bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice
Authors: Fernández-García Victoria , González-Ramos Silvia , Avendaño-Ortiz José , Martín-Sanz Paloma , Gómez-Coronado Diego , Delgado Carmen , Castrillo Antonio , Boscá Lisardo 
Published: July 2022

AbstractIn the course of atherogenesis, the spleen plays an important role in the regulation of extramedullary hematopoiesis, and in the control of circulating immune cells, which contributes to plaque progression. Here, we have investigated the role of splenic nucleotide-binding oligomerization domain 1 (NOD1) in the recruitment of circulating immune cells, as well as the involvement of this immune organ in extramedullary hematopoiesis in mice fed on a high-fat high-cholesterol diet (HFD). Under HFD conditions, the absence of NOD1 enhances the mobilization of immune cells, mainly neutrophils, from the bone marrow to the blood. To determine the effect of NOD1-dependent mobilization of immune cells under pro-atherogenic conditions, Apoe−/− and Apoe−/−Nod1−/− mice fed on HFD for 4 weeks were used. Splenic NOD1 from Apoe−/− mice was activated after feeding HFD as inferred by the phosphorylation of the NOD1 downstream targets RIPK2 and TAK1. Moreover, this activation was accompanied by the release of neutrophil extracellular traps (NETs), as determined by the increase in the expression of peptidyl arginine deiminase 4, and the identification of citrullinated histone H3 in this organ. This formation of NETs was significantly reduced in Apoe−/−Nod1−/− mice. Indeed, the presence of Ly6G+ cells and the lipidic content in the spleen of mice deficient in Apoe and Nod1 was reduced when compared to the Apoe−/− counterparts, which suggests that the mobilization and activation of circulating immune cells are altered in the absence of NOD1. Furthermore, confirming previous studies, Apoe−/−Nod1−/− mice showed a reduced atherogenic disease, and diminished recruitment of neutrophils in the spleen, compared to Apoe−/− mice. However, splenic artery ligation reduced the atherogenic burden in Apoe−/− mice an effect that, unexpectedly was lost in Apoe−/−Nod1−/− mice. Together, these results suggest that neutrophil accumulation and activity in the spleen are driven in part by NOD1 activation in mice fed on HFD, contributing in this way to regulating atherogenic progression.
CD146 increases stemness and aggressiveness in glioblastoma and activates YAP signaling
Authors: Liang Yuanke , Voshart Daniëlle , Paridaen Judith T. M. L. , Oosterhof Nynke , Liang Dong , Thiruvalluvan Arun , Zuhorn Inge S. , den Dunnen Wilfred F. A. , Zhang Guojun , Lin Haoyu , Barazzuol Lara , Kruyt Frank A. E. 
Published: July 2022

AbstractGlioblastoma (GBM), a highly malignant and lethal brain tumor, is characterized by diffuse invasion into the brain and chemo-radiotherapy resistance resulting in poor prognosis. In this study, we examined the involvement of the cell adhesion molecule CD146/MCAM in regulating GBM aggressiveness. Analyses of GBM transcript expression databases revealed correlations of elevated CD146 levels with higher glioma grades, IDH-wildtype and unmethylated MGMT phenotypes, poor response to chemo-radiotherapy and worse overall survival. In a panel of GBM stem cells (GSCs) variable expression levels of CD146 were detected, which strongly increased upon adherent growth. CD146 was linked with mesenchymal transition since expression increased in TGF-ß-treated U-87MG cells. Ectopic overexpression of CD146/GFP in GG16 cells enhanced the mesenchymal phenotype and resulted in increased cell invasion. Conversely, GSC23-CD146 knockouts had decreased mesenchymal marker expression and reduced cell invasion in transwell and GBM-cortical assembloid assays. Moreover, using GSC23 xenografted zebrafish, we found that CD146 depletion resulted in more compact delineated tumor formation and reduced tumor cell dissemination. Stem cell marker expression and neurosphere formation assays showed that CD146 increased the stem cell potential of GSCs. Furthermore, CD146 mediated radioresistance by stimulating cell survival signaling through suppression of p53 expression and activation of NF-κB. Interestingly, CD146 was also identified as an inducer of the oncogenic Yes-associated protein (YAP). In conclusion, CD146 carries out various pro-tumorigenic roles in GBM involving its cell surface receptor function, which include the stimulation of mesenchymal and invasive properties, stemness, and radiotherapy resistance, thus providing an interesting target for therapy.
Influence of intermediate roll shifting on strip shape in a CVC-6 tandem cold mill based on a 3D multi-stand FE model
Authors: Li Lianjie , Xie Haibo , Zhang Tao , Pan Di , Li Xingsheng , Chen Fenghua , Liu Tianwu , Liu Xu , Liu Hongqiang , Sun Li , Jiang Zhengyi 
Published: July 2022

