bluuebunny/crossref_metadata_2025_split huggingface dataset:
Method for determining of cytotoxicity based on the release of fluorescent proteins
Authors: Lifanov Dmitry , Zorigt Dulamsuren , Shabalina Evgenya , Khalil Abdullah , Gorbunov Konstantin , Petersen Elena 
Published: September 2024

AbstractThis paper describes a method for determining the cytotoxicity of chemical compounds based on the detection of fluorescent proteins - in this case, green fluorescent protein (GFP) and red fluorescent protein (RFP), which are released into the medium from dead cells. This method is similar in principle to the lactate dehydrogenase test (LDH test), but it does not require a reaction with a chromogenic substrate. This method also makes it possible to independently determine the viability of different lines when used in cocultures. Experiments were preformed on a classical monolayer, spheroids and 3D cultures in alginate hydrogel. Capecitabine was used as a model cytotoxic agent. We included liver cells (Huh7) in a coculture model and determined changes in the cytotoxicity levels of capecitabine against NCI-H1299 cells. The experimental part also found that there were differences in sensitivity to capecitabine depending on the type of 3D cultures used.
Genetic analyses identify shared genetic components related to autoimmune and cardiovascular diseases
Authors: Qiao Jun , Chang Minjing , Chen Miaoran , Zhao Yuhui , Hao Jiawei , Zhang Pengwei , Zhou Ruixin , Cai Liuyang , Liu Feng , Fan Xiaoping , Pauklin Siim , Zou Rongjun , Li Zhixiu , Feng Yuliang 
Published: September 2024

AbstractObjectivesAutoimmune diseases (ADs) play a significant and intricate role in the onset of cardiovascular diseases (CVDs). Our study aimed to elucidate the shared genetic etiology between Ads and CVDs.MethodsWe conducted genome-wide pleiotropy analyses to investigate the genetic foundation comprehensively and shared etiology of six ADs and six CVDs. We analyze the genetic architecture and genetic overlap between these traits. Then, SNP-level functional annotation identified significant genomic risk loci and potential causal variants. Gene-level analyses explored shared pleiotropic genes, followed by pathway enrichment analyses to elucidate underlying biological mechanisms. Finally, we assess potential causal pathways between ADs and CVDs.ResultsDespite negligible overall genetic connections, our results revealed a significant genetic overlap between ADs and CVDs, indicating a complex shared genetic architecture spread throughout the genome. The shared loci implicated several genes, includingATXN2,BRAP,SH2B3,ALDH2(all located at 12q24.11-12),RNF123,MST1R,RBM6, andUBA7(all located at 3p21.31), all of which are protein-coding genes. Top biological pathways enriched with these shared genes were related to the immune system and intracellular signal transduction.ConclusionsThe extensive genetic overlap with mixed effect directions between ADs and CVDs indicates a complex genetic relationship between these diseases. It suggests overlapping genetic risk may contribute to shared pathophysiological and clinical characteristics and may guide clinical treatment and management.
Introducing a framework for within-host dynamics and mutations modelling of H5N1 influenza infection in humans
Authors: Higgins Daniel , Looker Joshua , Sunnucks Robert , Carruthers Jonathan , Finnie Thomas , Keeling Matt J. , Hill Edward M. 
Published: September 2024

AbstractAvian influenza A(H5N1) poses a public health risk due to its pandemic potential should the virus mutate to become human-to-human transmissible. To date, reported influenza A(H5N1) human cases have typically occurred in the lower respiratory tract with a high case fatality rate. There is prior evidence of some influenza A(H5N1) strains being a small number of amino acid mutations away from achieving droplet transmissibility, possibly allowing them to be spread between humans. We present a mechanistic within-host influenza A(H5N1) infection model, novel for its explicit consideration of the biological differences between the upper and lower respiratory tracts. We then estimate a distribution of viral lifespans and effective replication rates in human H5N1 influenza cases. By combining our within-host model with a viral mutation model, we determine the probability of an infected individual generating a droplet transmissible strain of influenza A(H5N1) through mutation. For three mutations, we found a peak probability of approximately 10−3that a human case of H5N1 influenza produces at least one virion during the infectious period. Our findings provide insights into the risk of differing infectious pathways of influenza A(H5N1) (namely avian-human vs avian-mammal-human routes), demonstrating the three-mutation pathway being a cause of concern in human cases.
Phosphatidylethanolamines are the main lipid class altered in red blood cells from patients with VPS13A disease/chorea-acanthocytosis
Authors: Peikert Kevin , Spranger Adrian , Miltenberger-Miltenyi Gabriel , Glaß Hannes , Falkenburger Björn , Klose Christian , Tyteca Donatienne , Hermann Andreas 
Published: September 2024

