bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutamine deficiency promotes recurrence and metastasis in colorectal cancer through enhancing epithelial–mesenchymal transition
Authors: Sun Hongyan , Zhang Chuan , Zheng Yang , Liu Chenlu , Wang Xue , Cong Xianling 
Published: July 2022

Abstract
Background
Glutamine is the most abundant amino acid in the body and plays a vital role in colorectal cancer (CRC) cell metabolism. However, limited studies have investigated the clinical and prognostic significance of preoperative serum glutamine levels in patients with colorectal cancer, and the underlying mechanism has not been explored.

Methods
A total of 121 newly diagnosed CRC patients between 2012 and 2016 were enrolled in this study. Serum glutamine levels were detected, and their associations with clinicopathological characteristics, systemic inflammation markers, carcinoembryonic antigen (CEA) and prognosis were analysed. In addition, the effect of glutamine depletion on recurrence and metastasis was examined in SW480 and DLD1 human CRC cell lines, and epithelial–mesenchymal transition (EMT)-related markers were detected to reveal the possible mechanism.

Results
A decreased preoperative serum level of glutamine was associated with a higher T-class and lymph node metastasis (P < 0.05). A higher serum level of glutamine correlated with a lower CEA level (r = − 0.25, P = 0.02). Low glutamine levels were correlated with shorter overall survival (OS) and disease-free survival (DFS). Multivariate Cox regression analysis showed that serum glutamine was an independent prognostic factor for DFS (P = 0.018), and a nomogram predicting the probability of 1-, 3- and 5-year DFS after radical surgery was built. In addition, glutamine deficiency promoted the migration and invasion of CRC cells. E-cadherin, a vital marker of EMT, was decreased, and EMT transcription factors, including zeb1and zeb2, were upregulated in this process.

Conclusions
This study elucidated that preoperative serum glutamine is an independent prognostic biomarker to predict CRC progression and suggested that glutamine deprivation might promote migration and invasion in CRC cells by inducing the EMT process.
The recombinant Erns and truncated E2-based indirect enzyme-linked immunosorbent assays to distinguishably test specific antibodies against classical swine fever virus and bovine viral diarrhea virus
Authors: Yi Weicheng , Zhu Hongchang , Wu Yihan , Li Qingmei , Lou Wange , Zhao Haizhong , Pan Zishu 
Published: July 2022

Abstract
Background
Classical swine fever (CSF) virus is the causative agent of an economically important, highly contagious disease of pigs. CSFV is genetically and serologically related to bovine viral diarrhea virus (BVDV). BVDV infection in pigs can mimic CSF clinical signs, which cause difficulty in differentiation. Serological test for detection of virus specific antibodies is a valuable tool for diagnosis and surveillance of CSFV and BVDV infections in animals. The aim of this study was to develop the CSFV Erns and BVDV tE2 -based ELISAs to distinguishably test specific antibodies against CSFV and BVDV.

Methods
The CSFV Erns and truncated E2 (tE2, residues 690–865) of BVDV were expressed in E. coli and purified by Ni–NTA affinity chromatography, respectively. Employing Erns or tE2 protein as diagnostic antigen, indirect ELISAs were developed to distinguishably test specific antibodies against CSFV and BVDV. The specificity and sensitivity of ELISAs were evaluated using a panel of virus specific sera of pigs, immunized rabbits and immunized mice. A total 150 clinical serum samples from farm pigs were measured by the developed ELISAs and compared with virus neutralizing test (VNT).

Results
Indirect ELISA was established based on recombinant CSFV Erns or BVDV tE2 protein, respectively. No serological cross-reaction between antibodies against CSFV and BVDV was observed in sera of immunized rabbits, immunized mice or farm pigs by detections of the Erns and tE2 -based ELISAs. Compared to VNT, the CSFV Erns -based ELISA displayed a high sensitivity (93.3%), specificity (92.0%) and agreement rate (92.7%), and the sensitivity, specificity and agreement rate of BVDV tE2 -based ELISA was 92.3%, 95.2% and 94.7%, respectively.

