bluuebunny/crossref_metadata_2025 huggingface dataset:
Free Cholesterol Affects the Function and Localization of Human Na+/Taurocholate Cotransporting Polypeptide (NTCP) and Organic Cation Transporter 1 (OCT1)
Authors: Idowu Jessica Y. , Hagenbuch Bruno
Published: August 2022

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are associated with obesity. They are accompanied by increased levels of free cholesterol in the liver. Most free cholesterol resides within the plasma membrane. We assessed the impact of adding or removing free cholesterol on the function and localization of two hepatocellular uptake transporters: the Na+/taurocholate cotransporting polypeptide (NTCP) and the organic cation transporter 1 (OCT1). We used a cholesterol–MCD complex (cholesterol) to add cholesterol and methyl-β-cyclodextrin (MCD) to remove cholesterol. Our results demonstrate that adding cholesterol decreases NTCP capacity from 132 ± 20 to 69 ± 37 µL/mg/min and OCT1 capacity from 209 ± 66 to 125 ± 26 µL/mg/min. Removing cholesterol increased NTCP and OCT1 capacity to 224 ± 65 and 279 ± 20 µL/mg/min, respectively. In addition, adding cholesterol increased the localization of NTCP within lipid rafts, while adding or removing cholesterol increased OCT1 localization in lipid rafts. These results demonstrate that increased cholesterol levels can impair NTCP and OCT1 function, suggesting that the free cholesterol content of the liver can alter bile acid and drug uptake into the liver. This could explain the increased plasma bile acid levels in NAFLD and NASH patients and potentially lead to altered drug disposition.
Inhibition of α(1,6)fucosyltransferase: Effects on Cell Proliferation, Migration, and Adhesion in an SW480/SW620 Syngeneic Colorectal Cancer Model
Authors: López-Cortés Rubén , Muinelo-Romay Laura , Fernández-Briera Almudena , Gil-Martín Emilio
Published: August 2022

The present study explored the impact of inhibiting α(1,6)fucosylation (core fucosylation) on the functional phenotype of a cellular model of colorectal cancer (CRC) malignization formed by the syngeneic SW480 and SW620 CRC lines. Expression of the FUT8 gene encoding α(1,6)fucosyltransferase was inhibited in tumor line SW480 by a combination of shRNA-based antisense knockdown and Lens culinaris agglutinin (LCA) selection. LCA-resistant clones were subsequently assayed in vitro for proliferation, migration, and adhesion. The α(1,6)FT-inhibited SW480 cells showed enhanced proliferation in adherent conditions, unlike their α(1,6)FT-depleted SW620 counterparts, which displayed reduced proliferation. Under non-adherent conditions, α(1,6)FT-inhibited SW480 cells also showed greater growth capacity than their respective non-targeted control (NTC) cells. However, cell migration decreased in SW480 after FUT8 knockdown, while adhesion to EA.hy926 cells was significantly enhanced. The reported results indicate that the FUT8 knockdown strategy with subsequent selection for LCA-resistant clones was effective in greatly reducing α(1,6)FT expression in SW480 and SW620 CRC lines. In addition, α(1,6)FT impairment affected the proliferation, migration, and adhesion of α(1,6)FT-deficient clones SW480 and SW620 in a tumor stage-dependent manner, suggesting that core fucosylation has a dynamic role in the evolution of CRC.
Targeting Tumor Acidosis and Regulatory T Cells Unmasks Anti-Metastatic Potential of Local Tumor Ablation in Triple-Negative Breast Cancer
Authors: Nief Corrine A. , Gonzales Alana , Chelales Erika , Agudogo Júlia Sroda , Crouch Brian T. , Nair Smita K. , Ramanujam Nirmala
Published: August 2022

Triple-negative breast cancer (TNBC) is an immunologically heterogenous disease that lacks clinically actionable targets and is more likely to progress to metastatic disease than other types of breast cancer. Tumor ablation has been used to increase response rates to checkpoint inhibitors, which remain low for TNBC patients. We hypothesized that tumor ablation could produce an anti-tumor response without using checkpoint inhibitors if immunosuppression (i.e., Tregs, tumor acidosis) was subdued. Tumors were primed with sodium bicarbonate (200 mM p.o.) to reduce tumor acidosis and low-dose cyclophosphamide (100–200 mg/kg i.p.) to deplete regulatory T cells, as has been shown independently in previous studies. A novel injectable ablative was then used to necrose the tumor, release tumor antigens, and initiate an immune event that could create an abscopal effect. This combination of bicarbonate, cyclophosphamide, and ablation, called “BiCyclA”, was tested in three syngeneic models of TNBC: E0771 (C57BL/6), 67NR (BALB/c), and 4T1-Luc (BALB/c). In E0771 and 67NR, BiCyclA therapy significantly reduced tumor growth and cured 5/7 and 6/10 mice 50 days after treatment respectively. In the metastatic 4T1-Luc tumors, for which surgery and checkpoint inhibitors fail, BiCyclA cured 5/10 mice of primary tumors and lung metastases. Notably, CD4+ and CD8+ T cells were found to be crucial for the anti-metastatic response, and cured mice were able to resist tumor rechallenge, suggesting production of immune memory. Reduction of tumor acidity and regulatory T cells with ablation is a simple yet effective therapy for local and systemic tumor control with broad applicability as it is not limited by expensive supplies.
Experimental Evidence for Seed Metabolic Allometry in Barrel Medic (Medicago truncatula Gaertn.)
Authors: Domergue Jean-Baptiste , Lalande Julie , Beucher Daniel , Satour Pascale , Abadie Cyril , Limami Anis M. , Tcherkez Guillaume
Published: August 2022

