bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighborhood Socioeconomic Deprivation Associated with Fat Mass and Weight Status in Youth
Authors: Clennin Morgan , Brown Asia , Lian Min , Dowda Marsha , Colabianchi Natalie , Pate Russell R.
Published: September 2020

(1) Background: Few studies have examined the relationship between neighborhood socioeconomic deprivation (SED) and weight-related outcomes in youth, controlling for weight-related behaviors. Hence, the purpose of this study was to examine the association between neighborhood SED, weight status, and fat mass in a diverse sample of youth, before and after controlling for physical activity and diet. (2) Methods: The sample included 828 youth from the Transitions and Activity Changes in Kids study. Neighborhood SED was expressed as an index score at the census tract of residence. Height, weight, and body composition were measured and used to calculate fat mass index (FMI) and weight status. Moderate-to-vigorous physical activity (MVPA) and sedentary behavior (min/h) were measured via accelerometry. Diet quality was assessed via the Block Food Screener for Kids. Multilevel regression models were employed to examine these relationships. (3) Results: Neighborhood SED was significantly associated with FMI and weight status before and after controlling for MVPA, sedentary behavior, and diet. Notably, youth residing in the most deprived neighborhoods had significantly higher FMI and were 30% more likely to be overweight/obese (OR = 1.30; 95% CI = 1.03–1.65). (4) Conclusions: Greater neighborhood SED was consistently and significantly associated with higher fat mass index and increased likelihood of overweight/obesity among youth.
Increasing Rural Recruitment and Retention through Rural Exposure during Undergraduate Training: An Integrative Review
Authors: Holst Jens
Published: September 2020

Objectives: Ensuring nationwide access to medical care challenges health systems worldwide. Rural exposure during undergraduate medical training is promising as a means for overcoming the shortage of physicians outside urban areas, but the effectiveness is widely unknown. This integrative review assesses the effects of rural placements during undergraduate medical training on graduates’ likelihood to take up rural practice. Methods: The paper presents the results of a longitudinal review of the literature published in PubMed, Embase, Google Scholar and elsewhere on the measurable effects of rural placements and internships during medical training on the number of graduates in rural practice. Results: The combined database and hand search identified 38 suitable primary studies with rather heterogeneous interventions, endpoints and results, mostly cross-sectional and control studies. The analysis of the existing evidence exhibited predominantly positive but rather weak correlations between rural placements during undergraduate medical training and later rural practice. Beyond the initial scope, the review underpinned rural upbringing to be the strongest predictor for rural practice. Conclusions: This review confirms that rural exposure during undergraduate medical training to contributes to recruitment and retention in nonurban settings. It can play a role within a broader strategy for overcoming the shortage of rural practitioners. Rural placements during medical education turned out to be particularly effective for rural-entry students. Given the increasing funding being directed towards medical schools to produce graduates that will work rurally, more robust high-quality research is needed.
Cellular and Subcellular Localisation of Kv4-Associated KChIP Proteins in the Rat Cerebellum
Authors: Alfaro-Ruíz Rocío , Aguado Carolina , Martín-Belmonte Alejandro , Moreno-Martínez Ana Esther , Luján Rafael
Published: September 2020

