations.
The diadromous watersheds-ocean continuum: Managing diadromous fish as a community for ecosystem resilience
Authors: Ouellet Valerie , Collins Mathias J. , Kocik John F. , Saunders Rory , Sheehan Timothy F. , Ogburn Matthew B. , Trinko Lake Tara
Published: November 2022

Diadromous fishes play important ecological roles by delivering ecosystem services and making crucial connections along the watersheds-ocean continuum. However, it is difficult to fully understand the community-level impacts and cumulative benefits of diadromous fish migrations, as these species are most often considered individually or in small groups. Their interactions at a community level (e.g., interdependencies such as predation, co-migration, and habitat conditioning) and the connections between their ecosystem roles and functions (e.g., cumulative marine-derived nutrient contributions, impacts on stream geomorphology) are yet to be fully understood. Similarly, freshwater, estuarine, and marine ecosystems are often considered as independent parts, limiting understanding of the importance of connections across systems. We argue that not considering the ecosystem interdependence and importance of diadromous fish as a community currently hinders the implementation of the large-scale management required to increase ecosystem resilience and fish productivity across the full range of these species. We developed a conceptual model, the Diadromous Watersheds-Ocean Continuum (DWOC), that uses ecosystem services to promote a more holistic approach to the management of the diadromous community and encourages an integrated understanding of the ecosystem connections made by these species. DWOC provides a framework for discussions that can help identify research and management needs, discuss the trade-offs of different management options, and analyze what pressing questions impede the implementation of large-scale management solutions toward a more ecosystem-based management approach.
Hsa_circ_0074158 regulates the endothelial barrier function in sepsis and its potential value as a biomarker
Authors: Liao Haiyan , Chai Yan , Sun Yuming , Guo Zhe , Wang Xuesong , Wang Ziyi , Wang Ziwen , Wang Zhong
Published: November 2022

Background: Sepsis is one of the main causes of death in critically ill patients with high morbidity and mortality. Circular RNAs (CircRNAs) are aberrantly expressed, and play significant regulatory roles in many diseases. However, the expression profiles and functions of circRNAs in sepsis have not yet been fully clarified.

Methods: Our present study performed an RNA sequencing (RNA-seq) analysis to assess the expression profiles of circRNAs in vitro. We applied the quantitative real-time polymerase chain reaction (RT-qPCR) to verify the RNA-seq results. The analyses of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the competitive endogenous RNA (ceRNA) regulatory networks, were performed to explore the potential mechanism in sepsis. And then, significantly up-regulated differentially expressed (DE) circRNA, hsa_circ_0074158, was selected for further study. Hsa_circ_0074158 was silenced to investigate its regulatory function in sepsis, and the barrier function was also examined in vitro. Endothelial cell junctions were valued using Vascular endothelial cadherin (VE-cadherin), which was detected by immunofluorescence staining. We measured endothelial permeability by transendothelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran extravasation.

Results: In total, 203 significantly DE circRNAs, including 77 up-regulated and 126 down-regulated, were identified. In vitro, the RT-qPCR assay showed that the expression pattern of hsa_circ_0074158, hsa_circ_RSBN1L_11059, hsa_circ_0004188, and hsa_circ_0005564 were consistent with the results from RNA-seq analysis. The expression of hsa_circ_0074158 detected by RT-qPCR in vivo was also consistent with the RNA-seq results. The ceRNA networks, GO enrichment, and the KEGG pathway analyses revealed that circRNAs may be related to the barrier function in sepsis. The immunofluorescence assay showed that the suppression of hsa_circ_0074158 expression significantly enhanced the expression of VE-cadherin, which was suppressed in lipopolysaccharide (LPS)-induced sepsis. Additionally, hsa_circ_0074158 knockdown could partially reverse the LPS-induced TEER reduction and FITC-dextran extravasation elevation in sepsis.

Conclusion: In conclusion, we have found DE circRNAs could serve as potential biomarkers and therapeutic targets for sepsis. Hsa_circ_0074158 plays a vital role in sepsis and is related to the disruption of the endothelial barrier.
Case report: Familial glycogen storage disease type IV caused by novel compound heterozygous mutations in a glycogen branching enzyme 1 gene
Authors: Li Yiyang , Tian Chuan , Huang Si , Zhang Weijie , Liutang Qiuyu , Wang Yajun , Ma Guoda , Chen Riling
Published: November 2022

