bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring dyserythropoiesis in patients with myelodysplastic syndrome by imaging flow cytometry and machine‐learning assisted morphometrics
Authors: Rosenberg Carina A. , Bill Marie , Rodrigues Matthew A. , Hauerslev Mathias , Kerndrup Gitte B. , Hokland Peter , Ludvigsen Maja 
Published: December 2020

AbstractBackgroundThe hallmark of myelodysplastic syndrome (MDS) remains dysplasia in the bone marrow (BM). However, diagnosing MDS may be challenging and subject to inter‐observer variability. Thus, there is an unmet need for novel objective, standardized and reproducible methods for evaluating dysplasia. Imaging flow cytometry (IFC) offers combined analyses of phenotypic and image‐based morphometric parameters, for example, cell size and nuclearity. Hence, we hypothesized IFC to be a useful tool in MDS diagnostics.MethodsUsing a different‐from‐normal approach, we investigated dyserythropoiesis by quantifying morphometric features in a median of 5953 erythroblasts (range: 489–68,503) from 14 MDS patients, 11 healthy donors, 6 non‐MDS controls with increased erythropoiesis, and 6 patients with cytopenia.ResultsFirst, we morphometrically confirmed normal erythroid maturation, as immunophenotypically defined erythroid precursors could be sequenced by significantly decreasing cell‐, nuclear‐ and cytoplasm area. In MDS samples, we demonstrated cell size enlargement and increased fractions of macronormoblasts in late‐stage erythroblasts (both p < .0001). Interestingly, cytopenic controls with high‐risk mutational patterns displayed highly aberrant cell size morphometrics. Furthermore, assisted by machine learning algorithms, we reliably identified and enumerated true binucleated erythroblasts at a significantly higher frequency in two out of three erythroblast maturation stages in MDS patients compared to normal BM (both p = .0001).ConclusionWe demonstrate proof‐of‐concept results of the applicability of automated IFC‐based techniques to study and quantify morphometric changes in dyserythropoietic BM cells. We propose that IFC holds great promise as a powerful and objective tool in the complex setting of MDS diagnostics with the potential for minimizing inter‐observer variability.
An arbitrary Lagrangian–Eulerian‐based finite element strategy for modeling incompressible two‐phase flows
Authors: Potghan Nilesh , Jog Chandrashekhar S. 
Published: December 2020

AbstractIn this work, we develop a numerical strategy for solving two‐phase immiscible incompressible fluid flows in a general arbitrary Lagrangian–Eulerian framework. As we use a conforming mesh moving with one of the fluids, there is no need to track or reconstruct the interface explicitly. A sharp interface, discontinuity in the fluid properties, and the jump in the pressure field are all accurately modeled using the dummy‐node technique. One of the challenges that this work addresses is to obtain a C0‐continuous approximation for the surface tension force term on the reference configuration, and to obtain its consistent linearization within the context of a Newton–Raphson strategy. It is shown by means of various numerical examples that the strategy is computationally efficient and robust, and circumvents the need for remeshing upto significantly large deformations.
Individual differences in interoceptive accuracy and prediction error in motor functional neurological disorders: ADTIstudy
Authors: Sojka Petr , Diez Ibai , Bareš Martin , Perez David L. 
Published: December 2020

AbstractIn motor functional neurological disorders (mFND), relationships between interoception (a construct of high theoretical relevance to its pathophysiology) and neuroanatomy have not been previously investigated. This study characterized white matter in mFND patients compared to healthy controls (HCs), and investigated associations between fiber bundle integrity and cardiac interoception. Voxel‐based analysis and tractography quantified fractional anisotropy (FA) in 38 mFND patients compared to 38 HCs. Secondary analyses compared functional seizures (FND‐seiz;n= 21) or functional movement disorders (n= 17) to HCs. Network lesion mapping identified gray matter origins of implicated fiber bundles. Within‐group mFND analyses investigated relationships between FA, heartbeat tracking accuracy and interoceptive trait prediction error (discrepancies between interoceptive accuracy and self‐reported bodily awareness). Results were corrected for multiple comparisons, and all findings were adjusted for depression and trait anxiety. mFND and HCs did not show any between‐group interoceptive accuracy or FA differences. However, the FND‐seiz subgroup compared to HCs showed decreased integrity in right‐lateralized tracts: extreme capsule/inferior fronto‐occipital fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, and thalamic/striatum to occipital cortex projections. These alterations originated predominantly from the right temporoparietal junction and inferior temporal gyrus. In mFND patients, individual differences in interoceptive accuracy and interoceptive trait prediction error correlated with fiber bundle integrity originating from the insula, temporoparietal junction, putamen and thalamus among other regions. In this first study investigating brain‐interoception relationships in mFND, individual differences in interoceptive accuracy and trait prediction error mapped onto multimodal integration‐related fiber bundles. Right‐lateralized limbic and associative tract disruptions distinguished FND‐seiz from HCs.
A cross‐level analysis of organizational knowledge creation: How do transformational leaders interact with their subordinates' expertise and interpersonal relationships?
Authors: Jeong Shinhee 
Published: December 2020

