bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men
Authors: Gueugneau Marine , Coudy-Gandilhon Cécile , Chambon Christophe , Verney Julien , Taillandier Daniel , Combaret Lydie , Polge Cécile , Walrand Stéphane , Roche Frédéric , Barthélémy Jean-Claude , Féasson Léonard , Béchet Daniel
Published: April 2021

(1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified. Herein we performed omic profiling to decipher in muscle which dominating processes are associated with healthy aging and metabolic syndrome in old men. (2) Methods: This study included 15 healthy young, 15 healthy old, and 9 old men with metabolic syndrome. Old men were selected from a well-characterized cohort, and each vastus lateralis biopsy was used to combine global transcriptomic and proteomic analyses. (3) Results: Over-representation analysis of differentially expressed genes (ORA) and functional class scoring of pathways (FCS) indicated that healthy aging was mainly associated with upregulations of apoptosis and immune function and downregulations of glycolysis and protein catabolism. ORA and FCS indicated that with metabolic syndrome the dominating biological processes were upregulation of proteolysis and downregulation of oxidative phosphorylation. Proteomic profiling matched 586 muscle proteins between individuals. The proteome of healthy aging revealed modifications consistent with a fast-to-slow transition and downregulation of glycolysis. These transitions were reduced with metabolic syndrome, which was more associated with alterations in NADH/NAD+ shuttle and β-oxidation. Proteomic profiling further showed that all old muscles overexpressed protein chaperones to preserve proteostasis and myofiber integrity. There was also evidence of aging-related increases in reactive oxygen species but better detoxifications of cytotoxic aldehydes and membrane protection in healthy than in metabolic syndrome muscles. (4) Conclusions: Most candidate proteins and mRNAs identified herein constitute putative muscle biomarkers of healthy aging and metabolic syndrome in old men.
Application of CRISPR/Cas9 in Crop Quality Improvement
Authors: Liu Qier , Yang Fan , Zhang Jingjuan , Liu Hang , Rahman Shanjida , Islam Shahidul , Ma Wujun , She Maoyun
Published: April 2021

The various crop species are major agricultural products and play an indispensable role in sustaining human life. Over a long period, breeders strove to increase crop yield and improve quality through traditional breeding strategies. Today, many breeders have achieved remarkable results using modern molecular technologies. Recently, a new gene-editing system, named the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, has also succeeded in improving crop quality. It has become the most popular tool for crop improvement due to its versatility. It has accelerated crop breeding progress by virtue of its precision in specific gene editing. This review summarizes the current application of CRISPR/Cas9 technology in crop quality improvement. It includes the modulation in appearance, palatability, nutritional components and other preferred traits of various crops. In addition, the challenge in its future application is also discussed.
Could Lipoxins Represent a New Standard in Ischemic Stroke Treatment?
Authors: Tułowiecka Nikola , Kotlęga Dariusz , Bohatyrewicz Andrzej , Szczuko Małgorzata
Published: April 2021

Introduction: Cardiovascular diseases including stroke are one of the most common causes of death. Their main cause is atherosclerosis and chronic inflammation in the body. An ischemic stroke may occur as a result of the rupture of unstable atherosclerotic plaque. Cardiovascular diseases are associated with uncontrolled inflammation. The inflammatory reaction produces chemical mediators that stimulate the resolution of inflammation. One of these mediators is lipoxins—pro-resolving mediators that are derived from the omega-6 fatty acid family, promoting inflammation relief and supporting tissue regeneration. Aim: The aim of the study was to review the available literature on the therapeutic potential of lipoxins in the context of ischemic stroke. Material and Methods: Articles published up to 31 January 2021 were included in the review. The literature was searched on the basis of PubMed and Embase in terms of the entries: ‘stroke and lipoxin’ and ‘stroke and atherosclerosis’, resulting in over 110 articles in total. Studies that were not in full-text English, letters to the editor, and conference abstracts were excluded. Results: In animal studies, the injection/administration of lipoxin A4 improved the integrity of the blood–brain barrier (BBB), decreased the volume of damage caused by ischemic stroke, and decreased brain edema. In addition, lipoxin A4 inhibited the infiltration of neutrophils and the production of cytokines and pro-inflammatory chemokines, such as interleukin (Il-1β, Il-6, Il-8) and tumor necrosis factor-α (TNF-α). The beneficial effects were also observed after introducing the administration of lipoxin A4 analog—BML-111. BML-111 significantly reduces the size of a stroke and protects the cerebral cortex, possibly by reducing the permeability of the blood–brain barrier. Moreover, more potent than lipoxin A4, it has an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines and increasing the amount of anti-inflammatory cytokines. Conclusions: Lipoxins and their analogues may find application in reducing damage caused by stroke and improving the prognosis of patients after ischemic stroke.
Preventive Aspects of Early Resveratrol Supplementation in Cardiovascular and Kidney Disease of Developmental Origins
Authors: Hsu Chien-Ning , Hou Chih-Yao , Tain You-Lin
Published: April 2021

