bluuebunny/crossref_metadata_2025_split huggingface dataset:
A validated model for early prediction of group A streptococcal aetiology and clinical endpoints in necrotising soft tissue infections
Authors: Katz Sonja , Suijker Jaco , Skrede Steinar , Meij-de Vries Annebeth , Pijpe Anouk , Norrby-Teglund Anna , Palma Medina Laura M , Damås Jan K , Hyldegaard Ole , Solligård Erik , Svensson Mattias ,   PerAID/PerMIT/INFECT study group, Mosevoll Knut Anders , Martins dos Santos Vitor AP , Saccenti Edoardo 
Published: June 2024

AbstractObjectivesTo develop and externally validate machine learning models for predicting microbial aetiology and clinical endpoints, encompassing surgery, patient management, and organ support in Necrotising Soft Tissue Infections (NSTI).MethodsPredictive models for the presence of Group A Streptococcus (GAS) and for five clinical endpoints (risk of amputation, size of skin defect, maximum skin defect size, length of ICU stay, and need for renal replacement therapy) were built and trained using data from the prospective, international INFECT cohort (409 patients, 2013-2017), implementing unsupervised variable selection, and comparing several algorithms. SHapley Additive exPlanations (SHAP) analysis was used to interpret the model. GAS predictive models were externally validated using data from a Dutch retrospective multicenter cohort from the same calendar period (216 patients).ResultsEight variables available pre-surgery (age, diabetes, affected anatomical locations, prior surgical interventions, and creatinine and haemoglobin levels) sufficed for prediction of GAS aetiology with high discriminatory power in both the development (ROC-AUC: 0.828; 95%CI 0.763, 0.883) and validation cohort (ROC-AUC: 0.758; 95%CI 0.696, 0.821). The prediction of clinical endpoints related to surgical, patient management, and organs support aspects was unsuccessful.ConclusionAn externally validated prediction model for GAS aetiology before organ support aspects was unsuccessful, having implications for targeted treatment decisions of NSTI.
Short and midterm outcomes of surgical repair of acute type A aortic dissection concomitant CABG vs. ECMO support: A retrospective study
Authors: Zhang Dong , Zhu Gui-Jun , Gao Ming-Jun , Wei Xiang-Yang , Yan Zhe , Li Bin , Chen Xing-Peng , Wang Xiao-Lin , Shu Yu-Sheng 
Published: June 2024

ObjectiveIntraoperative surgical repair of acute type A aortic dissection, sometimes we would encounter special cases that failed to wean from CPB. In this study, we aimed to retrospectively analyze that the indication, clinical experience and short and midterm outcomes of surgical repair of acute type A aortic dissection concomitant CABG or ECMO support in patients who failed to wean from CPB.MethodsA total of 532 consecutive patients underwent emergent surgery for TAAD in a single institution between Jan 2018 and Jan 2023. And categorized into CABG group and ECMO group based on surgical approach. Preoperative, intraoperative and postoperative variables were assessed and analyzed. Outcomes of the patients were followed up until five years from discharge of hospital.ResultsOverall in-hospital mortality was determined to be 15.7% for CABG group and 73.3% for ECMO group (P=0.001). The operation time, CPB time, extracorporeal circulation assisted time, 24-hour traffic diversion in CABG group were less than ECMO group, and had statistically different between two groups (P=0.039,P=0.007,P<0.001,P<0.001). Higher morbidity of delayed chest closure, low cardiac output syndrome, and lower limb osteofascial compartment syndrome in the ECMO group than the CABG group, but not statistically significant (P=0.139,P=1,P=0.524).5-years follow-up mortality after discharge had no statistically different between two groups (P=1).ConclusionFor the patients who failed to wean from CPB, surgical repair of acute type A aortic dissection Concomitant CABG can provide more excellent short and midterm outcomes than ECMO support. However, concomitant CABG are also associated with long-term complications of the great saphenous vein embolization and severe tricuspid valve regurgitation.
Understanding the Sources of Performance in Deep Drug Response Models Reveals Insights and Improvements
Authors: Branson Nikhil , Cutillas Pedro R. , Bessant Conrad 
Published: June 2024

