bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of SMEs Empowerment in Bangka Belitung Islands Province in 2023
Authors: Febriyani Lintri , Leksono Binar Kukuh , Zulfikar Ahmad , Putra Juang
Published: January 2024

The Small and Medium-sized Enterprises (SMEs) sector is one of the backbones of the Indonesian economy, but it still faces various obstacles. The government aims to support SMEs through allocated funds. In the 2022 State Budget, Bangka Belitung Islands Province received an allocation of IDR 13.47 billion for the Economic Recovery cluster. Additionally, the Local Budget allocation of IDR 8.19 billion was divided into two programs: SMEs Empowerment (IDR 6.5 billion) and SMEs Development (IDR 1.69 billion). Among the SMEs, the largest sectors are Agriculture, Forestry, and Fisheries. However, SMEs in Bangka Belitung Islands Province have not fully optimized financing facilities, with only IDR 6 trillion accessed from the total credit ceiling of IDR 14.3 trillion offered by commercial banks. The proportion of People’s Business Credit/Ultra Micro Debtors to Bangka Belitung Islands Province SMEs is only 21.68 percent. Focused Group Discussions (FGDs) and surveys were conducted involving 42 SME actors to research the situation in Bangka Belitung Islands Province. The survey results highlighted that the availability of capital and limited access to marketing are the most significant obstacles for SMEs in the area. Furthermore, other challenges include inadequate technology/machinery, qualified human resources, training opportunities from relevant parties, and difficulties in obtaining raw materials. The survey also revealed that SME actors expect training in technical guidance and offline course classes, moving away from mere socialization methods.
Öğretmen Adaylarının Fizik Kaygılarını Yordayan Değişkenlerin C5.0 Karar Ağacı Algoritması ile İncelenmesi
Authors: Sütçü Kerem , Kırgın Özgür
Published: January 2024

Araştırmada, öğretmen adaylarının fizik kaygılarını yordayan değişkenlerin C5.0 karar ağacı algoritması ile incelenmesi amaçlanmıştır. İlişkisel araştırma niteliğinde olan bu çalışmada, veriler “Fizik Kaygı Ölçeği” ile 186 öğretmen adayından toplanmıştır. Araştırmadan elde edilen verilerin analizinde ilk aşamada İki Aşamalı Kümeleme Analizi, ikinci aşamada C5.0 Karar Ağacı Algoritması kullanılmıştır. Araştırmada öğretmen adaylarının çoğunun fizik dersi/sınav kaygılarının yüksek, matematik kaygılarının orta, fizik bilgisi eksikliği ve fizik laboratuvar kaygılarının düşük ve orta düzeyde olduğu ortaya çıkmıştır. Fizik dersi/sınav ve fizik bilgisi eksikliği kaygısı boyutu üzerinde etki düzeyi en yüksek olan değişkenin öğretmen adaylarının genel akademik not ortalamaları olduğu tespit edilmiştir. Bununla birlikte matematik kaygısı boyutu üzerinde öğretmen adaylarının yaşları ve fizik laboratuvarı kaygısı boyutu üzerinde ise öğretmen adaylarının cinsiyetleri olduğu tespit edilmiştir.
Öğrencilerin Sosyoekonomik Durumu, İçsel Motivasyonu ve Okulun Başarıya Verdiği Önemin Öğrencilerin Matematik Başarılarına Etkisi
Authors: Ersan Ozge , Çobanoğlu Aktan Derya
Published: January 2024

Bu çalışmada öğrencilerin sosyoekonomik durumu, matematik öğrenmeyi sevmeleri, okullarının akademik başarıya verdikleri önem ile öğrenci matematik başarısı arasındaki ilişki çok düzeyli yapısal eşitlik modeliyle (ÇDYEM) incelenmiştir. Araştırmada örneklem TIMSS 2011 çalışmasına katılan Türkiye’deki 5960 sekizinci sınıf öğrencisidir. Araştırma bulguları öğrencilerin matematik başarı varyansının %33’ünün okullar arası farklılıklardan, %67’sinin öğrenciler arası farklılıklardan kaynaklandığını göstermiştir. ÇDYEM’de, öğrenci düzeyinde öğrencilerin sosyoekonomik durum ve öğrencilerin matematik öğrenmeyi sevmeleri, okul düzeyinde yine sosyoekonomik durum ve okullarının matematik başarısına verdiği önem yer alarak her iki düzeyde de bu değişkenlerin matematik başarısıyla ilişkisi modellenmiştir. Bulgulara göre sosyoekonomik durumu yüksek olan öğrencilerin bireysel başarıları; dolayısıyla bu öğrencilerin bulunduğu okulların ortalama başarıları diğer okullara göre nispeten daha yüksektir. Okul düzeyindeki sosyoekonomik durumun okulun akademik başarıya önem vermesini pozitif yönde etkileyerek okulların daha yüksek başarıya sahip olmalarına katkı sağladığı görülmüştür. Ayrıca, matematik öğrenmeyi seven öğrencilerin daha yüksek matematik başarısına sahip olduğu bulgusuna ulaşılmıştır. Son olarak, araştırma bulgularına dayanarak eğitim politikaları kapsamında önerilerde bulunulmuştur.
PEMBUATAN SABUN CUCI PIRING UNTUK PENGEMBANGAN KETERAMPILAN IBU RUMAH TANGGA DAN UKM DI KELURAHAN BERTAIS, KOTA MATARAM
Authors: Idawati Sri , Hardani Hardani , Andriani Helmina , Widyan Rosnalia
Published: January 2024