The increase in the incidence of cardiovascular diseases (CVDs) and kidney disease has stimulated research for strategies that could prevent, rather than just treat, both interconnected disorders. Resveratrol, a polyphenolic compound with pleiotropic biofunctions, has shown health benefits. Emerging epidemiological data supports that early life environmental insults are regarded as increased risks of developing CVDs and kidney disease in adulthood. Conversely, both disorders could be reversed or postponed by shifting interventions from adulthood to earlier stage by so-called reprogramming. The purpose of this review is first to highlight current epidemiological studies linking cardiovascular and renal programming to resulting CVD and kidney disease of developmental origins. This will be followed by a summary of how resveratrol could exert a positive influence on CVDs and kidney disease. This review also presents an overview of the evidence documenting resveratrol as a reprogramming agent to protect against CVD and kidney disease of developmental origins from animal studies and to outline the advances in understanding the underlying molecular mechanisms. Overall, this review reveals the need for future research to further clarify the reprogramming effects of resveratrol before clinical translation.
MET Exon 14 Skipping: A Case Study for the Detection of Genetic Variants in Cancer Driver Genes by Deep Learning
Authors: Nosi Vladimir , Luca Alessandrì , Milan Melissa , Arigoni Maddalena , Benvenuti Silvia , Cacchiarelli Davide , Cesana Marcella , Riccardo Sara , Di Filippo Lucio , Cordero Francesca , Beccuti Marco , Comoglio Paolo M. , Calogero Raffaele A.
Published: April 2021

Background: Disruption of alternative splicing (AS) is frequently observed in cancer and might represent an important signature for tumor progression and therapy. Exon skipping (ES) represents one of the most frequent AS events, and in non-small cell lung cancer (NSCLC) MET exon 14 skipping was shown to be targetable. Methods: We constructed neural networks (NN/CNN) specifically designed to detect MET exon 14 skipping events using RNAseq data. Furthermore, for discovery purposes we also developed a sparsely connected autoencoder to identify uncharacterized MET isoforms. Results: The neural networks had a Met exon 14 skipping detection rate greater than 94% when tested on a manually curated set of 690 TCGA bronchus and lung samples. When globally applied to 2605 TCGA samples, we observed that the majority of false positives was characterized by a blurry coverage of exon 14, but interestingly they share a common coverage peak in the second intron and we speculate that this event could be the transcription signature of a LINE1 (Long Interspersed Nuclear Element 1)-MET (Mesenchymal Epithelial Transition receptor tyrosine kinase) fusion. Conclusions: Taken together, our results indicate that neural networks can be an effective tool to provide a quick classification of pathological transcription events, and sparsely connected autoencoders could represent the basis for the development of an effective discovery tool.
Differential miRNA Expression Profiling Reveals Correlation of miR125b-5p with Persistent Infection of Japanese Encephalitis Virus
Authors: Huang Chih-Wei , Tsai Kuen-Nan , Chen Yi-Shiuan , Chang Ruey-Yi
Published: April 2021

MicroRNAs (miRNAs) play versatile roles in multiple biological processes. However, little is known about miRNA’s involvement in flavivirus persistent infection. Here, we used an miRNA array analysis of Japanese encephalitis virus (JEV)-infected cells to search for persistent infection-associated miRNAs in comparison to acute infection. Among all differentially expressed miRNAs, the miR-125b-5p is the most significantly increased one. The high level of miR-125b-5p in persistently JEV-infected cells was confirmed by Northern analysis and real-time quantitative polymerase chain reaction. As soon as the cells established a persistent infection, a significantly high expression of miR-125b-5p was readily observed. Transfecting excess quantities of a miR-125b-5p mimic into acutely infected cells reduced genome replication and virus titers. Host targets of miR125b-5p were analyzed by target prediction algorithms, and six candidates were confirmed by a dual-luciferase reporter assay. These genes were upregulated in the acutely infected cells and sharply declined in the persistently infected cells. The transfection of the miR125b-5p mimic reduced the expression levels of Stat3, Map2k7, and Triap1. Our studies indicated that miR-125b-5p targets both viral and host sequences, suggesting its role in coordinating viral replication and host antiviral responses. This is the first report to characterize the potential roles of miR-125b-5p in persistent JEV infections.
Genistein Activates Transcription Factor EB and Corrects Niemann–Pick C Phenotype
Authors: Argüello Graciela , Balboa Elisa , Tapia Pablo J. , Castro Juan , Yañez María José , Mattar Pamela , Pulgar Rodrigo , Zanlungo Silvana
Published: April 2021

