bluuebunny/crossref_metadata_2025 huggingface dataset:
Definitive Chemoradiotherapy versus Radical Hysterectomy Followed by Tailored Adjuvant Therapy in Women with Early-Stage Cervical Cancer Presenting with Pelvic Lymph Node Metastasis on Pretreatment Evaluation: A Propensity Score Matching Analysis
Authors: Park Jongmoo , Kim Yeon-Joo , Song Mi-Kyung , Nam Joo-Hyun , Park Sang-Yoon , Kim Young-Seok , Kim Joo-Young
Published: July 2021

To compare the oncologic outcomes between chemoradiotherapy (CRT) and radical hysterectomy followed by tailored adjuvant therapy in patients with early cervical cancer presenting with pelvic lymph node metastasis. We retrospectively analyzed the medical records of women with early cervical cancer presenting with positive pelvic nodes identified on pretreatment imaging assessment. Propensity score matching was employed to control for the heterogeneity between two groups according to confounding factors. Overall survival, disease-free survival, and pattern of failure were compared between the two groups. A total of 262 patients were identified; among them, 67 received definitive CRT (group A), and 195 received hysterectomy (group B). Adjuvant therapy was administered to 88.7% of group B. There were no significant differences between group A and group B regarding the 5-year overall survival rates (89.2% vs. 89.0%) as well as disease-free survival rates (80.6% vs. 82.7%), and patterns of failure. Distant metastasis was the major failure pattern identified in both groups. In multivariate analysis, non-squamous histology was significantly associated with poorer overall survival. As there are no significant differences in 5-year OS, DFS, and patterns of failure, definitive CRT could avoid the combined modality therapy without compromising oncologic outcomes.
Comparative Efficacy and Safety of Lorlatinib and Alectinib for ALK-Rearrangement Positive Advanced Non-Small Cell Lung Cancer in Asian and Non-Asian Patients: A Systematic Review and Network Meta-Analysis
Authors: Ando Koichi , Manabe Ryo , Kishino Yasunari , Kusumoto Sojiro , Yamaoka Toshimitsu , Tanaka Akihiko , Ohmori Tohru , Sagara Hironori
Published: July 2021

To date, there have been no head-to-head randomized controlled trials (RCTs) comparing the safety and efficacy of lorlatinib and alectinib in anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) ALK-inhibitor‒naïve advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis comparing six treatment arms (lorlatinib, brigatinib, alectinib, ceritinib, crizotinib, and platinum-based chemotherapy) in overall participants and in Asian and non-Asian subgroups. Primary endpoints were progression-free survival (PFS), overall survival (OS), and grade 3 or higher adverse events (G3-AEs). There were no significant differences between lorlatinib and alectinib in overall participants for both PFS (hazard ratio [HR], 0.742; 95% credible interval [CrI], 0.466–1.180) and OS (HR, 1.180; 95% CrI, 0.590–2.354). In the Asian subgroup, there were no significant differences in PFS between lorlatinib and alectinib (HR, 1.423; 95% CrI, 0.748–2.708); however, in the non-Asian subgroup, PFS was significantly better with lorlatinib than with alectinib (HR, 0.388; 95% CrI, 0.195–0.769). The incidence of G3-AEs in overall participants was significantly higher with lorlatinib than with alectinib (risk ratio, 1.918; 95% CrI, 1.486–2.475). These results provide valuable information regarding the safety and efficacy of lorlatinib in ALK-p ALK-inhibitor‒naïve advanced NSCLC. Larger head-to-head RCTs are needed to validate the study results.
Systematic Roadmap for Cancer Drug Screening Using Zebrafish Embryo Xenograft Cancer Models: Melanoma Cell Line as a Case Study
Authors: Letrado Patricia , Mole Holly , Montoya María , Palacios Irene , Barriuso Jorge , Hurlstone Adam , Díez-Martínez Roberto , Oyarzabal Julen
Published: July 2021

Zebrafish embryo tumor transplant models are widely utilized in cancer research. Compared with traditional murine models, the small size and transparency of zebrafish embryos combined with large clutch sizes that increase statistical power and cheap husbandry make them a cost-effective and versatile tool for in vivo drug discovery. However, the lack of a comprehensive analysis of key factors impacting the successful use of these models impedes the establishment of basic guidelines for systematic screening campaigns. Thus, we explored the following crucial factors: (i) user-independent inclusion criteria, focusing on sample homogeneity; (ii) metric definition for data analysis; (iii) tumor engraftment criteria; (iv) image analysis versus quantification of human cancer cells using qPCR (RNA and gDNA); (v) tumor implantation sites; (vi) compound distribution (intratumoral administration versus alternative inoculation sites); and (vii) efficacy (intratumoral microinjection versus compound solution in media). Based on these analyses and corresponding assessments, we propose the first roadmap for systematic drug discovery screening in zebrafish xenograft cancer models using a melanoma cell line as a case study. This study aims to help the wider cancer research community to consider the adoption of this versatile model for cancer drug screening projects.
‘Palliative-D’—Vitamin D Supplementation to Palliative Cancer Patients: A Double Blind, Randomized Placebo-Controlled Multicenter Trial
Authors: Helde Frankling Maria , Klasson Caritha , Sandberg Carina , Nordström Marie , Warnqvist Anna , Bergqvist Jenny , Bergman Peter , Björkhem-Bergman Linda
Published: July 2021

