bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Exploration of Chinese Spring Festival Population Flow Patterns and Their Determinants Based on Spatial Interaction Model
Authors: Zhou Tao , Huang Bo , Liu Xiaoqian , He Guangqin , Gou Qiang , Huang Zhihui , Xie Cheng
Published: November 2020

Large-scale population flow reshapes the economic landscape and is affected by unbalanced urban development. The exploration of migration patterns and their determinants is therefore crucial to reveal unbalanced urban development. However, low-resolution migration datasets and insufficient consideration of interactive differences have limited such exploration. Accordingly, based on 2019 Chinese Spring Festival travel-related big data from the AMAP platform, we used social network analysis (SNA) methods to accurately reveal population flow patterns. Then, with consideration of the spatial heterogeneity of interactive patterns, we used spatially weighted interactive models (SWIMs), which were improved by the incorporation of weightings into the global Poisson gravity model, to efficiently quantify the effect of socioeconomic factors on migration patterns. These SWIMs generated the local characteristics of the interactions and quantified results that were more regionally consistent than those generated by other spatial interaction models. The migration patterns had a spatially vertical structure, with the city development level being highly consistent with the flow intensity; for example, the first-level developments of Beijing, Shanghai, Chengdu, Guangzhou, Shenzhen, and Chongqing occupied a core position. A spatially horizontal structure was also formed, comprising 16 closely related city communities. Moreover, the quantified impact results indicated that migration pattern variation was significantly related to the population, value-added primary and secondary industry, the average wage, foreign capital, pension insurance, and certain aspects of unbalanced urban development. These findings can help policymakers to guide population migration, rationally allocate industrial infrastructure, and balance urban development.
Correction: Islam, S., et al. Impaired Expression of Chloroplast HSP90C Chaperone Activates Plant Defense Responses with a Possible Link to a Disease-Symptom-Like Phenotype. International Journal of Molecular Science 2020, 21, 4202
Authors: Islam Shaikhul , Bhor Sachin Ashok , Tanaka Keisuke , Sakamoto Hikaru , Yaeno Takashi , Kaya Hidetaka , Kobayashi Kappei
Published: November 2020

The authors wish to make the following corrections to this paper [...]
Evaluation of the Effects of Particle Sizes of Silver Nanoparticles on Various Biological Systems
Authors: Kong In Chul , Ko Kyung-Seok , Koh Dong-Chan
Published: November 2020

Seven biological methods were adopted (three bacterial activities of bioluminescence, enzyme, enzyme biosynthetic, algal growth, seed germination, and root and shoot growth) to compare the toxic effects of two different sizes of silver nanoparticles (AgNPs). AgNPs showed a different sensitivity in each bioassay. Overall, the order of inhibitory effects was roughly observed as follows; bacterial bioluminescence activity ≈ root growth > biosynthetic activity of enzymes ≈ algal growth > seed germination ≈ enzymatic activity > shoot growth. For all bacterial activities (bioluminescence, enzyme, and enzyme biosynthesis), the small AgNPs showed statistically significantly higher toxicity than the large ones (p < 0.0036), while no significant differences were observed among other biological activities. The overall effects on the biological activities (except shoot growth) of the small AgNPs were shown to have about 4.3 times lower EC50 (high toxicity) value than the large AgNPs. These results also indicated that the bacterial bioluminescence activity appeared to be an appropriate method among the tested ones in terms of both sensitivity and the discernment of particle sizes of AgNPs.
Gene Expression Profiling in Huntington’s Disease: Does Comorbidity with Depressive Symptoms Matter?
Authors: Colpo Gabriela Delevati , Rocha Natalia Pessoa , Furr Stimming Erin , Teixeira Antonio Lucio
Published: November 2020

Huntington’s disease (HD) is an inherited neurodegenerative disease. Besides the well-characterized motor symptoms, HD is marked by cognitive impairment and behavioral changes. In this study, we analyzed the blood of HD gene carries using RNA-sequencing techniques. We evaluated samples from HD gene carriers with (n = 8) and without clinically meaningful depressive symptoms (n = 8) compared with healthy controls (n = 8). Groups were age- and sex-matched. Preprocessing of data and between-group comparisons were calculated using DESeq2. The Wald test was used to generate p-values and log2 fold changes. We found 60 genes differently expressed in HD and healthy controls, of which 21 were upregulated and 39 downregulated. Within HD group, nineteen genes were differently expressed between patients with and without depression, being 6 upregulated and 13 downregulated. Several of the top differentially expressed genes are involved in nervous system development. Although preliminary, our findings corroborate the emerging view that in addition to neurodegenerative mechanisms, HD has a neurodevelopmental component. Importantly, the emergence of depression in HD might be related to these mechanisms.
Interactions between Tumor Cells, Neurons, and Microglia in the Glioma Microenvironment
Authors: Radin Daniel P. , Tsirka Stella E.
Published: November 2020

