bluuebunny/crossref_metadata_2025_split huggingface dataset:
RUNX1/CD44 axis regulates the proliferation, migration, and immunotherapy of gliomas: A single-cell sequencing analysis
Authors: Zhang Hao , Cao Hui , Luo Hong , Zhang Nan , Wang Zeyu , Dai Ziyu , Wu Wantao , Liu Guodong , Xie Zongyi , Cheng Quan , Cheng Yuan 
Published: January 2023

BackgroundGlioma is one of the most common, primary, and lethal adult brain tumors because of its extreme aggressiveness and poor prognosis. Several recent studies relevant to the immune function of CD44, a transmembrane glycoprotein as a significant hyaluronic acid receptor, have achieved great success, revealing the critical role of CD44 in immune infiltration in gliomas. The overexpression of CD44 has been verified to correlate with cancer aggressiveness and migration, while the clinical and immune features of CD44 expression have not yet been thoroughly characterized in gliomas.MethodsMolecular and clinical data of glioma collected from publicly available genomic databases were analyzed.ResultsCD44 was up-expressed in malignant gliomas, notably in the 1p/19q non-codeletion cases, isocitrate dehydrogenase (IDH) wild-type, and mesenchymal subtypes in GBM samples. CD44 expression level strongly correlates with stromal and immune cells, mainly infiltrating the glioma microenvironment by single-cell sequencing analysis. Meanwhile, CD44 can be a promising biomarker in predicting immunotherapy responses and mediating the expression of PD-L1. Finally, RUNX1/CD44 axis could promote the proliferation and migration of gliomas.ConclusionsTherefore, CD44 was responsible for glioma growth and progression. It could potentially lead to a novel target for glioma immunotherapy or a prognostic biomarker.
Sequencing to identify pathogens in Tenebrio molitor: Implications in insects farmed for food and feed
Authors: Leierer Dewey , Olmstead Morgan , Oppert Brenda 
Published: January 2023

IntroductionThe farmed insect industry is increasing in number and size to meet the demand for sustainably-produced protein. Larger insect farms are prone to losses due to pathogens, and more information is needed regarding the health of insects reared for food and feed.MethodsIn this study, high throughput sequencing was used to identify potential pathogens in a colony of Tenebrio molitor (yellow mealworm, Coleoptera: Tenebrionidae) that exhibited increased mortality in immature stages with eventual colony collapse. Sequences also were obtained from a healthy new colony of T. molitor, as well as a recovered individual from the collapsed colony.ResultsScreening of sequences obtained from the colonies and their rearing diet indicated that the collapsed colony had low diversity in microbial taxa, with predominantly sequences from the families Staphylococcaeceae and Streptococcaceae constituting from 53 to 88% of the total microbial reads. Conversely, in the new colony and their rearing diet, microbial sequences were from more than 15 different taxa, with Lactobacilleceae the most prevalent but representing only 21% of the total microbial reads. Evidence indicates that Bacillus thuringiensis may have been involved in the collapse of the colony, leading to sepsis and microbial dysbiosis, although the source of the bacteria was not identified. Sequences from the recovered individual reflected a microbial flora profile that was intermediate between those of the diseased collapsed and new colonies.DiscussionThese findings have implications for insects reared in confined environments and provide a rapid method to screen insect colonies by sequencing healthy and potentially diseased individuals.
Pathways of methane removal in the sediment and water column of a seasonally anoxic eutrophic marine basin
Authors: Żygadłowska Olga M. , Venetz Jessica , Klomp Robin , Lenstra Wytze K. , van Helmond Niels A. G. M. , Röckmann Thomas , Wallenius Anna J. , Martins Paula Dalcin , Veraart Annelies J. , Jetten Mike S. M. , Slomp Caroline P. 
Published: January 2023