Niemann–Pick type C disease (NPCD) is a lysosomal storage disease (LSD) characterized by abnormal cholesterol accumulation in lysosomes, impaired autophagy flux, and lysosomal dysfunction. The activation of transcription factor EB (TFEB), a master lysosomal function regulator, reduces the accumulation of lysosomal substrates in LSDs where the degradative capacity of the cells is compromised. Genistein can pass the blood–brain barrier and activate TFEB. Hence, we investigated the effect of TFEB activation by genistein toward correcting the NPC phenotype. We show that genistein promotes TFEB translocation to the nucleus in HeLa TFEB-GFP, Huh7, and SHSY-5Y cells treated with U18666A and NPC1 patient fibroblasts. Genistein treatment improved lysosomal protein expression and autophagic flux, decreasing p62 levels and increasing those of the LC3-II in NPC1 patient fibroblasts. Genistein induced an increase in β-hexosaminidase activity in the culture media of NPC1 patient fibroblasts, suggesting an increase in lysosomal exocytosis, which correlated with a decrease in cholesterol accumulation after filipin staining, including cells treated with U18666A and NPC1 patient fibroblasts. These results support that genistein-mediated TFEB activation corrects pathological phenotypes in NPC models and substantiates the need for further studies on this isoflavonoid as a potential therapeutic agent to treat NPCD and other LSDs with neurological compromise.
Circulating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome
Authors: Signorini Cinzia , Leoncini Silvia , Durand Thierry , Galano Jean-Marie , Guy Alexandre , Bultel-Poncé Valérie , Oger Camille , Lee Jetty Chung-Yung , Ciccoli Lucia , Hayek Joussef , De Felice Claudio
Published: April 2021

Neuroprostanes, a family of non-enzymatic metabolites of the docosahexaenoic acid, have been suggested as potential biomarkers for neurological diseases. Objective biological markers are strongly needed in Rett syndrome (RTT), which is a progressive X-linked neurodevelopmental disorder that is mainly caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene with a predominant multisystemic phenotype. The aim of the study is to assess a possible association between MECP2 mutations or RTT disease progression and plasma levels of 4(RS)-4-F4t-neuroprostane (4-F4t-NeuroP) and 10(RS)-10-F4t-neuroprostane (10-F4t-NeuroP) in typical RTT patients with proven MECP2 gene mutation. Clinical severity and disease progression were assessed using the Rett clinical severity scale (RCSS) in n = 77 RTT patients. The 4-F4t-NeuroP and 10-F4t-NeuroP molecules were totally synthesized and used to identify the contents of the plasma of the patients. Neuroprostane levels were related to MECP2 mutation category (i.e., early truncating, gene deletion, late truncating, and missense), specific hotspot mutations (i.e., R106W, R133C, R168X, R255X, R270X, R294X, R306C, and T158M), and disease stage (II through IV). Circulating 4-F4t-NeuroP and 10-F4t-NeuroP were significantly related to (i) the type of MECP2 mutations where higher levels were associated to gene deletions (p ≤ 0.001); (ii) severity of common hotspot MECP2 mutation (large deletions, R168X, R255X, and R270X); (iii) disease stage, where higher concentrations were observed at stage II (p ≤ 0.002); and (iv) deficiency in walking (p ≤ 0.0003). This study indicates the biological significance of 4-F4t-NeuroP and 10-F4t-NeuroP as promising molecules to mark the disease progression and potentially gauge genotype–phenotype associations in RTT.
Myeloid and T-Cell Microenvironment Immune Features Identify Two Prognostic Sub-Groups in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms
Authors: Centonze Giovanni , Lagano Vincenzo , Sabella Giovanna , Mangogna Alessandro , Garzone Giovanna , Filugelli Martina , Belmonte Beatrice , Cattaneo Laura , Crisafulli Valentina , Pellegrinelli Alessio , Simbolo Michele , Scarpa Aldo , Spaggiari Paola , Brambilla Tatiana , Pusceddu Sara , Prinzi Natalie , Anichini Andrea , Tripodo Claudio , Milione Massimo
Published: April 2021

High-grade Gastroenteropancreatic Neuroendocrine neoplasms (H-NENs) comprehend well-differentiated tumors (NET G3) and poorly differentiated carcinomas (NEC) with proliferative activity indexes as mitotic count (MC) >20 mitoses/10 HPF and Ki-67 >20%. At present, no specific therapy for H-NENs exists and the several evidences of microenvironment involvement in their pathogenesis pave the way for tailored therapies. Forty-five consecutive cases, with available information about T-cell, immune, and non-immune markers, from surgical pathology and clinical databases of 2 Italian institutions were immunostained for Arginase, CD33, CD163 and CD66 myeloid markers. The association between features was assessed by Spearman’s correlation coefficient. A unsupervised K-means algorithm was used to identify clusters of patients according to inputs of microenvironment features and the relationship between clusters and clinicopathological features, including cancer-specific survival (CSS), was analyzed. The H-NEN population was composed of 6 (13.3%) NET G3 and 39 (86.7%) NEC. Overall, significant positive associations were found between myeloid (CD33, CD163 and Arginase) and T/immune markers (CD3, CD4, CD8, PD-1 and HLA-I). Myeloid and T-cell markers CD3 and CD8 identified two clusters of patients from unsupervised K-means analysis. Cases grouped in cluster 1 with more myeloid infiltrates, T cell, HLA and expression of inhibitory receptors and ligands in the stroma (PD-1, PD-L1) had significantly better CSS than patients in cluster 2. Multivariable analysis showed that Ki-67 (>55 vs. <55, HR 8.60, CI 95% 2.61–28.33, p < 0.0001) and cluster (1 vs. 2, HR 0.43, CI 95% 0.20–0.93, p = 0.03) were significantly associated with survival. High grade gastroenteropancreatic neuroendocrine neoplasms can be further classified into two prognostic sub-populations of tumors driven by different tumor microenvironments and immune features able to generate the framework for evaluating new therapeutic strategies.
Dysregulated Immunity and Immunotherapy after Sepsis
Authors: Darden Dijoia B. , Kelly Lauren S. , Fenner Brittany P. , Moldawer Lyle L. , Mohr Alicia M. , Efron Philip A.
Published: April 2021

