bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular and Renal Outcomes with SGLT-2 Inhibitors versus GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Network Meta-analysis
Authors: Yamada Takayuki , Wakabayashi Mako , Bhalla Abhinav , Chopra Nitin , Miyashita Hirotaka , Mikami Takahisa , Ueyama Hiroki , Fujisaki Tomohiro , Saigusa Yusuke , Yamaji Takahiro , Azushima Kengo , Urate Shingo , Suzuki Toru , Abe Eriko , Wakui Hiromichi , Tamura Kouichi 
Published: November 2020

Abstract
BackgroundEmerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients.MethodsWe performed a systematic literature search through October 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RA indirectly. Risk ratios (RRs) with corresponding 95% confidence interval (CI) were synthesized.ResultsThirteen studies were selected with a total of 24,887 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95 %CI]; 0.86 [0.74-0.99] and 0.68 [0.62-0.75], respectively). However, GLP-1 RAs did not reduce cardiovascular and renal risk (RR 0.91 [0.79-1.05] and 0.91 [0.81-1.02], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.9 [0.75-1.08]), while SGLT-2 inhibitors were associated with. a lower risk of renal events compared to GLP-1 RAs (RR 0.75 [0.64-0.87]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE than placebo (RR 0.81 [0.68-0.97]), while exendin-4 analogues did not (RR 1.03 [0.86-1.23]).ConclusionsIn patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact, while exendin-4 analogues did not.
A comparison of the demographics, injury patterns and outcome data for patients injured in motor vehicle collisions who are trapped compared to patients who are not trapped
Authors: Nutbeam Tim , Fenwick Rob , Smith Jason , Bouamra Omar , Wallis Lee , Stassen Willem 
Published: November 2020

Abstract
Background Motor vehicle collisions (MVCs) are a common cause of major trauma and death. Following an MVC, up to 40% of patients will be trapped in their vehicle. Extrication methods are focused on the prevention of secondary spinal injury through movement minimisation and mitigation. This approach is time consuming and patients may have time-critical injuries. The purpose of this study is to describe the outcomes and injuries of those trapped following an MVC: this will help guide meaningful patient-focused interventions and future extrication strategies.Methods We undertook a retrospective database study using the Trauma Audit and Research Network database. Patients were included if they were admitted to an English hospital following an MVC from 2012-2018. Patients were excluded when their outcomes were not known or if they were secondary transfers. Results This analysis identified 426,135 cases of which 63,625 patients were included: 6983 trapped and 56,642 not trapped. Trapped patients had a higher mortality (8.9% vs 5.0%, p<0.001). Spinal cord injuries were rare (0.29% of all extrications) but frequently (50.1%) associated with other severe injuries. Spinal cord injuries were more common in patients who were not trapped (p<0.001). Injury Severity Score (ISS) was higher in the trapped group 18 (IQR 10-29) vs 13 (IQR 9-22). Trapped patients had more deranged physiology with lower blood pressures, lower oxygen saturations and lower Glasgow comas Scale, GCS (all p<0.001). Trapped patients had more significant injuries of the head chest, abdomen and spine (all p<0.001) and an increased rate of pelvic injures with significant blood loss, blood loss from other areas or tension pneumothorax (all p<0.001). Conclusion Trapped patients are more likely to die than those who are not trapped. The frequency of spinal cord injuries is low, accounting for <0.3% of all patients extricated. Patients who are trapped are more likely to have time-critical injuries requiring intervention. Extrication takes time and when considering the frequency, type and severity of injuries reported here, the benefit of movement minimisation may be outweighed by the additional time taken. Improved extrication strategies should be developed which are evidence-based and allow for the expedient management of other life-threatening injuries.
WNT4 secreted by tumor tissues promotes tumor progression in colorectal cancer by activation of the Wnt/β-catenin signalling pathway
Authors: Yang Dongmei , Li Qing , Shang Renduo , Yao Liwen , Wu Lianlian , Zhang Mengjiao , Zhang Lihui , Xu Ming , Lu Zihua , Zhou Jie , Huang Li , Huang Xiaodong , Cheng Du , Yang Yanning , Yu Honggang 
Published: November 2020