Methane (CH4) is a key greenhouse gas. Coastal areas account for a major proportion of marine CH4 emissions. Eutrophication and associated bottom water hypoxia enhance CH4 production in coastal sediments. Here, we assess the fate of CH4 produced in sediments at a site in a seasonally anoxic eutrophic coastal marine basin (Scharendijke, Lake Grevelingen, the Netherlands) in spring (March) and late summer (September) in 2020. Removal of CH4 in the sediment through anaerobic oxidation with sulfate (SO42-) is known to be incomplete in this system, as confirmed here by only slightly higher values of δ13C-CH4 and δD-CH4 in the porewater in the shallow sulfate-methane-transition zone (~5-15 cm sediment depth) when compared to deeper sediment layers. In March 2020, when the water column was fully oxygenated, CH4 that escaped from the sediment was at least partially removed in the bottom water through aerobic oxidation. In September 2020, when the water column was anoxic below ~35 m water depth, CH4 accumulated to high concentrations (up to 73 µmol L-1) in the waters below the oxycline. The sharp counter gradient in oxygen and CH4 concentrations at ~35 m depth and increase in δ13C-CH4 and δD-CH4 above the oxycline indicate mostly aerobic water column removal of CH4. Water column profiles of particulate and dissolved Fe and Mn suggest redox cycling of both metals at the oxycline, pointing towards a potential role of metal oxides in CH4 removal. Water column profiles of NH4+ and NO3- indicate removal of both solutes near the oxycline. Analyses of 16S rRNA gene sequences retrieved from the water column reveal the presence of aerobic CH4 oxidizing bacteria (Methylomonadaceae) and anaerobic methanotrophic archaea (Methanoperedenaceae), with the latter potentially capable of NO3- and/or metal-oxide dependent CH4 oxidation, near the oxycline. Overall, our results indicate sediment and water column removal of CH4 through a combination of aerobic and anaerobic pathways, which vary seasonally. Some of the CH4 appears to escape from the surface waters to the atmosphere, however. We conclude that eutrophication may make coastal waters a more important source of CH4 to the atmosphere than commonly assumed.
SARS-CoV-2 epidemiology, antibody dynamics, and neutralisation capacity in Irish healthcare workers in the era of booster COVID-19 vaccinations
Authors: McGrath Jonathan , Kenny Claire , Nielsen Charlotte Salgaard , Domegan Lisa , Walsh Cathal , Rooney Peadar , Walsh Shane , Conlon Niall , Brady Gareth , Ibrahim Aya , Dunne Jean , McCormack William , Corcoran Niamh , Allen Niamh , Fleming Catherine , Bergin Colm 
Published: January 2023