Pelatihan serta praktek pembuatan sabun cuci piring cair di Kelurahan Bertais, Kota Mataram telah dilaksanakan dengan baik. Minimnya pengetahuan para ibu rumah tangga tentang cara pembuatan sabun cuci piring telah membuat tertutupnya peluang bisnis di Kelurahan Bertais. Pelatihan ini bertujuan untuk meningkatkan pengetahuan dan kreatifitas ibu rumah tangga dalam membuat sabun cuci piring cair yang bernilai jual. Dalam pelatihan ini peralatan produksinya mudah ditemukan dan bahan baku pembuatan mudah diperoleh di toko bahan kimia dan harganya sangat terjangkau. Pelatihan ini dimulai dengan pemberian materi terlebih dahulu mengenai sifat dan fungsi setiap bahan, kemudian dilanjutkan dengan praktek pembuatan sabun cuci piring cair. Setelah selesai pelatihan dari 25 peserta yang mengikuti pelatihan menunjukkan peningkatan pemahaman mengenai cara pembuatan sabun cuci piring cair yang baik dan benar.
MARKETING STRATEGY FOR MSME HEALTH BEVERAGE PRODUCTS
Authors: Sahbany Sri , Irawansyah Irawansyah , Riscal Detty Agustin , Hijriani Baiq Isti , Ustiawaty Jumari , Aminullah Andi Muhammad , Ismatullah Nurul Khatimah , Suhada Adriyan
Published: January 2024

In Indonesia, you often find drinks labeled "healthy drinks" which are commonly consumed by the public, but the process of making healthy drinks takes quite a lot of time and effort so it's not wrong, especially as the best-selling position is added by ready-to-drink drinks with contemporary flavor variants. Therefore, to overcome this problem, a new innovation was carried out by producing health drinks using local ingredients. The problem formulation taken is how to market health drinks. For this reason, the aim of the service regarding the marketing of health drinks is expected to be a breakthrough in making people aware to choose health drinks more wisely. The location of this service activity is in Bagikpolak Village, Labuapi District, West Lombok Regency. Socialization activities regarding the socialization of health drink marketing strategies have been carried out using lecture, discussion and question and answer methods. In general, this service activity ran smoothly. Based on this, the conclusion that can be drawn is that participants in service activities know beverage marketing strategies wisely, rationally and appropriately to convey to other communities.
SOSIALISASI SINTA DALAM UPAYA PENINGKATAN KAPASITAS DOSEN
Authors: Sukmana Dhika Juliana , Fardani Roushandy Asri , Hardani Hardani
Published: January 2024

SINTA adalah system informasi penelitian berbasis web yang dapat dijadikan sebagai indicator kinerja dan penting bagi pengembangan karir dosen. Bagi dosen baru, SINTA masih terdengar asing, sehingga perlu disosialisasikan. Tujuan kegiatan ini adalah untuk memberikan gambaran pengetahuan tentang SINTA bagi dosen baru. Kegiatan ini dilakukan dengan sosialisasi yang diiringi dengan tanya jawab. Hasil dari kegiatan ini adalah 100% peserta sudah memahami apa itu SINTA dan pentingnya ISNTA bagi perkembangan karir dosen.
Unleash the Potential of Mystery, Ghost & Paranormal Tourism through the lens of locals in Kuldhara, Rajasthan, India: A qualitative study
Authors: SINGH KULDEEP , Sharma Reena , Bagri S.C.
Published: January 2024

Mystery tourism is a novel topic related to travelling to events or destinations based on some stories, myths, beliefs of the host community or tourists. This also includes the myths and curiosity of locals and travelers about some known and unknown incidents or places. This paper aims to find out the experiences and perceptions of locals regarding mystery tourism in Kuldhara, Rajasthan. Ghost tours, paranormal investigations, and haunted stories have attracted many tourists to Kuldhara. In-depth interviews with 25 residents of Kuldhara, Rajasthan, reveal that residents have positive beliefs and ideologies regarding ghosts and paranormal activities. The study took in year (March 2022 to Feb 2023). The researchers identified purposive sampling and snow balling which has been used in previous studies too. This study is qualitative, and researchers employed thematic analysis techniques manually. Five major themes emerged from mystery tourism in Kuldhara, i.e., Myth & Tales, Perception of locals, Role of Government and Private bodies, Impact of mystery tourism and economic benefits. The study reveals that most locals face mysterious incidents and believe in ghosts and paranormal activities. This study generates curiosity among the readers and researchers to understand and explore the concepts of mystery tourism in a better way. Implications for developing mystery tourism attractions and support for resident well-being are offered.
Wine tourism and COVID-19: impacts and responses from the perspective of wine route’s wineries
Authors: Cerezo-Medina Alfonso , Peláez-Verdet Antonio , Gaspar-González Ana Isabel , Martin-Rojo Inmaculada Concepción
Published: January 2024