Despite significant strides made in understanding the pathophysiology of high-grade gliomas over the past two decades, most patients succumb to these neoplasias within two years of diagnosis. Furthermore, there are various co-morbidities associated with glioma and standard of care treatments. Emerging evidence suggests that aberrant glutamate secretion in the glioma microenvironment promotes tumor progression and contributes to the development of co-morbidities, such as cognitive defects, epilepsy, and widespread neurodegeneration. Recent data clearly illustrate that neurons directly synapse onto glioma cells and drive their proliferation and spread via glutamatergic action. Microglia are central nervous system-resident myeloid cells, modulate glioma growth, and possess the capacity to prune synapses and encourage synapse formation. However, current literature has yet to investigate the potential role of microglia in shaping synapse formation between neurons and glioma cells. Herein, we present the literature concerning glutamate’s role in glioma progression, involving hyperexcitability and excitotoxic cell death of peritumoral neurons and stimulation of glioma proliferation and invasion. Furthermore, we discuss instances in which microglia are more likely to sculpt or encourage synapse formation during glioma treatment and propose studies to delineate the role of microglia in synapse formation between neurons and glioma cells. The sex-dependent oncogenic or oncolytic actions of microglia and myeloid cells, in general, are considered in addition to the functional differences between microglia and macrophages in tumor progression. We also put forth tractable methods to safely perturb aberrant glutamatergic action in the tumor microenvironment without significantly increasing the toxicities of the standard of care therapies for glioma therapy.
Establishment of a Gene Signature to Predict Prognosis for Patients with Lung Adenocarcinoma
Authors: Li Zhaodong , Qi Fangyuan , Li Fan
Published: November 2020

Accumulating evidence indicates that the reliable gene signature may serve as an independent prognosis factor for lung adenocarcinoma (LUAD) diagnosis. Here, we sought to identify a risk score signature for survival prediction of LUAD patients. In the Gene Expression Omnibus (GEO) database, GSE18842, GSE75037, GSE101929, and GSE19188 mRNA expression profiles were downloaded to screen differentially expressed genes (DEGs), which were used to establish a protein-protein interaction network and perform clustering module analysis. Univariate and multivariate proportional hazards regression analyses were applied to develop and validate the gene signature based on the TCGA dataset. The signature genes were then verified on GEPIA, Oncomine, and HPA platforms. Expression levels of corresponding genes were also measured by qRT-PCR and Western blotting in HBE, A549, and PC-9 cell lines. The prognostic signature based on eight genes (TTK, HMMR, ASPM, CDCA8, KIF2C, CCNA2, CCNB2, and MKI67) was established, which was independent of other clinical factors. The risk model offered better discrimination between risk groups, and patients with high-risk scores tended to have poor survival rate at 1-, 3- and 5-year follow-up. The model also presented better survival prediction in cancer-specific cohorts of age, gender, clinical stage III/IV, primary tumor 1/2, and lymph node metastasis 1/2. The signature genes, moreover, were highly expressed in A549 and PC-9 cells. In conclusion, the risk score signature could be used for prognostic estimation and as an independent risk factor for survival prediction in patients with LUAD.
Recombinant Chromosome 7 Driven by Maternal Chromosome 7 Pericentric Inversion in a Girl with Features of Silver-Russell Syndrome
Authors: Catusi Ilaria , Bonati Maria Teresa , Mainini Ester , Russo Silvia , Orlandini Eleonora , Larizza Lidia , Recalcati Maria Paola
Published: November 2020

Maternal uniparental disomy of chromosome 7 is present in 5–10% of patients with Silver-Russell syndrome (SRS), and duplication of 7p including GRB10 (Growth Factor Receptor-Bound Protein 10), an imprinted gene that affects pre-and postnatal growth retardation, has been associated with the SRS phenotype. Here, we report on a 17 year old girl referred to array-CGH analysis for short stature, psychomotor delay, and relative macrocephaly. Array-CGH analysis showed two copy number variants (CNVs): a ~12.7 Mb gain in 7p13-p11.2, involving GRB10 and an ~9 Mb loss in 7q11.21-q11.23. FISH experiments performed on the proband’s mother showed a chromosome 7 pericentric inversion that might have mediated the complex rearrangement harbored by the daughter. Indeed, we found that segmental duplications, of which chromosome 7 is highly enriched, mapped at the breakpoints of both the mother’s inversion and the daughter’s CNVs. We postulate that pairing of highly homologous sequences might have perturbed the correct meiotic chromosome segregation, leading to unbalanced outcomes and acting as the putative meiotic mechanism that was causative of the proband’s rearrangement. Comparison of the girl’s phenotype to those of patients with similar CNVs supports the presence of 7p in a locus associated with features of SRS syndrome.
Stimulation of THP-1 Macrophages with LPS Increased the Production of Osteopontin-Encapsulating Exosome
Authors: Bai Gaowa , Matsuba Takashi , Niki Toshiro , Hattori Toshio
Published: November 2020