BackgroundThe PRECISE Study, a multi-phase cross-sectional seroprevalence study of anti-SARS-CoV-2 antibodies in Irish healthcare workers (HCW) investigated: (1) risk factors for SARS-CoV-2 seropositivity, (2) the durability of antibody responses in a highly vaccinated HCW cohort, and (3) the neutralisation capacity of detected antibodies, prior to booster COVID-19 vaccination.Materials and methodsSerology samples were collected across two hospital sites in November 2021 and analysed using the Roche Elecsys Anti-SARS-CoV-2/Elecsys-S Anti-SARS-CoV-2 assays to detect anti-nucleocapsid (N) and anti-spike (S) antibodies respectively. Paired serology results from prior study phases were used to analyse changes in individual HCW serostatus over time. Risk-factors for SARS-CoV-2 infection were assessed for demographic and work-related factors. Antibody neutralisation capacity was assessed in a subset of samples via an in vitro ACE2 binding enzyme-linked immunosorbent assay.Results2,344 HCW samples were analysed. Median age was 43 years (IQR 33–50) with 80.5% (n = 1,886) female participants. Irish (78.9%, n = 1,850) and Asian (12.3%, n = 288) were the most commonly reported ethnicities. Nursing/midwifery (39.3%, n = 922) was the most common job role. 97.7% of participants were fully vaccinated, with Pfizer (81.1%, n = 1,902) and AstraZeneca (16.1%, n = 377) the most common vaccines received. Seroprevalence for anti-SARS-CoV-2 antibodies indicating prior infection was 23.4%, of these 33.6% represented previously undiagnosed infections. All vaccinated participants demonstrated positive anti-S antibodies and in those with paired serology, no individual demonstrated loss of previously positive anti-S status below assay threshold for positivity. Interval loss of anti-N antibody positivity was demonstrated in 8.8% of previously positive participants with paired results. Risk factors for SARS-CoV-2 seropositivity suggestive of previous infection included age 18–29 years (aRR 1.50, 95% CI 1.19–1.90, p &lt; 0.001), India as country of birth (aRR 1.35, 95% CI 1.01–1.73, p = 0.036), lower education level (aRR 1.35, 95% CI 1.11–1.66, p = 0.004) and HCA job role (aRR 2.12, 95% CI 1.51–2.95, p &lt; 0.001). Antibody neutralisation varied significantly by anti-SARS-CoV-2 antibody status, with highest levels noted in those anti-N positive, in particular those with vaccination plus previous SARS-CoV-2 infection.ConclusionAll vaccinated HCWs maintained anti-S positivity prior to COVID-19 booster vaccination, however anti-N positivity was more dynamic over time. Antibody neutralisation capacity was highest in participants with COVID-19 vaccination plus prior SARS-CoV-2 infection.
Association between endocrine therapy and cognitive decline in breast cancer based on propensity score matching
Authors: Yin Yulian , Jin Lan , Chu Meiling , Zhou Yue , Tu Siyuan , Cheng Yifan , Ye Meina , Wu Jingjing , Chen Hongfeng 
Published: January 2023

PurposeTo study the status quo of the cognitive function of the breast cancer patients with (who went through) the endocrine therapy by the epidemiological investigation, analyze the key factor of the cognition impairment and explore the impact of the endocrine therapy time on the cognition decline after using Propensity Score Matching to balance the covariates.MethodsIn this study, the epidemiological questionnaire information was collected from 226 female breast cancer endocrine treatment patients who visited the Breast Clinic of Longhua Hospital Affiliated to Shanghai University of Chinese Medicine from November 2020 to February 2022, and the results of the overall cognitive function, the function test of each cognitive domain, the patient’s self-cognition, quality of life, and emotional status evaluation of the patients. In this study, according to the principle of random matching, the nearest matching method with a matching tolerance of 0.2 and a matching ratio of 1:2 was used for orientation score matching. After the covariant such as age, BMI, and duration of education were balanced, the effects of the duration of endocrine therapy on the overall cognitive function and the functions of each cognitive domain were analyzed.ResultsIn 226 cases of female breast cancer patients (who went through) the endocrine therapy, the propensity score matching was performed, ultimately, 99 were ruled out, successful matched ones were 49 of the cognition-decline group and 78 of the standard group. With age, education time, BMI and other covariates balanced, the endocrine therapy duration was the risk factor of the cognition impairment (P &lt; 0.05, OR = 1.296, 95% CI = 1.008−1.665), with the extension of endocrine treatment time, there was a rising risk of the cognition impairment (LLA statistic = 5.872, P &lt; 0.05). The cognitive domain scores in the cognition-decline group were lower than the standard group (P &lt; 0.05), but there was a difference in self-report cognition.ConclusionThe endocrine therapy duration was the risk factor for the cognition impairment of the breast cancer patients, and with prolonged endocrine treatment, there was a rising (an increasing) risk for the cognition impairment.
Regulation of autophagy and lipid accumulation under phosphate limitation in Rhodotorula toruloides
Authors: Wang Ya-nan , Liu Fang-jie , Liu Hong-di , Zhang Yue , Jiao Xiang , Ye Ming-liang , Zhao Zong-bao Kent , Zhang Su-fang 
Published: January 2023

