bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytical Protocols for Phobos Regolith Samples Returned by the Martian Moons Exploration (MMX) Mission
Authors: Fujiya Wataru , Furukawa Yoshihiro , Sugahara Haruna , Koike Mizuho , Bajo Ken-ichi , Chabot Nancy L. , Miura Yayoi N. , Moynier Frederic , Russell Sara S. , Tachibana Shogo , Takano Yoshinori , Usui Tomohiro , Zolensky Michael E. 
Published: December 2020

Abstract
Japan Aerospace Exploration Agency (JAXA) will launch a spacecraft in 2024 for a sample return mission from Phobos (Martian Moons eXploration: MMX). Touchdown operations are planned to be performed twice at different landing sites on the Phobos surface to collect >10 g of the Phobos surface materials with coring and pneumatic sampling systems on board. The Sample Analysis Working Team (SAWT) of MMX is now designing analytical protocols of the returned Phobos samples to shed light on the origin of the Martian moons as well as the evolution of the Mars-moon system. Observations of petrology and mineralogy, and measurements of bulk chemical compositions and stable isotopic ratios of, e.g., O, Cr, and Ti can provide crucial information about the origin of Phobos. If Phobos is a captured asteroid composed of primitive chondritic materials, as inferred from its reflectance spectra, the nature of organic matter as well as bulk H, N, and Zn isotopic compositions characterize the volatile materials in the samples and constrain the type of the captured asteroid. Cosmogenic and solar wind components, most pronounced in noble gas isotopic compositions, can reveal surface processes on Phobos. Long- and short-lived radionuclide chronometry such as 53Mn-53Cr and 87Rb-87Sr systematics can date pivotal events like impacts, thermal metamorphism, and aqueous alteration on Phobos. It should be noted that the Phobos regolith is expected to contain a small amount of materials delivered from Mars, which may be physically and chemically different from any Martian meteorites in our collection and thus are particularly precious. The analysis plan will be designed to detect such Martian materials, if any, from the returned samples dominated by the Phobos building blocks in curation procedures at JAXA before they are processed for further analyses.
Combined Detection of Circulating Tumor Cells, α-fetoprotein Heterogene-3 and α-fetoprotein in the Early Diagnosis of HCC for the Prediction of Efficacy, Prognosis, Recurrence after Microwave Ablation
Authors: Zhou Jian , Zhu Yue , Li Yi , Liu Kun , He Fei , Xu Sihuan , Li Xin , Li Li , Hu Junfang , Liu Yan 
Published: December 2020

Abstract
Background: Early diagnosis can significantly improve treatment outcomes for HCC patients. Microwave ablation (MWA) is an important treatment for HCC, there's a lack of specific tests for prognosis. This study investigated the predictive value of combined of AFP, AFP-L3, CTCs. Methods: 143 HCC patients as research subjects (HCC group), 102 liver cirrhosis patients as liver cirrhosis group, 127 hepatitis patients as hepatitis group, 110 healthy outpatients as normal control group. The levels of AFP, AFP-L3 and CTCs were detected, and ROC curve was used to analyze the clinical value of the detection with single and combined indicators in HCC diagnosis. Results: Compared with cirrhosis group, hepatitis group and normal control group, the levels of AFP, AFP-L3, CTCs in HCC group were significantly higher. AFP, AFP-L3, CTCs of patients in non-recurrent group, CR+PR group and OS>3 group were significantly lower than the recurrent group, SD+PD group, OS<3 years group. Conclusion: Combined detection of AFP, AFP-L3, CTCs can effectively make up for the shortcomings of the detection with single and pairwise indicators. It can’t only diagnose HCC in early, but also has a high clinical value in predicting the short-term efficacy, prognosis and recurrence of HCC patients after MWA treatment.
SRT2183 and SRT1720, but not Resveratrol, Inhibit Osteoclast Formation and Resorption in the Presence or Absence of Sirt1
Authors: Thiyagarajan Ramkumar , Rodríguez-Gonzalez Maria , Zaw Catherine , Seldeen Kenneth Ladd , Hernandez Mireya , Pang Manhui , Troen Bruce Robert 
Published: December 2020

