bluuebunny/crossref_metadata_2025_split huggingface dataset:
The profile and persistence of clinically critical antibiotic resistance genes and human pathogenic bacteria in manure-amended farmland soils
Authors: Zhu Lin , Lian Yulu , Lin Da , Lin Guoping , Wang Meizhen 
Published: November 2022

IntroductionMicrobial contamination in farmlands is usually underestimated and understudied. Different fertilization times and manure origins might introduce and change the microorganism diversity in farmland soils and thus might influence the abundance and persistence of microbial contamination including antibiotic resistance genes (ARGs), human bacterial pathogens (HBPs), and virulence factor genes (VFGs).MethodsA 0.5-/1.5-year fertilization experiment was performed, and metagenomic sequencing was conducted to quantify microbial contamination. The resistomes of soil samples revealed that ARGs against antibiotics which were extensively used in veterinary medicine as well as clinically critical ARGs (CCARGs) persisted in manure-amended soils. Here the extended-spectrum beta-lactamase and carbapenemase bla genes, the high-level mobilized colistin resistance gene mcr, the tigecycline resistance gene tet(X), and the vancomycin resistance gene van, all of which can circumvent the defense line of these “last-resort” antibiotics were selected to investigate CCARG pollution in farm environments.ResultsA total of 254 potential HBPs and 2106 VFGs were detected in soil samples. Overall, our results revealed that (1) farmland soils could serve as a reservoir of some important bla, mcr, tet(X), and van gene variants, (2) the diversity and relative abundance of HBPs and VFGs increased significantly with incremental fertilization times and were discrepant among different manureamended soils, and (3) most CCARGs and VFGs coexisted in HBPs.DisscusionThe results of this study suggested a biological risk of manure in spreading antimicrobial resistance and pathogenicity.
“Imagine this smart speaker to have a body”: An analysis of the external appearances and the characteristics that people associate with voice assistants
Authors: Carolus Astrid , Wienrich Carolin 
Published: November 2022

IntroductionModern digital devices, such as conversational agents, simulate human–human interactions to an increasing extent. However, their outward appearance remains distinctly technological. While research revealed that mental representations of technology shape users' expectations and experiences, research on technology sending ambiguous cues is rare.MethodsTo bridge this gap, this study analyzes drawings of the outward appearance participants associate with voice assistants (Amazon Echo or Google Home).ResultsHuman beings and (humanoid) robots were the most frequent associations, which were rated to be rather trustworthy, conscientious, agreeable, and intelligent. Drawings of the Amazon Echos and Google Homes differed marginally, but “human,” “robotic,” and “other” associations differed with respect to the ascribed humanness, consciousness, intellect, affinity to technology, and innovation ability.DiscussionThis study aims to further elaborate on the rather unconscious cognitive and emotional processes elicited by technology and discusses the implications of this perspective for developers, users, and researchers.
Cardiac MRI segmentation of the atria based on UU-NET
Authors: Wang Yi , Li Shu-Ting , Huang Jing , Lai Qing-Quan , Guo Yi-Fan , Huang Yin-Hui , Li Yuan-Zhe 
Published: November 2022

Background and objectiveIn today's society, people's work pressure, coupled with irregular diet, lack of exercise and other bad lifestyle, resulting in frequent cardiovascular diseases. Medical imaging has made great progress in modern society, among which the role of MRI in cardiovascular field is self-evident. Based on this research background, how to process cardiac MRI quickly and accurately by computer has been extensively discussed. By comparing and analyzing several traditional image segmentation and deep learning image segmentation, this paper proposes the left and right atria segmentation algorithm of cardiac MRI based on UU-NET network.MethodsIn this paper, an atrial segmentation algorithm for cardiac MRI images in UU-NET network is proposed. Firstly, U-shaped upper and lower sampling modules are constructed by using residual theory, which are used as encoders and decoders of the model. Then, the modules are interconnected to form multiple paths from input to output to increase the information transmission capacity of the model.ResultsThe segmentation method based on UU-NET network has achieved good results proposed in this paper, compared with the current mainstream image segmentation algorithm results have been improved to a certain extent. Through the analysis of the experimental results, the image segmentation algorithm based on UU-NET network on the data set, its performance in the verification set and online set is higher than other grid models. The DSC in the verification set is 96.7%, and the DSC in the online set is 96.7%, which is nearly one percentage point higher than the deconvolution neural network model. The hausdorff distance (HD) is 1.2 mm. Compared with other deep learning models, it is significantly improved (about 3 mm error is reduced), and the time is 0.4 min.ConclusionThe segmentation algorithm based on UU-NET improves the segmentation accuracy obviously compared with other segmentation models. Our technique will be able to help diagnose and treat cardiac complications.
Trends in hospitalizations and emergency department visits among women with hyperglycemia in pregnancy between 2008 and 2017 in Taiwan
Authors: Wang Jun-Sing , Chin Ming-Chu , Chen Jung-Fu , Huang Chien-Ning , Hwu Chii-Min , Ou Horng-Yih , Yang Yi-Sun , Hsu Chih-Cheng , Wang Chih-Yuan 
Published: November 2022