Implementation of protocolized surveillance, diagnosis, and management of septic patients, and of surgical sepsis patients in particular, is shown to result in significantly increased numbers of patients surviving their initial hospitalization. Currently, most surgical sepsis patients will rapidly recover from sepsis; however, many patients will not rapidly recover, but instead will go on to develop chronic critical illness (CCI) and experience dismal long-term outcomes. The elderly and comorbid patient is highly susceptible to death or CCI after sepsis. Here, we review aspects of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) endotype to explain the underlying pathobiology of a dysregulated immune system in sepsis survivors who develop CCI; then, we explore targets for immunomodulatory therapy.
PEComa—A Rare Liver Tumor
Authors: Krawczyk Marek , Ziarkiewicz-Wróblewska Bogna , Wróblewski Tadeusz , Podgórska Joanna , Grzybowski Jakub , Gierej Beata , Krawczyk Piotr , Nyckowski Paweł , Kornasiewicz Oskar , Patkowski Waldemar , Remiszewski Piotr , Zając Krzysztof , Grąt Michał
Published: April 2021

PEComa (perivascular epithelioid cell tumor) is a rare liver tumor. Decisions regarding patient management are currently based on a few small case series. The aim of this study was to report the clinicopathological features of PEComa in order to provide guidance for management, complemented by our own experience. This retrospective observational study included all patients with PEComa who underwent surgical treatment in two departments between 2002 and 2020. A total of 20 patients were diagnosed with PEComa following histopathological examination. The age of the patients ranged from 21 to 73 years. The majority of patients were women (85%). In most patients, the tumors were incidental. In diagnostic studies, PEComas with high arterial vascularization have been described. Liver resection was the treatment of choice. There was only one postoperative complication. During histopathological evaluation, tumors were composed mostly of epithelioid cells, rarely with spindle cell components, thick-walled vessels, and adipocytes in different proportions. Melanocytic markers (HMB45, MelanA) and at least one smooth muscle marker were expressed in all tumors. Features suggestive of malignancy were found in three cases. In conclusion, PEComa is a rare liver tumor that is usually diagnosed incidentally. In radiological studies, tumors with high arterial vascularization are observed. Liver resection is the treatment of choice.
PCSK9 and the Gut-Liver-Brain Axis: A Novel Therapeutic Target for Immune Regulation in Alcohol Use Disorder
Authors: Lee Ji Soo , O’Connell Emma M. , Pacher Pal , Lohoff Falk W.
Published: April 2021

Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by an impaired ability to control or stop alcohol intake and is associated with organ damage including alcohol-associated liver disease (ALD) and progressive neurodegeneration. The etiology of AUD is complex, but organ injury due to chronic alcohol use can be partially attributed to systemic and local inflammation along the gut-liver-brain axis. Excessive alcohol use can result in translocation of bacterial products into circulation, increased expression of pro-inflammatory cytokines, and activation of immune cells, including macrophages and/or microglia in the liver and brain. One potential mediator of this alcohol-induced inflammation is proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is primarily known for its regulation of plasma low-density lipoprotein cholesterol but has more recently been shown to influence inflammatory responses in the liver and brain. In rodent and post-mortem brain studies, chronic alcohol use altered methylation of the PCSK9 gene and increased expression of PCSK9 in the liver and cerebral spinal fluid. Additionally, PCSK9 inhibition in a rat model of ALD attenuated liver inflammation and steatosis. PCSK9 may play an important role in alcohol-induced pathologies along the gut-liver-brain axis and may be a novel therapeutic target for AUD-related liver and brain inflammation.
Patterns, Predictors, and Prognostic Value of Skeletal Muscle Mass Loss in Patients with Locally Advanced Head and Neck Cancer Undergoing Cisplatin-Based Chemoradiotherapy
Authors: Chargi Najiba , Wegner Inge , Markazi Navid , Smid Ernst , de Jong Pim , Devriese Lot , de Bree Remco
Published: April 2021