AbstractBackgroundVPS13A disease (chorea-acanthocytosis) is an ultra-rare disorder caused by loss of function mutations in VPS13A characterized by striatal degeneration and by red blood cell (RBC) acanthocytosis. VPS13A is a bridge-like protein mediating bulk lipid transfer at membrane contact sites.ObjectivesTo assess the lipid composition of patient-derived RBCs.MethodsRBCs collected from 5 VPS13A disease patients and 12 control subjects were analyzed by mass spectrometry (lipidomics).ResultsWhile we found no significant differences on the overall lipid class level, alterations in certain species were detected: phosphatidylethanolamine species with both longer chain length and higher unsaturation were increased in VPS13A disease samples. Specific ceramide, phosphatidylcholine and sphingomyelin species were also altered.ConclusionsThe presented alterations of particular lipid species in RBCs in VPS13A disease contribute to 1) the understanding of acanthocyte formation and 2) future biomarker identification. Lipid distribution seems to play a key role in the pathophysiology of VPS13A disease.
Large Language Models in Cardiology: A Systematic Review
Authors: Gendler Moran , Nadkarni Girish N , Sudri Karin , Cohen-Shelly Michal , Glicksberg Benjamin S , Efros Orly , Soffer Shelly , Klang Eyal 
Published: September 2024

AbstractPurposeThis review analyzes the application of large language models (LLMs), in the field of cardiology, with a focus on evaluating their performances across various clinical tasks.MethodsWe conducted a systematic literature search on PubMed for studies published up to April 14, 2024. Our search used a wide range of keywords related to LLMs and cardiology to capture various relevant terms. The risk of bias was evaluated using the QUADAS-2 tool.ResultsFifteen studies met the inclusion criteria, categorized into four domains: chronic and progressive cardiac conditions, acute cardiac events, cardiology education, and cardiac monitoring. Six studies addressing chronic conditions demonstrated variability in the accuracy and depth of LLM-generated responses. In acute cardiac scenarios, three articles showed that LLMs provided medical advice with mixed effectiveness, particularly in delivering CPR instructions. Two studies in educational cardiology revealed high accuracy in answering assessment questions and interpreting clinical cases. Finally, four articles on cardiac diagnostics showed that multimodal LLMs displayed a range of capabilities in ECGs interpretation, with some models performing at or exceeding the level of human specialists.ConclusionLLMs demonstrate considerable potential in the field of cardiology, particularly in educational applications and routine diagnostics. However, their performance remains inconsistent across various clinical scenarios, particularly in acute care settings where precision is critical. Enhancing their accuracy in interpreting real-world complex medical data and emergency response guidance is imperative before integration into clinical practice.
Prevalence of HIV1 Infection and Its Associated Factors among Exposed Infants at Shegaw Motta General Hospital, Ethiopia
Authors: Nigusie Destaw Kebede , Damitew Fantahun Getaneh , Melsew Kirubel Endalamaw , Zerefaw Girma , Nigusie Abebe Feneta 
Published: September 2024