AbstractAnti-cancer drug response prediction (DRP) using cancer cell lines plays a vital role in stratified medicine and drug discovery. Recently there has been a surge of new deep learning (DL) models for DRP that improve on the performance of their predecessors. However, different models use different input data types and neural network architectures making it hard to find the source of these improvements. Here we consider multiple published DRP models that report state-of-the-art performance in predicting continuous drug response values. These models take the chemical structures of drugs and omics profiles of cell lines as input. By experimenting with these models and comparing with our own simple benchmarks we show that no performance comes from drug features, instead, performance is due to the transcriptomics cell line profiles. Furthermore, we show that, depending on the testing type, much of the current reported performance is a property of the training target values. To address these limitations we create novel models (BinaryET and BinaryCB) that predict binary drug response values, guided by the hypothesis that this reduces the noise in the drug efficacy data. Thus, better aligning them with biochemistry that can be learnt from the input data. BinaryCB leverages a chemical foundation model, while BinaryET is trained from scratch using a transformer-type model. We show that these models learn useful chemical drug features, which is the first time this has been demonstrated for multiple DRP testing types to our knowledge. We further show binarising the drug response values is what causes the models to learn useful chemical drug features. We also show that BinaryET improves performance over BinaryCB, and over the published models that report state-of-the-art performance.
Glioma-derived M-CSF and IL-34 license M-MDSCs to suppress CD8+T cells in a NOS-dependent manner
Authors: Takacs Gregory P. , Garcia Julia S. , Hodges Caitlyn A. , Kreiger Christian J. , Sherman Alexandra , Harrison Jeffrey K. 
Published: June 2024

AbstractGlioblastoma (GBM) is the most common malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a subset of myeloid cells, expressing monocytic (M)-MDSC markers and dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate the TME. This study evaluated the mechanism of CCR2+/CX3CR1+M-MDSC differentiation and T cell suppressive function in murine glioma models. We determined that bone marrow-derived CCR2+/CX3CR1+cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Glioma secreted CSF1R ligands M-CSF and IL-34 were identified as key drivers of M-MDSC differentiation while adenosine and iNOS pathways were implicated in M-MDSC suppression of T cells. Mining a human GBM spatial RNAseq database revealed a variety of different pathways that M-MDSCs utilize to exert their suppressive function that are driven by complex niches within the microenvironment. These data provide a more comprehensive understanding of the mechanism of M-MDSCs in glioblastoma.Simple SummaryCurrently there are no effective therapies for glioblastoma. Infiltrating myeloid cells contribute significantly to the immune suppressive tumor microenvironment that is characteristic of GBM. Monocytic myeloid derived suppressor cells are chief immune suppressive cells found in the glioma microenvironment. Understanding the mechanisms of M-MDSC differentiation and T cell suppression is imperative for generating therapies that target this tumor supportive cell population. In this study we found that glioma secreted CSF1R ligands, M-CSF and IL-34, license M-MDSCs to suppress CD8 T cells. These M-MDSCs partially utilize nitric oxide synthase to illicit their suppressive activity. However, spatial RNAseq points to glioma microenvironment niches driving M-MDSC heterogeneity. Our findings identify key regulators of differentiation and suppressive mechanisms of M-MDSCs and confirm the importance of targeting this cell population in glioma.
Butterfly eggs prime anti-herbivore defense in an annual but not perennialArabidopsisspecies
Authors: Huve Maryse A. P. , Bittner Norbert , Kunze Reinhard , Hilker Monika , Remus-Emsermann Mitja N. P. , Paniagua Voirol Luis R. , Lortzing Vivien 
Published: June 2024