Abstract
Background: Osteoclastic bone resorption markedly increases with aging, leading to osteoporosis characterized by weak and fragile bones. Mice exhibit greater bone resorption and poor bone mass when Sirt1 is removed from their osteoclasts. Here we investigated the ex vivo impacts of putative Sirt1 activators, resveratrol (RSV), SRT2183 and SRT1720, on osteoclast formation and activity in primary mouse bone marrow cells (BMCs) derived from wild type (WT) and osteoclast specific Sirt1 knockout (OC-Sirt1KO) mice and in the RAW264.7 mouse macrophage cell line. Results: We found that SRT2183 and SRT1720 inhibit formation of osteoclasts and actin belts in both BMCs and RAW264.7 cells, whereas RSV does not. We also observed that the OC-Sirt1KO mice exhibited less bone mineral density, and the BMCs harvested from these mice yielded more osteoclasts than BMCs harvested from littermate controls. Interestingly, both SRT2183 and SRT1720 reduced osteoclast and actin belt formation in BMCs from OC-Sirt1KO mice. SRT2183 and SRT1720 also significantly disrupted actin belts of mature osteoclasts from WT mice BMCs, within 3 and 6 hours of administration. Furthermore, these compounds inhibited resorption activity of mature osteoclasts, while RSV did not. Conclusion: Our findings suggest SRT2183 and SRT1720 impede bone resorption by disrupting actin belts of mature osteoclasts, inhibit actin belt formation, and inhibit osteoclastogenesis even in the absence of Sirt1. Thus, further understanding the mechanism of action of these compounds may pave the way for potential new therapies in alleviating osteoporosis associated bone loss.
As a Newly-Discovered Component in Tumor Microenvironment RUFY4 Participates in Regulation of T cell via Cytokine-Interaction and Predicts Prognosis and Immunotherapy Responsiveness of Clear Cell Renal Carcinoma Patients
Authors: Miao Daojia , Shi Jian , Xiong Zhiyong , Yuan Changfei , Xiao Wen , Meng Xiangui , Chen Zhixian , Lv Qingyang , Xie Kairu , Yang Hongmei , Zhang Xiao-ping 
Published: December 2020

Abstract
Background: clear cell renal cell carcinoma (ccRCC) is one of the most lethal kinds of malignancies in urinary system and the existing immunotherapy have not achieved satisfactory outcomes. Therefore, this study aims to establish a brand-new gene signature for immune-infiltration and clinical outcome (overall survival and immunotherapy responsiveness) of patients with ccRCC. Methods: Based on RNA sequencing data and clinical information in the Cancer Genome Atlas Project (TCGA) database, we investigated proportions of immune cells in 611 samples by an online tool CIBERSORTx. Multivariate survival analysis was used to determine crucial survival-associated immune cells and immune-infiltration-related genes (IIRGs). Next ROC analysis was carried on to evaluate the ability of IIRGs to distinguish patients and functional enrichment analysis were implemented to explore potential interaction network between immune cells and IIRGs. Results: T cells follicular helper (TFHs) and T cells regulatory (Tregs) were highly infiltrated in the tumor microenvironment and their abundance ratios were independent prognostic factors for overall survival. Among IIRGs of TFHs and TREGs, RUFY4 was found to be highly activated in tumor microenvironment and its co-expression network was enriched in regulation of T cells via cytokine-cytokine receptor interactions.Conclusion: These two cells and RUFY4, considered prognostic biomarkers and immunotherapeutic predictors of ccRCC patients, might also simultaneously affect the regulatory network in tumor microenvironment (TME) through cytokine interactions.
Development and Testing of Relative Risk-Based Health Messages for Electronic Cigarette Products
Authors: Kimber Catherine , Cox Sharon , Frings Daniel , Albery Ian P. , Dawkins Lynne 
Published: December 2020