Osteopontin (OPN) mediates bone remodeling and tissue debridement. The OPN protein is cleaved, but it is unclear how full-length (FL)-OPN or its cleaved form perform their biological activities in target cells. We, therefore, performed the molecular characterization of OPN in exosomes (Exo). The Exo were isolated from lipopolysaccharide (LPS)-stimulated phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages. The Exo were also isolated from PMA-differentiated THP-1 macrophages. The Exo were identified using the qNano multiple analyzer (diameter 59–315 nm) and western blotting with a CD9 antibody. LPS-stimulated cells produced more particles than non-stimulated cells. The presence of the FL or the cleaved form of OPN was confirmed using western blot analysis. A mixture of FL and cleaved OPN was also measured using an ELISA system (Ud-OPN) and their presence in the Exo was confirmed. Ud/FL ratios became low after LPS stimulation, indicating the enhanced encapsulation of FL-OPN in the Exo by LPS. These findings suggest that LPS stimulation of human macrophages facilitates the synthesis of FL-OPN, which is cleaved in cells or the Exo after release. These findings indicate that Exo is a suitable vehicle to transfer OPN to the target cells.
The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1
Authors: Lai Lo , Shin Ga Yoon , Qiu Hongyu
Published: November 2020

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.
Deciphering the Therapeutic Resistance in Acute Myeloid Leukemia
Authors: Gurnari Carmelo , Pagliuca Simona , Visconte Valeria
Published: November 2020

Acute myeloid leukemia (AML) is a clonal hematopoietic disorder characterized by abnormal proliferation, lack of cellular differentiation, and infiltration of bone marrow, peripheral blood, or other organs. Induction failure and in general resistance to chemotherapeutic agents represent a hindrance for improving survival outcomes in AML. Here, we review the latest insights in AML biology concerning refractoriness to therapies with a specific focus on cytarabine and daunorubicin which still represent milestones agents for inducing therapeutic response and disease eradication. However, failure to achieve complete remission in AML is still high especially in elderly patients (40–60% in patients >65 years old). Several lines of basic and clinical research have been employed to improve the achievement of complete remission. These lines of research include molecular targeted therapy and more recently immunotherapy. In terms of molecular targeted therapies, specific attention is given to DNMT3A and TP53 mutant AML by reviewing the mechanisms underlying epigenetic therapies’ (e.g., hypomethylating agents) resistance and providing critical points and hints for possible future therapies overcoming AML refractoriness.
Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a “Two-Hit” Non-Genetic Mouse Model of Schizophrenia
Authors: Chang Yi-Chun , Li Wai-Yu , Lee Lukas Jyuhn-Hsiarn , Lee Li-Jen
Published: November 2020

Schizophrenia is a multifactorial developmental neuropsychiatric disorder. This study examined the interplay of maternal infection and postweaning social isolation, which are prenatal and postnatal risk factors, respectively. Pregnant mice received poly I:C or saline injection on gestation day 9 and the pups were weaned at postnatal day 28. After weaning, male offspring were randomly assigned into group-rearing and isolation-rearing groups. In their adulthood, we performed behavioral tests and characterized the histochemical features of their mesocorticolimbic structures. The sociability and anxiety levels were not affected by either manipulation, but synergistic effects of the two hits on stress-coping behavior was observed. Either of the single manipulations caused defects in sensorimotor gating, novel object recognition and spatial memory tests, but the combination of the two hits did not further exacerbate the disabilities. Prenatal infection increased the number of dopaminergic neurons in midbrain, whereas postweaning isolation decreased the GABAergic neurons in cortex. Single manipulation reduced the dendritic complexity and spine densities of neurons in the medial prefrontal cortex (mPFC) and dentate gyrus. Our results support the current perspective that disturbances in brain development during the prenatal or postnatal period influence the structure and function of the brain and together augment the susceptibility to mental disorders, such as schizophrenia.
Nitric Oxide Does Not Inhibit but Is Metabolized by the Cytochrome bcc-aa3 Supercomplex
Authors: Forte Elena , Giuffrè Alessandro , Huang Li-shar , Berry Edward A. , Borisov Vitaliy B.
Published: November 2020

Nitric oxide (NO) is a well-known active site ligand and inhibitor of respiratory terminal oxidases. Here, we investigated the interaction of NO with a purified chimeric bcc-aa3 supercomplex composed of Mycobacterium tuberculosis cytochrome bcc and Mycobacterium smegmatisaa3-type terminal oxidase. Strikingly, we found that the enzyme in turnover with O2 and reductants is resistant to inhibition by the ligand, being able to metabolize NO at 25 °C with an apparent turnover number as high as ≈303 mol NO (mol enzyme)−1 min−1 at 30 µM NO. The rate of NO consumption proved to be proportional to that of O2 consumption, with 2.65 ± 0.19 molecules of NO being consumed per O2 molecule by the mycobacterial bcc-aa3. The enzyme was found to metabolize the ligand even under anaerobic reducing conditions with a turnover number of 2.8 ± 0.5 mol NO (mol enzyme)−1 min−1 at 25 °C and 8.4 µM NO. These results suggest a protective role of mycobacterial bcc-aa3 supercomplexes against NO stress.
Antibiofilm Properties of Temporin-L on Pseudomonas fluorescens in Static and In-Flow Conditions
Authors: Di Somma Angela , Recupido Federica , Cirillo Arianna , Romano Alessia , Romanelli Alessandra , Caserta Sergio , Guido Stefano , Duilio Angela
Published: November 2020