IntroductionWe investigated health service utilization, including hospitalizations and emergency department visits, for women with hyperglycemia in pregnancy between 2008 and 2017 in Taiwan.MethodsData from the Health and Welfare Data Science Center were used to conduct this nationwide population-based study. We identified pregnant women and the date of childbirth according to Birth Certificate Applications from 2007 to 2018. The study population was divided into four groups: known DM, newly diagnosed DM, GDM, and no DM/GDM. To assess quality of healthcare during the gestation period, trends in 30-day readmission rate, number of emergency department visits/hospitalizations per 100 childbirths, and length of hospital stay from 2008 to 2017 were examined.ResultsA total of 1830511 childbirths and 990569 hospitalizations were identified for analyses. Between 2008 and 2017, women with hyperglycemia in pregnancy (known DM, newly diagnosed DM, and GDM) had a higher rate of hospitalization, a longer length of hospital stay, and higher rates of various maternal and fetal outcomes, compared with women with no DM/GDM. Nevertheless, the differences between women with GDM and those with no DM/GDM in the aforementioned outcome measures were modest. Women with GDM had a modest decrease in the 30-day readmission rate (p for trend 0.046) with no significant difference in the number of emergency department visits during the study period.DiscussionOur findings provide evidence of the quality of healthcare for women with GDM between 2008 and 2017 in Taiwan.
A nomogram model based on clinical markers for predicting malignancy of ovarian tumors
Authors: Gao Bingsi , Zhao Xingping , Gu Pan , Sun Dan , Liu Xinyi , Li Waixing , Zhang Aiqian , Peng Enuo , Xu Dabao 
Published: November 2022

ObjectiveThe aim of this study was to build a nomogram based on clinical markers for predicting the malignancy of ovarian tumors (OTs).MethodA total of 1,268 patients diagnosed with OTs that were surgically removed between October 2017 and May 2019 were enrolled. Clinical markers such as post-menopausal status, body mass index (BMI), serum human epididymis protein 4 (HE4) value, cancer antigen 125 (CA125) value, Risk of Ovarian Malignancy Algorithm (ROMA) index, course of disease, patient-generated subjective global assessment (PG-SGA) score, ascites, and locations and features of masses were recorded and analyzed (p 0.05). Significant variables were further selected using multivariate logistic regression analysis and were included in the decision curve analysis (DCA) used to assess the value of the nomogram model for predicting OT malignancy.ResultThe significant variables included post-menopausal status, BMI, HE4 value, CA125 value, ROMA index, course of disease, PG-SGA score, ascites, and features and locations of masses (p 0.05). The ROMA index, BMI (≥ 26), unclear/blurred mass boundary (on magnetic resonance imaging [MRI]/computed tomography [CT]), mass detection (on MRI/CT), and mass size and features (on type B ultrasound [BUS]) were screened out for multivariate logistic regression analysis to assess the value of the nomogram model for predicting OT malignant risk (p 0.05). The DCA revealed that the net benefit of the nomogram’s calculation model was superior to that of the CA125 value, HE4 value, and ROMA index for predicting OT malignancy.ConclusionWe successfully tailored a nomogram model based on selected clinical markers which showed superior prognostic predictive accuracy compared with the use of the CA125, HE4, or ROMA index (that combines both HE and CA125 values) for predicting the malignancy of OT patients.
Identification of potential ferroptosis-related biomarkers and a pharmacological compound in diabetic retinopathy based on machine learning and molecular docking
Authors: Liu Jingying , Li Xiaozhuang , Cheng Yanhua , Liu Kangcheng , Zou Hua , You Zhipeng 
Published: November 2022