Abstract
Background: Health messages on e-cigarette packs emphasise nicotine addiction or harms using similar wording to warnings on cigarette packs. These may not be appropriate for e-cigarettes which constitute a reduced risk alternative for smokers. This research aimed to i) develop and test a selection of relative risk messages for e-cigarette products; ii) compare these to the two current EU Tobacco Products Directive (TPD) nicotine addiction messages; and iii) explore differences between smokers, non-smokers and dual users. Method: Twenty-six messages focusing on either harm-reduction or cessation were developed and rated by multidisciplinary experts for accuracy, persuasiveness and clarity. The eight highest ranking messages were compared alongside the TPD messages in a sample of 983 European residents (316 smokers, 327 non-smokers, 340 dual users) on understandability, believability and convincingness. Results: On all three constructs combined, the two TPD messages rated the highest, closely followed by four relative risk messages “Completely switching to e-cigarettes lowers your risk of smoking related diseases”, “Use of this product is much less harmful than smoking”, “Completely switching to e-cigarettes is a healthier alternative to smoking”, and “This product presents substantially lower risks to health than cigarettes” which did not differ statistically from the TPD messages. Non-smokers rated TPD1 significantly higher overall than dual users. Dual users rated “This product is a safer alternative to smoking” significantly higher than non-smokers. Messages did not differ on understandability. Conclusions: These alternative messages provide a useful resource for future research and for policy makers considering updating e-cigarette product labelling.
A Novel Staging System and Clinical Predictive Nomogram for More Accurate Staging and Prognosis of Malignant Pancreatic Intraductal Papillary Mucinous Neoplasms: A Population-Based Study
Authors: Zhang Haoxiang , Gao Chenggang , Chen Jiaoshun , Wu Shihong , Bai Jianwei , Yin Tao 
Published: December 2020

Abstract
Background: The current guidelines of the American Joint Committee on Cancer (AJCC) for the staging of exocrine pancreatic tumors seem inapplicable to malignant pancreatic intraductal papillary mucinous neoplasms (IPMN). Therefore, we aimed to improve the accuracy of clinical staging and prognosis for malignant IPMN.Methods: We extracted data of 2001 patients with malignant IPMN from the Surveillance, Epidemiology, and End Results database between 2000 and 2016. Of these, 1401 patients were assigned to the primary cohort and 600 patients to the validation cohort.Results: In Kaplan-Meier analysis of the primary cohort, the current AJCC guidelines were unable to distinguish between certain tumor substages (IA and IB in the 7th, IB and IIA in the 8th). The modified system we regrouped based on the median overall survival and hazard ratios was superior in tumor stage classifications. Age > 70 years, tumors located in the body or tail, high-grade differentiated tumors, surgery, chemotherapy, and TNM stage were identified as independent predictive factors of overall survival. Compared to that of TNM-based systems, the concordance index of the clinical predictive nomogram significantly improved (0.819; 95% confidence interval, 0.805–0.833), with excellent area under the receiver operating characteristic curves (1-, 3-, and 5-year: 0.881, 0.889, and 0.879, respectively). The calibration curves also showed good agreement between prediction and actual observation. In the analysis of treatment modalities, surgery resulted in better survival for all resectable IPMN. Chemotherapy is the treatment of choice for locally advanced or distant metastases patients.Conclusion: Our modified staging system improves the distinction of tumor stages. The nomogram was a more accurate and clinically reliable tool in prognosis prediction of patients with IPMN.
Prediction of Differentially Expressed miRNAs as Potential Biomarkers for Aniridia-Associated Keratopathy based on Expression Profile Analyses
Authors: Zhang Daowei , Zhang Shenghai 
Published: December 2020

Abstract
Background: Aniridia is a rare hereditary disorder that affects most structures of the eyes. This autosomal dominant disorder is caused by haploinsufficiency of Pax6, a critical gene for proper development of the eye. This study attempted to identify novel diagnostic differentially expressed miRNAs and related mRNAs to develop a deeper understanding of the molecular mechanisms and to provide new ideas for the diagnosis and treatment of aniridia-associated keratopathy (AAK). Methods: The miRNA and mRNA expression data were downloaded from GEO for differential expression analysis. R programs, WGCNA, and miRNA targets were used to identify differentially expressed genes (DEGs). The R package was used to screen candidate miRNAs as potential biomarkers, and predicted targets and DEG intersections were determined. A regulatory network between optimal differentially expressed miRNA and DEGs was then constructed. Function analysis and pathway enrichment of miRNA and mRNA were both performed. In addition, transcription factors (TFs) of differential miRNAs and molecular compounds that may be efficient were predicted.Results: We used three methods to identify DEGs: 509 differential genes were screened by R, 1522 by WGCNA, and 732 by prediction of different miRNA targets. In total, 18 DEGs were found, encompassing 9 upregulated genes and 9 downregulated genes. Eight differentially expressed miRNAs were identified using the R package: five were upregulated and three were downregulated. Among them, three miRNAs (miR-204-5p, miR-224-5p, and miR-30a-5p) were considered optimal potential biomarkers, and their regulatory network with DEGs was created by Cytoscape. IL-4-mediated signaling events were the most enriched signaling pathways. Based on these DEGs, CHL1 and SOCS3 were most closely associated with clinical characteristics, which related to sex and stage separately.Conclusions: This study identified novel diagnostic differentially expressed miRNAs and related mRNAs by developing a deeper understanding of the molecular mechanisms, based on that we provided new ideas for the diagnosis and treatment of AAK.
Slope Analysis for the Prediction of Fluid Responsiveness by a Stepwise PEEP Elevation Recruitment Maneuver in Mechanically Ventilated Patients
Authors: VALLIER Sylvain , BOUCHET Jean-Baptiste , DESEBBE Olivier , FRANCOU Camille , RAPHAEL Darren , MOLLIEX Serge , GERGELE Laurent , MOREL Jerome 
Published: December 2020

