bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Complete Inventory of Long-Chain Polyunsaturated Fatty Acids Biosynthesis Pathway Enzymes in the Miniaturized Cyprinid Paedocypris Micromegethes
Authors: Sam Ka-Kei , Lau Nyok-Sean , Kuah Meng-Kiat , Lading Engkamat anak , Shu-Chien Alexander Chong 
Published: January 2022

Abstract
The capacity for long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis activity in a species depends on the enzymatic activities of fatty acyl desaturase (Fads) and elongation of very long-chain fatty acid (Elovl). The miniaturized fish Paedocypris micromegethes is a developmentally truncated cyprinid living in highly acidic water conditions in tropical peat swamps. The capacity for LC-PUFA biosynthesis in this species, which has a reduced genome size, is unknown. A high-quality de novo transcriptome assembly enabled the identification of a putative Fads2 and four Elovl. The Fads2 was verified as a P. micromegethes Fads2 ortholog with in vitro Δ5 and Δ6 activities. The Elovl sequences were established as an Elovl5, Elovl2, and two Elovl4 paralogs, namely Elovl4a and Elovl4b. These Elovl enzymes, mainly Elovl5 and Elovl2, fulfill the necessary C18, C20, and C22 PUFA elongation steps for LC-PUFA biosynthesis. Collectively, these results validate the presence of a complete repertoire of LC-PUFA biosynthesis enzymes in a tropical miniatured freshwater fish.
Short Term Clinical Outcomes of Intracranial Pressure Monitor Placement in Severe Traumatic Brain Injury
Authors: Foote Christopher Wayne , Doan Xuan-Lan , Guice Jordan , Cruz Bianca , Vanier Cheryl , Betancourt Alejandro , Palacio Carlos H. 
Published: January 2022

Abstract
Background : Intracranial pressure (ICP) monitoring has been recommended as a guiding tool for ICP treatment; however, data suggests invasive ICP monitoring had no better outcomes than those patients without it. We hypothesized that there is no difference in short term outcomes in patients with severe traumatic brain injury (TBI) who received invasive ICP monitoring compared to those who did not.

Methods : The trauma registry of a community Level II trauma center was queried from January 2015 to June 2020. Patients with severe TBI identified as Glasgow Coma Scale (GCS) ≤8 upon admission with an abnormal computed tomography (CT) scan, and those meeting Brain Injury Guideline (BIG) 3 (severe) were included. The data was analyzed in a logistic regression model to predict mortality, and a linear model to predict (log-transformed) hospital and ICU length of stay (LOS). Analyses were done in Rv4.0.2software.

Results : A total of 7,787 trauma patients were admitted during the study period, 592 were found to have GCS≤8 and of those, 118 met inclusion criteria. Forty-seven percent (n=55) received invasive ICP monitoring and 53 percent (n=63) did not. The majority (n=78, 66%) of patients were male. Median age was 35 for the ICP monitored group and 54 for the group with no ICP monitoring. The median GCS was 3 (IQR= 3,6) and the median ISS was 25 (IQR=17,26 or 27) for both groups. The ICU LOS was 5.3 days and hospital LOS 6.2 days longer for patients with ICP monitor compared to those without ICP monitor (p=0.001). The mortality rate of patients who received an ICP monitor was 19 in 55 (35%) compared to 27 of 63 (42%) for those who did not (p=0.84).

Conclusions : Patients with severe traumatic brain injury who received invasive ICP monitors had an increased ICU and hospital length of stay and no mortality difference when compared to those who did not. The use of an ICP monitor did not improve outcomes in this population of severe TBI patients, particularly for those who did not require neurosurgery.

