bluuebunny/crossref_metadata_2025 huggingface dataset:
Trajectory Tracking of Underactuated Unmanned Surface Vessels: Non-Singular Terminal Sliding Control with Nonlinear Disturbance Observer
Authors: Xu Donghao , Liu Zipeng , Zhou Xueqian , Yang Liu , Huang Ling
Published: March 2022

An underactuated unmanned surface vessel (USV) is a nonholonomic system, in which trajectory tracking is a challenging problem that has drawn more and more attention from researchers recently. The control of trajectory tracking is of critical importance since it determines whether the task can be carried out successfully. In this paper, a non-singular terminal sliding model (NTSM) controller is proposed for the trajectory tracking control of the underactuated USV, with a nonlinear disturbance observer which is designed to measure complex environmental disturbances such as wind, waves, and currents. Exploratory simulations were carried out and the results show that the proposed controller is effective and robust for the trajectory tracking of underactuated USVs in the presence of environmental disturbances.
Neutron Activation Analysis of PM10 for Air Quality of an Industrial Region in the Czech Republic: A Case Study
Authors: Niedobová Barbora , Badawy Wael M. , Dmitriev Andrey Yu. , Jančík Petr , Chepurchenko Olica E. , Bulavin Maksim V. , Belova Maria O.
Published: March 2022

This work was conducted to focus on pollutant transmission between Poland and Czechia at the most polluted area in the Czech Republic, the Moravian Silesian region. Instrumental neutron activation analysis (INAA) and multivariate statistical analyses were used to determine the mass fractions of inorganic air pollutants accumulated on filters. Particle matters of sizes smaller than 10 µm (PM10) were collected using a high-volume sampler (SAM Hi 30 AUTO WIND). Pollutants PM10 were collected on Whatman QM-A Quartz Microfiber Filters of 150 mm in diameter based on various wind conditions. These filters were irradiated by neutron flux at the experimental reactor IBR-2 at the Joint Institute of Nuclear Research in Dubna, RF. Irradiated samples were measured by gamma spectrometry techniques using HPGe detectors. In total, results are shown for 49 samples (from March to July 2021) and five field blank filters. The mass fractions of 24 elements (Sc, Cr, Fe, Ni, Co, Zn, Se, As, Br, Rb, Mo, Sb, Ba, Cs, La, Ce, Sm, Eu, Tb, Yb, Hf, Au, Th, and U) were determined. The sources of pollution were specified using correlation and exploratory factor analyses and including meteorological conditions. A strong positive correlation was shown between the elements Cr, As, Br, Co, Fe, Sc, Se, Sm, Th, La, and Ce. Elemental exposure to PM10 can be divided based on the factor loadings of common chemical components into three main pollution sources. According to the wind rose, the pollution came from the southeast/west direction; therefore, we can assume that the pollution most likely originated from the metallurgic complex (steel and iron production in the southeast, and a coking plant, metal foundry, and generation plant in the west).
Meniscus Matrix Structural and Biomechanical Evaluation: Age-Dependent Properties in a Swine Model
Authors: Aidos Lucia , Modina Silvia Clotilde , Millar Valentina Rafaela Herrera , Peretti Giuseppe Maria , Mangiavini Laura , Ferroni Marco , Boschetti Federica , Di Giancamillo Alessia
Published: March 2022

The analysis of the morphological, structural, biochemical, and mechanical changes of the Extracellular Matrix (ECM), which occur during meniscus development, represents the goal of the present study. Medial fully developed menisci (FD, 9-month-old pigs), partially developed menisci (PD, 1-month-old piglets), and not developed menisci (ND, from stillbirths) were collected. Cellularity and glycosaminoglycans (GAGs) deposition were evaluated by ELISA, while Collagen 1 and aggrecan were investigated by immunohistochemistry and Western blot analyses in order to be compared to the biomechanical properties of traction and compression tensile forces, respectively. Cellularity decreased from ND to FD and GAGs showed the opposite trend (p < 0.01 both). Collagen 1 decreased from ND to FD, as well as the ability to resist to tensile traction forces (p < 0.01), while aggrecan showed the opposite trend, in accordance with the biomechanics: compression test showed that FD meniscus greatly resists to deformation (p < 0.01). This study demonstrated that in swine meniscus, clear morphological and biomechanical changes follow the meniscal maturation and specialization during growth, starting with an immature pattern (ND) to the mature organized meniscus of the FD, and they could be useful to understand the behavior of this structure in the light of its tissue bioengineering.
Correction: Tan et al. A Systematic Review of the Effects of Caffeine on Basketball Performance Outcomes. Biology 2022, 11, 17
Authors: Tan Zhi Sen , Sim Alexiaa , Kawabata Masato , Burns Stephen F.
Published: March 2022

The authors wish to make a correction to the published version of the paper [...]
Histamine Intolerance—A Kind of Pseudoallergic Reaction
Authors: Zhao Ying , Zhang Xiaoyan , Jin Hengxi , Chen Lu , Ji Jiang , Zhang Zhongwei
Published: March 2022