The K+ channel interacting proteins (KChIPs) are a family of cytosolic proteins that interact with Kv4 channels, leading to higher current density, modulation of channel inactivation and faster recovery from inactivation. Using immunohistochemical techniques at the light and electron microscopic level combined with quantitative analysis, we investigated the cellular and subcellular localisation of KChIP3 and KChIP4 to compare their distribution patterns with those for Kv4.2 and Kv4.3 in the cerebellar cortex. Immunohistochemistry at the light microscopic level demonstrated that KChIP3, KChIP4, Kv4.2 and Kv4.3 proteins were widely expressed in the cerebellum, with mostly overlapping patterns. Immunoelectron microscopic techniques showed that KChIP3, KChIP4, Kv4.2 and Kv4.3 shared virtually the same somato-dendritic domains of Purkinje cells and granule cells. Application of quantitative approaches showed that KChIP3 and KChIP4 were mainly membrane-associated, but also present at cytoplasmic sites close to the plasma membrane, in dendritic spines and shafts of Purkinje cells (PCs) and dendrites of granule cells (GCs). Similarly, immunoparticles for Kv4.2 and Kv4.3 were observed along the plasma membrane and at intracellular sites in the same neuron populations. In addition to the preferential postsynaptic distribution, KChIPs and Kv4 were also distributed presynaptically in parallel fibres and mossy fibres. Immunoparticles for KChIP3, KChIP4 and Kv4.3 were detected in parallel fibres, and KChIP3, KChIP4, Kv4.2 and Kv4.3 were found in parallel fibres, indicating that composition of KChIP and Kv4 seems to be input-dependent. Together, our findings unravelled previously uncharacterised KChIP and Kv4 subcellular localisation patterns in neurons, revealed that KChIP have additional Kv4-unrelated functions in the cerebellum and support the formation of macromolecular complexes between KChIP3 and KChIP4 with heterotetrameric Kv4.2/Kv4.3 channels.
Proteostasis and Proteotoxicity in the Network Medicine Era
Authors: Lualdi Marta , Alberio Tiziana , Fasano Mauro
Published: September 2020

Neurodegenerative proteinopathies are complex diseases that share some pathogenetic processes. One of these is the failure of the proteostasis network (PN), which includes all components involved in the synthesis, folding, and degradation of proteins, thus leading to the aberrant accumulation of toxic protein aggregates in neurons. The single components that belong to the three main modules of the PN are highly interconnected and can be considered as part of a single giant network. Several pharmacological strategies have been proposed to ameliorate neurodegeneration by targeting PN components. Nevertheless, effective disease-modifying therapies are still lacking. In this review article, after a general description of the PN and its failure in proteinopathies, we will focus on the available pharmacological tools to target proteostasis. In this context, we will discuss the main advantages of systems-based pharmacology in contrast to the classical targeted approach, by focusing on network pharmacology as a strategy to innovate rational drug design.
Immunohistological Expression of SOX-10 in Triple-Negative Breast Cancer: A Descriptive Analysis of 113 Samples
Authors: Kriegsmann Katharina , Flechtenmacher Christa , Heil Jörg , Kriegsmann Jörg , Mechtersheimer Gunhild , Aulmann Sebastian , Weichert Wilko , Sinn Hans-Peter , Kriegsmann Mark
Published: September 2020

Background: SRY-related HMG-box 10 (SOX-10) is commonly expressed in triple negative breast cancer (TNBC). However, data on the biological significance of SOX-10 expression is limited. Therefore, we investigated immunhistological SOX-10 expression in TNBC and correlated the results with genetic alterations and clinical data. Methods: A tissue microarray including 113 TNBC cases was stained by SOX-10. Immunohistological data of AR, BCL2, CD117, p53 and Vimentin was available from a previous study. Semiconductor-based panel sequencing data including commonly altered breast cancer genes was also available from a previous investigation. SOX-10 expression was correlated with clinicopathological, immunohistochemical and genetic data. Results: SOX-10 was significantly associated with CD117 and Vimentin, but not with AR expression. An association of SOX-10 with BCL2, EGFR or p53 staining was not observed. SOX-10-positive tumors harbored more often TP53 mutations but less frequent mutations of PIK3CA or alterations of the PIK3K pathway. SOX-10 expression had no prognostic impact either on disease-free, distant disease-free, or overall survival. Conclusions: While there might be a value of SOX-10 as a differential diagnostic marker to identify metastases of TNBC, its biological role remains to be investigated.
Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review
Authors: Wang Shao-Cheng , Chen Yuan-Chuan , Chen Shaw-Ji , Lee Chun-Hung , Cheng Ching-Ming
Published: September 2020

Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut–brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.
Mass Spectrometry Imaging as a Potential Tool to Investigate Human Osteoarthritis at the Tissue Level
Authors: Lee Yea-Rin , Briggs Matthew T. , Condina Mark R. , Puddy Hamish , Anderson Paul H. , Hoffmann Peter , Kuliwaba Julia S.
Published: September 2020

