bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Roles of Calcium Signaling in the Development of Non-Alcoholic Fatty Liver Disease
Authors: Chen Chien-Chih , Hsu Li-Wen , Chen Kuang-Den , Chiu King-Wah , Chen Chao-Long , Huang Kuang-Tzu
Published: December 2021

The liver plays a central role in energy metabolism. Dysregulated hepatic lipid metabolism is a major cause of non-alcoholic fatty liver disease (NAFLD), a chronic liver disorder closely linked to obesity and insulin resistance. NAFLD is rapidly emerging as a global health problem with currently no approved therapy. While early stages of NAFLD are often considered benign, the disease can progress to an advanced stage that involves chronic inflammation, with increased risk for developing end-stage disease including fibrosis and liver cancer. Hence, there is an urgent need to identify potential pharmacological targets. Ca2+ is an essential signaling molecule involved in a myriad of cellular processes. Intracellular Ca2+ is intricately compartmentalized, and the Ca2+ flow is tightly controlled by a network of Ca2+ transport and buffering proteins. Impaired Ca2+ signaling is strongly associated with endoplasmic reticulum stress, mitochondrial dysfunction and autophagic defects, all of which are etiological factors of NAFLD. In this review, we describe the recent advances that underscore the critical role of dysregulated Ca2+ homeostasis in lipid metabolic abnormalities and discuss the feasibility of targeting Ca2+ signaling as a potential therapeutic approach.
Genetic Profiles and Risk Stratification in Adult De Novo Acute Myeloid Leukaemia in Relation to Age, Gender, and Ethnicity: A Study from Malaysia
Authors: Ambayya Angeli , Moorman Anthony V. , Sathar Jameela , Eswaran Jeyanthy , Sulong Sarina , Hassan Rosline
Published: December 2021

Hitherto, no data describing the heterogeneity of genetic profiles and risk stratifications of adult acute myeloid leukaemia (AML) in Southeast Asia are reported. This study assessed genetic profiles, Moorman’s hierarchical classification, and ELN 2017-based risk stratifications in relation to age, gender, and ethnicity in Malaysian adult AML patients. A total of 854 AML patients: male (52%), female (48%) were recruited comprising three main ethnic groups: Malays (59%), Chinese (32%) and Indians (8%). Of 307 patients with abnormal karyotypes: 36% exhibited translocations; 10% deletions and 5% trisomies. The commonest genotype was FLT3-ITD-NPM1wt (276/414; 66.7%). ELN 2017 risk stratification was performed on 494 patients, and 41% were classified as favourable, 39% as intermediate and 20% as adverse groups. More females (47%) were in the favourable risk group compared to males (37%), whereas adverse risk was higher in patients above 60 (24%) of age compared to below 60 (18%) patients. We observed heterogeneity in the distribution of genetic profiles and risk stratifications between the age groups and gender, but not among the ethnic groups. Our study elucidated the diversity of adult AML genetic profiles between Southeast Asians and other regions worldwide.
Effect of Low-Dose Ionizing Radiation on the Expression of Mitochondria-Related Genes in Human Mesenchymal Stem Cells
Authors: Kostyuk Svetlana V. , Proskurnina Elena V. , Konkova Marina S. , Abramova Margarita S. , Kalianov Andrey A. , Ershova Elizaveta S. , Izhevskaya Vera L. , Kutsev Sergey I. , Veiko Natalia N.
Published: December 2021

The concept of hormesis describes a phenomenon of adaptive response to low-dose ionizing radiation (LDIR). Similarly, the concept of mitohormesis states that the adaptive program in mitochondria is activated in response to minor stress effects. The mechanisms of hormesis effects are not clear, but it is assumed that they can be mediated by reactive oxygen species. Here, we studied effects of LDIR on mitochondria in mesenchymal stem cells. We have found that X-ray radiation at a dose of 10 cGy as well as oxidized fragments of cell-free DNA (cfDNA) at a concentration of 50 ng/mL resulted in an increased expression of a large number of genes regulating the function of the mitochondrial respiratory chain complexes in human mesenchymal stem cells (MSC). Several genes remained upregulated within hours after the exposure. Both X-ray radiation and oxidized cfDNA resulted in upregulation of FIS1 and MFN1 genes, which regulated fusion and fission of mitochondria, within 3–24 h after the exposure. Three hours after the exposure, the number of copies of mitochondrial DNA in cells had increased. These findings support the hypothesis that assumes oxidized cell-free DNA as a mediator of MSC response to low doses of radiation.
Mapping and Characterization of HCMV-Specific Unconventional HLA-E-Restricted CD8 T Cell Populations and Associated NK and T Cell Responses Using HLA/Peptide Tetramers and Spectral Flow Cytometry
Authors: Rousselière Amélie , Delbos Laurence , Bressollette Céline , Berthaume Maïlys , Charreau Béatrice
Published: December 2021