The aim of the ‘Palliative-D’ study was to test the hypothesis that correction of vitamin D deficiency reduces opioid use in cancer patients admitted to palliative care. A multicenter randomized, placebo-controlled, double-blind trial in three home-based palliative care facilities in Sweden was performed. Patients with advanced cancer and 25-hydroxyvitamin D < 50 nmol/L were randomized to vitamin D3 4000 IU/day or placebo for 12 weeks. The primary endpoint was the difference of long-acting opioid use (fentanyl ug/h) between the groups during 12 weeks, based on four time points. Secondary outcomes included changes in antibiotic use, fatigue and Quality of Life (QoL). A total of 244 patients were randomized, and 150 patients completed the 12 weeks. The major reason for drop-out was death due to cancer. The vitamin D-group had a significantly smaller increase of opioid doses compared to the placebo-group; beta coefficient −0.56 (p = 0.03), i.e., 0.56 µg less fentanyl/h per week with vitamin D treatment. Vitamin D-reduced fatigue assessed with ESAS was −1.1 points after 12 weeks (p < 0.01). Antibiotic use or QoL did not differ significantly between the groups. The treatment was safe and well-tolerated. In conclusion, correction of vitamin D deficiency may have positive effects on opioid use and fatigue in palliative cancer patients, but only in those with a survival time more than 12 weeks.
Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis
Authors: Das Bhaba K. , Kannan Aarthi , Nguyen Quy , Gogoi Jyoti , Zhao Haibo , Gao Ling
Published: July 2021

Merkel cell carcinoma (MCC) is an often-lethal skin cancer with increasing incidence and limited treatment options. Although immune checkpoint inhibitors (ICI) have become the standard of care in advanced MCC, 50% of all MCC patients are ineligible for ICIs, and amongst those treated, many patients develop resistance. There is no therapeutic alternative for these patients, highlighting the urgent clinical need for alternative therapeutic strategies. Using patient-derived genetic insights and data generated in our lab, we identified aurora kinase as a promising therapeutic target for MCC. In this study, we examined the efficacy of the recently developed and highly selective AURKA inhibitor, AK-01 (LY3295668), in six patient-derived MCC cell lines and two MCC cell-line-derived xenograft mouse models. We found that AK-01 potently suppresses MCC survival through apoptosis and cell cycle arrest, particularly in MCPyV-negative MCC cells without RB expression. Despite the challenge posed by its short in vivo durability upon discontinuation, the swift and substantial tumor suppression with low toxicity makes AK-01 a strong potential candidate for MCC management, particularly in combination with existing regimens.
The Role of Surgery in Lung Cancer Treatment: Present Indications and Future Perspectives—State of the Art
Authors: Montagne François , Guisier Florian , Venissac Nicolas , Baste Jean-Marc
Published: July 2021

Non-small cell lung cancers (NSCLC) are different today, due to the increased use of screening programs and of innovative systemic therapies, leading to the diagnosis of earlier and pre-invasive tumors, and of more advanced and controlled metastatic tumors. Surgery for NSCLC remains the cornerstone treatment when it can be performed. The role of surgery and surgeons has also evolved because surgeons not only perform the initial curative lung cancer resection but they also accompany and follow-up patients from pre-operative rehabilitation, to treatment for recurrences. Surgery is personalized, according to cancer characteristics, including cancer extensions, from pre-invasive and local tumors to locally advanced, metastatic disease, or residual disease after medical treatment, anticipating recurrences, and patients’ characteristics. Surgical management is constantly evolving to offer the best oncologic resection adapted to each NSCLC stage. Today, NSCLC can be considered as a chronic disease and surgery is a valuable tool for the diagnosis and treatment of recurrences, and in palliative conditions to relieve dyspnea and improve patients’ comfort.
Cardiac Amyloidosis: Diagnostic Tools for a Challenging Disease
Authors: Migliaccio Marco , Iodice Franco , Di Mauro Marco , Iannuzzi Angela , Pacileo Roberta , Caiazza Martina , Esposito Augusto
Published: July 2021

Amyloidosis is a group of diseases in which amyloid fibrils build up in tissues, leading to organ dysfunction. Cardiac involvement is observed in immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) and, when it occurs, the prognosis worsens. Cardiac tissue infiltration can lead to restrictive cardiomyopathy with clinical signs of diastolic heart failure, without reduction of ejection fraction (HFpEF). The aim of multiple and less invasive diagnostic tests is to discern peculiar characteristics and reach the diagnosis without performing an invasive endomyocardial biopsy. These diagnostic tools allow early diagnosis, and they are crucial to best benefit from target therapy. In this review article, we describe the mechanism behind amyloid fibril formation, infiltration of tissues, and consequent clinical signs, focusing on the diagnostic tools and the red flags to obtain a diagnosis.
Reassessment of Gene-Elusive Familial Dilated Cardiomyopathy Leading to the Discovery of a Homozygous AARS2 Variant—The Importance of Regular Reassessment of Genetic Findings
Authors: Bhardwaj Priya , Vissing Christoffer Rasmus , Stampe Niels Kjær , Rossing Kasper , Christensen Alex Hørby , Jensen Thomas Hartvig Lindkær , Winkel Bo Gregers
Published: July 2021