Osteoarthritis (OA) is the most common degenerative joint disease, predicted to increase in incidence year by year due to an ageing population. Due to the biological complexity of the disease, OA remains highly heterogeneous. Although much work has been undertaken in the past few years, underlying molecular mechanisms leading to joint tissue structural deterioration are not fully understood, with only few validated markers for disease diagnosis and progression being available. Discovery and quantitation of various OA-specific biomarkers is still largely focused on the bodily fluids which does not appear to be reliable and sensitive enough. However, with the advancement of spatial proteomic techniques, several novel peptides and proteins, as well as N-glycans, can be identified and localised in a reliable and sensitive manner. To summarise the important findings from OA biomarker studies, papers published between 2000 and 2020 were searched via Google Scholar and PubMed. Medical subject heading (MeSH) terms ‘osteoarthritis’, ‘biomarker’, ‘synovial fluid’, ‘serum’, ‘urine’, ’matrix-assisted laser desorption/ionisation’, ‘mass spectrometry imaging’, ‘proteomic’, ‘glycomic’, ‘cartilage’, ‘synovium’ AND ‘subchondral bone’ were selectively used. The literature search was restricted to full-text original research articles and written only in English. Two main areas were reviewed for OA biomarker studies: (1) an overview of disease-specific markers detected from different types of OA bio-samples, and (2) an up-to-date summary of the tissue-specific OA studies that have utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI). Overall, these OA biomarkers could provide clinicians with information for better the diagnosis, and prognosis of individual patients, and ultimately help facilitate the development of disease-modifying treatments.
Immobilization of BMP-2 and VEGF within Multilayered Polydopamine-Coated Scaffolds and the Resulting Osteogenic and Angiogenic Synergy of Co-Cultured Human Mesenchymal Stem Cells and Human Endothelial Progenitor Cells
Authors: Godoy-Gallardo Maria , Portolés-Gil Núria , López-Periago Ana M. , Domingo Concepción , Hosta-Rigau Leticia
Published: September 2020

We have previously reported the fabrication of a polycaprolactone and hydroxyapatite composite scaffold incorporating growth factors to be used for bone regeneration. Two growth factors were incorporated employing a multilayered coating based on polydopamine (PDA). In particular, Bone morphogenetic protein-2 (BMP-2) was bound onto the inner PDA layer while vascular endothelial growth factor (VEGF) was immobilized onto the outer one. Herein, the in vitro release of both growth factors is evaluated. A fastest VEGF delivery followed by a slow and more sustained release of BMP-2 was demonstrated, thus fitting the needs for bone tissue engineering applications. Due to the relevance of the crosstalk between bone-promoting and vessel-forming cells during bone healing, the functionalized scaffolds are further assessed on a co-culture setup of human mesenchymal stem cells and human endothelial progenitor cells. Osteogenic and angiogenic gene expression analysis indicates a synergistic effect between the growth factor-loaded scaffolds and the co-culture conditions. Taken together, these results indicate that the developed scaffolds hold great potential as an efficient platform for bone-tissue applications.
Targeting Nonsense: Optimization of 1,2,4-Oxadiazole TRIDs to Rescue CFTR Expression and Functionality in Cystic Fibrosis Cell Model Systems
Authors: Pibiri Ivana , Melfi Raffaella , Tutone Marco , Di Leonardo Aldo , Pace Andrea , Lentini Laura
Published: September 2020

Cystic fibrosis (CF) patients develop a severe form of the disease when the cystic fibrosis transmembrane conductance regulator (CFTR) gene is affected by nonsense mutations. Nonsense mutations are responsible for the presence of a premature termination codon (PTC) in the mRNA, creating a lack of functional protein. In this context, translational readthrough-inducing drugs (TRIDs) represent a promising approach to correct the basic defect caused by PTCs. By using computational optimization and biological screening, we identified three new small molecules showing high readthrough activity. The activity of these compounds has been verified by evaluating CFTR expression and functionality after treatment with the selected molecules in cells expressing nonsense–CFTR–mRNA. Additionally, the channel functionality was measured by the halide sensitive yellow fluorescent protein (YFP) quenching assay. All three of the new TRIDs displayed high readthrough activity and low toxicity and can be considered for further evaluation as a therapeutic approach toward the second major cause of CF.
Umbilical Cord Mesenchymal Stem Cell-Derived Nanovesicles Potentiate the Bone-Formation Efficacy of Bone Morphogenetic Protein 2
Authors: Lim Songhyun , Lyu Hao-Zhen , Lee Ju-Ro , Han Shi Huan , Lee Jae Hyup , Kim Byung-Soo
Published: September 2020