AbstractDrawing on organizational knowledge creation theory, this study examined the associations of organizational knowledge creation with employee expertise and quality of interpersonal relationships. It also examined the moderating roles of transformational leadership in explaining these relationships. Hierarchical linear modeling was performed to analyze multilevel data collected from 218 employees across 44 teams in diverse U.S. organizations. The study results indicated that employee expertise, quality of interpersonal relationships, and transformational leadership are positively associated with organizational knowledge creation. Unexpectedly, a negative moderating role of transformational leadership was found when explaining the relationship between organizational knowledge creation and quality of interpersonal relationships. It showed no moderating effect of transformational leadership in explaining the organizational knowledge creation and employee expertise relationship. The findings improve our understanding of organizational knowledge creation and enabling conditions and provide meaningful insights into the role of transformational leadership interacting with relationships in teams. The implications of these findings for research and practice are also discussed.
ESG investment: What do we learn from its interaction with stock, currency and commodity markets?
Authors: Andersson Emil , Hoque Mahim , Rahman Md Lutfur , Uddin Gazi Salah , Jayasekera Ranadeva 
Published: December 2020

AbstractThis paper examines ESG portfolio's causal relationship with conventional and ethical equity prices, exchange rates and commodity prices. Using multi‐scale wavelet decomposition, asset returns are decomposed into three timescales (short‐, medium‐ and long‐term), and a three‐step filtered framework is used to explore dynamic non‐linear linkages. We document significant bidirectional causal relationship between ESG, conventional and ethical equity portfolio returns. While the causality persists from the short‐ to medium‐term, it is relatively weaker in the long‐term. We further observe statistically significant causality running from ESG portfolio returns to currency and commodity returns. This causality is strongest in the short‐term, turns weaker in the medium‐term and, in some instances, disappears in the long‐term. These results are generally robust for the use of original returns and VAR‐filtered returns. However, as we control for conditional heteroskedasticity in the return series, the causality appears weaker particularly between ESG portfolio and commodity returns. Our results have important implications for planning portfolio allocation and devising hedging and diversification strategies.
Stock market development and nexus of market liquidity: The case of Fiji
Authors: Saliya Candauda Arachchige 
Published: December 2020

AbstractThe purpose of this paper is twofold: First, to explore the macroeconomic and institutional factors influencing stock market development (SMD) in Fiji during the period 1996–2018 and second, to explore the causes of the prolonged sluggish nature of the South Pacific Stock Exchange (SPX) in Fiji. A mixed‐method approach was employed: autoregressive distributed lag (ARDL) testing framework was used to estimate the influence of the structural determinants in Fiji while descriptive and narrative analysis was used to explain the status of the SPX. The study findings partially confirmed the findings of previous studies. The findings that economic growth promotes SMD while inflation is negatively correlated to SMD were consistent with previous findings. However, the finding that regulatory quality and banking sector development have negative impacts on SMD was contrary to the findings of previous studies. Many determinants, which have been shown to have significant impact on SMD in other studies, did not show any significant impact on the SPX in the Fijian context, particularly the stock market liquidity showed no correlation to SMD and not distributed normally. Exploration of the nexus of the market liquidity reveals that present regulatory conditions are not conducive for the stock market to be vibrant and suggests eliminating excessive paperwork and entry restrictions are critical, not only to attract new players to the market but also to increase trading volumes. We argue that the concentration of ownership and market disintegration resulted in the current sluggish status of the SPX.
Testing monotonicity of conditional treatment effects under regression discontinuity designs
Authors: Hsu Yu‐Chin , Shen Shu 
Published: December 2020

