bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stopping antibacterial prophylaxis in pediatric allogeneic hematopoietic cell transplantation: An internal audit
Authors: Wintjes Nina , Krämer Katja , Kolve Hedwig , Mohring Daniela , Schaumburg Frieder , Rossig Claudia , Burkhardt Birgit , Groll Andreas H. 
Published: December 2023

AbstractBackgroundAntibacterial prophylaxis in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) is controversial and not recommended by international guidelines. We analyzed relevant posttransplant outcomes following discontinuation of antibacterial prophylaxis at a major European pediatric transplant center.MethodsThe single‐center retrospective audit included all pediatric allogeneic HCT patients (pts) transplanted between 2011 and 2020 before (≤2014) and after (≥2015) stopping routine antibacterial prophylaxis with penicillin, metronidazole, and ciprofloxacin upon start of the conditioning regimen. The primary endpoint was overall survival until the first hospital discharge. Secondary endpoints included the occurrence of fever; bacterial infections; and cumulative days with antibacterial agents until discharge.ResultsA total of 257 HCT procedures were performed in 249 pts (median age: 10 years, range, 0.2–22.5) for leukemia/lymphoma (n = 150) and nonmalignant disorders (n = 107). Of these, 104 procedures were performed before (cohort 1) and 153 after (cohort 2) stopping prophylaxis. Overall survival until discharge was 90.4% in cohort 1 and 96.1% in cohort 2 (p = .06). No differences were observed in the occurrence of fever (92.3 vs. 94.1%; p = .57) and bacterial infections (34.6 vs. 25.5%; p = .11). The median number of days on antibacterial agents was significantly lower in cohort 2 (39 vs. 34; p = .002). Detection rates of resistant organisms were overall low.ConclusionIn this single‐center audit, the stop of routine antibacterial prophylaxis had no effect on the occurrence of fever, bacterial infections, resistant organisms, and GVHD. Overall antibiotic use was significantly reduced, and survival was noninferior to the historical control cohort.
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House dust mite allergens, store‐operated Ca2+ channels and asthma
Authors: Parekh Anant B. 
Published: December 2023

AbstractThe house dust mite is the principal source of aero‐allergen worldwide. Exposure to mite‐derived allergens is associated with the development of asthma in susceptible individuals, and the majority of asthmatics are allergic to the mite. Mite‐derived allergens are functionally diverse and activate multiple cell types within the lung that result in chronic inflammation. Allergens activate store‐operated Ca2+ release‐activated Ca2+ (CRAC) channels, which are widely expressed in multiple cell types within the lung that are associated with the pathogenesis of asthma. Opening of CRAC channels stimulates Ca2+‐dependent transcription factors, including nuclear factor of activated T cells and nuclear factor‐κB, which drive expression of a plethora of pro‐inflammatory cytokines and chemokines that help to sustain chronic inflammation. Here, I describe drivers of asthma, properties of mite‐derived allergens, how the allergens are recognized by cells, the signalling pathways used by the receptors and how these are transduced into functional effects, with a focus on CRAC channels. In vivo experiments that demonstrate the effectiveness of targeting CRAC channels as a potential new therapy for treating mite‐induced asthma are also discussed, in tandem with other possible approaches.
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Genetic dissection of the degradation pathways for the mycotoxin fusaric acid in
Burkholderia ambifaria
T16
Authors: Vinacour Matias , Moiana Mauro , Forné Ignasi , Jung Kirsten , Bertea Micaela , Calero Valdayo Patricia M. , Nikel Pablo I. , Imhof Axel , Palumbo Miranda C. , Fernández Do Porto Dario , Ruiz Jimena A. 
Published: December 2023