Wine tourism is a subsector of gastronomic tourism that, according to the World Tourism Organisation, has been increasingly in demand among visitors worldwide. The Serranía de Ronda has an outstanding wine-growing tradition, but the region has had to deal with one of the most significant challenges in recent times: the coronavirus disease-19 pandemic. This study analyzed the crisis’s impacts on wine tourism along the Ronda and Malaga Wine Route, winemakers’ perceptions of these effects, and how wineries reacted. Exploratory mixed-methods research was carried out using a combination of primary and secondary sources. The results were compared to other studies that have also sought to analyse wineries’ recovery strategies associated with the pandemic. The findings have practical implications that can help wine tourism providers improve their resilience during future pandemics.
Geotourism management for sustainable development of tourism: A bibliometric analysis of the main research areas and domains of knowledge
Authors: Hernández-Garrido Rocío , Orts-Cardador Jaime , Perez-Calañas Cinta
Published: January 2024

Geotourism has attracted an increasing academic interest in recent years due to the new demands of society for sustainable and alternative destinations and its their effective management is essential. This study conducts a comprehensive bibliometric analysis of geotourism management covering research published from 1991 to June 2023. The objective of this study is to perform a bibliometric analysis to demonstrate the current research and key findings on geotourism management. In addition, we identify the existing limitations in the current literature to show research trends and future directions. To achieve this objective, we analysed 813 publications with 10,937 cited references from Web of Science. Our analysis encompassed three key bibliometric techniques (co-authorship, co-citation and co-occurrence of keywords). The main results show the increasing popularity and investigations in geotourism and destination management. Using mapping techniques, our study shows the relevance of research in geoconservation, sustainable tourism and, to a lesser extent, in geological heritage. The findings contribute to a broad and diverse understanding of the management of geotourism, which can provide insights for DMOs and policymakers in establishing proper management in geotourism to ensure conservation in geodestinations.
Extracellular vesicles as next-generation therapeutics and biomarkers in amyloidosis: a new frontier
Authors: Phan Thanh Huyen , Reed Joanne H.
Published: January 2024

Nanoparticles hold a great potential for therapeutic targeting due to their ability to improve the stability of encapsulated cargo and promote the transport of cargo across membranes to reach to the target site. Most commercially available nanomedicines are simple synthetic liposomes, however, there are numerous side effects due to their off-target delivery and rapid clearance from the bloodstream. Recently, attention has moved toward extracellular vesicles (EVs)–lipid bilayer enclosed particles released by cells (size ranging from 30 to 10,000 nm in diameter). EVs carry and transport lipids, proteins, and nucleic acids from their parental cells to recipient cells, hence they play a key role in intercellular communication. The ability of EVs to cross biological barriers including the blood brain barrier has generated significant attention to explore them as potential biomarkers and natural drug delivery vehicles for various therapeutics and small molecules. EVs have also been implicated in disease pathogenesis by transmitting pathogenic proteins between cells, making them promising biomarkers for disease diagnosis and monitoring. In this review, we will focus on the potential and challenges of EVs as biomarkers, drug delivery vehicles and next-generation therapeutics. Finally, we will explore misfolded protein disorders, amyloidosis, as a case study for how EVs may contribute to disease pathology and how EVs could be applied in the clinic as diagnostic and prognostic biomarkers of amyloid diseases.
Component-based estimation of recovery time and time-related expenses after hurricane events
Authors: Wei Zhuoxuan , Pinelli Jean-Paul , Gurley Kurtis , Hamid Shahid , Flannery Gail
Published: January 2024

Introduction: Due to hurricane damage, building residents or businesses must be relocated during the recovery time, which leads to time-related expenses (TRE), also known as additional living expenses (ALE) or extra expense coverage (EEC) or business interruption insurance (BIC). TRE are difficult to predict since they depend on the damage and time necessary to repair the building as well as on external factors such as damaged utilities and the availability of labor and materials, among other issues.

Methods: In this study, we developed a new TRE hurricane vulnerability model for mid/high-rise buildings. The model combines estimates of repair time (Trepair), delay time (Tdelay), and utilities downtime (Tdown) to predict overall recovery time (Treco).

Results: The outputs of the model include 1) TRE vulnerability matrices, which yield probabilities of Trepair, Tdelay, Tdown, Treco, and TRE conditional on either maximum 3-s wind speed or overall building damage ratio; 2) the corresponding vulnerability curves, which yield the mean values as a function wind speed or damage ratio.

Discussion: Insurers can use these results to project TRE, and emergency managers and urban planners can use the recovery times to characterize the resilience of coastal communities. This paper summarizes the methodology and illustrates its implementation and results. The selected results of Treco are compared with the recovery times provided using the HAZUS-MH Hurricane Model.
Mucosal microbiome of surgically treated terminal ileal Crohn’s disease
Authors: Loch Florian N. , Kamphues Carsten , Menzel Peter , Schwarzer Rolf , Beyer Katharina , Schineis Christian
Published: January 2024