Abstract
Objective:Assessment of fluid responsiveness is problematic in intensive care unit patients. Lung recruitment maneuvers (LRM) can be used as a functional test to predict fluid responsiveness. We propose a new test to predict fluid responsiveness in mechanically ventilated patients, analyzing the variations of central venous pressure (CVP) and systemic arterial parameters during a prolonged sigh breath LRM without the use of a cardiac output measuring device. Design:Prospective observational cohort study.Setting:Intensive Care Unit, Saint-Etienne University Central Hospital.Patients:Patients under mechanical ventilation, equipped with invasive arterial blood pressure, CVP, pulse contour analysis (PICCOTM), requiring volume expansion, with no right ventricular dysfunction.Interventions:None.Measurements and Main Results:CVP, systemic arterial parameters and stroke volume (SV) were recorded during prolonged LRM followed by a 500mL fluid expansion to asses fluid responsiveness. 25 patients were screened, 18 patients were analyzed. 9 patients were responders to volume expansion and 9 were not. Evaluation of hemodynamics parameters suggested the use of a linear interpolation model. Slopes for systolic aortic pressure, pulse pressure (PP), CVP and SV were all significantly different between responders and non-responders during pressure increase phase of LRM (STEP-UP) (p = 0.022, p = 0.014, p= 0.006 and p = 0.038, respectively). PP and CVP slopes during STEP-UP were strongly predictive of fluid responsiveness with an AUC of 0.926 (95% CI, 0.78 to 1.00), sensitivity = 100%, specificity = 89% and an AUC = 0.901 (95% CI, 0.76 to 1.00), sensibility = 78%, specificity = 100%, respectively. Combining sensitivity of PP and specificity of CVP, fluid responsiveness prediction can be obtained with 100% sensibility and 100% specificity (AUC=0.96; 95% CI, 0.90 to 1.00). 1 patient presented inconclusive values using the grey zone approach (5.5%).Conclusions:In patients under mechanical ventilation with no right cardiac dysfunction, the association of PP and CVP slope analysis during a prolonged sigh breath lung recruitment maneuver seems to offer a very promising method for fluid responsiveness prediction without the use and cost of a cardiac output measurement device.Trial registration: NCT04304521, IRBN902018/CHUSTERegistered 11 March 2020, Fluid responsiveness predicted by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients (STEP-PEEP)https://www.clinicaltrials.gov/ct2/show/NCT04304521?term=NCT04304521&cntry=FR&draw=2&rank=1
Prognostic Value of Muscle Mass Measured via Brain Computed Tomography in Neurocritically Ill Patients
Authors: Lee Yun Im , Ko Ryoung-Eun , Ahn Joonghyun , Carriere Keumhee C. , Ryu Jeong-Am 
Published: December 2020

Abstract
Background

To investigate whether skeletal muscle mass estimated via brain computed tomography (CT) can be used to predict neurological outcomes in neurocritically ill patients.
Methods

This is a retrospective, observational study. Adult patients who were admitted to the neurosurgical intensive care unit (ICU) in tertiary hospital from January 2010 to September 2019 were eligible. We included patients who were hospitalized in the neurosurgical ICU for more than 7 days. Cross-sectional areas of paravertebral muscle at the first cervical vertebra level (C1-CSA) and temporalis muscle thickness (TMT) on brain CT were measured to evaluate skeletal muscle mass. Primary outcome was Glasgow Outcome Scale score at 3 months.
Results