Low skeletal muscle mass (SMM) is associated with toxicities and decreased survival in head and neck cancer (HNC). Chemoradiotherapy (CRT) may exaggerate loss of SMM. We investigated the changes in SMM, their predictors, and prognostic impact of SMM in patients treated with CRT between 2012 and 2018. Skeletal muscle area (SMA) segmentation was performed on pre- and post-CRT imaging. Observed changes in SMM were categorized into: (I) Stable, (II) moderate gain (III), moderate loss, (IV) large gain, and (V) large loss. In total, 235 HNC patients were included, of which 39% had stable SMM, 55% moderate loss, 13% moderate gain, 0.4% large loss, and 0.4% large gain of SMM. After CRT, SMA decreased compared to pre-CRT (31.6 cm2 versus 33.3 cm2, p < 0.01). The key predictor was a body mass index (BMI) of ≥30 kg/m2 (OR 3.6, 95% CI 1.4–9.3, p < 0.01). Low SMM at diagnosis (HR 2.1; 95% CI 1.1–4.1, p = 0.03) and an HPV-positive oropharyngeal tumor (HR 0.1; 95% CI 0.01–0.9, p = 0.04) were prognostic for overall survival. Changes in SMM were not prognostic for survival. Loss of SMM is highly prevalent after CRT and a high BMI before treatment may aid in identifying patients at risk.
Idiopathic Peripheral Retinal Telangiectasia in Adults: A Case Series and Literature Review
Authors: Gawęcki Maciej
Published: April 2021

Idiopathic peripheral retinal telangiectasia (IPT), often termed as Coats disease, can present in a milder form with the onset in adulthood. The goal of this case series study and literature review was to describe and classify different presenting forms and treatment of this entity and to review contemporary methods of its management. Six cases of adult onset IPT were described with the following phenotypes based on fundus ophthalmoscopy, fluorescein angiography, and optical coherence tomography findings: IPT without exudates or foveal involvement, IPT with peripheral exudates without foveal involvement, IPT with peripheral exudates and cystoid macular edema, and IPT with peripheral and macular hard exudates. Treatments applied in this series included observation, laser photocoagulation, and anti-vascular endothelial growth factor (VEGF) treatment with variable outcomes depending upon the extent of IPT, the aggressiveness of laser treatment, and the stringency of follow-up. The accompanying literature review suggests that ablative therapies, especially laser photocoagulation, remain the most effective treatment option in adult-onset IPT, with anti-VEGF therapy serving as an adjuvant procedure. Close follow-up is necessary to achieve and maintain reasonable good visual and morphological results.
Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients
Authors: Wang Zhitao , Jiang Rui , Li Qian , Wang Huiping , Tao Qianshan , Zhai Zhimin
Published: April 2021

Myeloid-derived suppressor cells (MDSCs) are defined as negative regulators that suppress the immune response through a variety of mechanisms, which usually cluster in cancer, inflammation, and autoimmune diseases. This study aims to investigate the correlation between M-MDSCs and the clinical features of diffuse large B-cell lymphoma (DLBCL) patients, as well as the possible accumulation mechanism of M-MDSCs. The level of M-MDSCs is significantly increased in newly diagnosed and relapsed DLBCL patients. Regarding newly diagnosed DLBCL patients, the frequency of M-MDSCs is positively correlated with tumor progression and negatively correlated with overall survival (OS). More importantly, the level of M-MDSCs can be defined as a biomarker for a poor prognosis in DLBCL patients. Additionally, interleukin-35 (IL-35) mediates the accumulation of M-MDSCs in DLBCL patients. Anti-IL-35 treatment significantly reduces levels of M-MDSCs in Ly8 tumor-bearing mice. Thus, M-MDSCs are involved in the pathological process of DLBCL. Targeting M-MDSCs may be a promising therapeutic strategy for the treatment of DLBCL patients.
Determinants of Infant Adiposity across the First 6 Months of Life: Evidence from the Baby-bod study
Authors: Herath Manoja P. , Ahuja Kiran D. K. , Beckett Jeffrey M. , Jayasinghe Sisitha , Byrne Nuala M. , Hills Andrew P.
Published: April 2021

Excess adiposity in infancy may predispose individuals to obesity later in life. The literature on determinants of adiposity in infants is equivocal. In this longitudinal cohort study, we investigated pre-pregnancy, prenatal and postnatal determinants of different adiposity indices in infants, i.e., fat mass (FM), percent FM (%FM), fat mass index (FMI) and log-log index (FM/FFMp), from birth to 6 months, using linear mixed-effects regression. Body composition was measured in 322, 174 and 109 infants at birth and 3 and 6 months afterwards, respectively, utilising air displacement plethysmography. Positive associations were observed between gestation length and infant FM, maternal self-reported pre-pregnancy body mass index and infant %FM, and parity and infant %FM and FMI at birth. Surprisingly, maternal intake of iron supplements during pregnancy was associated with infant FM, %FM and FMI at 3 months and FM/FFMp at 6 months. Male infant sex and formula feeding were negatively associated with all adiposity indices at 6 months. In conclusion, pre-pregnancy and pregnancy factors influence adiposity during early life, and any unfavourable impacts may be modulated postnatally via infant feeding practices. Moreover, as these associations are dependent on the adiposity indices used, it is crucial that researchers use conceptually and statistically robust approaches such as FM/FFMp.
Seroprevalence of Antibodies against SARS-CoV-2 in Children with Juvenile Idiopathic Arthritis a Case-Control Study
Authors: Opoka-Winiarska Violetta , Grywalska Ewelina , Korona-Glowniak Izabela , Matuska Katarzyna , Malm Anna , Roliński Jacek
Published: April 2021