HCMV drives complex and multiple cellular immune responses, which causes a persistent immune imprint in hosts. This study aimed to achieve both a quantitative determination of the frequency for various anti-HCMV immune cell subsets, including CD8 T, γδT, NK cells, and a qualitative analysis of their phenotype. To map the various anti-HCMV cellular responses, we used a combination of three HLApeptide tetramer complexes (HLA-EVMAPRTLIL, HLA-EVMAPRSLLL, and HLA-A2NLVPMVATV) and antibodies for 18 surface markers (CD3, CD4, CD8, CD16, CD19, CD45RA, CD56, CD57, CD158, NKG2A, NKG2C, CCR7, TCRγδ, TCRγδ2, CX3CR1, KLRG1, 2B4, and PD-1) in a 20-color spectral flow cytometry analysis. This immunostaining protocol was applied to PBMCs isolated from HCMV− and HCMV+ individuals. Our workflow allows the efficient determination of events featuring HCMV infection such as CD4/CD8 ratio, CD8 inflation and differentiation, HCMV peptide-specific HLA-EUL40 and HLA-A2pp65CD8 T cells, and expansion of γδT and NK subsets including δ2−γT and memory-like NKG2C+CD57+ NK cells. Each subset can be further characterized by the expression of 2B4, PD-1, KLRG1, CD45RA, CCR7, CD158, and NKG2A to achieve a fine-tuned mapping of HCMV immune responses. This assay should be useful for the analysis and monitoring of T-and NK cell responses to HCMV infection or vaccines.
The Role of Birch Tar in Changing the Physicochemical and Biocidal Properties of Polylactide-Based Films
Authors: Richert Agnieszka , Olewnik-Kruszkowska Ewa , Dąbrowska Grażyna B. , Dąbrowski Henryk P.
Published: December 2021

The objective of this study was to produce bactericidal polymer films containing birch tar (BT). The produced polymer films contain PLA, plasticiser PEG (5% wt.) and birch tar (1, 5 and 10% wt.). Compared to plasticised PLA, films with BT were characterised by reduced elongation at break and reduced water vapour permeability, which was the lowest in the case of film with 10% wt. BT content. Changes in the morphology of the produced materials were observed by performing scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis; the addition of BT caused the surface of the film to be non-uniform and to contain recesses. FTIR analysis of plasticised PLA/BT films showed that the addition of birch tar did not change the crystallinity of the obtained materials. According to ISO 22196: 2011, the PLA film with 10% wt. BT content showed the highest antibacterial effect against the plant pathogens A. tumefaciens, X. campestris, P. brassicacearum, P. corrugata, P. syringae. It was found that the introduction of birch tar to plasticised PLA leads to a material with biocidal effect and favourable physicochemical and structural properties, which classifies this material for agricultural and horticultural applications.
Photolon Nanoporous Photoactive Material with Antibacterial Activity and Label-Free Noncontact Method for Free Radical Detection
Authors: Buzalewicz Igor , Hołowacz Iwona , Matczuk Anna K. , Guźniczak Mateusz , Skrzela Dominika , Karwańska Magdalena , Wieliczko Alina , Kowal Katarzyna , Ulatowska-Jarża Agnieszka
Published: December 2021

The worldwide increase in bacterial resistance and healthcare-associated bacterial infections pose a serious threat to human health. The antimicrobial photodynamic method reveals the opportunity for a new therapeutic approach that is based on the limited delivery of photosensitizer from the material surface. Nanoporous inorganic–organic composites were obtained by entrapment of photosensitizer Photolon in polysiloxanes that was prepared by the sol–gel method. The material was characterized by its porosity, optical properties (fluorescence and absorbance), and laser-induced antimicrobial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The permanent encapsulation of Photolon in the silica coating and the antimicrobial efficiency was confirmed by confocal microscope and digital holotomography. The generation of free radicals from nanoporous surfaces was proved by scanning Kelvin probe microscopy. For the first time, it was confirmed that Kelvin probe microscopy can be a label-free, noncontact alternative to other conventional methods based on fluorescence or chemiluminescence probes, etc. It was confirmed that the proposed photoactive coating enables the antibacterial photodynamic effect based on free radicals released from the surface of the coating. The highest bactericidal efficiency of the proposed coating was 87.16%. This coating can selectively limit the multiplication of bacterial cells, while protecting the environment and reducing the risk of surface contamination.
CRISPR/Cas9 Genome Editing vs. Over-Expression for Fluorescent Extracellular Vesicle-Labeling: A Quantitative Analysis
Authors: Strohmeier Karin , Hofmann Martina , Hauser Fabian , Sivun Dmitry , Puthukodan Sujitha , Karner Andreas , Sandner Georg , Le Renard Pol-Edern , Jacak Jaroslaw , Mairhofer Mario
Published: December 2021

Over-expression of fluorescently-labeled markers for extracellular vesicles is frequently used to visualize vesicle up-take and transport. EVs that are labeled by over-expression show considerable heterogeneity regarding the number of fluorophores on single particles, which could potentially bias tracking and up-take studies in favor of more strongly-labeled particles. To avoid the potential artefacts that are caused by over-expression, we developed a genome editing approach for the fluorescent labeling of the extracellular vesicle marker CD63 with green fluorescent protein using the CRISPR/Cas9 technology. Using single-molecule sensitive fluorescence microscopy, we quantitatively compared the degree of labeling of secreted small extracellular vesicles from conventional over-expression and the CRISPR/Cas9 approach with true single-particle measurements. With our analysis, we can demonstrate a larger fraction of single-GFP-labeled EVs in the EVs that were isolated from CRISPR/Cas9-modified cells (83%) compared to EVs that were isolated from GFP-CD63 over-expressing cells (36%). Despite only single-GFP-labeling, CRISPR-EVs can be detected and discriminated from auto-fluorescence after their up-take into cells. To demonstrate the flexibility of the CRISPR/Cas9 genome editing method, we fluorescently labeled EVs using the HaloTag® with lipid membrane permeable dye, JaneliaFluor® 646, which allowed us to perform 3D-localization microscopy of single EVs taken up by the cultured cells.
Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite
Authors: Deininger Christian , Wagner Andrea , Heimel Patrick , Salzer Elias , Vila Xavier Monforte , Weißenbacher Nadja , Grillari Johannes , Redl Heinz , Wichlas Florian , Freude Thomas , Tempfer Herbert , Teuschl-Woller Andreas Herbert , Traweger Andreas
Published: December 2021