BackgroundIt is known that autophagy is essential for cell survival under stress conditions. Inorganic phosphate (Pi) is an essential nutrient for cell growth and Pi-limitation can trigger autophagy and lipid accumulation in oleaginous yeasts, yet protein (de)-phosphorylation and related signaling events in response to Pi limitation and the molecular basis linking Pi-limitation to autophagy and lipid accumulation remain elusive.ResultsHere, we compared the proteome and phosphoproteome of Rhodotorula toruloides CGMCC 2.1389 under Pi-limitation and Pi-repletion. In total, proteome analysis identified 3,556 proteins and the phosphoproteome analysis identified 1,649 phosphoproteins contained 5,659 phosphosites including 4,499 pSer, 978 pThr, and 182 pTyr. We found Pi-starvation-induced autophagy was regulated by autophagy-related proteins, but not the PHO pathway. When ATG9 was knocked down, the engineered strains produced significantly less lipids under Pi-limitation, suggesting that autophagy required Atg9 in R. toruloides and that was conducive to lipid accumulation.ConclusionOur results provide new insights into autophagy regulation under Pi-limitation and lipid accumulation in oleaginous yeast, which should be valuable to guide further mechanistic study of oleaginicity and genetic engineering for advanced lipid producing cell factory.
Aeromonas hydrophila ST251 and Aeromonas dhakensis are major emerging pathogens of striped catfish in Vietnam
Authors: Bartie Kerry L. , Ngô Thao P. H. , Bekaert Michaël , Hoang Oanh Dang Thi , Hoare Rowena , Adams Alexandra , Desbois Andrew P. 
Published: January 2023

IntroductionAeromonads are ubiquitous in aquatic environments and several species are opportunistic pathogens of fish. Disease losses caused by motile Aeromonas species, particularly Aeromonas hydrophila, can be challenging in intensive aquaculture, such as at striped catfish (Pangasianodon hypophthalmus) farms in Vietnam. Outbreaks require antibiotic treatments, but their application is undesirable due to risks posed by resistance. Vaccines are an attractive prophylactic and they must protect against the prevalent strains responsible for ongoing outbreaks.MethodsThis present study aimed to characterize A. hydrophila strains associated with mortalities in striped catfish culture in the Mekong Delta by a polyphasic genotyping approach, with a view to developing more effective vaccines.ResultsDuring 2013–2019, 345 presumptive Aeromonas spp. isolates were collected at farms in eight provinces. Repetitive element sequence-based PCR, multi-locus sequence typing and whole-genome sequencing revealed most of the suspected 202 A. hydrophila isolates to belong to ST656 (n = 151), which corresponds to the closely-related species Aeromonas dhakensis, with a lesser proportion belonging to ST251 (n = 51), a hypervirulent lineage (vAh) of A. hydrophila already causing concern in global aquaculture. The A. dhakensis ST656 and vAh ST251 isolates from outbreaks possessed unique gene sets compared to published A. dhakensis and vAh ST251 genomes, including antibiotic-resistance genes. The sharing of resistance determinants to sulphonamides (sul1) and trimethoprim (dfrA1) suggests similar selection pressures acting on A. dhakensis ST656 and vAh ST251 lineages. The earliest isolate (a vAh ST251 from 2013) lacked most resistance genes, suggesting relatively recent acquisition and selection, and this underscores the need to reduce antibiotics use where possible to prolong their effectiveness. A novel PCR assay was designed and validated to distinguish A. dhakensis and vAh ST251 strains.DiscussionThis present study highlights for the first time A. dhakensis, a zoonotic species that can cause fatal human infection, to be an emerging pathogen in aquaculture in Vietnam, with widespread distribution in recent outbreaks of motile Aeromonas septicaemia in striped catfish. It also confirms vAh ST251 to have been present in the Mekong Delta since at least 2013. Appropriate isolates of A. dhakensis and vAh should be included in vaccines to prevent outbreaks and reduce the threat posed by antibiotic resistance.
Combined transcriptome and proteome analysis of Bcfrp1 involved in regulating the biosynthesis of abscisic acid and growth in Botrytis cinerea TB-31
Authors: Chen Dongbo , Shu Dan , Wei Zhao , Luo Di , Yang Jie , Li Zhemin , Tan Hong 
Published: January 2023