Biofilms consist of a complex microbial community adhering to biotic or abiotic surfaces and enclosed within a protein/polysaccharide self-produced matrix. The formation of this structure represents the most important adaptive mechanism that leads to antibacterial resistance, and therefore, closely connected to pathogenicity. Antimicrobial peptides (AMPs) could represent attractive candidates for the design of new antibiotics because of their specific characteristics. AMPs show a broad activity spectrum, a relative selectivity towards their targets (microbial membranes), the ability to act on both proliferative and quiescent cells, a rapid mechanism of action, and above all, a low propensity for developing resistance. This article investigates the effect at subMIC concentrations of Temporin-L (TL) on biofilm formation in Pseudomonas fluorescens (P. fluorescens) both in static and dynamic conditions, showing that TL displays antibiofilm properties. Biofilm formation in static conditions was analyzed by the Crystal Violet assay. Investigation of biofilms in dynamic conditions was performed in a commercial microfluidic device consisting of a microflow chamber to simulate real flow conditions in the human body. Biofilm morphology was examined using Confocal Laser Scanning Microscopy and quantified via image analysis. The investigation of TL effects on P. fluorescens showed that when subMIC concentrations of this peptide were added during bacterial growth, TL exerted antibiofilm activity, impairing biofilm formation both in static and dynamic conditions. Moreover, TL also affects mature biofilm as confocal microscopy analyses showed that a large portion of preformed biofilm architecture was clearly perturbed by the peptide addition with a significative decrease of all the biofilm surface properties and the overall biomass. Finally, in these conditions, TL did not affect bacterial cells as the live/dead cell ratio remained unchanged without any increase in damaged cells, confirming an actual antibiofilm activity of the peptide.
Evaluating the Investment Climate for China’s Cross-Border E-Commerce: The Application of Back Propagation Neural Network
Authors: Lei Yi , Qiu Xiaodong
Published: November 2020

China’s cross-border e-commerce will usher in a new golden age of development. Based on seven countries which include the Russian Federation, Mongolia, Ukraine, Kazakhstan, Tajikistan, Kyrgyzstan and Belarus along the “Belt and Road”, an evaluation system for cross-border e-commerce investment climate indicators is established in this study. This research applied the entropy method twice to evaluate the investment climate of seven countries based on 5 years panel data comprehensively and these countries are then classified into politics-oriented and industry-oriented countries, and then the weight of indicators for each category is analyzed. In addition, cross-border e-commerce investors are proposed to prioritize industry-oriented countries. Back propagation neural network algorithm is used to map the existing data and optimize the evaluation index system in combination with the genetic algorithm. This research denotes the effort to find out the index evaluation combination corresponding to the best overall score, make the established evaluation index system applicable to other countries, and provide reference for cross-border e-commerce investors when evaluating the investment climate in each country. This study provides the important practical implications in the sustainable development of China’s cross-border e-commerce environment.
Water Dipping of Auxin Coated Chrysanthemum Cuttings Confers Protection against Insect Herbivores
Authors: Mouden Sanae , Leiss Kirsten A. , Uthe Henriette , Klinkhamer Peter G.L.
Published: November 2020

Auxins are commonly used for commercial propagation of chrysanthemums by stem cuttings. Recent studies imply that these root-promoting hormones also affect plant defense responses. The underlying motive of this study stems from the serendipitous observation that water dipping of auxin-coated cuttings beneficially affected thrips herbivory. Therefore, the primary objective of this investigation was to explore the role of indole-3-butyric acid (IBA) in relation to herbivore susceptibility in chrysanthemum. We observed contrasting findings concerning the physical presence of IBA and it’s role in promoting susceptibility of cuttings to thrips, which may in part be explained by the phenotypical variations of cuttings generated from mother plants. Nonetheless, we repeatedly demonstrated considerable protection, in some experiments up to 37%, against thrips and leaf miner upon water dipping of IBA-coated cuttings. Assessment of polyphenol oxidase activity (PPO), 14 days after dipping treatment, suggests that neither direct induction nor priming of plant defenses are involved. Future experiments aimed at understanding the early signaling events may help to explain the underlying mechanisms involved in conferring herbivore protection. We propose a dual role for auxins in early integrated pest management strategies to maximize plant development and minimize herbivory through feasible, cost-effective water dipping treatments.
Morphological, Genetic and Biological Evidences to Understand Meromacrus Rondani Diversity: New Species and Early Stages (Diptera: Syrphidae)
Authors: Ricarte Antonio , Souba-Dols Gabriel J. , Skevington Jeffrey H. , Quinto Javier , García Mª Ángeles Marcos
Published: November 2020

Meromacrus is a genus of conspicuous syrphids with saprophagous larvae, ranging from the southern United States to Argentina and Chile. However, this genus is in need of a taxonomic revision. Adults reared from larvae collected in Mexico and Peru, and other material available at different institutional collections were examined. Meromacrus cactorum sp. nov., from Peru, Meromacrus yucatense sp. nov., from Mexico, their puparia and breeding sites were described. A key to Meromacrus puparia is provided. The holotypes of Meromacrus canusium, Meromacrus gloriosus, Meromacrus laconicus and Meromacrus melmoth were also examined. The name Meromacrus draco is proposed as a junior synonym of M. gloriosus. Larvae of M. cactorum sp. nov. were found in decaying columnar cacti in Peru, while those of M. yucatense sp. nov. in a rot-hole of a Ceiba pentandra stump. Obtained results on both taxonomy and biology of these species serve as a first step towards a revision of the entire genus.
Growing the Rhinophorid Tree: Three New Species and Their Phylogenetic Implications (Diptera: Rhinophoridae)
Authors: Gisondi Silvia , Pape Thomas , Shima Hiroshi , Cerretti Pierfilippo
Published: November 2020

