bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Tabletop X-Ray Tomography Instrument for Nanometer-Scale Imaging: Reconstructions
Authors: Levine Zachary , Alpert Bradley , Dagel Amber , Fowler Joseph , Jiminez Edward , Nakamura Nathan , Swetz Daniel , Szypryt Paul , Thompson Kyle , Ullom Joel 
Published: October 2022

Abstract
We show three-dimensional reconstructions of a region of an integrated circuit from a 130 nm copper process. The reconstructions employ x-ray computed tomography, measured with a new and innovative high-magnification x-ray microscope. The instrument uses a focused electron beam to generate x rays in a 100 nm spot and energy-resolving x-ray detectors that minimize
backgrounds and hold promise for identification of materials within the sample. The x-ray generation target, a layer of platinum, is fabricated on the circuit wafer itself. A region of interest is imaged from a limited range of angles and without physically removing the region from the larger circuit. The reconstruction is consistent with the circuit’s design file.
RUPP Th17s cause Hypertension and Mitochondrial Dysfunction in the Kidney and Placenta during Pregnancy
Authors: Fitzgerald Sarah , Deer Evangeline , Hogg James , Cornelius Denise C. , Turner Ty , Amaral Lorena M. , Ibrahim Tarek , LaMarca Babbette , Herrock Owen , Hoang Ngoc , Campbell Nathan , Edwards Kristin 
Published: October 2022

Abstract
BACKGROUND
Preeclampsia (PE), new-onset hypertension (HTN), and organ dysfunction during the second half of pregnancy, is associated with an increase in inflammatory immune cells, including T helper 17 (Th17) cells. Studies have demonstrated that mitochondrial (mt) dysfunction is important in the pathogenesis of PE though causative factors have yet to be fully identified. Although Th17 cells, natural killer (NK) cells, and mt dysfunction contribute to HTN in the reduced uterine perfusion pressure (RUPP) rat model, the role of Th17 cells or IL-17 in mt dysfunction is unknown. Therefore, we hypothesize that RUPP stimulated Th17 cells cause HTN and mt dysfunction, which is alleviated with the blockade of IL-17.
METHODS
On gestational day 12 (GD12), RUPP Th17 cells were transferred into normal pregnant (NP) Sprague Dawley rats. A subset of NP + RUPPTh17 rats received IL-17RC (100pg/day) on GD14-19. Blood pressure (MAP), NK cells, and mt function were measured on GD19 in all groups.
RESULTS
MAP increased in response to NP + RUPP Th17 compared to NP rats and was lowered with IL-17RC. Circulating and placental NK cells increased with NP + RUPP Th17 compared to NP and were lowered with IL-17RC. Renal mtROS increased in NP + RUPP Th17 compared to NP and was normalized with IL-17RC. Similar to PE women, placental mtROS decreased in NP + RUPP Th17 and was normalized with IL-17RC.
CONCLUSION
Our results indicate that IL-17RC inhibition normalizes HTN, NK cell activation, and multi-organ mt dysfunction caused by Th17 cells stimulated in response to placental ischemia.
Anti-inflammatory effects of CBD in human microglial cells latently and actively infected with HIV-1 virus
Authors: Yndart Adriana , Llaguno Lorgelys , Madepalli Lakshmana , Vashist Arti , Nair Madhavan 
Published: October 2022

Abstract
Human immunodeficiency virus (HIV) infection is associated with a chronic inflammatory stage and continuous inflammasome pathway activation. We studied the anti-inflammatory effects of the compound cannabidiol (CBD) in comparison with Δ (9)-tetrahydrocannabinol [Δ(9)-THC] in human microglial cells (HC69) latently and actively infected with HIV. Our results demonstrated that CBD reduced the production of various inflammatory cytokines and chemokines such as MIF, SERPIN E1, IL6, IL8, GM-CSF, MCP-1, CXCL1, CXCL10, and IL1 β compared to Δ(9)-THC treatment. In addition, CBD produced the deactivation of caspase 1, which plays a significant role in the inflammasome cascade. Furthermore, CBD significantly reduced the expression of HIV. Our study demonstrate that CBD which is anti-inflammatory which does not cause psychotropic effects compared to THC will be of therapeutic significance against HIV-1 infections.
Bioinformatics-based Exploration of the Molecular Mechanism of Autophagy-related Differentially Expressed Genes in Psoriasis and Atopic Dermatitis
Authors: Yang Lijuan , Zhu Dongning , Dang Yanling , Jia Yu , Zhao Chan 
Published: October 2022