Conclusion
The newly developed ELISAs are highly specific and sensitive and would be valuable tools for serological diagnosis for CSFV and BVDV infections.
Single session therapy in pediatric healthcare: the value of adopting a strengths-based approach for families living with neurological disorders
Authors: Mulligan Janice , Olivieri Heather , Young Katarina , Lin Jia , Anthony Samantha J. 
Published: July 2022

Abstract
Background
Pediatric patients with neurological disorders often require lifelong management of symptoms and behaviours that can result in enduring emotional burden, stress and impacted health-related quality of life. Single session therapy (SST) draws upon patients’ existing skills and knowledge and has emerged as a therapeutic approach to address pediatric patient and family needs in a timely manner. This study aimed to assess the clinical effectiveness of SST for pediatric patients with neurological disorders and their families, considering self-efficacy, distress, anxiety, therapeutic alliance and client satisfaction, as well as perceptions of whether SST met their pressing needs.

Methods
A convergent parallel mixed-methods design included quantitative data collection via five standardized questionnaires across three time points and qualitative data collection through semi-structured interviews. Quantitative and qualitative data were analyzed independently and then integrated.

Results
The study comprised of 135 participants, including patients, parents and siblings across diverse neurological conditions. Scores of self-efficacy and anxiety in children, and distress and anxiety in adults, improved significantly after the SST. Notably, changes in anxiety in adults remained significant five to seven weeks after the SST. Seventeen participants participated in 12 semi-structured interviews. Participants described that SST (1) was a missing piece in ongoing clinical care, (2) illuminated existing strengths and resilience, and (3) effected a lasting impact beyond the single session.

Conclusions
SST may be a promising initial, strengths-based treatment to support the short-term and potentially long-term needs of pediatric patients with neurological disorders and their families by emphasizing existing strengths, supporting therapeutic alliance and cultivating hope.
Sporadic medullary thyroid cancer: a systematic review and meta-analysis of clinico-pathological and mutational characteristics predicting recurrence
Authors: Cosway Benjamin , Fussey Jonathan , Kim Dae , Wykes James , Elliott Michael , Smith Joel 
Published: July 2022

Abstract
Introduction
Sporadic medullary thyroid cancer accounts for 75% of all medullary thyroid cancers and presents at a more advanced disease stage than its hereditary counterparts. Yet there is little evidence to support risk stratification of patients according to risk of recurrence.

Methods
A systematic review and meta-analysis was performed investigating clinical and pathological factors that are associated with recurrent disease in patients with medullary thyroid cancer.

Results
10 studies totalling 458 patients were included in the meta-analyses. T3 and T4 disease (OR 9.33 (95% CI 2.5 – 34.82) p = 0.0009.), AJCC stage III and IV disease (OR 13.34 (95% CI 2.9 – 60.3) p = 0.0008) and the presence of nodal disease (OR 7.28 (95% CI 7.2–43.3) p = 0.03) were all associated with recurrent disease. RET mutations (OR 0.08 (95% CI -0.03–0.19) p = 0.17) and RET 918 T mutations (OR 1.77 (95% CI 0.804.0) P = 0.17) were not associated with disease recurrence. It was not possible to pool data with respect to extrathyroidal extension, extracapsular extension, peri-neural and lymphovascular invasion and RAS mutations.

Conclusion
T3 and T4 disease, AJCC stage III and IV disease and the presence of nodal disease are associated with recurrent disease. The heterogeneous reporting of recurrence and the lack of individual patient data precludes larger scale meta-analyses. Future research in this area should involve collaboration to establish standardised definitions of disease recurrence.
PM2.5 promotes NSCLC carcinogenesis through translationally and transcriptionally activating DLAT-mediated glycolysis reprograming
Authors: Chen Qianqian , Wang Yiling , Yang Lin , Sun Liyuan , Wen Yuxin , Huang Yongyi , Gao Kaiping , Yang Wenhan , Bai Feng , Ling Lijuan , Zhou Zizi , Zhang Xiaoming , Xiong Juan , Zhai Rihong 
Published: July 2022

Abstract
Background
Airborne fine particulate matter (PM2.5) has been associated with lung cancer development and progression in never smokers. However, the molecular mechanisms underlying PM2.5-induced lung cancer remain largely unknown. The aim of this study was to explore the mechanisms by which PM2.5 regulated the carcinogenesis of non-small cell lung cancer (NSCLC).