There is limited data on the effect of the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) on pediatric rheumatology. We examined the prevalence of antibodies against SARS-CoV-2 in children with juvenile idiopathic arthritis (JIA) and a negative history of COVID-19 and the correlation of the presence of these antibodies with disease activity measured by juvenile arthritis disease activity score (JADAS). In total, 62 patients diagnosed with JIA, under treatment with various antirheumatic drugs, and 32 healthy children (control group) were included. Serum samples were analyzed for inflammatory markers and antibodies and their state evaluated with the juvenile arthritis disease activity score (JADAS). JIA patients do not have a higher seroprevalence of anti-SARS-CoV-2 antibodies than healthy subjects. We found anti-SARS-CoV-2 antibodies in JIA patients who did not have a history of COVID-19. The study showed no unequivocal correlation between the presence of SARS-CoV-2 antibodies and JIA activity; therefore, this relationship requires further observation. We also identified a possible link between patients’ humoral immune response and disease-modifying antirheumatic treatment, which will be confirmed in follow-up studies.
Can Deep Learning Using Weight Bearing Knee Anterio-Posterior Radiograph Alone Replace a Whole-Leg Radiograph in the Interpretation of Weight Bearing Line Ratio?
Authors: Moon Hyun-Doo , Choi Han-Gyeol , Lee Kyong-Joon , Choi Dong-Jun , Yoo Hyun-Jin , Lee Yong-Seuk
Published: April 2021

Weight bearing whole-leg radiograph (WLR) is essential to assess lower limb alignment such as weight bearing line (WBL) ratio. The purpose of this study was to develop a deep learning (DL) model that predicts the WBL ratio using knee standing AP alone. Total of 3997 knee AP & WLRs were used. WBL ratio was used for labeling and analysis of prediction accuracy. The WBL ratio was divided into seven categories (0, 0.1, 0.2, 0.3, 0.4, 0.5, and 0.6). After training, performance of the DL model was evaluated. Final performance was evaluated using 386 subjects as a test set. Cumulative score (CS) within error range 0.1 was set with showing maximum CS in the validation set (95% CI, 0.924–0.970). In the test set, mean absolute error was 0.054 (95% CI, 0.048–0.061) and CS was 0.951 (95% CI, 0.924–0.970). Developed DL algorithm could predict the WBL ratio on knee standing AP alone with comparable accuracy as the degree primary physician can assess the alignment. It can be the basis for developing an automated lower limb alignment assessment tool that can be used easily and cost-effectively in primary clinics.
Sex Differences in Lipid Profile across the Life Span in Patients with Type 2 Diabetes: A Primary Care-Based Study
Authors: Ambrož Martina , de Vries Sieta T. , Vart Priya , Dullaart Robin P. F. , Roeters van Lennep Jeanine , Denig Petra , Hoogenberg Klaas
Published: April 2021

We assessed sex differences across the life span in the lipid profile of type 2 diabetes (T2D) patients treated and not treated with statins. We used the Groningen Initiative to ANalyze Type 2 diabetes Treatment database, which includes T2D patients from the north of the Netherlands. Patients with a full lipid profile determined between 2010 and 2012 were included. We excluded patients treated with other lipid-lowering drugs than statins. Sex differences in low- and high-density lipoprotein cholesterol (LDL-c and HDL-c) and triglyceride (TG) levels across 11 age groups stratified by statin treatment were assessed using linear regression. We included 26,849 patients (51% women, 55% treated with statins). Without statins, women had significantly lower LDL-c levels than men before the age of 45 years, similar levels between 45 and 49 years, and higher levels thereafter. With statins, similar LDL-c levels were shown up to the age of 55, and higher levels in women thereafter. Women had significantly higher HDL-c levels than men, regardless of age or statin treatment. Men had significantly higher TG levels up to the age of 55 and 60, depending on whether they did not take or took statins, respectively, and similar levels thereafter. When managing cardiovascular risk in patients with T2D, attention is needed for the menopausal status of women and for TG levels in younger men.
Effect of Boundary Conditions on Fluid–Structure Coupled Modal Analysis of Runners
Authors: Liu Dianhai , Xia Xiang , Yang Jing , Wang Zhengwei
Published: April 2021