Crohn’s disease (CD) is associated with changes in the microbiome. The role of these changes and their precise association with disease course and activity remain ambiguous. In this prospective single-center study, the mucosal microbiome of surgical CD and non-CD patients was compared at the time of surgery. Microbial analyses were individually performed for ileal and colonic tissue samples obtained during surgery using 16S-rRNA-gene amplicon sequencing. Three groups out of the 46 included patients were formed: 1) a study group of CD of patients who received ileocecal resection due to CD involvement (CD study, n=10); 2) a control group of non-CD of patients who received intestinal resection due to indications other than CD (non-CD control, n=27); and 3) a second control group of CD who underwent resection of the intestine not affected by CD (CD non-affected control, n=9). Species richness and Shannon diversity were not different between all formed groups and regions analyzed (p>0.05). Several significant taxonomic differences were seen at the phylum-, order-, and genus-levels between the formed groups, such as a decrease of Firmicutes (phylum-level) and an increase of Bacteroides and Escherichia/Shigella/Pseudescherichia (genus-level) in CD study – colon vs. the non-CD control – colon (p ≤ 0.05). The CD non-affected control presented the largest amount of differentially abundant taxa in comparison to the other groups. These results underline that CD is accompanied by changes in affected and non-affected intestinal regions compared to non-CD controls. This study contributes the mucosal microbiome of a well-defined subset of surgical CD patients without confounding aspects of the fecal microbiome or regional microbial differences to the existing literature.
Salvianolic acids and its potential for cardio-protection against myocardial ischemic reperfusion injury in diabetes
Authors: Jiang Yuxin , Cai Yin , Han Ronghui , Xu Youhua , Xia Zhengyuan , Xia Weiyi
Published: January 2024

The incidence of diabetes and related mortality rate increase yearly in modern cities. Additionally, elevated glucose levels can result in an increase of reactive oxygen species (ROS), ferroptosis, and the disruption of protective pathways in the heart. These factors collectively heighten the vulnerability of diabetic individuals to myocardial ischemia. Reperfusion therapies have been effectively used in clinical practice. There are limitations to the current clinical methods used to treat myocardial ischemia-reperfusion injury. As a result, reducing post-treatment ischemia/reperfusion injury remains a challenge. Therefore, efforts are underway to provide more efficient therapy. Salvia miltiorrhiza Bunge (Danshen) has been used for centuries in ancient China to treat cardiovascular diseases (CVD) with rare side effects. Salvianolic acid is a water-soluble phenolic compound with potent antioxidant properties and has the greatest hydrophilic property in Danshen. It has recently been discovered that salvianolic acids A (SAA) and B (SAB) are capable of inhibiting apoptosis by targeting the JNK/Akt pathway and the NF-κB pathway, respectively. This review delves into the most recent discoveries regarding the therapeutic and cardioprotective benefits of salvianolic acid for individuals with diabetes. Salvianolic acid shows great potential in myocardial protection in diabetes mellitus. A thorough understanding of the protective mechanism of salvianolic acid could expand its potential uses in developing medicines for treating diabetes mellitus related myocardial ischemia-reperfusion.
Does the green finance reform and innovation experimental zone policy reduce carbon emission intensity? Evidence from Chinese cities
Authors: Yang Yun , Peng Chunli
Published: January 2024

The reduction of carbon emission intensity cannot be achieved without policy support, of which green financial policy is a major component. The main aim of this study is to discuss the causality between the green finance reform and innovation (GFRI) experimental zone policy and the intensity of carbon emissions in China. Using data from 265 Chinese cities from 2005 to 2021, this study applies a time-varying difference-in-differences (DID) model to assess the effect of the GFRI experimental zone policy on the intensity of carbon emissions. The heterogeneity of impacts and the parallel-serial mediation effect of this experimental zone policy are discussed further. The following main findings are obtained. (1) The GFRI experimental zone policy dramatically reduces carbon emission intensity, and this effect is more prominent in cities with large sizes of credit and bond finance. (2) After considering the heterogeneity of government environmental concerns and fiscal pressures, this study reveals that the effect of the GFRI experimental zone policy on reducing carbon emission intensity is weaker in cities with high numbers of environmental protection penalties and fiscal pressures. As the number of environmental penalties and fiscal pressures increases, the effect of the GFRI experimental zone policy on reducing carbon emission intensity decreases; that is, the phenomenon of environmental protection paradoxes and policy conflicts has emerged. (3) Increasing financing for green projects and decreasing the energy intensity of the industry are the primary mediating channels for GFRI experimental zone policy to reduce carbon emission intensity, but the mediating channels for boosting green innovation and promoting energy structure adjustment are not prominent. Moreover, the total effect of the GFRI experimental zone policy on reducing carbon emission intensity is 72% direct and more than 20% indirect. This study concludes that in regions with high fiscal pressure, governments should rely more on green finance to decrease carbon emission intensity. Meanwhile, a green finance policy must be more supportive of zero-carbon energy production and reduce direct environmental penalties to decrease carbon emission intensity in the future.
A comprehensive evaluation method for moisture and aging state of oil-immersed paper bushings based on dielectric modulus and K-nearest neighbor algorithm
Authors: Liang Zhengping , Sun Yongbin , Cheng Hao , Zhang Na , Li Bo , Liu Yang , Fang Yan , Zhang Yiyi
Published: January 2024

The insulation performance of oil-immersed paper bushings is prone to deteriorate, primarily due to moisture intrusion and thermal aging. The frequency domain spectroscopy (FDS) method is commonly employed to assess the insulation condition of the bushing. However, identifying and extracting relaxation polarization information from the low-frequency region of the FDS curve can be challenging, and there is little research about the condition evaluation under the combined effects of aging states and moisture content. To address this issue, this article uses the Taylor formula mathematical model to extract characteristic parameters from the dielectric modulus curve of OIP bushings and uses the KNN algorithm to achieve the evaluation of aging and moisture status. Then, the effectiveness and accuracy of the proposed method are validated on three field OIP bushings. The results demonstrate that the evaluation accuracy of the proposed method exceeds 83%, which has significant advantages compared to other classification algorithms. The innovation of this article lies in extracting new feature parameters and combining them with intelligent classification algorithms to evaluate the moisture and aging state of the bushing.
Research on the relationship between social capital and sustainable livelihood: evidences from reservoir migrants in the G Autonomous Prefecture, China
Authors: Zhang Huashan , Cao Zhijie , Zhou Kexin , Ji Yuanyuan
Published: January 2024

