bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixotrophic microalgal mixed cultures for cheese whey valorization
Authors: de Almeida Maria Paula Giulianetti , Mondini Camille , Bruant Guillaume , Tremblay Julien , Mockaitis Gustavo , Weissbrodt David G. 
Published: October 2023

AbstractMicroalgae cultivation, and phycoremediation, can be a polishing step in wastewater treatment. Depending on the stream utilized for microalgal cultivation, biomass can be contaminated with considerable quantities of heavy metals and xenobiotics. Given the economic value of microalgae bioproducts, we suggest coupling anaerobic fermentation with microalgae mixotrophic growth. Cheese whey, a product from cheese production, has a 2022 forecast production of 160.7 million m3year−1in which about 66.5 million m3y−1is used as animal feed, fertilizers or illegally discharged causing eutrophication. Anaerobic fermentation of cheese whey produces volatile fatty acids (VFAs) such as acetate which serves as an organic carbon source for photoorganoheterotrophic microalgal biomass growth. Our work selected three organic sources derived from cheese whey: 40% demineralized whey powder (WPC40), lactose, and acetate. In photolitoautotrophic conditions, green phototrophic growth was successful. In batch tests, acetate was the best organic carbon source among photoorganoheterotrophs with a higher yield of 1.15 mg VSS mg Carbon−1(C) in anaerobic conditions. Also, acetate uptake was thought to be via the glyoxylate cycle. When upscaling the experiment in a chemostat, a lower dilution rate of 0.17 d−1was more suitable for green photoorganoheterotrophs selection, as they were not washed out in the process. These findings show that acetate uptake by microalgae in mixotrophic regimes must be better understood as well as reinforce the advantages of coupling microalgal biomass growth with cheese whey acidogenic fermentation, avoiding contaminations as in phycoremediation processes and fully valorizing cheese whey.Graphical abstract
Rapid DNA methylation-based classification of pediatric brain tumours from ultrasonic aspirate specimens
Authors: Simon Michèle , Kuschel Luis P. , von Hoff Katja , Yuan Dongsheng , Driever Pablo Hernáiz , Hain Elisabeth G. , Koch Arend , Capper David , Schulz Matthias , Thomale Ulrich-Wilhelm , Euskirchen Philipp 
Published: October 2023

AbstractBackgroundAlthough cavitating ultrasonic aspirators are commonly used in neurosurgical procedures, the suitability of ultrasonic aspirator-derived tumor material for diagnostic procedures is still controversial. Here, we explore the feasibility of using ultrasonic aspirator-resected tumor tissue to classify otherwise discarded sample material by fast DNA methylation-based analysis using low pass nanopore whole genome sequencing.Methodsultrasonic aspirator-derived specimens from pediatric patients undergoing brain tumour resection were subjected to low-pass nanopore whole genome sequencing. DNA methylation-based classification using a neural network classifier and copy number variation analysis were performed. Tumor purity was estimated from copy number profiles. Results were compared to microarray (EPIC)-based routine neuropathological histomorphological and molecular evaluation.Results18 samples with confirmed neuropathological diagnosis were evaluated. All samples were successfully sequenced and passed quality control for further analysis. DNA and sequencing characteristics from ultrasonic aspirator-derived specimens were comparable to routinely processed tumor tissue. Classification of both methods was concordant regarding methylation class in 16/18 (89%) cases. Application of a platform-specific threshold for nanopore-based classification ensured a specificity of 100%, whereas sensitivity was 78%. Copy number variation profiles were generated for all cases and matched EPIC results in 16/18 (89%) samples, even allowing the identification of diagnostically or therapeutically relevant genomic alterations.ConclusionMethylation-based classification of pediatric CNS tumors based on ultrasonic aspirator-reduced and otherwise discarded tissue is feasible using time- and cost-efficient nanopore sequencing.
A comparison of the EQ-5D-5L and the SF-6Dv2 among patients with hypertrophic obstructive cardiomyopathy
Authors: Wang Xiaoyu , Sang Haiqiang , Meng Rui , Su Xin , Liu Peng 
Published: October 2023