AbstractBackgroundHuman immunodeficiency virus (HIV)/acquired immunodeficiency syndrome is a leading cause of death and disease burden. Following this, vertical transmission is the main source of HIV infection on children globally. Morbidity and mortality among HIV-exposed infants are still the main health challenges in Ethiopia. Therefore, the aim of this study was to determine the prevalence of HIV1infection and its associated factors among exposed infants at Shegaw Motta General Hospital, Ethiopia.MethodsHospital-based cross-sectional study was conducted on exposed infants at Shegaw Motta General Hospital from September 1, 2022 to July 30, 2023. The consecutive convenience sampling technique was used to select study participants. Whole blood sample was collected from mothers and infants. Laboratory tests like early infant diagnosis, cluster of differentiation 4 counts and viral load were performed using standard operating procedure. Then, the data were entered into EpiData version 3.1 and analyzed by SPSS version 20. Finally, bivariable and multivariable logistic regressions were carried out to identify factors significantly associated (P<0.05).ResultsOut of 155 infants, about 79(50.9%) infants were females and87(56.1%) was urban resident. Furthermore, majority of infants were born from mothers who could not able to write and read 88(56.8%) and maternal ages range from 25-34years were 138(89.0%). The overall prevalence of HIV1 infection among exposed infants was6(3.87%) with (95%CI: 2.9-8.2). Pregnant women had not antennal care (AOR=7.281,P= 0.001), home delivery (AOR= 3.239,P=0.001), maternal not received antiretroviral prophylaxis (AOR = 9.213,P= 0.001), infants not intake nevirapine prophylaxis (AOR=2.560,P= 0.007) and maternal high viral load (AOR= 5.120,P= 0.004) were the factors associated with HIV infection among exposed infants.ConclusionThe HIV1 infection among exposed infants was still high (3.87%). Pregnant women had not antenatal care follow up, home delivery, maternal high viral load, and not receiving antiretroviral prophylaxis, infant not intake nevirapine prophylaxis increases the risk of HIV1 infection. Therefore, health facilities should strictly strengthen the PMTCT service by providing maternal antiretroviral prophylaxis, infant nevirapine prophylaxis, promoting antenatal care service, early screening maternal viral load and scale up skilled delivery to eliminate HIV infection among exposed infants.
Safety and Efficacy of Metformin for Idiopathic Intracranial Hypertension. A U.S-Based Real-World Data Retrospective Multicenter Cohort Study
Authors: Azzam Ahmed Y. , Nassar Mahmoud , Al Zomia Ahmed Saad , Elswedy Adam , Morsy Mahmoud M. , Mohamed Adham A. , Elamin Osman , Elsayed Omar S. , Azab Mohammed A. , Essibayi Muhammed Amir , Wu Jin , Dmytirw Adam A. , Altschul David J. 
Published: September 2024

AbstractIntroductionIdiopathic intracranial hypertension (IIH) remains a challenging condition to manage, with limited therapeutic options. This study investigated the potential of metformin as a novel treatment for IIH, exploring its effects on disease outcomes and safety profile.MethodsWe conducted a retrospective cohort study using the TriNetX database, analyzing data from 2009 to August 2024. Patients diagnosed with IIH were included, with exclusions for other causes of elevated intracranial pressure and pre-existing diabetes. Propensity score matching was employed to balance cohorts according to age, sex, race, ethnicity, Hemoglobin A1C, and baseline body mass index (BMI) at the time of metformin initiation. Outcomes were assessed at various follow-up points up to 24 months.ResultsOur study initially comprised 1,268 patients in the metformin group and 49,262 in the control group, with notable disparities in several parameters. Post-matching, both cohorts were refined to 1,267 patients each after matching with metformin group. Metformin-treated patients showed significantly lower risks of papilledema, headache, and refractory IIH status at all follow-up points (p<0.0001). The metformin group also had reduced rates of therapeutic spinal punctures and acetazolamide continuation. BMI reductions were more pronounced in the metformin group, with significant differences observed from 6 months onward (p<0.0001). Notably, metformin’s beneficial effects persisted independently of BMI changes. The safety profile of metformin was favorable, with no significant differences in adverse events compared to the control group which did not receive metformin during the study timeframe.ConclusionsOur study provides evidence for metformin’s potential as a disease-modifying therapeutic approach in IIH, demonstrating improvements across multiple outcomes. The benefits appear to extend beyond weight loss, suggesting complex mechanisms of action. These findings warrant further investigation through prospective clinical trials to establish metformin’s role in IIH management and explore its underlying therapeutic mechanisms.
Harnessing Random Peptide Mixtures to Overcome Multidrug-Resistant Fungal Infections
Authors: Adeoye John , Belo Yael , Rocha Marina , Hayby Hilla , Hayouka Zvi , Shlezinger Neta 
Published: September 2024