Histamine intolerance (HIT) is a common disorder associated with impaired histamine metabolism. Notwithstanding, it is often misdiagnosed as other diseases because of its lack of specific clinical manifestations. HIT did not gain traction until the early 21st century. In this review, we will focus on the latest research and elaborate on the clinical manifestations of HIT, including its manifestations in special populations such as atopic dermatitis (AD) and chronic urticaria (CU), as well as the latest understanding of its etiology and pathogenesis. In addition, we will explore the latest treatment strategies for HIT and the treatment of specific cases.
The Vasoactive Effect of Perivascular Adipose Tissue and Hydrogen Sulfide in Thoracic Aortas of Normotensive and Spontaneously Hypertensive Rats
Authors: Golas Samuel , Berenyiova Andrea , Majzunova Miroslava , Drobna Magdalena , Tuorkey Muobarak J. , Cacanyiova Sona
Published: March 2022

The objective of this study was to investigate the vasoregulatory role of perivascular adipose tissue (PVAT) and its mutual interaction with endogenous and exogenous H2S in the thoracic aorta (TA) of adult normotensive Wistar rats and spontaneously hypertensive rats (SHRs). In SHRs, hypertension was associated with cardiac hypertrophy and increased contractility. Regardless of the strain, PVAT revealed an anticontractile effect; however, PVAT worsened endothelial-dependent vasorelaxation. Since H2S produced by both the vascular wall and PVAT had a pro-contractile effect in SHRs, H2S decreased the sensitivity of adrenergic receptors to noradrenaline in Wistar rats. While H2S had no contribution to endothelium-dependent relaxation in Wistar rats, in SHRs, H2S produced by the vascular wall had a pro-relaxant effect. We observed a larger vasorelaxation induced by exogenous H2S donor in SHRs than in Wistar rats. Additionally, in the presence of PVAT, this effect was potentiated. We demonstrated that PVAT of the TA aggravated endothelial function in SHRs. However, H2S produced by the TA vascular wall had a pro-relaxation effect, and PVAT revealed anti-contractile activity mediated by the release of an unknown factor and potentiated the vasorelaxation induced by exogenous H2S. All these actions could represent a form of compensatory mechanism to balance impaired vascular tone regulation.
The Limits between Schizophrenia and Bipolar Disorder: What Do Magnetic Resonance Findings Tell Us?
Authors: Dobri Mirona Letitia , Diaz Alexandre Paim , Selvaraj Sudhakar , Quevedo Joao , Walss-Bass Consuelo , Soares Jair C. , Sanches Marsal
Published: March 2022

Schizophrenia and bipolar disorder, two of the most severe psychiatric illnesses, have historically been regarded as dichotomous entities but share many features of the premorbid course, clinical profile, genetic factors and treatment approaches. Studies focusing on neuroimaging findings have received considerable attention, as they plead for an improved understanding of the brain regions involved in the pathophysiology of schizophrenia and bipolar disorder. In this review, we summarize the main magnetic resonance imaging findings in both disorders, aiming at exploring the neuroanatomical and functional similarities and differences between the two. The findings show that gray and white matter structural changes and functional dysconnectivity predominate in the frontal and limbic areas and the frontotemporal circuitry of the brain areas involved in the integration of executive, cognitive and affective functions, commonly affected in both disorders. Available evidence points to a considerable overlap in the affected regions between the two conditions, therefore possibly placing them at opposite ends of a psychosis continuum.
Urban Metabolism and Spontaneous Architectural Growth: A Sustainable Strategy Featuring Participatory Co-Construction by Multiple Stakeholders
Authors: Chen Fei , Chen Yifan
Published: March 2022

Several studies have linked urban metabolism with sustainable development goals, but few studies have addressed how architectural design could contribute to the linkage. Japanese Architectural Metabolism promotes the empowering of individuals and encourages spontaneous growth through urban metabolism. However, Architectural Metabolism has lacked (1) links with sustainable urban development goals, (2) realistic and powerful strategies, and (3) the ability to keep up with information technology. Whether and how architectural design can contribute to sustainable and spontaneous urban growth remains unclear. This paper presents case studies of the growth and renewal of formal and informal urban organisms in East Asia. The cases reveal that sustainable spontaneous urban growth should be linked with a strong governance system as well as adaptive architectural and construction technology that is easy to master by users. This paper argues that the conditional basis of contemporary Chinese urban development can support the spontaneous growth of architecture. Finally, a design strategy is proposed that reconstructs participatory co-construction among the government, social investors, and users with information and adaptive construction technology. Its purpose is to realize the orderly metabolism and spontaneous growth of buildings and achieve economically, socially, and ecologically sustainable development.
Targeting the Non-Canonical NF-κB Pathway in Chronic Lymphocytic Leukemia and Multiple Myeloma
Authors: Burley Thomas A. , Kennedy Emma , Broad Georgia , Boyd Melanie , Li David , Woo Timothy , West Christopher , Ladikou Eleni E. , Ashworth Iona , Fegan Christopher , Johnston Rosalynd , Mitchell Simon , Mackay Simon P. , Pepper Andrea G. S. , Pepper Chris
Published: March 2022