Level of Evidence: Level IV
Glycoproteomics revealed novel N-glycosylation biomarkers for early diagnosis of lung adenocarcinoma cancers
Authors: Fang Kai , Long Qin , Liao Zhonghua , Zhang Chaoyu , Jiang Zhiqiang 
Published: January 2022

Abstract
Circulating biomarkers play important roles in diagnosis of malignant tumors. N-glycosylation is an important post-translation patter and obviously affect biological behaviors of malignant tumor cells. However, the role of N-glycosylation sites in early diagnosis of tumors still remains further investigation. In this study, plasma from 20 lung adenocarcinoma (LUAD), which were all classified as stage I, as well as 20 normal controls (NL) were labeled and screened by mass spectrometry (MS). Total 39 differential N-glycosylation sites were detected in LUAD, 17 were up-regulated and 22 were down-regulated. In all differential sites, ITGB3-680 showed highest potential in LUAD which showed 99.2% AUC, 95.0% SP and 95.0% SN. Besides, APOB-1523 (AUC: 89.0%, SP: 95.0%, SN: 70.0%), APOB-2982 (AUC: 86.8%, SP: 95.0%, SN: 45.0%) and LPAL2-101 (AUC: 81.1%, SP: 95.0%, SN: 47.4%) also acted as candidate biomarkers in LUAD. Combination analysis was then performed by random forest model, all samples were divided into training group (16 cases) and testing group (4 cases) and conducted by feature selection, machine learning, integrated model of classifier and model evaluation. And the results indicated that combination of differential sites could reach 100% AUC in both training and testing group. Taken together, our study revealed multiple N-glycosylation sites which could be applied as candidate biomarkers for early diagnosis diagnosis of LUAD.
Comprehensive bioinformatic analysis reveals a cancer-associated fibroblast gene signature as a poor prognostic factor and potential therapeutic target in gastric cancer
Authors: Ucaryilmaz-Metin Cemre , Ozcan Gulnihal 
Published: January 2022

Abstract
Background: Gastric cancer is one of the deadliest cancers in the world. The lack of prognostic markers and efficient molecular targets limits the success of current therapies. Therefore, we aimed to identify new prognostic markers and therapeutic targets in gastric cancer.
Methods: We analyzed four GEO gene expression datasets with a network-based approach. We used The Cancer Genome Atlas (TCGA) stomach adenocarcinoma data as the validation set. Since all the hub genes indicated the cancer-associated fibroblast infiltration in gastric tumors, we performed a stepwise multivariate Cox regression analysis to identify a poor prognostic gene signature for cancer-associated fibroblast infiltration. Lastly, we searched the drug databases for drugs that target the signature genes.
Results: Our network-based approach revealed the extracellular matrix components COL1A1, COL1A2, COL3A1, COL5A1, FN1, and SPARC as the central genes in gastric cancer. These genes were overexpressed and displayed poor prognostic significance in TCGA stomach adenocarcinoma samples. We demonstrated the substantial correlation between these genes and the cancer-associated fibroblast infiltration in gastric cancer. The stepwise multivariate Cox regression elucidated COL1A1 and COL5A1, together with ITGA4, Emilin1, and TSPAN9 as poor prognostic signature genes for the cancer-associated fibroblast infiltration. The search on drug databases revealed: collagenase clostridium histolyticum, ocriplasmin, and halofuginone which target collagen subunits; and natalizumab, firategrast, and BIO-1211 which target ITGA4 as the potential drugs for further investigation.
Conclusions: Our study demonstrated the central role of extracellular matrix components secreted and remodeled by the cancer-associated fibroblasts in gastric cancer. The cancer-associated fibroblast gene signature we identified in this study carries a high potential as a predictive tool for poor prognosis in gastric cancer patients. Elucidating the mechanisms by which the signature genes contribute to poor patient outcomes can lead to the discovery of more potent molecular-targeted agents and; increase the therapeutic success in gastric cancer.
Uplink Cell-Free Massive MIMO-NOMA Systems Based on Group-Level Successive Interference Cancellation
Authors: Cui Tao , Liu Chengcheng , Du Peng , Song Rongfang 
Published: January 2022

Abstract
Non-orthogonal multiple access (NOMA) and multiple-input multiple-output (MIMO) are viewed as promising techniques to meet the demands for high spectrum efficiency and massive connectivity in future wireless communication. In this paper, a novel framework for realizing transmission in cell-free massive MIMO-NOMA system with deep integration between MIMO and NOMA is proposed. A new method is developed to divide users into different groups according to their equivalent path loss, then ``group-level successive interference cancellation'' (GSIC) is used to cancel inter-group interference when demodulating users. Based on the new framework, a rigorous closed-form expression of achievable sum rate in uplink cell-free massive MIMO-NOMA system is derived. Besides, a parallel iterative method is used to obtain the best power control scheme. It is shown by simulations that the proposed scheme can effectively reduce total power consumption and outperforms the orthogonal multiple access (OMA) transmission and the traditional SIC-NOMA schemes based on user clustering.
Enhancing the Capacity of the Mental Health and Substance Use Health Workforce to Meet Population Needs: Insights From a Facilitated Virtual Policy Dialogue
Authors: Leslie Kathleen , Bartram Mary , Atanackovic Jelena , Chamberland-Rowe Caroline , Tulk Christine , Bourgeault Ivy 
Published: January 2022