SummaryResearchers are often interested in the relationship between treatment effects and observed individual heterogeneity. This paper proposes the first nonparametric monotonicity test for conditional treatment effects under the popular regression discontinuity framework. The proposed test examines whether the average treatment effect or the local average treatment effect has a monotonic relationship with some of the observed individual characteristics. We show consistency and asymptotic uniform size control of the proposed test, and apply the test to study treatment effect heterogeneity in two empirical settings.
Relationship between osteoid formation and iron deposition induced by chronic cadmium exposure in ovariectomized rats
Authors: Wako Yumi , Hiratsuka Hideaki , Kurotaki Tetsurou , Tsuchitani Minoru , Umemura Takashi 
Published: December 2020

AbstractItai‐itai (Japanese, “It hurts! It hurts!”) disease (IID), a form of osteomalacia, can be induced in ovariectomized rats by long‐term administration of cadmium (Cd). This IID rat model shows severe anemia, severe nephropathy, and osteomalacia accompanied by iron (Fe) deposition at the mineralization front. We characterized the pathogenesis of Cd‐induced bone lesions by investigating the relationship between Fe deposition and osteoid tissue formation in ovariectomized rats. The rats were injected with CdCl2 (0.5 mg/kg) for 70 weeks, with or without co‐injection of erythropoietin (EPO) for varying lengths of time to elucidate whether EPO prevents and/or cures anemia, and, with the restoration from anemia, lessens the osteoid tissue formation. Necropsies were performed at 25, 50, or 70 weeks. Fe deposition at the mineralization front of bone was found at 50 weeks and increased thereafter. Animals injected with EPO showed decreased Fe deposition, although there was no relation between EPO administration and osteoid formation in the femur. Because the increase in bone lesion severity was independent of the amount of Fe deposition, we suggest that Fe deposition is not involved in the etiology of Cd‐induced femoral bone lesions.
Tendon‐like tether formation for tongue‐base advancement in an ovine model using a novel implant device intended for the surgical management of obstructive sleep apnoea
Authors: Hendricks Rushdi , Hofmann Elena , Peres Jade , Prince Sharon , Hille Jos , Davies Neil H. , Bezuidenhout Deon 
Published: December 2020

AbstractObstructive sleep apnoea (OSA) is a serious debilitating condition with significant morbidity and mortality affecting almost one billion adults globally. The current gold standard in the non‐surgical management of airway collapse is continuous positive airway pressure (CPAP). However, non‐compliance leads to a high abandon rate (27–46%). While there are multiple sites of airway obstruction during sleep, the tongue base is recognized as the key player in the pathogenesis of OSA. Poor outcomes of current tongue suspension devices are due to fracture, slippage or migration of devices. Three tongue tethering device groups, namely a polydioxanone/polyurethane combination (PDO + PU) treatment group, a PDO analytical control group, and a polypropylene (PP) descriptive control group, were implanted into 22 sheep (75–85 kg) in a two‐phased study. After implant times of 8, 16, and 32 weeks, sheep were serially euthanized to allow for explantation of their tongues and chins. The PDO + PU devices remodeled during the 32‐week implant period into a hybrid biological tendon‐like tether through the process of gradual degradation of the PDO and collagen deposition as shown by electrophoresis, histology and mechanical testing. The control PDO device degraded completely after 32 weeks and the PP devices remained intact. The hybrid biological tendon‐like tether exhibited a break‐strength of 60 N, thus exceeding the maximum force to overcome upper airway collapse.
Fabrication of bioactive novel scaffold by solid‐state reaction sintering for bone regeneration
Authors: López Erika , Viatela Yrina , Prado Miguel , Biolatti Vanesa , Bagnatto Carolina 
Published: December 2020

AbstractIn this work we present a new type of scaffold obtained by solid‐state reaction, simultaneous sintering of a mixture of precursor oxides, carbonates, and organic substances, the latter used for pore generation. Having variable local composition, exhibits excellent overall physicochemical and bioactivity response. Open porosity is about 50%–60% and its permeability 10−11 m2. X‐ray diffraction exhibits the presence of a sodium‐calcium silicate and sodium‐calcium phosphate crystalline phases. Additionally, by mechanical compression tests the range of failure stress obtained for the scaffolds was 0.3–1.1 MPa. The bioactivity and dissolution rate of the scaffolds were evaluated by in vitro tests. After 1 week soaking in simulated body fluid, the formation of a continuous hydroxyapatite layer, which does not differentiate local compositions, was observed. Our results from cell culture tests clearly indicate that during hydroxyapatite layer formation, scaffolds do not liberate any cytotoxic substances. Moreover, cells seeded in the hydroxyapatite‐covered scaffolds grew better than the control.
Targeting H3K9 methyltransferase G9a and its related molecule GLP as a potential therapeutic strategy for cancer
Authors: Rahman Ziaur , Bazaz Mohd. Rabi , Devabattula Geetanjali , Khan Mohd. Abrar , Godugu Chandraiah 
Published: December 2020