In this study, we evaluated an NF-κB inducing kinase (NIK) inhibitor, CW15337, in primary chronic lymphocytic leukemia (CLL) cells, CLL and multiple myeloma (MM) cell lines and normal B- and T-lymphocytes. Basal NF-κB subunit activity was characterized using an enzyme linked immunosorbent assay (ELISA), and the effects of NIK inhibition were then assessed in terms of cytotoxicity and the expression of nuclear NF-κB subunits following monoculture and co-culture with CD40L-expressing fibroblasts, as a model of the lymphoid niche. CW15337 induced a dose-dependent increase in apoptosis, and nuclear expression of the non-canonical NF-κB subunit, p52, was correlated with sensitivity to CW15337 (p = 0.01; r2 = 0.39). Co-culture on CD40L-expressing cells induced both canonical and non-canonical subunit expression in nuclear extracts, which promoted in vitro resistance against fludarabine and ABT-199 (venetoclax) but not CW15337. Furthermore, the combination of CW15337 with fludarabine or ABT-199 showed cytotoxic synergy. Mechanistically, CW15337 caused the selective inhibition of non-canonical NF-κB subunits and the transcriptional repression of BCL2L1, BCL2A1 and MCL1 gene transcription. Taken together, these data suggest that the NIK inhibitor, CW15337, exerts its effects via suppression of the non-canonical NF-κB signaling pathway, which reverses BCL2 family-mediated resistance in the context of CD40L stimulation.
Pharmacologic Strategies for Post-Transplant Maintenance in Acute Myeloid Leukemia: It Is Time to Consider!
Authors: Abou Dalle Iman , El Cheikh Jean , Bazarbachi Ali
Published: March 2022

Patients with high-risk acute myeloid leukemia are offered allogeneic hematopoietic cell transplantation (allo-HCT) in first remission to reduce risk of relapse. However, disease recurrence remains the major reason of allo-HCT failure, occurring in around 35–45% of patients, and leading to dismal outcomes. Strategies to reduce the risk of relapse are greatly needed, especially in the early post-transplant phase where the graft-versus-leukemia (GVL) effect is not yet activated. Some practices include the use of myeloablative conditioning regimens, close monitoring of measurable residual disease and donor chimerism, rapid tapering of immunosuppression, and implementation of pre-emptive strategies as the use of donor lymphocyte infusion. However, it’s time to consider prophylactic pharmacologic interventions post allo-HCT that aim at maintaining leukemic clones under control by both direct cytotoxic activity and by enhancing the GVL effect. In this current review, available data on drugs targeting epigenetic pathways like azacitidine, or actionable mutations like FLT3 and IDH1/2 inhibitors used as maintenance post allo-HCT, will be discussed.
Immune-Checkpoint Inhibitors for Malignant Pleural Mesothelioma: A French, Multicenter, Retrospective Real-World Study
Authors: Assié Jean-Baptiste , Crépin Florian , Grolleau Emmanuel , Canellas Anthony , Geier Margaux , Grébert-Manuardi Aude , Akkache Nabila , Renault Aldo , Hauss Pierre-Alexandre , Sabatini Marielle , Bonnefoy Valentine , Cortot Alexis , Wislez Marie , Gauvain Clément , Chouaïd Christos , Scherpereel Arnaud , Monnet Isabelle
Published: March 2022

Backgrounds: Malignant pleural mesothelioma (MPM) is a cancer with poor prognosis. Second-line and onward therapy has many options, including immune-checkpoint inhibitors with demonstrated efficacy: 10–25% objective response rate (ORR) and 40–70% disease-control rate (DCR) in clinical trials on selected patients. This study evaluated real-life 2L+ nivolumab efficacy in MPM patients and looked for factors predictive of response. Methods: This retrospective study included (September 2017–July 2021) all MPM patients managed in 11 French centers. Results: The 109 enrolled patients’ characteristics were: median age: 69 years; 67.9% men; 82.6% epithelioid subtype. Strictly, second-line nivolumab was given to 51.4%. Median PFS and OS were 3.8 (3.2–5.9) and 12.8 (9.2–16.4) months. ORR was 17/109 (15.6%); 34/109 patients had a stabilized disease (DCR 46.8%). Univariable analysis identified several parameters as significantly (p < 0.05) prognostic of OS [HR (95% CI)]: biphasic subtype: 3.3 (1.52–7.0), intermediate Lung Immune Prognostic Index score: 0.46 (0.22–0.99), progression on the line preceding nivolumab: 2.1 (1.11–3.9) and age > 70 years: 2.5 (1.5–4.0). Multivariable analyses retained only biphasic subtype: 3.57 (1.08–11.8) and albumin < 25 g/L: 10.28 (1.5–70.7) as significant and independent predictors. Conclusions: Second-line and onward nivolumab is effective against MPM in real life but with less effectiveness in >70 years. Ancillary studies are needed to identify the predictive factors.
Ion Channel Drugs Suppress Cancer Phenotype in NG108-15 and U87 Cells: Toward Novel Electroceuticals for Glioblastoma
Authors: Mathews Juanita , Kuchling Franz , Baez-Nieto David , Diberardinis Miranda , Pan Jen Q. , Levin Michael
Published: March 2022

Glioblastoma is a lethal brain cancer that commonly recurs after tumor resection and chemotherapy treatment. Depolarized resting membrane potentials and an acidic intertumoral extracellular pH have been associated with a proliferative state and drug resistance, suggesting that forced hyperpolarization and disruption of proton pumps in the plasma membrane could be a successful strategy for targeting glioblastoma overgrowth. We screened 47 compounds and compound combinations, most of which were ion-modulating, at different concentrations in the NG108-15 rodent neuroblastoma/glioma cell line. A subset of these were tested in the U87 human glioblastoma cell line. A FUCCI cell cycle reporter was stably integrated into both cell lines to monitor proliferation and cell cycle response. Immunocytochemistry, electrophysiology, and a panel of physiological dyes reporting voltage, calcium, and pH were used to characterize responses. The most effective treatments on proliferation in U87 cells were combinations of NS1643 and pantoprazole; retigabine and pantoprazole; and pantoprazole or NS1643 with temozolomide. Marker analysis and physiological dye signatures suggest that exposure to bioelectric drugs significantly reduces proliferation, makes the cells senescent, and promotes differentiation. These results, along with the observed low toxicity in human neurons, show the high efficacy of electroceuticals utilizing combinations of repurposed FDA approved drugs.
Transcriptional Profiling of Malignant Melanoma Reveals Novel and Potentially Targetable Gene Fusions
Authors: Darabi Sourat , Elliott Andrew , Braxton David R. , Zeng Jia , Hodges Kurt , Poorman Kelsey , Swensen Jeff , Shanthappa Basavaraja U. , Hinton James P. , Gibney Geoffrey T. , Moser Justin , Phung Thuy , Atkins Michael B. , In Gino K. , Korn Wolfgang M. , Eisenberg Burton L. , Demeure Michael J.
Published: March 2022