Abstract
Atopic dermatitis (AD) and psoriasis are both chronic recurrent inflammatory skin diseases. However, research on AD and psoriasis co-morbidity is still in early stages and limited to clinical manifestations. In this study, we studied the role of autophagy-related genes in AD and psoriasis by used integrated bioinformatics methods. We obtained differentially expressed genes (DEGs) for psoriasis and AD by analyzing the datasets GSE14905(psoriasis) and GSE32924(atopic dermatitis). We further identified autophagy-related DEGs by intersecting above-obtained DEGs with autophagy-related genes. Then we performed Gene Ontology (GO), Kyoto Encyclopedia Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). And hub genes were identified by constructing protein-protein interaction (PPI) networks. Finally, we conducted ROC validation of hub genes and explored the correlation of hub genes with other molecules and immune cells in atopic dermatitis and psoriasis. Finally, we concluded that the 13 autophagy-related genes are involved in the pathogenesis and progression of AD and psoriasis by regulating cell cycle, cellular components eradication and drug metabolisms, and could predict the onset and severity of diseases.
Recognizing and monitoring infectious sources of schistosomiasis by developing deep learning models with high-resolution remote sensing images
Authors: Xue Jing-Bo , Xia Shang , Wang Xin-Yi , Huang Lu-Lu , Huang Liang-Yu , Hao Yu-Wan , Zhang Li-Juan , Li Shi-Zhu 
Published: October 2022

Abstract
Objective: This study aimed to develop deep learning models with high-resolution remote sensing images for recognizing and monitoring livestock bovine, which is an intermedia source of Schistosoma japonicuminfection, and to evaluate the effectiveness of developed models for real-world application.
Methods: The dataset of livestock bovine’s spatial distribution was constructed based on high-resolution remote sensing images. The images were further divided into training and test datasets for model development. Two recognition models based on deep learning methods (ENVINet5 and Mask R-CNN; were developed with reference to the training datasets. The performance of the developed models was evaluated by the performance metrics of precision, recall, and F1-score.
Results: A total of 50 typical image areas were selected, and 1,125 bovine objectives were labeled by the ENVINet5 model and 1,277 bovine objectives were labeled by
the Mask R-CNN model. For the ENVINet5 model, a total 1,598 records of bovine distribution were recognized. The model precision and recall were 81.85% and 80.24%, respectively. The F1 score was 0.807. For the Mask R-CNN mode, 1,679 records of bovine objectives were identified. The model precision and recall were 87.32% and 85.16%, respectively. The F1 score was 0.865. When applying the developed models to real-world schistosomiasis-endemicregions, there were 63 bovine objectives in the original image, 53 records were extracted using the ENVINet5 model, and 57 records were extracted using the Mask R-CNN model. The successful recognition ratios were 84.1% and 90.5% for the respectively developed models.
Conclusion: For the control of schistosomiasis, it is feasible to recognize and monitor livestock bovine by developing deep learning models with high-resolution remote sensing images. The ENVINet5 model can use a few training images to create training datasets with a reasonable accuracy of segmentation. The ENVINet5 model is very feasible for when bovine distribution is low in structure with few samples. The Mask R-CNN model needs to create labels along the target object and requires a long time for data training. The Mask R-CNN model is good in the framework design and runs highly efficiently. The livestock recognition models developed using deep learning methods with high-resolution remote sensing images very accurately recognize the spatial distribution of livestock, which could enable precise control of schistosomiasis.
Identification and validation of a novel survival prediction model based on the T cell phenotype in tumor immune microenvironment and peripheral blood for the prognosis in gastric cancer
Authors: ma jing , Li Jianhui , He Nan , Qian Meirui , Lu Yuanyuan , Wang Xin , Wu Kaichun 
Published: October 2022