IntroductionAbscisic acid (ABA) is an important sesquiterpene compound that regulates the stress resistance of plants. Botrytis cinerea can synthesize ABA via the mevalonic acid pathway. To identify the functional genes that are involved in the biosynthesis of ABA, we performed insertion mutagenesis into B. cinerea TB-31.MethodsWe obtained the ABA-reduced mutant E154 by insertion mutagenesis, and we identified the insertion site was located upstream of the gene bcfrp1 by Thermal asymmetric interlaced PCR. We performed a detailed phenotypic characterization of the bcfrp1 knockout and complementation mutants in TB-31. Furthermore, transcriptome and proteome analyses were conducted to explore how bcfrp1 affects the level of the ABA biosynthesis.ResultsThe bcfrp1 gene encodes an F-box protein. The phenotypic results confirmed the positive contribution of bcfrp1 to the biosynthesis of ABA and growth. Between TB-31 and ΔBcfrp1, we obtained 4,128 and 1,073 differentially expressed genes and proteins, respectively. The impaired ABA biosynthesis in the ΔBcfrp1 mutants was primarily affected by the different levels of expression of the ABA biosynthetic gene cluster and the genes involved in the mevalonic acid pathway. In addition, we further characterized the differentially expressed genes and proteins that participated in the growth, secondary metabolism, and signal transduction in B. cinerea based on the transcriptome and proteome data.DiscussionThis research based on the transcriptome and proteome analyses to display the changes after the deletion of bcfrp1 in B. cinerea TB-31, will help us to explore the molecular mechanism of ABA biosynthesis in B. cinerea.
Brain blood vessel autoantibodies in patients with NMDA and GABAA receptor encephalitis: identification of unconventional Myosin-X as target antigen
Authors: Li Lucie Y. , Kreye Jakob , Burek Malgorzata , Cordero-Gomez César , Barthel Paula C. , Sánchez-Sendín Elisa , Kornau Hans-Christian , Schmitz Dietmar , Scharf Madeleine , Meybohm Patrick , Reincke S. Momsen , Prüss Harald , Höltje Markus 
Published: January 2023

Introduction: The antibody repertoire from CSF-derived antibody-secreting cells and memory B-cells in patients with encephalitis contains a considerable number of antibodies that do not target the disease-defining autoantigen such as the GABA or NMDA receptors. This study focuses on the functional relevance of autoantibodies to brain blood vessels in patients with GABAA and NMDA receptor encephalitis.Methods: We tested 149 human monoclonal IgG antibodies from the cerebrospinal fluid of six patients with different forms of autoimmune encephalitis on murine brain sections for reactivity to blood vessels using immunohistochemistry. Positive candidates were tested for reactivity with purified brain blood vessels, effects on transendothelial electrical resistance (TEER), and expression of tight junction proteins as well as gene regulation using human brain microvascular endothelial hCMEC/D3 cells as in vitro blood-brain barrier model. One blood-vessel reactive antibody was infused intrathecally by pump injection in mice to study in vivo binding and effects on tight junction proteins such as Occludin. Target protein identification was addressed using transfected HEK293 cells.Results: Six antibodies reacted with brain blood vessels, three were from the same patient with GABAAR encephalitis, and the other three were from different patients with NMDAR encephalitis. One antibody from an NMDAR encephalitis patient, mAb 011-138, also reacted with cerebellar Purkinje cells. In this case, treatment of hCMEC/D3 cells resulted in decreased TEER, reduced Occludin expression, and mRNA levels. Functional relevance in vivo was confirmed as Occludin downregulation was observed in mAb 011-138-infused animals. Unconventional Myosin-X was identified as a novel autoimmune target for this antibody.Discussion: We conclude that autoantibodies to blood vessels occur in autoimmune encephalitis patients and might contribute to a disruption of the blood-brain barrier thereby suggesting a potential pathophysiological relevance of these antibodies.
Gene panel analysis of 119 index patients with suspected periodic paralysis in Japan
Authors: Yuan Jun-Hui , Higuchi Yujiro , Hashiguchi Akihiro , Ando Masahiro , Yoshimura Akiko , Nakamura Tomonori , Hiramatsu Yu , Sakiyama Yusuke , Takashima Hiroshi 
Published: January 2023

