bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1+ Neutrophils mediate Susceptibility during Systemic Inflammatory Response in Non-Alcoholic Fatty Liver Disease
Authors: Barros Cleyson da Cruz Oliveira , Kanashiro Alexandre , da Silva Gabriel Victor Lucena , Cebinelli Guilherme Cesar Martelossi , Leiria Luiz Osório , Cunha Thiago Mattar , Alves Filho José Carlos , Cunha Fernando Queiroz 
Published: October 2024

AbstractNon-alcoholic fatty liver disease (NAFLD) is a pathological condition affecting individuals worldwide. Patients with NAFLD are more susceptible to systemic inflammation, such as sepsis, which accelerates liver damage. However, the immunological mechanisms that trigger the hyper-inflammatory responses in individuals with NAFLD remain unknown. In the present study, we reported that short-term HFCD (Choline Deficient High Fat Diet)-fed mice, which did not show significative signs of hepatic damage and inflammation in the first two weeks, are more susceptible to mortality after lipopolysaccharide (LPS) challenge. Mechanistically, endotoxemic mice show an excessive accumulation of NK-producing IFN-γ cells in liver tissue triggering the recruitment and polarization of a distinct neutrophil subset, characterized by high PD-L1 expression and massive TNFα production. Remarkably, genetic inhibition of IFN-γ or pharmacological blockade of PD-L1 effectively modulated the excessive recruitment of these neutrophils to the liver and TNFα release, thereby preventing hepatic damage and reducing the severity of host mortality. Thus, these results support the design of novel effective strategies to control hyperinflammatory responses in patients with HFCDs and consequently prevent hepatic damage and mortality..
Sustainability in the laboratory: evaluating the reuseability of microtiter plates for PCR and fragment detection
Authors: Berthelsen Ane Liv , Paijmans Anneke J. , Forcada Jaume , Hoffman Joseph Ivan 
Published: October 2024

1.SummarySingle-use plastics (SUPs) are indispensable in laboratory research, but their disposal contributes substantially to environmental pollution. Consequently, reusing common SUP items such as microtiter plates represents a promising strategy for improving laboratory sustainability. However, the key challenge lies in determining whether SUP reuse can be implemented without sacrificing data quality. To investigate this, we conducted a simple experiment to assess the impact of reusing microtiter plates on microsatellite genotyping accuracy. Plates previously used for PCR and fragment detection were cleaned opting for an environmentally friendly approach using regular soap and then reused. Our results indicate that, while reusing PCR plates significantly increases genotyping error rates due to residual DNA contamination, detection plates can be reused without compromising data quality. Our approach offers laboratories a practical and sustainable option for reducing SUP waste and costs while maintaining research integrity.
Ductal pancreatic cancer interception by FGFR2 abrogation
Authors: Tonelli Claudia , Deschênes Astrid , Gaeth Victoria , Jensen Amanda , Vithlani Nandan , Yao Melissa A. , Zhao Zhen , Park Youngkyu , Tuveson David A. 
Published: October 2024

ABSTRACTActivating KRAS mutations are a key feature of pancreatic ductal adenocarcinoma (PDA) and drive tumor initiation and progression. However, mutant KRAS by itself is weakly oncogenic. The pathways that cooperate with mutant KRAS to induce tumorigenesis are less-defined. Analyzing organoids and murine and human pancreatic specimens, we found that the receptor tyrosine kinase FGFR2 was progressively up-regulated in mutant KRAS-driven metaplasia, pre-neoplasia and Classical PDA. Using genetic mouse models, we showed that FGFR2 supported mutant KRAS-driven transformation of acinar cells by promoting proliferation and MAPK pathway activation. FGFR2 abrogation significantly delayed tumor formation and extended the survival of these mice. Furthermore, we discovered that FGFR2 collaborated with EGFR and dual blockade of these receptor signaling pathways significantly reduced mutant KRAS-induced pre-neoplastic lesion formation.Together, our data have uncovered a pivotal role for FGFR2 in the early phases of pancreatic tumorigenesis, paving the way for future therapeutic applications of FGFR2 inhibitors for pancreatic cancer interception.STATEMENT OF SIGNIFICANCEMutant KRAS-expressing pancreatic intraepithelial neoplasias (PanINs), the precursor lesions of PDA, are prevalent in the average healthy adult but rarely advance to invasive carcinoma. Here, we discovered that FGFR2 promoted PDA progression by amplifying mutant KRAS signaling and that inactivation of FGFR2 intercepted disease progression.
Identification of SLC35A1 as an essential host factor for the transduction of multi-serotype recombinant adeno-associated virus (AAV) vectors
Authors: Zhang Xiujuan , Hao Siyuan , Feng Zehua , Ning Kang , Kuz Cagla Aksu , McFarlin Shane , Richart Donovan , Cheng Fang , Zhang-Chen Ander , McFarlane Richenda , Yan Ziying , Qiu Jianming 
Published: October 2024