Abstract
Background
The correlation and difference of T cells phenotype between peripheral blood lymphocytes (PBLs) and tumor immune microenvironment (TIME) in patients with gastric cancer (GC) is not clear. We aimed to characterize the phenotypes of CD8+ T cells in tumor infiltrating lymphocytes (TILs) and PBLs in patients with different outcomes and to establish a useful survival prediction model.
Methods
Multiplex immunofluorescence staining and flow cytometry were used to detect the expression of inhibitory molecule (IM) and active marker (AM) in CD8+TILs and PBLs, respectively. The role of these parameters in 3-year prognosis was assessed by receiver operating characteristic. Then, we divided patients into two TIME clusters (TIME-A/B) and two PBL clusters (PBL-A/B) by unsupervised hierarchical clustering based on the results of multivariate analysis, and used Kaplan-Meier method to analyze the difference in prognosis between each group. Finally, we constructed and compared three survival prediction models based on Cox regression analysis, and further validated the efficiency and accuracy in the internal and external cohort.
Results
The percentage of PD-1+CD8+TILs, TIM-3+CD8+TILs, PD-L1+CD8+TILs, PD-L1+CD8+PBLs and the density of PD-L1+CD8+TILs were independent risk factors, while the percentage of TIM-3+CD8+PBLs was an independent protective factor. The patients in TIME-B showed a worse 3-year overall survival (OS) (HR: 3.256, 95%CI: 1.318–8.043, P = 0.006), with a higher density of PD-L1+CD8+TILs (P < 0.001) and percentage of PD-1+CD8+TILs (P = 0.017) and PD-L1+CD8+TILs (P < 0.001) compared to TIME-A group. The patients in PBL-B showed a higher positivity of PD-L1+CD8+PBLs (P = 0.042), LAG-3+CD8+PBLs (P < 0.001), TIM-3+CD8+PBLs (P = 0.003), PD-L1+CD4+PBLs (P = 0.001), LAG-3+CD4+PBLs (P < 0.001) and poorer 3-year OS (HR: 0.124, 95%CI: 0.017–0.929, P = 0.015) compared to PBL-A group. In our three survival prediction models, Model 3, which was based on the percentage of TIM-3+CD8+PBLs, PD-L1+CD8+TILs and PD-1+CD8+TILs, showed the best sensitivity (0.950, 0.914), specificity (0.852, 0.857) and accuracy (κ = 0.787, P < 0.001; κ = 0.771, P < 0.001) in the internal and external cohort, respectively.
Conclusion
We established a comprehensive and robust survival prediction model based on the T cell phenotype in TIME and PBLs for the prognosis in GC.
Characterization of a novel crocetin glycosyltransferase UGTCs4 involved in two steps of glycosylation in crocin biosynthesis from crocus cultured cell
Authors: Lai Chengxia , Yang Ni , Yusuyin Mayila , Zhang Dawei , Yang Yanlong , Li Chunping , Xu Haijiang 
Published: October 2022

Abstract
crocins, water-soluble apocarotenoids, are a kind of crocetin glucosyl-esters that are due to the action of glycosyltransferases that are added glucose moieties to crocetin. To date, the glycosyltransferases involved in crocin biosynthesis are gradually discovered in the plant kingdom. In this work, a putative crocetin glycosyltransferase UGTCs4was first functionally characterized from cultured crocus cells. The constructed model of UGTCs4 based on the given model of UGT75L2 showed that highly structural similarity with that of UGT75L6 and UGT74AD1, suggesting a common function specializing in glycosylation of the glucose moieties of crocetin glucosides. Function characterization demonstrated that UGTCs4 could glycosylate crocetin yielding crocetin-monoglycoside(crocin 5) and crocetin-diglycoside(crocin 3) which were produced in a time-dependent manner. This work represents, to our knowledge, the first functional identification of a C. sativus crocetin glycosyltransferase involved in the crocin biosynthetic pathway employing the purified recombinant protein.
Dual FGFR and VEGFR inhibition synergistically restrain hexokinase 2-dependent lymphangiogenesis and immune escape in intrahepatic cholangiocarcinoma
Authors: Peng Min , Huang Yamei , Shen Chuanlai , Yu Weiping , Li Hui , Gu Jinyang 
Published: October 2022