Seed size is often considered to be an important trait for seed quality, i.e., vigour and germination performance. It is believed that seed size reflects the quantity of reserve material and thus the C and N sources available for post-germinative processes. However, mechanisms linking seed size and quality are poorly documented. In particular, specific metabolic changes when seed size varies are not well-known. To gain insight into this aspect, we examined seed size and composition across different accessions of barrel medic (Medicago truncatula Gaertn.) from the genetic core collection. We conducted multi-elemental analyses and isotope measurements, as well as exact mass GC–MS metabolomics. There was a systematic increase in N content (+0.17% N mg−1) and a decrease in H content (–0.14% H mg−1) with seed size, reflecting lower lipid and higher S-poor protein quantity. There was also a decrease in 2H natural abundance (δ2H), due to the lower prevalence of 2H-enriched lipid hydrogen atoms that underwent isotopic exchange with water during seed development. Metabolomics showed that seed size correlates with free amino acid and hexoses content, and anticorrelates with amino acid degradation products, disaccharides, malic acid and free fatty acids. All accessions followed the same trend, with insignificant differences in metabolic properties between them. Our results show that there is no general, proportional increase in metabolite pools with seed size. Seed size appears to be determined by metabolic balance (between sugar and amino acid degradation vs. utilisation for storage), which is in turn likely determined by phloem source metabolite delivery during seed development.
Effectiveness of SARS-CoV-2 Vaccines for Short- and Long-Term Immunity: A General Overview for the Pandemic Contrast
Authors: Inchingolo Alessio Danilo , Malcangi Giuseppina , Ceci Sabino , Patano Assunta , Corriero Alberto , Vimercati Luigi , Azzollini Daniela , Marinelli Grazia , Coloccia Giovanni , Piras Fabio , Barile Giuseppe , Settanni Vito , Mancini Antonio , De Leonardis Nicole , Garofoli Grazia , Palmieri Giulia , Isacco Ciro Gargiulo , Rapone Biagio , Scardapane Arnaldo , Curatoli Luigi , Quaranta Nicola , Ribezzi Mario , Massaro Maria , Jones Megan , Bordea Ioana Roxana , Tartaglia Gianluca Martino , Scarano Antonio , Lorusso Felice , Macchia Luigi , Larocca Angela Maria Vittoria , Aityan Sergey Khachatur , Tafuri Silvio , Stefanizzi Pasquale , Migliore Giovanni , Brienza Nicola , Dipalma Gianna , Favia Gianfranco , Inchingolo Francesco
Published: August 2022

Background: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines’ immunization findings. Methods: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. Results: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by using a special enzyme (TMPRSS2). Once the virion is quietly accommodated, it releases its RNA. Proteins and RNA are used in the Golgi apparatus to produce more viruses that are released. Concerning the therapies, different protocols have been developed in observance of the disease severity and comorbidity with a consistent reduction in the mortality rate. Currently, different vaccines are currently in phase IV but a remarkable difference in efficiency has been detected concerning the more recent SARS-CoV-2 variants. Conclusions: Among the many questions in this pandemic state, the one that recurs most is knowing why some people become more seriously ill than others who instead contract the infection as if it was a trivial flu. More studies are necessary to investigate the efficiency of the treatment protocols and vaccines for the more recent detected SARS-CoV-2 variant.
Kidney Injuries and Evolution of Chronic Kidney Diseases Due to Neonatal Hyperoxia Exposure Based on Animal Studies
Authors: Huang Liang-Ti , Chen Chung-Ming
Published: August 2022

Preterm birth interrupts the development and maturation of the kidneys during the critical growth period. The kidneys can also exhibit structural defects and functional impairment due to hyperoxia, as demonstrated by various animal studies. Furthermore, hyperoxia during nephrogenesis impairs renal tubular development and induces glomerular and tubular injuries, which manifest as renal corpuscle enlargement, renal tubular necrosis, interstitial inflammation, and kidney fibrosis. Preterm birth along with hyperoxia exposure induces a pathological predisposition to chronic kidney disease. Hyperoxia-induced kidney injuries are influenced by several molecular factors, including hypoxia-inducible factor-1α and interleukin-6/Smad2/transforming growth factor-β, and Wnt/β-catenin signaling pathways; these are key to cell proliferation, tissue inflammation, and cell membrane repair. Hyperoxia-induced oxidative stress is characterized by the attenuation or the induction of multiple molecular factors associated with kidney damage. This review focuses on the molecular pathways involved in the pathogenesis of hyperoxia-induced kidney injuries to establish a framework for potential interventions.
Stem Cell-Based Therapies for Inflammatory Bowel Disease
Authors: Zhang Hua-Min , Yuan Shuo , Meng Huan , Hou Xiao-Ting , Li Jiao , Xue Jia-Chen , Li You , Wang Qi , Nan Ji-Xing , Jin Xue-Jun , Zhang Qing-Gao
Published: August 2022

Inflammatory bowel disease (IBD) is a chronic, relapsing disease that severely affects patients’ quality of life. The exact cause of IBD is uncertain, but current studies suggest that abnormal activation of the immune system, genetic susceptibility, and altered intestinal flora due to mucosal barrier defects may play an essential role in the pathogenesis of IBD. Unfortunately, IBD is currently difficult to be wholly cured. Thus, more treatment options are needed for different patients. Stem cell therapy, mainly including hematopoietic stem cell therapy and mesenchymal stem cell therapy, has shown the potential to improve the clinical disease activity of patients when conventional treatments are not effective. Stem cell therapy, an emerging therapy for IBD, can alleviate mucosal inflammation through mechanisms such as immunomodulation and colonization repair. Clinical studies have confirmed the effectiveness of stem cell transplantation in refractory IBD and the ability to maintain long-term remission in some patients. However, stem cell therapy is still in the research stage, and its safety and long-term efficacy remain to be further evaluated. This article reviews the upcoming stem cell transplantation methods for clinical application and the results of ongoing clinical trials to provide ideas for the clinical use of stem cell transplantation as a potential treatment for IBD.
Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic Development
Authors: Qi Qi , Wang Qianqian , Liu Kailing , Bian Jiangyue , Yu Zhixuan , Hou Jian
Published: August 2022