IntroductionGenetic factors are recognized as the major reason for patients with periodic paralysis. The goal of this study was to determine the genetic causes of periodic paralysis in Japan.MethodsWe obtained a Japanese nationwide case series of 119 index patients (108 men and 11 women) clinically suspected of periodic paralysis, and a gene panel analysis, targeting CACNA1S, SCN4A, and KCNJ2 genes, was conducted.ResultsFrom 34 cases, 25 pathogenic/likely pathogenic/unknown significance variants were detected in CACNA1S (nine cases), SCN4A (19 cases), or KCNJ2 (six cases), generating a molecular diagnostic rate of 28.6%. In total, seven variants have yet been found linked to periodic paralysis previously. The diagnostic yield of patients with hypokalemic and hyperkalemic periodic paralyzes was 26.2 (17/65) and 32.7% (17/52), respectively. A considerably higher yield was procured from patients with than without positive family history (18/25 vs. 16/94), onset age ≤20 years (24/57 vs. 9/59), or recurrent paralytic attacks (31/94 vs. 3/25).DiscussionThe low molecular diagnostic rate and specific genetic proportion of the present study highlight the etiological complexity of patients with periodic paralysis in Japan.
Givinostat for Becker muscular dystrophy: A randomized, placebo-controlled, double-blind study
Authors: Comi Giacomo P. , Niks Erik H. , Vandenborne Krista , Cinnante Claudia M. , Kan Hermien E. , Willcocks Rebecca J. , Velardo Daniele , Magri Francesca , Ripolone Michela , van Benthem Jules J. , van de Velde Nienke M. , Nava Simone , Ambrosoli Laura , Cazzaniga Sara , Bettica Paolo U. 
Published: January 2023

ObjectiveNo treatments are approved for Becker muscular dystrophy (BMD). This study investigated the efficacy and safety of givinostat, a histone deacetylase pan-inhibitor, in adults with BMD.MethodsMales aged 18–65 years with a diagnosis of BMD confirmed by genetic testing were randomized 2:1 to 12 months treatment with givinostat or placebo. The primary objective was to demonstrate statistical superiority of givinostat over placebo for mean change from baseline in total fibrosis after 12 months. Secondary efficacy endpoints included other histological parameters, magnetic resonance imaging and spectroscopy (MRI and MRS) measures, and functional evaluations.ResultsOf 51 patients enrolled, 44 completed treatment. At baseline, there was greater disease involvement in the placebo group than givinostat, based on total fibrosis (mean 30.8 vs. 22.8%) and functional endpoints. Mean total fibrosis did not change from baseline in either group, and the two groups did not differ at Month 12 (least squares mean [LSM] difference 1.04%; p = 0.8282). Secondary histology parameters, MRS, and functional evaluations were consistent with the primary. MRI fat fraction in whole thigh and quadriceps did not change from baseline in the givinostat group, but values increased with placebo, with LSM givinostat–placebo differences at Month 12 of −1.35% (p = 0.0149) and −1.96% (p = 0.0022), respectively. Adverse events, most mild or moderate, were reported by 88.2% and 52.9% patients receiving givinostat and placebo.ConclusionThe study failed to achieve the primary endpoint. However, there was a potential signal from the MRI assessments suggesting givinostat could prevent (or slow down) BMD disease progression.