bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memoirs of an Academic Rōnin: Religious Studies and Mentorship in the Age of Post-Truth
Authors: Ambasciano Leonardo 
Published: November 2020

Abstract
The present article offers a selection of recollections about the author’s professional relationship with his mentor during his cursus studiorum as a graduate student and as a Ph.D. candidate. These memories are preceded by a series of critical reflections on the current state of both Religious Studies and the History of Religions, with a comparative focus on the 1960 scientific mandate of the International Association for the History of Religions (IAHR) and the UK institutional conflation of Theology and Religious Studies (TRS) through the lenses of the early and pioneering Italian experience.
Hopefully, these notes will also prompt a much-needed frank conversation on such delicate topics.
Links between Large-Scale Modes of Climate Variability and Synoptic Weather Patterns in the Southern Indian Ocean
Authors: Udy Danielle G. , Vance Tessa R. , Kiem Anthony S. , Holbrook Neil J. , Curran Mark A. J. 
Published: November 2020

AbstractWeather systems in the southern Indian Ocean (SIO) drive synoptic-scale precipitation variability in East Antarctica and southern Australia. Improved understanding of these dynamical linkages is beneficial to diagnose long-term climate changes from climate proxy records as well as informing regional weather and climate forecasts. Self-organizing maps (SOMs) are used to group daily 500-hPa geopotential height (z500; ERA-Interim) anomalies into nine regional synoptic types based on their dominant patterns over the SIO (30°–75°S, 40°–180°E) from January 1979 to October 2018. The pattern anomalies represented include four meridional, three mixed meridional–zonal, one zonal, and one transitional node. The frequency of the meridional nodes shows limited association with the phase of the southern annular mode (SAM), especially during September–November. The zonal and mixed patterns were nevertheless strongly and significantly correlated with SAM, although the regional synoptic representation of SAM+ conditions was not zonally symmetric and was represented by three separate nodes. We recommend consideration of how different synoptic conditions vary the atmospheric representation of SAM+ in any given season in the SIO. These different types of SAM+ mean a hemispheric index fails to capture the regional variability in surface weather conditions that is primarily driven by the synoptic variability rather than the absolute polarity of the SAM.
On the Correspondence between Seasonal Forecast Biases and Long-Term Climate Biases in Sea Surface Temperature
Authors: Ma Hsi-Yen , Siongco A. Cheska , Klein Stephen A. , Xie Shaocheng , Karspeck Alicia R. , Raeder Kevin , Anderson Jeffrey L. , Lee Jiwoo , Kirtman Ben P. , Merryfield William J. , Murakami Hiroyuki , Tribbia Joseph J. 
Published: November 2020

AbstractThe correspondence between mean sea surface temperature (SST) biases in retrospective seasonal forecasts (hindcasts) and long-term climate simulations from five global climate models is examined to diagnose the degree to which systematic SST biases develop on seasonal time scales. The hindcasts are from the North American Multimodel Ensemble, and the climate simulations are from the Coupled Model Intercomparison Project. The analysis suggests that most robust climatological SST biases begin to form within 6 months of a realistically initialized integration, although the growth rate varies with location, time, and model. In regions with large biases, interannual variability and ensemble spread is much smaller than the climatological bias. Additional ensemble hindcasts of the Community Earth System Model with a different initialization method suggest that initial conditions do matter for the initial bias growth, but the overall global bias patterns are similar after 6 months. A hindcast approach is more suitable to study biases over the tropics and subtropics than over the extratropics because of smaller initial biases and faster bias growth. The rapid emergence of SST biases makes it likely that fast processes with time scales shorter than the seasonal time scales in the atmosphere and upper ocean are responsible for a substantial part of the climatological SST biases. Studying the growth of biases may provide important clues to the causes and ultimately the amelioration of these biases. Further, initialized seasonal hindcasts can profitably be used in the development of high-resolution coupled ocean–atmosphere models.
Lung ultrasound assessment of acute respiratory distress syndrome caused by coronavirus disease 2019: An observational study
Authors: Li Ruiting , Liu Hong , Qi Hong , Yuan Yin , Zou Xiaojing , Huang Haiyan , Wan Jia , Lv Zheng , Ouyang Yaqi , Pan Shangwen , Zhao Xin , Shu Huaqing , Shang You 
Published: November 2020