AbstractIntermediate roll shifting (IRS) is widely used for improving the strip shape in the six-high tandem cold mill, but most related studies are limited to a single stand. To fill the knowledge gap, a three-dimensional (3D) multi-stand elastic–plastic finite element (FE) model was developed for a continuously variable crown (CVC)-6 tandem cold mill using data transfer, which was then validated by industrial experimental results. Based on this FE model, the effects of the IRS on the strip crown, strip flatness, loaded roll gap profile and contact normal stress between rolls at each stand were quantitatively analysed. The results show that from Stand 1 (S1) to Stand 5 (S5), the regulation ability of the IRS on the strip crown shows a decreasing trend, which depends on the strip plastic rigidity; in contrast, the regulation ability on the quadratic flatness experiences an obvious increase from S1 to Stand 4 (S4), then a drop at S5, while the IRS exerts little effect on the quartic flatness and quartic crown of the loaded roll gap. Moreover, the most uniform distribution of contact normal stress emerges at different IRSs from S1 to S5. These findings can contribute to a better understanding of the role of the IRS in controlling the strip shape during tandem cold rolling (TCR).
Going deeper into the toxicokinetics of synthetic cannabinoids: in vitro contribution of human carboxylesterases
Authors: Wagmann Lea , Stiller Rebecca G. , Fischmann Svenja , Westphal Folker , Meyer Markus R. 
Published: July 2022

AbstractSynthetic cannabinoids (SC) are new psychoactive substances known to cause intoxications and fatalities. One reason may be the limited data available concerning the toxicokinetics of SC, but toxicity mechanisms are insufficiently understood so far. Human carboxylesterases (hCES) are widely known to play a crucial role in the catalytic hydrolysis of drugs (of abuse). The aim of this study was to investigate the in vitro contribution of hCES to the metabolism of the 13 SC 3,5-AB-5F-FUPPYCA, AB-5F-P7AICA, A-CHMINACA, DMBA-CHMINACA, MBA-CHMINACA, MDMB-4F-BINACA, MDMB-4en-PINACA, MDMB-FUBICA, MDMB-5F-PICA, MMB-CHMICA, MMB-4en-PICA, MMB-FUBINACA, and MPhP-5F-PICA. The SC were incubated with recombinant hCES1b, hCES1c, or hCES2 and analyzed by liquid chromatography–ion trap mass spectrometry to assess amide or ester hydrolysis in an initial activity screening. Enzyme kinetic studies were performed if sufficient hydrolysis was observed. No hydrolysis of the amide linker was observed using those experimental conditions. Except for MDMB-5F-PICA, ester hydrolysis was always detected if an ester group was present in the head group. In general, SC with a terminal ester bearing a small alcohol part and a larger acyl part showed higher affinity to hCES1 isozymes. Due to the low hydrolysis rates, enzyme kinetics could not be modeled for the SC with a tert-leucine-derived moiety, but hydrolysis reactions of MPhP-5F-PICA and of those containing a valine-derived moiety followed classic Michaelis–Menten kinetics. In conclusion, drug–drug/drug–food interactions or hCES polymorphisms may prolong the half-life of SC and the current results help to estimate the risk of toxicity in the future after combining them with activity and clinical data.
Targeted detection of cancer cells during biopsy allows real-time diagnosis of pulmonary nodules
Authors: Kennedy Gregory T. , Azari Feredun S. , Bernstein Elizabeth , Nadeem Bilal , Chang Ashley , Segil Alix , Sullivan Neil , Encarnado Emmanuel , Desphande Charuhas , Kucharczuk John C. , Leonard Kaela , Low Philip S. , Chen Silvia , Criton Aline , Singhal Sunil 
Published: July 2022

Abstract

Background
The diagnostic yield of biopsies of solitary pulmonary nodules (SPNs) is low, particularly in sub-solid lesions. We developed a method (NIR-nCLE) to achieve cellular level cancer detection during biopsy by integrating (i) near-infrared (NIR) imaging using a cancer-targeted tracer (pafolacianine), and (ii) a flexible NIR confocal laser endomicroscopy (CLE) system that can fit within a biopsy needle. Our goal was to assess the diagnostic accuracy of NIR-nCLE ex vivo in SPNs.