Glycogen storage disease type IV (GSD IV), caused by a mutation in the glycogen branching enzyme 1 (GBE1) gene, is a rare metabolic disorder with an autosomal recessive inheritance that involves the liver, neuromuscular, and cardiac systems. Here, we reported a case of familial GSD IV induced by novel compound heterozygous mutations in GBE1. The proband (at age 1) and her younger brother (at age 10 months) manifested hepatosplenomegaly, liver dysfunction, and growth retardation at onset, followed by progressive disease deterioration to liver cirrhosis with liver failure. During the disease course, the proband presented rare intractable asymptomatic hypoglycemia. The liver pathology was in line with GSD IV. Both cases carried pathogenic compound heterozygous mutations in GBE1 mutations, i.e., a missense mutation (c.271T>A, p. W91R) in exon 2 and a deletion mutation in partial exons 3–7. Both mutations are first reported. The internationally pioneered split-liver transplantation was performed during progression to end-stage liver disease, and the patients had normal liver function and blood glucose after. This study broadens the mutation spectrum of the GBE1 gene and the phenotypic spectrum of GSD IV.
Eastern king prawn Penaeus plebejus stock enhancement—Genetic evidence that hatchery bred prawns have survived in the wild after release
Authors: Premachandra H. K. A. , Becker Alistair , Taylor Matthew D. , Knibb Wayne
Published: November 2022

Eastern king prawn (Penaeus plebejus) is endemic to eastern Australia and is of high commercial and recreational value. As part of a recreational fisheries enhancement initiative, hatchery reared juveniles from Queensland were released into two, more Southern New South Wales (NSW) estuaries between 2014 and 2015. Responsible stock enhancement programs rely on knowledge of the population structure of the released species. Previously, in consideration of fisheries data, it was assumed the king prawn populations in Australia are one single breeding stock. In the present study, our first aim was to test this posit of no genetic differentiation using mtDNA control region (mtCR) sequences from the wild samples collected from four estuaries ranging from Queensland/NSW border (source of the stocked animals) to Southern NSW. The second objective was to test for signals of hatchery-released animals in the two stocked estuaries. All four surveyed populations had an extremely high level of haplotype diversity (average h = 99.8%) and low level of haplotype sharing between populations. Estimates of PhiPT values were <0.01 or close to zero and AMOVA test did not indicate any significant differences among populations. Further, phylogenetic analysis and principal coordinate analysis did not support division of samples by population. Collectively these results suggest that eastern king prawn populations along the NSW coast can be considered as a single stock and stocking from the Queensland samples will not necessarily impact the genetic composition of the overall stock. After stocking of two estuaries, sharing of haplotypes was moderate to very high in the stocked sites (>80% in some collections) but negligible in the two unstocked estuaries (≤2%, which is assumed to be background coancestry unrelated to the hatchery). Moreover, some haplotypes present in the hatchery broodstock were detected in stocked sites, but not in unstocked sites. The highest stocking signal was detected in the estuary which becomes isolated from the sea by sand barrier suggesting such “lakes” maybe more favourable for stocking than estuaries directly open to the sea. Findings in the current study should assist in designing and implementation of future prawn stocking programs.
Safety and immunogenicity of heterologous recombinant protein subunit vaccine (ZF2001) booster against COVID-19 at 3–9-month intervals following two-dose inactivated vaccine (CoronaVac)
Authors: Liao Yuting , Chen Yingping , Chen Bo , Liang Zhenzhen , Hu Xiaosong , Xing Bo , Yang Juan , Zheng Qianhui , Hua Qianhui , Yan Chuanfu , Lv Huakun
Published: November 2022

Background

In response to SARS-CoV-2 mutations and waning antibody levels after two-dose inactivated vaccines, we assessed whether a third dose of recombinant protein subunit vaccine (ZF2001) boosts immune responses.

Methods

An open-label single-center non-random trial was conducted on people aged 18 years and above at five sites in China. All participants received a two-dose inactivated vaccine (CoronaVac) as their prime doses within 3–9 months of the trial. Primary outcomes were safety and immunogenicity, primarily the geometric mean titers (GMTs) of neutralizing antibodies to live wildtype SARS-CoV-2.

Results

A total of 480 participants (median age, 51; range 21–84 years) previously vaccinated with two-dose CoronaVac received a third booster dose of ZF2001 3–4, 5–6, or 7–9-months later. The overall incidence of adverse reactions within 30 days after vaccination was 5.83% (28/480). No serious adverse reactions were reported after the third dose of ZF2001. GMTs in the 3–4-, 5–6-, and 7–9-month groups before vaccination were 3.96, 4.60, and 3.78, respectively. On Day 14, GMTs increased to 33.06, 47.51, and 44.12, respectively. After the booster, GMTs showed no significant difference among the three prime-boost interval groups (all P>0.05). Additionally, GMTs in older adults were lower than those in younger adults on Day 14 for the three groups (P=0.0005, P<0.0001, and P<0.0001).