AbstractWhile plant anti-herbivore defenses of the annual plant speciesArabidopsis thalianawere shown to be primable byPieris brassicaeeggs, the primability of the phylogenetically closely related perennialArabidopsis lyratahas not yet been investigated. Previous studies revealed that closely related wild Brassicaceae plant species, the annualBrassica nigraand the perennialBrassica oleracea, exhibit an egg-primable defense trait, even though they have different life spans. Here, we tested whetherP. brassicaeeggs prime anti-herbivore defenses of the perennialA. lyrata. We exposedA. lyratatoP. brassicaeeggs and larval feeding and assessed their primability by i) determining the biomass ofP. brassicaelarvae after feeding on plants with and without priorP. brassicaeegg deposition and ii) investigating the plant transcriptomic response after egg deposition and/or larval feeding. For comparison, these studies were also conducted withA. thaliana.Consistent with previous findings,A. thaliana’s response to priorP. brassicaeegg deposition negatively affected conspecific larvae feeding uponA. thaliana. However, this was not observed inA. lyrata.Arabidopsis thalianaresponded toP. brassicaeeggs with strong transcriptional reprogramming, whereasA. lyrataresponses to eggs were negligible. In response to larval feeding,A. lyrataexhibited a greater transcriptome change compared toA. thaliana. Among the strongly feeding-inducedA. lyratagenes were those that are egg-primed in feeding-inducedA. thaliana, i.e.,CAX3, PR1,PR5andPDF1.4.These results suggest thatA. lyratacompensates for its lack of egg-mediated primability by a stronger response to larval feeding.
Co-utilization of microalgae and heterotrophic microorganisms improves wastewater treatment efficiency
Authors: Takahashi Miiku , Karitani Yukino , Yamada Ryosuke , Matsumoto Takuya , Ogino Hiroyasu 
Published: June 2024

AbstractWastewater treatment using co-culture systems of microalgae and heterotrophic microorganisms is expected to be useful under atmospheric dilute carbon dioxide conditions. In this study, we investigated the combination of microalgae and heterotrophic microorganisms to improve the efficiency of wastewater treatment. Furthermore, to elucidate the cause of the changes in wastewater treatment efficiency in the co-culture system, changes in gene expression were revealed through transcriptome analysis. Three types of microalgae and five heterotrophic microorganisms were used in combination for wastewater treatment. The combination ofChlamydomonas reinhardtiiNIES-2238 andSaccharomyces cerevisiaeSH-4 showed the highest wastewater treatment efficiency. Using this combination for artificial wastewater treatment, the removal rates of TOC (Total organic carbon), PO43-, and NH4+reached 80%, 93%, and 63%, respectively, after 18 h of treatment. Transcriptome analysis revealed that the combined wastewater treatment altered the expression of 1371 and 692 genes inC. reinhardtiiandS. cerevisiae, respectively. The genes upregulated inC. reinhardtiiincluded those related to molecular and ion transport. Genes upregulated inS. cerevisiaeincluded those related to cell protection from various types of damage and stress. To the best of our knowledge, this is the first study to show that a combination of green algae and yeast improves the efficiency of wastewater treatment. As both the green algaC. reinhardtiiand the yeastS. cerevisiaeare highly safe microorganisms, the establishment of their effective combination for wastewater treatment is highly significant.
HLH-30/TFEB rewires the chaperone network to promote proteostasis under conditions of Coenzyme A and Iron-Sulfur Cluster Deficiency
Authors: Shalash Rewayd , Levi-Ferber Mor , von Chrzanowski Henrik , Atrash Mohammad Khaled , Shav-Tal Yaron , Henis-Korenblit Sivan 
Published: June 2024

ABSTARCTThe maintenance of a properly folded proteome is critical for cellular function and organismal health, and its age-dependent collapse is associated with a wide range of diseases. Here, we find that despite the central role of Coenzyme A as a molecular cofactor in hundreds of cellular reactions, limiting Coenzyme A levels inC. elegansand in human cells, by inhibiting the conserved pantothenate kinase, promotes proteostasis. Impairment of the cytosolic iron-sulfur clusters formation pathway, which depends on Coenzyme A, similarly promotes proteostasis and acts in the same pathway. Proteostasis improvement by Coenzyme A/iron-sulfur cluster deficiencies are dependent on the conserved HLH-30/TFEB transcription factor. Strikingly, under these conditions, HLH-30 promotes proteostasis by potentiating the expression of select chaperone genes providing a chaperone-mediated proteostasis shield, rather than by its established role as an autophagy and lysosome biogenesis promoting factor. This reflects the versatile nature of this conserved transcription factor, that can transcriptionally activate a wide range of protein quality control mechanisms, including chaperones and stress response genes alongside autophagy and lysosome biogenesis genes. These results highlight TFEB as a key proteostasis-promoting transcription factor and underscore it and its upstream regulators as potential therapeutic targets in proteostasis-related diseases.
Propidium monoazide is unreliable for quantitative live-dead molecular assays
Authors: Kaur Simerdeep , Ortiz Laura Bran , Rudakov Grigorii , Verma Mohit S. 
Published: June 2024

