bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of the human choline transporter-like protein CTL2 causes hearing impairment and a rare red blood cell phenotype
Authors: Koehl Bérengère , Vrignaud Cédric , Mikdar Mahmoud , Nair Thankam S. , Yang Lucy , Laiguillon Guy , Anselme-Martin Sophie , Giroux-Lathuile Claudine , Kenz Hanane El , Hermine Olivier , Mohandas Narla , Cartron Jean Pierre , Colin Yves , Detante Olivier , Le Van Kim Caroline , Carey Thomas E. , Azouzi Slim , Peyrard Thierry 
Published: May 2022

AbstractRecent genome-wide association and murine studies identified the human neutrophil antigen -3a/b polymorphism (HNA-3a/b) in SLC44A2 (rs2288904-G/A) as a risk factor in venous thromboembolism (VTE). The choline transporter-like protein CTL2 encoded by the SLC44A2 gene plays an important role in platelet aggregation and neutrophil interaction with the von Willebrand factor. By investigating alloantibodies to a high-prevalence antigen of unknown specificity, found in patients with a rare blood type, we showed that CTL2 is also expressed in red blood cells and carries a new blood group system. Furthermore, we identified three siblings of European ancestry who are homozygous for a large deletion in SLC44A2, resulting in complete CTL2 deficiency. Interestingly, the first-ever reported CTL2-deficient individuals suffer from progressive hearing impairment, recurrent arterial aneurysms and epilepsy. In contrast to Slc44a2-/- mice, CTL2null individuals showed normal platelet aggregation and do not suffer from any apparent hematological disorders. In addition, CD34+ cells from CTL2null patients undergo normal ex vivo erythropoiesis, indicating that CTL2 is not essential for erythroid proliferation and differentiation. Overall, our findings confirm the function of CTL2 in hearing preservation and provide new insights into the possible role of this protein in maintaining cerebrovascular homeostasis.
A meta-analysis of structural MRI studies of the brain in systemic lupus erythematosus (SLE)
Authors: Cox Jennifer G. , de Groot Marius , Cole James H. , Williams Steven C. R. , Kempton Matthew J. 
Published: May 2022

ABSTRACTObjectiveA comprehensive search of published literature in brain volumetry was conducted in three autoimmune diseases – Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Ulcerative Colitis (UC) with the intention of performing a meta-analysis of published data. Due to lack of data in RA and UC the reported meta-analysis was limited to SLE.MethodsThe MEDLINE database was searched for studies from 1988 through March 2022. A total of 175 papers met the initial inclusion criteria and 16 were included in a random effects meta-analysis. The reduction in the number of papers included in the final analysis is primarily due to the lack of overlap in measured and reported brain regions.ResultsA significantly lower volume was seen in patients with SLE in the hippocampus, corpus callosum and total gray matter volume measurements as compared to age and sex matched controls. There were not enough studies to perform a meta-analysis for RA and UC; instead we include a summary of published volumetric studies.ConclusionsThe meta-analyses revealed structural brain abnormalities in patients with SLE suggesting that lower global brain volumes are associated with disease status. This volumetric difference was seen in both the hippocampus and corpus callosum and total gray matter volume measurements. These results indicate both gray and white matter involvement in SLE and suggest there may be both localised and global reductions in brain volume.KEY MESSAGESWhat’s already known on this topicCentral nervous system effects of lupus are common, however, agreement on principally affected neuroanatomical regions is lacking.What this study addsThis study combines the volumetric neuroimaging data from previously published SLE literature in a meta-analysis. The hippocampus, corpus callosum and total gray matter volume in patients with SLE is smaller than in age and sex matched controls. Additionally, a summary of published data in RA and UC is provided.How this study might affect research, practice or policyThis is the first meta-analysis on neuroimaging studies of volume differences in SLE. The regions identified can inform further research on disease progression and therapy evaluation targeted at brain volumetric changes in SLE.These results provide specific regions of interest to further explore in the central treatment and management of SLE. While these regions are shown to be directly affected, additional brain regions may be implicated. Further research to understand the potential link between these volumetric measurements and behavioural/cognitive changes observed in patients with lupus is warranted.
Implication of Hepsin from primary tumor in the prognosis of colorectal cancer patients
Authors: Zaragoza-Huesca David , Nieto-Olivares Andrés , García-Molina Francisco , Ricote Guillermo , Montenegro Sofía , Sánchez-Cánovas Manuel , Garrido-Rodríguez Pedro , Peñas-Martínez Julia , Vicente Vicente , Martínez Francisco , Luisa-Lozano María , Carmona-Bayonas Alberto , Martínez-Martínez Irene 
Published: May 2022