Abstract
Background: Timely knowledge mobilization has become increasingly critical during the COVID-19 pandemic and complicated by the need to establish or maintain lines of communication between researchers and decision-makers virtually. Our recent pan-Canadian research study on the mental health and substance use health (MHSUH) workforce during the pandemic identified key policy barriers impacting this essential workforce. To bridge the evidence-policy gap in addressing these barriers, we held a facilitated virtual policy dialogue. This paper discusses the insights generated at this virtual policy dialogue and highlights how this integrated knowledge mobilization strategy can help drive evidence-based policy.Methods: We held a three-hour virtual policy dialogue with 46 stakeholders and policy-decision makers as the final phase in our year-long mixed-methods research study. The event was part of our integrated knowledge mobilization strategy and was designed to generate stakeholder-driven policy implications and priority actions based on our research findings. The data collected from the virtual policy dialogue included transcripts from the small group breakout rooms and main sessions, reflective field notes, and the final report from the external facilitator. Coded data were thematically analyzed to inform our understanding of the prioritization of the policy implications and action items.Results: Facilitated virtual policy dialogues generate rich qualitative insights that guide community-informed knowledge mobilization strategies and promote evidence-informed policy. Our policy dialogue identified actionable policy recommendations with equity as a cross-cutting theme. Adapting policy dialogues to virtual formats and including technology-assisted facilitation can offer advantages for equitable stakeholder participation, allow for deeper analysis, and help build consensus regarding evidence-based policy priorities.Conclusions: Our facilitated virtual policy dialogue was a key knowledge mobilization strategy for our research on the capacity of the Canadian MHSUH workforce to respond to the COVID-19 pandemic. Our policy dialogue allowed us to engage a diverse group of MHSUH workforce stakeholders in a meaningful action-oriented way, provided an avenue to get feedback on our research findings, and generated prioritized action items that incorporated the knowledge and experience of these MHSUH workforce stakeholders.
A Novel Tree Shrew Model of Chronic Experimental Autoimmune Uveitis and its Disruptive Application Efficiency
Authors: Hu Kaijiao , Lv Longbao , Huang Hui , Yin Guangnian , Gao Jie , Liu Jianping , Yang Yaying , Zeng Wenxin , Chen Yan , Zhang Ni , Zhang Feiyan , Ma Yuhua , Chen Feilan 
Published: January 2022