AbstractPropidium monoazide (PMA) is a dye that distinguishes between live and dead cells in molecular assays like Polymerase Chain Reaction (PCR). It works by cross-linking to the DNA of cells that have compromised membranes or extracellular DNA upon photoactivation, making the DNA inaccessible for amplification. Currently, PMA is used to detect viable pathogens and alleviate systemic bias in the microbiome analysis of samples using 16S rRNA gene sequencing. In these applications, treated samples consist of different amounts of dead bacteria and a range of bacterial strains, variables that can affect the performance of PMA and lead to inconsistent findings across various research studies. To evaluate the effectiveness of PMA, we used a sensitive qPCR assay and post-treatment sample concentration to determine PMA activity accurately under varying sample conditions. We report that PMA is unreliable for viability assays when the concentration and composition of the bacterial mixture are unknown. PMA is only suitable for qualitatively assessing viability in samples containing a known number of dead microbes or extracellular DNA.
CEBPBas a potential biomarker for prognosis and immune infiltration in clear cell renal cell carcinoma
Authors: Ren Yaoqiang , Qiao Baoping , Wei Min , Tian Quanfa , Guo Wenke 
Published: June 2024

AbstractClear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer subtype with poor prognosis.This study explores the expression and clinical significance of the CCAAT/enhancer-binding protein betaCEBPBgene in ccRCC. RNA sequencing, gene amplification, and mutation data were sourced from TCGA, UCSC XENA, and cBioPortal. Data processing involved the STAR workflow and R software for statistical analysis and visualization. Experimental validation used immunohistochemistry and RT-qPCR on 58 patient tissue samples. Functional pathway enrichment was performed using GO-KEGG and GSEA analyses, and PPI networks were constructed with STRING and Cytoscape. Immune infiltration and survival analyses were conducted using Spearman correlation and Cox regression models.Results showed significantly higherCEBPBexpression in ccRCC tissues compared to adjacent normal tissues. Clinical variable grouping indicated significant differences inCEBPBexpression. Enrichment analyses identified involvement in complement and coagulation cascades and carbon metabolism. PPI networks highlighted strong interactions with STAT3 and EP300. Immune infiltration analysis revealed significant correlations with multiple immune cell types. HighCEBPBexpression was linked to poor prognosis and demonstrated high diagnostic accuracy for ccRCC.Author summaryKidney Renal Clear Cell Carcinoma (KIRC) is a major subtype of renal cancer with significant clinical implications. This study investigates the role ofCEBPB, a transcription factor, in KIRC using RNA sequencing data from TCGA and GTEx databases. We analyzedCEBPBexpression, mutation status, and its correlation with clinical features and immune infiltration. Our findings reveal elevatedCEBPBexpression in tumor tissues, significantly associated with advanced T, N, M stages and poor overall survival. Functional analyses indicate thatCEBPBinteracts with key proteins and pathways involved in tumorigenesis. Additionally, highCEBPBexpression correlates with increased immune cell infiltration, suggesting its role in tumor-immune interactions. This research highlightsCEBPBas a potential prognostic biomarker and therapeutic target in KIRC, offering new insights for clinical management and treatment strategies.
Incidence of Chronic Recurrent Multifocal Osteomyelitis in Children and Adolescents in the UK and Republic of Ireland
Authors: Chia Daphne Theresa , Toms Andoni , Sanghrajka Anish , Ramanan Athimalaipet , Killeen Orla G , Ilea Cristina , Mahmood Kamran , Compeyrot-Lacassagne Sandrine , Bailey Kathryn , Martin Neil , Armon Kate , Suo Chenqu 
Published: June 2024