ABSTRACTBackgroundHepsin is a type II transmembrane serine protease whose functions include degradation of the extracellular matrix and activation of factor VII. In many tumors, hepsin dysregulation leads to tumor invasion by proteolysis of pericellular components. Colorectal cancer is a tumor with high thrombotic and metastatic risk, but the role of hepsin is unknown.ObjectivesTo study the correlations between hepsin expression in the primary tumor and different clinical-histopathological variables in patients with localized and metastatic colorectal cancer.MethodsA cohort of 287 patients, 169 with localized colorectal cancer and 118 with metastases at diagnosis, was recruited. Tissue microarrays were made from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin levels were determined and the association with clinical-histopathological variables was evaluated using the chi-square and Kruskal-Wallis tests. Time-to-event results and cumulative incidence functions were calculated using Kaplan-Meier and Aalen-Johansen estimators, in combination with Cox and Fine&Gray multivariate models.ResultsIn patients with localized colorectal cancer, high intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). In this context, according to multivariable Cox regression, medium and high intensity of hepsin expression versus low intensity was associated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value=0.035, and hazard ratio 3.30, p-value=0.012, respectively), being a more accurate prognostic factor than classic histological variables. Also, in patients with localized colorectal cancer, the cumulative incidence of thrombosis at 5 years increased significantly with higher hepsin levels (p-value = 0.038). According to the multivariate Fine&Gray regression, the medium and high intensity of hepsin with respect to the low intensity, was associated with an increase in thrombotic risk (hazard ratio 7.71, p-value=0.043 and hazard ratio 9.02, p-value=0.028, respectively). This relationship between hepsin and thrombosis was independent of previous tumor relapse (p-value = 0.036). In patients with metastatic colorectal cancer, low intensity of hepsin was associated with a low degree of tumor differentiation (p-value <0.001) and spread to more than one metastatic site (p-value = 0.023).ConclusionHepsin is a potential biomarker of thrombosis and metastasis in patients with localized colorectal cancer. Validation in a larger series and clarification of the underlying mechanism may be helpful in evaluating these patients. In metastatic patients, Hepsin behaves in a paradoxical way with respect to differentiation and invasion processes.
Clinical Performance of Direct RT-PCR Testing of Raw Saliva for Detection of SARS-CoV-2 in Symptomatic and Asymptomatic Individuals
Authors: Castillo-Bravo Rosa , Lucca Noel , Lai Linyi , Marlborough Killian , Brychkova Galina , Lonergan Charlie , O’Grady Justin , Alikhan Nabil-Fareed , Trotter Alexander J. , Page Andrew J. , Smyth Breda , McKeown Peter C. , Feenstra Jelena D. M. , Ulekleiv Camilla , Sorel Oceane , Gandhi Manoj , Spillane Charles 
Published: May 2022