Although hydropower serves as a clean alternative energy source, the global challenge of resettlement due to dam construction underscores the importance of sustainable livelihoods in achieving the targets of the Sustainable Development Goals (SDGs). In recent years, the sustainable livelihood theory has offered a new perspective for examine the development of livelihoods of reservoir migrants after relocation. However, in-depth relationship between social capital and sustainable livelihoods has not been explored. In this study, three hydropower resettlement areas were selected in the G Autonomous Prefecture of China as an example. Our investigation delved into the influence of social networks, social norms, and social trust on the livelihoods of reservoir migrants. Study employed semi-structured interviews, participant observation, and qualitative analysis to explore this impact. The results show that the traditional social capital stock of reservoir migrants, dominated by family, neighborhood and religious networks, has declined. Therefore, the structural function of modern social capital should be strengthened by increasing the social trust of reservoir migrants in institutions and civil society organizations. The contribution of livelihood diversification in poverty reduction by 2030 (SDG-1) was realized by focusing on the role of social capital to promote infrastructure, improve living conditions and increase employment opportunities for migrants. The findings further point to the need to fully respect the customs and lifestyles of ethnic minorities during the resettlement process of reservoir migrants in order to preserve the role played by their traditional social capital, thereby promoting the sustainable development of the livelihoods of reservoir migrants.
Expanding the genetic spectrum of mitochondrial diseases in Tunisia: novel variants revealed by whole-exome sequencing
Authors: Gouiza Ismail , Hechmi Meriem , Zioudi Abir , Dallali Hamza , Kheriji Nadia , Charif Majida , Le Mao Morgane , Galai Said , Kraoua Lilia , Ben Youssef-Turki Ilhem , Kraoua Ichraf , Lenaers Guy , Kefi Rym
Published: January 2024

Introduction: Inherited mitochondrial diseases are the most common group of metabolic disorders caused by a defect in oxidative phosphorylation. They are characterized by a wide clinical and genetic spectrum and can manifest at any age. In this study, we established novel phenotype–genotype correlations between the clinical and molecular features of a cohort of Tunisian patients with mitochondrial diseases.

Materials and methods: Whole-exome sequencing was performed on five Tunisian patients with suspected mitochondrial diseases. Then, a combination of filtering and bioinformatics prediction tools was utilized to assess the pathogenicity of genetic variations. Sanger sequencing was subsequently performed to confirm the presence of potential deleterious variants in the patients and verify their segregation within families. Structural modeling was conducted to study the effect of novel variants on the protein structure.

Results: We identified two novel homozygous variants in NDUFAF5 (c.827G>C; p.Arg276Pro) and FASTKD2 (c.496_497del; p.Leu166GlufsTer2) associated with a severe clinical form of Leigh and Leigh-like syndromes, respectively. Our results further disclosed two variants unreported in North Africa, in GFM2 (c.569G>A; p.Arg190Gln) and FOXRED1 (c.1261G>A; p.Val421Met) genes, and we described the first case of fumaric aciduria in a Tunisian patient harboring the c.1358T>C; p.Leu453Pro FH variant.

Conclusion: Our study expands the mutational and phenotypic spectrum of mitochondrial diseases in Tunisia and highlights the importance of next-generation sequencing to decipher the pathomolecular mechanisms responsible for these disorders in an admixed population.
Mft1, identified from a genome-wide screen of the yeast haploid mutants, mediates cell cycle arrest to counteract quinoxaline-induced toxicity
Authors: Sulaiman Abdallah Alhaj , Al-Ansari Dana E. , Ali Reem , Aouida Mustapha , Ramotar Dindial
Published: January 2024

Quinoxaline is a heterocyclic compound with a two-membered ring structure that undergoes redox cycling to produce toxic free radicals. It has antiviral, antibacterial, antifungal, and antitumor activities. However, the biological functions that are involved in mounting a response against the toxic effects of quinoxaline have not been investigated. Herein, we performed a genome-wide screen using the yeast haploid mutant collection and reported the identification of 12 mutants that displayed varying sensitivity towards quinoxaline. No mutant was recovered that showed resistance to quinoxaline. The quinoxaline-sensitive mutants were deleted for genes that encode cell cycle function, as well as genes that belong to other physiological pathways such as the vacuolar detoxification process. Three of the highly sensitive gene-deletion mutants lack the DDC1, DUN1, and MFT1 genes. While Ddc1 and Dun1 are known to perform roles in the cell cycle arrest pathway, the role of Mft1 remains unclear. We show that the mft1Δ mutant is as sensitive to quinoxaline as the ddc1Δ mutant. However, the double mutant ddc1Δ mft1Δ lacking the DDC1 and MFT1 genes, is extremely sensitive to quinoxaline, as compared to the ddc1Δ and mft1Δ single mutants. We further show that the mft1Δ mutant is unable to arrest in the G2/M phase in response to the drug. We conclude that Mft1 performs a unique function independent of Ddc1 in the cell cycle arrest pathway in response to quinoxaline exposure. This is the first demonstration that quinoxaline exerts its toxic effect likely by inducing oxidative DNA damage causing cell cycle arrest. We suggest that clinical applications of quinoxaline and its derivatives should entail targeting cancer cells with defective cell cycle arrest.
Loss-of-function variant in the LRR domain of SLITRK2 implicated in a neurodevelopmental disorder
Authors: Afsar Tayyaba , Fu Hongxia , Khan Hammal , Ali Zain , Zehri Zamrud , Zaman Gohar , Abbas Safdar , Mahmood Arif , Alam Qamre , Hu Junjian , Razak Suhail , Umair Muhammad
Published: January 2024