AbstractBackgroundHypertrophic obstructive cardiomyopathy (HOCM) is a serious and complex chronic disease severely affecting patients’ daily lives and health-related quality of life (HRQoL). The psychometric performance of generic preference-based instruments has not been compared in Chinese patients with HOCM. We aimed to identify an applicable vehicle to determine HRQoL and explore the psychometric properties of SF-6Dv2 and EQ- 5D-5L in adults with HOCM. The interchangeability of the tools in cost-utility analysis was also investigated.MethodsWe collected data from 131 patients with HOCM from the First Affiliated Hospital of Zhengzhou University, China. Assessments were performed on the day of admission and three and six months after discharge using SF-6Dv2 and EQ-5D-5L. The responses were converted to utility values using the corresponding Chinese value sets. The tool distributions were explored, and the floor and ceiling effects were analyzed. The agreement was assessed using intra-class correlation coefficients (ICCs) and Bland–Altman plots. Convergent validity was tested using Spearman’s rank correlation coefficient. Known group validity was measured across various clinical and sociodemographic indicators using relative efficiency (RE) statistics.ResultsThe mean utility scores for SF-6Dv2 and EQ-5D- 5L at baseline and 6-month follow-up were 0.61, 0.62, 0.736, and 0.797, respectively. The EQ-5D-5L and SF-6Dv2 distribution scores showed no normality. EQ-5D-5L was more sensitive to changes over time and showed a moderate to good correlation with the SF-6Dv2 (ICC: 0.598–0.862). The instruments’ agreement and convergent validity worsened in patients with a higher New York Heart Association (NYHA) cardiac function classification and lower general health status. SF-6Dv2 showed higher relative efficiency statistics and a greater ability to distinguish external health status.ConclusionsThe measured results can be used for future cost-utility analyses. SF-6Dv2 and EQ-5D-5L presented different results and should not be used interchangeably. SF-6Dv2 is optimal for detecting differences between subgroups with various health states.
Estimated transmission dynamics of SARS-CoV-2 variants from wastewater are robust to differential shedding
Authors: Dreifuss David , Huisman Jana S. , Rusch Johannes C. , Caduff Lea , Ganesanandamoorthy Pravin , Devaux Alexander J. , Gan Charles , Stadler Tanja , Kohn Tamar , Ort Christoph , Beerenwinkel Niko , Julian Timothy R. 
Published: October 2023

AbstractThe COVID-19 pandemic has accelerated the development and adoption of wastewater-based epidemiology. Wastewater samples can provide genomic information for detecting and assessing the spread of SARS-CoV-2 variants in communities and for estimating important epidemiological parameters such as the growth advantage of the variant. However, despite demonstrated successes, epidemiological data derived from wastewater suffers from potential biases. Of particular concern are differential shedding profiles that different variants of concern exhibit, because they can shift the relationship between viral loads in wastewater and prevalence estimates derived from clinical cases. Using mathematical modeling, simulations, and Swiss surveillance data, we demonstrate that this bias does not affect estimation of the growth advantage of the variant and has only a limited and transient impact on estimates of the effective reproduction number. Thus, population-level epidemiological parameters derived from wastewater maintain their advantages over traditional clinical-derived estimates, even in the presence of differential shedding among variants.
Cardiovascular and Neurological Outcomes in Patients Treated with Edoxaban for Atrial Fibrillation and Characteristics in Patients with Cancer
Authors: Cheng Kai-Hung , Tu Hung-Pin , Cheng Kai-Chun , Scherrer-Crosbie Marielle , Hsu Ting-Yuan 
Published: October 2023