AbstractRT-qPCR tests based on RNA extraction from nasopharyngeal swab samples are promoted as the “gold standard” for SARS-CoV-2 detection. However, self-collected saliva samples offer a non-invasive alternative more suited to high-throughput testing. This study evaluated the performance of TaqPath COVID-19 Fast PCR Combo Kit 2.0 assay for detection of SARS-CoV-2 in raw saliva relative to a lab-developed direct RT-qPCR test (SalivaDirect-based PCR) and a RT-qPCR test based on RNA extraction from NPS samples. Both samples were collected from symptomatic and asymptomatic individuals (N=615). Saliva samples were tested for SARS-CoV-2 using the TaqPath COVID-19 Fast PCR Combo Kit 2.0 and the SalivaDirect-based PCR, while RNA extracts from NPS samples were tested by RT-qPCR according to the Irish national testing system. The TaqPath™ COVID-19 Fast PCR detected SARS-CoV-2 in 52 saliva samples, of which 51 were also positive with the SalivaDirect-based PCR. 49 samples displayed concordant results with the NPS extraction-based method, while three samples were positive on raw saliva. Among the negative samples, 10 discordant cases were found with the TaqPath COVID-19 Fast PCR (PPA–85.7%; NPA–99.5%), when compared to the RNA extraction-based NPS method, performing similarly to the SalivaDirect-based PCR (PPA-87.5%; NPA-99.5%). The direct RT-qPCR testing of saliva samples shows high concordance with NPS extraction-based method for SARS-CoV-2 detection, providing a cost-effective and highly-scalable system for high-throughput COVID-19 rapid-testing.
Common Genetic Risk Factors in ASD and ADHD Co-occurring Families
Authors: Zhou Anbo , Cao Xiaolong , Mahaganapathy Vaidhyanathan , Azaro Marco , Gwin Christine , Wilson Sherri , Buyske Steven , Bartlett Christopher W. , Flax Judy F. , Brzustowicz Linda M. , Xing Jinchuan 
Published: May 2022

AbstractAutism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two major neurodevelopmental disorders that frequently co-occur. However, the genetic mechanism of the co-occurrence remains unclear. The New Jersey Language and Autism Genetics Study (NJLAGS) collected more than 100 families with at least one member affected by ASD. NJLAGS families show a high prevalence of ADHD and provide a good opportunity to study shared genetic risk factors for ASD and ADHD. The linkage study of the NJLAGS families revealed regions on chromosomes 12 and 17 that are significantly associated with ADHD. Using whole genome sequencing data on 272 samples from 73 NJLAGS families, we identified potential risk genes for ASD and ADHD. Within the linkage regions, we identified 36 genes that are associated with ADHD using a pedigree-based gene prioritization approach.KDM6B(Lysine Demethylase 6B) is the highest-ranking gene, which is a known risk gene for neurodevelopmental disorders, including ASD and ADHD. At the whole genome level, we identified 207 candidate genes from the analysis of both small variants and structure variants, including both known and novel genes. Using enrichment and protein-protein interaction network analyses, we identified gene ontology terms and pathways enriched for ASD and ADHD candidate genes, such as cilia function and cation channel activity. Candidate genes and pathways identified in our study provide a better understanding of the genetic etiology of ASD and ADHD and will lead to new diagnostic or therapeutic interventions for ASD and ADHD in the future.
No evidence for detectable direct effects of magnetic field on cellular autofluorescence
Authors: Uzhytchak Mariia , Smolková Barbora , Frtús Adam , Stupakov Alexandr , Lunova Mariia , Scollo Federica , Hof Martin , Jurkiewicz Piotr , Sullivan Gareth John , Dejneka Alexandr , Lunov Oleg 
Published: May 2022

ABSTRACTDramatically increased levels of electromagnetic radiation in the environment have raised concerns over the potential health hazards of electromagnetic fields. Various biological effects of magnetic fields have been proposed. Despite decades of intensive research, the molecular mechanisms procuring cellular responses remain largely unknown. The current literature is conflicting with regards to evidence that magnetic fields affect functionality directly at cellular level. Therefore, a search for potential direct cellular effects of magnetic fields represents a cornerstone that may propose an explanation for potential health hazards associated with magnetic fields. Recently, it was postulated that autofluorescence of HeLa cells is magnetic field sensitive, relying on single-cell imaging kinetic measurements. Here, we explore the utility of this approach by undertaking a screen for magnetic sensitivity of cellular autofluorescence in statistically relevant numbers (90-107) of HeLa cells. We did not observe any changes in cellular autofluorescence decay, when a modulated magnetic field was applied. We present a number of arguments indicating weak points in the analysis of magnetic field effects based on the imaging of cellular autofluorescence decay. Our work indicates that new methods are required to elucidate the effects of magnetic fields at the cellular level.
Oversharing by honey bees and the spread of viruses
Authors: Lamas Zachary S. , Ryabov Eugene V. , Hawthorne David J. , Evans Jay D. 
Published: May 2022