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.
Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology
Authors: Dyakin Victor V. , Dyakina-Fagnano Nuka V. , Mcintire Laura B. , Uversky Vladimir N.
Published: December 2021

In humans, age-associated degrading changes, widely observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psychological abilities, and memory. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, genome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirality, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition of protein structure, makes them prone to multiple types of enzymatic and spontaneous PTMs, including racemization and isomerization. Spontaneous racemization leads to the loss of the balanced prevalent chirality. Advanced biological aging related to irreversible PTMs SP has been associated with the nontrivial interplay between somatic (molecular aging) and mental (psychological aging) health conditions. Through stress response systems (SRS), the environmental and psychological stressors contribute to the age-associated “collapse” of protein homochirality. The role of prevalent protein chirality and entropy of protein folding in biological aging is mainly overlooked. In a more generalized context, the time-dependent shift from enzymatic to the non-enzymatic transformation of biochirality might represent an important and yet underappreciated hallmark of aging. We provide the experimental arguments in support of the racemization theory of aging.
OsBIC1 Directly Interacts with OsCRYs to Regulate Leaf Sheath Length through Mediating GA-Responsive Pathway
Authors: Li Cong , Wang Xin , Zhang Liya , Zhang Chunyu , Yu Chunsheng , Zhao Tao , Liu Bin , Li Hongyu , Liu Jun
Published: December 2021

Cryptochrome 1 and 2 (CRY1 and CRY2) are blue light receptors involved in the regulation of hypocotyl elongation, cotyledon expansion, and flowering time in Arabidopsisthaliana. Two cryptochrome-interacting proteins, Blue-light Inhibitor of Cryptochrome 1 and 2 (BIC1 and BIC2), have been found in Arabidopsis. BIC1 plays critical roles in suppressing the physiological activities of CRY2, which include the blue light-dependent dimerization, phosphorylation, photobody formation, and degradation process, but the functional characterization of BIC protein in other crops has not yet been performed. To investigate the function of BIC protein in rice (Oryza sativa), two homologous genes of Arabidopsis BIC1 and BIC2, namely OsBIC1 and OsBIC2 (OsBICs), were identified. The overexpression of OsBIC1 and OsBIC2 led to increased leaf sheath length, whereas mutations in OsBIC1 displayed shorter leaf sheath in a blue light intensity-dependent manner. OsBIC1 regulated blue light-induced leaf sheath elongation through direct interaction with OsCRY1a, OsCRY1b, and OsCRY2 (OsCRYs). Longitudinal sections of the second leaf sheath demonstrated that OsBIC1 and OsCRYs controlled leaf sheath length by influencing the ratio of epidermal cells with different lengths. RNA-sequencing (RNA-seq) and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis further proved that OsBIC1 and OsCRYs regulated similar transcriptome changes in regulating Gibberellic Acids (GA)-responsive pathway. Taken together, these results suggested that OsBIC1 and OsCRYs worked together to regulate epidermal cell elongation and control blue light-induced leaf sheath elongation through the GA-responsive pathway.
Circulating Nucleic Acid-Based Biomarkers of Type 2 Diabetes
Authors: Padilla-Martinez Felipe , Wojciechowska Gladys , Szczerbinski Lukasz , Kretowski Adam
Published: December 2021

Type 2 diabetes (T2D) is a deficiency in how the body regulates glucose. Uncontrolled T2D will result in chronic high blood sugar levels, eventually resulting in T2D complications. These complications, such as kidney, eye, and nerve damage, are even harder to treat. Identifying individuals at high risk of developing T2D and its complications is essential for early prevention and treatment. Numerous studies have been done to identify biomarkers for T2D diagnosis and prognosis. This review focuses on recent T2D biomarker studies based on circulating nucleic acids using different omics technologies: genomics, transcriptomics, and epigenomics. Omics studies have profiled biomarker candidates from blood, urine, and other non-invasive samples. Despite methodological differences, several candidate biomarkers were reported for the risk and diagnosis of T2D, the prognosis of T2D complications, and pharmacodynamics of T2D treatments. Future studies should be done to validate the findings in larger samples and blood-based biomarkers in non-invasive samples to support the realization of precision medicine for T2D.
T-Cell Response against Varicella Zoster Virus in Patients with Multiple Sclerosis during Relapse and Remission
Authors: Pérez-Saldívar Miriam , Ordoñez Graciela , Pineda Benjamín , Sotelo Julio , Martínez-Palomo Adolfo , Flores-Rivera José , Espinosa-Cantellano Martha
Published: December 2021