AbstractBACKGROUNDDirect oral anticoagulants (DOACs) outperform warfarin in vascular and bleeding events in atrial fibrillation (AF) patients. Yet, effects of DOACs on congestive heart failure (CHF) and Alzheimer’s disease (AD) remain less explored.METHODSUsing the Taiwan National Health Insurance Research Database, a nationwide retrospective cohort study was conducted. The study matched 5,683 non-valvular atrial fibrillation (NVAF) edoxaban patients with 11,366 warfarin patients, and 703 NVAF with cancer (NVAF-C) edoxaban patients with 1,406 warfarin patients. Vasular and non-vascular outcomes, with focuses on CHF and AD, were compared between the edoxaban and warfarin users.RESULTSEdoxaban significantly lowered adjusted hazrad ratio (aHR) of all-cause mortality, hospitalization for gastrointestinal bleeding, and CHF (0.37, 0.74, and 0.26, respectively, in NVAF; 0.39, 0.67, and 0.31, respectively, in NVAF-C, allp< 0.05), compared to warfarin. Edoxaban was associated with significantly lower aHRs of acute myocardial infarction, peripheral artery disease, venous thromboembolism, pulmonary embolism, and AD (0.71, 0.48, 0.55, 0.20, and 0.66, respectively; allp< 0.05) in NVAF patients versus warfarin. However, edoxaban had higher aHR of hospitalized bleeding (1.19,p= 0.002) than warfarin in NVAF patients, but not in NVAF-C patients.CONCLUSIONSEdoxaban demonstrated lowered CHF risks in both NVAF and NVAF-C patients, and reduced AD occurrence in NVAF patients versus warfarin. These findings advocate for edoxaban’s use in AF cases.CLINICAL PERSPECTIVEWhat Is New?The study reveals that in patients with atrial fibrillation (AF), edoxaban, a direct oral anticoagulant (DOAC), demonstrates significant advantages over warfarin. Notably, edoxaban is associated with a reduced risk of congestive heart failure (CHF) and Alzheimer’s disease (AD) when compared to warfarin.Clinical Implications?These findings have important clinical implications. Edoxaban appears to be a superior anticoagulant choice for AF patients, as it lowers the risk of CHF and AD. This highlights the potential of edoxaban to improve patient outcomes and underscores its relevance for managing AF cases.
CYP2C19Polymorphisms and Clinical Outcomes Following Percutaneous Coronary Intervention (PCI) in the Million Veterans Program
Authors: Chanfreau-Coffinier Catherine , Friede Kevin A. , Plomondon Mary E. , Lee Kyung Min , Lu Zhenyu , Lynch Julie A. , DuVall Scott L. , Vassy Jason L. , Waldo Stephen W. , Cleator John H. , Maddox Thomas M. , Rader Daniel J. , Assimes Themistocles L. , Damrauer Scott M. , Tsao Philip S. , Chang Kyong-Mi , Voora Deepak , Giri Jay , Tuteja Sony ,   VA Million Veteran Program
Published: October 2023

AbstractBackgroundCYP2C19loss-of-function (LOF) alleles decrease the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS). The impact of genotype in stable ischemic heart disease (SIHD) is unclear.ObjectivesDetermine the association ofCYP2C19genotype with major adverse cardiac events (MACE) after PCI for ACS or SIHD.MethodsMillion Veterans Program (MVP) participants age <65 years with a PCI documented in the VA Clinical Assessment, Reporting and Tracking (CART) Program between 1/1/2009 to 9/30/2017, treated with clopidogrel were included. Time to MACE defined as the composite of all-cause death, stroke or myocardial infarction within 12 months following PCI.ResultsAmong 4,461 Veterans (mean age 59.1 ± 5.1 years, 18% Black); 44% had ACS, 56% had SIHD and 29% carried aCYP2C19LOF allele. 301 patients (6.7%) experienced MACE while being treated with clopidogrel, 155 (7.9%) in the ACS group and 146 (5.9%) in the SIHD group. Overall, MACE was not significantly different between LOF carriers vs. noncarriers (adjusted hazard ratio [HR] 1.18, confidence interval [95%CI] 0.97-1.45, p=0.096). Among patients presenting with ACS, MACE risk in LOF carriers versus non-carriers was numerically higher (HR 1.30, 95%CI 0.98-1.73, p=0.067). There was no difference in MACE risk in patients with SIHD (HR 1.09, 95%CI 0.82-1.44; p=0.565).ConclusionsCYP2C19LOF carriers presenting with ACS treated with clopidogrel following PCI experienced a numerically greater elevated risk of MACE events.CYP2C19LOF genotype is not associated with MACE among patients presenting with SIHD.
A non-canonical Arp2/3 complex is essential forPlasmodiumDNA segregation and transmission of malaria
Authors: Hentzschel Franziska , Jewanski David , Sokolowski Yvonne , Agarwal Pratika , Kraeft Anna , Hildenbrand Kolja , Dorner Lilian P. , Singer Mirko , Frischknecht Friedrich , Marti Matthias 
Published: October 2023

AbstractThe malaria-causing parasitePlasmodiumhas a complex life cycle involving both vertebrate and mosquito hosts. Sexual stages or gametocytes are the only stage competent for transmission to mosquitoes. Formation of flagellated male gametes from gametocytes requires rapid rounds of genome replication. Here we discovered a non-canonicalPlasmodiumactin-related protein 2/3 (Arp2/3) complex essential for DNA segregation during male gametogenesis.PlasmodiumArp2/3 dynamically localizes within the nucleus to the endomitotic spindles and interacts with a kinetochore protein. Deletion of key Arp2/3 subunits or interfering with actin polymerisation leads to the formation of sub-haploid male gametes and a complete block in transmission through delayed developmental arrest at the oocyst stage. Our work identified an evolutionary divergent protein complex in malaria parasites that offers potential targets for transmission-blocking interventions.
Extracellular domain, hinge, and transmembrane determinants affecting surface CD4 expression of a novel anti-HIV chimeric antigen receptor (CAR) construct
Authors: Zenere Giorgio , Wu Chengxiang , Midkiff Cecily C. , Johnson Nathan M. , Grice Christopher P. , Wimley William C. , Kaur Amitinder , Braun Stephen E. 
Published: October 2023