Abstract

Background Intrahepatic cholangiocarcinoma (iCCA) patients often lose the chance of radical resection due to early lymphatic metastasis. And most of the therapy in cholangiocarcinoma has been limited and ineffective. Herein, we examined the role of FGF and VEGF pathways in regulating lymphangiogenesis and PD-L1 expression. We also validated the possibility to achieve a powerful anti-lymphangiogenesis effect and improve the immunocompetence with combination therapy in iCCA. Methods The expression of FGFR1 and VEGFR3 in primary lymphatic endothelial cells (LECs) were detected by Flow cytometry. The lymphngiogenic function of FGF and VEGF were evaluated in LECs and iCCA xenograft mice model. The relationship between VEGF and hexokinase2 (HK2) was validated in LECs by western blot, immunofluorescence and luciferase reporter assays. The therapeutic efficacy of infigratinib in combination with SAR131675 were assessed in LECs and xenograft models. Microarray analysis was used to evaluate the pathological relevance between FGFR1 and VEGFR3 with HK2 in human lymphatic vessels. PD-L1 expression in LECs affected by combined treatment were analysis by flow cytometry and western blot. Results FGF promoted lymphangiogenesis through c-MYC-dependent modulation of HK2. In addition, VEGFC also upregulated HK2 expression. Mechanically, VEGFC phosphorylated PI3K/Akt/mTOR axis to upregulate HIF-1α expression at the translational level, HIF-1α then bind to the HK2 promoter region for transcriptional activation. More importantly, dual FGFR and VEGFR inhibition with infigratinib and SAR131675 almost completely inhibited lymphangiogenesis in LECs and iCCA xenograft mice model. Histologically, high HK2 expression in lymphatic vessels were significantly associated with poor iCCA prognosis and the expression of HK2, FGFR1 and VEGFR3 in lymphatic vessels were related to lymph node metastasis in intrahepatic cholangiocarcinoma. Meanwhile, FGFR1 and VEGFR3 were significantly correlated with HK2 in lymphatic vessels. Furthermore, the combination of infigratinib and SAR131675 significantly reduced PD-L1 expression in LECs through inhibiting lactic acid production. Conclusions Dual FGFR and VEGFR inhibition restrain lymphangiogenesis through suppression c-MYC-dependent and HIF-1α-mediated HK2 expression respectively. Decreased HK2 down-regulated glycolytic activity and further attenuated PD-L1 expression. Our findings suggest that dual FGFR and VEGFR blocking is an effective novel combination strategy to inhibit lymphangiogenesis and improve the immunocompetence in iCCA.
Unparalleled details of soft tissues in a Cretaceous ant
Authors: Zhuang Yuhui , Xu Wenjing , Zhang Guojie , Mai Huijuan , Li Xiaoqin , He Hong , Ran Hao , Liu Yu 
Published: October 2022

Abstract
For social insects such as ants, the internal organs are important in understanding their eusocial behaviour and evolution. Such organs, however, are rarely preserved on fossils. In each of the few cases reporting exceptionally fossilized soft tissues in arthropods, only one of the nervous, muscular or cardiovascular systems was described. Here, we report a female specimen (gyne) of the extinct ant group – †Zigrasimecia – included in a Cretaceous amber piece from Kachin, Myanmar, with an almost complete system formed by various internal organs. These include the brain, the main exocrine system, part of the digestive tract, and several muscle clusters. Our findings expand the knowledge of fossil ants to their internal anatomy. As the gyne bears a morphologically unique labrum, the internal and external features of our specimen suggest that the early ant may have special ecological habits during the Cretaceous period.
Toward precision biomarker RAI therapy of well-differentiated thyroid cancer: linking administered radioactivity (MBq) to a prescribed lesion radiation-absorbed dose (cGy)
Authors: Mauguen Audrey , Grewal Ravinder , Augensen Finn , Abusamra Murad , Mahajan Sonia , Jayaprakasam Vetri Sudar , Osborne Joseph , Pentlow Keith , Haque Sofia , Fagin James , Schoder Heiko , Tuttle Michael , Ho Alan , Humm John , Larson Steven 
Published: October 2022

Abstract
Purpose

To introduce a biomarker-based dosimetry method for radioactive iodine 131I therapy (RAI) of metastatic differentiated thyroid cancer (mDTC), adapted to the underlying heterogeneity of lesions’ radiation-absorbed dose (RAD) in cGy, and permitting 1) estimates of RAD/lesion with known precision and 2) optimization of patient-specific administered amount of radioactive iodine (131I) in MBq.

Methods

Patients referred for RAI therapy of mDTC were enrolled in institutionally approved protocols. A total of 208 mDTC lesions (in 21 patients) with SUV > 1 underwent quantitative PET scans at 24, 48, 72, and 120 hours post-administration of 222 MBq of theranostic NaI-124I to determine the individual lesion RAD (in cGy) based on MIRD 2020 guidance. Using a general estimating equation, a prediction curve for biomarker development was generated in the form of a best-fit regression line and 95% prediction interval, correlating individual predicted lesion RAD metrics, with candidate biomarkers (“predictors”) such as SUV and activity in microcurie per gram, from a single imaging timepoint.