BackgroundDiabetic retinopathy (DR), a neurovascular disease, is a leading cause of visual loss worldwide and severely affects quality of life. Several studies have shown that ferroptosis plays an important role in the pathogenesis of DR; however, its molecule mechanism remains incompletely elucidated. Hence, this study aimed to investigate the pathogenesis of ferroptosis and explore potential ferroptosis-related gene biomarkers and a pharmacological compound for treating DR.MethodsFerroptosis-related differentially expressed genes (DEGs) were identified in the GSE102485 dataset. Functional enrichment analyses were then performed and a protein-protein interaction (PPI) network was constructed to screen candidates of ferroptosis-related hub genes (FRHGs). FRHGs were further screened based on least absolute shrinkage and selection operator (LASSO) regression and random forest algorithms, and were then validated with the GSE60436 dataset and previous studies. A receiver operating characteristic (ROC) curve monofactor analysis was conducted to evaluate the diagnostic performance of the FRHGs, and immune infiltration analysis was performed. Moreover, the pharmacological compound targeting the FRHGs were verified by molecular docking. Finally, the FRHGs were validated using quantitative real-time polymerase chain reaction (qRT-PCR) analysis.ResultsThe 40 ferroptosis-related DEGs were extracted, and functional enrichment analyses mainly implicated apoptotic signaling, response to oxidative stress, ferroptosis, and lipid and atherosclerosis pathways. By integrating the PPI, LASSO regression, and random forest analyses to screen the FRHGs, and through validation, we identified five FRHGs that performed well in the diagnosis (CAV1, CD44, NOX4, TLR4, and TP53). Immune infiltration analysis revealed that immune microenvironment changes in DR patients may be related to these five FRHGs. Molecular docking also showed that glutathione strongly bound the CAV1 and TLR4 proteins. Finally, the upregulated expression of FRHGs (CD44, NOX4, TLR4, and TP53) was validated by qRT-PCR analysis in human retinal capillary endothelial cells cultured under high-glucose environment.ConclusionsCAV1, CD44, NOX4, TLR4, and TP53 are potential biomarkers for DR and may be involved in its occurrence and progression by regulating ferroptosis and the immune microenvironment. Further, glutathione exhibits potential therapeutic efficacy on DR by targeting ferroptosis. Our study provides new insights into the ferroptosis-related pathogenesis of DR, as well as its diagnosis and treatment.
Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma
Authors: Yuan Xianggui , Li Xian , Huang Yurong , Jin Xueli , Liu Hui , Zhao Aiqi , Zhang Weiping , Qian Wenbin , Liang Yun 
Published: November 2022

IntroductionRelapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) has poor clinical outcomes when treated with conventional salvage chemotherapy. Monotherapy using zanubrutinib, a selective Bruton’s tyrosine kinase (BTK) inhibitor, has achieved modest antitumor effect in R/R DLBCL. Here we aimed to evaluate the efficacy and safety of zanubrutinib plus salvage chemotherapy in R/R DLBCL patients.MethodsWe retrospectively reviewed R/R DLBCL patients who were administered with zanubrutinib plus salvage chemotherapy in our center between January, 2019 and December, 2021. Targeted panel sequencing of 11 lymphoma-related genes was performed on 8 patients with poor responses to zanubrutinib-based chemotherapy.Results27 R/R DLBCL patients were enrolled. Median age at this study was 59 years (range, 15-72). The best overall response rate (ORR) was 74.1% and complete remission rate was 33.3%. With a median follow-up of 11 months (range, 1-17), the median progression-free survival (PFS) was 8.1 months, and the overall survival (OS) was not achieved. The most common grade-3/4 adverse events were neutropenia (70.4%), thrombocytopenia (66.7%), and febrile neutropenia (33.3%). In multivariate analysis, early treatment and overall response after chemotherapy were independent favorable prognostic factors for PFS. Overall response after chemotherapy was an independent favorable factor for OS. Among the 8 patients with poor response to zanubrutinib-based treatment, the majority of patients had NOTCH2 mutations (n=8, 100%) and TP53 mutations (n=7, 87.5%). However, these patients achieved an ORR of 75% at 3 months after CD19-CAR-T cell therapy (including 4 cases of complete remission and 2 cases of partial remission). With a median follow-up of 9 months from CAR-T cell infusion (range, 1-16 months), the median PFS was 14.5 months, and the median OS was not reached. ConclusionWith high efficacy and manageable tolerability, zanubrutinib plus salvage chemotherapy may be a potential treatment option for R/R DLBCL. CAR-T cell therapy may be a priority strategy for these poor responders to BTKi-based treatment.
Pro-resolving and anti-arthritic properties of the MC1 selective agonist PL8177
Authors: Garrido-Mesa Jose , Thomas Bethan Lynne , Dodd John , Spana Carl , Perretti Mauro , Montero-Melendez Trinidad 
Published: November 2022

