bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different doses of prucalopride in treating chronic idiopathic constipation: a meta-analysis and Bayesian analysis
Authors: Yang Tao , Wang Kaili , Cao Yibo , Wen Jianxia , Wei Shizhang , Li Haotian , Yang Xiangdong , Xiao Tianbao 
Published: February 2021

ObjectiveThis study aims to explore the incremental benefit of different doses of prucalopride in treating chronic idiopathic constipation (CIC).MethodsPubMed, EMBASE, MEDLINE, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP medicine information and Wanfang databases were comprehensively searched up to March 2020. Prospective trials with different doses of prucalopride versus placebo were selected. The frequency of spontaneous bowel movements (SBMs) per week and the treatment-emergent adverse events (TEAEs), such as headache, arrhythmia, diarrhoea, dizziness, nausea and vomiting, were first synthesised in a meta-analysis. The probability of optimal dose of prucalopride was then ranked by random-effects within Bayesian analysis.Results14 high-quality randomised controlled trials with 4328 patients were ultimately included. SBMs per week increased significantly after using 1 mg (OR: 2.40, 95% CI 1.32 to 4.37), 2 mg (OR: 2.55, 95% CI 1.93 to 3.36) and 4 mg (OR: 2.51, 95% CI 1.92 to 3.28) prucalopride. Bayesian analysis demonstrated 1 mg dose obtained the maximum SBMs per week (OR: 3.31, 95% credible interval 1.72 to 6.16, probability rank=0.70) indirectly compared with 2 mg and 4 mg doses. TEAEs were higher significantly in 2 mg (risk ratio (RR): 1.20, 95% CI 1.09 to 1.33) and 4 mg (RR: 1.14, 95% CI 1.07 to 1.22) prucalopride. The 1 mg dose did not reach statistical significance (RR: 1.17, 95% CI 0.94 to 1.44).ConclusionsThe study concludes that 1 mg dose at commencement could be safer in treating CIC and that 2 mg prucalopride could be more efficacious in terms of SBMs per week outcome receiving.PROSPERO registration numberCRD42019136679.
Protected code blue: using in situ simulation to develop a protected code blue and modify staff training protocol—experience in a large community teaching hospital during the COVID-19 pandemic
Authors: Youssef Fady A , Patel Monique , Park Hyunsoon , Patel Jay V , Leo James , Tanios Maged A 
Published: February 2021

The surge in clinical demand, shortage in personal protective equipment and high-exposure risk for healthcare workers during the COVID-19 pandemic has challenged hospital common practices and forced a reassessment of care delivery models. Code blue teams are highly specialised units that partake in life-saving situations that can jeopardise the safety of team members. There is a paucity of guidance in regards to proper infection control measures to protect the responders.This study describes a methodical approach to assessing vulnerabilities to transmission of SARS-CoV-2 within existing code blue practices, modalities to limit the number of code blue team responders and modifications to the protocol at a large community teaching hospital. The effort undertaken faced challenges due to the nature of the pandemic and the increased demand on healthcare workers. Quality improvement methods facilitated our protocol design and implementation. To this date, there has been no identified COVID-19 disease in any protected code blue (PCB) team members. We recommend that similar practices be considered and adopted widely and practised periodically.
Identifying research waste from surgical research: a protocol for assessing compliance with the IDEAL framework and recommendations
Authors: Yu Jiajie , Shan Fei , Hirst Allison , McCulloch Peter , Li Youping , Sun Xin 
Published: February 2021