AbstractChimeric antigen receptor (CAR)-T cells have demonstrated clinical potential, but current receptors still need improvements to be successful against chronic HIV infection. In this study, we address some requirements of CAR motifs for strong surface expression of a novel anti-HIV CAR by evaluating important elements in the extracellular, hinge, and transmembrane (TM) domains. When combining a truncated CD4 extracellular domain and CD8α hinge/TM, the novel CAR did not express extracellularly but was detectable intracellularly. By shortening the CD8α hinge, CD4-CAR surface expression was partially recovered and addition of the LYC motif at the end of the CD8α TM fully recovered both intracellular and extracellular CAR expression. Mutation of LYC to TTA or TTC showed severe abrogation of CAR expression by flow cytometry and confocal microscopy. Additionally, we determined that CD4-CAR surface expression could be maximized by the removal of FQKAS motif at the junction of the extracellular domain and the hinge region. CD4-CAR surface expression also resulted in cytotoxic CAR T cell killing of HIV Env+target cells. In this study, we identified elements that are crucial for optimal CAR surface expression, highlighting the need for structural analysis studies to establish fundamental guidelines of CAR designs.
Widespread fungal-bacterial competition for magnesium enhances antibiotic resistance
Authors: Hsieh Yu-Ying Phoebe , Sun Wanting Wendy , Young Janet M. , Cheung Robin , Hogan Deborah A. , Dandekar Ajai A. , Malik Harmit S. 
Published: October 2023

AbstractFungi and bacteria coexist in many polymicrobial communities, yet the molecular basis of their interactions remains poorly understood. Using unbiased genomic approaches, we discover that the fungusCandida albicanssequesters essential Mg2+ions from the bacteriumPseudomonas aeruginosa. In turn, the bacterium competes using a Mg2+transporter, MgtA. We show that Mg2+sequestration by fungi is a general mechanism of antagonism against gram-negative bacteria. But the resultant Mg2+limitation enhances bacterial resistance to polymyxin antibiotics like colistin, which target gram-negative bacterial membranes. Experimental evolution reveals that bacteria in co-culture with fungi become phenotypically, but not genetically, resistant to colistin; antifungal treatment renders resistant bacteria from co-cultures to become colistin-sensitive. Fungal-bacterial nutritional competition may thus profoundly impact treatments of polymicrobial infections with antibiotics of last resort.One Sentence SummaryMagnesium sequestration by fungi lowers bacterial fitness but enhances antibiotic resistance.
Loss of Dna2 nuclease activity results in decreased Exo1-mediated resection at DNA double strand breaks
Authors: Mojumdar Aditya , Granger Courtney , Lunke Martine , Cobb Jennifer A. 
Published: October 2023

AbstractA DNA double strand break (DSB) is one of the most dangerous types of DNA damage that is repaired largely by homologous recombination (HR) or non-homologous end-joining (NHEJ). The interplay of repair factors at the break directs which pathway is used, and a subset of these factors also function in more mutagenic alternative (alt) repair pathways. Resection is a key event in repair pathway choice and extensive resection, which is a hallmark of HR, is mediated by two nucleases, Exo1 and Dna2. We observed differences in resection and repair outcomes in cells harbouring nuclease deaddna2-1 compared todna2Δpif1-m2 that could be attributed to the level of Exo1 recovered at DSBs. Cells harbouringdna2-1 showed reduced Exo1 localization, increased NHEJ, and a greater defect in resection compared to cells whereDNA2was deleted. Both the decreased level of resection and the increased rate of NHEJ indna2-1 mutants were reversed upon deletion ofKU70or ectopic expression of Exo1. By contrast, whenDNA2was deleted, Exo1 and Ku70 recovery levels did not change, however Nej1 increased as did the frequency of alt-EJ/ MMEJ repair. Our findings demonstrate that decreased Exo1 at DSBs contributed to the resection defect in cells expressing inactive Dna2 and highlight the complexity of understanding how functionally redundant factors are regulatedin vivoto promote genome stability.Graphical Abstract
Image-Based Consensus Molecular Subtyping in Rectal Cancer Biopsies and Response to Neoadjuvant Chemoradiotherapy
Authors: Lafarge Maxime W , Domingo Enric , Sirinukunwattana Korsuk , Wood Ruby , Samuel Leslie , Murray Graeme , Richman Susan D , Blake Andrew , Sebag-Montefiore David , Gollins Simon , Klieser Eckhard , Neureiter Daniel , Huemer Florian , Greil Richard , Dunne Philip , Quirke Philip , Weiss Lukas , Rittscher Jens , Maughan Tim , Koelzer Viktor H 
Published: October 2023