Background:An outbreak of coronavirus disease 2019 (COVID-19) took place in Wuhan, China, by the end of 2019, and the disease continues to spread all over the world. The number of patients is increasing rapidly, a large number of infected patients is critically ill, and the mortality is high. However, information on COVID-19 patients is limited, and its clinical characteristics have not been fully studied.Objectives:To compare the performances of point-of-care lung ultrasound (LUS) and bedside chest X-ray in assessing the condition of COVID-19 patients with acute respiratory distress syndrome (ARDS).Methods:This observational study enrolled 42 COVID-19 patients with ARDS who were admitted to the Department of Critical Care Medicine of the Wuhan Union Hospital from February to April 2020. The point-of-care LUS characteristics of the COVID-19 patients with ARDS were summarized, and the performances of LUS and bedside chest X-ray in assessing the patient’s condition were compared.Results:Most of the 42 patients were elderly individuals with chronic clinical diseases. The proportion of patients older than 60 years old was 85.7%. All patients were given invasive mechanical ventilation; eight (19.0%) of them received venovenous extracorporeal membrane oxygenation support. LUS has evident advantages in detecting lung consolidation, patchy shadows, and pleural thickening, and pleural line changes in particular. The receiver operating characteristic analysis indicated that the sensitivity, Youden index, and kappa value for detecting COVID-19 patients with ARDS were higher for LUS than the chest X-ray.Conclusion:LUS has better diagnostic accuracy and sensitivity in COVID-19 patients with ARDS than the chest X-ray.
Myocardial Tissue Characterization By T2 Mapping in Thalassemia Major
Authors: Pepe Alessia , Martini Nicola , Borrello Rita , Positano Vincenzo , Pistoia Laura , Maggio Aurelio , Guerrini Giulia , Sorrentino Francesco , Paci Cristina , Visceglie Domenico , Pedrinelli Roberto , Meloni Antonella 
Published: November 2020

Introduction.The presence of iron deposits results in a significant reduction in all magnetic resonance imaging (MRI) relaxation times (T1, T2 and T2*). In the clinical setting the T2* technique is the method of choice for cardiac iron quantification and it has revolutionized the management of patients with hemoglopinopathies.
Purpose.To compare myocardial T2 against T2* in patients with thalassemia major (TM) for myocardial iron characterization.
Methods.133 TM patients (79 females, 38.4±11.3 years) enrolled in the Extension Myocardial Iron Overload in Thalassemia (eMIOT) Network were considered.
T2 and T2* images were acquired, respectively, with multi-echo fast-spin-echo and gradient-echo sequences. Global heart T2 and T2* values were obtained by averaging the values in all 16 myocardial segments.
The normal T2 range was established as mean±2 standard deviations on data acquired on 80 healthy volunteers (males: 48-56 ms and females: 50-57 ms). The lower limit of normal for global heart T2*, established on the same healthy population, was 32 ms.
Results.A significant correlation was detected between global heart T2 and T2* values (R=0.577; P&lt;0.0001) (Figure).
Out of the 113 (84.9%) patients with a normal global heart T2* value, none had a decreased global heart T2 value, while 58 (51.3%) had an increased T2 value.
Out of the 20 patents with a decreased global heart T2* value, only 10 (50%) had also a reduced T2 value. Conversely, 9 (45.0%) had a normal global heart T2 value and one (4.5) showed an increased T2 value.
The 59 patients with increased global heart T2 value were significantly older than the remaining patients (40.8±10.5 vs 36.4±11.6 years; P=0.019)
Conclusion.All patients with decreased T2 value had also a decreased T2* value and in half of the patients iron load was undetected by T2, suggesting that T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment. However, more than half of TM patients had an increased T2 value, thus may be caused by the presence of myocardial inflammation and/or edema. So, T2 mapping could reveal subclinical myocardial involvement in TM patients.
Figure