Methods
Paralleled ribosome sequencing (Ribo-seq) and RNA sequencing (RNA-seq) were performed to identify PM2.5-associated genes for further study. Quantitative real time-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC) were used to determine mRNA and protein expression levels in tissues and cells. The biological roles of PM2.5 and PM2.5-dysregulated gene were assessed by gain- and loss-of-function experiments, biochemical analyses, and Seahorse XF glycolysis stress assays. Human tissue microarray analysis and 18F-FDG PET/CT scans in patients with NSCLC were used to verify the experimental findings. Polysome fractionation experiments, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assay were implemented to explore the molecular mechanisms.

Results
We found that PM2.5 induced a translation shift towards glycolysis pathway genes and increased glycolysis metabolism, as evidenced by increased L-lactate and pyruvate concentrations or higher extracellular acidification rate (ECAR) in vitro and in vivo. Particularly, PM2.5 enhanced the expression of glycolytic gene DLAT, which promoted glycolysis but suppressed acetyl-CoA production and enhanced the malignancy of NSCLC cells. Clinically, high expression of DLAT was positively associated with tumor size, poorer prognosis, and SUVmax values of 18F-FDG-PET/CT scans in patients with NSCLC. Mechanistically, PM2.5 activated eIF4E, consequently up-regulating the expression level of DLAT in polysomes. PM2.5 also stimulated transcription factor Sp1, which further augmented transcription activity of DLAT promoter.

Conclusions
This study demonstrated that PM2.5-activated overexpression of DLAT and enhancement in glycolysis metabolism contributed to the tumorigenesis of NSCLC, suggesting that DLAT-associated pathway may be a therapeutic target for NSCLC.
ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42
Authors: Zhang Xin , Ren Liangliang , Wu Junhua , Feng Rongni , Chen Yunyang , Li Ronggang , Wu Meimei , Zheng Mingzhu , Wu Xing Gui , Luo Wanjun , He Hongle , Huang Yanming , Tang Miaoling , Li Jun 
Published: July 2022

Abstract
Background
The extravasation capability of hepatocellular carcinoma (HCC) cells plays a vital role in distant metastasis. However, the underlying mechanism of extravasation in HCC lung metastasis remains largely unclear.

Methods
The expression of ARHGEF37 in human HCC specimens and HCC cell lines was examined by quantitative RT-PCR, western blot, and immunohistochemistry (IHC) analyses. The biological roles and mechanisms of ARHGEF37/Cdc42 in promoting lung metastasis were investigated in vitro and in vivo using cell lines, patient samples, xenograft models.

Results
In the current study, we found that Rho guanine nucleotide exchange factor 37 (ARHGEF37) was upregulated in human HCC samples and was associated with tumor invasiveness, pulmonary metastasis and poor prognosis. Overexpressing ARHGEF37 significantly enhanced the extravasation and metastatic capability of HCC cells via facilitating tumor cell adhesion to endothelial cells and trans-endothelial migration. Mechanistically, ARHGEF37 directly interacted with and activated Cdc42 to promote the invadopodia formation in HCC cells, which consequently disrupted the interaction between endothelial cells and pericytes. Importantly, treatment with ZCL278, a specific inhibitor of Cdc42, dramatically inhibited the attachment of ARHGEF37-overexpressing HCC cells to endothelial cells, and the adherence and extravasation in the lung alveoli, resulting in suppression of lung metastasis in mice.

Conclusion
Our findings provide a new insight into the underlying mechanisms on the ARHGEF37 overexpression-mediated extravasation and pulmonary metastasis of HCC cells, and provided a potential therapeutic target for the prevention and treatment of HCC pulmonary metastasis.
Senescence in osteoarthritis: from mechanism to potential treatment
Authors: Liu Yikai , Zhang Zian , Li Tao , Xu Hao , Zhang Haining 
Published: July 2022

AbstractOsteoarthritis (OA) is an age-related cartilage degenerative disease, and chondrocyte senescence has been extensively studied in recent years. Increased numbers of senescent chondrocytes are found in OA cartilage. Selective clearance of senescent chondrocytes in a post-traumatic osteoarthritis (PTOA) mouse model ameliorated OA development, while intraarticular injection of senescent cells induced mouse OA. However, the means and extent to which senescence affects OA remain unclear. Here, we review the latent mechanism of senescence in OA and propose potential therapeutic methods to target OA-related senescence, with an emphasis on immunotherapies. Natural killer (NK) cells participate in the elimination of senescent cells in multiple organs. A relatively comprehensive discussion is presented in that section. Risk factors for OA are ageing, obesity, metabolic disorders and mechanical overload. Determining the relationship between known risk factors and senescence will help elucidate OA pathogenesis and identify optimal treatments.
Neutrophil extracellular traps promote thrombogenicity in cerebral venous sinus thrombosis
Authors: Jin Jiaqi , Qiao Shan , Liu Jie , Li Wenqiang , Wang Fang , Gao Xin , Tian Jiawei , Wang Nan , Zhang Jiheng , Dong Jiawei , li Haiyun , Wang Jianjun , Hu Shaoshan , Zhou Peng 
Published: July 2022