Background: AARS2 encodes the mitochondrial protein alanyl-tRNA synthetase 2 (MT-AlaRS), an important enzyme in oxidative phosphorylation. Variants in AARS2 have previously been associated with infantile cardiomyopathy. Case summary: A 4-year-old girl died of infantile-onset dilated cardiomyopathy (DCM) in 1996. Fifteen years later, her 21-year-old brother was diagnosed with DCM and ultimately underwent heart transplantation. Initial sequencing of 15 genes discovered no pathogenic variants in the brother at the time of his diagnosis. However, 9 years later re-screening in an updated screening panel of 129 genes identified a homozygous AARS2 (c.1774C > T) variant. Sanger sequencing of the deceased girl confirmed her to be homozygous for the AARS2 variant, while both parents and a third sibling were all found to be unaffected heterozygous carriers of the AARS2 variant. Discussion: This report underlines the importance of repeated and extended genetic screening of elusive families with suspected hereditary cardiomyopathies, as our knowledge of disease-causing mutations continuously grows. Although identification of the genetic etiology in the reported family would not have changed the clinical management, the genetic finding allows genetic counselling and holds substantial value in identifying at-risk relatives.
Enhancing CO2 Conversion to CO over Plasma-Deposited Composites Based on Mixed Co and Fe Oxides
Authors: Kierzkowska-Pawlak Hanna , Ryba Małgorzata , Fronczak Maciej , Kapica Ryszard , Sielski Jan , Sitarz Maciej , Zając Patryk , Łyszczarz Klaudia , Tyczkowski Jacek
Published: July 2021

The hydrogenation of CO2 to produce CO and H2O, known as reverse-water-gas shift reaction (RWGS) is considered to be an important CO2 valorization pathway. This work is aimed at proposing the thin-film catalysts based on iron and cobalt oxides for this purpose. A series of Fe–Co nanocomposites were prepared by the plasma-enhanced chemical vapor deposition (PECVD) from organic cobalt and iron precursors on a wire-mesh support. The catalysts were characterized by SEM/EDX, XPS, XRD, and Raman spectroscopy and studied for hydrogenation of CO2 in a tubular reactor operating in the temperature range of 250–400 °C and atmospheric pressure. The Co-based catalyst, containing crystalline CoO phase, exhibited high activity toward CH4, while the Fe-based catalyst, containing crystalline Fe2O3/Fe3O4 phases, was less active and converted CO2 mainly into CO. Regarding the Fe–Co nanocomposites (incl. Fe2O3/Fe3O4 and CoO), even a small fraction of iron dramatically inhibited the production of methane. With increasing the atomic fraction of iron in the Fe–Co systems, the efficiency of the RWGS reaction at 400 °C increased up to 95% selectivity to CO and 30% conversion of CO2, which significantly exceeded the conversion for pure iron–based films (approx. 9%). The superior performance of the Fe–Co nanocomposites compared to “pure” Co and Fe–based films was proposed to be explained by assuming changes in the electronic structure of the catalyst resulting from the formation of p–n junctions between nanoparticles of cobalt and iron oxides.
Correlation of Morphology Evolution with Carrier Dynamics in InN Films Heteroepitaxially Grown by MOMBE
Authors: Lai Fang-I , Yang Jui-Fu , Lin Woei-Tyng , Chen Wei-Chun , Hsu Yu-Chao , Kuo Shou-Yi
Published: July 2021

In this study, we report the catalyst-free growth of n-type wurtzite InN, along with its optical properties and carrier dynamics of different surface dimensionalities. The self-catalyzed epitaxial growth of InN nanorods grown by metal–organic molecular-beam epitaxy on GaN/Al2O3(0001) substrates has been demonstrated. The substrate temperature is dominant in controlling the growth of nanorods. A dramatic morphological change from 2D-like to 1D nanorods occurs with decreasing growth temperature. The InN nanorods have a low dislocation density and good crystalline quality, compared with InN films. In terms of optical properties, the nanorod structure exhibits strong recombination of Mahan excitons in luminescence, and an obvious spatial correlation effect in phonon dispersion. The downward band structure at the nanorod surface leads to the photon energy-dependent lifetime being upshifted to the high-energy side.
Glucose Conversion into 5-Hydroxymethylfurfural over Niobium Oxides Supported on Natural Rubber-Derived Carbon/Silica Nanocomposite
Authors: Khumho Rujeeluk , Yousatit Satit , Ngamcharussrivichai Chawalit
Published: July 2021

5-Hydroxymethylfurfural (HMF) is one of the most important lignocellulosic biomass-derived platform molecules for production of renewable fuel additives, liquid hydrocarbon fuels, and value-added chemicals. The present work developed niobium oxides (Nb2O5) supported on mesoporous carbon/silica nanocomposite (MCS), as novel solid base catalyst for synthesis of HMF via one-pot glucose conversion in a biphasic solvent. The MCS material was prepared via carbonization using natural rubber dispersed in hexagonal mesoporous silica (HMS) as a precursor. The Nb2O5 supported on MCS (Nb/MCS) catalyst with an niobium (Nb) loading amount of 10 wt.% (10-Nb/MCS) was characterized by high dispersion, and so tiny crystallites of Nb2O5, on the MCS surface, good textural properties, and the presence of Bronsted and Lewis acid sites with weak-to-medium strength. By varying the Nb loading amount, the crystallite size of Nb2O5 and molar ratio of Bronsted/Lewis acidity could be tuned. When compared to the pure silica HMS-supported Nb catalyst, the Nb/MCS material showed a superior glucose conversion and HMF yield. The highest HMF yield of 57.5% was achieved at 93.2% glucose conversion when using 10-Nb/MCS as catalyst (5 wt.% loading with respect to the mass of glucose) at 190 °C for 1 h. Furthermore, 10-Nb/MCS had excellent catalytic stability, being reused in the reaction for five consecutive cycles during which both the glucose conversion and HMF yield were insignificantly changed. Its superior performance was ascribed to the suitable ratio of Brønsted/Lewis acid sites, and the hydrophobic properties generated from the carbon moieties dispersed in the MCS nanocomposite.
Dysregulation of miRNAs Targeting the IGF-1R Pathway in Pancreatic Ductal Adenocarcinoma
Authors: Dobre Maria , Herlea Vlad , Vlăduţ Cătălina , Ciocîrlan Mihai , Balaban Vasile Daniel , Constantinescu Gabriel , Diculescu Mircea , Milanesi Elena
Published: July 2021