Invasive melanoma is the deadliest type of skin cancer, with 101,110 expected cases to be diagnosed in 2021. Recurrent BRAF and NRAS mutations are well documented in melanoma. Biologic implications of gene fusions and the efficacy of therapeutically targeting them remains unknown. Retrospective review of patient samples that underwent next-generation sequencing of the exons of 592 cancer-relevant genes and whole transcriptome sequencing for the detection of gene fusion events and gene expression profiling. Expression of PDL1 and ERK1/2 was assessed by immunohistochemistry (IHC). There were 33 (2.6%) cases with oncogenic fusions (14 novel), involving BRAF, RAF1, PRKCA, TERT, AXL, and FGFR3. MAPK pathway-associated genes were over-expressed in BRAF and RAF1 fusion-positive tumors in absence of other driver alterations. Increased expression in tumors with PRKCA and TERT fusions was concurrent with MAPK pathway alterations. For a subset of samples with available tissue, increased phosphorylation of ERK1/2 was observed in BRAF, RAF1, and PRKCA fusion-positive tumors. Oncogenic gene fusions are associated with transcriptional activation of the MAPK pathway, suggesting they could be therapeutic targets with available inhibitors. Additional analyses to fully characterize the oncogenic effects of these fusions may support biomarker driven clinical trials.
18F-Fluorodeoxyglucose PET/CT for Early Prediction of Outcomes in Patients with Advanced Lung Adenocarcinomas and EGFR Mutations Treated with First-Line EGFR-TKIs
Authors: Huang Yu-Erh , Tsai Ying-Huang , Huang Yu-Jie , Lung Jr-Hau , Ho Kuo-Wei , Yen Tzu-Chen , Chan Sheng-Chieh , Chen Shu-Tian , Tsai Ming-Feng , Hung Ming-Szu
Published: March 2022

This study aims to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in early prediction of response and survival following epithelial growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) therapy in patients with advanced lung adenocarcinomas and EGFR mutations. Thirty patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKIs were prospectively evaluated between November 2012 and May 2015. EGFR mutations were quantified by delta cycle threshold (dCt). 18F-FDG PET/CT was performed before and 2 weeks after treatment initiation. PET response was assessed based on PET Response Criteria in Solid Tumors (PERCIST). Baseline and percentage changes in the summed standardized uptake value, metabolic tumor volume (bsumMTV and ΔsumMTV, respectively), and total lesion glycolysis of ≤5 target lesions/patient were calculated. The association between parameters (clinical and PET) and non-progression disease after 3 months of treatment in CT based on the Response Evaluation Criteria in Solid Tumors Version 1.1 (nPD3mo), progression-free survival (PFS), and overall survival (OS) were tested. The median follow-up time was 19.6 months. The median PFS and OS were 12.0 and 25.3 months, respectively. The PERCIST criteria was an independent predictor of nPD3mo (p = 0.009), dCt (p = 0.014) and bsumMTV (p = 0.014) were independent predictors of PFS, and dCt (p = 0.014) and ΔsumMTV (p = 0.005) were independent predictors of OS. 18F-FDG PET/CT achieved early prediction of outcomes in patients with advanced lung adenocarcinomas and EGFR mutations receiving EGFR-TKIs.
Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma
Authors: Ljokjel Borghild , Haave Hilde , Lybak Stein , Vintermyr Olav Karsten , Helgeland Lars , Aarstad Hans Jørgen
Published: March 2022

Head and neck cancer (HNC) is the sixth most common cancer worldwide. Oropharyngeal (OP) cancers are of special interest because of possible underlying HPV infection which is tied to prognosis. Influxes of inflammatory cells into tumors may vary with prognoses. We wanted to study whether the number of tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) in tumors correlated to HPV status and predicted 5-year disease-specific survival (DSS). Formalin-fixed paraffin-embedded (FFPE) biopsies cut sections from 170 patients treated for OP cancer were stained by immunohistochemistry and evaluated for the number of CD68 (+) TAMs, CD3 (+), and Foxp3 (+) (T regulatory) TILs. From FFPE slides HPV by PCR and p16 by immunohistochemistry were established. From FFPE Hematoxylin-Eosin slides, levels of tumor nuclear polymorphism, tumor invasion, desmoplasia, and inflammation were determined as previously published. Levels of TIL CD3 (+) and TIL Foxp3 (+) were increased among the HPV (+) compared to the HPV (−) patients. High levels of TIL Foxp3 (+) and CD68 (+) macrophages predicted better 5-year DSS. TIL Foxp3 (+) levels predicted independent of age, gender, TNM stage, and HPV infection as well as level of stromal desmoplasia, tumor invasion, and nuclear polymorphism, but more pronounced among tumor HPV (+) than HPV (−) patients.
Topical Bimiralisib Shows Meaningful Cutaneous Drug Levels in Healthy Volunteers and Mycosis Fungoides Patients but No Clinical Activity in a First-in-Human, Randomized Controlled Trial
Authors: Wind Selinde , Jansen Manon , Rijsbergen Melanie , van Esdonk Michiel , Ziagkos Dimitrios , Cheng Wing , Niemeyer-van der Kolk Tessa , Korsten John , Gruszka Agnieszka , Schmitz-Rohmer Debora , Bonnel David , Legouffe Raphael , Barré Florian , Bekkenk Marcel , de Haas Ellen , Quint Koen , Schnidar Harald , Rolli Melanie , Streefkerk Henk , Burggraaf Jacobus , Vermeer Maarten , Rissmann Robert
Published: March 2022