Conclusion

Heterologous boosting with ZF2001 was safe and immunogenic, and prime-boost intervals did not affect the immune response. The immune response was weaker in older than younger adults.
CD4+CD25+ T regulatory cells in renal transplantation
Authors: Cheung Jason , Zahorowska Beata , Suranyi Michael , Wong Jeffrey K. W. , Diep Jason , Spicer Stephen T. , Verma Nirupama D. , Hodgkinson Suzanne J. , Hall Bruce M.
Published: November 2022

The immune response to an allograft activates lymphocytes with the capacity to cause rejection. Activation of CD4+CD25+Foxp3+T regulatory cells (Treg) can down-regulate allograft rejection and can induce immune tolerance to the allograft. Treg represent <10% of peripheral CD4+T cells and do not markedly increase in tolerant hosts. CD4+CD25+Foxp3+T cells include both resting and activated Treg that can be distinguished by several markers, many of which are also expressed by effector T cells. More detailed characterization of Treg to identify increased activated antigen-specific Treg may allow reduction of non-specific immunosuppression. Natural thymus derived resting Treg (tTreg) are CD4+CD25+Foxp3+T cells and only partially inhibit alloantigen presenting cell activation of effector cells. Cytokines produced by activated effector cells activate these tTreg to more potent alloantigen-activated Treg that may promote a state of operational tolerance. Activated Treg can be distinguished by several molecules they are induced to express, or whose expression they have suppressed. These include CD45RA/RO, cytokine receptors, chemokine receptors that alter pathways of migration and transcription factors, cytokines and suppression mediating molecules. As the total Treg population does not increase in operational tolerance, it is the activated Treg which may be the most informative to monitor. Here we review the methods used to monitor peripheral Treg, the effect of immunosuppressive regimens on Treg, and correlations with clinical outcomes such as graft survival and rejection. Experimental therapies involving ex vivo Treg expansion and administration in renal transplantation are not reviewed.
Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in mice
Authors: Garcia-Dominguez Dario , Henry Carole , Ma LingZhi , Jani Hardik , Amato Nicholas J. , Manning Taylor , Freyn Alec , Davis Heather , Hsiao Chiaowen Joyce , Li Mengying , Koch Hillary , Elbashir Sayda , DiPiazza Anthony , Carfi Andrea , Edwards Darin , Bahl Kapil
Published: November 2022

For a vaccine to achieve durable immunity and optimal efficacy, many require a multi-dose primary vaccination schedule that acts to first “prime” naive immune systems and then “boost” initial immune responses by repeated immunizations (ie, prime-boost regimens). In the context of the global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 2-dose primary vaccination regimens were often selected with short intervals between doses to provide rapid protection while still inducing robust immunity. However, emerging post-authorization evidence has suggested that longer intervals between doses 1 and 2 for SARS-CoV-2 vaccines may positively impact robustness and durability of immune responses. Here, the dosing interval for mRNA-1273, a messenger RNA based SARS-CoV-2 vaccine administered on a 2-dose primary schedule with 4 weeks between doses, was evaluated in mice by varying the dose interval between 1 and 8 weeks and examining immune responses through 24 weeks after dose 2. A dosing interval of 6 to 8 weeks generated the highest level of antigen-specific serum immunoglobulin G binding antibody titers. Differences in binding antibody titers between mRNA-1273 1 µg and 10 µg decreased over time for dosing intervals of ≥4 weeks, suggesting a potential dose-sparing effect. Longer intervals (≥4 weeks) also increased antibody-dependent cellular cytotoxicity activity and numbers of antibody-secreting cells (including long-lived plasma cells) after the second dose. An interval of 6 to 8 weeks elicited the strongest CD8+ T-cell responses, while an interval of 3 weeks elicited the strongest CD4+ T-cell response. Overall, these results suggest that in a non-pandemic setting, a longer interval (≥6 weeks) between the doses of the primary series for mRNA-1273 may induce more durable immune responses.
Artificial intelligence-based immunoprofiling serves as a potentially predictive biomarker of nivolumab treatment for advanced hepatocellular carcinoma
Authors: Lee Jan-Mou , Hung Yi-Ping , Chou Kai-Yuan , Lee Cheng-Yun , Lin Shian-Ren , Tsai Ya-Han , Lai Wan-Yu , Shao Yu-Yun , Hsu Chiun , Hsu Chih-Hung , Chao Yee
Published: November 2022

Immune checkpoint inhibitors (ICI) have been applied in treating advanced hepatocellular carcinoma (aHCC) patients, but few patients exhibit stable and lasting responses. Moreover, identifying aHCC patients suitable for ICI treatment is still challenged. This study aimed to evaluate whether dissecting peripheral immune cell subsets by Mann-Whitney U test and artificial intelligence (AI) algorithms could serve as predictive biomarkers of nivolumab treatment for aHCC. Disease control group carried significantly increased percentages of PD-L1+ monocytes, PD-L1+ CD8 T cells, PD-L1+ CD8 NKT cells, and decreased percentages of PD-L1+ CD8 NKT cells via Mann-Whitney U test. By recursive feature elimination method, five featured subsets (CD4 NKTreg, PD-1+ CD8 T cells, PD-1+ CD8 NKT cells, PD-L1+ CD8 T cells and PD-L1+ monocytes) were selected for AI training. The featured subsets were highly overlapping with ones identified via Mann-Whitney U test. Trained AI algorithms committed valuable AUC from 0.8417 to 0.875 to significantly separate disease control group from disease progression group, and SHAP value ranking also revealed PD-L1+ monocytes and PD-L1+ CD8 T cells exclusively and significantly contributed to this discrimination. In summary, the current study demonstrated that integrally analyzing immune cell profiling with AI algorithms could serve as predictive biomarkers of ICI treatment.