Background: Pancreatic ductal adenocarcinoma (PDAC), the most prevalent neoplastic lethal pancreatic disease, has a poor prognosis and an increasing incidence. The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is considered to be a contributing factor to the progression, metastasis, and therapy resistance of PDAC. Currently available treatment options for PDAC are limited, but microRNAs (miRNAs) may represent a new therapeutic strategy for targeting genes involved in the IGF-1R signaling pathway. Method: We investigated the expression levels of 21 miRNAs involved in the IGF-1R signaling pathway in pancreatic tissue from 38 patients with PDAC and 11 controls (five patients with chronic pancreatitis and six patients with normal pancreatic tissue). Results: We found 19 differentially expressed miRNAs between the PDAC cases and the controls. In particular, miR-100-5p, miR-145-5p, miR-29c-3p, miR-9-5p, and miR-195-5p were exclusively downregulated in PDAC tissue but not in chronic pancreatitis or normal pancreatic tissues; both control types presented similar levels. We also identified miR-29a-3p, miR-29b-3p, and miR-7-5p as downregulated miRNAs in PDAC tissues as compared with normal tissues but not with pancreatitis tissues. Conclusions: We identified a panel of miRNAs that could represent putative therapeutic targets for the development of new miRNA-based therapies for PDAC.
Age-Dependent Distinct Distributions of Dendritic Cells in Autoimmune Dry Eye Murine Model
Authors: Jung Young-Ho , Ryu Jin-Suk , Yoon Chang-Ho , Kim Mee-Kum
Published: July 2021

We investigated whether aging-dependent changes in dendritic cell (DC) distributions are distinct in autoimmune dry eye compared with an aging-related murine model. Corneal staining and tear secretion were evaluated in young and aged C57BL/6 (B6) and NOD.B10.H2b mice (NOD). In the corneolimbus, lacrimal gland (LG), and mesenteric lymph node (MLN), CD11b− and CD11b+ DCs, CD103+ DCs and MHC-IIhi B cells were compared between young and aged B6 and NOD mice. With increased corneal staining, tear secretion decreased in both aged B6 and NOD mice (p < 0.001). In both aged B6 and NOD mice, the percentages of corneolimbal CD11b+ DCs were higher (p < 0.05) than those in young mice. While, the percentages of lymph nodal CD103+ DCs were higher in aged B6 and NOD mice (p < 0.05), the percentages of corneolimbal CD103+ DCs were only higher in aged NOD mice (p < 0.05). In aged NOD mice, the proportions of lacrimal glandial and lymph nodal MHC-IIhi B cells were also higher than those in young mice (p < 0.05). It indicates that corneolimbal or lacrimal glandial distribution of CD103+ DCs or MHC-IIhi B cells may be distinct in aged autoimmune dry eye models compared to those in aged immune competent murine models.
Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheumatoid Arthritis
Authors: Roszkowski Leszek , Ciechomska Marzena
Published: July 2021

Monocytes/macrophages play a central role in chronic inflammatory disorders, including rheumatoid arthritis (RA). Activation of these cells results in the production of various mediators responsible for inflammation and RA pathogenesis. On the other hand, the depletion of macrophages using specific antibodies or chemical agents can prevent their synovial tissue infiltration and subsequently attenuates inflammation. Their plasticity is a major feature that helps the switch from a pro-inflammatory phenotype (M1) to an anti-inflammatory state (M2). Therefore, understanding the precise strategy targeting pro-inflammatory monocytes/macrophages should be a powerful way of inhibiting chronic inflammation and bone erosion. In this review, we demonstrate potential consequences of different epigenetic regulations on inflammatory cytokines production by monocytes. In addition, we present unique profiles of monocytes/macrophages contributing to identification of new biomarkers of disease activity or predicting treatment response in RA. We also outline novel approaches of tuning monocytes/macrophages by biologic drugs, small molecules or by other therapeutic modalities to reduce arthritis. Finally, the importance of cellular heterogeneity of monocytes/macrophages is highlighted by single-cell technologies, which leads to the design of cell-specific therapeutic protocols for personalized medicine in RA in the future.
HDL in Atherosclerotic Cardiovascular Disease: In Search of a Role
Authors: Casula Manuela , Colpani Ornella , Xie Sining , Catapano Alberico L. , Baragetti Andrea
Published: July 2021

For a long time, high-density lipoprotein cholesterol (HDL-C) has been regarded as a cardiovascular disease (CVD) protective factor. Recently, several epidemiological studies, while confirming low plasma levels of HDL-C as an established predictive biomarker for atherosclerotic CVD, indicated that not only people at the lowest levels but also those with high HDL-C levels are at increased risk of cardiovascular (CV) mortality. This “U-shaped” association has further fueled the discussion on the pathophysiological role of HDL in CVD. In fact, genetic studies, Mendelian randomization approaches, and clinical trials have challenged the notion of HDL-C levels being causally linked to CVD protection, independent of the cholesterol content in low-density lipoproteins (LDL-C). These findings have prompted a reconsideration of the biological functions of HDL that can be summarized with the word “HDL functionality”, a term that embraces the many reported biological activities beyond the so-called reverse cholesterol transport, to explain this lack of correlation between HDL levels and CVD. All these aspects are summarized and critically discussed in this review, in an attempt to provide a background scenario for the “HDL story”, a lipoprotein still in search of a role.
Optimization of Exopolysaccharide (EPS) Production by Rhodotorula mucilaginosa sp. GUMS16
Authors: Okoro Oseweuba Valentine , Gholipour Amir Reza , Sedighi Faezeh , Shavandi Amin , Hamidi Masoud
Published: July 2021