Mycosis fungoides (MF) is a subtype of CTCL with a low incidence and high medical need for novel treatments. The objective of this randomized, placebo-controlled, double-blinded, first-in-human study was to evaluate safety, efficacy, cutaneous and systemic pharmacokinetics (PK) of topical bimiralisib in healthy volunteers (HVs) and MF patients. In this trial, a total of 6 HVs and 19 early-stage MF patients were treated with 2.0% bimiralisib gel and/or placebo. Drug efficacy was assessed by the Composite Assessment of Index Lesion Severity (CAILS) score, supported by objective measuring methods to quantify lesion severity. PK blood samples were collected frequently and cutaneous PK was investigated in skin punch biopsies on the last day of treatment. Local distribution of bimiralisib in HVs showed a mean exposure of 2.54 µg/g in the epidermis. A systemic concentration was observed after application of a target dose of 2 mg/cm2 on 400 cm2, with a mean Cavg of 0.96 ng/mL. Systemic exposure of bimiralisib was reached in all treated MF patients, and normalized plasma concentrations showed a 144% increased exposure compared to HVs, with an observed mean Cavg of 4.49 ng/mL and a mean cutaneous concentration of 5.3 µg/g. No difference in CAILS or objective lesion severity quantification upon 42 days of once-daily treatment was observed in the MF patient group. In general, the treatment was well tolerated in terms of local reactions as well as systemic adverse events. In conclusion, we showed that topical bimiralisib treatment leads to (i) meaningful cutaneous drug levels and (ii) well-tolerated systemic drug exposure in MF patients and (iii) a lack of clinical efficacy, in need of further exploration due to numerous unknown factors, before depreciation of topical bimiralisib as a novel therapeutic drug for CTCLs.
Automated Global Longitudinal Strain Assessment in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia
Authors: Gonzalez-Manzanares Rafael , Castillo Juan , Molina Jose , Ruiz-Ortiz Martin , Mesa Dolores , Ojeda Soledad , Anguita Manuel , Pan Manuel
Published: March 2022

There is limited evidence that supports the use of the global longitudinal strain (GLS) in long-term cardiac monitoring of childhood acute lymphoblastic leukemia survivors (CLSs). Our aim was to assess the utility of automated GLS to detect left ventricular systolic dysfunction (LVSD) in long-term CLSs. Asymptomatic and subclinical LVSD were defined as LVEF < 50% and GLS < 18.5%, respectively. Echocardiographic measurements and biomarkers were compared with a control group. Inverse probability weighting was used to reduce confounding. Regression models were used to identify factors associated with LVEF and GLS in the survivors. Ninety survivors with a median follow-up of 18 (11–26) years were included. The prevalence of LVSD was higher using GLS than with LVEF (26.6% vs. 12.2%). The measurements were both reduced as compared with the controls (p < 0.001). There were no differences in diastolic parameters and NT-ProBNP. Survivors were more likely to have Hs-cTnI levels above the detection limit (40% vs. 17.2%, p = 0.006). The dose of anthracycline was associated with LVEF but not with GLS in the survivors. Biomarkers were not associated with GLS or LVEF. In conclusion, LVSD detection using automated GLS was higher than with LVEF in long-term CLSs. Its incorporation into clinical routine practice may improve the surveillance of these patients.
Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR)
Authors: Muñoz Velasco Raúl , Jiménez Sánchez Paula , García García Ana , Blanco Martinez-Illescas Raquel , Pastor Senovilla Ángela , Lozano Yagüe Marian , Trento Alfonsina , García-Martin Rosa María , Navarro Diego , Sainz Bruno , Rodríguez Peralto José Luis , Sánchez-Arévalo Lobo Víctor Javier
Published: March 2022

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler BPTF (Bromodomain PHD Finger Transcription Factor) as a therapeutic target in PDA. BPTF-silencing dramatically reduced cell proliferation and migration in vitro and in vivo in human and mouse PDA cell lines. Moreover, BPTF-silencing reduces the IC50 of gemcitabine in vitro and enhanced its therapeutic effect in vivo. Mechanistically, BPTF is required for c-MYC recruitment to the promoter of ABC-transporters and its downregulation facilitates gemcitabine accumulation in tumour cells, increases DNA damage, and a generates a strong synergistic effect in vivo. We show that BPTF is a therapeutic target in pancreatic ductal adenocarcinoma due to its strong effect on proliferation and in response to gemcitabine.
A Theoretical Study of the Oxygen Release Mechanisms of a Cu-Based Oxygen Carrier during Chemical Looping with Oxygen Uncoupling
Authors: Wang Minjun , Zhang Shixiong , Xia Ming , Wang Mengke
Published: March 2022