ABSTRACTWe conducted a genome-wide CRISPR/Cas9 screen in suspension 293-F cells transduced with rAAV5. The highly selected genes revealed after two rounds of screens included the previously reportedKIAA039L,TM9SF2, andRNF121, along with a cluster of genes involved in glycan biogenesis, Golgi apparatus localization and endoplasmic reticulum penetration. In this report, we focused on solute carrier family 35 member A1 (SLC35A1), a Golgi apparatus-localized cytidine 5’-monophosphate-sialic acid (CMP-SIA) transporter. We confirmed thatSLC35A1knockout (KO) significantly decreased rAAV5 transduction to a level lower than that observed inKIAA0319LorTM9SF2KO cells. AlthoughSLC35A1KO drastically reduced the expression of α2,6-linked SIA on the cell surface, the expression of α2,3-linked SIA, as well as the cell binding and internalization of rAAV5, were only moderately affected. Moreover,SLC35A1KO significantly diminished the transduction of AAV multi-serotypes, including rAAV2 and rAAV3 which do not utilize SIAs for primary attachment. Notably, the SLC35A1 KO markedly increased transduction of rAAV9 and rAAV11, which primarily attach to cells via binding to galactose. Further analyses revealed thatSLC35A1KO significantly decreased vector nuclear import. More importantly, although the C-terminal cytoplasmic tail deletion (ΔC Tail) mutant of SLC35A1 did not drastically decrease SIA expression, it significantly decreased rAAV transduction, as well as vector nuclear import, suggesting the C-tail is critical in these processes. Furthermore, the T128A mutant significantly decreased SIA expression, but still supported rAAV transduction and nuclear import. These findings highlight the involvement of the CMP-SIA transporter in the intracellular trafficking of rAAV vectors post-internalization.IMPORTANCErAAV is an essential tool for gene delivery in the treatment of genetic disorders, yet the mechanisms of rAAV transduction remain partially understood. GPR108 is vital for the transduction of most rAAV vectors, but not for rAAV5. We aimed to identify host factors that impact AAV5 transduction akin to GPR108. Using a genome-wide CRISPR/Cas9 screen in 293-F cells, we identified SLC35A1, a Golgi apparatus-localized CMP-sialic acid transporter that transports CMP-sialic acid from cytoplasm into the Golgi apparatus for sialylation, is essential to rAAV transduction. Further studies across various AAV serotypes showed SLC35A1 significantly affects vector nuclear import post-internalization. These results underscore the crucial role of SLC35A1 in intracellular trafficking beyond the initial cell attachment of rAAV.
Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease
Authors: Du Muzi , Akerman Suleyman C. , Fare Charlotte M. , Ruan Linhao , Vidensky Svetlana , Mamedova Lyudmila , Lee Joshua , Rothstein Jeffrey D. 
Published: October 2024