Abstract
Background
Neutrophil extracellular traps (NETs) contribute to the creation of a coagulation state in various diseases. Currently, it is not clear whether NETs are present in the thrombi and plasma of patients with cerebral venous sinus thrombosis (CVST). This study aimed to investigate the presence of NETs in thrombi and blood samples from CVST patients and the procoagulant activity (PCA) of NETs during the progression of CVST.

Results
Thrombi obtained from CVST patients undergoing thrombectomy were examined by immunochemistry using neutrophil elastase (NE), CD66b and citrullinated histone H3(citH3). The presence of NET markers in samples from 37 CVST patients and 32 healthy people was evaluated by ELISA. NET-producing neutrophils and neutrophil-platelet (PLT) aggregates were examined in samples obtained from CVST patients and healthy people by flow cytometry. The TAT complex in plasma sample from each group was detected by ELISA to evaluate the procoagulant activity of NETs in CVST patients. Neutrophils from healthy subjects were treated with PLT-rich plasma in the presence of anti-PF4 antibodies or an autophagy inhibitor and analyzed by flow cytometry and confocal microscopy. After treatment with NETs, the expression of von Willebrand factor (VWF), tissue factor (TF) and CD31 in human brain microvascular endothelial cells (HBMECs) was measured by confocal microscopy and western blotting. Our results showed that NETs were abundant in the plasma and thrombi from CVST patients. Platelet factor 4 (PF4) from CVST PLTs induced NET generation through autophagy. NETs could induce PCA by modulating TF and phosphatidylserine (PS) in CVST. NETs also disrupted the endothelial barrier and transformed ECs into a procoagulant phenotype to exacerbate thrombogenicity.

Conclusions
NET generation was mediated by PF4 from PLTs through autophagy and contribute to thrombosis in CVST patients.
RH simulation model for canvas paintings protected by an aluminium backplate and an additional hygroscopic layer
Authors: Ferrer Santi , Campo-Francés Gema , Grau-Bové Josep , Bautista-Morenilla Iris , Nualart-Torroja Anna 
Published: July 2022

Abstract
To protect a canvas easel painting, a common conservation strategy is to add a back plate at the stretcher, creating a closed air void. This plate protects not only from dust but mainly from temperature and relative humidity (RH) variations in the room and moisture changes in the wall on which it is hanging. The addition of hygroscopic layers can reduce the amplitude and change phase of humidity oscillations. This paper proposes a new mathematical model that can be used to predict moisture levels within the canvas when this conservation strategy is applied. The model is compared against the temperature and RH detailed experimental data, captured and shown in the latest paper by Padfield et al. Back protection of canvas painting. Our paper presents values of T, RH and mixing ratio (MR) obtained at the different layers of an easel painting, protected and unprotected, with cotton and without it, submitted to different room and wall temperature and RH cycles. The experimental results show a phase displacement between the canvas temperatures and the corresponding RH values in the canvas air boundary layer. In some cases this phase shift, which is an unexpected behaviour, allows RH and temperatures to achieve their maximum value at the same time. The purpose of the model is to simulate the RH response at the different air boundary layers inside the air void, such as the canvas, the aluminium back plate, and the hygroscopic cotton protection, produced by cyclic variations of temperature in the room or the wall. The model is built simulating four interrelated processes: the canvas permeation flow, the air infiltration rate between room and void, the equilibrium moisture content (EMC) and the vapour sorption rate for the canvas and the cotton. A key innovation of the model is the dependence between EMC, sorption rate, and RH condition, which captures the counter-intuitive behaviours observed in the data. The model results agree with the experimental results. The developed tool allows the interpretation of the processes involved and to extend the simulations to other cases, materials, and conditions.
Efficient management of the nitritation-anammox microbiome through intermittent aeration: absence of the NOB guild and expansion and diversity of the NOx reducing guild suggests a highly reticulated nitrogen cycle
Authors: Palomo Alejandro , Azevedo Daniela , Touceda-Suárez María , Domingo-Félez Carlos , Mutlu A. Gizem , Dechesne Arnaud , Wang Yulin , Zhang Tong , Smets Barth F. 
Published: July 2022