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is one of the most potent osteogenic factors used to treat bone loss. However, at higher doses, rhBMP-2 does not necessarily increase bone formation but rather increases the incidence of adverse side effects. Here, we investigated whether umbilical cord mesenchymal stem cell (UCMSC)-derived nanovesicles (NVs) further increase the in vivo bone formation at high doses of rhBMP-2. In the presence of UCMSC-derived NVs, proliferation, migration, and tube formation of human umbilical vein endothelial cells were stimulated in vitro. Furthermore, migration and osteogenesis of human bone marrow-derived mesenchymal stem cells were stimulated. To examine the efficacy of UCMSC-derived NVs on in vivo bone formation, collagen sponges soaked with rhBMP-2 and UCMSC-derived NVs were used in athymic nude mice with calvarial defects. At a high rhBMP-2 dosage (500 ng/mL), UCMSC-derived NVs significantly promoted bone formation in calvarial defects; however, the UCMSC-derived NVs alone did not induce in vivo bone formation. Our results indicate that UCMSC-derived NVs can potentiate the bone formation efficacy of rhBMP-2 at a high dosage.
Bordetella holmesii Lipopolysaccharide Hide and Seek Game with Pertussis: Structural Analysis of the O-Specific Polysaccharide and the Core Oligosaccharide of the Type Strain ATCC 51541
Authors: Ucieklak Karolina , Koj Sabina , Niedziela Tomasz
Published: September 2020

Whooping cough is a highly contagious disease caused predominantly by Bordetella pertussis, but it also comprises of a pertussis-like illness caused by B. holmesii. The virulence factors of B. holmesii and their role in the pathogenesis remain unknown. Lipopolysaccharide is the main surface antigen of all Bordetellae. Data on the structural features of the lipopolysaccharide (LPS) of B. holmesii are scarce. The poly- and oligosaccharide components released by mild acidic hydrolysis of the LPS were separated and investigated by 1H and 13C NMR spectroscopy, mass spectrometry, and chemical methods. The structures of the O-specific polysaccharide and the core oligosaccharide of B. holmesii ATCC 51541 have been identified for the first time. The novel pentasaccharide repeating unit of the B. holmesii O-specific polysaccharide has the following structure: {→2)-α-l-Rhap-(1→6)-α-d-Glcp-(1→4)-[β-d-GlcpNAc-(1→3]-α-d-Galp-(1→3)-α-d-GlcpNAc-(1→}n. The SDS-PAGE and serological cross-reactivities of the B. holmesii LPS suggested the similarity between the core oligosaccharides of B. holmesii ATCC 51541 and B. pertussis strain 606. The main oligosaccharide fraction contained a nonasaccharide. The comparative analysis of the NMR spectra of B. holmesii core oligosaccharide fraction with this of the B. pertussis strain 606 indicated that the investigated core oligosaccharides were identical.
Recent Progress in Carbon Nanotube Polymer Composites in Tissue Engineering and Regeneration
Authors: Lekshmi Gangadhar , Sana Siva Sankar , Nguyen Van-Huy , Nguyen Thi Hong Chuong , Nguyen Chinh Chien , Le Quyet Van , Peng Wanxi
Published: September 2020

Scaffolds are important to tissue regeneration and engineering because they can sustain the continuous release of various cell types and provide a location where new bone-forming cells can attach and propagate. Scaffolds produced from diverse processes have been studied and analyzed in recent decades. They are structurally efficient for improving cell affinity and synthetic and mechanical strength. Carbon nanotubes are spongy nanoparticles with high strength and thermal inertness, and they have been used as filler particles in the manufacturing industry to increase the performance of scaffold particles. The regeneration of tissue and organs requires a significant level of spatial and temporal control over physiological processes, as well as experiments in actual environments. This has led to an upsurge in the use of nanoparticle-based tissue scaffolds with numerous cell types for contrast imaging and managing scaffold characteristics. In this review, we emphasize the usage of carbon nanotubes (CNTs) and CNT–polymer composites in tissue engineering and regenerative medicine and also summarize challenges and prospects for their potential applications in different areas.
LncRNAs in the Type I Interferon Antiviral Response
Authors: Suarez Beatriz , Prats-Mari Laura , Unfried Juan P. , Fortes Puri
Published: September 2020