The Cu-based oxygen carrier is a promising material in the chemical looping with oxygen uncoupling (CLOU) process, while its performance in the CLOU is significantly dependent on the oxygen release properties. However, the study of oxygen release mechanisms in CLOU is not comprehensive enough. In this work, the detailed oxygen release mechanisms of CuO(110) and CuO(111) are researched at an atomic level using the density functional theory (DFT) method, including the formation of O2, the desorption of O2 and the diffusion of O anion, as well as the analysis of the density of states. The results show that (1) the most favorable pathway for O2 formation and desorption occurs on the CuO(110) surface of O-terminated with energy barriers of 1.89 eV and 3.22 eV, respectively; (2) the most favorable pathway for O anion diffusion occurs in the CuO(110) slab with the lowest energy barrier of 0.24 eV; and (3) the total density of states for the O atoms in the CuO(110) slab shifts to a lower energy after an O vacancy formation. All of the above results clearly demonstrate that the CuO(110) surface plays a significantly important role in the oxygen release reaction, and the oxygen vacancy defect should be conducive to the reactivity of oxygen release in a Cu-based oxygen carrier.
A Novel 3D Culture System Using a Chitin-Based Polysaccharide Material Produces High-Quality Allogeneic Human UCMSCs with Dispersed Sphere Morphology
Authors: Kida Katsuhiko , Kanaki Tatsuro , Gao Shuang , Hatanaka Daisuke , Iwakami Masashi , Liu Shuai , Horikawa Masato , Ono Minoru , Chang Dehua
Published: March 2022

Mesenchymal stem cell (MSC) transplantation, in particular allogeneic transplantation, is a promising therapy for a variety of diseases. However, before performing allograft treatment it is necessary to find suitable donors, establish culture methods that maintain cell quality, and reduce cell production costs. Here, we present a new method of producing allogeneic MSCs combining human umbilical cord-derived mesenchymal stem cells (UCMSCs) and chitin-based polysaccharide fibers (Cellhesion® MS). UCMSC numbers significantly increased, and cells grew as dispersed spheres on Cellhesion® MS. Subsequent biological analyses showed that the expression levels of stemness-related and migration-related genes were significantly upregulated, including octamer-binding transcription factor 4 (OCT4), Nanog homeobox (NANOG), and C-X-C chemokine receptor type 4 (CXCR4). The secretion levels of paracrine factors such as prostaglandin E2 (PGE2), TNFα-stimulating gene (TSG)-6, fibroblast growth factor 2 (bFGF), and Angiogenin (Ang) from UCMSCs using Cellhesion® MS were significantly higher than with microcarrier and U-bottom plate culture. In addition, culture supernatant from UCMSCs with Cellhesion® MS had better angiogenic potential than that from monolayer cultured UCMSCs. Furthermore, we succeeded in a scaled-up culture of UCMSCs with Cellhesion® MS using a closed culture bag. Therefore, Cellhesion® MS is a key material for producing high-quality UCMSCs in a three-dimensional (3D) culture system.
Self-Efficacy, Optimism, and Academic Performance as Psychoeducational Variables: Mediation Approach in Students
Authors: Usán Pablo , Salavera Carlos , Quílez-Robres Alberto
Published: March 2022

Background: During the various stages of education, adolescents undergo emotional and motivational experiences that can play key roles in their development. This study aims to analyse the relationship among academic self-efficacy, optimism, and academic performance. Methods: This study comprised 1852 adolescent (male, N = 956, 51.61% and female, N = 896, 48.38%) aged 12–19 years (M = 14.77; SD = 1.80) from twelve secondary schools in Spain. The instruments used for the evaluation were the Academic Self-Efficacy Scale (ASES) and the Life Orientation Test—Revised (LOT-R); the students’ average marks were used to measure their academic performance. Results: The results of the study revealed significant correlations among self-efficacy, optimism and academic performance. Conclusions: These results emphasise the importance of academic self-efficacy as a mediating variable between the other two variables as well as its central role in the promotion of adaptive behaviours in the classroom, leading to adequate personal development, helping to prevent early school dropout and contributing to a more satisfactory academic experience.
A Comparative Study of Autonomous Object Detection Algorithms in the Maritime Environment Using a UAV Platform
Authors: Vasilopoulos Emmanuel , Vosinakis Georgios , Krommyda Maria , Karagiannidis Lazaros , Ouzounoglou Eleftherios , Amditis Angelos
Published: March 2022

Maritime operations rely heavily on surveillance and require reliable and timely data that can inform decisions and planning. Critical information in such cases includes the exact location of objects in the water, such as vessels, persons, and others. Due to the unique characteristics of the maritime environment, the location of even inert objects changes through time, depending on the weather conditions, water currents, etc. Unmanned aerial vehicles (UAVs) can be used to support maritime operations by providing live video streams and images from the area of operations. Machine learning algorithms can be developed, trained, and used to automatically detect and track objects of specific types and characteristics. EFFECTOR is an EU-funded project, developing an Interoperability Framework for maritime surveillance. Within the project, we developed an embedded system that employs machine learning algorithms, allowing a UAV to autonomously detect objects in the water and keep track of their changing position through time. Using the on-board computation unit of the UAV, we ran and present the results of a series of comparative tests among possible architecture sizes and training datasets for the detection and tracking of objects in the maritime environment. We tested architectures based on their efficiency, accuracy, and speed. A combined solution for training the datasets is suggested, providing optimal efficiency and accuracy.
Determinants of the Cancer Drug Funding Process in Canada
Authors: Gotfrit Joanna , Jackson Ashley , Shin John J. W. , Stewart David J. , Mallick Ranjeeta , Wheatley-Price Paul
Published: March 2022