Three new species of Rhinophoridae (Aporeomyia elaphocerasp. nov., Baniassa pennatasp. nov. from the Oriental Region, and Phyto mambillasp. nov. from the Afrotropical Region) are described, illustrated and compared with congeners. Genus-level affiliation of the new species is based on a morphology-based phylogeny, preliminarily accepting a paraphyletic Phyto Robineau-Desvoidy awaiting incorporation of molecular data. Keys to the species of the genus Aporeomyia Pape & Shima as well as to the Afrotropical species of the genus Phyto Robineau-Desvoidy are given.
Pornography Use in Adolescents and Its Clinical Implications
Authors: Farré Josep M. , Montejo Angel L. , Agulló Miquel , Granero Roser , Chiclana Actis Carlos , Villena Alejandro , Maideu Eudald , Sánchez Marta , Fernández-Aranda Fernando , Jiménez-Murcia Susana , Mestre-Bach Gemma
Published: November 2020

(1) Background: The Differential Susceptibility to Media Effects Model (DSMM) suggests that pornography use effects are conditional and they depend on dispositional, developmental, and social differential susceptibility variables. This framework also highlights that the differential susceptibility variables act as predictors of pornography use and as moderators of the effect of pornography on criterion variables. (2) Methods: By administering a survey to n = 1500 adolescents, we tested whether these assumptions were met. (3) Results: Pornography use was related to being male and older, having a bisexual or undefined sexual orientation, higher substance use, being non-Muslim, and reporting sexual interest and the use of the media to obtain sexual information. Structural Equation Modeling (SEM) showed that higher levels in the criterion variables were directly related to pornography use, older age, substance use, and being women. Some mediational links also emerged. Pornography use mediated between the age and criterion variables. Moreover, substance use mediated the association between age and gender with the criterion variables. (4) Conclusions: Our findings support the clinical applicability of the theoretical DSMM framework. Knowing adolescent pornography consumers’ profiles and the impact of pornography on this population would allow for the designing of more effective prevention and regulation proposals.
Multiple Myeloma: Clinical Updates from the American Society of Clinical Oncology Annual Scientific Symposium 2020
Authors: Devarakonda Srinivas , Cottini Francesca , Bumma Naresh , Khan Abdullah , Sharma Nidhi , Chaudhry Maria , Benson Don , Rosko Ashley , Efebera Yvonne
Published: November 2020

The novel clinical data for plasma cell neoplasms (smoldering myeloma, multiple myeloma, and AL amyloidosis) that were presented in the 2020 American Society of Clinical Oncology virtual scientific symposium are summarized here. Data from large phase-3 studies (CASSIOPEIA, ENDURANCE, and TOURMALINE-MM4 trials) and phase-2 studies (SWOG 1211, GMMG CONCEPT trials) for newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplantation are described. Updates from previous important studies for multiple myeloma (STaMINA) along with studies on three different chimeric antigen receptor (CAR-) T cell products are also described. Results of clinical studies involving the use of anti-myeloma drugs with novel mechanisms of action such as immunoconjugates, selinexor, venetoclax, monoclonal antibodies, and data on minimal residual disease (MRD) are discussed. These data provide an overview of the efficacy and safety of the various treatments in multiple myeloma and could lead to changes in our clinical practice, which could pave the path for a “cure” in myeloma.
Efficacy and Safety of Combined Extracts of Cornus officinalis and Ribes fasciculatum for Body Fat Reduction in Overweight Women
Authors: Park Eunkuk , Lee Chang Gun , Kim Jeonghyun , Kang Jae-Heon , Cho Young Gyu , Jeong Seon-Yong
Published: November 2020