Ten-eleven translocation (Tet) dioxygenases can induce DNA demethylation by catalyzing 5-methylcytosine(5mC) to 5-hydroxymethylcytosine(5hmC), and play important roles during mammalian development. In mouse, Tet1 and Tet2 are not expressed in pronucleus-staged embryos and are not involved in the genomic demethylation of early zygotes. Here, we investigated the influence of Tet1 and Tet2 on methylation of parental genomes by ectopically expressing Tet1 and Tet2 in zygotes. Immunofluorescence staining showed a marked 5hmC increase in the maternal pronucleus after injection of Tet1 or Tet2 mRNA into zygotes. Whole-genome bisulfite sequencing further revealed that Tet2 greatly enhanced the global demethylation of both parental genomes, while Tet1 only promoted the paternal demethylation. Tet1 and Tet2 overexpression altered the DNA methylation across genomes, including various genic elements and germline-specific differently methylated regions. Tet2 exhibited overall stronger demethylation activity than Tet1. Either Tet1 or Tet2 overexpression impaired preimplantation embryonic development. These results demonstrated that early expression of Tet1 and Tet2 could substantially alter the zygotic methylation landscape and damage embryonic development. These findings provide new insights into understanding the function of Tet dioxygenases and the mechanism of DNA methylation in relation to embryogenesis.
Brain Energy Metabolism in Ischemic Stroke: Effects of Smoking and Diabetes
Authors: Sifat Ali Ehsan , Nozohouri Saeideh , Archie Sabrina Rahman , Chowdhury Ekram Ahmed , Abbruscato Thomas J.
Published: August 2022

Proper regulation of energy metabolism in the brain is crucial for maintaining brain activity in physiological and different pathophysiological conditions. Ischemic stroke has a complex pathophysiology which includes perturbations in the brain energy metabolism processes which can contribute to worsening of brain injury and stroke outcome. Smoking and diabetes are common risk factors and comorbid conditions for ischemic stroke which have also been associated with disruptions in brain energy metabolism. Simultaneous presence of these conditions may further alter energy metabolism in the brain leading to a poor clinical prognosis after an ischemic stroke event. In this review, we discuss the possible effects of smoking and/or diabetes on brain glucose utilization and mitochondrial energy metabolism which, when present concurrently, may exacerbate energy metabolism in the ischemic brain. More research is needed to investigate brain glucose utilization and mitochondrial oxidative metabolism in ischemic stroke in the presence of smoking and/or diabetes, which would provide further insights on the pathophysiology of these comorbid conditions and facilitate the development of therapeutic interventions.
miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer
Authors: Meng Wei , Li Yanli , Chai Binshu , Liu Xiaomin , Ma Zhongliang
Published: August 2022

Lung cancer is the leading cause of cancer death worldwide. miR-199a, which has two mature molecules: miR-199a-3p and miR-199a-5p, plays an important biological role in the genesis and development of tumors. We collected recent research results on lung cancer and miR-199a from Google Scholar and PubMed databases. The biological functions of miR-199a in lung cancer are reviewed in detail, and its potential roles in lung cancer diagnosis and treatment are discussed. With miR-199a as the core point and a divergence outward, the interplay between miR-199a and other ncRNAs is reviewed, and a regulatory network covering various cancers is depicted, which can help us to better understand the mechanism of cancer occurrence and provide a means for developing novel therapeutic strategies. In addition, the current methods of diagnosis and treatment of lung cancer are reviewed. Finally, a conclusion was drawn: miR-199a inhibits the development of lung cancer, especially by inhibiting the proliferation, infiltration, and migration of lung cancer cells, inhibiting tumor angiogenesis, increasing the apoptosis of lung cancer cells, and affecting the drug resistance of lung cancer cells. This review aims to provide new insights into lung cancer therapy and prevention.
Metabolic Remodeling with Hepatosteatosis Induced Vascular Oxidative Stress in Hepatic ERK2 Deficiency Mice with High Fat Diets
Authors: Kujiraoka Takehiko , Kagami Kazuki , Kimura Toyokazu , Ishinoda Yuki , Shiraishi Yasunaga , Ido Yasuo , Endo Shogo , Satoh Yasushi , Adachi Takeshi
Published: August 2022