Disclosures
Pistoia: Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.
CD34+ Positive Myelodysplastic Cells with Ring Sideroblasts or SF3B1 Mutation Produce High Erythroferrone and GDF15
Authors: Horiguchi Hiroto , Kobune Masayoshi , Ono Kento , Shimoyama Saori , Fujita Chisa , Goto Akari , Ikeda Hiroshi , Iyama Satoshi 
Published: November 2020

Background. Iron absorption from gastrointestinal tract was enhanced in a subset of patients with myelodysplastic syndrome (MDS) exhibiting ineffective erythropoiesis. Duodenal iron absorption was achieved via an iron transporter divalent metal transporter (DMT)-1 and ferroportin which was downregulated by hepatic hepcidin. Recently, three erythroid regulators such as growth differentiation factor 15 (GDF15), twisted gastrulation protein homolog 1 (TWSG1) and erythroferrone (ERFE) which down regulated hepatic hepcidin production has been identified. However, it has been not yet clarified which molecules could contribute to the increased iron absorption in patients with MDS.
Materials and Methods. In the present study, we examined the expression level of GDF15, TWSG1 and ERFE mRNA during ex vivo erythroid differentiation from sodium butyrate (SB)-treated K562 and CD34+ bone marrow (BM) cells in the presence of 4 U/mL erythropoietin (EPO), 100 U/mL interleukin-3, 10 ng/mL stem cell factor, 20 ng/mL insulin-like growth factor (IGF)-1 and 500 micro g/mL iron-saturated transferrin. We further analyzed the expression level of GDF15 and ERFE by using a GEO dataset (GSE58831). GEO dataset was downloaded as a matrix by GEOquery package (Bioconductor). The numerical data of the matrix were normalized by quantile normalization using limma package. Clinical and sequencing data were downloaded from supplementary materials. Those were combined with a GEO dataset (GSE58831) before analysis.
Results. The levels of ERFE and GDF15 mRNA were dramatically increased during erythroid differentiation from SB-treated K562 and normal CD34+ cells in response to EPO in vitro. Using GEO data sets (GSE58831), the levels of ERFE and GDF15 mRNA in CD34+ cells derived from MDS patients were significantly elevated as compared with that from healthy volunteers. Importantly, the levels of ERFE and GDF15 mRNA in CD34+ cells in a subset of MDS with ring sideroblasts (RS) or SF3B1 mutation were significantly and highly elevated as compared with other subsets of MDS (GSE58831). Additionally, the supernatant derived from SB-treated K562 reduced hepcidin level in HepG2 in the presence of EPO.
Conclusion. These results suggested that productions of ERFE and GDF15 in CD34+ MDS cells with RS or SF3B1 mutation may be associated with abnormal iron metabolism via hepcidin reduction. These findings may be useful to understanding the high ferritin level in a subset of MDS patients.
Figure 1

Disclosures
Kobune: Takeda Pharmaceutical Company: Research Funding; Alexion Pharmaceuticals Inc: Research Funding; Novartis Pharma K.K.: Research Funding; ONO PHARMACEUTICAL CO., LTD: Research Funding. Ikeda:Alexion Pharmaceuticals Inc: Research Funding; Takeda Pharmaceutical Company Limited: Research Funding; Novartis Pharma K.K.: Research Funding; Sanofi K.K.: Research Funding; ONO PHARMACEUTICAL CO., LTD: Research Funding.
Frequency and Stimulation of NPM1-Specific Immune Responses By Anti-PD1 Antibodies in NPM1-Mutated AML
Authors: Greiner Jochen , Schneider Vanessa , Schrezenmeier Hubert , Wiesneth Markus , Hofmann Susanne , Götz Marlies 
Published: November 2020