Exopolysaccharides (EPSs) are important biopolymers with diverse applications such as gelling compounds in food and cosmetic industries and as bio-flocculants in pollution remediation and bioplastics production. This research focuses on enhancing crude EPS production from Rhodotorula mucilaginosa sp. GUMS16 using the central composite design method in which five levels of process variables of sucrose, pH, and ammonium sulfate were investigated with sucrose and ammonium sulfate serving as carbon and nitrogen sources during microbial incubation. The optimal crude EPS production of 13.48 g/100 mL was achieved at 1 g/100 mL of sucrose concentration, 14.73 g/100 mL of ammonium sulfate at pH 5. Variations in ammonium sulfate concentrations (1.27–14.73 g/100 mL) presented the most significant effects on the crude EPS yield, while changes in sucrose concentrations (1–5 g/100 mL) constituted the least important process variable influencing the EPS yield. The Rhodotorula mucilaginosa sp. GUMS16 may have the potential for large-scale production of EPS for food and biomedical applications.
Singlet/Triplet State Anti/Aromaticity of CyclopentadienylCation: Sensitivity to Substituent Effect
Authors: Stojanović Milovan , Aleksić Jovana , Baranac-Stojanović Marija
Published: July 2021

It is well known that singlet state aromaticity is quite insensitive to substituent effects, in the case of monosubstitution. In this work, we use density functional theory (DFT) calculations to examine the sensitivity of triplet state aromaticity to substituent effects. For this purpose, we chose the singlet state antiaromatic cyclopentadienyl cation, antiaromaticity of which reverses to triplet state aromaticity, conforming to Baird’s rule. The extent of (anti)aromaticity was evaluated by using structural (HOMA), magnetic (NICS), energetic (ISE), and electronic (EDDBp) criteria. We find that the extent of triplet state aromaticity of monosubstituted cyclopentadienyl cations is weaker than the singlet state aromaticity of benzene and is, thus, slightly more sensitive to substituent effects. As an addition to the existing literature data, we also discuss substituent effects on singlet state antiaromaticity of cyclopentadienyl cation.
Carbon Monoxide Therapy Using Hybrid Carbon Monoxide-Releasing/Nrf2-Inducing Molecules through a Neuroprotective Lens
Authors: Cavicchioli Flavia , Cesarotti Izzy M. , Fangman Madison , Lua Josh , Hautamaki Raymond , Doré Sylvain
Published: July 2021

Carbon monoxide (CO) has long been known for its toxicity. However, in recent decades, new applications for CO as a therapeutic compound have been proposed, and multiple forms of CO therapy have since been developed and studied. Previous research has found that CO has a role as a gasotransmitter and promotes anti-inflammatory and antioxidant effects, making it an avenue of interest for medicine. Such effects are possible because of the Nrf2/HO1 pathway, which has become a target for therapy development because its activation also leads to CO release. Currently, different forms of treatment involving CO include inhaled CO (iCO), carbon monoxide-releasing molecules (CORMs), and hybrid carbon monoxide-releasing molecules (HYCOs). In this article, we review the progression of CO studies to develop possible therapies, the possible mechanisms involved in the effects of CO, and the current forms of therapy using CO.
Influence of Parental Attitudes on Formation of Psychological Resilience and Adherence to Medical Regime in Adolescents after Liver or Renal Transplantation
Authors: Biernacka Marta , Jakubowska-Winecka Anna , Kaliciński Piotr
Published: July 2021

Identifying the causes of poor disease control and medication non-adherence is indispensable so that patients can benefit from treatment. The aim of our study was to determine the relationship between parental attitudes, the development of psychological resilience, and systematic medication adherence in a group of adolescents after kidney and liver transplantation. The analysis included the results obtained from 96 families. A total of 52 patients after kidney transplantation and 44 patients after liver transplantation, aged 12–18 years and their parents were examined. The types of parental attitudes were assessed using the Parental Attitude Scale. The patient’s resilience was determined with the Resiliency Assessment Scale. The MMAS-8 was used to assess the regularity of medication-taking behavior. A total of 61% of the patients in the study group displayed high levels of psychological resilience. The analyses showed a positive correlation between resilience and the systematic taking of medication by the patients. Moreover, it was found that the analyzed link between psychological resilience on the degree of the regularity of medication intake was enhanced by a specific type of parental attitude. The obtained results confirm the importance of psychological resources in developing better disease control. The relationship between the type of parental attitudes and medication adherence indicates the need to take into account the family context during the child’s treatment.
Hepatic Gene Expression Changes in Rats Internally Exposed to Radioactive 56MnO2 Particles at Low Doses
Authors: Ruslanova Bakhyt , Abishev Zhaslan , Chaizhunussova Nailya , Shabdarbayeva Dariya , Tokesheva Sholpan , Amantayeva Gaukhar , Kairkhanova Ynkar , Stepanenko Valeriy , Hoshi Masaharu , Fujimoto Nariaki
Published: July 2021