BackgroundMelanocortins are peptides endowed with anti-inflammatory and pro-resolving activities. Many of these effects are mediated by the Melanocortin receptor 1 (MC1) as reported in several experimental settings. As such, MC1 can be a viable target for the development of new therapies that mimic endogenous pro-resolving mediators. The aim of this study was to assess the immunopharmacology of a selective MC1 agonist (PL8177) in vitro and in a mouse model of inflammatory arthritis.MethodsPL8177 and the natural agonist αMSH were tested for activation of mouse and human Melanocortin receptors (MC1,3,4,5), monitoring cAMP accumulation and ERK1/2 phosphorylation, using transiently transfected HEK293A cells. The anti-inflammatory and pro-resolving effects of PL8177 and αMSH were evaluated using mouse peritoneal Macrophages. Finally, a model of K/BxN serum transfer induced arthritis was used to determine the in vivo potential of PL8177.ResultsPL8177 activates mouse and human MC1 with apparent EC50 values of 0.01 and 1.49 nM, respectively, using the cAMP accumulation assay. Similar profiles were observed for the induction of ERK phosphorylation (EC50: 0.05 and 1.39 nM). PL8177 displays pro-resolving activity (enhanced Macrophage efferocytosis) and counteracts the inflammatory profile of zymosan-stimulated macrophages, reducing the release of IL-1β, IL-6, TNF-α and CCL-2. In the context of joint inflammation, PL8177 (3mg/kg i.p.) reduces clinical score, paw swelling and incidence of severe disease as well as the recruitment of immune cells into the arthritic joint.ConclusionThese results demonstrate that the MC1 agonism with PL8177 affords therapeutic effects in inflammatory conditions including arthritis.SignificanceDrugs targeting the Melanocortin system have emerged as promising therapeutics for several conditions including inflammation or obesity. Multiple candidates are under clinical development, and some have already reached approval. Here we present the characterization of a novel drug candidate, PL8177, selective for the Melanocortin 1 receptor (MC1), demonstrating its selectivity profile on cAMP and ERK1/2 phosphorylation signaling pathways, of relevance as selective drugs will translate into lesser off-target effect. PL8177 also demonstrated, not only anti-inflammatory activity, but pro-resolving actions due to its ability to enhance efferocytosis (i.e. the phagocytosis of apoptotic cells), endowing this molecule with therapeutic advantages compared to classical anti-inflammatory drugs. Using a mouse model of inflammatory arthritis, the compound demonstrated in vivo efficacy by reducing clinical score, paw swelling and overall disease severity. Taken together, these results present Melanocortin-based therapies, and specifically targeting MC1 receptor, as a promising strategy to manage chronic inflammatory diseases.
Carbon fiber-reinforced epoxy with 100% fiber recycling by transesterification reactions
Authors: Wu Jianqiao , Pan Ying , Ruan Ziyi , Zhao Ziji , Ai Jing , Ban Jinghai , Jing Xianghai 
Published: November 2022