We previously demonstrated the marked hepatosteatosis and endothelial dysfunction in hepatocyte-specific ERK2 knockout mice (LE2KO) with a high-fat/high-sucrose diet (HFHSD), but detailed metabolic changes and the characteristics in insulin-sensitive organs were not tested. This study aimed to characterize metabolic remodeling with changes in insulin-sensitive organs, which could induce endothelial dysfunction in HFHSD-LE2KO. The serum glucose and fatty acid (FA) were modestly higher in HFHSD-LE2KO than HFHSD-Control. FA synthesis genes were up-regulated, which was associated with the decreased phosphorylation of AMPK and ACC, and with the up-regulation of SREBP-1 in the liver from HFHSD-LE2KO. In FA and amino acids fraction analysis, arachidonic acid/eicosapentaenoic acid ratio, L-ornithine/arginine ratio, asymmetric dimethylarginine and homocysteine levels were elevated in HFHSD-LE2KO. Insulin-induced phosphorylation of AKT was blunted in skeletal muscle. Serum leptin and IL-1β were elevated, and serum adiponectin was decreased with the enlargement of epididymal adipocytes. Finally, the enhanced superoxide levels in the aorta, which were blunted with CCCP, apocynin, and tempol, were observed in HFHSD-LE2KO. A pre-incubation of aortic rings with tempol improved endothelial dysfunction in HFHSD-LE2KO. HFHSD-LE2KO revealed an acceleration of FA synthesis in the liver leading to insulin resistance in skeletal muscle and the enlargement of visceral adipocytes. Global metabolic remodeling such as changes in arginine metabolism, ω3/ω6 ratio, and adipocytokines, could affect the vascular oxidative stress and endothelial dysfunction in HFHSD-LE2KO.
Effects of Different Gluten Proteins on Starch’s Structural and Physicochemical Properties during Heating and Their Molecular Interactions
Authors: Yang Tao , Wang Pei , Zhou Qin , Zhong Yingxin , Wang Xiao , Cai Jian , Huang Mei , Jiang Dong
Published: August 2022

Starch–gluten interactions are affected by biopolymer type and processing. However, the differentiation mechanisms for gluten–starch interactions during heating have not been illuminated. The effects of glutens from two different wheat flours (a weak-gluten (Yangmai 22, Y22) and a medium-strong gluten (Yangmai 16, Y16)) on starch’s (S) structural and physicochemical properties during heating and their molecular interactions were investigated in this study. The results showed that gluten hindered the gelatinization and swelling of starch during heating when temperature was below 75 °C, due to competitive hydration and physical barriers of glutens, especially in Y22. Thus, over-heating caused the long-range molecular order and amylopectin branches of starch to be better preserved in the Y22-starch mixture (Y22-S) than in the Y16-starch mixture (Y16-S). Meanwhile, the starch’s degradation pattern during heating in turn influenced the polymerization of both glutens. During heating, residual amylopectin branching points restricted the aggregation and cross-linking of gluten proteins due to steric hindrance. More intense interaction between Y16 and starch during heating mitigated the steric hindrance in starch–gluten networks, which was due to more residual short-range ordered starch and hydrogen bonds involved in the formation of starch–gluten networks in Y16-S during heating.
Advances in the Molecular Mechanisms of Abscisic Acid and Gibberellins Functions in Plants 2.0
Authors: Quesada Víctor
Published: August 2022

Abscisic acid (ABA) and gibberellins (GA) are two important hormones that antagonistically regulate many aspects of plant growth and development [...]
Technical Validation and Clinical Implications of Ultrasensitive PCR Approaches for EGFR-Thr790Met Mutation Detection in Pretreatment FFPE Samples and in Liquid Biopsies from Non-Small Cell Lung Cancer Patients
Authors: Simarro Javier , Pérez-Simó Gema , Mancheño Nuria , Ansotegui Emilio , Muñoz-Núñez Carlos Francisco , Gómez-Codina José , Juan Óscar , Palanca Sarai
Published: August 2022

In pretreatment tumor samples of EGFR-mutated non-small cell lung cancer (NSCLC) patients, EGFR-Thr790Met mutation has been detected in a variable prevalence by different ultrasensitive assays with controversial prognostic value. Furthermore, its detection in liquid biopsy (LB) samples remains challenging, being hampered by the shortage of circulating tumor DNA (ctDNA). Here, we describe the technical validation and clinical implications of a real-time PCR with peptide nucleic acid (PNA-Clamp) and digital droplet PCR (ddPCR) for EGFR-Thr790Met detection in diagnosis FFPE samples and in LB. Limit of blank (LOB) and limit of detection (LOD) were established by analyzing negative and low variant allele frequency (VAF) FFPE and LB specimens. In a cohort of 78 FFPE samples, both techniques showed an overall agreement (OA) of 94.20%. EGFR-Thr790Met was detected in 26.47% of cases and was associated with better progression-free survival (PFS) (16.83 ± 7.76 vs. 11.47 ± 1.83 months; p = 0.047). In LB, ddPCR was implemented in routine diagnostics under UNE-EN ISO 15189:2013 accreditation, increasing the detection rate of 32.43% by conventional methods up to 45.95%. During follow-up, ddPCR detected EGFR-Thr790Met up to 7 months before radiological progression. Extensively validated ultrasensitive assays might decipher the utility of pretreatment EGFR-Thr790Met and improve its detection rate in LB studies, even anticipating radiological progression.
Live Drosophila melanogaster Larvae Deter Oviposition by Drosophila suzukii
Authors: Tungadi Trisna D. , Shaw Bethan , Powell Glen , Hall David R. , Bray Daniel P. , Harte Steven J. , Farman Dudley I. , Wijnen Herman , Fountain Michelle T.
Published: August 2022

The worldwide invasive insect pest, Drosophila suzukii Matsumura (spotted-wing Drosophila), lays eggs in soft and stone fruit before harvest. Hatched larvae cause fruit collapse and significant economic losses. Current control methods rely primarily on foliar insecticide applications, which are not sustainable long-term solutions due to regulatory restrictions and the risk of insecticide resistance developing. We showed before that D. suzukii were deterred from laying eggs on artificial media previously visited by its sister species—Drosophila melanogaster. In the current study, laboratory choice test experiments were conducted to identify which D. melanogaster life stage (eggs, larvae, or adult) deterred D. suzukii oviposition. We demonstrated that the presence of live D. melanogaster larvae on the egg-laying media consistently deterred D. suzukii oviposition. Drosophila melanogaster cuticular hydrocarbons (CHCs) were examined as candidate for the oviposition deterrent. CHCs of larval and adult D. melanogaster and D. suzukii were analyzed. In both species, the composition of the CHCs of larvae was similar to that of adults, although quantities present were much lower. Furthermore, the CHC profiles of the two species were markedly different. However, when assayed as deterrents in the laboratory choice test experiment, CHC extracts from D. melanogaster did not deter oviposition by D. suzukii.
The Role of Non-Cognitive Factors in Prospective Memory in Older Adults
Authors: Grob Emmanuelle , Ghisletta Paolo , Kliegel Matthias
Published: August 2022