We have studied the biological effects of the internal exposure to radioactive manganese-56 dioxide (56MnO2), the major radioisotope dust found in soil after atomic bomb explosions. Our previous study of blood chemistry indicated a possible adverse effect of 56MnO2 on the liver. In the present study, we further examined the effects on the liver by determining changes in hepatic gene expressions. Male Wistar rats were exposed to 56MnO2 particles (three groups with the whole-body doses of 41, 90, and 100 mGy), stable MnO2 particles, or external 60Co γ-rays (2 Gy), and were examined together with the non-treated control group on postexposure day 3 and day 61. No histopathological changes were observed in the liver. The mRNA expression of a p53-related gene, the cyclin-dependent kinase inhibitor 1A, increased in 56MnO2 as well as in γ-ray irradiated groups on postexposure day 3 and day 61. The expression of a stress-responsive gene, nuclear factor κB, was also increased by 56MnO2 and γ-rays on postexposure day 3. However, the expression of cytokine genes (interleukin-6 or chemokine ligand 2) or fibrosis-related TGF-β/Smad genes (Tgfb1, Smad3, or Smad4) was not altered by the exposure. Our data demonstrated that the internal exposure to 56MnO2 particles at less than 0.1 Gy significantly affected the short-term gene expressions in the liver in a similar manner with 2 Gy of external γ-irradiation. These changes may be adaptive responses because no changes occurred in cytokine or TGF-β/Smad gene expressions.
Characterisation of Electroplated Gold Coatings for Dental Applications: Estimation of Thickness Using Non-Destructive Electron-Probe Microanalysis Related to Plating Time
Authors: Walton Terry R
Published: July 2021

Objectives: This study aimed to measure non-destructively gold (Au) electrodeposited on a high-gold alloy by modulating coating time and comparing this to sputtering Au to known thicknesses. Methods: Au was electrodeposited (plated) on 11 high-gold alloy plates (A–K) at 2.8V between 20 and 220 min. Seven Au strips were sputter coated on the same alloy to known thicknesses (range 50–500 nm). Energy dispersive X-ray spectroscopy (EDS) was used to measure minimal electron energy (E0) required to penetrate Au coatings and generate x-ray signals of 1% atomic palladium (Pd) from the underlying alloy for test samples and Au strips. % Pd X-ray concentration at maximum 30 kV was also obtained. The obtained signal–thickness relationship of known Au strip thicknesses was used to calculate Au thickness on the A–K samples based on two analytical relations. Energy dispersive X-ray fluorescence spectroscopy (XRF) was used as a complementary method to ensure coating thickness estimations were accurate. Results: EDS values for all reference and unknown thicknesses were obtained and verified with XRF. Correlating these signals with the Data Analysis Software and matching with known plating times allowed estimation of Au thickness of the unknown samples (range 27–425 nm). Estimated thicknesses were shown to have a linear relationship with plating time except for samples C–D, where there was an inverted relationship. Significance: A non-destructive method for measuring electrodeposited thickness of Au on high-gold alloys related to plating time was developed and verified. There is a linear relationship to Au thickness and plating time between 20 and 220 min.
Effect of Mullite Film Layers on the High-Temperature Oxidation Resistance of AISI 304 Stainless Steel
Authors: Ma Jing , Wen Ning , Wang Ruiyang , Wang Jiangang , Zhang Xin , Li Jianhui , Chen Yiqing
Published: July 2021

Protective coating is an effective way to extend materials’ high-temperature service life. In order to improve the high-temperature oxidation resistance of AISI 304 stainless steel, mullite films with different layers were successfully prepared by the sol-gel method and the sintering process on the surface of stainless steel. The effect of the film layers on the high-temperature oxidation resistance of stainless steel at 900 °C for 100 h was studied. The analysis results of oxidation kinetics, X-rays diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive analysis (EDS) show that Al1.4Si0.3O2.7 mullite film effectively improved the high-temperature oxidation resistance of stainless steel. The sample with three-layer mullite film has the best high-temperature oxidation resistance. The mass gain and oxidation spalling mass are only 4.6% and 34.5% of those of the uncoated sample after 100 h cyclic oxidation at 900 °C. A chromium oxide layer was formed at the interface of mullite film and the substrate during the sintering process. The generation of selective Cr2O3 scale was promoted at the cyclic oxidation stage so that the sample with three-layers has excellent high-temperature oxidation resistance.
Influence of the Curing and Annealing Temperatures on the Properties of Solution Processed Tin Oxide Thin Films
Authors: Avis Christophe , Jang Jin
Published: July 2021

We report the effect of the curing (Tcuring) and annealing (Tanneal) temperatures on the structural, electrical, and optical properties of solution processed tin oxide. Tanneal was varied from 300 to 500 °C, and Tcuring from 200 °C to Tanneal. All Tanneal lead to a polycrystalline phase, but the amorphous phase was observed at Tanneal = 300 °C and Tcuring ranging from 250 to 300 °C. This could be explained by the melting point of the precursor (SnCl2), occurring at 250 °C. The crystallinity can be effectively controlled by the annealing temperature, but the curing temperature dramatically affects the grain size. We can reach grain sizes from 5–10 nm (Tcuring = 200 °C and Tanneal = 300 °C) to 30–50 nm (Tcuring = 500 °C and Tanneal = 500 °C). At a fixed Tanneal, Hall mobilities, carrier concentration, and conductivity increased with the curing temperature. The Hall mobility was in the range of 1 to 9.4 cm2/Vs, the carrier concentration was 1018 to 1019 cm−3, and the conductivity could reach ~20 S/cm when the grain size was 30–50 nm. The optical transmittance, the optical bandgap, the refractive index, and the extinction coefficient were also analyzed and they show a correlation with the annealing process.
Inverse Columnar-Equiaxed Transition (CET) in 304 and 316L Stainless Steels Melt by Electron Beam for Additive Manufacturing (AM)
Authors: Miyata Yuichiro , Okugawa Masayuki , Koizumi Yuichiro , Nakano Takayoshi
Published: July 2021