Carbon fiber (CF)-reinforced epoxy is the most commonly used advanced composite with high performance. However, these composites usually face intractable disposal problems in their lifecycles, due to the stable cross-linked network structures of epoxy. To address this dilemma, this work proposes a facile yet efficient strategy for recycling carbon fibers from traditional carbon fiber-reinforced epoxy composites using epoxy–anhydride systems as a matrix. Diglycidyl ester of aliphatic cyclo (DGEAC) and methylhexahydrophthalic anhydride (MHHPA) were used as matrix, while T300 woven carbon fiber was used as reinforcement, to construct the composites CF/DGEAC/MHHPA. The epoxy matrix exhibited a high glass transition temperature (Tg = 126°C), high decomposition temperature (Td5 = 300°C), and good solvent resistance. By using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as a catalyst, the DGEAC/MHHPA networks could be degraded completely in ethylene glycol (EG) at 180°C within 6 h because of transesterification reactions between EG and the networks. Taking advantage of this result, a fiber recycling process was developed for carbon fiber composites, where the cross-linked networks of epoxy could be degraded with 100% carbon fiber recycling. Furthermore, the recycled carbon fiber maintained nearly 100% similarity in surface microscopic morphology and chemical structure compared with virgin carbon fiber. This work proposes a simple and efficient strategy for recycling carbon fiber from traditional high-performance composites, offering a convenient concept for the cyclic utilization of advanced composites.
Beneficial effects of bempedoic acid treatment in polycystic kidney disease cells and mice
Authors: Hallows Kenneth R. , Li Hui , Saitta Biagio , Sepehr Saman , Huang Polly , Pham Jessica , Wang Jonathan , Mancino Valeria , Chung Eun Ji , Pinkosky Stephen L. , Pastor-Soler Núria M. 
Published: November 2022

ADPKD has few therapeutic options. Tolvaptan slows disease but has side effects limiting its tolerability. Bempedoic acid (BA), an ATP citrate-lyase (ACLY) inhibitor FDA-approved for hypercholesterolemia, catalyzes a key step in fatty acid/sterol synthesis important for cell proliferation. BA is activated by very long-chain acyl-CoA synthetase (FATP2) expressed primarily in kidney and liver. BA also activates AMPK. We hypothesized that BA could be a novel ADPKD therapy by inhibiting cyst growth, proliferation, injury, and metabolic dysregulation via ACLY inhibition and AMPK activation. Pkd1-null kidney cell lines derived from mouse proximal tubule (PT) and collecting duct (IMCD) were grown in 2D or 3D Matrigel cultures and treated ± BA, ± SB-204990 (another ACLY inhibitor) or with Acly shRNA before cyst analysis, immunoblotting or mitochondrial assays using MitoSox and MitoTracker staining. Pkd1fl/fl; Pax8-rtTA; Tet-O-Cre C57BL/6J mice were induced with doxycycline injection on postnatal days 10 and 11 (P10-P11) and then treated ± BA (30 mg/kg/d) ± tolvaptan (30–100 mg/kg/d) by gavage from P12-21. Disease severity was determined by % total-kidney-weight-to-bodyweight (%TKW/BW) and BUN levels at euthanasia (P22). Kidney and liver homogenates were immunoblotted for expression of key biomarkers. ACLY expression and activity were upregulated in Pkd1-null PT and IMCD-derived cells vs. controls. Relative to controls, both BA and SB-204990 inhibited cystic growth in Pkd1-null kidney cells, as did Acly knockdown. BA inhibited mitochondrial superoxide production and promoted mitochondrial elongation, suggesting improved mitochondrial function. In ADPKD mice, BA reduced %TKW/BW and BUN to a similar extent as tolvaptan vs. untreated controls. Addition of BA to tolvaptan caused a further reduction in %TKW/BW and BUN vs. tolvaptan alone. BA generally reduced ACLY and stimulated AMPK activity in kidneys and livers vs. controls. BA also inhibited mTOR and ERK signaling and reduced kidney injury markers. In liver, BA treatment, both alone and together with tolvaptan, increased mitochondrial biogenesis while inhibiting apoptosis. We conclude that BA and ACLY inhibition inhibited cyst growth in vitro, and BA decreased ADPKD severity in vivo. Combining BA with tolvaptan further improved various ADPKD disease parameters. Repurposing BA may be a promising new ADPKD therapy, having beneficial effects alone and along with tolvaptan.