AbstractObtaining efficient autotrophic ammonia removal (akapartial nitritation-anammox, or PNA) requires a balanced microbiome with abundant aerobic and anaerobic ammonia oxidizing bacteria and scarce nitrite oxidizing bacteria. Here, we analyzed the microbiome of an efficient PNA process that was obtained by sequential feeding and periodic aeration. The genomes of the dominant community members were inferred from metagenomes obtained over a 6 month period. ThreeBrocadiaspp. genomes and threeNitrosomonasspp. genomes dominated the autotrophic community; no NOB genomes were retrieved. Two of theBrocadiaspp. genomes lacked the genomic potential for nitrite reduction. A diverse set of heterotrophic genomes was retrieved, each with genomic potential for only a fraction of the denitrification pathway. A mutual dependency in amino acid and vitamin synthesis was noted between autotrophic and heterotrophic community members. Our analysis suggests a highly-reticulated nitrogen cycle in the examined PNA microbiome with nitric oxide exchange between the heterotrophs and the anammox guild.
Proteomic, mechanical, and biochemical development of tissue-engineered neocartilage
Authors: Bielajew Benjamin J. , Donahue Ryan P. , Lamkin Elliott K. , Hu Jerry C. , Hascall Vincent C. , Athanasiou Kyriacos A. 
Published: July 2022

Abstract

Background
The self-assembling process of cartilage tissue engineering is a promising technique to heal cartilage defects, preventing osteoarthritic changes. Given that chondrocytes dedifferentiate when expanded, it is not known if cellular expansion affects the development of self-assembled neocartilage. The objective of this study was to use proteomic, mechanical, and biochemical analyses to quantitatively investigate the development of self-assembled neocartilage derived from passaged, rejuvenated costal chondrocytes.

Methods
Yucatan minipig costal chondrocytes were used to create self-assembled neocartilage constructs. After 1, 4, 7, 14, 28, 56, or 84 days of self-assembly, constructs were analyzed through a variety of histological, biomechanical, biochemical, and proteomic techniques.

Results
It was found that temporal trends in neocartilage formation are similar to those seen in native hyaline articular cartilage development. For example, between days 7 and 84 of culture, tensile Young’s modulus increased 4.4-times, total collagen increased 2.7-times, DNA content decreased 69.3%, collagen type II increased 1.5-times, and aggrecan dropped 55.3%, mirroring trends shown in native knee cartilage. Importantly, collagen type X, which is associated with cartilage calcification, remained at low levels (≤ 0.05%) at all neocartilage developmental time points, similar to knee cartilage (< 0.01%) and unlike donor rib cartilage (0.98%).

Conclusions
In this work, bottom-up proteomics, a powerful tool to interrogate tissue composition, was used for the first time to quantify and compare the proteome of a developing engineered tissue to a recipient tissue. Furthermore, it was shown that self-assembled, costal chondrocyte-derived neocartilage is suitable for a non-homologous approach in the knee.
Toward a more comprehensive modeling of sequential lineups
Authors: Kellen David , McAdoo Ryan M. 
Published: July 2022

AbstractSequential lineups are one of the most commonly used procedures in police departments across the USA. Although this procedure has been the target of much experimental research, there has been comparatively little work formally modeling it, especially the sequential nature of the judgments that it elicits. There are also important gaps in our understanding of how informative different types of judgments can be (binary responses vs. confidence ratings), and the severity of the inferential risks incurred when relying on different aggregate data structures. Couched in a signal detection theory (SDT) framework, the present work directly addresses these issues through a reanalysis of previously published data alongside model simulations. Model comparison results show that SDT modeling can provide elegant characterizations of extant data, despite some discrepancies across studies, which we attempt to address. Additional analyses compare the merits of sequential lineups (with and without a stopping rule) relative to showups and delineate the conditions in which distinct modeling approaches can be informative. Finally, we identify critical issues with the removal of the stopping rule from sequential lineups as an approach to capture within-subject differences and sidestep the risk of aggregation biases.