IntroductionApproximately £1130 billion was invested in research worldwide in 2016, and 9.6% of this was on biomedical research. However, about 85% of biomedical research investment is wasted. The Lancet published a series to identify five categories relating to research waste and in 2014. Some categories of research waste in surgery are avoidable by complying with the Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework for it enables researchers to design, conduct and report surgical studies robustly and transparently. This review aims to examine the extent to which surgical studies adhered to the IDEAL framework and estimate the amount of overall research waste that could be avoided if compliance was improved.MethodsWe will search for potential studies published in English and between 1 January 2018 and 31 December 2018 via PubMed. Teams of paired reviewers will screen titles, abstracts and full texts independently. Two researchers will extract data from each paper. Data will be collected about general information and specialised information in each stage, and our IDEAL Compliance Appraisal tool will be used to analyse included studies. Descriptive statistics and χ2or Fisher’s exact tests for comparisons will be presented.DiscussionOur study will provide important information about whether compliance with the specific IDEAL Recommendations has reduced research waste in surgical and therapeutic device studies. And we will identify particular key aspects that are worse and need to focus on improving those in future education.
Back to simplicity: a four-marker blood cell score to quantify prognostically relevant myeloid cells in melanoma patients
Authors: Huber Veronica , Di Guardo Lorenza , Lalli Luca , Giardiello Daniele , Cova Agata , Squarcina Paola , Frati Paola , Di Giacomo Anna Maria , Pilla Lorenzo , Tazzari Marcella , Camisaschi Chiara , Arienti Flavio , Castelli Chiara , Rodolfo Monica , Beretta Valeria , Di Nicola Massimo , Maio Michele , Del Vecchio Michele , de Braud Filippo , Mariani Luigi , Rivoltini Licia 
Published: February 2021

BackgroundMyeloid-derived suppressor cells (MDSC), a cornerstone of cancer-related immunosuppression, influence response to therapy and disease outcomes in melanoma patients. Nevertheless, their quantification is far from being integrated into routine clinical practice mostly because of the complex and still evolving phenotypic signatures applied to define the cell subsets. Here, we used a multistep downsizing process to verify whether a core of few markers could be sufficient to capture the prognostic potential of myeloid cells in peripheral blood mononuclear cells (PBMC) of metastatic melanoma patients.MethodsIn baseline frozen PBMC from a total of 143 stage IIIc to IV melanoma patients, we first assessed the relevant or redundant expression of myeloid and MDSC-related markers by flow cytometry (screening set, n=23 patients). Subsequently, we applied the identified panel to the development set samples (n=59 patients undergoing first/second-line therapy) to obtain prognostic variables associated with overall survival (OS) and progression-free survival (PFS) by machine learning adaptive index modeling. Finally, the identified score was confirmed in a validation set (n=61) and compared with standard clinical prognostic factors to assess its additive value in patient prognostication.ResultsThis selection process led to the identification of what we defined myeloid index score (MIS), which is composed by four cell subsets (CD14+, CD14+HLA-DRneg, CD14+PD-L1+ and CD15+ cells), whose frequencies above cut-offs stratified melanoma patients according to progressively worse prognosis. Patients with a MIS=0, showing no over-threshold value of MIS subsets, had the best clinical outcome, with a median survival of >33.6 months, while in patients with MIS 1→3, OS deteriorated from 10.9 to 6.8 and 6.0 months as the MIS increased (p<0.0001, c-index=0.745). MIS clustered patients into risk groups also according to PFS (p<0.0001). The inverse correlation between MIS and survival was confirmed in the validation set, was independent of the type of therapy and was not interfered by clinical prognostic factors. MIS HR was remarkably superior to that of lactate dehydrogenase, tumor burden and neutrophil-to-lymphocyte ratio.ConclusionThe MIS >0 identifies melanoma patients with a more aggressive disease, thus acting as a simple blood biomarker that can help tailoring therapeutic choices in real-life oncology.
Phosphorylation of SMAD3 in immune cells predicts survival of patients with early stage non-small cell lung cancer
Authors: Marwitz Sebastian , Ballesteros-Merino Carmen , Jensen Shawn M , Reck Martin , Kugler Christian , Perner Sven , Drömann Daniel , Goldmann Torsten , Fox Bernard A 
Published: February 2021