Background: Neurodevelopmental disorders are characterized by different combinations of intellectual disability (ID), communication and social skills deficits, and delays in achieving motor or language milestones. SLITRK2 is a postsynaptic cell-adhesion molecule that promotes neurite outgrowth and excitatory synapse development.

Methods and Results: In the present study, we investigated a single patient segregating Neurodevelopmental disorder. SLITRK2 associated significant neuropsychological issues inherited in a rare X-linked fashion have recently been reported. Whole-exome sequencing and data analysis revealed a novel nonsense variant [c.789T>A; p.(Cys263*); NM_032539.5; NP_115928.1] in exon 5 of the SLITRK2 gene (MIM# 300561). Three-dimensional protein modeling revealed substantial changes in the mutated SLITRK2 protein, which might lead to nonsense-medicated decay.

Conclusion: This study confirms the role of SLITRK2 in neuronal development and highlights the importance of including the SLITRK2 gene in the screening of individuals presenting neurodevelopmental disorders.
Complex patterns on HEp-2 indirect immunofluorescence assay in a large sample referred for anti-cell autoantibodies detection
Authors: Santos Wilton Ferreira S. , Cantuária Ana Paula de Castro , Félix Daniele de Castro , Guimarães Natália Carvalho , de Melo Igor Cabral Santos
Published: January 2024

Introduction

The combination of patterns is a frequent and challenging situation in the daily laboratory routine of autoantibodies testing using HEp-2 cells indirect immunofluorescence assay (HEp-2-IFA). Recently, the Brazilian Consensus on Autoantibodies (BCA) named these combinations as complex patterns (CPs) and organized them into 3 subtypes: multiple, mixed, and composite. This study aimed to describe the most frequent combinations of HEp-2-IIF patterns according to this new nomenclature.

Methods

Routine HEp-2-IFA results reported in January and June 2017 were reviewed using the new BCA classification. Visual pattern recognition was performed by experts on HEp-2-IFA readings, using the International Consensus on Antinuclear Antibodies (ANA) Patterns (ICAP) and BCA recommendations.

Results

54,990 serum samples from different patients were tested for ANA-HEp-2, and 11,478 (20.9%) were positive at a titer ≥ 1/80. Among these positive samples, 1,111 (9.7%) displayed CPs, divided into 95 different combinations. A higher proportion of CPs was observed in the pediatric age group. Multiple, mixed, and composite patterns were present in 85.3, 5.4, and 9.5% of the samples, respectively. In the multiple/mixed pattern group (n=1,005), double, triple, and quadruple combinations (ICAP/BCA codes) were observed in 97.7%, 2.2%, and 0.1%, respectively. The double nuclear pattern was the most prevalent combination observed (67.6%). The most common CPs registered were AC-4 (nuclear fine speckled) + AC-6,7 (nuclear discrete dots) (n=264); AC-2 (nuclear dense fine speckled) + AC-6,7 (n=201); AC-4+AC-8,9,10 (nucleolar) (n=129); and AC-3 (centromere)+AC-4 (n=124). All of these combinations were in the multiple subgroup.

Conclusion

Almost 10% of positive results in the HEp-2 procedure displayed CPs. Among the 3 subtypes of CPs proposed, the multiple pattern was the most prevalent, especially in the pediatric population. The AC-4, AC-2, and AC-6,7 were the most prevalent single patterns observed in the combinations described in this study. There was a significant association between age and the prevalence of most combined patterns. The AC-4+AC-6,7 combination was the most prevalent complex pattern detected regardless of the age group. The AC-2+AC-6,7 was more prevalent in younger individuals. The concepts involved in the CPs definition should add value to the reading and interpretation of the HEp-2-IIF assay.
Possible connection between intestinal tuft cells, ILC2s and obesity
Authors: Yang Hong , Huang Yu-Xing , Xiong Pei-Yu , Li Jin-Qian , Chen Ji-Lan , Liu Xia , Gong Yan-Ju , Ding Wei-Jun
Published: January 2024

Intestinal tuft cells (TCs) are defined as chemosensory cells that can “taste” danger and induce immune responses. They play a critical role in gastrointestinal parasite invasion, inflammatory bowel diseases and high-fat diet-induced obesity. Intestinal IL-25, the unique product of TCs, is a key activator of type 2 immunity, especially to promote group 2 innate lymphoid cells (ILC2s) to secret IL-13. Then the IL-13 mainly promotes intestinal stem cell (ISCs) proliferation into TCs and goblet cells. This pathway formulates the circuit in the intestine. This paper focuses on the potential role of the intestinal TC, ILC2 and their circuit in obesity-induced intestinal damage, and discussion on further study and the potential therapeutic target in obesity.
Immunogenicity and efficacy of an oral live-attenuated vaccine for bovine Johne’s disease
Authors: Eshraghisamani Razieh , Facciuolo Antonio , Harman-McKenna Victoria , Illanes Oscar , De Buck Jeroen
Published: January 2024

