bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of outcomes between novel oral anticoagulants and warfarin monotherapy in patients with left atrial appendage closure: A systematic review and meta-analysis
Authors: Sun Bing , Chen Rui Rui , Gao Chao , Tao Ling 
Published: October 2022

BackgroundPivotal trials of percutaneous left atrial appendage closure (LAAC) used dedicated post-procedure antithrombotic protocols. However, there is no consensus on the selection of new oral anticoagulants (NOAC) and warfarin monotherapy after LAAC. This study aims to compare NOAC with warfarin monotherapy for efficacy and safety in patients undergoing LAAC.MethodsA database search was conducted using PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov for trials that compared NOAC with warfarin monotherapy after LAAC. The effective outcomes included any major adverse events (all-cause death, stroke, major bleeding) and their individual components. Safety outcomes included all-cause death, major bleeding, total bleeding, DRT, and PDL &gt;5 mm.ResultsWe included 10 non-randomized clinical trials with 10,337 patients, of whom 4,960 patients received NOAC, while 5,377 patients received warfarin. There were no statistically significant differences in any major adverse events (LogOR: −0.11, 95% CI: −0.27, 0.04, P = 0.16), stroke (LogOR: 0.00, 95% CI: −0.42, 0.42, P = 1.00), all-cause death (LogOR: −0.23, 95% CI: −0.48, 0.02, P = 0.07), major bleeding (LogOR: −0.22, 95% CI: −0.45, 0.01, P = 0.06). NOAC was associated with a significant reduction in total bleeding (LogOR: −1.01, 95% CI: −1.47, −0.55, P &lt; 0.0001) compared to warfarin. No statistically significant differences were found in DRT (LogOR: −0.19, 95% CI: −0.15, 0.52, P = 0.27) and PDL &gt;5 mm (LogOR: 0.19, 95% CI: −0.33, 0.72, P = 0.47). Meta-regression and subgroup analysis showed that total bleeding (LogOR: −1.56, 95% CI: −2.15, −0.97, P &lt; 0.001) was significantly lower in the NOAC group in the subgroup of &lt;75 y.ConclusionAfter LAAC, NOAC monotherapy was associated with a lower risk of bleeding compared to warfarin monotherapy for 45 days. There was no significant difference between NOAC and warfarin in terms of other results.Systematic review registrationwww.york.ac.uk/inst/crd, identifier: CRD42022361244.
Contribution of anthropogenic vibration sources to crack growth in natural rock arches
Authors: Finnegan Riley , Moore Jeffrey R. , Geimer Paul R. 
Published: October 2022

Natural arches are culturally valued rock landforms common in sedimentary rocks of the Colorado Plateau and additionally occur broadly around the world. Recent notable collapses of some of these landforms have highlighted the need to better understand the mechanics of their failure. While environmentally driven weathering has been the focus of most previous studies of arch collapse, comparably little attention has been given to anthropogenic vibration sources and how these often slight- to moderate-magnitude shaking events might steadily weaken arches over time. We collected 12–15 months of continuous ambient vibration data from arches and nearby bedrock in both anthropogenically ‘noisy’ and ‘quiet’ locations and used these datasets to develop an annual model of arch peak ground velocity based on magnitude-cumulative frequency distributions. Working from these models, we added vibration events of varying magnitude or frequency of occurrence, informed by field data, imitating arch vibration in response to different anthropogenic activities such as helicopter flights or induced earthquakes. We then applied subcritical fracture mechanics principles to predict annual crack growth rates in an idealized arch under these different vibration conditions. Our results demonstrate that in a single year, cracks grow minimally longer (∼1%) in ‘noisy’ environments than in areas not experiencing anthropogenic vibration energy. Few (1+) 30-s moderate-magnitude events (∼15 mm/s) or many (&gt;37,000) 30-s low-magnitude events (∼2 mm/s) cause markedly increased crack growth. Our approach provides a valuable new framework for assessing the range and frequency of occurrence of vibrations experienced by an arch, and for predicting arch damage. Our results, in turn, yield important new outputs applicable in support of conservation management of these and similar landforms world-wide under exposure to a range of human-induced vibration activity.
Late Cryogenian and late Paleozoic ice ages on the São Francisco craton, east Brazil
Authors: Uhlein Gabriel J. , Uhlein Alexandre 
Published: October 2022