AbstractTMEM106B is a lysosomal/late endosome protein that is a potent genetic modifier of multiple neurodegenerative diseases as well as general aging. Recently, TMEM106B was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention to TMEM106B pathology and the potential role of TMEM106B aggregation in disease. In the context of neurodegenerative diseases, TMEM106B has been studiedin vivousing animal models of neurodegeneration, but these studies rely on overexpression or knockdown approaches. To date, endogenous TMEM106B pathology and its relationship to known canonical pathology in animal models has not been reported. Here, we analyze histological patterns of TMEM106B in murine models ofC9ORF72-related amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), SOD1-related ALS, and tauopathy and compare these to postmortem human tissue from patients with C9-ALS/FTD, Alzheimer’s disease (AD), and AD with limbic-predominant age-related TDP-43 encephalopathy (AD/LATE). We show that there are significant differences between TMEM106B pathology in mouse models and human patient tissue. Importantly, we also identified convergent evidence from both murine models and human patients that links TMEM106B pathology to TDP-43 nuclear clearance specifically in C9-ALS. Similarly, we find a relationship at the cellular level between TMEM106B pathology and phosphorylated Tau burden in Alzheimer’s disease. By characterizing endogenous TMEM106B pathology in both mice and human postmortem tissue, our work reveals considerations that must be taken into account when analyzing data fromin vivomouse studies and elucidates new insights supporting the involvement of TMEM106B in the pathogenesis and progression of multiple neurodegenerative diseases.
Modeling the potential impacts of outpatient antiviral treatment in reducing influenza-associated hospitalizations in the United States
Authors: Morris Sinead E. , Mathis Sarabeth M. , Reeves Emily , Chung Jessie R. , Borchering Rebecca K. , Lewis Nathaniel M. , Masalovich Svetlana , Garg Shikha , Uyeki Timothy M. , Iuliano A. Danielle , Tenforde Mark W. , Reed Carrie , Biggerstaff Matthew 
Published: October 2024

AbstractBackgroundSeasonal influenza causes an estimated 100,000–710,000 hospitalizations annually in the United States (U.S.). Treatment with antiviral medications, such as oseltamivir, can reduce risks of hospitalization among people with influenza-associated illness. The U.S. Centers for Disease Control and Prevention recommends initiating antiviral treatment as soon as possible for outpatients with suspected or confirmed influenza who have severe or progressive illness or are at higher risk of influenza complications.MethodsWe developed a probabilistic model to estimate the impact of antiviral treatment in reducing hospitalizations among U.S. outpatients with influenza. Parameters were informed by seasonal influenza surveillance platforms and stratified by age group and whether individuals had a medical condition associated with higher risk of influenza complications. We modeled different scenarios for influenza antiviral effectiveness and outpatient testing and prescribing practices, then compared our results to a baseline scenario in which antivirals were not used.ResultsAcross the modeled scenarios, antiviral treatment resulted in 1,215–14,184 fewer influenza-associated hospitalizations on average compared to the baseline scenario (a 0.2%–2.7% reduction). The greatest effects occurred among adults ≥65 years and individuals with conditions associated with higher risk of influenza complications. Modeling 50% improvements in access to care, testing, prescribing, and treatment resulted in greater potential impacts, with over 71,000 (13.3%) influenza-associated hospitalizations averted on average compared to baseline.ConclusionsOur results support recommendations to prioritize outpatient antiviral treatment among older adults and others at higher risk of influenza complications. Improving access to prompt testing and treatment among outpatients with suspected influenza could reduce hospitalizations substantially.SummaryWe probabilistically modeled influenza antiviral treatment among outpatients with influenza virus infection in the United States. Antiviral treatment reduced influenza-associated hospitalizations, with the greatest impacts among adults ≥65 years and persons with conditions associated with higher risk of influenza complications.
Mammary Epithelial Migration is EMT-Independent
Authors: Chen Jing , ma Rongze , Deng Zhixuan , Lu Yunzhe , Zhou Jiecan , Xia Kun , Klein Ophir D. , Lu Pengfei 
Published: October 2024