AbstractThe development of deep learning (DL) models to predict the consensus molecular subtypes (CMS) from histopathology images (imCMS) is a promising and cost-effective strategy to support patient stratification. Here, we investigate whether imCMS calls generated from whole slide histopathology images (WSIs) of rectal cancer (RC) pre-treatment biopsies are associated with pathological complete response (pCR) to neoadjuvant long course chemoradiotherapy (LCRT) with single agent fluoropyrimidine.DL models were trained to classify WSIs of colorectal cancers stained with hematoxylin and eosin into one of the four CMS classes using a multi-centric dataset of resection and biopsy specimens (n=1057 WSIs) with paired transcriptional data. Classifiers were tested on a held out RC biopsy cohort (ARISTOTLE) and correlated with pCR to LCRT in an independent dataset merging two RC cohorts (ARISTOTLE, n=114 and SALZBURG, n=55 patients).DL models predicted CMS with high classification performance in multiple comparative analyses. In the independent cohorts (ARISTOTLE, SALZBURG), cases with WSIs classified as imCMS1 had a significantly higher likelihood of achieving pCR (OR=2.69, 95%CI 1.01-7.17, p=0.048). Conversely, imCMS4 was associated with lack of pCR (OR=0.25, 95%CI 0.07-0.88, p=0.031). Classification maps demonstrated pathologist-interpretable associations with high stromal content in imCMS4 cases, associated with poor outcome. No significant association was found in imCMS2 or imCMS3.imCMS classification of pre-treatment biopsies is a fast and inexpensive solution to identify patient groups that could benefit from neoadjuvant LCRT. The significant associations between imCMS1/imCMS4 with pCR suggest the existence of predictive morphological features that could enhance standard pathological assessment.
Human Placenta-Derived Mesenchymal Stem Cells Stimulate Neuronal Regeneration By Promoting Axon Growth And Restoring Neuronal Activity
Authors: de Laorden Elvira H. , Simón Diana , Milla Santiago , Portela-Lomba María , Mellén Marian , Sierra Javier , de la Villa Pedro , Moreno-Flores María Teresa , Iglesias Maite 
Published: October 2023

ABSTRACTCell therapy is a cutting-edge medical approach that involves the use of cells to treat various diseases and conditions. It harnesses the remarkable regenerative and reparative abilities of cells to restore or replace damaged tissues and promote healing.In the last decades, mesenchymal stem cells (MSCs) have become the cornerstone of cellular therapy due to their unique characteristics. Specifically human placenta-derived mesenchymal stem cells (hPMSCs) are highlighted for their unique features, including ease to isolate, non-invasive techniques for large scale cell production, significant immunomodulatory capacity, and a high ability to migrate to injuries. Researchers are exploring innovative techniques to overcome the low regenerative capacity of Central Nervous System (CNS) neurons, with one promising avenue being the development of tailored mesenchymal stem cell therapies capable of promoting neural repair and recovery. In this context, we have evaluated hPMSCs as candidate for CNS lesion regeneration using a skillful co-culture model system. Indeed, we have demonstrated the hPMSCs ability to stimulate damaged rat-retina neurons regeneration by promoting axon growth and restoring neuronal activity both under normoxia and hypoxia conditions. With our model we have obtained neuronal regeneration values of 10-12% and axonal length per neuron rates of 19.99±0.77, μm/neuron. To assess whether the regenerative capabilities of hPMSCs are contact-dependent effects or it is mediated through paracrine mechanisms, we carried out transwell co-culture and conditioned medium experiments confirming the role of secreted factors in axonal regeneration. It was found that hPMSCs produce brain derived, nerve growth factors (BDNF, NGF) and Neurotrophin-3, involved in the process of neuronal regeneration and restoration of their physiological activity of neurons. The capability to access axonal physiology is crucial for studying information processing among neurons in healthy and diseased states. We confirm the success of our treatment using the patch clamp technique to study ionic currents in individual isolated living cells, confirming that in our model the regenerated neurons are electrophysiologically active.