The miniature paleocontinent in the region of the São Francisco River valley, in eastern Brazil, holds the record of two different glacial epochs. The late Cryogenian Jequitaí Formation from the Bambuí Group is up to 100 m thick and covers areas mainly in the central São Francisco craton. Evidences for glacial sedimentation are beautifully preserved E-W grooves and striations, dropstones within fine-grained rocks, and a full set of diamictites enclosing a rich and complex depositional history. The Jequitaí Formation is in close link with the tectonic evolution of the São Francisco paleocontinent and the West Gondwana amalgamation. From west, the precocious Paranapanema and São Francisco blocks collision in late Cryogenian flexured the foreland lithosphere and created depozones that were infilled by glacial sediments. Toward east, the rifting and opening of the Adamastor Ocean allowed thick glacial and non-glacial deposits to form through subaqueous gravitational sedimentation. From west to east, proximal and distal glaciomarine, glaciocontinental, and non-glacial resedimentation are identified and linked to the evolving continental masses and climate during the Cryogenian and beginning of Ediacaran. The late Paleozoic Santa Fé Group is the youngest record of glaciation on the São Francisco craton. It is 60–80 m thick and yields consistent and confident glacial evidences such as N-S striations on top of Cambrian sandstones, ice-rafted debris, and rain-out diamictite, all preserved in small and patchy areas in the west-central São Francisco craton. Paleocurrents suggest a northern ice center and sedimentary facies indicate deposition in continental lakes and rivers. Although late Paleozoic, its age is poorly constrained and likely correlated with the uppermost Itararé Group (Taciba Formation) of Paraná Basin in south Brazil. Deglaciation and strong isostatic adjustments make up the termination of the Santa Fé Group sedimentary record and depict a glaciocontinental system evolved on an interior stable continental crust. The late Neoproterozoic Jequitaí Formation and the late Paleozoic Santa Fé Group are parts of the earth’s sedimentary history preserving a rich record of climate, tectonic, and surface processes in part controlled by the evolving continental masses on the São Francisco craton.
TM6SF2 rs58542926 is related to hepatic steatosis, fibrosis and serum lipids both in adults and children: A meta-analysis
Authors: Li Xue-Ying , Liu Zheng , Li Li , Wang Hai-Jun , Wang Hui 
Published: October 2022

Background and aimsFindings about the associations between transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 and nonalcoholic fatty liver disease have not been consistently replicated, particularly in steatosis and fibrosis. The present study aimed to investigate the associations between the rs58542926T allele and the spectrum of NAFLD and its related metabolic phenotypes.MethodsSystematic literature research was performed to analyse the associations between rs58542926 and the spectrum of NAFLD and its related metabolic phenotypes. A random effects meta-analysis with a dominant genetic model was applied.ResultsData from 123,800 individuals across 44 studies were included in the current meta-analysis.rs58542926 T allele was associated with an increased risk of NAFLD in both adults (OR=1.62; 95% CI: 1.40, 1.86) and children (OR=2.87; 95% CI: 1.85, 4.46). Children had a stronger association with NAFLD (P=0.01). rs58542926 T allele was also positively associated with steatosis progression (mean difference=0.22; 95% CI: 0.05, 0.39) and fibrosis stage (OR=1.50; 95% CI: 1.20, 1.88) in adults. The TM6SF2 rs58542926 T allele was positively associated with ALT in both adults and children (both P&lt;0.01) and only with higher AST in adults (P&lt;0.01). The rs58542926 T allele was negatively associated with serum total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TGs) in both adults and children (all P&lt;0.01).The serum level of TG was much lower in adults than in children (P&lt;0.01).ConclusionTM6SF2 rs58542926 is involved in the entire spectrum of NAFLD and its related metabolic phenotype, and differences in serum lipid levels were observed between adults and children.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288163.
Obesity and periodontitis: A systematic review and updated meta-analysis
Authors: Kim Chang Min , Lee Soobin , Hwang Wonjun , Son Eunjeong , Kim Tae Woo , Kim Kihun , Kim Yun Hak 
Published: October 2022