Abstract
Background: Wingless and Int-related protein (Wnt) ligands are aberrantly expressed in patients with colorectal cancer (CRC). However, the aberrant level of Wnt ligands in serum have not been explored. Here, we aimed to identify the levels of WNT4 in serum and explored its oncogenic role in CRC Methods: The Oncomine database was used to analyze the relationship between WNT4 and the prognosis of CRC. ELISA was performed to measure WNT4 levels in serum and conditioned medium from fresh CRC tissues and adjacent normal tissues. Western blot and immunohistochemistry were carried out to measure the expression of WNT4 in human CRC tissues and adjacent normal tissues. The migration and invasion of CRC cells were determined by trans-well assay, and the effects of WNT4 on CRC invasion and metastasis in vivo were verified by tumor xenograft in nude mice. Cancer-associated fibroblasts (CAFs) and angiogenesis in subcutaneous nodules were detected by immunofluorescence (IF). In addition, the suspended spheres formation and tube formation assay were performed to explore the effects of WNT4 on CAFs and angiogenesis respectively. Results: WNT4 was significantly upregulated in serum of CRC patients, and CRC tissues were identified as an important source of elevated WNT4 levels in CRC patients. Interestingly, elevated levels of WNT4 in serum were downregulated after tumor resection. Furthermore, we found that WNT4 contributed to epithelial-to-mesenchymal transition (EMT) and activated fibroblasts by activating the WNT4/β-catenin pathway in vitro and in vivo. Moreover, angiogenesis was induced via the WNT4/β-catenin/Ang2 pathway. Those effects could be reversed by ICG-001, a β-catenin/TCF inhibitor. Conclusion: Our findings indicated that serum levels of WNT4 may be a potential biomarker for CRC. WNT4 secreted by colorectal cancer tissues promote the progression of CRC by inducing EMT, activate fibroblasts and promote angiogenesis through the canonical Wnt/β-catenin signalling pathway.
Differential response of digesta- and mucosa-associated intestinal microbiota to dietary black soldier fly (Hermetia illucens) larvae meal in seawater phase Atlantic salmon (Salmo salar)
Authors: Li Yanxian , Bruni Leonardo , Jaramillo-Torres Alexander , Gajardo Karina , Kortner Trond M. , Krogdahl Åshild 
Published: November 2020

Abstract
Background: Intestinal digesta is commonly used for studying responses of microbiota to dietary shifts, yet evidence is accumulating that it represents an incomplete view of the intestinal microbiota. The present work aims to investigate the differences between digesta- and mucosa-associated intestinal microbiota in Atlantic salmon (Salmo salar) and how they may respond differently to dietary perturbations. In a 16-week seawater feeding trial, Atlantic salmon were fed either a commercially-relevant reference diet or an insect meal diet containing ~15% black soldier fly (Hermetia illucens) larvae meal. The digesta- and mucosa-associated distal intestinal microbiota were profiled by 16S rRNA gene sequencing. Results: Regardless of diet, we observed substantial differences between digesta- and mucosa-associated intestinal microbiota. Microbial richness and diversity were much higher in the digesta than the mucosa. The insect meal diet altered the distal intestinal microbiota resulting in higher microbial richness and diversity. The diet effect, however, depended on the sample origin. Digesta-associated intestinal microbiota showed more pronounced changes than the mucosa-associated microbiota. Multivariate association analyses identified two mucosa-enriched taxa, Brevinema andersonii and Spirochaetaceae, associated with the expression of genes related to immune responses and barrier function in the distal intestine, respectively. Conclusions: Our data show that salmon intestinal digesta and mucosa harbor microbial communities with clear differences. Mucosa-associated intestinal microbiota seems more resilient to variations in the diet composition than digesta-associated intestinal microbiota. To fully unveil the response of intestinal microbiota to dietary changes, concurrent profiling of digesta- and mucosa-associated intestinal microbiota is recommended whenever feasible.
Inhibition of Ref(2)P, the Drosophila homologue of p62/SQSTM1, increases lifespan and leads to motor function decline
Authors: Hurley Emily P. , Staveley Brian Ernest 
Published: November 2020