A key neuro-cognitive function that promotes autonomy and everyday functioning in old age is prospective memory (PM), defined as the capacity to remember to carry out intentions in the future. This study aimed at understanding if non-cognitive factors of metacognition and motivation are related to event-based and time-based laboratory PM, as well as to naturalistic PM in older adults, above and beyond the influences of neuropsychological determinants. We applied regression analyses predicting individual differences in classical PM tasks, in a sample of 99 healthy older participants (aged 64–88 years). Results indicated that metacognition, measured as memory self-efficacy and perceived competence in cognitive tasks, was related to laboratory time-based PM. Consistency of interests, a motivational factor, was associated with naturalistic PM. None of the non-cognitive factors related to event-based PM. Our study underlines the importance of considering non-cognitive characteristics when evaluating PM capacity, a key component of cognitive aging.
Children in Tokyo Have a Long Sustained Axial Length from Age 3 Years: The Tokyo Myopia Study
Authors: Maruyama Tomoki , Yotsukura Erisa , Torii Hidemasa , Mori Kiwako , Inokuchi Mikako , Tokumura Mitsuaki , Hazra Debabrata , Ogawa Mamoru , Hanyuda Akiko , Tsubota Kazuo , Kurihara Toshihide , Negishi Kazuno
Published: August 2022

Background: myopia prevalence is high among Japanese schoolchildren, but the underlying causes are unclear. Objective: To examine the distributions of ocular biometry and refraction and their associations with lifestyle variables among Japanese schoolchildren. Methods: This cross-sectional school-based study included 2140 children aged 3–14 years in Tokyo, Japan, and evaluated the distributions under non-cycloplegic conditions and the associated environmental factors. Results: The prevalence of spherical equivalent (SE) ≤−0.75 diopter among preschoolers (aged 3–6 years), elementary school students (aged 6–11 years), and junior high school students (aged 12–14 years) was 49.7%, 72.4%, and 87.7%, respectively. Multiple linear regression analyses showed that the time spent using digital devices was associated positively with lens thickness (β = 0.010; p < 0.050) but not SE, axial length, or vitreous chamber depth. The time spent reading was associated negatively with lens thickness (β = −0.012; p < 0.050), SE (β = −0.152; p < 0.010), axial length (β = 0.110; p < 0.001), and vitreous chamber depth (β = 0.110; p < 0.001). Conclusions: The data indicated that almost half of preschoolers may be myopic. The association with the lens thickness differed depending on the type of near work performed.
Increased T-bet/GATA-3 and ROR-γt /Foxp3 Ratios in Cerebrospinal Fluid as Potential Criteria for Definite Neuro-Behçet’s Disease
Authors: Belghith Meriam , Maghrebi Olfa , Cherif Aroua , Bahrini Khadija , Saied Zakaria , Belal Samir , Sassi Samia Ben , Barbouche Mohamed-Ridha , Kchaou Mariem
Published: August 2022

When the central nervous system (CNS) is the primary affected site in an initial attack of Behçet’s disease (BD), the differential diagnosis is particularly challenging. Some cases remain unclassified or qualified as probable neuro-Behçet’s disease (NBD). Several cytokines are involved in the immunopathogenesis of this disease; however, studies establishing the differential cytokine pattern between probable and definite NBD are scarce. Twenty-eight parenchymal NBD patients, diagnosed according to the International Consensus Recommendation (ICR) criteria and classified into definite (D-NBD; n = 17) and probable (P-NBD; n = 11), were sampled at their first neurological symptoms, and compared with healthy control subjects (n = 20). Oligoclonal bands (OCB) of IgG were detected by isoelectric focusing on agarose, and immunoblotting of matched serum and cerebrospinal fluid (CSF) sample pairs. T cell cytokines (INF-γ, IL-4, IL-17, and IL-10) and transcription factors related to Th1, Th2, Th17, and T regulatory populations (respectively T-bet, GATA-3, ROR-γt, and Foxp3) were studied by quantitative RT-PCR in peripheral blood mononuclear cells (PBMCs) and CSF cells. Inflammatory cytokines such as IL-6, TNF-α, and IL-1β were also analyzed. CSF OCB pattern 2 was present in only 1 out of 28 neuro-Behçet’s patients who belonged to the P-NBD group. Two D-NBD patients had OCB in CSF showing pattern 4. In the D-NBD CSF samples, IL-17 and IL-10 expressions were significantly elevated compared to P-NBD. Moreover, D-NBD patients had increased levels of T-bet/GATA-3 and ROR-γt/Foxp3 ratios compared to P-NBD. Furthermore, a significant increase of CSF IL-6 in D-NBD, compared to P-NBD and the controls, was found. In addition to the increased IL-6 level, the data obtained suggest the existence in D-NBD patients of a significantly disrupted balance between Th17 effector and T regulatory cells, as reflected by the enhanced ROR-γt/Foxp3 ratio. This could be considered as an additional criterion for definite neuro-Behçet’s disease.
Effect of Sound Coding Strategies on Music Perception with a Cochlear Implant
Authors: Leterme Gaëlle , Guigou Caroline , Guenser Geoffrey , Bigand Emmanuel , Bozorg Grayeli Alexis
Published: August 2022