Background: Canada has a publicly funded healthcare system with a complex drug funding process. After Health Canada approval to market a drug, the pan-Canadian Oncology Drug Review (pCODR) (now renamed the CADTH reimbursement review) makes a non-binding funding recommendation to the Canadian provinces (except Quebec), which each then decide whether the drug will be publicly funded. We identified the determinants of funding in this process. Methods: We analyzed drugs for advanced lung (n = 15), breast (n = 8), colorectal (CRC) (n = 7), melanoma (n = 10), and neuroendocrine (NET) (n = 3) cancers undergoing the funding decision process from 2011 to 2019. Determinants of funding assessed in the model included list price, cancer type, drug class, and pCODR recommendation. The primary outcome was the correlation between list price and time to funding (TTF: Health Canada approval to first provincial funding). Secondary outcomes included an exploratory analysis of predictors of drug funding. Results: We analyzed 43 drugs: targeted agents 72%, immunotherapy 20%, chemotherapy 7%. A total of 72% were funded in at least one province. Median TTF was 379 days (IQR 203–601). Median list price (28-day course) was CAD 8213 (IQR CAD 5391–9445). Higher list price was not correlated with TTF (correlation coefficient −0.20, p = 0.28). There was no association between list price and pCODR recommendation or the decision to fund in at least one province. A positive pCODR recommendation correlated with the provinces’ funding decisions (p < 0.001), where 89% of drugs with a positive recommendation were funded and 100% of drugs with a negative recommendation were not funded. Tumor type was predictive of TTF (p < 0.001): CRC drugs were the slowest at a median of 2541 days (IQR 702–4379), and NETs were the quickest at a median of 0 days (IQR 0–502). Cancer type predicted decision to fund in at least one province (p = 0.005), with funding for 100% of NET drugs at the high end and 29% of CRC drugs at the low end. Drug class was predictive of TTF (p = 0.01): 465 days (IQR 245–702) for targeted agents, 443 days (IQR 298–587) for chemotherapy, and 339 days (IQR 164–446) for immunotherapy. Conclusions: Determinants of drug funding included cancer type, drug class, and pCODR recommendation but not list price. Factors other than cost were more heavily weighted in the funding decisions of cancer drugs in Canadian provinces.
Diagnostics Literacy Advocacy Model for Vulnerable Populations
Authors: Mashamba-Thompson Tivani P.
Published: March 2022

Evidence shows that vulnerable populations have lower levels of health literacy, resulting in poor health-seeking behavior and poor uptake of diagnostics. Being health literate promotes health care-seeking behavior and improves engagement with diagnostic services. In this editorial, I define health literacy in the context of access to technology for enabling disease screening, diagnosis and linkage to care. I refer to health literacy in this context as diagnostics literacy. The COVID-19 pandemic has taught us that vulnerable populations are disproportionately disadvantaged by the disruptive measures put in place to control the spread of the virus. Many vulnerable populations are still experiencing short-and longer-term socio-economic consequences. I propose a multi-level diagnostics literacy advocacy model to help improve diagnostic uptake among vulnerable populations.
Missing Values in Panel Data Unit Root Tests
Authors: Karavias Yiannis , Tzavalis Elias , Zhang Haotian
Published: March 2022

Missing data or missing values are a common phenomenon in applied panel data research and of great interest for panel data unit root testing. The standard approach in the literature is to balance the panel by removing units and/or trimming a common time period for all units. However, this approach can be costly in terms of lost information. Instead, existing panel unit root tests could be extended to the case of unbalanced panels, but this is often difficult because the missing observations affect the bias correction which is usually involved. This paper contributes to the literature in two ways; it extends two popular panel unit root tests to allow for missing values, and secondly, it employs asymptotic local power functions to analytically study the impact of various missing-value methods on power. We find that zeroing-out the missing observations is the method that results in the greater test power, and that this result holds for all deterministic component specifications, such as intercepts, trends and structural breaks.
How Diversity Fails: An Empirical Investigation of Organizational Status and Policy Implementation on Three Public Campuses
Authors: byrd derria
Published: March 2022

Although diversity has been a guiding preoccupation in higher education for several decades, organizational diversity practice, i.e., what happens when colleges and universities implement diversity plans, is rarely a subject of inquiry. As a result, there is relatively little empirical understanding of why diversity has failed to significantly advance racial equity on college campuses. In response, this ethnographic, collective case study draws on interviews with 54 respondents, archival and organizational documents, and campus observations to interrogate diversity practice on three campuses of different status in one public system in the U.S. This study employs Bourdieu’s theory of practice, specifically institutional habitus as an analytic lens, to examine the influence of campus social status on diversity practice related to a statewide policy. Findings reveal that each campus has a unique institutional habitus—that is, a status-linked sense of campus identity, constraints, and opportunities—that prefigured and, on most campuses, derailed diversity practice in response to the policy. Only the middle-status campus made any substantive progress. By juxtaposing these findings, this analysis demonstrates that diversity practice does not exist within a campus vacuum; instead, it is inevitably influenced, constrained, or aided by the institutional habitus of the organizational environment. The paper concludes by arguing that organizational change efforts that recognize diversity work as a situated organizational practice that reflects broader power relations can better challenge inequities to spur transformative change across educational levels and contexts.
Methodological Contributions to Educational Research on the Formation of Social Thought
Authors: Ortega-Sánchez Delfín , Pérez-González Carlos
Published: March 2022