Methods
Twenty patients with SPNs were preoperatively infused with pafolacianine. Following resection, specimens were inspected to identify the lesion of interest. NIR-nCLE imaging followed by tissue biopsy was performed within the lesion and in normal lung tissue. All imaging sequences (n = 115) were scored by 5 blinded raters on the presence of fluorescent cancer cells and compared to diagnoses by a thoracic pathologist.

Results
Most lesions (n = 15, 71%) were adenocarcinoma-spectrum malignancies, including 7 ground glass opacities (33%). Mean fluorescence intensity (MFI) by NIR-nCLE for tumor biopsy was 20.6 arbitrary units (A.U.) and mean MFI for normal lung was 6.4 A.U. (p < 0.001). Receiver operating characteristic analysis yielded a high area under the curve for MFI (AUC = 0.951). Blinded raters scored the NIR-nCLE sequences on the presence of fluorescent cancer cells with sensitivity and specificity of 98% and 97%, respectively. Overall diagnostic accuracy was 97%. The inter-observer agreement of the five raters was excellent (κ = 0.95).

Conclusions
NIR-nCLE allows sensitive and specific detection of cancer cells in SPNs. This technology has far-reaching implications for diagnostic needle biopsies and intraprocedural decision-making.
Radionuclide imaging and therapy directed towards the tumor microenvironment: a multi-cancer approach for personalized medicine
Authors: van der Heide Circe D. , Dalm Simone U. 
Published: July 2022

Abstract
Targeted radionuclide theranostics is becoming more and more prominent in clinical oncology. Currently, most nuclear medicine compounds researched for cancer theranostics are directed towards targets expressed in only a small subset of cancer types, limiting clinical applicability. The identification of cancer-specific targets that are (more) universally expressed will allow more cancer patients to benefit from these personalized nuclear medicine–based interventions. A tumor is not merely a collection of cancer cells, it also comprises supporting stromal cells embedded in an altered extracellular matrix (ECM), together forming the tumor microenvironment (TME). Since the TME is less genetically unstable than cancer cells, and TME phenotypes can be shared between cancer types, it offers targets that are more universally expressed. The TME is characterized by the presence of altered processes such as hypoxia, acidity, and increased metabolism. Next to the ECM, the TME consists of cancer-associated fibroblasts (CAFs), macrophages, endothelial cells forming the neo-vasculature, immune cells, and cancer-associated adipocytes (CAAs). Radioligands directed at the altered processes, the ECM, and the cellular components of the TME have been developed and evaluated in preclinical and clinical studies for targeted radionuclide imaging and/or therapy. In this review, we provide an overview of the TME targets and their corresponding radioligands. In addition, we discuss what developments are needed to further explore the TME as a target for radionuclide theranostics, with the hopes of stimulating the development of novel TME radioligands with multi-cancer, or in some cases even pan-cancer, application.
Deep Learning–driven classification of external DICOM studies for PACS archiving
Authors: Jonske Frederic , Dederichs Maximilian , Kim Moon-Sung , Keyl Julius , Egger Jan , Umutlu Lale , Forsting Michael , Nensa Felix , Kleesiek Jens 
Published: July 2022

Abstract
Objectives
Over the course of their treatment, patients often switch hospitals, requiring staff at the new hospital to import external imaging studies to their local database. In this study, the authors present MOdality Mapping and Orchestration (MOMO), a Deep Learning–based approach to automate this mapping process by combining metadata analysis and a neural network ensemble.

Methods
A set of 11,934 imaging series with existing anatomical labels was retrieved from the PACS database of the local hospital to train an ensemble of neural networks (DenseNet-161 and ResNet-152), which process radiological images and predict the type of study they belong to. We developed an algorithm that automatically extracts relevant metadata from imaging studies, regardless of their structure, and combines it with the neural network ensemble, forming a powerful classifier. A set of 843 anonymized external studies from 321 hospitals was hand-labeled to assess performance. We tested several variations of this algorithm.

Results
MOMO achieves 92.71% accuracy and 2.63% minor errors (at 99.29% predictive power) on the external study classification task, outperforming both a commercial product (82.86% accuracy, 1.36% minor errors, 96.20% predictive power) and a pure neural network ensemble (72.69% accuracy, 10.3% minor errors, 99.05% predictive power) performing the same task. We find that the highest performance is achieved by an algorithm that combines all information into one vote-based classifier.

Conclusion
Deep Learning combined with metadata matching is a promising and flexible approach for the automated classification of external DICOM studies for PACS archiving.