Obesity is a medical condition that presents excessive fat accumulation with high risk of serious chronic diseases. The aim of this clinical trial is to investigate the anti-obesity effects of Cornus officinalis (CO) and Ribes fasciculatum (RF) on body fat reduction in Korean overweight women. A total of 147 overweight female participants enrolled in double-blinded clinical trial for 12 weeks and 76 participants completed the clinical study. Participants were treated with four CO and RF mixture (COEC; 400 mg per tablet) or four placebo tablets once a day. Obesity associated parameters (body weight, body mass index (BMI), waist circumference, waist-to-hip ratio, body fat percentage and body fat mass) and safety assessment were analyzed. After 12 weeks of COEC treatment, primary outcomes such as body fat percentage (0.76% vs. 0.01%; p = 0.022) and mass (1.1 kg vs. 0.5 kg; p = 0.049) were significantly decreased. In addition, the results were statistically significant between the COEC and placebo groups, strongly indicated that COEC had anti-obesity effects on overweight women. Secondary outcomes—including body weight, waist and hip circumference, waist-to-hip ratio, body mass index and computed tomography measurement of visceral fat area, subcutaneous fat area, total abdominal fat area and visceral-to-subcutaneous fat ratio—were reduced in COEC-treated group, but no statistical differences were found between the COEC and placebo groups. The safety assessment did not differ between the two groups. These results suggest that treatment of COEC extract reduces body fat percentage and mass in Korean overweight women, indicating it as a protective functional agent for obesity.
Clinical Features and Pathogenic Mechanisms of Gastrointestinal Injury in COVID-19
Authors: Mitsuyama Keiichi , Tsuruta Kozo , Takedatsu Hidetoshi , Yoshioka Shinichiro , Morita Masaru , Niwa Mikio , Matsumoto Satoshi
Published: November 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the global coronavirus disease 2019 (COVID-19) outbreak. Along with the respiratory tract, the gastrointestinal (GI) tract is one of the main extra-pulmonary targets of SARS-CoV-2 with respect to symptom occurrence and is a potential route for virus transmission, most likely due to the presence of angiotensin-converting enzyme 2. Therefore, understanding the mechanisms of GI injury is crucial for a harmonized therapeutic strategy against COVID-19. This review summarizes the current evidence for the clinical features of and possible pathogenic mechanisms leading to GI injury in COVID-19.
Influence of Drilling Technique on the Radiographic, Thermographic, and Geomorphometric Effects of Dental Implant Drills and Osteotomy Site Preparations
Authors: Fraguas de San José Lara , Ruggeri Filippo Maria , Rucco Roberta , Zubizarreta-Macho Álvaro , Alonso Pérez-Barquero Jorge , Riad Deglow Elena , Hernández Montero Sofía
Published: November 2020

The aim of this comparative study is to analyze the influence of drilling technique on the radiographic, thermographic, and geomorphometric effects of dental implant drills and osteotomy site preparations. One hundred and twenty osteotomy site preparations were performed on sixty epoxy resin samples using three unused dental implant drill systems and four drilling techniques performed with a random distribution into the following study groups: Group A: drilling technique performed at 800 rpm with irrigation (n = 30); Group B: drilling technique performed at 45 rpm without irrigation (n = 30); Group C: drilling technique performed at 45 rpm with irrigation (n = 30); and Group D: drilling technique performed at 800 rpm without irrigation (n = 30). The osteotomy site preparation morphologies performed by the 4.1 mm diameter dental implant drills from each study group were analyzed and compared using a cone beam computed tomography (CBCT) scan. The termographic effects generated by the 4.1 mm diameter dental implant drills from each study group were registered using a termographic digital camera and the unused and 4.1 mm diameter dental implant drills that were used 30 times from each study group were exposed to a micro computed tomography (micro-CT) analysis to obtain a Standard Tessellation Language (STL) digital files that determined the wear comparison by geomorphometry. Statistically significant differences were observed between the thermographic and radiographic results of the study groups (p < 0.001). The effect of cooling significatively reduced the heat generation during osteotomy site preparation during high-speed drilling; furthermore, osteotomy site preparation was not affected by the wear of the dental implant drills after 30 uses, regardless of the drilling technique.
Professional Assessment of the Impact of COVID-19 on Handling NET Patients
Authors: Krug Sebastian , Garbe Jakob , König Senta , Ungewiss Hanna , Michl Patrick , Rinke Anja , Schrader Jörg
Published: November 2020

The treatment and monitoring of patients with neuroendocrine tumors (NET) has been a major challenge during the COVID-19 pandemic. In a survey, we investigated the influence of COVID-19 on the care of NET patients in the German speaking countries Germany, Austria and Switzerland. The multidisciplinarity of all treating physicians in the outpatient and inpatient sector was reflected in our survey. Furthermore, we were able to present findings pertaining to the university and non-university medical care. Overall, only a minority of appointments were cancelled, mostly as a result of medical prioritization and less for fear of infection by patients. In the university sector, longer delays for diagnostic measures were observed in comparison to non-university care. During the COVID-19 crisis, NET patients rarely changed their current therapy, but the pandemic impacted the assessment of the different treatment modalities at risk of developing severe COVID-19 disease. This survey provides the first real-world data on the treatment of NET patients from the physicians’ perspective during the COVID-19 crisis. Despite delays in diagnostic procedures and outpatient appointments, only a minority of physicians foresee a major impact of COVID-19 on NET patient care.
Recent Updates and Advances in the Use of Glycated Albumin for the Diagnosis and Monitoring of Diabetes and Renal, Cerebro- and Cardio-Metabolic Diseases
Authors: Giglio Rosaria Vincenza , Lo Sasso Bruna , Agnello Luisa , Bivona Giulia , Maniscalco Rosanna , Ligi Daniela , Mannello Ferdinando , Ciaccio Marcello
Published: November 2020