BackgroundThe interplay of immune and cancer cells takes place in the tumor microenvironment where multiple signals are exchanged. The transforming growth factor beta (TGFB) pathway is known to be dysregulated in lung cancer and can impede an effective immune response. However, the exact mechanisms are yet to be determined. Especially which cells respond and where does this signaling take place with respect to the local microenvironment.MethodsHuman non-small cell lung cancer samples were retrospectively analyzed by multiplexed immunohistochemistry for SMAD3 phosphorylation and programmed death ligand 1 expression in different immune cells with respect to their localization within the tumor tissue. Spatial relationships were studied to examine possible cell-cell interactions and analyzed in conjunction with clinical data.ResultsTGFB pathway activation in CD3, CD8, Foxp3 and CD68 cells, as indicated by SMAD3 phosphorylation, negatively impacts overall and partially disease-free survival of patients with lung cancerindependent of histological subtype. A high frequency of Foxp3 regulatory T cells positive for SMAD3 phosphorylation in close vicinity of CD8 T cells within the tumor discriminate a rapidly progressing group of patients with lung cancer.ConclusionsTGFB pathway activation of local immune cells within the tumor microenvironment impacts survival of early stage lung cancer. This might benefit patients not eligible for targeted therapies or immune checkpoint therapy as a therapeutic option to re-activate the local immune response.
Influence of injection technique, drug formulation and tumor microenvironment on intratumoral immunotherapy delivery and efficacy
Authors: Muñoz Nina M. , Williams Malea , Dixon Katherine , Dupuis Crystal , McWatters Amanda , Avritscher Rony , Manrique Soraya Zorro , McHugh Kevin , Murthy Ravi , Tam Alda , Naing Aung , Patel Sapna P. , Leach David , Hartgerink Jeffrey D. , Young Simon , Prakash Punit , Hwu Patrick , Sheth Rahul A. 
Published: February 2021

BackgroundIntratumoral delivery of immunotherapeutics represents a compelling solution to directly address local barriers to tumor immunity. However, we have previously shown that off-target delivery is a substantial problem during intratumoral injections; this can lead to diminished drug efficacy and systemic toxicities. We have identified three variables that influence intratumoral drug delivery: injection technique, drug formulation and tumor microenvironment. The purpose of this study was to characterize the impact of modifications in each variable on intratumoral drug delivery and immunotherapy efficacy.MethodsIntratumoral injections were performed in a hybrid image-guided intervention suite with ultrasound, fluoroscopy and CT scanning capabilities in both rat and mouse syngeneic tumor models. Intratumoral drug distribution was quantified by CT volumetric imaging. The influence of varying needle design and hydrogel-based drug delivery on the immune response to a stimulator of interferon genes (STING) agonist was evaluated using flow cytometry and single cell RNA sequencing. We also evaluated the influence of tumor stiffness on drug injection distribution.ResultsVariations in needle design, specifically with the use of a multiside hole needle, led to approximately threefold improvements in intratumoral drug deposition relative to conventional end-hole needles. Likewise, delivery of a STING agonist through a multiside hole needle led to significantly increased expression of type I interferon-associated genes and ‘inflammatory’ dendritic cell gene signatures relative to end-hole STING agonist delivery. A multidomain peptide-based hydrogel embedded with a STING agonist led to substantial improvements in intratumoral deposition; however, the hydrogel was noted to generate a strong immune response against itself within the target tumor. Evaluation of tumor stroma on intratumoral drug delivery revealed that there was a greater than twofold improvement in intratumoral distribution in soft tumors (B16 melanoma) compared with firm tumors (MC38 colorectal).ConclusionsInjection technique, drug formulation and tumor stiffness play key roles in the accurate delivery of intratumoral immunotherapeutics.
Intratumoral CXCL13+CD8+T cell infiltration determines poor clinical outcomes and immunoevasive contexture in patients with clear cell renal cell carcinoma
Authors: Dai Siyuan , Zeng Han , Liu Zhaopei , Jin Kaifeng , Jiang Wenbin , Wang Zewei , Lin Zhiyuan , Xiong Ying , Wang Jiajun , Chang Yuan , Bai Qi , Xia Yu , Liu Li , Zhu Yu , Xu Le , Qu Yang , Guo Jianming , Xu Jiejie 
Published: February 2021