ABSTRACTEpithelial tissues are traditionally considered immobile, requiring epithelial-to-mesenchymal transition (EMT) for individual or collective cell migration as mesenchymal cells. However, recent studies indicate that the mammary epithelium migrates via mechanisms distinct from mesenchymal collectives. Here, we demonstrate that mammary epithelium does not undergo EMT before migration, as evidenced by cellular and molecular characteristics, including EMT marker expression at the mRNA, protein, localization, and transcriptomic levels. Contrary to established models, cell-cell adhesion is not diminished but is required for epithelial migration. Furthermore,Snail1does not repress cell-cell adhesion but instead plays a pivotal role in directing epithelial migration by regulating processes such as the directional movement of individual cells viaCdc42ep5. Our findings reveal the existence of both stationary and migratory states within the epithelium, providing new insights into how epithelial tissues transition between these states, with broad implications for organogenesis and cancer biology.
Knowledge Graphs and Explainable AI for Drug Repurposing on Rare Diseases
Authors: Perdomo-Quinteiro P. , Wolstencroft K. , Roos M. , Queralt-Rosinach N. 
Published: October 2024

ABSTRACTArtificial Intelligence (AI)-based drug repurposing is an emerging strategy to identify drug candidates to treat rare diseases. However, cutting-edge algorithms based on Deep Learning (DL) typically don’t provide a human understandable explanation supporting their predictions. This is a problem because it hampers the biologists’ ability to decide which predictions are the most plausible drug candidates to test in costly lab experiments. In this study, we proposerd-explainera novel AI drug repurposing method for rare diseases which obtains possible drug candidates together with human understandable explanations. The method is based on Graph Neural Network (GNN) technology and explanations were generated as semantic graphs using state-of-the-art eXplainable AI (XAI). The model learns features from current background knowledge on the target rare disease structured as a Knowledge Graph (KG), which integrates curated facts and their evidence on different biomedical entities such as symptoms, drugs, genes and ortholog genes. Our experiments demonstrate that our method has excellent performance that is superior to state-of-the-art models. We investigated the application of XAI on drug repurposing for rare diseases and we prove our method is capable of discovering plausible drug candidates based on testable explanations. The data and code are publicly available athttps://github.com/PPerdomoQ/rare-disease-explainer.HighlightsWe demonstrated the use of graph-based explainable AI for drug repurposing on rare diseases to accelerate sound discovery of new therapies for this underrepresented group.We developedrd-explainerfor rare disease specific drug research for faster translation. It predicts drugs to treat symptoms/phenotypes, it is highly performant and novel candidates are plausible according to evidence in the scientific literature and clinical trials. Key is that it learns a GNN model that is trained on a knowledge graph built specifically for a rare disease. We providerd-explainercode freely available for the community.rd-explaineris researcher-centric interpretable ML for hypothesis generation and lab-in-the-loop drug research. Explanations of predictions are semantic graphs in line with human reasoning.We detected an effect of knowledge graph topology on explainability. This highlights the importance of knowledge representation for the drug repurposing task.
Hydroxyurea induces ER stress and cytoplasmic protein aggregation
Authors: Sánchez-Molina Ana , Bernal Manuel , Posligua-García Joel D. , Pérez-Pulido Antonio J. , de Cubas Laura , Hidalgo Elena , Salas-Pino Silvia , Daga Rafael R. 
Published: October 2024

ABSTRACTThe endoplasmic reticulum (ER) lumen provides the proper redox environment for disulfide bond formation, which is required for the appropriate folding of proteins that enter the secretory pathway and constitute membranes. Defective protein folding in the ER activates proteostatic mechanisms that are now beginning to be elucidated. Here, we show that hydroxyurea (HU) causes ER stress and triggers a transient perinuclear ER expansion, which leads to the clustering of nuclear pore complexes. This striking phenotype is mimicked by diamide (DIA), a specific thiol stress inductor, and prevented or rapidly reverted by dithiothreitol, a dithiol-reducing agent, suggesting that ER expansion is caused by disulfide stress. ER expansion induced by HU or DIA depends on glutathione (GSH), is Ire1-independent, and is associated with a unique transcriptome program that differs from the canonical unfolding protein response (UPR). The ER luminal expansion accumulates Hsp70 Bip1 chaperone, and it evolves parallel with the appearance of cytoplasmic protein aggregates containing heat stress proteins (HSPs), indicating that both HU and DIA are impinging on protein folding. Thus, our data reveal that HU induces disulfide stress that impinges on protein folding in the cytoplasm and ER.
Determinants of consumers’ attitude towards mobile wallet adoption in Somalia
Authors: Mukhtar Yonis Ali , Barre Galad Mohamed 
Published: October 2024