Abstract
Background: Previous studies have established several animal models for experimental autoimmune uveitis (EAU) in rodents without the human fovea. This study aimed to develop and disrupt the application of a novel EAU model in tree shrews with a cone-dominated retina resembling the human fovea.Methods: Tree shrews were immunized with six inter-photoreceptor retinoid-binding proteins (IRBPs) in Freund’s adjuvant. Immunized tree shrews were clinically and pathologically evaluated for the development and characteristics of EAU. IRBP-specific T-cell proliferation and serum cytokine production of tree shrews were evaluated to determine immune responses. Gene-expression profiles were analyzed in the eyes of tree shrews under EAU immunization with screened IRBP to identify differentially expressed genes (DEGs). The disruptive effects of the DEG RGS4 inhibitor CCG 203769 and dihydroartemisinin on the EAU were investigated to evaluate the potential application of tree shrew EAU.Results: Tree shrew IRBP1197–1211 and bovine R14 successfully induced chronic EAU with predominate features of mild vasculitis, diffuse inflammatory infiltration, and retinal damage in the tree shrews. Immunohistological results showed that ionized calcium–binding adaptor molecule-1 (Iba-1)+ macrophages, purinergic receptor P2Y, G-protein–coupled 12 (P2RY12)+ microglia, and CD11c+ dendritic cells, CD4+ and CD8+ T-cells were the main infiltrating cells in the ciliary body, retina, and choroid during the development of disease. IRBP-specific lymphocyte proliferation and pathogenic T helper (Th) 1 and Th17 responses were observed in tree shrew EAU. DEGs in the R14 group were involved in regulation of cell-substrate adhesion, adenylate cyclase activity, and ruffle, and DEGs in the IRBP1197–1211 group were enriched in the supramolecular complex and the microtubule. In particular, the pathways of bacterial invasion of epithelial cells and inflammatory mediator regulation of TRP channels were significantly enriched in the R14 group. RGS4 inhibition and dihydroartemisinin can significantly alleviate the inflammatory severity of EAU by reducing the retinal pathological injuries after treatment.Conclusions: Our study first established a novel chronic EAU in tree shrews elicited by R14 and IRBP1197-1211, probably by altering important pathways and genes related to microglia infiltration, photoreceptor damages, and T-cell responses, thereby allowing the pathogenesis and therapeutics study of the fovea-involved visual disturbance in human uveitis.
PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Authors: Kim Ju Won , Lim Ah Reum , You Ji Young , Lee Jung Hyun , Song Sung Eun , Lee Nam Kwon , Jung Seung Pil , Cho Kyu Ran , Kim Cheol Yong , PARK Kyong Hwa 
Published: January 2022

Abstract
PurposeMutations in PIK3CA gene occur frequently in patients with breast cancer. Activating PIK3CA mutations have been shown to confer resistance to human epidermal growth factor receptor (HER)2-targeted treatments. In this retrospective study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in HER2-positive (HER2+) breast cancer patients.MethodsWe reviewed the clinical information of patients with HER2 + breast cancer who received HER2-targeted therapy for early stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and mutated PIK3CA (PIK3CAm), among those selected for the study. Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment.ResultsData from 90 patients with HER2 + breast cancer were analyzed. Overall, 34 patients had pathogenic PIK3CA mutations (37.8%). The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than in the PIK3CAw group. Sequencing revealed differences in the Mutational landscape between PIK3CAm and PIK3CAw tumors.Conclusion HER2+ breast cancer patients with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Our results suggest that HER2+ breast cancer patients with PIK3CA mutations have an unmet clinical need.
Upregulated LINC01088 Facilitates Malignant Phenotypes and Immune Escape of Colorectal Cancer by Regulating microRNAs/G3BP1/PD-L1 axis
Authors: Wang Shukui , Li Chenmeng , Pan Bei , Wang Xuhong , Qin Jian , Liu Xiangxiang , Gao Tianyi , Sun Huiling , Pan Yuqin 
Published: January 2022

Abstract
Purpose: Long intergenic non-coding RNA LINC01088 is a newly discovered long non-coding RNA. Its biological function in colorectal cancer (CRC) remains unknown. Methods: Here, 36 paired CRC and para-cancerous tissues were collected. In vitro, fluorescence in situ hybridization assay, qPCR, western blotting analysis and cellular functional experiments, RNA immunoprecipitation (RIP) assay and dual-luciferase reporter system analysis were performed. In vivo, xenograft tumor mouse models were generated. Besides, patient-derived intestinal organoid (PDO) was used ex vivo. Results: We found that LINC01088 was significantly upregulated in colorectal cancer tissues and CRC cell lines compared to adjacent normal tissues and colonic epithelial cells. High LINC01088 expression was associated with poor outcome in CRC. LINC01088 was mainly located in the cytoplasm. LINC01088 knockdown suppressed the proliferation, migration, invasion, and immune escape of colorectal cancer cells. Mechanistically, LINC01088 bound directly to miR-548b-5p and miR-548c-5p that were significantly upregulated G3BP1 expression, altering CRC cell phenotypes. In mouse xenograft models, LINC01088 knockdown restrained tumor growth and lung metastasis. Further, G3BP1 overexpression reversed LINC01088-knockdown mediated inhibitory effects on tumor growth. Notably, LINC01088 knockdown downregulated PD-L1 expression, while G3BP1 overexpression restored PD-L1 expression in xenograft tumors. Besides, LINC01088 knockdown repressed CRC organoid growth ex vivo. Conclusion: Overall, these findings suggested that LINC01088 directly targeted miR-548b-5p and miR-548c-5p promoting G3BP1 and PD-L1 expression, which facilitated colorectal cancer progression and immune escape.
Comparison Study of Time-varying Seismic Fragility of Precast Segmental and Cast-in-place Bridge Columns in High-speed Railway Bridges
Authors: Liang Yan , Li Qing-He , Li Pan-Jie , Shu Jing-Xiao , Cao Yang 
Published: January 2022