BackgroundChemokine (C-X-C motif) ligand 13 (CXCL13) was known as a selective chemotaxis for B cells, a product of follicular helper CD4+T cells (TFH) and a contributor to tertiary lymphoid structures (TLS). Although secretion and function of CXCL13 produced by TFHhave been deeply explored, the immune function and prognostic significance of CXCL13 secreted by CD8+T cells still remain unrevealed. This study aims to investigate the clinical merit of CXCL13+CD8+T cells in clear cell renal cell carcinoma (ccRCC).MethodsWe analyzed prognostic value and immune contexture that associated with CXCL13+CD8+T cells infiltration level in a total of 755 patients from Zhongshan Hospital cohort (n=223) and The Cancer Genome Atlas cohort (n=532). In vitro analyses were conducted on 42 samples of resected tumor tissue from Zhongshan Hospital in order to detect the immune status of CXCL13+CD8+T cells and total CD8+T cells. Immunohistochemistry (IHC) and flow cytometry were applied to characterize immune cells and portray the tumor microenvironment (TME) in ccRCC.ResultsIntratumoral CXCL13+CD8+T cells abundance was associated with inferior overall survival and disease-free survival. CXCL13+CD8+T cells possessed higher level of immune checkpoints like programmed cell-death protein 1 (PD-1), T-cell immunoglobulin mucin 3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), higher Ki-67 expression and lower tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) expression. Total CD8+T cells in high-level CXCL13+CD8+T cells infiltration subgroup exhibited elevated exhausted markers (PD-1, Tim-3, TIGIT) and descended activated markers (TNF-α, IFN-γ) without quantity variance. Furthermore, the abundance of intratumoral CXCL13+CD8+T cell was correlated with immunoevasive TME accompanied by increased T helper 2 cells, tumor-associated macrophages, Foxp3+regulatory T cells, TLS and decreased natural killer cells, GZMB+cells.ConclusionsIntratumoral CXCL13+CD8+T cells infiltration indicated inferior clinical outcome in patients with ccRCC. CXCL13+CD8+T cells possessed increased exhausted markers, decreased effector molecules and better proliferation ability. CXCL13+CD8+T cells abundance impaired total CD8+T cells’ immune function. Intratumoral CXCL13+CD8+T cells abundance was associated with immunoevasive contexture. The abundance of CXCL13+CD8+T cells was an independent prognosticator and a potential immunotherapeutic target marker for ccRCC treatment.
Prognostic comparison of atrial and ventricular functional mitral regurgitation
Authors: Okamoto Chisato , Okada Atsushi , Nishimura Kunihiro , Moriuchi Kenji , Amano Masashi , Takahama Hiroyuki , Amaki Makoto , Hasegawa Takuya , Kanzaki Hideaki , Fujita Tomoyuki , Kobayashi Junjiro , Yasuda Satoshi , Izumi Chisato 
Published: February 2021

ObjectiveAtrial functional mitral regurgitation (A-FMR) has been suggested as a new aetiology of functional MR (MR); however, its prognosis and prognostic predictors are not fully elucidated. Aim of this study was to investigate the prognosis and prognostic predictors of A-FMR in comparison with ventricular functional MR (V-FMR).MethodsThree hundred and seventy-eight consecutive patients with moderate-to-severe or severe functional MR were studied. Functional MR was classified into V-FMR (N=288) and A-FMR (N=90) depending on the alterations of left ventricle (LV) or left atrium (LA) along with clinical context and diagnosis of ischaemic heart disease or cardiomyopathy.ResultsDuring a median follow-up of 4.1 (2.0–6.7) years, all-cause mortality, cardiovascular mortality and heart failure (HF) hospitalisation occurred in 98 (26%), 81 (21%) and 177 (47%) patients, respectively, and rates of these events and the composite end point of all-cause mortality and HF hospitalisation were consistently higher in V-FMR than A-FMR (unadjusted HR 1.762 (95% CI 1.250 to 2.438), p<0.001; adjusted HR 1.654 (95% CI 1.027 to 2.664), p=0.038, for the composite end point). Further analysis showed different prognostic predictors between V-FMR and A-FMR; while age and LA volume index were independent prognostic predictors of both V-FMR and A-FMR, systolic blood pressure and B-type natriuretic peptide were also those of V-FMR, and estimated glomerular filtration rate, LV end-systolic dimension and tricuspid regurgitation were also those of A-FMR.ConclusionsThe prognosis of V-FMR was significantly worse than that of A-FMR, and prognostic predictors were different between V-FMR and A-FMR. Our study suggests the importance of discriminating A-FMR and V-FMR, and that different treatment strategies may be considered for each aetiology.
Characterization of altered mafic and ultramafic rocks using portable XRF geochemistry and portable Vis-NIR spectrometry
Authors: Adams Cameron , Dentith Michael , Fiorentini Marco 
Published: February 2021