The goal of this study was to evaluate the music perception of cochlear implantees with two different sound processing strategies. Methods: Twenty-one patients with unilateral or bilateral cochlear implants (Oticon Medical®) were included. A music trial evaluated emotions (sad versus happy based on tempo and/or minor versus major modes) with three tests of increasing difficulty. This was followed by a test evaluating the perception of musical dissonances (marked out of 10). A novel sound processing strategy reducing spectral distortions (CrystalisXDP, Oticon Medical) was compared to the standard strategy (main peak interleaved sampling). Each strategy was used one week before the music trial. Results: Total music score was higher with CrystalisXDP than with the standard strategy. Nine patients (21%) categorized music above the random level (>5) on test 3 only based on mode with either of the strategies. In this group, CrystalisXDP improved the performances. For dissonance detection, 17 patients (40%) scored above random level with either of the strategies. In this group, CrystalisXDP did not improve the performances. Conclusions: CrystalisXDP, which enhances spectral cues, seemed to improve the categorization of happy versus sad music. Spectral cues could participate in musical emotions in cochlear implantees and improve the quality of musical perception.
Lower SARS-CoV-2 Seroprevalence among Cancer Patients in Sub-Saharan Africa
Authors: Tso For Yue , Lidenge Salum J. , Ngowi John R. , Peña Phoebe B. , Clegg Ashley A. , Ngalamika Owen , Mwita Chacha J. , Mwaiselage Julius , Wood Charles
Published: August 2022

Background: Despite the high COVID-19 morbidity and mortality rates across the world, the reported rates in sub-Saharan Africa (SSA), which has a higher burden of other infectious diseases and overwhelmed healthcare systems, remain relatively low. This study aims to better understand the potential factors that contribute to this phenomenon, especially among cancer patients who are considered as a high-risk group for developing severe COVID-19. Methods: Plasma samples collected during the COVID-19 pandemic from SARS-CoV-2 unvaccinated cancer and potential blood donor populations were analyzed for SARS-CoV-2 (spike and nucleocapsid proteins) antibodies by an immunofluorescence assay. The relationships between SARS-CoV-2 seroprevalences and study variables were determined using a logistic regression analysis. Results: High seroprevalence against the SARS-CoV-2 spike and nucleocapsid proteins were found among the SARS-CoV-2 unvaccinated COVID-19 pandemic populations in SSA. However, the cancer patients demonstrated a lower seroprevalence compared to potential blood donors. There was also an association between mild COVID-19 symptoms with prior tuberculosis vaccination among cancer patients. Conclusion: Cancer patients in SSA tend to have a relatively lower SARS-CoV-2 seroprevalence compared to potential blood donors recruited from the same geographic locations during the COVID-19 pandemic. More study is required to determine its cause and potential impact on SARS-CoV-2 vaccination among cancer patients.
Obstetric Outcomes after Perforation of Uterine Cavity
Authors: Schwarzman Polina , Baumfeld Yael , Mastrolia Salvatore Andrea , Yaniv-Salem Shimrit , Leron Elad , Silberstein Tali
Published: August 2022

We aimed to evaluate the pregnancy characteristics and obstetric outcomes in patients after perforation of the uterus. Study design: A retrospective cohort study was conducted and included all patients who were diagnosed with uterine perforation and treated in a tertiary referral medical center between the years 1996 and 2018. Up to two deliveries after perforations were investigated. Results: During the study period, 51 women were diagnosed with uterine perforation during gynecological procedures, including intrauterine device (IUD) insertion. The mean age of patients at the time of diagnosis was 27.9 (±4.7) years. The majority, 76.5% (n = 39), experienced perforation during IUD insertion, and 23.5% (n = 12) of the patients experienced perforation during surgical procedures. Most of the patients were multiparous or grand multiparous, 45.8. % (n = 22) and 39.6% (n = 19) respectively. Anteflexed uterus was found in 86.4% of the patients (n = 38). Five patients (9.8%) had pelvic abscesses after the IUD insertion. A total of 50 patients had 71 deliveries subsequent to uterine perforation. One patient experienced intrauterine fetal death due to fetal malformations. One patient experienced uterine rupture. No other major obstetric complications were noted. Conclusions: Uterine perforation may be associated with adverse obstetric outcomes. The possibility of uterine rupture must be considered while managing the deliveries of patients after uterine perforation. Moreover, a larger cohort and further studies are needed to establish an association between uterine perforation and adverse outcomes of the subsequent deliveries.
Treatment Options in AF Patients with Cancer; Focus on Catheter Ablation
Authors: Garibaldi Silvia , Chianca Michela , Fabiani Iacopo , Emdin Michele , Piacenti Marcello , Passino Claudio , Aimo Alberto , Fedele Antonella , Cipolla Carlo Maria , Cardinale Daniela Maria
Published: August 2022