Key Points
• The algorithm can successfully identify 76 medical study types across seven modalities (CT, X-ray angiography, radiographs, MRI, PET (+CT/MRI), ultrasound, and mammograms).
• The algorithm outperforms a commercial product performing the same task by a significant margin (> 9% accuracy gain).
• The performance of the algorithm increases through the application of Deep Learning techniques.
Should the early surgery threshold be moved to 72 h in over-85 patients with hip fracture? A single-center retrospective evaluation on 941 patients
Authors: De Luca Alessandro , Murena Luigi , Zanetti Michela , De Colle Paolo , Ratti Chiara , Canton Gianluca 
Published: July 2022

Abstract
Aim
Aim of the study was to assess whether early surgery and other clinical and orthogeriatric parameters could affect mortality rate in hip fracture patients aged > 85.

Materials and methods
Data regarding a 42-month period were retrospectively obtained from the institutional medical records and registry data. Gender, age, fracture pattern, surgical technique, type of anesthesia, timing of surgical intervention (within 24, 48 or 72 h from admission), days of hospitalization, mortality rate divided in intra-hospital, at 30 days and at 1 year were collected for the whole population. Some additional data were collected for an orthogeriatric subgroup.

Results
941 patients were considered, with a mean age of 89 years. Surgery was performed within 24, 48 and 72 h in 24.4%, 54.5% and 66.1% of cases, respectively. Intra-hospital mortality rate resulted to be 3.4%, while mortality at 30 days and 1 year resulted to be 4.5% and 31%, respectively. Early surgery within 48 and 72 h were significantly associated with a lower intra-hospital and 30-day mortality rate. In the orthogeriatric subgroup (394 patients), a significant association with a higher mortality rate was found for general anesthesia, number of comorbidities, ADL (Activities of Daily Living) < 3, transfer to other departments.

Conclusions
In over-85 hip fracture patients, the threshold for early surgery might be moved to 72 h to allow patients pre-operative stabilization and medical optimization as intra-hospital and 30-day mortality rates remain significantly lower. Advanced age, male sex, number of comorbidities, pre-operative dependency in ADL, general anesthesia, length of hospitalization and transfer to other departments were significantly related to mortality rate.
The clinical relevance of serum versus CSF NMDAR autoantibodies associated exclusively with psychiatric features: a systematic review and meta-analysis of individual patient data
Authors: Blackman Graham , Lim Mao Fong , Pollak Thomas , Al-Diwani Adam , Symmonds Mkael , Mazumder Asif , Carter Ben , Irani Sarosh , David Anthony 
Published: July 2022

Abstract
Background
A variety of psychiatric syndromes are associated with NMDAR autoantibodies; however, their clinical relevance when only present in the serum is unclear. We explored whether patients with CSF NMDAR autoantibodies could be distinguished from patients with serum-only NMDAR autoantibodies.

Methods
The electronic databases MEDLINE, EMBASE, PubMed, and PsycINFO were searched. Articles reporting adult patients with isolated psychiatric features and positive for NMDAR autoantibodies with relevant investigations were included. Patient level meta-analysis compared patients positive for CSF NMDAR autoantibodies with patients positive for serum NMDAR autoantibodies, but negative for CSF NMDAR autoantibodies. Dichotomous data were analysed using crude odds ratios (OR), whilst continuous data were analysed using Mann–Whitney Test (U). The protocol was prospectively registered (CRD42018082210).

Results
Of 4413 publications, 42 were included, reporting 79 patients. Median age was 34 years (IQR 19 years); 56% (45/79) were female and 24% (16/68) had a tumour. In total, 41 patients were positive for CSF autoantibodies and 20 were positive for serum-only autoantibodies. Patients with CSF autoantibodies were significantly more likely to be female (p < 0.001) and have a rapid (< 3 month) onset of symptoms (p = 0.02) than patients with serum-only autoantibodies. They were also more likely to present with psychosis (p < 0.001), exhibit EEG (p = 0.006), MRI (p = 0.002), and CSF (p = 0.001) abnormalities, but less likely to present with insomnia (p = 0.04).

Conclusions
Patients with an isolated psychiatric syndrome with CSF NMDAR autoantibodies can potentially be distinguished from those with serum-only NMDAR autoantibodies based on clinicodemographic and investigation findings.
Association between lipid trajectories during pregnancy and risk of postpartum glucose intolerance after gestational diabetes mellitus: a cohort study
Authors: Yang Zhuofan , Li Zhuyu , Cheng Yunjiu , Chen Peisong , Wang Dongyu , Chen Haitian , Chen Wei , Wang Zilian 
Published: July 2022

Abstract
Aims
To assess lipid trajectories throughout pregnancy in relation to early postpartum glucose intolerance in women with gestational diabetes mellitus (GDM).