ABSTRACT

Fusaric acid (FA) is a mycotoxin produced by several
Fusarium
species.
Burkholderia ambifaria
T16 is a rhizosphere bacterium, able to use FA as sole nitrogen, carbon, and energy source. By screening a transposon insertional library, combined with proteomic analysis, genes and enzymes involved in the microbial degradation of FA were identified for the first time. A functional 2-methylcitrate cycle, an anaplerotic pathway where propionyl-coenzyme A (CoA) is converted to pyruvate and succinate, was shown to be essential for growth in the presence of FA. The proteomic profile of
B. ambifaria
T16 showed that more than 50 enzymes (including those belonging to the 2-methylcitrate cycle, fatty acid metabolism, valine catabolism, and flavin biosynthesis) were significantly more abundant when growing on FA than on citrate. Flavin mononucleotide (FMN)-dependent luciferases like monooxygenase (LLM) are shown to catalyze the pyridine-ring cleavage reaction of several N-heterocyclic compounds. Deletion of a gene encoding a predicted LLM enzyme that was highly upregulated during growth on FA, completely abolished the capability of
B. ambifaria
T16 to grow with this mycotoxin as sole nitrogen, carbon, and energy source. Re-introduction of the wild type gene was able to restore growth. The mentioned gene is part of a gene cluster of unknown function that we termed
fua
, due to its probable role in fusaric acid catabolism. Our results suggest that the LLM encoded in the
fua
cluster catalyzes the pyridine-ring opening reaction during FA degradation, and that propionyl-CoA is one of the intermediates of FA catabolism in
B. ambifaria
T16.

IMPORTANCE

Fusaric acid (FA) is an important virulence factor produced by several
Fusarium
species. These fungi are responsible for wilt and rot diseases in a diverse range of crops. FA is toxic for animals, humans and soil-borne microorganisms. This mycotoxin reduces the survival and competition abilities of bacterial species able to antagonize
Fusarium
spp., due to its negative effects on viability and the production of antibiotics effective against these fungi. FA biodegradation is not a common characteristic among bacteria, and the determinants of FA catabolism have not been identified so far in any microorganism. In this study, we identified genes, enzymes, and metabolic pathways involved in the degradation of FA in the soil bacterium
Burkholderia ambifaria
T16. Our results provide insights into the catabolism of a pyridine-derivative involved in plant pathogenesis by a rhizosphere bacterium.
On the Existence of Radially Symmetric Solutions for the $ p $-Laplace Equation with Strong Gradient Nonlinearities
Authors: Tersenov Ar. S. 
Published: December 2023

AbstractWe consider the Dirichlet problem for the $ p $-Laplace equation
in presence of a gradient not satisfying the Bernstein–Nagumo type condition.
We define some class of gradient nonlinearities,
for which we prove the existence of a radially symmetric solution with a Hölder continuous derivative.
Genotype–phenotype correlations in paediatric and adolescent phaeochromocytoma and paraganglioma: a cross-sectional study
Authors: Seabrook Amanda , Vasudevan Anand , Neville Kristen , Gerstl Brigitte , Benn Diana , Smith Janine , Kirk Judy , Gill Anthony , Clifton-Bligh Roderick , Tucker Katherine 
Published: December 2023

Phaeochromocytoma (PC) and paraganglioma (PGL) syndromes associated with germline pathogenic variants are associated with high morbidity and mortality. Establishing genotype–phenotype correlations within a young population is challenging due to their rare occurrence.ObjectiveTo describe genotype–phenotype correlations in paediatric and adolescent patients diagnosed with PC/PGL. To establish the incidence of PC/PGL in a young population and prevalence of germline pathogenic variants within this group.Study designWe conducted a cross-sectional study of patients diagnosed with a PC/PGL aged 0–21 years old who were reviewed within Familial Cancer Services within New South Wales and the Australian Capital Territory, Australia.ResultsA germline pathogenic variant was detected in 80% (24/30) of patients;SDHB: n=12,VHL: n=11, andMAX: n=1. Only patients harbouring a germline pathogenic variant reported a family history of syndromic tumours, those with apparently sporadic disease did not (62.5% versus 0%, p=0.02). All patients withVHLpresented with an adrenal tumour compared with 25% of those withSDHB(100% versus 25%, p=0.01). Occurrence of multiple primary PC/PGL was seen in patients withVHLhowever was absent in patients withSDHB(36% versus 0%, p=0.03). Incidence rate of paediatric PC/PGL was 0.45 cases per million person years.ConclusionsPC/PGL diagnosed in children and adolescents were strongly associated with germline pathogenic variants inVHLorSDHB. These patients should be referred to specialist services for family counselling and genetic testing along followed by investigations for the detection of bilateral, multifocal or metastatic disease, and lifelong surveillance for recurrent disease.
Long-term effect of orthokeratology on choroidal thickness and choroidal contour in myopic children
Authors: Xu Shengsong , Wang Mengyi , Lin Sijia , Jiang Jinyun , Yu Mengting , Tang Xianghua , Xie Danxi , Lu Mingxin , Li Zhouyue , Yang Xiao 
Published: December 2023