The proper functioning of the immune system requires a robust control over a delicate equilibrium between an ineffective response and immune overactivation. Poor responses to viral insults may lead to chronic or overwhelming infection, whereas unrestrained activation can cause autoimmune diseases and cancer. Control over the magnitude and duration of the antiviral immune response is exerted by a finely tuned positive or negative regulation at the DNA, RNA, and protein level of members of the type I interferon (IFN) signaling pathways and on the expression and activity of antiviral and proinflammatory factors. As summarized in this review, committed research during the last decade has shown that several of these processes are exquisitely regulated by long non-coding RNAs (lncRNAs), transcripts with poor coding capacity, but highly versatile functions. After infection, viruses, and the antiviral response they trigger, deregulate the expression of a subset of specific lncRNAs that function to promote or repress viral replication by inactivating or potentiating the antiviral response, respectively. These IFN-related lncRNAs are also highly tissue- and cell-type-specific, rendering them as promising biomarkers or therapeutic candidates to modulate specific stages of the antiviral immune response with fewer adverse effects.
Association of the Qualitative Clock Drawing Test with Progression to Dementia in Non-Demented Older Adults
Authors: Umegaki Hiroyuki , Suzuki Yusuke , Yamada Yosuke , Komiya Hitoshi , Watanabe Kazuhisa , Nagae Masaaki , Kuzuya Masafumi
Published: September 2020

To evaluate the predictability of progression of cognitive impairment to dementia using qualitative clock drawing test (CDT) scores, we administered both the CDT using Cahn et al.’s qualitative scoring system and the Mini-Mental State Examination (MMSE) to assess cognitive function in non-demented older individuals attending a memory clinic at a university hospital. Patients visiting the clinic for assessment of cognitive function between January 2015 and December 2019 were enrolled, and only those who were diagnosed as not having dementia at the time of initial assessment completed a follow-up assessment at 1 y (n = 163). To examine any association of qualitative CDT score with progression to dementia, multiple logistic regression analysis was conducted with the change in diagnosis from non-dementia to dementia at 1 y as the dependent variable. A total of 26 participants (16.0%) were diagnosed as having converted to dementia. Multiple logistic regression analysis revealed that both the qualitative CDT score using Cahn et al.’s scoring system and the existence of conceptual deficits were significantly associated with progression to dementia at 1 y after initial assessment of cognitive function, irrespective of the MMSE score, among non-demented older individuals. The CDT may be a useful predictor of progression to dementia in primary care settings.
Therapeutic Efficacy of Human Embryonic Stem Cell-Derived Multipotent Stem/Stromal Cells in Diabetic Detrusor Underactivity: A Preclinical Study
Authors: Shin Jung Hyun , Ryu Chae-Min , Ju Hyein , Yu Hwan Yeul , Song Sujin , Hong Ki-Sung , Chung Hyung-Min , Park Juhyun , Shin Dong-Myung , Choo Myung-Soo
Published: September 2020