Longer life expectancy along with advancements in cancer and atrial fibrillation (AF) therapies and treatment strategies have led to an increase in the number of individuals with both diseases. As a result, the complicated management of these patients has become crucial, necessitating individualised treatment that considers the bi-directional relationship between these two diseases. On the one hand, giving appropriate pharmaceutical therapy is exceptionally difficult, considering the recognised thromboembolic risk posed by AF and malignancy, as well as the haemorrhagic risk posed by cancer. The alternative pulmonary vein isolation (PVI) ablation, on the other hand, has been inadequately explored in the cancer patient population; there is yet inadequate data to allow the clinician to unambiguously select patients that can undertake this therapeutic intervention. The goal of this review is to compile the most valuable data and supporting evidence about the characteristics, care, and therapy of cancer patients with AF. Specifically, we will evaluate the pharmaceutical options for a proper anticoagulant therapy, as well as the feasibility and safety of PVI in this population.
Evaluation of Right Ventricular Function and Myocardial Microstructure in Fetal Hypoplastic Left Heart Syndrome
Authors: Ma Jing , Yuan Yaping , Zhang Li , Chen Shizhen , Cao Haiyan , Hong Liu , Liu Juanjuan , Song Xiaoyan , Shi Jiawei , Zhang Yi , Cui Li , Zhou Xin , Xie Mingxing
Published: August 2022

Right ventricular (RV) function is one of the critical factors affecting the prognosis of fetuses with hypoplastic left heart syndrome (HLHS). Our study objectives included assessment of cardiac function and comprehensive measurement of cardiac microstructure. We retrospectively studied 42 fetuses diagnosed as HLHS by echocardiography. Myocardial deformation of the right ventricular wall was calculated automatically in offline software. Postmortem cardiac imaging for three control fetal hearts and four HLHS specimens was performed by a 9.4T DTI scanner. Myocardial deformation parameters of the RV (including strain, strain rate, and velocity) were significantly lower in HLHS fetuses (all p < 0.01). FA values increased (0.18 ± 0.01 vs. 0.21 ± 0.02; p < 0.01) in HLHS fetuses, but MD reduced (1.3 ± 0.15 vs. 0.88 ± 0.13; p < 0.001). The HLHS fetuses’ RV lateral base wall (−7.31 ± 51.91 vs. −6.85 ± 31.34; p = 0.25), middle wall (1.71 ± 50.92 vs. −9.38 ± 28.18; p < 0.001), and apical wall (−6.19 ± 46.61 vs. −11.16 ± 29.86, p < 0.001) had HA gradient ascent but HA gradient descent in the anteroseptal wall (p < 0.001) and inferoseptal wall (p < 0.001). RV basal lateral wall HA degrees were correlated with RVGLS (R2 = 0.97, p = 0.02). MD values were positively correlated with RVGLS (R2 = 0.93, p = 0.04). Our study found morphological and functional changes of the RV in HLHS fetuses, and cardiac function was related to the orientation patterns of myocardial fibers. It may provide insight into understanding the underlying mechanisms of impaired RV performance in HLHS.
Factors Associated with Traumatic Diaphragmatic Rupture among Patients with Chest or Abdominal Injury: A Nationwide Study from Japan
Authors: Katayama Yusuke , Tanaka Kenta , Ishida Kenichiro , Hirose Tomoya , Tachino Jotaro , Nakao Shunichiro , Umemura Yutaka , Kiyohara Kosuke , Ojima Masahiro , Kiguchi Takeyuki , Kitamura Tetsuhisa , Oda Jun
Published: August 2022

Background: Blunt traumatic diaphragmatic rupture (TDR) is a rare condition that is seen in patients with blunt thoracoabdominal trauma. However, factors that are associated with blunt TDR have not been fully revealed. The purpose of this study was to evaluate the factors that are associated with blunt TDR in trauma patients with a chest or abdominal injury using nationwide trauma registry data in Japan. Method: This study was a retrospective observational study with a 15-year study period from 2004 to 2018. We included trauma patients with a chest or abdominal Abbreviated Injury Score of two or more. We evaluated the relationship between confounding factors such as mechanism of injury and blunt TDR with multivariable logistic regression analysis. Results: This study included 65,110 patients, of whom 496 patients (0.8%) suffered blunt TDR. Factors that were associated with blunt TDR were disturbance of consciousness (adjusted OR [AOR]: 1.639, 95% CI: 1.326–2.026), FAST positive (AOR: 2.120, 95% CI: 1.751–2.567), front seat passenger (AOR: 1.748, 95% CI: 1.129–2.706), and compression injury by heavy object (AOR: 1.677, 95% CI: 1.017–2.765). Conclusion: This study revealed several factors that are associated with blunt TDR. The results of this study may be useful for clinicians when estimating blunt TDR.
Determinants of Lack of Recovery from Dependency and Walking Ability Six Months after Hip Fracture in a Population of People Aged 65 Years and Over
Authors: González Marcos Enrique , González García Enrique , González-Santos Josefa , González-Bernal Jerónimo J. , del Pilar Martín-Rodríguez Adoración , Santamaría-Peláez Mirian
Published: August 2022

Background: Hip fracture in the elderly means that between a quarter and a half of patients do not regain the levels of independence and walking ability that they previously had, according to the literature, after the fracture. Material and methods: Retrospective study of 537 patients aged ≥65 years who survived at the sixth month after fracturing their hip, of which the age, sex, type of fracture, surgical risk, independence (BI), walking ability, cognitive level (PS), comorbidities, indicated drugs, complications, surgical delay, hospital stay, and surgical technique are known. Using Pearson’s χ2 test, all the variables were contrasted with respect to the limitation or not, at the sixth month of the recovery of both independence and pre-admission walking ability. Multivariate analysis provides the necessary adjustment to the previous contrast. Results: We have found that age and PS ≥ 5 at admission limit recovery from both dependency and walking ability. Surgical risk, independence (BI) upon admission, anemia, and constipation during the hospital stay limit the recovery of the BI. Worsening of walking ability during the hospital stay and the type of extra-articular fracture, which was surgically treated by osteosynthesis, limit the recovery of walking ability. Conclusions: The factors previously exposed, and perhaps the fact that patients with hip fractures are not routinely referred to rehabilitation, explain the high proportion of patients who do not recover their previous independency (36%) or walking ability (45%) to the fact of fracturing.
Surgery for Xanthogranulomatous Pyelonephritis: A Comparison of Midline Transperitoneal and Flank Retroperitoneal Laparotomy Approaches to Nephrectomy
Authors: Tsao Shu-Han , Wang Chien-Ho , Juang Horng-Heng , Lin Yu-Hsiang , Yang Pei-Shan , Chang Phei-Lang , Chen Chien-Lun , Hou Chen-Pang
Published: August 2022