The main purpose of social science education is the formation of social thought for the understanding of reality from its critical and creative dimensions and for the intervention and democratic participation of a responsible and committed citizenship; that is, the formation of citizens capable of living democratically with each other and of participating in the social, labor, cultural, and political life of their world, and trying to improve it [...]
An Adaptive Output Feedback Controller for Boost Converter
Authors: Zhang Xiaoyu , He Wei , Zhang Yanqin
Published: March 2022

The main contribution of this paper is to propose an adaptive reduced-order state observer for boost converter to reconstruct the inductor current and load conductance. Note that the unknown parameter appears in the output dynamics, which poses a detectability obstacle, imposing a more stringent requirement on the system behavior. As a result, the design of an adaptive reduced-order state observer is more challenging. In this paper, using the dynamic extension technique, we transform the state observation into the parameter estimation. Constructing the parameter observer, the current and load conductance can be estimated. Introducing the estimated terms to a saturated PI passivity-based control, an adaptive output feedback saturated controller is presented. To assess the control performance, the simulation and experimental results are given.
Lab-Tec@Home: A Cost-Effective Kit for Online Control Engineering Education
Authors: Sotelo David , Sotelo Carlos , Ramirez-Mendoza Ricardo A. , López-Guajardo Enrique A. , Navarro-Duran David , Niño-Juárez Elvira , Vargas-Martinez Adriana
Published: March 2022

It is widely recognized that a hands-on laboratory experience is useful in control engineering education. Herein, the students overcome the main gaps between theoretical knowledge and experimental setups. Nowadays, in times of crisis due to the COVID-19 pandemic, virtual and remote laboratories are emerging as primary educational resources. However, in virtual labs, the students are not exposed to real life issues (i.e., equipment problems, noise, etc.) while in remote labs, communication and connectivity problems arise (i.e., network security, synchronization management, internet speed, etc.). Henceforth, this work presents an unpublished educational project named Lab-Tec@Home, and the aim of this research is to expand the access of hands-on control education at the undergraduate level. Here, students easily assemble a cost-effective laboratory kit at home and use it on their own computing devices connected with the external MATLAB/SimulinkTM application. Thus, students can test and validate theoretical concepts of control engineering such as: system model identification, and PID control design and test. The assessment results show that the proposed educational project enhances the learning experience and has outstanding positive feedback of more than 290 students who undertook massive flexible digital courses at Tecnologico de Monterrey. This makes the proposed educational project mainly suitable for control engineering courses.
An Investigation on Hybrid Particle Swarm Optimization Algorithms for Parameter Optimization of PV Cells
Authors: Singh Abha , Sharma Abhishek , Rajput Shailendra , Bose Amarnath , Hu Xinghao
Published: March 2022

The demands for renewable energy generation are progressively expanding because of environmental safety concerns. Renewable energy is power generated from sources that are constantly replenished. Solar energy is an important renewable energy source and clean energy initiative. Photovoltaic (PV) cells or modules are employed to harvest solar energy, but the accurate modeling of PV cells is confounded by nonlinearity, the presence of huge obscure model parameters, and the nonattendance of a novel strategy. The efficient modeling of PV cells and accurate parameter estimation is becoming more significant for the scientific community. Metaheuristic algorithms are successfully applied for the parameter valuation of PV systems. Particle swarm optimization (PSO) is a metaheuristic algorithm inspired by animal behavior. PSO and derivative algorithms are efficient methods to tackle different optimization issues. Hybrid PSO algorithms were developed to improve the performance of basic ones. This review presents a comprehensive investigation of hybrid PSO algorithms for the parameter assessment of PV cells. This paper presents how much work is conducted in this field, and how much work can additionally be performed to improve this strategy and create more ideal arrangements of an issue. Algorithms are compared on the basis of the used objective function, type of diode model, irradiation conditions, and types of panels. More importantly, the qualitative analysis of algorithms is performed on the basis of computational time, computational complexity, convergence rate, search technique, merits, and demerits.
RDNet: Rate–Distortion-Based Coding Unit Partition Network for Intra-Prediction
Authors: Yao Chao , Xu Chenming , Liu Meiqin
Published: March 2022

High efficiency video coding (HEVC) has been finalized as the most widely utilized video coding standard, jointly developed by ITU-T, VCEG, and MPEG. In HEVC, the quad-tree structure of the coding unit partition is one of the most substantial modules and provides significant coding gains following huge coding time. In this paper, a rate–distortion-based coding unit partition network (RDNet) is proposed to make partition decisions based on the statistical features. RDNet is composed of a prediction sub-network and a target sub-network, where the prediction sub-network is used to predict the CU partition modes of the intra-prediction and the target sub-network is designed to optimize the network parameters by evaluating the rate–distortion cost, respectively. To balance the prediction accuracy and the rate–distortion loss, a parameter-exchanging strategy is applied to control the parameters’ sharing between two networks. Experimental results prove that our model can reduce the encoding time of HEVC by 55.83~71.72% with an efficient BD-BR of 2.876~3.347%, and the ablation study evaluates the ability of our strategy on balancing the trade-off between coding accuracy and inference speed.