According to Hunt’s columnar-to-equiaxed transition (CET) criterion, which is generally accepted, a high-temperature gradient (G) in the solidification front is preferable to a low G for forming columnar grains. Here, we report the opposite tendency found in the solidification microstructure of stainless steels partially melted by scanning electron beam for powder bed fusion (PBF)-type additive manufacturing. Equiaxed grains were observed more frequently in the region of high G rather than in the region of low G, contrary to the trend of the CET criterion. Computational thermal-fluid dynamics (CtFD) simulation has revealed that the fluid velocity is significantly higher in the case of smaller melt regions. The G on the solidification front of a small melt pool tends to be high, but at the same, the temperature gradient along the melt pool surface also tends to be high. The high melt surface temperature gradient can enhance Marangoni flow, which can apparently reverse the trend of equiaxed grain formation.
NeuroTec Sitem-Insel Bern: Closing the Last Mile in Neurology
Authors: Schindler Kaspar A. , Nef Tobias , Baud Maxime O. , Tzovara Athina , Yilmaz Gürkan , Tinkhauser Gerd , Gerber Stephan M. , Gnarra Oriella , Warncke Jan D. , Schütz Narayan , Knobel Samuel E. J. , Schmidt Markus H. , Krack Paul , Fröhlich Flavio , Sznitman Raphael , Rothen Simon , Bassetti Claudio L. A.
Published: July 2021

Neurology is focused on a model where patients receive their care through repeated visits to clinics and doctor’s offices. Diagnostic tests often require expensive and specialized equipment that are only available in clinics. However, this current model has significant drawbacks. First, diagnostic tests, such as daytime EEG and sleep studies, occur under artificial conditions in the clinic, which may mask or wrongly emphasize clinically important features. Second, early detection and high-quality management of chronic neurological disorders require repeat measurements to accurately capture the dynamics of the disease process, which is impractical to execute in the clinic for economical and logistical reasons. Third, clinic visits remain inaccessible to many patients due to geographical and economical circumstances. Fourth, global disruptions to daily life, such as the one caused by COVID-19, can seriously harm patients if access to in-person clinical visits for diagnostic and treatment purposes is throttled. Thus, translating diagnostic and treatment procedures to patients’ homes will convey multiple substantial benefits and has the potential to substantially improve clinical outcomes while reducing cost. NeuroTec was founded to accelerate the re-imagining of neurology and to promote the convergence of technological, scientific, medical and societal processes. The goal is to identify and validate new digital biomarkers that can close the last mile in neurology by enabling the translation of personalized diagnostics and therapeutic interventions from the clinic to the patient’s home.
How Does Circadian Rhythm Shape Host-Parasite Associations? A Comparative Study on Infection Patterns in Diurnal and Nocturnal Raptors
Authors: Gao Kai , Zhou Bing , Yang Li-Xing , Dong Lu , Huang Xi , Deng Wen-Hong
Published: July 2021

Infection patterns of parasites, including their prevalence, diversity and host specificity, can be impacted by many biological and environmental factors, but no study has focused on the circadian rhythms of vertebrate hosts, which may affect susceptibilities and encounter rates between hosts and vectors and further shape host-parasite associations. In this study, we focused on avian haemosporidians, a classical model in studies of host-parasite associations, and investigated the infection patterns in rescued raptors brought to the Beijing Raptor Rescue Center during 2007–2020. We first assessed the association between prevalence and host biotic traits; haemosporidian prevalence was higher in the nocturnal raptors than in the diurnal raptors, and the prevalence of Haemoproteus and Leucocytozoon in the nocturnal raptors was significantly higher than that in the diurnal raptors. Furthermore, we analysed the phylogenetic relationship and host-parasite network-level differences of haemosporidian parasites in diurnal and nocturnal raptors, and demonstrated that the lineages infecting the diurnal and nocturnal raptors were not clearly separated, but the nocturnal lifestyle led to a more specialized host-parasite network structure. These variations in host-parasite associations may be driven by different susceptibilities of the hosts and the diversity or abundance of vectors during the day and night. Our study provides new insight into host-parasite associations shaped by circadian rhythm and calls for more studies on the underlying mechanisms of parasite infection.
Quantitative Multispectral Imaging Differentiates Melanoma from Seborrheic Keratosis
Authors: Bozsányi Szabolcs , Farkas Klára , Bánvölgyi András , Lőrincz Kende , Fésűs Luca , Anker Pálma , Zakariás Sára , Jobbágy Antal , Lihacova Ilze , Lihachev Alexey , Lange Marta , Bliznuks Dmitrijs , Medvecz Márta , Kiss Norbert , Wikonkál Norbert M.
Published: July 2021