Xanthogranulomatous pyelonephritis (XGP) is a rare inflammatory disease often associated with high morbidity and mortality. Whether the midline transperitoneal or the flank retroperitoneal approach is superior remains unknown. We searched through pathology databases and reviewed 86 patients with an XGP diagnosis from 2000 to 2021 at our institution. After the patients who did not meet the inclusion criteria were excluded, 35 patients who had undergone nephrectomy through the midline transperitoneal or the flank retroperitoneal laparotomy approach were recruited. Nine (25.71%) of the thirty-five patients underwent nephrectomy through a midline approach, whereas twenty-six (74.29%) received a flank approach. Patients in the midline approach group had a longer surgical time (p = 0.03) than those in the flank approach group. In addition, patients in the flank approach group took less time after surgery to resume oral intake than those in the midline approach group (p = 0.01). No significant differences in the rates of intraoperative and postoperative complications such as peritonitis or intraabdominal infection were observed between the groups. For the patients with XGP who are good candidates for surgery, nephrectomy is a relatively safe surgical treatment method. Both surgical methods produced favorable surgical outcomes, and the patients who received these methods had similar complication rates.
A Generalized Method for In-Process Defect Detection in Friction Stir Welding
Authors: Hunt Johnathon B. , Mazzeo Brian A. , Sorensen Carl D. , Hovanski Yuri
Published: August 2022

Friction stir welding (FSW) is an advantageous solid-state joining process that is suitable for many materials in multiple industries. In an industrial setting, manufacturers are actively seeking faster welding speeds to increase throughput. Increasing welding speed limits the size of defect-free parameter windows, which may increase the frequency of defects. The push for faster welding speeds emphasizes the need for economical non-destructive evaluation (NDE) for FSW, like any other type of welding. This work introduces a generalized defect detection method that recognizes the stochastic nature of the FSW process, and that can be generally applied to FSW of a material across a dynamic range of process parameters and welding conditions. When applied to aluminum friction stir-welded blanks at speeds ranging from 1500 to 3000 mm/min with varying ranges of tool tilts, the methodology proved 100% effective at positive detection when defects were present with zero scrap rate. Furthermore, additional development demonstrated the proposed stochastic approach can be used to detect the spatial location of a defect within a weld with 94% detection accuracy and a 4.2% scrap rate.
The Octopus Trap of Takotsubo and Stroke: Genetics, Biomarkers and Clinical Management
Authors: Canavero Isabella , Rifino Nicola , Bussotti Maurizio , Carrozzini Tatiana , Potenza Antonella , Gorla Gemma , Pollaci Giuliana , Storti Benedetta , Parati Eugenio Agostino , Gatti Laura , Bersano Anna
Published: August 2022

Takotsubo cardiomyopathy (TC) is a reversible cardiomyopathy mimicking an acute coronary syndrome, usually observed in response to acute stress situations. The association between acute ischemic stroke and TC is already known, since it has been previously reported that ischemic stroke can be both a consequence and a potential cause of TC. However, the precise pathophysiological mechanism linking the two conditions is still poorly understood. The aim of our review is to expand insights regarding the genetic susceptibility and available specific biomarkers of TC and to investigate the clinical profile and outcomes of patients with TC and stroke. Since evidence and trials on TC and stroke are currently lacking, this paper aims to fill a substantial gap in the literature about the relationship between these pathologies.
The Role of Angiotensin Receptor Blockers in the Personalized Management of Diabetic Neuropathy
Authors: Kostourou Danai-Thomais , Milonas Dimitrios , Polychronopoulos Georgios , Sofogianni Areti , Tziomalos Konstantinos
Published: August 2022

Neuropathy is a frequent complication of diabetes mellitus (DM) and is associated with the increased risk ofamputation and vascular events. Tight glycemic control is an important component inthe prevention of diabetic neuropathy. However, accumulating data suggest that angiotensin receptor blockers (ARBs) might also be useful in this setting. We discuss the findings of both experimental and clinical studies that evaluated the effects of ARBs on indices of diabetic neuropathy. We also review the implicated mechanisms of the neuroprotective actions of these agents. Overall, it appears that ARBs might be a helpful tool for preventing and delaying the progression of diabetic neuropathy, but more data are needed to clarify their role in the management of this overlooked complication of DM.
Decentralized Blockchain-Based IoT Data Marketplaces
Authors: Christidis John , Karkazis Panagiotis A. , Papadopoulos Pericles , Leligou Helen C. (Nelly)
Published: August 2022

In present times, the largest amount of data is being controlled in a centralized manner. However, as the data are in essence the fuel of any application and service, there is a need to make the data more findable and accessible. Another problem with the data being centralized is the limited storage as well as the uncertainty of their authenticity. In the Internet of Things (IoT) sector specifically, data are the key to develop the most powerful and reliable applications. For these reasons, there is a rise on works that present decentralized marketplaces for IoT data with many of them exploiting blockchain technology to offer security advantages. The main contribution of this work is to review the existing works on decentralized IoT data marketplaces and discuss important design aspects and options so as to guide (a) the prospective user to select the IoT data marketplace that matches their needs and (b) the potential designer of a new marketplace to make insightful decisions.