AbstractInvasive fungal infections, characterized by high mortality rates, present a growing health concern due to the limited spectrum of effective drugs, escalating numbers of immunocompromised patients, and the rapid emergence of drug resistance. Addressing this challenge requires alternative therapeutic strategies. Candidate drugs should fulfill key requirements to qualify for clinical use, including negligible host toxicity, highin vitroandin vivoantifungal activity,in vivostability, and modes of actions that reduce the potential for the emergence of resistant strains. Antimicrobial peptides (AMPs) stand out as a promising class of compounds to combat antimicrobial resistance. Capitalizing on the unique characteristics of AMPs, we have developed a novel approach, to synthesize random peptide mixtures (RPMs) with robust bactericidal properties against drug-resistant bacteria. Here, we evaluate the antifungal potential of RPMs. Our findings demonstrate high potency of RPMs againstCandida auris, a newly emerged multidrug-resistant human fungal pathogen. In vitro studies demonstrated the effective eradication ofC. aurisby FK20 RPMs, with scanning electron microscopy revealing substantial damage to the fungal outer membrane, while confocal microscopy confirms their ability to penetrateC. auriscells. Importantly, our study elucidates that FK20 RPMs effectively hinder the development of resistance inC. auris, as confirmed by experimental evolution assays. Moreover, a synergistic effect is observed when combining FK20 RPMs with the antifungal drug caspofungin, effectively inhibiting biofilm formation. Lastly, we demonstrate the significant therapeutic potential of FK20 RPM in a murine model of systemic candidiasis. Our findings underscore the promise of RPMs as novel, efficacious, and safe treatment for drug-resistant fungal infections.
Model-guided gene circuit design for engineering genetically stable cell populations in diverse applications
Authors: Sechkar Kirill , Steel Harrison 
Published: September 2024

AbstractMaintaining engineered cell populations’ genetic stability is a key challenge in synthetic biology. Synthetic genetic constructs compete with a host cell’s native genes for expression resources, burdening the cell and impairing its growth. This creates a selective pressure favouring mutations which alleviate this growth defect by removing synthetic gene expression. Non-functional mutants thus spread in cell populations, eventually making them lose engineered functions. Past work has attempted to limit mutation spread by coupling synthetic gene expression to survival. However, these approaches are highly context-dependent and must be tailor-made for each particular synthetic gene circuit to be retained.In contrast, we develop and analyse a biomolecular controller which depresses mutant cell growth independently of the mutated synthetic gene’s identity. Modelling shows how our design can be deployed alongside various synthetic circuits without any re-engineering of its genetic components, outperforming extant gene-specific mutation spread mitigation strategies. Our controller’s performance is evaluated using a novel simulation approach which leverages resource-aware cell modelling to directly link a circuit’s design parameters to its population-level behaviour.Our design’s adaptability promises to mitigate mutation spread in an expanded range of applications, whilst our analyses provide a blueprint for using resource-aware cell models in circuit design.
Transcriptomic profiling of ‘CandidatusLiberibacter asiaticus’ in different citrus tissues reveals novel insights into Huanglongbing pathogenesis
Authors: Lovelace Amelia H. , Wang Chunxia , Levy Amit , Ma Wenbo 
Published: September 2024