Mycobacterium avium subsp. paratuberculosis (MAP), the etiological agent of Johne’s disease (JD) in ruminants, establishes a prolonged and often lifelong enteric infection. The implementation of control measures for bovine JD has faced obstacles due to the considerable expenses involved in disease surveillance and hindered by unreliable and inadequate diagnostic tests, emphasizing the need for an effective vaccine that can stimulate mucosal immunity in the gastrointestinal tract. Previous investigations have demonstrated that deletion of the BacA gene in MAP produces an attenuated strain that can transiently colonize the calf small intestine while retaining its capacity to stimulate systemic immune responses similar to wildtype MAP strains. This study assessed the efficacy of the BacA gene deletion MAP strain, referred to as the BacA vaccine, when administered orally to young calves. The research aimed to evaluate its effectiveness in controlling MAP intestinal infection and to investigate the immune responses elicited by mucosal vaccination. The study represents the first evaluation of an enteric modified live MAP vaccine in the context of an oral MAP challenge in young calves. Oral immunization with BacA reduced MAP colonization specifically in the ileum and ileocecal valve. This partially protective immune response was associated with an increased frequency of CD4+ and CD8+ T cells with a pro-inflammatory phenotype (IFNγ+/TNFα+) in vaccinated animals. Moreover, re-stimulated PBMCs from vaccinated animals showed increased expression of IFNγ, IP-10, IL-2, and IL-17 at 10- and 12-weeks post challenge. Furthermore, immunophenotyping of blood leukocytes revealed that vaccinated calves had increased levels of T cells expressing cell-surface markers consistent with long-term central memory. Overall, our findings provide new insights into the development and immunogenicity of a modified live MAP vaccine against bovine JD, demonstrating oral vaccination can stimulate host immune responses that can be protective against enteric MAP infection.
Identifying biomarkers deciphering sepsis from trauma-induced sterile inflammation and trauma-induced sepsis
Authors: Papareddy Praveen , Selle Michael , Partouche Nicolas , Legros Vincent , Rieu Benjamin , Olinder Jon , Ryden Cecilia , Bartakova Eva , Holub Michal , Jung Klaus , Pottecher Julien , Herwald Heiko
Published: January 2024

Objective

The purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients.

Background

Accurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective.

Methods

In this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation.

Results

By comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis.

Conclusions

Our findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.
Engineered T cells from induced pluripotent stem cells: from research towards clinical implementation
Authors: Netsrithong Ratchapong , Garcia-Perez Laura , Themeli Maria
Published: January 2024

Induced pluripotent stem cell (iPSC)-derived T (iT) cells represent a groundbreaking frontier in adoptive cell therapies with engineered T cells, poised to overcome pivotal limitations associated with conventional manufacturing methods. iPSCs offer an off-the-shelf source of therapeutic T cells with the potential for infinite expansion and straightforward genetic manipulation to ensure hypo-immunogenicity and introduce specific therapeutic functions, such as antigen specificity through a chimeric antigen receptor (CAR). Importantly, genetic engineering of iPSC offers the benefit of generating fully modified clonal lines that are amenable to rigorous safety assessments. Critical to harnessing the potential of iT cells is the development of a robust and clinically compatible production process. Current protocols for genetic engineering as well as differentiation protocols designed to mirror human hematopoiesis and T cell development, vary in efficiency and often contain non-compliant components, thereby rendering them unsuitable for clinical implementation. This comprehensive review centers on the remarkable progress made over the last decade in generating functional engineered T cells from iPSCs. Emphasis is placed on alignment with good manufacturing practice (GMP) standards, scalability, safety measures and quality controls, which constitute the fundamental prerequisites for clinical application. In conclusion, the focus on iPSC as a source promises standardized, scalable, clinically relevant, and potentially safer production of engineered T cells. This groundbreaking approach holds the potential to extend hope to a broader spectrum of patients and diseases, leading in a new era in adoptive T cell therapy.
Type 2 innate lymphoid cells are not involved in mouse bladder tumor development
Authors: Schneider Anna K. , Domingos-Pereira Sonia , Cesson Valérie , Polak Lenka , Fallon Padraic G. , Zhu Jinfang , Roth Beat , Nardelli-Haefliger Denise , Derré Laurent
Published: January 2024

Therapies for bladder cancer patients are limited by side effects and failures, highlighting the need for novel targets to improve disease management. Given the emerging evidence highlighting the key role of innate lymphoid cell subsets, especially type 2 innate lymphoid cells (ILC2s), in shaping the tumor microenvironment and immune responses, we investigated the contribution of ILC2s in bladder tumor development. Using the orthotopic murine MB49 bladder tumor model, we found a strong enrichment of ILC2s in the bladder under steady-state conditions, comparable to that in the lung. However, as tumors grew, we observed an increase in ILC1s but no changes in ILC2s. Targeting ILC2s by blocking IL-4/IL-13 signaling pathways, IL-5, or IL-33 receptor, or using IL-33-deficient or ILC2-deficient mice, did not affect mice survival following bladder tumor implantation. Overall, these results suggest that ILC2s do not contribute significantly to bladder tumor development, yet further investigations are required to confirm these results in bladder cancer patients.
Spatial distribution of trace elements and potential contamination sources for surface sediments of the North-Western Black Sea, Romania
Authors: Bucşe Andra , Pârvulescu Oana Cristina , Vasiliu Dan , Rădulescu Florina , Lupaşcu Naliana , Ispas Bogdan Adrian
Published: January 2024