Results

In the 169 lesions (in 15 patients) that received 131I therapy, individual lesion cGy varied over 3 logs with a median of 22,000 cGy, confirming that heterogeneity of lesion RAD was profound. Initial findings from the prediction curve on all 208 lesions confirmed that 48h SUV was the best predictor of lesion RAD and permitted calculation of the 131I required (in MBq) to achieve a lesional threshold dose for response (2,000 cGy) in more than 95% of lesions.

Conclusions

Based on MIRD lesion RAD estimates and regression statistics, we propose and report initial feasibility for an 124I-PET-based dosimetry biomarker for RAI in patients with mDTC. This approach enables clinicians to select personalized (precision) therapeutic administration of radioactivity (MBq) to achieve a desired target lesion-absorbed doses (cGy) for > 95% of all lesions using a single 48-hour measurement 124I-PET image.
NCT04462471, Registered July 8, 2020.
NCT03647358, Registered Aug 27, 2018.
Large-scale analysis of sheep rumen metagenome profiles captured by reduced representation sequencing reveals individual profiles are influenced by the environment and genetics of the host
Authors: Hess Melanie K. , Hodgkinson Hannah E. , Hess Andrew S. , Zetouni Larissa , Budel Juliana C.C. , Henry Hannah M. , Donaldson Alistair , Bilton Timothy P. , Stijn Tracey C. van , Kirk Michelle R. , Dodds Ken G. , Brauning Rudiger , McCulloch Alan F. , Hickey Sharon M. , Johnson Patricia L. , Jonker Arjan , Morton Nickolas , Hendy Shaun , Oddy V. Hutton , Janssen Peter H. , McEwan John C. , Rowe Suzanne J. 
Published: October 2022

Abstract
Background
Producing animal protein while reducing the animal’s impact on the environment, e.g., through improved feed efficiency and lowered methane emissions, has gained interest in recent years. Genetic selection is one possible path to reduce the environmental impact of livestock production, but these traits are difficult and expensive to measure on many animals. The rumen microbiome may serve as a proxy for these traits due to its role in feed digestion. Restriction enzyme-reduced representation sequencing (RE-RRS) is a high-throughput and cost-effective approach to rumen metagenome profiling, but the systematic (e.g., sequencing) and biological factors influencing the resulting reference based (RB) and reference free (RF) profiles need to be explored before widespread industry adoption is possible.
Results
Metagenome profiles were generated by RE-RRS of 4,479 rumen samples collected from 1,708 sheep, and assigned to eight groups based on diet, age, time off feed, and country (New Zealand or Australia) at the time of sample collection. Systematic effects were found to have minimal influence on metagenome profiles. Diet was a major driver of differences between samples, followed by time off feed, then age of the sheep. The RF approach resulted in more reads being assigned per sample and afforded greater resolution when distinguishing between groups than the RB approach. Normalizing relative abundances within the sampling Cohort abolished structures related to age, diet, and time off feed, allowing a clear signal based on methane emissions to be elucidated. Genus-level abundances of rumen microbes showed low-to-moderate heritability and repeatability and were consistent between diets.
Conclusions
Variation in rumen metagenomic profiles was influenced by diet, age, time off feed and genetics. Not accounting for environmental factors may limit the ability to associate the profile with traits of interest. However, these differences can be accounted for by adjusting for Cohort effects, revealing robust biological signals. The abundances of some genera were consistently heritable and repeatable across different environments, suggesting that metagenomic profiles could be used to predict an individual’s future performance, or performance of its offspring, in a range of environments. These results highlight the potential of using rumen metagenomic profiles for selection purposes in a practical, agricultural setting.
A Zur-mediated transcriptional regulation of the zinc export system
Authors: Ducret Verena , Gonzalez Diego , Leoni Sara , Valentini Martina , Perron Karl 
Published: October 2022

Abstract
The control of cellular zinc (Zn) concentrations by dedicated import and export systems is essential for the survival and virulence of Pseudomonas aeruginosa. The transcription of its many Zn transporters is therefore tightly regulated by a known set of transcription factors involved in either the import or the export of Zn. In this work, we show that the Zur protein, a well-known repressor of Zn import, plays a dual role and functions in both import and export processes. In a situation of Zn excess, Zur represses Zn entry, but also activates the transcription of czcR, a positive regulator of the Zn export system. To achieve this, Zur binds at two sites, located by DNA footprinting in the region downstream the czcR transcription start site. In agreement with this regulation, a delay in induction of the efflux system is observed in the absence of Zur and Zn resistance is affected. The discovery of this regulation highlights a new role of Zur as global regulator of Zn homeostasis in P. aeruginosa disclosing an important link between Zur and zinc export.