AbstractH3K9 methyltransferase (G9a) and its relevant molecule GLP are the SET domain proteins that specifically add mono, di and trimethyl groups on to the histone H3K9, which lead to the transcriptional inactivation of chromatin and reduce the expression of cancer suppressor genes, which trigger growth and progress of several cancer types. Various studies have demonstrated that overexpression of H3K9 methyltransferase G9a and GLP in different kinds of tumors, like lung, breast, bladder, colon, cervical, gastric, skin cancers, hepatocellular carcinoma and hematological malignancies. Several G9a and GLP inhibitors such as BIX‐01294, UNC0642, A‐366 and DCG066 were developed to combat various cancers; however, there is a need for more effective and less toxic compounds. The current molecular docking study suggested that the selected new compounds such as ninhydrin, naphthoquinone, cysteamine and disulfide cysteamine could be suitable molecules as a G9a and GLP inhibitors. Furthermore, detailed cell based and preclinical animal studies are required to confirm their properties. In the current review, we discussed the role of G9a and GLP mediated epigenetic regulation in the cancers. A thorough literature review was done related to G9a and GLP. The databases used extensively for retrieval of information were PubMed, Medline, Scopus and Science‐direct. Further, molecular docking was performed using Maestro Schrodinger version 9.2 software to investigate the binding profile of compounds with Human G9a HMT (PDB ID: 3FPD, 3RJW) and Human GLP MT (PDB ID: 6MBO, 6MBP).
Signal transducer and activator of transcription 3 mediates apoptosis inhibition through reducing mitochondrial ROS and activating Bcl‐2 in gemcitabine‐resistant lung cancer A549 cells
Authors: Liu Jian‐Sheng , Yeh Chun‐An , Huang I‐Chieh , Huang Guan‐Yu , Chiu Chih‐Hao , Mahalakshmi B. , Wen Su‐Ying , Huang Chih‐Yang , Kuo Wei‐Wen 
Published: December 2020

AbstractLung cancer is a leading cause of cancer‐related death worldwide. In this study, we used lung adenocarcinoma cells as a model, as lung adenocarcinoma has the highest mortality rate among all lung cancers. For the past few years, medical treatments or lung cancer have been limited because of chemotherapy resistance. Therefore, understanding the pathogenesis of the development of drug resistance in lung cancer is urgent. Gemcitabine is widely prescribed in the chemotherapeutic treatment of lung cancers. In this study, we developed gemcitabine‐resistant lung adenocarcinoma cells (A549‐GR) from the A549 cell line. The results showed that apoptotic protein expression and reactive oxygen species (ROS) generation were reduced in A549‐GR cells compared to A549 cells. Interestingly, we found that signal transducer and activator of transcription 3 (STAT3) translocated to the nucleus and mitochondria to affect the apoptotic pathway and ROS generation, respectively. Furthermore, treatment with STAT3 small interfering RNA diminished the increase in ROS production, proliferation and antiapoptotic proteins in A549‐GR cells. Taken together, the study demonstrated that STAT3 acts as an essential regulator and moderates apoptosis through two major mechanisms to induce gemcitabine resistance in cells; and these findings provide a potential target for the treatment of gemcitabine‐resistant lung cancer.
Natural history and optimal treatment strategy of intraductal papillary mucinous neoplasm of the pancreas: Analysis using a nomogram and Markov decision model
Authors: Han Youngmin , Jang Jin‐Young , Oh Moon Young , Kim Hyeong Seok , Byun Yoonhyeong , Kang Jae Seung , Kim Se Hyung , Lee Kyoung‐Bun , Kim Hongbeom , Kwon Wooil 
Published: December 2020