Among 189 patients, 167 (88.4%) survived until discharge from the hospital. Of these survivors, 81 (42.9%) patients had favorable neurologic outcomes. Initial TMT values and follow-up TMT values were higher in patients with favorable neurologic outcome compared to those with poor neurological outcome (p = 0.003 and p = 0.001, respectively). Initial the C1-CSA/body surface area was greater in patients with poor neurological outcome than in those with favorable outcome (p = 0.029). In multivariable analysis, age (adjusted odds ratio [OR]: 2.05, 95% confidence interval [CI]: 1.543–2.724), BMI (adjusted OR: 0.74, 95% CI: 0.638–0.849), use of mannitol (adjusted OR: 27.45, 95% CI: 4.833–155.860), change of C1-CSA (adjusted OR: 1.36, 95% CI: 1.054–1.761), and change of TMT (adjusted OR: 1.27, 95% CI: 1.028–1.576) were significantly associated with poor neurological outcome (Hosmer–Lemeshow test, Chi-square = 11.4, df = 8, p = 0.178) with the areas under curve of 0.803 (95% CI 0.740–0.866) using 10-fold cross validation method. Especially, the risk of poor neurologic outcome was proportional to changes of C1-CSA and TMT.
Conclusions

In this study, the follow-up skeletal muscle mass at first week from ICU admission, based on changes in C1-CSA and TMT, was associated with neurological prognosis in neurocritically ill patients. Eventually, brain CT-measured sarcopenia may be helpful in predicting poor neurological outcomes in these patients.
A machine-learning approach for dynamic prediction of sepsis-induced coagulopathy in critically ill patients with sepsis: an integrated analysis of the MIMIC-IV and eICU-CRD databases
Authors: Zhao Qin-Yu , Liu Le-Ping , Luo Jing-Chao , Luo Yan-Wei , Wang Huan , Zhang Yi-Jie , Gui Rong , Tu Guo-Wei , Luo Zhe 
Published: December 2020

Abstract
Background

Sepsis-induced coagulopathy (SIC) denotes an increased mortality rate and poorer prognosis in septic patients.
Methods

Machine-learning models were developed based on septic patients who were older than 18 years and stayed in intensive care units (ICUs) for more than 24 hours in Medical Information Mart for Intensive Care (MIMIC)-IV. Eighty-eight potential predictors were extracted, and 15 various machine-learning models assessed the daily risk of SIC. The most potent model was selected based on its accuracy and Area Under the receiver operating characteristic Curve (AUC), followed by fine-grained hyperparameter adjustment using the Bayesian Optimization Algorithm. The effects of features on prediction scores were measured using the SHapley Additive exPlanations (SHAP) values. A compact model was developed, based on 15 features selected according to their importance and clinical availability. Two models were compared with Logistic Regression and SIC scores in terms of SIC prediction. Additionally, an external validation was performed in the eICU Collaborative Research Database (eICU-CRD).
Results

Of 11362 patients in MIMIC-IV included in the final cohort, a total of 6744 (59%) patients had SIC during sepsis, and 16183 samples were extracted. The model named Categorical Boosting (CatBoost) had the greatest AUC in our study (0.869 [0.850, 0.886]). Coagulation profile and renal function indicators are the most important features to predict SIC. A compact model was developed with the AUC of 0.854 [0.832, 0.872], while the AUCs of Logistic Regression and SIC scores were 0.746 [0.735, 0.755] and 0.709 [0.687, 0.733], respectively. A cohort of 35252 septic patients in eICU-CRD was analyzed. The AUCs of the full and the compact models in external validation were 0.842 [0.837, 0.846] and 0.803 [0.798, 0.809], respectively, which were still larger than those of Logistic Regression (0.660 [0.653, 0.667]) and SIC scores (0.752 [0.747, 0.757]). Prediction results can be illustrated by using SHAP values in the instance level, which makes our models clinically interpretable.
Conclusions

We developed two models which were able to dynamically predict the risk of SIC in septic patients better than conventional Logistic Regression and SIC scores. Prediction results of our two models can be interpreted by using SHAP values.