BackgroundA previous 2014 meta-analysis reported a positive association between obesity and periodontitis. It was considered necessary to update the recently published papers and to analyse subgroups on important clinical variables that could affect the association between obesity and periodontitis. Therefore, we updated the latest studies and attempted to derive more refined results.MethodsAll observational studies were eligible for inclusion. The Newcastle–Ottawa scale was used to qualitatively evaluate the risk of bias. Subgroup analyses were conducted for patients aged 18–34, 35–54, and 55+ years and the countries (European countries, USA, Brazil, Japan, Korea, and other Asian countries).ResultsThirty-seven full-text articles were included. Obesity conferred increased odds of periodontal disease with an odds ratio (1.35, 95% CI: 1.05–1.75). In the subgroup analysis by age, the odds ratio was the highest in the 18–34 years group (2.21, 95% CI: 1.26–3.89). In the subgroup analysis by country, European countries had the highest odds ratio (2.46, 95% CI: 1.11–5.46).ConclusionDespite the differences in degree, a positive association between obesity and periodontitis was found regardless of country or age. Therefore, medical professionals should try to prevent periodontitis by controlling patient weights, and more studies should be conducted to determine the association between obesity and oral health.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022301343.
High expression of MARVELD3 as a potential prognostic biomarker for oral squamous cell carcinoma
Authors: Huang Ke , Meng Yucheng , Lu Jiyuan , Xu Lingdan , Wang Shiqi , Wang Huihui , Xu Zhaoqing 
Published: October 2022

Objectives: Tight junction-associated marvel proteins (TAMP) is a transmembrane protein whose members are associated with tight junctions between cells and epithelial remodeling. MARVEL domain containing 3 (MARVELD3) is one of the members of the TAMP. MARVELD3, as a novel tight junction protein involved in bicellular tight junction assembly, has attracted growing attention in the field of oncology. This study aimed to investigate the prognostic role of MARVELD3 and to determine how it functions in tumorigenesis in oral squamous cell carcinoma (OSCC), thus providing additional data to help the guidance of clinical practice.Materials and Methods: RNA-seq data and relevant clinical information were obtained from TCGA. Bioinformatics means used in this study included differential gene expression analysis, KM survival curve analysis, univariate and multivariate Cox regression analyses, nomogram analysis, ROC curve analysis, methylation level analysis, gene function enrichment analysis, and immune cell infiltration analysis.Results:MARVELD3 was significantly higher expressed in OSCC tissue than in normal tissue, and the overall survival of the high expression group was significantly lower than that of the normal group. Univariate and multivariate Cox regression analyses showed that MARVELD3 could serve as an independent contributing factor to poor OSCC prognosis. The nomograms and ROC curves supported the results above. Its expression was negatively correlated with DNA methylation sites. Analysis of PPI networking and gene functional enrichment showed that MARVELD3 was involved in the functional activities of DNA and RNA and was associated with immune cell infiltration.Conclusion: The high expression of MARVELD3 is associated with poor prognosis in OSCC, and MARVELD3 could be recognized as a novel independent prognostic factor for OSCC.
A novel risk score based on immune-related genes for hepatocellular carcinoma as a reliable prognostic biomarker and correlated with immune infiltration
Authors: Long Meiying , Zhou Zihan , Wei Xueyan , Lin Qiuling , Qiu Moqin , Zhou Yunxiang , Chen Peiqin , Jiang Yanji , Wen Qiuping , Liu Yingchun , Li Runwei , Zhou Xianguo , Yu Hongping 
Published: October 2022

BackgroundImmunological-related genes (IRGs) play a critical role in the immune microenvironment of tumors. Our study aimed to develop an IRG-based survival prediction model for hepatocellular carcinoma (HCC) patients and to investigate the impact of IRGs on the immune microenvironment.MethodsDifferentially expressed IRGs were obtained from The Genomic Data Commons Data Portal (TCGA) and the immunology database and analysis portal (ImmPort). The univariate Cox regression was used to identify the IRGs linked to overall survival (OS), and a Lasso-regularized Cox proportional hazard model was constructed. The International Cancer Genome Consortium (ICGC) database was used to verify the prediction model. ESTIMATE and CIBERSORT were used to estimate immune cell infiltration in the tumor immune microenvironment (TIME). RNA sequencing was performed on HCC tissue specimens to confirm mRNA expression.ResultsA total of 401 differentially expressed IRGs were identified, and 63 IRGs were found related to OS on the 237 up-regulated IRGs by univariate Cox regression analyses. Finally, five IRGs were selected by the LASSO Cox model, including SPP1, BIRC5, STC2, GLP1R, and RAET1E. This prognostic model demonstrated satisfactory predictive value in the ICGC dataset. The risk score was an independent predictive predictor for OS in HCC patients. Immune-related analysis showed that the immune infiltration level in the high-risk group was higher, suggesting that the 5-IRG signature may play an important role in mediating immune escape and immune resistance in the TIME of HCC. Finally, we confirmed the 5-IRG signature is highly expressed in 65 HCC patients with good predictive power.ConclusionWe established and verified a new prognosis model for HCC patients based on survival-related IRGs, and the signature could provide new insights into the prognosis of HCC.
Endostatin induces normalization of blood vessels in colorectal cancer and promotes infiltration of CD8+ T cells to improve anti-PD-L1 immunotherapy
Authors: Chu Xiao-Dong , Bao Hui , Lin Yu-Jian , Chen Ruo-Xi , Zhang Yi-Ran , Huang Ting , He Jia-Shuai , Huangfu Shu-Chen , Pan Yun-Long , Ding Hui 
Published: October 2022