AbstractDeformed wing virus (DWV) is an emerging insect pathogen efficiently transmitted through communicable and vector-borne routes with Apis mellifera. Continual transmission of DWV between hosts and vectors is required for maintenance of the pathogen within the population, and this vector-host-pathogen system offers unique disease transmission dynamics for pathogen maintenance between vector and a social host. In a series of experiments, we study how vector-vector, host-host and host-vector transmission routes maintain DWV in a honey bee population. We found co-infestations on shared hosts allowed for movement of DWV from mite to mite. Additionally, two social behaviors of the honeybee, trophallaxis and cannibalization of pupae, provide routes for communicable transmission from bee to bee. Communicable circulation of the virus solely amongst hosts was then shown to act as a reservoir of DWV for naïve Varroa to acquire and subsequently vector the pathogen. Our findings illustrate communicable transmission between hosts can maintain and influence the future acquisition and vectoring of a pathogen by a vector. There are a handful of other infectious diseases, both zoonotic and which impact human health, that have potentially similar transmission dynamics.
The spatiotemporal dynamics of recognition memory for complex versus simple auditory sequences
Authors: Fernández Rubio G. , Brattico E. , Kotz S. A. , Kringelbach M. L. , Vuust P. , Bonetti L. 
Published: May 2022

AbstractDifferently from visual recognition, auditory recognition is a process relying on the organization of single elements that evolve in time. Here, we aimed to discover the spatiotemporal dynamics of this cognitive function by adopting a novel strategy for varying the complexity of musical sequences. We selected traditional tonal musical sequences and altered the distance between pitches to obtain matched atonal sequences. We then recorded the brain activity of 71 participants using magnetoencephalography (MEG) while they listened to and later recognized auditory sequences constructed according to simple (tonal) or complex (atonal) conventions. Results reveal qualitative changes in neural activity dependent on stimulus complexity: recognition of tonal sequences engaged hippocampal and cingulate areas, whereas recognition of atonal sequences mainly activated the auditory processing network. Our findings highlight the involvement of a cortico-subcortical brain network for auditory recognition and support the idea that stimulus complexity qualitatively alters the neural pathways of recognition memory.
Novel synergistic combinations of last-line antibiotics and FDA-approved drugs against Klebsiella pneumoniae revealed by in vitro synergy screenings
Authors: Gómara-Lomero Marta , Aínsa José Antonio , Ramón-García Santiago 
Published: May 2022

AbstractTreatment of infections caused by multi-drug resistant (MDR) enterobacteria remains challenging due to the limited therapeutic options. Drug repurposing could accelerate the development of urgently needed successful interventions. This work aimed to identify and characterize novel drug combinations againstKlebsiella pneumoniaebased on the concepts of synergy and drug repurposing. We performed a semi-qualitative high-throughput synergy screening (sHTSS) with tigecycline, colistin and fosfomycin (last-line antibiotics against MDR Enterobacteriaceae) combined with an FDA-library containing 1,430 clinically approved drugs. Selected hits were further validated by secondary checkerboard (CBA) and time-kill (TKA) assays. Our sHTSS results yielded 37, 31 and 41 hits showing synergy with tigecycline, colistin and fosfomycin, respectively. Most hits (75%) were known antibiotics. Non-antibiotic compounds included other anti-infective agents (7%), antineoplastics (7%) or antipsychotics (3%). Overall, 15.09% and 65.85% of hits were further confirmed by CBA and TKA, respectively, indicating that TKA is more useful than CBA for the validation of synergistic combinations. Accordingly, TKA were used for synergy classification based on determination of the bactericidal activities at 8, 24 and 48 hours. Twenty-seven combinations were validated with effective synergistic activity againstK. pneumoniaeby TKA, six of them novel non-antibiotic combinations. Based on our observations we conclude that repurposing approaches allowed to enhance the activity of last-line antibiotics in the treatment of MDRK. pneumoniae. sHTSS paired to TKA was a powerful tool for the identification of novel synergistic drug combinations againstK. pneumoniae. Further pre-clinical studies might support the translational potential of these novel combinations.
Insights into plastic biodegradation: community composition and functional capabilities of the superworm (Zophobas morio) microbiome in styrofoam feeding trials
Authors: Sun Jiarui , Prabhu Apoorva , Aroney Samuel , Rinke Christian 
Published: May 2022