AbstractBackground/PurposeWith the increase in detection of intraductal papillary mucinous neoplasms (IPMN), a tailored approach is needed. This study was aimed at exploring the natural history of IPMN and suggest optimal treatment based on malignancy risk using a nomogram and Markov decision model.MethodsPatients with IPMN who underwent surveillance or surgery were included. Changes in worrisome features/high‐risk stigmata and malignancy conversion rate were assessed. Life expectancy and quality‐adjusted life year (QALY) were compared using a nomogram predicting malignancy.ResultsOverall, 2006 patients with histologically confirmed or radiologically typical IPMN were enrolled. Of these, 1773 (88.4%), 81 (4.0%), and 152 (7.6%), respectively, had branch duct (BD)‐, main duct‐, and mixed‐type IPMN at initial diagnosis. The cumulative risk of developing worrisome feature or high‐risk stigmata was 19.0% and 35.0% at 5‐ and 10‐year follow‐up, respectively. The progression of malignancy rate at 10‐year follow‐up was 79.9% for main and mixed IPMNs and 5.9% for BD‐IPMN. Nomogram‐based malignancy risk prediction is well correlated with natural history based on pathologic biopsy and shows good stratification of survival. The decision model recommends surgery to maximize survival and QALY especially in those with >35% malignancy risk.ConclusionsCompared with main duct‐ and mixed‐type IPMN, which have a high risk of malignancy (79.9%), BD‐IPMN is very indolent (5.9%). The nomogram‐based decision model suggests surgery rather than surveillance for patients with a high malignancy risk. The optimal treatment strategy between surgery and surveillance should consider patients' health status, malignancy risk, and centers' experience.
Comparison Between Diffusion‐Weighted MRI and 123I‐mIBG Uptake in Primary High‐Risk Neuroblastoma
Authors: Privitera Laura , Hales Patrick W. , Musleh Layla , Morris Elizabeth , Sizer Natalie , Barone Giuseppe , Humphries Paul , Cross Kate , Biassoni Lorenzo , Giuliani Stefano 
Published: December 2020

BackgroundHigh‐risk neuroblastoma (HR‐NB) has a variable response to preoperative chemotherapy. It is not possible to differentiate viable vs. nonviable residual tumor before surgery.PurposeTo explore the association between apparent diffusion coefficient (ADC) values from diffusion‐weighted magnetic resonance imaging (DW‐MRI), 123I‐meta‐iodobenzyl‐guanidine (123I‐mIBG) uptake, and histology before and after chemotherapy.Study TypeRetrospective.SubjectsForty patients with HR‐NB.Field Strength/Sequence1.5T axial DW‐MRI (b = 0,1000 s/mm2) and T2‐weighted sequences. 123I‐mIBG scintigraphy planar imaging (all patients), with additional 123I‐mIBG single‐photon emission computed tomography / computerized tomography (SPECT/CT) imaging (15 patients).AssessmentADC maps and 123I‐mIBG SPECT/CT images were coregistered to the T2‐weighted images. 123I‐mIBG uptake was normalized with a tumor‐to‐liver count ratio (TLCR). Regions of interest (ROIs) for primary tumor volume and different intratumor subregions were drawn. The lower quartile ADC value (ADC25prc) was used over the entire tumor volume and the overall level of 123I‐mIBG uptake was graded into avidity groups.Statistical TestsAnalysis of variance (ANOVA) and linear regression were used to compare ADC and MIBG values before and after treatment. Threshold values to classify tumors as viable/necrotic were obtained using ROC analysis of ADC and TLCR values.ResultsNo significant difference in whole‐tumor ADC25prc values were found between different 123I‐mIBG avidity groups pre‐ (P = 0.31) or postchemotherapy (P = 0.35). In the “intratumor” analysis, 5/15 patients (prechemotherapy) and 0/14 patients (postchemotherapy) showed a significant correlation between ADC and TLCR values (P < 0.05). Increased tumor shrinkage was associated with lower pretreatment tumor ADC25prc values (P < 0.001); no association was found with pretreatment 123I‐mIBG avidity (P = 0.17). Completely nonviable tumors had significantly lower postchemotherapy ADC25prc values than tumors with >10% viable tumor (P < 0.05). Both pre‐ and posttreatment TLCR values were significantly higher in patients with >50% viable tumor than those with 10–50% viable tumor (P < 0.05).Data Conclusion123I‐mIBG avidity and ADC values are complementary noninvasive biomarkers of therapeutic response in HR‐NB.Level of Evidence4.Technical Efficacy Stage3.