AbstractObjectivesChronic Recurrent Multifocal Osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis (CNO), is a rare autoinflammatory condition affecting the bones in children and teenagers. The actual incidence of CRMO remains uncertain. The objective of this study is to identify the incidence of CRMO in children and young people under the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). We also aim to delineate the demographics, clinical presentation, investigations, initial management and healthcare needs for children and adolescents with CRMO.MethodsWe conducted monthly surveys among all paediatric consultants and paediatric orthopaedic surgeons to identify patients newly diagnosed with CRMO between October 2020 and November 2022. A standardised questionnaire was sent to reporting clinicians to collect further information.ResultsOver the surveillance period, 288 patients were reported, among which, 165 confirmed and 20 probable cases were included in the analysis. The highest incidences were among 8-10 year-olds. A two-to-one female-to-male difference in incidence was observed, and male patients were more likely to present with multifocal disease. A negative correlation was observed between reporting clavicular and leg pain. Investigation-wise, 80.0% of patients were reported to have undergone whole-body MRI and 51.1% had bone biopsies. The most common initial treatments were NSAIDs (93.9%) and bisphosphonates (44.8%).ConclusionThis study estimates an average annual CRMO incidence of 0.65 cases per 100,000 children and adolescents in the UK and ROI. These findings establish a crucial baseline for ongoing research and improvement in the care of individuals with CRMO.Key MessagesThe estimated annual incidence of CRMO is 0.65 per 100,000 children and adolescents aged <16.Two-fold higher incidence in females to males was found, with the highest incidence in 8-10 year-olds.Male patients are more likely to present with multifocal disease compared with females.
Genetic surveillance ofPlasmodium falciparumreveals rapid population changes following first-line treatment policy revisions in the Greater Mekong Subregion
Authors: Verschuuren Tess D , Wasakul Varanya , Thuy-Nhien Nguyen , Booth Ethan , Quang Huynh Hong , Thang Ngo Duc , Chindavongsa Keobouphaphone , Sovannaroth Siv , Banouvong Virasak , Sengsavath Viengphone , Mayxay Mayfong , Tuyen Nguyen Thi Kim , Phuong Vo Ngoc Lam , Trung Pham Duc , Gonçalves Sónia , Chen Soun , Phalivong Sonexay , Xayvanghang Saiamphone , Mahaphontrakoon Supaporn , Pearson Richard D , Newton Paul N , Maude Richard J , Ashley Elizabeth A , Ariani Cristina V , Simpson Victoria J , Day Nicholas P , Dondorp Arjen M , Miotto Olivo 
Published: June 2024

ABSTRACTBackgroundGenetic surveillance ofPlasmodium falciparum (Pf)is an important tool for tracking antimalarial resistant strains, informing decision-making by National Malaria Control Programmes (NMCPs). Here, we present an analysis of 5,754 samples collected by the GenRe-Mekong project, in collaboration with NMCPs in the Greater Mekong Subregion (GMS), powered by new user-friendly visualization tools developed to translate genomic data into accessible actionable information.MethodsSamples collected from patients presenting at public health facilities between 2017 and 2022 were genotyped using the SpotMalaria platform. Output data included genotypes for markers of antimalarial resistance, and genetic barcodes for analysis of relatedness. We developed the grcMalaria R package, which allows users to specify sample selection criteria, and produce geographical maps of prevalence, diversity and relatedness. It also identifies circulating parasite clusters, characterizing their drug resistance profile and mapping their spread.ResultsSince 2020, a rapid reduction inPfincidence was observed, alongside a decline of the KEL1/PLA1 lineage resistant to dihydroartemisinin-piperaquine (DHA-PPQ), previously dominant in the eastern GMS. The frequency ofplasmepsin2/3amplifications, associated with piperaquine resistance, dropped from 62% in 2017-2019 to 2% in the first half of 2022. This coincided with a switch in frontline therapy, away from DHA-PPQ, in Cambodia, Thailand, and Vietnam. Artemisinin resistance levels remained high, with a regional prevalence of 89% in 2022. No evidence of emerging mefloquine resistance was found.ConclusionRoutine genetic surveillance ofPfcan reveal changes in parasite populations in response to public health interventions, especially when its results are translated into intuitive graphical visualizations, providing actionable information for NMCPs.