ABSTRACTPlastics are inexpensive and widely used organic polymers, but their high durability hinders biodegradation. Polystyrene, including extruded polystyrene also known as styrofoam, is among the most commonly produced plastics worldwide and is recalcitrant to microbial degradation. In this study, we assessed changes in the gut microbiome of superworms (Zophobas morio) reared on bran, polystyrene, or under starvation conditions over a three weeks’ time period. Superworms on all diets were able to complete their life cycle to pupae and imago, although superworms reared on polystyrene had minimal weight gains, resulting in lower pupation rates. The change in microbial gut communities from baseline differed considerably between diet groups, with polystyrene and starvation groups characterized by a loss of microbial diversity and the presence of opportunistic pathogens. Inferred microbial functions enriched in the polystyrene group included transposon movements, membrane restructuring, and adaptations to oxidative stress. We detected several encoded enzymes with reported polystyrene and styrene degradation abilities, supporting previous reports of polystyrene degrading bacteria in the superworm gut. By recovering metagenome-assembled genomes (MAGs) we linked phylogeny and functions and identified genera includingPseudomonas, RhodococcusandCorynebacterium, that possess genes associated with polystyrene degradation. In conclusion, our results provide the first metagenomic insights into the metabolic pathways used by the gut microbiome of superworms to degrade polystyrene. Our results also confirm that superworms can survive on polystyrene feed, however, this diet has considerable negative impacts on host gut microbiome diversity and health.Impact StatementIncreasing plastic pollution is a major environmental problem, and a recently proposed way to counteract this trend is to embrace a circular economy, in which used materials are recycled, rather than disposed of. An important step to facilitate this process is to invent new approaches for upcycling of plastic waste to desirable consumer products. Microbial plastic degradation and conversion is likely to play a considerable part in shaping a circular economy, by engineering microbes or their enzymes to bio-upcycle plastic waste. A first step towards actualizing this goal is to identify microbes that can degrade polystyrene and to investigate the enzymes and pathways involved. Our study represents the first metagenomic analysis of an insect gut microbiome on a polystyrene diet. It identifies bacteria with polystyrene and styrene degrading abilities, and infers enzymes and pathways involved in these reactions. Therefore, our results contribute towards understanding microbial polystyrene degradation and will provide a base for future investigations into microbial upcycling of plastic waste.
Mannose metabolism inhibition sensitizes acute myeloid leukemia cells to cytarabine and FLT3 inhibitor therapy by modulating fatty acid metabolism to drive ferroptotic cell death
Authors: Woodley Keith , Dillingh Laura S , Giotopoulos George , Madrigal Pedro , Rattigan Kevin M , Philippe Celine , Dembitz Vilma , Magee Aoife M.S , Asby Ryan , van de Lagemaat Louie N , Mapperley Christopher , James Sophie C , Prehn Jochen H.M , Tzelepis Konstantinos , Rouault-Pierre Kevin , Vassiliou George S , Kranc Kamil R , Helgason G Vignir , Huntly Brian J.P , Gallipoli Paolo 
Published: May 2022

AbstractResistance to standard and novel therapies remains the main obstacle to cure in acute myeloid leukemia (AML) and is often driven by metabolic adaptations which are therapeutically actionable. Here we identify inhibition of mannose-6-phosphate isomerase (MPI), the first enzyme in the mannose metabolism pathway, as a sensitizer to both cytarabine and FLT3 inhibitors across multiple AML models. Mechanistically, we identify a connection between mannose metabolism and fatty acid metabolism, that is mediated via preferential activation of the ATF6 arm of the unfolded protein response (UPR). This in turn leads to cellular accumulation of polyunsaturated fatty acids, lipid peroxidation and ferroptotic cell death in AML cells. Our findings provide further support to the role of rewired metabolism in AML therapy resistance, unveil a novel connection between two apparently independent metabolic pathways and support further efforts to achieve eradication of therapy-resistant AML cells by sensitizing them to ferroptotic cell death.