Nucelophosmin1 (NPM1) is one of the most commonly mutated genes in AML, represents a distinct entity according to the WHO and is commonly associated with a favorable prognosis. We described specific immune responses against immunogenic epitopes derived from the mutational region of NPM1 in AML and specific immune responses against leukemic progenitor and stem cells (LPC/LSC). Immune responses play an increasing role in AML treatment options. However, the role of Immuncheckpoint inhibition is still controversially discussed in AML.
In this work, we investigated NPM1 specific immune responses but also responses against other leukemia associated antigens (LAA) like PRAME (P300), Wilms' Tumor 1 (WT1) and RHAMM (R3) in an extended cohort. We investigated these immune responses in LSC/LPC using colony-forming immunoassays (CFI) and ELISpots. We examine whether immuncheckpoint inhibition using the anti-programmed death 1 (anti-PD-1) antibody might increase immune responses against stem cell like cells, comparing NPM1-mutated (NPM1mut) to NPM1 wildtype (NPM1wt) patients.
In AML NPM1mut patients, specific immune responses of cytotoxic T cells against the epitope NPM1 showed a mean reduction of colonies in CFI of 27%, for P300 of 38%, for WT1 of 32% and for R3 of 42%. NPM1wt patients showed a mean reduction of colonies in CFI of for P300 of 28%, for WT1 of 28% and for R3 of 41%. Results are comparable, for NPM1mut and NPM1wt patients, there were immune responses seen in all epitopes.
When adding the anti-PD-1 antibody to CFI, in NPM1mut patients the mean additional inhibition using NPM1 as target was 47%, and for the other epitopes: P300 23%, WT1 27% and R3 26%. For NPM1WT patients, the additional inhibition with the addition of anti-PD-1 to CFI was for P300 25%, for WT1 34% and for R3 23%.
For the NPM1 epitope, 8 of 10 NPM1mut patients showed an immune response and 3/10 showed reduction in CFI of &gt; 50%. The NPM1 epitope displayed an additional reduction with anit-PD-1 in all 10 NPM1mut Patients and in 6 of 10 a reduction of &gt; 50%. Thus, especially the NPM1 specific immune responses are strong in NPM1mut patients by adding anti-PD-1.
Taken together, the anti-PD-1 antibody increases specific T cell responses of LAA-stimulated CTL and the cytotoxic effect of T cells against LPC/LSC. The effect was strongest in NPM1mut patients against the immunogenic epitope derived from the mutational region of NPM1 and even stronger when adding anti-PD-1. These data suggest there could be a NPM1 mutation directed immunotherapeutic approach using LAA-directed vaccination strategies in NPM1-mutated AML and combination with anti-PD-1 antibodies might open new application possibilities.

Disclosures
Greiner: BMS: Research Funding. Schrezenmeier:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding.
Detection of Myeloid and Clonal Expansion Related Gene Mutations By Whole-Exome Sequencing in Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Chen Fangfei , Han Bing , Li Jian 
Published: November 2020