To predict the resonance characteristics of hydraulic machinery, it is necessary to accurately calculate the natural modes of the runners in the operating environment. However, in the existing research, the boundary conditions of the numerical modal analysis of the runner were not unified. In this paper, numerical modal analysis of a prototype Francis pump turbine runner was carried out using the acoustic–structure coupling method. The results of three different constraints were compared. The influence of the energy loss on the chamber wall on the natural modes of the runner was studied by the absorption boundary. The results show that the constraint condition (especially the rotating shaft) has significant impacts on the torsional mode, the radial mode, the 1 nodal-diameter mode, and the 0 nodal-circle mode, and the maximum differences in the natural frequencies under different conditions are 69.3%, 56.4%, 35.1%, and 9.4%, respectively. The change of the natural frequencies is closely related to the modal shapes. On the other hand, the energy loss on the wall mainly affects the nodal-circle modes, and the influence on other modes is negligible. The results can provide references for the design and resonance characteristics analysis of hydraulic machinery runners.
Systemic Resistance in Chilli Pepper against Anthracnose (Caused by Colletotrichum truncatum) Induced by Trichoderma harzianum, Trichoderma asperellum and Paenibacillus dendritiformis
Authors: Yadav Mukesh , Dubey Manish Kumar , Upadhyay Ram Sanmukh
Published: April 2021

In the present study, Paenibacillus dendritiformis, Trichoderma harzianum, and Trichoderma asperellum were appraised as potential biocontrol agents that induce resistance in chilli (Capsicum annuum) against the devastating pathogen Colletotrichum truncatum, which causes anthracnose. Bright-field and scanning electron micrographs showed the hyphal degradation, lysis, and abnormal swelling in C. truncatum against P. dendritiformis in a dual plate assay. Under greenhouse conditions, chilli seeds pretreated with P. dendritiformis, T. asperellum, T. harzianum, and T. asperellum + T. harzianum by soil soak method inflicted an induced systemic resistance (ISR) in chilli against a C. truncatum-challenged condition. In chilli, the disease index percentage was significantly reduced in the T. asperellum + T. harzianum-treated seeds, followed by the T. harzianum-, T. asperellum-, and P. dendritiformis-treated seeds as compared to the untreated and challenged, respectively. Chilli seeds were primed with T. asperellum + T. harzianum (78.67%), which revealed maximum disease protection under the challenged condition, followed by T. harzianum (70%), T. asperellum (64%), and P. dendritiformis (56%) as compared to untreated and C. truncatum-challenged (6%) condition served as control. The seeds that were pretreated with biocontrol agents (BCAs) inflicted ISR against C. truncatum by enhancing the activity of defence-related enzymes (superoxide dismutase (SOD), peroxidase (POX), polyphenol oxidase (PPO), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX) and phenylalanine ammonia-lyase (PAL)), accumulating phenolic compounds, and increasing the relative chlorophyll content in chilli. Nitroblue tetrazolium (NBT) and 3,3′-Diaminobenzidine (DAB) stains were used to detect the accumulation of superoxide anion and hydrogen peroxide that appeared nearby the fungal infection sites. The accumulation of reactive oxygen species (O2− and H2O2) in the pathogen-inoculated leaves was a maximum of 48 hpi, followed by P. dendritiformis, T. asperellum, T. harzianum, and T. asperellum + T. harzianum treated tissue upon C. truncatum-challenged condition as compared to the control. Overall, our results showed the potential of T. harzianum, T. asperellum, and P. dendritiformis as biocontrol agents that prevent infection by C. truncatum and inflict an induced systemic resistance in chilli by enhancing the biosynthesis of phenolic compounds, defence and antioxidative enzymes, and reducing the lesion development and reactive oxygen species accumulation. This is the first report of induced systemic resistance against anthracnose in chilli obtained by application of T. harzianum, T. asperellum and P. dendritiformis, through seed priming.
Trichoderma Biological Control to Protect Sensitive Maize Hybrids against Late Wilt Disease in the Field
Authors: Degani Ofir , Dor Shlomit
Published: April 2021

Late wilt, a disease severely affecting maize fields throughout Israel, is characterized by the relatively rapid wilting of maize plants from the tasseling stage to maturity. The disease is caused by the fungus Magnaporthiopsis maydis, a soil and seed-borne pathogen. The pathogen is controlled traditionally through the use of maize cultivars having reduced sensitivity to the disease. Nevertheless, such cultivars may lose their immunity after several years of intensive growth due to the presence of high virulent isolates of M. maydis. Alternative effective and economical chemical treatment to the disease was recently established but is dependent on the use of a dripline assigned for two adjacent rows and exposes the risk of fungicide resistance. In the current work, eight marine and soil isolates of Trichoderma spp., known for high mycoparasitic potential, were tested as biocontrol agents against M. maydis. An in vitro confront plate assay revealed strong antagonistic activity against the pathogen of two T. longibrachiatum isolates and of T. asperelloides. These species produce soluble metabolites that can inhibit or kill the maize pathogen in submerged and solid media culture growth assays. In greenhouse experiments accompanied by real-time PCR tracking of the pathogen, the Trichoderma species or their metabolites managed to improve the seedlings’ wet biomass and reduced the pathogen DNA in the maize roots. A follow-up experiment carried out through a whole growth session, under field conditions, provided important support to the Trichoderma species’ beneficial impact. The direct addition of T. longibrachiatum and even more T. asperelloides to the seeds, with the sowing, resulted in a yield improvement, a significant increase in the growth parameters and crops, to the degree of noninfected plants. These bioprotective treatments also restricted the pathogen DNA in the host tissues (up to 98%) and prevented the disease symptoms. The results encourage more in-depth research to uncover such biological agents’ potential and the methods to implement them in commercial fields. If adequately developed into final products and combined with other control methods, the biological control could play an important role in maize crop protection against Late wilt.
Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy
Authors: Chen Shu-Fang , Pan Hsiu-Yung , Huang Chi-Ren , Huang Jyun-Bin , Tan Teng-Yeow , Chen Nai-Ching , Hsu Chung-Yao , Chuang Yao-Chung
Published: April 2021