IntroductionThe purpose of this study was to evaluate recombinant human endostatin (rHE)-induced normalization of the tumor vasculature in colorectal cancer (CRC) and to evaluate the therapeutic effects of combined treatment with rHE and a programmed death ligand-1 (PD-L1) inhibitor.MethodsA mouse subcutaneous tumorigenesis model was established to evaluate the antitumor effects of endostatin combined with a PD-L1 inhibitor on CRC. Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DW MRI) was used to evaluate changes in the intratumor microcirculation in response to combined treatment with endostatin and a PD-L1 inhibitor. The infiltration density and function of CD8+ T cells in tumors were evaluated using flow cytometry. Finally, clinical specimens were used to evaluate the expression area of tumor vascular pericytes and CD8+ T cells in tumor tissues.ResultsThe antitumor effects of endostatin combined with a PD-L1 inhibitor were significantly greater than those of endostatin or a PD-L1 inhibitor alone. On the ninth day of intervention, the endostatin group showed significantly higher pseudo diffusion parameter (D*) and microvascular volume fraction (F) values in tumors than those in the control group or PD-L1 group. After 27 days of intervention, the endostatin groups showed significantly lower levels of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β than those in the control group. Treatment of CD8+ T cells with endostatin for 24 h did not alter the expression levels of markers of reduced T-cell activity. However, endostatin reversed the VEGF-mediated inhibition of the secretion of interferon (IFN)-γ from T cells. The results in CRC clinical samples showed that treatment with endostatin induced significantly higher infiltration of CD8+ T cells compared with treatment that did not include endostatin. Furthermore, the expression area of pericytes was significantly positively related to the infiltration density of CD8+ T cells and overall survival time.ConclusionEndostatin improved the antitumor effects of PD-L1 inhibitors on CRC, significantly increased the activity of CD8+ T cells, and synergistically improved the tumor treatment effect of the two inhibitors.
In-silico evaluation of adenoviral COVID-19 vaccination protocols: Assessment of immunological memory up to 6 months after the third dose
Authors: Stolfi Paola , Castiglione Filippo , Mastrostefano Enrico , Di Biase Immacolata , Di Biase Sebastiano , Palmieri Gianna , Prisco Antonella 
Published: October 2022

BackgroundThe immune response to adenoviral COVID-19 vaccines is affected by the interval between doses. The optimal interval is unknown.AimWe aim to explore in-silico the effect of the interval between vaccine administrations on immunogenicity and to analyze the contribution of pre-existing levels of antibodies, plasma cells, and memory B and T lymphocytes.MethodsWe used a stochastic agent-based immune simulation platform to simulate two-dose and three-dose vaccination protocols with an adenoviral vaccine. We identified the model’s parameters fitting anti-Spike antibody levels from individuals immunized with the COVID-19 vaccine AstraZeneca (ChAdOx1-S, Vaxzevria). We used several statistical methods, such as principal component analysis and binary classification, to analyze the correlation between pre-existing levels of antibodies, plasma cells, and memory B and T cells to the magnitude of the antibody response following a booster dose.Results and conclusionsWe find that the magnitude of the antibody response to a booster depends on the number of pre-existing memory B cells, which, in turn, is highly correlated to the number of T helper cells and plasma cells, and the antibody titers. Pre-existing memory T cytotoxic cells and antibodies directly influence antigen availability hence limiting the magnitude of the immune response. The optimal immunogenicity of the third dose is achieved over a large time window, spanning from 6 to 16 months after the second dose. Interestingly, after any vaccine dose, individuals can be classified into two groups, sustainers and decayers, that differ in the kinetics of decline of their antibody titers due to differences in long-lived plasma cells. This suggests that the decayers may benefit from a tailored boosting schedule with a shorter interval to avoid the temporary loss of serological immunity.
Prospective surveillance of Zika virus at the end of the Americas’ outbreak: An unexpected outcome
Authors: Rivas Enrique , Ojeda Joyce , Garcia-Rivera Enid J. , Rivera Doris M. , Arredondo José L. , Medina Eduardo López , Aguirre Floriberto , Bernal Luis , Chen Zhenghong , Petit Celine , Guranathan Sanjay , Heinrichs Jon H. , Áñez Germán , Noriega Fernando 
Published: October 2022