An association between varicella zoster virus (VZV) and multiple sclerosis (MS) has been reported in Mexican populations. The aim of this study was to compare the response of T cells from MS patients, during relapse and remission, to in vitro stimulation with VZV, adenovirus (AV) and Epstein–Barr virus (EBV). Proliferation and cytokine secretion of T cells from 29 relapsing-remitting MS patients and 38 healthy controls (HC) were analyzed by flow cytometry after stimulating with VZV, AV or EBV. IgG and IgM levels against VZV and EBV were quantified using Enzyme-Linked Immunosorbent Assay. Relapsing MS patients showed a higher percentage of responding CD4+ and CD8+ T cells against VZV compared to AV. In HC and remitting MS patients, proliferation of CD4+ T cells was higher when stimulated with VZV as compared to EBV. Moreover, T cells isolated from remitting patients secreted predominantly Th1 cytokines when cell cultures were stimulated with VZV. Finally, high concentration of anti-VZV IgG was found in sera from patients and controls. The results support previous studies of an VZV-MS association in the particular population studied and provide additional information about the possible role of this virus in the pathogenesis of MS.
Pharmacological Inhibition of CCR2 Signaling Exacerbates Exercise-Induced Inflammation Independently of Neutrophil Infiltration and Oxidative Stress
Authors: Tominaga Takaki , Huang Jiapeng , Suzuki Katsuhiko
Published: December 2021

Although exercise-induced humoral factors known as exerkines benefit systemic health, the role of most exerkines has not been investigated. Monocyte chemoattractant protein-1 (MCP-1) is a representative chemokine whose circulating concentrations increase after exercise, and it is one of the exerkines. MCP-1 is a ligand for CC chemokine receptor 2 (CCR2), which is expressed on monocytes, macrophages, and muscle cells. However, there is no information on the role of CCR2 signaling in exercise. Therefore, to investigate the research question, we administrated CCR2 antagonist or PBS to mice to inhibit CCR2 signaling before and after exercise. Our results showed that CCR2 signaling inhibition promoted exercise-induced macrophage infiltration and inflammation 24 h after exercise in muscle. CCR2 signaling inhibition also exacerbated exercise-induced inflammation immediately after exercise in muscle. However, neutrophil infiltration and oxidative stress had no contribution to exercise-induced inflammation by CCR2 signaling inhibition. CCR2 signaling inhibition also exacerbated exercise-induced inflammation immediately after exercise in kidney, liver, and adipose tissues. To summarize, pharmacological inhibition of CCR2 signaling exacerbated exercise-induced inflammation independently of neutrophil infiltration and oxidative stress.
Suitable Areas for Apiculture Expansion Determined by Antioxidant Power, Chemical Profiles, and Pesticide Residues in Caldcluvia paniculata Honey and Beeswax Samples
Authors: Mejías Enrique , Gómez Carlos , Garrido Tatiana
Published: December 2021

Forty-two samples of Tiaca Honey (Caldcluvia paniculata) obtained from beehives belonging to 14 apiaries (three honey samples per apiary) were collected at the end of January near Osorno (40°34′ S, 73°8′ W), Puyehue (40°40′ S, 72°37′ W) and Frutillar 41°7′ S, 72°59′ W) covering an area of 1240 km2. They presented the highest phenol contents (0.36 mg gallic acid equivalent/kg) and antioxidant power (1.27 mM equivalent of Fe+2/g of sample), and were among the highest for antiradical activity. Phenol contents and antioxidant power (r = 0.72, p-value < 0.01) and total phenol contents and antiradical activity (r = 0.69; p-value < 0.01) displayed linear correlations. Only two beeswax samples showed residues of the pesticide fenhexamid. The respective sites (Purranque [40°55′ S, 73°10′ W] and Coligual [40°49′ S, 72°54′ W]) were the only areas located near active farms. Additionally, the m/z value 163.1091 was found as an element to identify honeys. Data were used to construct a mapped suitability index ranking for pesticide-free areas with high biological quality. The provided chemical profiles will aid local beekeepers in obtaining international certifications, particularly for the EU market. In turn, the constructed maps indicate suitable areas for apiculture expansion, while differentiated pesticide detection in honey and beeswax requires further comparative research.
Reliability of Morphological and PCR Methods for the Official Diagnosis of Aethina tumida (Coleoptera: Nitidulidae): A European Inter-Laboratory Comparison
Authors: Franco Stéphanie , Cougoule Nicolas , Tison Amandine , Del Cont Aurélie , Gastaldi Cristina , Consortium ILC , Duquesne Véronique
Published: December 2021

The Small Hive Beetle (Aethina tumida Murray, 1867) is an invasive scavenger of honeybees. Originally endemic in sub-Saharan Africa, it is regulated internationally in order to preserve the areas still free from this species. To ensure the reliability of official diagnoses in case of introduction, an inter-laboratory comparison was organised on the identification of A. tumida by morphology and real-time PCR. Twenty-two National Reference Laboratories in Europe participated in the study and analysed 12 samples with adult coleopterans and insect larvae. The performance of the laboratories was evaluated in terms of sensitivity and specificity. Sensitivity was satisfactory for all the participants and both types of methods, thus fully meeting the diagnostic challenge of confirming all truly positive cases as positive. Two participants encountered specificity problems. For one, the anomaly was minor whereas, for the other, the issues concerned a larger number of results, especially real-time PCR, which probably were related to inexperience with this technique. The comparison demonstrated the reliability of official diagnosis, including the entire analytical process of A. tumida identification: from the first step of the analysis to the expression of opinions. The performed diagnostic tools, in parallel with field surveillance, are essential to managing A. tumida introduction.
Performance of Copeptin for Early Diagnosis of Acute Coronary Syndromes: A Systematic Review and Meta-Analysis of 14,139 Patients
Authors: Szarpak Lukasz , Lapinski Marcin , Gasecka Aleksandra , Pruc Michal , Drela Wiktoria L. , Koda Mariusz , Denegri Andrea , Peacock Frank W. , Jaguszewski Miłosz J. , Filipiak Krzysztof J.
Published: December 2021