Diabetes mellitus is a heterogeneous and dysmetabolic chronic disease in which the laboratory plays a fundamental role, from diagnosis to monitoring therapy and studying complications. Early diagnosis and good glycemic control should start as early as possible to delay and prevent metabolic and cardio-vascular complications secondary to this disease. Glycated hemoglobin is currently used as the reference parameter. The accuracy of the glycated hemoglobin dosage may be compromised in subjects suffering from chronic renal failure and terminal nephropathy, affected by the reduction in the survival of erythrocytes, with consequent decrease in the time available for glucose to attach to the hemoglobin. In the presence of these renal comorbidities as well as hemoglobinopathies and pregnancy, glycated hemoglobin is not reliable. In such conditions, dosage of glycated albumin can help. Glycated albumin is not only useful for short-term diagnosis and monitoring but predicts the risk of diabetes, even in the presence of euglycemia. This protein is modified in subjects who do not yet have a glycemic alteration but, as a predictive factor, heralds the risk of diabetic disease. This review summarizes the importance of glycated albumin as a biomarker for predicting and stratifying the cardiovascular risk linked to multiorgan metabolic alterations.
Predicting Morphodynamics for Beach Intertidal Systems in the North Sea: A Space-Time Stochastic Approach
Authors: Bogaert Patrick , Montreuil Anne-Lise , Chen Margaret
Published: November 2020

The ability to accurately predict beach morphodynamics is of primary interest for coastal scientists and managers. With this goal in mind, a stochastic model of a sandy macrotidal barred beach is developed that is based on cross-shore elevation profiles. Intertidal elevation was monitored from monthly to annually for 19 years through Real Time Kinematics-GPS (RTK-GPS) and LiDAR surveys, and monthly during two years with an RTK-GPS. In addition, during two campaigns of about two weeks, intensive surveys on a daily basis were performed with an RTK-GPS on a different set of profiles. Based on the measurements, space and time variograms are constructed in order to assess the spatial and temporal dependencies of these elevations. A separable space-time covariance model is then built from them in order to generate a large number of plausible future profiles at arbitrary time instants t+τ, starting from observed profiles at time instants t. For each simulation, the total displaced sand volume is computed and a distribution is obtained. The mean of this distribution is in good agreement with the total displaced sand volume measured on the profiles, provided that they are lower than 45 m3/m. The time variogram also shows that 90% of maximum variability is reached for a time interval τ of three years. These results demonstrate how the temporal evolution of an integrated property, like the total displaced sand volume, can be estimated over time. This suggests that a similar stochastic approach could be useful for estimating other properties as long as one is able to capture the stochastic space-time variability of the underlying processes.
Epibenthic Harmful Marine Dinoflagellates from Fuerteventura (Canary Islands), with Special Reference to the Ciguatoxin-Producing Gambierdiscus
Authors: Bravo Isabel , Rodríguez Francisco , Ramilo Isabel , Afonso-Carrillo Julio
Published: November 2020

The relationship between the ciguatoxin-producer benthic dinoflagellate Gambierdiscus and other epibenthic dinoflagellates in the Canary Islands was examined in macrophyte samples obtained from two locations of Fuerteventura Island in September 2016. The genera examined included Coolia, Gambierdiscus, Ostreopsis, Prorocentrum, Scrippsiella, Sinophysis, and Vulcanodinium. Distinct assemblages among these benthic dinoflagellates and preferential macroalgal communities were observed. Vulcanodinium showed the highest cell concentrations (81.6 × 103 cells gr−1 wet weight macrophyte), followed by Ostreopsis (25.2 × 103 cells gr−1 wet weight macrophyte). These two species were most represented at a station (Playitas) characterized by turfy Rhodophytes. In turn, Gambierdiscus (3.8 × 103 cells gr−1 wet weight macrophyte) and Sinophysis (2.6 × 103 cells gr−1 wet weight macrophyte) were mostly found in a second station (Cotillo) dominated by Rhodophytes and Phaeophytes. The influence of macrophyte’s thallus architecture on the abundance of dinoflagellates was observed. Filamentous morphotypes followed by macroalgae arranged in entangled clumps presented more richness of epiphytic dinoflagellates. Morphometric analysis was applied to Gambierdiscus specimens. By large, G. excentricus was the most abundant species and G. australes occupied the second place. The toxigenic potential of some of the genera/species distributed in the benthic habitats of the Canary coasts, together with the already known presence of ciguatera in the region, merits future studies on possible transmission of their toxins in the marine food chain.
Outcomes of Antifungal Prophylaxis in High-Risk Haematological Patients (AML under Intensive Chemotherapy): The SAPHIR Prospective Multicentre Study
Authors: Gangneux Jean-Pierre , Padoin Christophe , Michallet Mauricette , Saillio Emeline , Kumichel Alexandra , Peffault de La Tour Régis , Ceballos Patrice , Gastinne Thomas , Pigneux Arnaud
Published: November 2020

Antifungal prophylaxis (AFP) is recommended by international guidelines for patients with acute myeloid leukaemia (AML) undergoing induction chemotherapy and allogeneic hematopoietic cell transplantation. Nonetheless, treatment of breakthrough fungal infections remains challenging. This observational, prospective, multicentre, non-comparative study of patients undergoing myelosuppressive and intensive chemotherapy for AML who are at high-risk of invasive fungal diseases (IFDs), describes AFP management and outcomes for 404 patients (65.6% newly diagnosed and 73.3% chemotherapy naïve). Ongoing chemotherapy started 1.0 ± 4.5 days before inclusion and represented induction therapy for 79% of participants. In 92.3% of patients, posaconazole was initially prescribed, and 8.2% of all patients underwent at least one treatment change after 17 ± 24 days, mainly due to medical conditions influencing AFP absorption (65%). The mean AFP period was 24 ± 32 days, 66.8% stopped their prophylaxis after the high-risk period and 31.2% switched to a non-prophylactic treatment (2/3 empirical, 1/3 pre-emptive/curative). Overall, 9/404 patients (2.2%) were diagnosed with probable or proven IFDs. During the follow-up, 94.3% showed no signs of infection. Altogether, 20 patients (5%) died, and three deaths (0.7%) were IFD-related. In conclusion, AFP was frequently prescribed and well tolerated by these AML patients, breakthrough infections incidence and IFD mortality were low and very few treatment changes were required.
Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment
Authors: Jakšić Daniela , Sertić Miranda , Kocsubé Sándor , Kovačević Ivana , Kifer Domagoj , Mornar Ana , Nigović Biljana , Šegvić Klarić Maja
Published: November 2020