PurposeTo investigate the long-term effect of orthokeratology (ortho-k) on the choroidal thickness and choroidal contour in myopic children.MethodsSubjects were from a conducted 2-year randomised clinical trial. Children (n=80) aged 8–12 years with spherical equivalent refraction of −1.00 to −6.00D were randomly assigned to the control group (n=40) and ortho-k group (n=40). Optical coherence tomography images were collected at the baseline, 1-month, 6-month, 12-month, 18-month and 24-month visits, then the choroidal thickness and choroid contour were calculated. Axial length (AL) and other ocular biometrics were also measured.ResultsDuring 2 years, in the control group, the choroidal thickness became thinning and the choroidal contour became prolate with time at all visits (all p<0.001). Ortho-k can improve the choroidal thickness (all p<0.001) and maintain the choroidal contour at all visits (all p<0.05). In the ortho-k group, the choroidal contour was less changed in the temporal than nasal (p=0.008), and the choroidal thickness was more thickening in the temporal 3 mm (p<0.001). Two-year change in choroidal thickness was significantly associated with the 2-year AL change in the control group (r=−0.52, p<0.001), however, this trend was broken by ortho-k (r=−0.05, p=0.342). After being adjusted by other variables in the multivariable regression model, the effect of ortho-k on choroidal thickness was stable.ConclusionsIn the current 2-year prospective study, ortho-k can improve the choroidal thickness and maintain the choroidal contour, but this effect diminished in a long term. Further study with larger sample size and longer follow-up is warranted to refine this issue.
Evolution of atrophied T2 lesion volume in primary-progressive multiple sclerosis: results from the phase 3 ORATORIO study
Authors: Zivadinov Robert , Pei Jinglan , Clayton David , Goldman Donna E , Winger Ryan C , Cabatingan Mark S , Dwyer Michael G , Bergsland Niels 
Published: December 2023

BackgroundAtrophied T2-lesion volume (aT2-LV) is an exploratory imaging marker in multiple sclerosis (MS) reflecting the volume of lesions subsumed into cerebrospinal fluid (CSF).ObjectiveTo investigate the effect of ocrelizumab (OCR) versus placebo (PBO) over 120 weeks on the accumulation of aT2-LV in a double-blind placebo-controlled (DBP) phase 3, primary-progressive (PP) MS study (ORATORIO;NCT01194570).MethodsThis post-hoc, MRI-blinded analysis evaluated 732 PPMS randomised to OCR (488) or PBO (244). Atrophied T2-LV was calculated by overlaying baseline T2-lesion masks on follow-up CSF maps. Clinical data from DBP and open-label extension (OLE) periods were available. Treatment effect was evaluated by a mixed-effect model with repeated measures, while logistic regression explored the association of aT2-LV at week 120 and clinical outcomes in the OLE period.ResultsOCR treatment significantly reduced accumulation of aT2-LV compared with PBO (319.4 mm3vs 366.1 mm3, p=0.015) at 120 weeks. OCR showed superiority over PBO in reducing aT2-LV in patients who developed confirmed disability progression (CDP) during the DBP period at 12 (CDP12) and 24 (CDP24) weeks for the composite of Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test and Timed 25-Foot Walk test. Accumulation of aT2-LV at week 120 was related to CDP12-EDSS (p=0.018) and CDP24-EDSS (p=0.022) in the OLE for the patients who were treated by PBO in the DBP only.ConclusionsOCR showed a significant effect of reducing the accumulation of aT2-LV in PPMS in the DBP period and was related to CDP-EDSS in OLE only in the PBO arm.
Micromechanical study of loess permeability and seepage erosion based on microstructure functional basic unit and seepage simulation in pore domain
Authors: Wang Weiping , Li Xi-An , Dong Haoyang , Chai Hao , Yang Wenfu 
Published: December 2023