Diagnosis of acute coronary syndrome (ACS) based on copeptin level may enable one to confirm or rule-out acute myocardial infarction (AMI) with higher sensitivity and specificity, which may in turn further reduce mortality rate and decrease the economic costs of ACS treatment. We conducted a systematic review and meta-analysis to investigate the relationship between copeptin levels and type of ACS. We searched Scopus, PubMed, Web of Science, Embase, and Cochrane to locate all articles published up to 10 October 2021. We evaluated a meta-analysis with random-effects models to evaluate differences in copeptin levels. A total of 14,139 patients (4565 with ACS) were included from twenty-seven studies. Copeptin levels in AMI and non-AMI groups varied and amounted to 68.7 ± 74.7 versus 14.8 ± 19.9 pmol/L (SMD = 2.63; 95% CI: 2.02 to 3.24; p < 0.001). Copeptin levels in the AMI group was higher than in the unstable angina (UAP) group, at 51.9 ± 52.5 versus 12.8 ± 19.7 pmol/L (SMD = 1.53; 95% CI: 0.86 to 2.20; p < 0.001). Copeptin levels in ST-elevation myocardial infarction (STEMI) versus non-ST elevation myocardial infarction (NSTEMI) patient groups were 54.8 ± 53.0 versus 28.7 ± 46.8 pmol/L, respectively (SMD = 1.69; 95% CI: = 0.70 to 4.09; p = 0.17). In summary, elevated copeptin levels were observed in patients with ACS compared with patients without ACS. Given its clinical value, copeptin levels may be included in the assessment of patients with ACS as well as for the initial differentiation of ACS.
Association of Sarcopenia with Osteopenia and Osteoporosis in Community-Dwelling Older Korean Adults: A Cross-Sectional Study
Authors: Lee Do-Youn , Shin Sunghoon
Published: December 2021

Sarcopenia and bone disorders, such as osteopenia and osteoporosis, are common musculoskeletal disorders in older adults. Therefore, this study aimed to establish the association between sarcopenia and bone disorders such as osteoporosis and osteopenia according to sex. We analyzed 3077 participants from the 2008–2011 Korean National Health and Nutrition Examination Survey aged 65 years or older. After adjusting for all covariates, such as physical examinations, exercise, and nutrient intake (model 4), the odds ratios for the association between sarcopenia and bone disorders were 2.051 (95% confidence interval [CI]: 1.498–2.808) in osteopenia and 2.258 (95% CI: 1.584–3.218) in osteoporosis. However, when sex was analyzed separately, the odds ratio was significantly different in men (osteopenia—2.068, 95% CI: 1.462–2.924; osteoporosis—3.247, 95% CI: 1.953–5.399), but not in women. Therefore, the results of this study show an association between sarcopenia and bone disorders in older Korean adults. Sarcopenia is significantly related to osteopenia and osteoporosis, especially in men, when stratified by sex.
Coronary Microvascular Vasodilatory Function: Related Clinical Features and Differences According to the Different Coronary Arteries and Types of Coronary Spasm
Authors: Teragawa Hiroki , Oshita Chikage , Uchimura Yuko , Akazawa Ryota , Orita Yuichi
Published: December 2021

Background: In the clinical setting; the microvascular vasodilatory function test (MVFT) with a pressure wire has been used in ischaemia patients with non-obstructive coronary arteries (INOCA), including vasospastic angina (VSA) and microvascular angina (MVA). The exact factors that affect the microvascular vasodilatory function (MVF) in such patients are still unknown. We aimed to identify the factors, including clinical parameters and lesion characteristics, affecting the MVF in such patients. Methods: A total of 53 patients who underwent coronary angiography, spasm provocation tests (SPTs) and MVFTs were enrolled. In the MVFT, the coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were measured. Of the 53 patients, MVFT data in the left anterior descending coronary artery (LAD) were obtained from 49 patients, and the clinical parameters were checked in all of them. Based on the results of the SPT, coronary spasms were divided into focal spasm, diffuse spasm, and microvascular spasm (MVS). To assess the lesion characteristics influencing MVF, MVFT data were compared according to the types of coronary spasm and coronary vessels in 73 vessels of the 53 patients. Results: In 49 patients who underwent the MVFT in the LAD, the IMR was higher in active smokers (n = 7) than in former smokers (n = 15) and never smokers (n = 27, p < 0.01). In the 73 coronary arteries in this study, the type of coronary spasm did not correlate with the CFR or IMR, whereas a higher IMR were more frequently observed in cases of focal spasm than in cases of diffuse spasm (p = 0.03). In addition, the IMR was higher in the right coronary artery (RCA) than in the LAD (p = 0.02). Conclusion: These results indicate that the smoking status affected the MVF in patients with INOCA, suggesting the possibility of improvement in the MVF by smoking cessation in such patients. In addition, in the assessment of MVF, it may be important to take into account which coronary artery or types of coronary spasm are being evaluated.
Elevated TAT in COVID-19 Patients with Normal D-Dimer as a Predictor of Severe Respiratory Failure: A Retrospective Analysis of 797 Patients
Authors: Takeshita Yuichiro , Terada Jiro , Hirasawa Yasutaka , Kinoshita Taku , Tajima Hiroshi , Koshikawa Ken , Kinouchi Toru , Isaka Yuri , Shionoya Yu , Fujikawa Atsushi , Tada Yuji , Nakaseko Chiaki , Tsushima Kenji
Published: December 2021