It is essential to determine the concentrations of metals/metalloids in marine sediments and their contamination status to develop appropriate pollution control strategies and/or improve existing ones. Spatial distribution of aluminum (Al) and some trace elements, i.e., arsenic (As), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn), accumulated in surface sediments of the north-western (NW) Black Sea (Romanian zone) was evaluated. Sediment samples were collected in 2019 from 32 stations located at water depths in the range of 12.7–149 m. The mean values ± standard deviations (SD) of element concentrations were as follows: 3.9 ± 1.6% for Al, 11.2 ± 10.2 mg/kg for As, 64.8 ± 27.0 mg/kg for Cr, 32.7 ± 15.0 mg/kg for Cu, 0.10 ± 0.09 mg/kg for Hg, 45.3 ± 23.8 mg/kg for Ni, 24.6 ± 9.6 mg/kg for Pb, and 68.0 ± 28.0 mg/kg for Zn. These values are not significantly different (p > 0.05) from those found in a previous study on surface sediments collected in 2018 from 22 stations located in the same area, but at lower water depths (13.5–67 m). Contamination factor (CF) was used to assess the contamination status of surface sediments. The mean values of CF (0.26–1.23) reveal low to moderate contamination with Pb and low contamination with the other elements. Principal component analysis (PCA) and correlation analysis indicated that As, Cu, Ni, Hg, Pb, and Zn were associated with clay, silt, and organic matter, suggesting that these elements mainly came from the Danube discharges and also from local anthropogenic sources, whereas Al, Cr, and partly Hg, Pb, and Zn originated from rock/soil weathering and erosion. The concentration levels of As, Cu, Hg, Ni, Pb, Zn, TOC, silt, and clay were higher in sediments collected from stations generally located at higher water depths (up to 118 m), suggesting that the TEs associated with the finer carriers were transported offshore by currents and waves, whereas the concentration levels of Al, Cr, Hg, and Zn were higher in sediments with lower levels of CaCO3 content (10.1–24.3%), collected from shallower stations (water depths of 12.7–42.0 m).
Performance of high-belite calcium sulfoaluminate cement subjected to hydrochloric acid and sulfuric acid
Authors: Huo Guang , Jiang Xinchao , Sun Xiaoheng , Li Hui , Shi Hongxing
Published: January 2024

The high-belite calcium sulfoaluminate cement (HB-CSA) has displayed outstanding acid resistance. However, further research is needed to understand the mechanism behind its acid resistance fully. This study investigates the resistance of a new type of HB-CSA to hydrochloric and sulfuric acid. Additionally, the impact of the ye'elimite (C4A3S¯)-to-gypsum (CS¯) ratio on the acid resistance of HB-CSA is discussed. The resistance performance is investigated by flexural strength and resistance index analyses, X-ray diffraction (XRD), thermogravimetric analysis (TGA), electronic computed tomography (CT) scans, and scanning electron microscopy (SEM). The results show that the HB-CSA exhibits superior resistance to sulfuric acid and hydrochloric acid compared to Portland cement. The absence of portlandite contributes to the enhanced performance of HB-CSA. In addition, as the C4A3S¯-to-CS¯ ratio decreases, the content of Aft in HB-CSA increases, leading to an increase in the acid resistance of HB-CSA.
Ultrasonography-guided radiofrequency ablation of vascular malformations—The moving shot technique
Authors: Sporns Peter B. , Psychogios Marios , Blackham Kristine , Zech Christoph , Wildgruber Moritz , Takes Martin
Published: January 2024

Purpose

To describe a novel ultrasound-guided technique for percutaneous radiofrequency ablation of vascular malformations—the “moving shot technique.”

Methods

Preliminary observational cohort study, conducted from June 1, 2019, to January 31, 2021, including all consecutive patients diagnosed with vascular malformations who were treated with ultrasound-guided radiofrequency ablation using the moving shot technique. Only patients who had undergone at least one unsuccessful previous treatment were included (sclerotherapy with ethanol/aethoxysklerol or embolization/surgery).

Results

Eight patients with a median age of 22 years (interquartile range, 13–31) were included. Patients had different vascular malformations consisting of 1 arteriovenous malformation, 4 venous malformations, and 1 each a mixed venous-lymphatic malformation, a glomuvenous malformation and a FAVA (fibroadipose vascular anomaly). Malformations were located at the limbs in 5 patients (62.5%), the subcutaneous/intramuscular tissue of the body in 2 patients (25%) and at the chin in 1 patient (12.5%). Clinical symptoms were pain in 8 patients (100%), swelling in 6 patients (75%), and partial immobility in 4 patients (50%). All patients showed an improvement of clinical symptoms after treatment with 7 (87.5%) being completely asymptomatic and 1 (12.5%) showing improvement of immobility and pain. No procedural complications, such as nerve damage or skin burns occurred.

Conclusion

The moving shot technique using ultrasonography-guided radiofrequency ablation is a promising technique for the interventional treatment of vascular malformations and should be validated in multicenter-approaches.