ABSTRACT‘CandidatusLiberibacter asiaticus’ (Las) is a gram-negative bacterial pathogen associated with citrus huanglongbing (HLB) or greening disease. Las is transmitted by the Asian citrus psyllid (ACP) where it colonizes the phloem tissue, resulting in substantial economic losses to citrus industry worldwide. Despite extensive efforts, effective management strategies against HLB remain elusive, necessitating a deeper understanding of the pathogen’ s biology. Las undergoes cell-to-cell movement through phloem flow and colonizes different tissues in which Las may have varying interactions with the host. Here, we investigate the transcriptomic landscape of Las in citrus seed coat vasculatures, enabling a complete gene expression profiling of Las genome and revealing unique transcriptomic patterns compared to previous studies using midrib tissues. Comparative transcriptomics between seed coat, midrib and ACP identified specific responses and metabolic states of Las in different host tissue. Two Las virulence factors that exhibit higher expression in seed coat can suppress callose deposition. Therefore, they may contribute to unclogging sieve plate pores during Las colonization in seed coat vasculature. Furthermore, analysis of regulatory elements uncovers a potential role of LuxR-type transcription factors in regulating Liberibacter effector gene expression during plant colonization. Together, this work provides novel insights into the pathogenesis of the devastating citrus HLB.FundingThis work is supported by USDA National Institute of Food and Agriculture award No. 2020-70029-33197 to W.M and A.L.
A study of mediating and moderating effects on the relationship between audit quality and integrated reporting quality among Jordanian firms
Authors: Abu Afifa Malik , Saleh Isam , Abu Al-Nadi Rahaf 
Published: September 2024

PurposeThe purpose of this research is to investigate the link between external audit quality and integrated reporting (IR) quality in the Jordanian market, a developing market. Furthermore, the research model considers the mediating effect of earnings management practices and the moderating effect of board gender diversity. As a result, it intends to provide further empirical evidence in this area.Design/methodology/approachThis research investigates its model using data from Jordanian services companies listed on the Amman Stock Exchange (ASE) during the period 2013–2022. With 430 company-year observations, the current research’s sample includes all companies in the research population for which complete data were available during the period under investigation. Data relevant to the research setting were obtained from annual disclosures and the ASE's database.FindingsThe findings of this research show that audit firm size and audit firm specialty have a positive influence on IR quality, but audit firm tenure does not. External audit quality (as proxied by the size, specialty and turnover of the audit firm) had a negative impact on earnings management practices, while earnings management practices had a negative impact on IR quality. Additionally, the findings reveal that earnings management practices completely mediate the relationship between two external audit quality proxies (audit firm size and audit firm specialty) and IR quality. Furthermore, in terms of the moderating impact of board gender diversity, it is obvious that board gender diversity favorably moderates the relationships between all external audit quality proxies and IR quality.Originality/valueUsing agency theory and stakeholder theory, this investigation fills a gap in previous literature by adding scientific explanations and empirical evidence from the Jordanian market, a developing market, in the context of the impact of audit quality on IR quality, mediated by earnings management and moderated by board gender diversity.
Exploring opportunities and challenges in promoting interethnic tolerance as a social good through virtual influencers
Authors: Levkov Nikola , Santa Mijalche , Kitanovikj Bojan 
Published: September 2024

Purpose
This paper aims to understand how virtual influencers (VIs) can promote interethnic tolerance, online, among youth as a social good.

Design/methodology/approach
This paper conducted qualitative research using interpretive analysis with RTA (Reflexive Thematic Analysis) on data collected through focus groups.

Findings
This paper revealed that the quality of the VI’s content is a leading factor influencing VI's ability to promote interethnic tolerance, but creating content that is constantly authentic, appealing and inclusive to diverse ethnic groups in a particular context is challenging.

Research limitations/implications
The study has some limitations related to the specific context on which it is focused and therefore transferring the findings to different contextual conditions requires caution, and also can be extended with positivist validation.

Practical implications
Findings from our study can drive future projects where real VI artifacts will play the role of a mediator in building strong relational trust among youth belonging to different ethnic groups. The findings indicate that VIs can be effectively used to foster interethnic tolerance if involve diverse team members who understand the ethnic culture deeply and social media experts, to create high-quality content to overcome some limitations.

Social implications
VIs can be used as social interventions to promote interethnic tolerance and to reduce prejudices and anxiety in online youth communication.

Originality/value
To the best of the authors’ knowledge, no known studies investigated the potential of VIs for promoting interethnic tolerance among ethnically diverse youth groups. Hence, this study paves the way for further refinement on using cutting-edge technology for social good, since it is highly challenging, often resulting in wasted money.