Abstract
Objective: Sequestosome 1 (p62/SQSTM1) is a multifunctional scaffold/adaptor protein encoded by the p62/SQSTM1 gene with function in cellular homeostasis. Mutations in the p62/SQSTM1 gene have been known to be associated with patients with Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and Parkinson Disease (PD). The aim of the present study was to create a novel model of human neurogenerative disease in Drosophila melanogaster by altering the expression of Ref(2)P, the Drosophila orthologue of the human p62/SQSTM1 gene. Ref(2)P expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time.Results: Inhibition of Ref(2)P resulted in a significantly increased median lifespan in the motor neurons, followed by a severe decline in motor skills. Inhibition of Ref(2)P in the dopaminergic neurons resulted in a significant, but minimal increase in median lifespan, accompanied by a drastic decline in locomotor function. Inhibition of Ref(2)P in the ddc-Gal4-expressing neurons resulted in a significant increase in median lifespan, while dramatically reducing motor function.
Integrated analyses of miRNA and mRNA profiles in leukocytes and serums in traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome and Pi-wei damp-heat syndrome resulting from chronic atrophic gastritis
Authors: You Leiming , Zhang Shen , Li Ting’an , Sang Xiaopu , Li Kunyu , Wang Wei , Gao Xinhui , Wu Jiarui , Huang Guangrui , Wang Ting , Xu Anlong 
Published: November 2020

Abstract
Background: To investigate the microRNA (miRNA)-gene interactions underlying leukocyte functions and characteristics, especially the potential serum biomarkers, implicated in the traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome (PQDS) and Pi-wei damp-heat syndrome (PDHS) resulting from chronic atrophic gastritis (CAG). Methods: Using RNA/miRNA-sequencing approach, compared with healthy control population, we identified the PDHS- or PQDS-specific miRNAs and genes in leukocytes or serums, especially the Zheng (syndrome)-specific miRNA-gene interactions, and further decoded their functions and pathways. Results: Despite being the TCM-defined Zhengs resulting from the same disease of CAG, the Zheng-specific genes and miRNAs were not same. The PDHS-specific leukocyte genes were mainly involved in defense and immune responses, including NOD-like receptor signaling and several synapses-related pathways. The expression upregulation of PDHS-specific genes enriched in the neutrophil degranulation pathway, indicated the enhanced leukocyte degranulation activation. The PQDS-specific genes in leukocytes were implicated in inflammatory response, extracellular matrix (ECM) organization and collagen catabolism. They could be enriched in MAPK and IL17 signaling and helper T cell differentiation pathways, especially the pathways associated with cell-to-cell adhesion/junction and communication such as cell adhesion molecules, ECM organization and ECM-receptor interaction, probably contributing to the characteristics and functions of leukocytes. Also, the experimentally-supported miRNA-gene interactions, concerned with COL4A2, COL26A1, SPP1 and PROCR, were implicated in the regulation of pathways related to cell-to-cell adhesion/junction and communication, suggesting the potential roles of the PQDS-specific miRNA-gene interactions for the characteristic and functional changes of leukocytes. Interestingly, the PQDS-specific miRNAs in the serums and the corresponding leukocytes, seemed to have the common roles in contributing to the characteristics and functions of leukocytes. Importantly, the hsa-miR-122-5p could be a potential biomarker, capable of being contained and carried in plasma exosomes and much higher expression in both the leukocytes and corresponding serums in the CAG patients with PQDS rather than PDHS. Conclusions: These results may provide new insights into the characteristic and functional changes of leukocytes in the two Zhengs, PDHS and PQDS, especially the miRNA-mediated gene regulation underlying leukocyte characteristics and functions, with potential leukocyte and serum biomarkers for future application in integrative medicine.Trial registration: ClinicalTrials.gov, NCT02915393. Registered on September 17, 2016.
Rhizosphere community selection reveals bacteria associated with reduced root disease&nbsp;
Authors: Paulitz Timothy , Yin Chuntao , Vargas Juan M. Casa , Schlatter Daniel C. , Hagerty Christina H. , Hulbert Scot H. 
Published: November 2020