Mycotoxin-producing Aspergilli (Circumdati, Flavi, and Nigri), usually associated with contaminated food, may also cause respiratory disorders and are insufficiently studied in water-damaged indoor environments. Airborne (N = 71) and dust borne (N = 76) Aspergilli collected at post-flood and control locations in Croatia resulted in eleven different species based on their calmodulin marker: A. ochraceus, A. ostianus, A. pallidofulvus, A. sclerotiorum, and A. westerdijkiae (Circumdati); A. flavus (Flavi); and A. tubingensis, A. welwitschiae, A. niger, A. piperis, and A. uvarum (Nigri). Most of the airborne (73%) and dust borne (54%) isolates were found at post-flood locations, and the highest concentrations measured in indoor air (5720 colony-forming units (CFU)/m3) and dust (2.5 × 105 CFU/g) were up to twenty times higher than in the control locations. A. flavus dominated among airborne isolates (25%) at the unrepaired locations, while 56% of the dust borne Aspergilli were identified as A. tubingensis and A. welwitschiae. The ability of identified isolates to produce mycotoxins aflatoxin B1 (AFB1), fumonisin B2 (FB2), and ochratoxin A were assessed by LC-MS analysis. All ochratoxin A (OTA)-producing Circumdati belonged to A. westerdijkiae (13.7 ± 15.81 µg/mL); in the section, FlaviA. flavus produced AFB1 (2.51 ± 5.31 µg/mL), while A. welwitschiae and A. niger (section Nigri) produced FB2 (6.76 ± 13.51 µg/mL and 11.24 ± 18.30 µg/mL, respectively). Water damage dominantly supported the occurrence of aflatoxigenic A. flavus in indoor environments. Yet unresolved, the causal relationship of exposure to indoor Aspergilli and adverse health effects may support the significance of this research.
Impact of Single-Nucleotide Polymorphisms of CTLA-4, CD80 and CD86 on the Effectiveness of Abatacept in Patients with Rheumatoid Arthritis
Authors: Marquez Pete Noelia , Maldonado Montoro María del Mar , Pérez Ramírez Cristina , Sánchez Martín Almudena , Martínez de la Plata Juan Enrique , Martínez Martínez Fernando , Caliz Caliz Rafael , Daddaoua Abdelali , Ramírez Tortosa María del Carmen , Jiménez Morales Alberto
Published: November 2020

Abatacept (ABA) is used as a first-line treatment in patients diagnosed with moderate and severe rheumatoid arthritis (RA). The interindividual response to ABA therapy is very variable in these patients. The objective of our study was therefore to investigate the role of polymorphisms of the CTLA-4, CD80 and CD86 genes, as well as that of clinical factors of the disease, in the response to ABA in patients with RA. A retrospective cohort study was carried out in 109 patients receiving treatment with ABA and diagnosed with RA. The genetic variables were analyzed using real-time PCR with TaqMan® probes. The patients were classified according to the European League Against Rheumatism (EULAR) criteria at 6 and 12 months from start of treatment. The independent variables associated with higher EULAR response were lower duration of previous biologic disease-modifying anti-rheumatic drugs and lower baseline values of the disease activity score 28 after 6 months of ABA treatment; and lower baseline patient’s visual analogue scale (PVAS) after 12 months. In addition, a significant association was found between duration of ABA treatment, non-administration of concomitant glucocorticoids and lower baseline values of the number of inflamed joints and erythrocyte sedimentation rate clinical variables, with remission of the disease after 6 months’ treatment with ABA. Finally, remission of the disease after 12 months’ treatment with ABA was associated with earlier age at start of ABA therapy and lower number of previous biologic therapies (BTs). The CTLA-4rs5742909-T allele and the CTLA-4rs231775-G allele were found to be associated with satisfactory EULAR response and low disease activity (LDA) after 12 months’ treatment with ABA (CTLA-4rs5742909 T vs. CC; OR = 5.88; CI95% = 1.48–23.29 and OR = 4.75; CI95% = 1.35–17.94, respectively, and CTLA-4rs231775 G vs. AA, OR = 3.48; CI95% = 1.20–10.09 and OR = 4.68; CI95% = 1.49–17.94, respectively). In conclusion, patients with RA treated with ABA showed better EULAR response and LDA rate when they had the CTLA-4 rs5742909-T or CTLA-4 rs231775-G polymorphisms; furthermore, this remission rate increased in patients that began ABA treatment earlier, those with a lower number of previous BTs and those with a lower PVAS value.