The vast majority of geological disasters in loess-covered areas are caused by seepage erosion in loess. Therefore, this study focuses on the microscopic mechanism of loess seepage erosion and constructs a loess microstructure model based on particle “core + coat”. On this basis, the scanning electron microscope (SEM) photos are imported into COMSOL to simulate the micro-scale seepage in the pore domain. Through the actual permeability test, combined with the micro-quantitative information obtained by Image-Pro-Plus and Arcgis, the micro-factors affecting loess permeability are quantitatively analyzed by grey relational analysis. The results show that the dry density affects the porosity of loess and ultimately determines the permeability of loess. Different pore types and proportions lead to different seepage erosion of loess. The erosion process mainly occurs at the junction of pores. The sudden increase of velocity, pressure drop, and maximum shear rate at the throat indicate that this area is the main action area of loess seepage erosion. The research results of this study provide an important theoretical basis for the research and prevention of geological disasters and engineering diseases related to seepage deformation and failure in loess area.
Droplet Growth or Evaporation Does Not Buffer the Variability in Supersaturation in Clean Clouds
Authors: Anderson Jesse C. , Helman Ian , Shaw Raymond A. , Cantrell Will 
Published: December 2023

Abstract
Water vapor supersaturation in clouds is a random variable that drives activation and growth of cloud droplets. The Pi Convection–Cloud Chamber generates a turbulent cloud with a microphysical steady state that can be varied from clean to polluted by adjusting the aerosol injection rate. The supersaturation distribution and its moments, e.g., mean and variance, are investigated for varying cloud microphysical conditions. High-speed and collocated Eulerian measurements of temperature and water vapor concentration are combined to obtain the temporally resolved supersaturation distribution. This allows quantification of the contributions of variances and covariances between water vapor and temperature. Results are consistent with expectations for a convection chamber, with strong correlation between water vapor and temperature; departures from ideal behavior can be explained as resulting from dry regions on the warm boundary, analogous to entrainment. The saturation ratio distribution is measured under conditions that show monotonic increase of liquid water content and decrease of mean droplet diameter with increasing aerosol injection rate. The change in liquid water content is proportional to the change in water vapor concentration between no-cloud and cloudy conditions. Variability in the supersaturation remains even after cloud droplets are formed, and no significant buffering is observed. Results are interpreted in terms of a cloud microphysical Damköhler number (Da), under conditions corresponding to , i.e., the slow-microphysics regime. This implies that clouds with very clean regions, such that is satisfied, will experience supersaturation fluctuations without them being buffered by cloud droplet growth.

Significance Statement
The saturation ratio (humidity) in clouds controls the growth rate and formation of cloud droplets. When air in a turbulent cloud mixes, the humidity varies in space and time throughout the cloud. This is important because it means cloud droplets experience different growth histories, thereby resulting in broader size distributions. It is often assumed that growth and evaporation of cloud droplets buffers out some of the humidity variations. Measuring these variations has been difficult, especially in the field. The purpose of this study is to measure the saturation ratio distribution in clouds with a range of conditions. We measure the in-cloud saturation ratio using a convection cloud chamber with clean to polluted cloud properties. We found in clouds with low concentrations of droplets that the variations in the saturation ratio are not suppressed.
Predictive value of CCL2 in the prognosis and immunotherapy response of glioblastoma multiforme
Authors: Deng Longfei , Ren Jie , Li Benqin , Wang Yinggang , Jiang Nianfen , Wang Yi , Cui Hongjuan 
Published: December 2023

Abstract
Background
Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor with a poor prognosis. The C-C motif chemokine ligand 2 (CCL2) has shown abnormal expression associated with progression of multiple malignancies, however, its role in predicting the prognosis and immunotherapy response of GBM remains poorly understood.

Results
CCL2 was highly expressed in GBM as analyzed by integrating CGGA, GEPIA and UALCAN online platforms, and further verified by histologic examinations, qRT-PCR analysis, and independent GEO datasets. CCL2 could serve as an independent prognostic factor for both the poor overall survival and progression-free survival of GBM patients based on TCGA data, univariate and multivariate cox analyses. Functional enrichment analysis revealed that CCL2 mainly participated in the regulation of chemokine signaling pathway and inflammatory response. Further, CCL2 expression was positively correlated with CD4 T cells, macrophages, neutrophils and myeloid dendritic cells infiltrating GBM as calculated by the TIMER2.0 algorithm. Importantly, the tumor immune dysfunction and exclusion (TIDE) algorithm showed that in CCL2-high GBM group, the expression of CD274, CTLA4, HAVCR2 and other immune checkpoints were significantly increased, and the immune checkpoint blockade (ICB) therapy was accordingly more responsive.