Abstract
Background: Microbes benefit plants by increasing nutrient availability, producing plant growth hormones, and protecting against pathogens. However, it is largely unknown how plants change root microbial communities. Results: In this study, we used a multi-cycle selection system and infection by the soilborne fungal pathogen Rhizoctonia solani AG8 (hereafter AG8) to examine how plants impact the rhizosphere bacterial community and recruit beneficial microorganisms to suppress soilborne fungal pathogens and promote plant growth. Successive plantings dramatically enhanced disease suppression on susceptible wheat cultivars to AG8 in the greenhouse. Accordingly, analysis of the rhizosphere soil microbial community using deep sequencing of 16S rRNA genes revealed distinct bacterial community profiles assembled over successive wheat plantings. Moreover, the cluster of bacterial communities formed from the AG8-infected rhizosphere was distinct from those without AG8 infection. Interestingly, the bacterial communities from the rhizosphere with the lowest wheat root disease gradually separated from those with the worst wheat root disease over planting cycles. Successive monocultures and application of AG8 increased the abundance of some bacterial genera which have potential antagonistic activities, such as Chitinophaga, Pseudomonas, Chryseobacterium, and Flavobacterium, and a group of plant growth-promoting (PGP) and nitrogen-fixing microbes, including Pedobacter, Variovorax, and Rhizobium. Furthermore, 47 bacteria isolates belong to 35 species were isolated. Among them, eleven and five exhibited antagonistic activities to AG8 and Rhizoctonia oryzae in vitro, respectively. Notably, Janthinobacterium displayed broad antagonism against the soilborne pathogens Pythium ultimum, AG8, and R. oryzae in vitro, and disease suppressive activity to AG8 in soil. Conclusions: Our results demonstrated that successive wheat plantings and pathogen infection can shape the rhizosphere microbial communities and specifically accumulate a group of beneficial microbes. Our findings suggest that soil community selection may offer the potential for addressing agronomic concerns associated with plant diseases and crop productivity.
Validation of the BATT score for prehospital risk stratification of traumatic haemorrhagic death: Usefulness for tranexamic acid treatment criteria.
Authors: Ageron Francois-Xavier , Coats Timothy J , Darioli Vincent , Roberts Ian 
Published: November 2020

Abstract
Background: Tranexamic acid reduces surgical blood loss and reduces deaths from bleeding in trauma patients. Tranexamic acid must be given urgently, preferably by paramedics at the scene of the injury or in the ambulance. We developed a simple score (Bleeding Audit Triage Trauma score) to predict death from bleeding.Methods: We conducted an external validation of the BATT score using data from the UK Trauma Audit Research Network (TARN) from 1st January 2017 to 31st December 2018. We evaluated the impact of tranexamic acid treatment thresholds in trauma patients.Results: We included 104,862 trauma patients with an injury severity score of 9 or above. Tranexamic acid was administered to 9,915 (9%) patients. Of these 5,185 (52%) received prehospital tranexamic acid. The BATT score had good accuracy (Brier score=6%) and good discrimination (C-statistic 0.90; 95% CI 0.89-0.91). Calibration in the large showed no substantial difference between predicted and observed death due to bleeding (1.15% versus 1.16%; P=0.81). Pre-hospital tranexamic acid treatment of trauma patients with a BATT score of 2 or more would avoid 210 bleeding deaths by treating 61,598 patients instead of avoiding 55 deaths by treating 9,915 as currently. Conclusion: The BATT score identifies trauma patient at risk of significant haemorrhage. A score of 2 or more would be an appropriate threshold for pre-hospital tranexamic acid treatment.
Varicella Zoster Virus Anterior Uveitis Complicated by Thalamic Stroke
Authors: Anthony Casey , Costarides Anastasios P. , Yeh Steven , Shantha Jessica G. 
Published: November 2020