Abstract
Anxiety about the long-term seismic performance of precast segmental bridge columns (PSBCs) limits their wide application in harsh environments and high intensities. However, railway route selection inevitably occurs in offshore areas, and it is urgent to study the seismic performance of the PSBC considering environmental erosion and seismic effects. In order to To study the application of precast segmental bridge columns (PSBCs) in offshore high intensity areas, this paper comprehensively compares the time-varying seismic fragility of precast segmental and cast-in-place bridge columns (CPBCs) in high-speed railway bridges. Based on an offshore high-speed railway column, finite element models of representative PSBCs and CPBCs are established and verified by experiments. Then, the verified finite models are utilized to implement the time-varying fragility analysis by considering chloride ion erosion under four damage states. The main conclusions are as follows: the exceeding probabilities of PSBC and CPBC are close in intact bridges under different damage states and seismic intensities. With the prolongation of bridge service time, the exceeding probabilities of PSBC increase more rapidly than those of CPBC due to the discontinuity of PSBC segments, which leads to the acceleration of corrosion of steel bars. When the columns reach the design working life, the exceeding probability and PGA median of PSBC are higher than those of CPBC columns under four damage states. Taking the medium damage state as an example, the maximum exceeding probability of PSBC and CPBC was 97.2% and 89.1% at the medium damage state, and the PGA median of PSBC was 24% lower than that of CPBC at 100 years. This work provides a theoretical foundation for the better application of PSBC in offshore high intensity areas.
Who Should do What? Comparing EQ-5D-3L and EQ-5D-5L Proxy-ratings by Informal Caregivers and Health Professional for People with Dementia
Authors: Michalowsky Bernhard , Hoffmann Wolfgang , Mohr Wiebke , Rädke Anika , Xie Feng 
Published: January 2022

Abstract
Background: Assessing health-related quality of life (HRQoL) among persons with dementia poses several challenges due to cognitive decline and limited perception. As a result, proxy ratings by family members or health professionals are used. The EQ-5D is the most commonly used generic and preference-based HRQoL instrument. Methodological drawbacks of the three-level version (EQ-5D-3L) prompted the development of the five-level version (EQ-5D-5L) by expanding the range in the domains. However, no comparison of the psychometric properties of both versions and different proxy ratings exist so far. Therefore, the objective of this study was to compare the psychometric properties of the EQ-5D-5L and EQ-5D-3L by application of different proxy ratings in dementia.Methods: The EQ-5D-3L and -5L were completed by n=52 family caregivers and one care-manager at baseline and three and six months later. In total, 106 caregiver and 133 care manager proxy ratings were completed. The EQ-5D-3L and 5L were evaluated in terms of acceptability, agreement, ceiling effects, redistribution properties and inconsistency, informativity (Shannon, H', and Shannon Evenness, J', indices) as well as convergent and discriminative validity. Results: Mean proxy index scores were higher for the 5L than the 3L. Missing values occurred less frequently in both proxy ratings and versions (<1%). Agreement between both measures was high but higher in caregiver than care-manager ratings (ICC 0.885 vs. 0.840). The relative ceiling effect decreased for the 3L compared to 5L by 56% in the caregiver- and 75% in the care-manager-rating. Inconsistency between both versions was low. Informativity increased from the 3L to the 5L version in both proxy ratings. The 5L also demonstrated a better discriminative ability than the 3L, especially in the caregiver rating. Compared with the 3L, the 5L had better convergent validity, especially for caregiver ratings.Conclusion: The EQ-5D-5L had high feasibility and acceptability and was superior by a reduction of ceiling effects and an improvement in informativity, discriminative ability and convergent validity. Proxy ratings by informal caregivers demonstrated better psychometric properties than professional care-manager ratings.