Conclusions
CCL2 can be used as a predictor of prognosis as well as immunotherapy response in GBM, offering potential clinical implications.
Integrative analysis of TBI data reveals Lgmn as a key player in immune cell-mediated ferroptosis
Authors: Yan Liyan , Han Xiaonan , Zhang Mingkang , Fu Yikun , Yang Fei , Li Qian , Cheng Tian 
Published: December 2023

Abstract
Background
Traumatic brain injury (TBI) is a central nervous system disease caused by external trauma, which has complex pathological and physiological mechanisms. The aim of this study was to explore the correlation between immune cell infiltration and ferroptosis post-TBI.

Methods
This study utilized the GEO database to download TBI data and performed differentially expressed genes (DEGs) and ferroptosis-related differentially expressed genes (FRDEGs) analysis. DEGs were further analyzed for enrichment using the DAVID 6.8. Immunoinfiltration cell analysis was performed using the ssGSEA package and the Timer2.0 tool. The WGCNA analysis was then used to explore the gene modules in the data set associated with differential expression of immune cell infiltration and to identify the hub genes. The tidyverse package and corrplot package were used to calculate the correlations between hub genes and immune cell infiltration and ferroptosis-marker genes. The miRDB and TargetScan databases were used to predict complementary miRNAs for the Hub genes selected from the WGCNA analysis, and the DIANA-LncBasev3 tool was used to identify target lncRNAs for the miRNAs, constructing an mRNA-miRNA-lncRNA regulatory network.

Results
A total of 320 DEGs and 21 FRDEGs were identified in GSE128543. GO and KEGG analyses showed that the DEGs after TBI were primarily associated with inflammation and immune response. Xcell and ssGSEA immune infiltration cell analysis showed significant infiltration of T cell CD4+ central memory, T cell CD4+ Th2, B cell memory, B cell naive, monocyte, macrophage, and myeloid dendritic cell activated. The WGCNA analysis identified two modules associated with differentially expressed immune cells and identified Lgmn as a hub gene associated with immune infiltrating cells. Lgmn showed significant correlation with immune cells and ferroptosis-marker genes, including Gpx4, Hspb1, Nfe2l2, Ptgs2, Fth1, and Tfrc. Finally, an mRNA-miRNA-lncRNA regulatory network was constructed using Lgmn.

Conclusion
Our results indicate that there is a certain correlation between ferroptosis and immune infiltrating cells in brain tissue after TBI, and that Lgmn plays an important role in this process.
Screening of four lysosome-related genes in sepsis based on RNA sequencing technology
Authors: Chen Guihong , Zhang Wen , Wang Chenglin , Chen Muhu , Hu Yingchun , Wang Zheng 
Published: December 2023

Abstract
Purpose
Screening of lysosome-related genes in sepsis patients to provide direction for lysosome-targeted therapy.

Methods
Peripheral blood samples were obtained from 22 patients diagnosed with sepsis and 10 normal controls for the purpose of RNA sequencing and subsequent analysis of differential gene expression. Concurrently, lysosome-related genes were acquired from the Gene Ontology database. The intersecting genes between the differential genes and lysosome-related genes were then subjected to PPI, GO and KEGG analyses. Core genes were identified through survival analysis, and their expression trends in different groups were determined using meta-analysis. Single-cell RNA sequencing was used to clarify the cellular localization of core genes.

Results
The intersection of 1328 sepsis-differential genes with 878 lysosome-related genes yielded 76 genes. PPI analysis showed that intersecting genes were mainly involved in Cellular process, Response to stimulus, Immune system process, Signal transduction, Lysosome. GO and KEGG analysis showed that intersecting genes were mainly involved in leukocyte mediated immunity, cell activation involved in immune response, lytic vacuole, lysosome. Survival analysis screened four genes positively correlated with sepsis prognosis, namely GNLY, GZMB, PRF1 and RASGRP1. The meta-analysis revealed that the expression levels of these four genes were significantly higher in the normal control group compared to the sepsis group, which aligns with the findings from RNA sequencing data. Furthermore, single-cell RNA sequencing demonstrated that T cells and NK cells exhibited high expression levels of GNLY, GZMB, PRF1, and RASGRP1.

Conclusion
GNLY, GZMB, PRF1, and RASGRP1, which are lysosome-related genes, are closely linked to the prognosis of sepsis and could potentially serve as novel research targets for sepsis, offering valuable insights for the development of lysosome-targeted therapy. The clinical trial registration number is ChiCTR1900021261, and the registration date is February 4, 2019.