PurposeThis study aims to empirically investigate the factors that influence consumers' attitudes and intentions to use mobile wallets in the context of Somalia. Additionally, the study examines the role of attitude as a mediator between independent variables and the dependent variable.Design/methodology/approachA multidisciplinary model is proposed, building on the Technology Acceptance Model (TAM), the Unified Theory of Acceptance and Use of Technology (UTAUT) and other relevant research on factors influencing technology adoption. Data were collected using a questionnaire, and convenience sampling was employed to select the respondents. A total of 321 respondents participated in the survey. Fifteen hypotheses were formulated, and PLS-SEM and SPSS software were used to estimate and test the hypothesized model.FindingsThe results show that factors including attitude, lifestyle condition (LC), perceived ease of use (PEOU) and perceived usefulness (PU) have a direct effect on the intention to use mobile wallets. However, facilitating conditions (FC), quality of internet connection (QIC), security (SEC) and trust do not have a direct effect on mobile wallet adoption. On the other hand, attitude mediates the relationship between facilitating conditions, lifestyle compatibility, perceived ease of use, perceived usefulness, quality of internet connection, security and mobile wallet adoption. Consumer attitude does not mediate the relationship between trust and mobile wallet adoption.Research limitations/implicationsThis empirical study was conducted only in Mogadishu, thus limiting its geographic scope. Future research on mobile wallets should consider more cities in Somalia. The data were collected at a specific point in time. Given the rapidly changing rate of mobile wallet usage, a longitudinal study might be warranted. Additionally, other variables such as relative advantage, perceived benefits, risk and additional factors could be considered.Practical implicationsAs lifestyle conditions, perceived ease of use and perceived usefulness emerged as important constructs for mobile wallet acceptance, there is a need to develop the best ease of use, the most suitable conditions and the highest perceived usefulness. The findings have managerial implications that can help banks providing mobile wallet services to increase the usage and adoption of their services.Originality/valueMobile wallets have introduced new digital payment options for consumers while also providing businesses and marketers with enhanced opportunities to promote their products and services online. However, there is limited research on the adoption of mobile wallets in Somalia. This study may be the first in Somalia to investigate mobile wallet adoption with a larger sample size compared to previous studies. It also proposes and validates additional constructs not included in the original model.
Empowering farmer community with technology modernisation to improve rice farming performance through demonstration farms in East Java, Indonesia
Authors: Mariyono Joko , Kuntariningsih Apri 
Published: October 2024

Purpose
Rice is a strategic commodity and staple food; thus, rice productivity should grow faster than the population. A public agricultural agency launched technology modernisation to improve rice farm performance. This study aims to assess the impact of technology modernisation on rice farming performance and evaluate farmer acceptance of such technology.

Design/methodology/approach
This study was conducted in 2023-2024, based on selected demonstration farms (demfarm) carried out during 2021-2022 in East Java, Indonesia, one of the rice bowls. Microeconomic theory of production and the double-differences approach were used as fundamental analyses. Farmers were purposively selected to participate in the demfarm. For comparison, farmers with existing technology adjacent to the demfarm were chosen accordingly. Rice production is considered an economic performance indicator, and factors related to socio-demographic and technical aspects were conceptualised using innovation and diffusion theory.

Findings
The results of demfarm were apparent. Technology modernisation improved rice farming’s economic performance. Farmer acceptance of such technology was relatively high at the first stage. There was no conflict between technology and local culture and norms. The technological package will likely be disseminated to farmers after adequate socialisation.

Research limitations/implications
This study engaged farmer innovators and early adopters in the demonstration farm. This needs more actions from farmers who are not categorised as innovators and early adopters, which dominate the farmer population.

Practical implications
Extension officials need field guidance to ensure continual technology adoption because of technology complexity.

Originality/value
The originality of the study is based on a field experiment and direct observation throughout a crop cycle, and the analysis is established using a solid theory and analytical framework.