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation—the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)—all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.
Efficacy and Safety of Multi-Session Transcranial Direct Current Stimulation on Social Cognition in Schizophrenia: A Study Protocol for an Open-Label, Single-Arm Trial
Authors: Yamada Yuji , Inagawa Takuma , Yokoi Yuma , Shirama Aya , Sueyoshi Kazuki , Wada Ayumu , Hirabayashi Naotsugu , Oi Hideki , Sumiyoshi Tomiki
Published: April 2021

Backgrounds: Social cognition is defined as the mental operations underlying social behavior. Patients with schizophrenia elicit impairments of social cognition, which is linked to poor real-world functional outcomes. In a previous study, transcranial direct current stimulation (tDCS) improved emotional recognition, a domain of social cognition, in patients with schizophrenia. However, since social cognition was only minimally improved by tDCS when administered on frontal brain areas, investigations on the effect of tDCS on other cortical sites more directly related to social cognition are needed. Therefore, we present a study protocol to determine whether multi-session tDCS on superior temporal sulcus (STS) would improve social cognition deficits of schizophrenia. Methods: This is an open-label, single-arm trial, whose objective is to investigate the efficacy and safety of multi-session tDCS over the left STS to improve social cognition in patients with schizophrenia. The primary outcome measure will be the Social Cognition Screening Questionnaire. Neurocognition, functional capacity, and psychotic symptoms will also be evaluated by the Brief Assessment of Cognition in Schizophrenia, UCSD Performance-Based Skills Assessment-Brief, and Positive and Negative Syndrome Scale, respectively. Data will be collected at baseline, and 4 weeks after the end of intervention. If social cognition is improved in patients with schizophrenia by tDCS based on this protocol, we may plan randomized controlled trial.
The Challenging Diagnosis of Pediatric Multisystem Inflammatory Syndrome Associated with Sars-Cov-2 Infection-Two Case Reports and Literature Review
Authors: Ionescu Marcela Daniela , Taras Roxana , Dombici Bianca , Balgradean Mihaela , Berghea Elena Camelia , Nicolescu Alin
Published: April 2021

Severe acute respiratory coronavirus 2 (SARS-CoV-2) is a novel coronavirus discovered in 2019 that caused the coronavirus disease 2019 (COVID19). During the last year, over 70 million people were infected and more than 1.5 million people died. Despite the tremendous number of people infected, children were less affected and presented milder forms of the disease. A short time after the pandemic was declared, a new hyperinflammatory syndrome resembling Kawasaki disease (KD) was described in children with confirmed or suspected SARS-CoV-2 infection named multisystem inflammatory syndrome in children (MIS-C). The incidence of MIS-C is low and it has a polymorphous clinical presentation, making the diagnosis difficult. Although the incidence is reduced, there is a high risk of cardiovascular complications. In order to raise awareness, we present the cases of two pediatric patients diagnosed with MIS-C in our clinic.
Draft Methodology of the Age Management Implementation in Human Resource Management in a Transport Company
Authors: Hlatká Martina , Stopka Ondrej , Bartuška Ladislav , Stopková Mária , Yordanova Daniela N. , Gross Patrik , Sádlo Petr
Published: April 2021

At present, companies should definitely be able to adapt to their environment. It entails being able to successfully predict and eliminate flaws and undesirable steps which may result in negative consequences. It can only be executed by careful consideration of three basic enterprise’s components which comprise the following: material resources, financial resources and human resources. An effective corporate coordination and human resource management is a cornerstone of the enterprise’s success while these components are of the same importance to this success. To this end, the aim of this manuscript is to design innovative recruitment procedures when using age management approach for a specific transport company; in particular, its human resource management is taken into consideration. In the initial parts of the manuscript, an analysis of quantitative and qualitative data is performed, wherein introduction into the addressed subject, relevant literature review, as well as description of utilized data and methods within the conducted research are elaborated. Consequently, in a case study section, the Work Ability Index (WAI) method is used to focus on the chosen group of employees in order to profoundly investigate their work abilities. The very examination of employees’ life cycle encompasses multiple age categories and measures a decrease in their work ability level. As for the ensuing (final) parts of the manuscript, a thorough evaluation of results obtained, appropriate discussion and, last but not least, conclusion section are compiled, in which the most imperative findings of the performed investigation are comprehensively summarized. Following the above, the purpose of this study is to compile a novel methodological procedure in terms of using the principles of age management in human resource management; specifically, in an opted transport company, and thus helping towards more effective and sustainable corporate recruitment strategy.