Melanoma is a melanocytic tumor that is responsible for the most skin cancer-related deaths. By contrast, seborrheic keratosis (SK) is a very common benign lesion with a clinical picture that may resemble melanoma. We used a multispectral imaging device to distinguish these two entities, with the use of autofluorescence imaging with 405 nm and diffuse reflectance imaging with 525 and 660 narrow-band LED illumination. We analyzed intensity descriptors of the acquired images. These included ratios of intensity values of different channels, standard deviation and minimum/maximum values of intensity of the lesions. The pattern of the lesions was also assessed with the use of particle analysis. We found significantly higher intensity values in SKs compared with melanoma, especially with the use of the autofluorescence channel. Moreover, we found a significantly higher number of particles with high fluorescence in SKs. We created a parameter, the SK index, using these values to differentiate melanoma from SK with a sensitivity of 91.9% and specificity of 57.0%. In conclusion, this imaging technique is potentially applicable to distinguish melanoma from SK based on the analysis of various quantitative parameters. For this application, multispectral imaging could be used as a screening tool by general physicians and non-experts in the everyday practice.
Cord Blood Extracellular Vesicles Analyzed by Flow Cytometry with Thresholding Using 405 nm or 488 nm Laser Leads to Concurrent Results
Authors: Pekárková Kristýna , Soukup Jakub , Kostelanská Marie , Širc Jan , Straňák Zbyněk , Holada Karel
Published: July 2021

Extracellular vesicles (EVs) from liquid biopsies are extensively analyzed by flow cytometry, a technology that is continuously evolving. Thresholding utilizing a violet 405 nm laser side scatter (VSSC) has recently been implemented. Here, we collected set of large EV (lEV) samples from cord blood, which we analyzed using a standard flow cytometer improved via a 405 nm laser side scatter. Samples were analyzed using two distinct thresholding methods—one based on VSSC, and one based on VSSC combined with fluorescence thresholding on stained phosphatidylserine. Through these thresholding methods, we compared lEVs from pre-term births and control cord blood. Double-labeled lEVs with platelet CD36+/CD41+, activated platelet CD41+/CD62P+ and endothelial CD31+/CD105+ antibodies were used. Apart from comparing the two groups together, we also correlated measured lEVs with the thresholding methods. We also correlated the results of this study with data analyzed in our previous study in which we used a conventional 488 nm laser SSC. We did not find any difference between the two cord blood groups. However, we found highly concurrent data via our correlation of the thresholding methods, with correlation coefficients ranging from 0.80 to 0.96 even though the numbers of detected lEVs differed between thresholding methods. In conclusion, our approaches to thresholding provided concurrent data and it seems that improving the cytometer with the use of a VSSC increases its sensitivity, despite not being particularly critical to the validity of flow cytometric studies that compare pathological and physiological conditions in liquid biopsies.
Cerebral Autoregulation during Postural Change in Patients with Cervical Spinal Cord Injury—A Carotid Duplex Ultrasonography Study
Authors: Kee Joo-Hyun , Han Jun-Hyeong , Moon Chang-Won , Cho Kang Hee
Published: July 2021

Patients with a spinal cord injury (SCI) frequently experience sudden falls in blood pressure during postural change. Few studies have investigated whether the measurement of blood flow velocity within vessels can reflect brain perfusion during postural change. By performing carotid duplex ultrasonography (CDU), we investigated changes in cerebral blood flow (CBF) during postural changes in patients with a cervical SCI, determined the correlation of CBF change with presyncopal symptoms, and investigated factors affecting cerebral autoregulation. We reviewed the medical records of 100 patients with a cervical SCI who underwent CDU. The differences between the systolic blood pressure, diastolic blood pressure, and CBF volume in the supine posture and after 5 min at 50° tilt were evaluated. Presyncopal symptoms occurred when the blood flow volume of the internal carotid artery decreased by ≥21% after tilt. In the group that had orthostatic hypotension and severe CBF decrease during tilt, the body mass index and physical and functional scores were lower than in other groups, and the proportion of patients with a severe SCI was high. The higher the SCI severity and the lower the functional score, the higher the possibility of cerebral autoregulation failure. CBF should be assessed by conducting CDU in patients with a high-level SCI.
Topological Data Analysis for Eye Fundus Image Quality Assessment
Authors: Avilés-Rodríguez Gener José , Nieto-Hipólito Juan Iván , Cosío-León María de los Ángeles , Romo-Cárdenas Gerardo Salvador , Sánchez-López Juan de Dios , Radilla-Chávez Patricia , Vázquez-Briseño Mabel
Published: July 2021

The objective of this work is to perform image quality assessment (IQA) of eye fundus images in the context of digital fundoscopy with topological data analysis (TDA) and machine learning methods. Eye health remains inaccessible for a large amount of the global population. Digital tools that automize the eye exam could be used to address this issue. IQA is a fundamental step in digital fundoscopy for clinical applications; it is one of the first steps in the preprocessing stages of computer-aided diagnosis (CAD) systems using eye fundus images. Images from the EyePACS dataset were used, and quality labels from previous works in the literature were selected. Cubical complexes were used to represent the images; the grayscale version was, then, used to calculate a persistent homology on the simplex and represented with persistence diagrams. Then, 30 vectorized topological descriptors were calculated from each image and used as input to a classification algorithm. Six different algorithms were tested for this study (SVM, decision tree, k-NN, random forest, logistic regression (LoGit), MLP). LoGit was selected and used for the classification of all images, given the low computational cost it carries. Performance results on the validation subset showed a global accuracy of 0.932, precision of 0.912 for label “quality” and 0.952 for label “no quality”, recall of 0.932 for label “quality” and 0.912 for label “no quality”, AUC of 0.980, F1 score of 0.932, and a Matthews correlation coefficient of 0.864. This work offers evidence for the use of topological methods for the process of quality assessment of eye fundus images, where a relatively small vector of characteristics (30 in this case) can enclose enough information for an algorithm to yield classification results useful in the clinical settings of a digital fundoscopy pipeline for CAD.