ObjectiveThe French Polynesia Zika virus (ZIKV) outbreak (2013–2014) broadened the known manifestations of ZIKV disease (ZVD) to include neural and congenital syndromes. A subsequent epidemic in the Americas (2015–2016) caused &gt;685,000 suspected/confirmed cases before seemingly disappearing as fast as it expanded. A study was implemented (2017–2018) to detect ZVD cases in the region (Mexico, Honduras, Colombia and Puerto Rico), with the aim of validating surveillance methodology so as to increase sensitivity in case detection, which would have potential application for future vaccine development endeavors.Study design and settingTo identify potential cases, we focused on signs/symptoms that were frequently associated with ZVD for confirmation by PCR. Serostatus and seroconversion were evaluated by ZIKV non-structural protein 1 blockade-of-binding enzyme-linked immunosorbent assay (BOB ELISA) and microneutralization assay.ResultsOverall, 2,400 participants aged 15–40 years were enrolled; 959 (40.0%) had signs/symptoms that could be associated with ZVD: axillary temperature ≥37°C (64.3%), myalgia (60.8%) and arthralgia (58.6%). Three suspected cases were virologically confirmed. Zika seroprevalence was high at study initiation (52.6% [BOB ELISA] and 56.0% [microneutralization assay]). In participants who were Zika seronegative, low seroconversion rates were observed after one year follow-up (3.6% [BOB ELISA] and 3.1% [microneutralization assay]).ConclusionThe ZIKV continued to circulate in the Americas at very low levels following the 2015–2016 outbreak. The epidemiological factors driving Zika’s rapid rise and decline remain poorly understood.Clinical trial registrationClinicaltrials.gov: NCT03158233 BARDA (Contract # HHSO100201600039C) WHO Universal Trial Number: U1111-1183-5687.
Gut microbiota diversity and specific composition during immunotherapy in responders with non-small cell lung cancer
Authors: Shoji Fumihiro , Yamaguchi Masafumi , Okamoto Masaki , Takamori Shinkichi , Yamazaki Koji , Okamoto Tatsuro , Maehara Yoshihiko 
Published: October 2022

Cancer immunotherapy including immune checkpoint inhibitors (ICI) has revolutionized non-small cell lung cancer (NSCLC) therapy. Recently, the microbiota status “before” initiation of ICI therapy has been emphasized as a predictive biomarker in patients undergoing ICI therapy. However, the microbiota diversity and composition “during” ICI therapy is unknown. This multicenter, prospective observational study analyzed both saliva and feces from 28 patients with NSCLC. We performed 16S ribosomal RNA gene sequencing, then analyzed associations of oral and gut microbiota diversity or composition with ICI response. At the genus level, the alpha diversity of the gut microbiota was significantly greater in responders (n = 17) than in non-responders (n = 11) (Chao 1, p = 0.0174; PD whole tree, p = 0.0219; observed species, p = 0.0238; Shannon, p = 0.0362), while the beta diversity of the gut microbiota was significantly different (principal coordinates analysis, p = 0.035). Compositional differences in the gut microbiota were observed between the two groups; in particular, g_Blautia was enriched in responders, whereas o_RF32 order unclassified was enriched in non-responders. The progression-free survival (PFS) of patients enriched gut microbiota of g_Blautia was significantly longer [median survival time (MST): not reached vs. 549 days, p = 0.0480] and the PFS of patients with gut microbiota of o_RF32 unclassified was significantly shorter (MST: 49 vs. 757 days, p = 0.0205). There were no significant differences between groups in the oral microbiota. This study revealed a strong association between gut microbiota diversity and ICI response in NSCLC patients. Moreover, specific gut microbiota compositions may influence the ICI response. These findings might be useful in identifying biomarkers to predict ICI response.