Although previous studies have revealed that elevated D-dimer in the early stage of coronavirus 2019 (COVID-19) indicates pulmonary intravascular coagulation, the state of coagulation/fibrinolysis disorder with normal D-dimer is unknown. The study aimed to investigate how coagulation/fibrinolysis markers affect severe respiratory failure in the early stage of COVID-19. Among 1043 patients with COVID-19, 797 patients were included in our single-center retrospective study. These 797 patients were divided into two groups, the normal D-dimer and elevated D-dimer groups and analyzed for each group. A logistic regression model was fitted for age, sex, body mass index (BMI) ≥ 30 kg/m2, fibrinogen ≥ 617 mg/dL, thrombin-antithrombin complex (TAT) ≥ 4.0 ng/mL, and plasmin-alpha2-plasmin inhibitor-complex (PIC) > 0.8 µg/mL. A multivariate analysis of the normal D-dimer group demonstrated that being male and TAT ≥ 4.0 ng/mL significantly affected severe respiratory failure. In a multivariate analysis of the elevated D-dimer group, BMI ≥ 30 kg/m2 and fibrinogen ≥ 617 mg/dL significantly affected severe respiratory failure. The elevated PIC did not affect severe respiratory failure in any group. Our study demonstrated that hypercoagulation due to SARS-CoV-2 infection may occur even during a normal D-dimer level, causing severe respiratory failure in COVID-19.
Pleomorphic Adenoma of the Parotid Gland and the Parapharyngeal Space: Two Diametrically Opposing Surgical Philosophies for the Same Histopathologic Entity?
Authors: Hornung Benita , Constantinidis Jannis , Thimsen Vivian , Agaimy Abbas , Koch Michael , Gostian Antoniu-Oreste , Sievert Matti , Müller Sarina , Iro Heinrich , Mantsopoulos Konstantinos
Published: December 2021

Background: The aim of this study was to investigate the histopathologic findings in parotid and parapharyngeal pleomorphic adenomas and draw conclusions concerning the surgical strategy. Methods: Retrospective study of medical charts of patients with resected pleomorphic adenomas (PA) between 2005 and 2020 at two tertiary medical referral centers. Histologic specimens were reexamined by an experienced head and neck pathologist. Patients with insufficient/incomplete data were excluded from our study sample. Results: A total of 844 patients formed our study sample (291 men, 553 women, average age 48.9 years); 786 cases had a PA in the parotid gland (PG) (93.1%), and the remaining 58 cases had a PA in the parapharyngeal space (PS) (6.9%). Recurrences were detected in 8/844 cases (7/786 in the PG, 1/58 in the PS, 0.94% in total) with a mean follow-up time of 86.7 months (10–189 months) with no statistically significant differences between the study groups (p = 0.527). Our analysis showed that parapharyngeal pleomorphic adenomas are characterized by a lower incidence of an intact anatomical capsule (71.4% vs. 82.6%, p = 0.035) and a remarkably more frequent occurrence of satellite nodules (20.7% vs. 7.5%, p < 0.001). Conclusions: The more challenging histopathologic profile of parapharyngeal pleomorphic adenomas points towards the fact that parapharyngeal surgery should remain in the hands of experienced surgeons at high-volume centers.
Intraoperative 3D Comparison of Round and Anatomical Breast Implants: Dispelling a Myth
Authors: Lotter Luisa , Zucal Isabel , Brébant Vanessa , Heine Norbert , Hartmann Robin , Mueller Karolina , Prantl Lukas , Schiltz Daniel
Published: December 2021

Background: Thanks to 3D imaging, it is possible to measure the influence of different parameters on breast augmentation. In this study, we compare the effect of different shapes and sizes of breast implants on the topography of the resulting breast. Furthermore, the impact of different breast implants on inter-landmark distances and on changes of the nipple position was assessed. Methods: This interventional prospective study was carried out on 10 female patients after collecting informed consent. 3D scans of the native and augmented breasts were performed intraoperatively with small, medium, and large sizes of both anatomical and round implants, resulting in a total of n = 130 single breast scans. These scans were analyzed for topographic shift quantification, nipple migration, and inter-landmark distances of the breast. Results: Implant size, but not implant shape leads to significant topographic shifts of the breast (p < 0.001 and p = 0.900, respectively). Both round and anatomical implants lead to a significantly higher volumetric increase in the upper quadrants compared to the lower quadrants (p < 0.001). Nipple migration into the superomedial quadrant was seen in about 90% of augmentations. No evident differences in inter-landmark distances were observed when round and anatomical implants of different sizes were compared. Conclusions: Implant size rather than shape influences the postoperative aesthetic results. No significant difference in topographic shift was found comparing round and anatomical implants, suggesting that both implant shapes result in comparable aesthetic outcomes.
Effectiveness of Learning Systems from Common Image File Types to Detect Osteosarcoma Based on Convolutional Neural Networks (CNNs) Models
Authors: Loraksa Chanunya , Mongkolsomlit Sirima , Nimsuk Nitikarn , Uscharapong Meenut , Kiatisevi Piya
Published: December 2021