Abstract
We report a case of varicella zoster virus (VZV)-associated anterior uveitis in a patient with weight loss, arthritis and signs of inflammatory bowel disease. Her clinical course included the development of a thalamic stroke secondary to VZV cerebral vasculopathy. Following antiviral therapy, the patient’s neurologic symptoms recovered and her ophthalmic findings improved.
Relationship between tumor mutational burden and maximum standardized uptake value in 2-[18F]FDG PET (positron emission tomography) scan in cancer patients
Authors: Jahromi Amin Haghighat , Barkauskas Donald A , Zabel Matthew , Goodman Aaron M. , Frampton Garret , Nikanjam Mina , Hoh Carl K , Kurzrock Razelle 
Published: November 2020

Abstract
Purpose: Deriving links between imaging and genomic markers is an evolving field. 2-[18F]FDG PET/CT (18F-fluorodeoxyglucose Positron Emission Tomography- Computed Tomography) is commonly used for cancer imaging, with maximum standardized uptake value (SUVmax) as the main quantitative parameter. Tumor mutational burden (TMB), the quantitative variable obtained using next-generation sequencing on a tissue biopsy sample, is a putative immunotherapy response predictor. We report the relationship between TMB and SUVmax, linking these two important parameters.Methods: In this pilot study, we analyzed 1923 patients with diverse cancers and available TMB values. Overall, 273 patients met our eligibility criteria in that they had no systemic treatment prior to imaging/biopsy, and also had 2-[18F]FDG PET/CT within six months prior to the tissue biopsy, to ensure acceptable temporal correlation between imaging and genomic evaluation.Results: We found a linear correlation between TMB and SUVmax (p<0.001). In the multivariate analysis, only TMB independently correlated with SUVmax whereas age, gender and tumor organ did not.Conclusion: Our observations link SUVmax in readily available, routinely used, and non-invasive 2-[18F]FDG PET/CT imaging to the TMB, which requires a tissue biopsy and time to process. Since higher TMB has been implicated as a prognostic biomarker for better outcomes after immunotherapy, further investigation will be needed to determine if SUVmax can stratify patient response to immunotherapy.
Title: Vitamin D Receptor Bsm I Polymorphism and Osteoporosis Risk in postmenopausal women: A Meta-Analysis from 42 Studies
Authors: Liao JunLong , Qin Qiang , Zhou YongSheng , Ma RuPing , Zhou HeChao , Gu MaoRong , Feng Yunping , Wang BoYuan , Yang Ling 
Published: November 2020

Abstract
Objective: This study aimed to quantitatively summarize the evidence for VDR BsmI gene polymorphism and osteoporosis risk in postmenopausal women. Materials and Methods: The PubMed, EMBASE, Weipu, CNKI, and Wanfang database were searched for eligible studies. Case-control studies containing available genotype frequencies of B/b were chosen, and Odds ratio (OR) with ­­­95% confidence interval (CI) was used to assess the strength of this association. Results: 4485 osteoporosis and 5490 controls were identified in our meta-analysis. In the stratified analysis, a significant association was observed between VDR BsmI gene polymorphism and osteoporosis susceptibility in Caucasians (additive model: OR=0.809, 95% CI 0.678~0.965, p=0.019, recessive model: OR=0.736, 95% CI 0.568~0.955, p=0.021, and co-dominant model: bb vs. BB OR=0.701, 95% CI 0.511~0.962 p= 0.028), and we failed to find any significant relationship in Asians. Conclusion: The present meta-analysis suggests that VDR BsmI genotype is associated with increased risk of postmenopausal osteoporosis in Caucasians but not in Asians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between VDR BsmI polymorphism and osteoporosis in postmenopausal women.