Methods
This prospective cohort study included 221 Chinese women with GDM who completed plasma lipid test in each trimester of pregnancy and oral glucose tolerance test at 6–9 weeks postdelivery between January 1, 2018 and January 8, 2020. Using the group-based trajectory modeling, total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol(HDL-c) were identified separately as three trajectories: low, moderate, and high trajectory. The associations between lipid trajectories and early postpartum glucose intolerance were all evaluated.

Results
Seventy-three participants developed postpartum glucose intolerance. For patients in low, moderate and high trajectory, the incidence of postpartum glucose intolerance was 38.4%, 34.9%, and 17.9%, respectively. GDM women with lower LDL-c trajectories presented a higher risk of postpartum glucose intolerance. The adjusted odds ratio (95% CI) for glucose intolerance was 3.14 (1.17–8.39) in low LDL-c trajectory and 2.68 (1.05–6.85) in moderate trajectory when compared with the high one. However, TC trajectory was not associated with the risk of postpartum glucose intolerance, nor were TG trajectory and HDL-c trajectory. Moreover, a significant difference of insulin sensitivity was observed in participants with different LDL-c trajectories; participants in high LDL-c trajectory had the highest insulin sensitivity, whereas the women in low LDL-c trajectory had the lowest insulin sensitivity (P = 0.02).

Conclusions
The high trajectory of LDL-c during pregnancy may play a protective role on postpartum glucose intolerance in women with GDM. Further studies are warranted to explore the underlying mechanism.
Trial registration The study was reviewed and approved by the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University (reference number: [2014]No. 93). All participants provided written informed consent forms, and the ethics committee approved this consent procedure.
Interlaboratory comparisons of chemical measurements: Quo Vadis?
Authors: Meija Juris , Possolo Antonio 
Published: July 2022

AbstractIn numerous articles and editorials, many of which were published in ACQUAL, Paul De Bièvre laid out challenges time and again about how the application of statistical methods can help improve our understanding of chemical measurements. Paul’s insights and incisive criticism were as illuminating and as provocative as in all other areas that he looked into—from counting to consensus building, from the validity of common statistical assumptions to the impact of model uncertainty. This memorial contribution briefly revisits some of these concerns illustrated by examples from interlaboratory comparisons and proposes an optimistic outlook for how the statistical arts practised in close collaboration between chemist and statistician will continue to add value to the chemical sciences.
Highly perturbed genes and hub genes associated with type 2 diabetes in different tissues of adult humans: a bioinformatics analytic workflow
Authors: De Silva Kushan , Demmer Ryan T. , Jönsson Daniel , Mousa Aya , Forbes Andrew , Enticott Joanne 
Published: July 2022

AbstractType 2 diabetes (T2D) has a complex etiology which is not yet fully elucidated. The identification of gene perturbations and hub genes of T2D may deepen our understanding of its genetic basis. We aimed to identify highly perturbed genes and hub genes associated with T2D via an extensive bioinformatics analytic workflow consisting of five steps: systematic review of Gene Expression Omnibus and associated literature; identification and classification of differentially expressed genes (DEGs); identification of highly perturbed genes via meta-analysis; identification of hub genes via network analysis; and downstream analysis of highly perturbed genes and hub genes. Three meta-analytic strategies, random effects model, vote-counting approach, and p value combining approach, were applied. Hub genes were defined as those nodes having above-average betweenness, closeness, and degree in the network. Downstream analyses included gene ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, metabolomics, COVID-19-related gene sets, and Genotype-Tissue Expression profiles. Analysis of 27 eligible microarrays identified 6284 DEGs (4592 downregulated and 1692 upregulated) in four tissue types. Tissue-specific gene expression was significantly greater than tissue non-specific (shared) gene expression. Analyses revealed 79 highly perturbed genes and 28 hub genes. Downstream analyses identified enrichments of shared genes with certain other diabetes phenotypes; insulin synthesis and action-related pathways and metabolomics; mechanistic associations with apoptosis and immunity-related pathways; COVID-19-related gene sets; and cell types demonstrating over- and under-expression of marker genes of T2D. Our approach provided valuable insights on T2D pathogenesis and pathophysiological manifestations. Broader utility of this pipeline beyond T2D is envisaged.