Osteosarcoma is a rare bone cancer which is more common in children than in adults and has a high chance of metastasizing to the patient’s lungs. Due to initiated cases, it is difficult to diagnose and hard to detect the nodule in a lung at the early state. Convolutional Neural Networks (CNNs) are effectively applied for early state detection by considering CT-scanned images. Transferring patients from small hospitals to the cancer specialized hospital, Lerdsin Hospital, poses difficulties in information sharing because of the privacy and safety regulations. CD-ROM media was allowed for transferring patients’ data to Lerdsin Hospital. Digital Imaging and Communications in Medicine (DICOM) files cannot be stored on a CD-ROM. DICOM must be converted into other common image formats, such as BMP, JPG and PNG formats. Quality of images can affect the accuracy of the CNN models. In this research, the effect of different image formats is studied and experimented. Three popular medical CNN models, VGG-16, ResNet-50 and MobileNet-V2, are considered and used for osteosarcoma detection. The positive and negative class images are corrected from Lerdsin Hospital, and 80% of all images are used as a training dataset, while the rest are used to validate the trained models. Limited training images are simulated by reducing images in the training dataset. Each model is trained and validated by three different image formats, resulting in 54 testing cases. F1-Score and accuracy are calculated and compared for the models’ performance. VGG-16 is the most robust of all the formats. PNG format is the most preferred image format, followed by BMP and JPG formats, respectively.
Review on Additive Manufacturing of Multi-Material Parts: Progress and Challenges
Authors: Hasanov Seymur , Alkunte Suhas , Rajeshirke Mithila , Gupta Ankit , Huseynov Orkhan , Fidan Ismail , Alifui-Segbaya Frank , Rennie Allan
Published: December 2021

Additive manufacturing has already been established as a highly versatile manufacturing technique with demonstrated potential to completely transform conventional manufacturing in the future. The objective of this paper is to review the latest progress and challenges associated with the fabrication of multi-material parts using additive manufacturing technologies. Various manufacturing processes and materials used to produce functional components were investigated and summarized. The latest applications of multi-material additive manufacturing (MMAM) in the automotive, aerospace, biomedical and dentistry fields were demonstrated. An investigation on the current challenges was also carried out to predict the future direction of MMAM processes. It was concluded that further research and development is needed in the design of multi-material interfaces, manufacturing processes and the material compatibility of MMAM parts.
Effects of Trichoderma strigosellum in Eucalyptus urophylla Development and Leaf-Cutting Ant Behavior
Authors: Batista Kamilla Otoni Marques , Silva Dayara Vieira , Nascimento Vitor L. , de Souza Danival José
Published: December 2021

Fungal endophytes can protect plants against herbivory and be used to control leaf-cutting ants. In this study, we aimed to evaluate the potential of endophytic colonization of Eucalyptus urophylla by three filamentous fungal species and their influence on the plant development and foraging behavior of Atta sexdens. The study design was completely randomized and comprised a factorial scheme of 4 × 3, three antagonistic fungal species (Escovopsis sp., Metarhizium anisopliae, and Trichoderma strigosellum) of the leaf-cutting ant, and one control and three inoculation methods (conidial suspension via foliar spray [FS] and soil drench [SD] inoculation, and seedlings inoculated with mycelium [SWM]). The SWM method allowed T. strigosellum to colonize all plant organs, and these plants exhibited higher height, leaf number, shoot dry mass, and total dry mass than the ones subjected to the other inoculation methods. The SWM method increased the plant height than the control plants and those inoculated with Escovopsis sp. and M. anisopliae. Trichoderma strigosellum, previously isolated from soil, colonized E. urophylla plants and positively influenced their development, as demonstrated by the SWM method. Trichoderma strigosellum promoted the increase in E. urophylla height compared with when the FS and SD methods were used (by 19.62% and 18.52%, respectively). Our results reveal that A. sexdens workers preferentially began cutting the leaves from plants not previously colonized by T. strigosellum. This behavior can be explained by modifications in the phenotypic traits of the eucalyptus leaves.
A Simple Predictive Score to Distinguish between Disseminated Histoplasmosis and Tuberculosis in Patients with HIV
Authors: Nacher Mathieu , Drak Alsibai Kinan , Epelboin Loïc , Abboud Philippe , About Frédégonde , Demar Magalie , Djossou Félix , Blaizot Romain , Douine Maylis , Sabbah Nadia , Vignier Nicolas , Adriouch Leila , Lucarelli Aude , Boutrou Mathilde , Couppié Pierre , Adenis Antoine
Published: December 2021

Disseminated histoplasmosis is a common differential diagnosis of tuberculosis in disease-endemic areas. We aimed to find a predictive score to orient clinicians towards disseminated histoplasmosis or tuberculosis when facing a non-specific infectious syndrome in patients with advanced HIV disease. We reanalyzed data from a retrospective study in Cayenne Hospital between January 1997–December 2008 comparing disseminated histoplasmosis and tuberculosis: 100 confirmed disseminated histoplasmosis cases and 88 confirmed tuberculosis cases were included. A simple logit regression model was constructed to predict whether a case was tuberculosis or disseminated histoplasmosis. From this model, a score may be obtained, where the natural logarithm of the probability of disseminated histoplasmosis/tuberculosis = +3.917962 × WHO performance score (1 if >2, 0 if ≤2) −1.624642 × Pulmonary presentation (1 yes, 0 no) +2.245819 × Adenopathies > 2 cm (1 yes, 0 no) −0.015898 × CD4 count − 0.001851 × ASAT − 0.000871 × Neutrophil count − 0.000018 × Platelet count + 6.053793. The area under the curve was 98.55%. The sensitivity of the model to distinguish between disseminated histoplasmosis and tuberculosis was 95% (95% CI = 88.7–98.3%), and the specificity was 93% (95% CI = 85.7.3–97.4%). In conclusion, we here present a clinical-biological predictive score, using simple variables available on admission, that seemed to perform very well to discriminate disseminated histoplasmosis from tuberculosis in French Guiana in well characterized patients.
Effect of Issatchenkia terricola WJL-G4 on Deacidification Characteristics and Antioxidant Activities of Red Raspberry Wine Processing
Authors: He Hongying , Yan Yuchen , Dong Dan , Bao Yihong , Luo Ting , Chen Qihe , Wang Jinling
Published: December 2021