The accurate characterization of mafic and ultramafic rocks is a challenging but necessary task given the spatial and genetic relationship of mineralization with specific lithologies (e.g. komatiite hosted nickel-sulfides preferentially associated with cumulate-rich ultramafic rocks). Rock classification is further complicated as most mafic and ultramafic rocks have undergone varying degrees of alteration. The accuracy and reproducibility of characterization can be significantly improved by using portable energy dispersive X-ray fluorescence (pXRF) chemical data with portable visible and near-infrared (pVis-NIR) mineralogical data.
A new workflow using pXRF and pVis-NIR is presented and used to reliably characterize mafic and ultramafic rocks from the Yilgarn Craton, Western Australia. The workflow involves six steps:

(1)
Mitigate and identify compound processing and closure issues.
For example, we used a pXRF with helium flush to reliably and rapidly measure light elements and mitigate closure, i.e. problems related to data failing to sum to 100%.

(2)
Identify and exclude geochemically heterogeneous samples.
Heterogeneity may be unrelated to alteration and caused by veining or small-scale structure interleaving of different rock types. Geochemical heterogeneity was evaluated using skewness and kurtosis of SiO
2
data.

(3)
Relate rocks from similar magmatic, weathering and alteration events.
This was achieved by interpreting data grouping of Vis-NIR ferric and ferrous iron data via a 852 nm/982 nm reflectance v. 651 nm/982 nm reflectance plot and the ferrous abundance index. Unrepresentative data were omitted.

(4)
Correct XRF iron data, and characterize lithology and alteration.
Values ascribed to regions in the TAS (total alkali silica) diagram were used to approximate FeO and Fe
2
O
3
. Subsequently, geochemical indices (e.g. Mg#) were used to characterize the alteration box plot.

(5)
Characterize fractionation in detail.
Fractionation variation diagrams were used to interpret fractionation, e.g. MgO v. Al
2
O
3
, Ca/Al v. Al
2
O
3
, Ni/Cr v. Ni/Ti, and MgO v. Cr.

(6)
Identify and quantify talc alteration and serpentinization.
This included the use of a new alteration plot (Mg# v. 1410 nm
RAD
/Albedo) to estimate serpentinization and identify relationships between serpentine, carbonate, chlorite and talc abundances.

The results and observations contained in this contribution have important implications for progressive technologies such as core logging platforms that are equipped with pXRF and pVis-NIR instruments.
Ultramafic mantle xenoliths in the Late Cenozoic volcanic rocks of the Antarctic Peninsula and Jones Mountains, West Antarctica
Authors: Leat Philip T. , Ross Aidan J. , Gibson Sally A. 
Published: February 2021

Abstract
Abundant mantle-derived ultramafic xenoliths occur in Cenozoic (7.7–1.5 Ma) mafic alkaline volcanic rocks along the former active margin of West Antarctica, that extends from the northern Antarctic Peninsula to Jones Mountains. The xenoliths are restricted to post-subduction volcanic rocks that were emplaced in fore-arc or back-arc positions relative to the Mesozoic–Cenozoic Antarctic Peninsula volcanic arc. The xenoliths are spinel-bearing, include harzburgites, lherzolites, wehrlites and pyroxenites, and provide the only direct evidence of the composition of the lithospheric mantle underlying most of the margin. The harzburgites may be residues of melt extraction from the upper mantle (in a mid-ocean ridge type setting), that accreted to form oceanic lithosphere, which was then subsequently tectonically emplaced along the active Gondwana margin. An exposed highly depleted dunite–serpentinite upper mantle complex on Gibbs Island, South Shetland Islands, supports this interpretation. In contrast, pyroxenites, wehrlites and lherzolites reflect percolation of mafic alkaline melts through the lithospheric mantle. Volatile and incompatible trace element compositions imply that these interacting melts were related to the post-subduction magmatism which hosts the xenoliths. The scattered distribution of such magmatism and the history of accretion suggest that the dominant composition of sub-Antarctic Peninsula lithospheric mantle is likely to be harzburgitic.