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease presented with hemolysis, cytopenia and thrombosis. Apart from PIGA gene on hematopoietic stem cells which accounts for the glycosylphosphatidylinositol (GPI) anchor deficiency on the cell membrane, other mutations have also been detected in PNH through whole-exome sequencing (WES). However, the characteristics of mutations in patients with PNH and genes which may contribute to PNH clonal expansion have not been well defined.
Methods: Peripheral blood samples were collected from 41 patients with PNH, among them samples from 6 patients were further separated into CD59- and CD59+ fractions by CD59 magnetic beads. Gene mutations were tested by whole-exome sequencing(WES). 178 genes commonly mutated in myeloid cancer were analyzed in the sequencing results, as well as their correlation with clinical indicators. Mutated genes correlated with cell proliferation were compared between sorted CD59+ and CD59- cells.
Results: The most frequently mutated myeloid cancer-related genes were MAP3K4 and CSMD1 (12.2% respectively). Among them, RUNX1T1 mutation was found to be correlated with larger clone size, higher level of uncombined bilirubin, and lower level of hemoglobin (P&lt;0.05). No other correlation between clinical parameters and gene mutations were found. The proportion of mutations (DNMT3A、RUNX1、JAK2、JAK3、CSMD1) which have been shown to indicate poor outcome in patients with aplastic anemia decreased as PNH clone increased (p=0.026). Mutations related to cell proliferation tended to happen more frequently in CD59- fractions compared with CD59+ fractions of the same patient (P=0.062).
Conclusions: Myeloid cancer-related mutations can be detected in patients with PNH with some correlation with clinical manifestations. Larger PNH clone may "save" patients from mutation indicating poor prognosis. CD59- fractions seemed to carry more proliferation related mutations, which may contribute to PNH clonal expansion.

Disclosures
No relevant conflicts of interest to declare.
Case Reports of Treating Abdominal Necrotizing Fasciitis Wit Platelet Rich Plasma
Authors: Wang Shujun , Chen Baoan 
Published: November 2020

ObjectivePRP(platelet rich plasma) promotes wound healing by various growth factors including VEGF, TGF-β, PDGF and EGF, all those growth factors are released by activated platelets.
MethodsPRP is applied externally to the necrotizing fasciitis wound after activated with 10% calcium gluconate, then with dressing fixed. PRP is used once a day after the wound is cleaned. The wound area is measured once, wound tissue type and drainage is recorded. Granulation area and percentage are calculated.
ResultsThe case one patient underwent negative pressure drainage treatment before the treatment of PRP. The wound area was 49.41cm2, involving the entire skin layer, with little fluid exudation. The skin around the wound was dry and curving. After 6 times of PRP treatment, the wound was reduced to 15.4cm2 without exudation, and the tissue type was fresh granulation, with 100% granulation proportion. The wound was kept clean after discharge, and reduced to 1.25cm2 after 1 month without special treatment. The wound was fully healed after 2 months, and there was no wound or rupture after the follow up visit of 12 months. The case two patient underwent negative pressure drainage treatment on the wound surface. The wound area was 106.25cm2 and the depth was 1.0cm. The whole skin was involved with stealth. After 21 times of PRP treatment, the wound was reduced to 64.35cm2, and the tissue type was carrion + granulation, which accounted for 85.73%. After autologous skin graft, 100% survived, and the wound was followed up without rupture 10 months later.
ConclusionPRP is a safe and effective method for the treatment of necrotizing fasciitis and promotes wound healing through the release of various growth factors by α-particles in activated platelets. PRP provides a new and effective treatment method for the treatment of necrotizing fasciitis by creating conditions for skin graft, shortening the length of hospital stay, and even eliminating the need for skin graft treatment for some wounds.
Key words: PRP, necrotizing fasciitis, wound

Disclosures
No relevant conflicts of interest to declare.
The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients
Authors: Gui Lin , Wang Fei , Shi Jinning , Chen Baoan 
Published: November 2020

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: We retrospectively reviewed the data for 60 multiple myeloma patients who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University from August 2011 to March 2020. According to NLR、MLR、PLR, the patients were divided into the low NLR group (NLR&lt;3.61) or high NLR group (NLR≥3.61), low MLR group (MLR&lt;0.33) or high MLR group (MLR ≥0.33), low PLR group (PLR&lt; 129.78) and high PLR group (PLR ≥129.78). Overall survival time (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of onset was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin, lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR≥129.78、HGB&lt;100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR≥129.78、HGB&lt;100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis.
Key Wordsmultiple myeloma; overall survival; NLR; PLR; MLR

Disclosures
No relevant conflicts of interest to declare.