Our previous study isolated a novel Issatchenkia terricola WJL-G4, which exhibited a potent capability of reducing citric acid. In the current study, I. terricola WJL-G4 was applied to decrease the content of citric acid in red raspberry juice, followed by the red raspberry wine preparation by Saccharomyces cerevisiae fermentation, aiming to investigate the influence of I. terricola WJL-G4 on the physicochemical properties, organic acids, phenolic compounds and antioxidant activities during red raspberry wine processing. The results showed that after being treated with I. terricola WJL-G4, the citric acid contents in red raspberry juice decreased from 19.14 ± 0.09 to 6.62 ± 0.14 g/L, which was further declined to 5.59 ± 0.22 g/L after S. cerevisiae fermentation. Parameters related to CIELab color space, including L*, a*, b*, h°, and ∆E* exhibited the highest levels in samples after I. terricola WJL-G4 fermentation. Compared to the red raspberry wine pretreated without deacidification (RJO-SC), wine pretreated by I. terricola WJL-G4 (RJIT-SC) exhibited significantly decreased contents of gallic acid, cryptochlorogenic acid, and arbutin, while significantly increased contents of caffeic acid, sinapic acid, raspberry ketone, quercitrin, quercetin, baicalein, and rutin. Furthermore, the antioxidant activities including DPPH· and ABTS+· radical scavenging were enhanced in RJIT-SC group as compared to RJO-SC. This work revealed that I. terricola WJL-G4 had a great potential in red raspberry wine fermentation.
Biosynthesis Pathways, Transport Mechanisms and Biotechnological Applications of Fungal Siderophores
Authors: Pecoraro Lorenzo , Wang Xiao , Shah Dawood , Song Xiaoxuan , Kumar Vishal , Shakoor Abdul , Tripathi Keshawanand , Ramteke Pramod W. , Rani Rupa
Published: December 2021

Iron (Fe) is the fourth most abundant element on earth and represents an essential nutrient for life. As a fundamental mineral element for cell growth and development, iron is available for uptake as ferric ions, which are usually oxidized into complex oxyhydroxide polymers, insoluble under aerobic conditions. In these conditions, the bioavailability of iron is dramatically reduced. As a result, microorganisms face problems of iron acquisition, especially under low concentrations of this element. However, some microbes have evolved mechanisms for obtaining ferric irons from the extracellular medium or environment by forming small molecules often regarded as siderophores. Siderophores are high affinity iron-binding molecules produced by a repertoire of proteins found in the cytoplasm of cyanobacteria, bacteria, fungi, and plants. Common groups of siderophores include hydroxamates, catecholates, carboxylates, and hydroximates. The hydroxamate siderophores are commonly synthesized by fungi. L-ornithine is a biosynthetic precursor of siderophores, which is synthesized from multimodular large enzyme complexes through non-ribosomal peptide synthetases (NRPSs), while siderophore-Fe chelators cell wall mannoproteins (FIT1, FIT2, and FIT3) help the retention of siderophores. S. cerevisiae, for example, can express these proteins in two genetically separate systems (reductive and nonreductive) in the plasma membrane. These proteins can convert Fe (III) into Fe (II) by a ferrous-specific metalloreductase enzyme complex and flavin reductases (FREs). However, regulation of the siderophore through Fur Box protein on the DNA promoter region and its activation or repression depend primarily on the Fe availability in the external medium. Siderophores are essential due to their wide range of applications in biotechnology, medicine, bioremediation of heavy metal polluted environments, biocontrol of plant pathogens, and plant growth enhancement.
Enzymatic Bioprospecting of Fungi Isolated from a Tropical Rainforest in Mexico
Authors: Peraza-Jiménez Karla , De la Rosa-García Susana , Huijara-Vasconselos José Javier , Reyes-Estebanez Manuela , Gómez-Cornelio Sergio
Published: December 2021

The humid tropical environment provides an ideal place for developing a high diversity of plants; this is why it is an interesting site for the enzymatic bioprospecting of fungi that are responsible for the recycling of organic matter in an efficient and accelerated way and whose enzymes could have multiple biotechnological applications. For this study, 1250 isolates of macroscopic and microscopic fungal morphotypes were collected from soil, leaf litter, and wood. One hundred and fifty strains (50 from each source) were selected for the enzymatic screening. From the first phase, 51 strains with positive activity for laccase, protease, amylase, xylanase, and lipase enzymes were evaluated, of which 20 were isolated from leaf litter, 18 from the soil, and 13 from wood. The 10 best strains were selected for the enzymatic quantification, considering the potency index and the production of at least two enzymes. High laccase activity was detected for Trametes villosa FE35 and Marasmius sp. CE25 (1179 and 710.66 U/mg, respectively), while Daedalea flavida PE47 showed laccase (521.85 U/mg) and protease activities (80.66 U/mg). Fusarium spp. PH79 and FS400 strains had amylase (14.0 U/mg, 49.23 U/mg) and xylanase activities (40.05 U/mg, 36.03 U/mg) respectively. These results confirm the enzymatic potential of fungi that inhabit little-explored tropical rainforests with applications in industry.