Mesenchymal stem/stromal cell (MSC) therapy is a promising approach for treatment of as yet incurable detrusor underactivity (DUA), which is characterized by decreased detrusor contraction strength and/or duration, leading to prolonged bladder emptying. In the present study, we demonstrated the therapeutic potential of human embryonic stem cell (ESC)-derived multipotent MSCs (M-MSCs) in a diabetic rat model of DUA. Diabetes mellitus (DM) was induced by intraperitoneal injection of streptozotocin (STZ) (50 mg/kg) into 8-week-old female Sprague-Dawley rats. Three weeks later, various doses of M-MSCs (0.25, 0.5, and 1 × 106 cells) or an equivalent volume of PBS were injected into the outer layer of the bladder. Awake cystometry, organ bath, histological, and gene expression analyses were evaluated 1 week (short-term) or 2 and 4 weeks (long-term) after M-MSC transplantation. STZ-induced diabetic rats developed DUA, including phenotypes with significantly longer micturition intervals, increased residual urine amounts and bladder capacity, decreased micturition pressure on awake cystometry, and contractile responses to various stimuli in organ bath studies. Muscle degeneration, mast cell infiltration, fibrosis, and apoptosis were present in the bladders of DM animals. A single local transplantation of M-MSCs ameliorated DUA bladder pathology, including functional changes and histological evaluation, and caused few adverse outcomes. Immunostaining and gene expression analysis revealed that the transplanted M-MSCs supported myogenic restoration primarily by engrafting into bladder tissue via pericytes, and subsequently exerting paracrine effects to prevent apoptotic cell death in bladder tissue. The therapeutic efficacy of M-MSCs was superior to that of human umbilical cord-derived MSCs at the early time point (1 week). However, the difference in efficacy between M-MSCs and human umbilical cord-derived MSCs was statistically insignificant at the later time points (2 and 4 weeks). Collectively, the present study provides the first evidence for improved therapeutic efficacy of a human ESC derivative in a preclinical model of DM-associated DUA.
Reference Intervals for Platelet Counts in the Elderly: Results from the Prospective SENIORLAB Study
Authors: Hermann Wolfgang , Risch Lorenz , Grebhardt Chris , Nydegger Urs E. , Sakem Benjamin , Imperiali Mauro , Renz Harald , Risch Martin
Published: September 2020

Currently, age- and sex-independent reference limits (RLs) are frequently used to interpret platelet counts in seniors. We aimed to define and validate reference intervals (RIs) for platelet counts within the framework of the prospective SENIORLAB study. Subjectively healthy Swiss individuals aged 60 years and older were prospectively included and followed for morbidity and mortality. Participants who had circumstances known to affect platelet counts were excluded. The obtained RIs were validated with indirect statistical methods. Frequencies of abnormal platelet counts in a population-based setting, including 41.5% of the entire age-specific population of the Principality of Liechtenstein, were compared by using age- and sex-independent RIs and the RLs obtained in the present study. For males (n = 542), 95% RIs for platelet counts were defined as follows: 150–300 × 109/L (60–69 years); 130–300 × 109/L (70–79 years); and 120–300 × 109/L (80 years and above). For females (n = 661), the consolidated age-independent 95% RI was 165–355 × 109/L. These RI values were validated by indirect RI determination of 51,687 (30,392 female/21,295 male) patients of the same age. Age- and sex-independent RIs exhibited imbalanced frequencies of abnormal platelet counts between the two sexes, which were corrected by introducing age- and sex-specific RLs. In conclusion, females have higher platelet counts than males. Whereas the upper RL for males remains constant, the lower RL decreases with age. We propose to abandon the practice of employing sex- and age-independent RL for platelet counts in the elderly.
Immunohistochemical Characterization of Immune Infiltrate in Tumor Microenvironment of Glioblastoma
Authors: Rahimi Koshkaki Hassan , Minasi Simone , Ugolini Alessio , Trevisi Gianluca , Napoletano Chiara , Zizzari Ilaria G. , Gessi Marco , Giangaspero Felice , Mangiola Annunziato , Nuti Marianna , Buttarelli Francesca R. , Rughetti Aurelia
Published: September 2020

Background: Glioblastoma (GBM) is the most common primary malignant brain cancer in adults, with very limited therapeutic options. It is characterized by a severe immunosuppressive milieu mostly triggered by suppressive CD163+ tumor-associated macrophages (TAMs). The efficacy of immune checkpoint inhibitor interventions aimed at rescuing anti-tumor immunity has not been proved to date. Thus, it is critically important to investigate the immunomodulatory mechanisms acting within the GBM microenvironment for the better design of immunotherapeutic strategies. Methods: The immunohistochemical analysis of a panel of immune biomarkers (CD3, FoxP3, CD163, IDO, PDL-1, PD-1 and TIGIT) was performed in paired samples of the tumor core (TC) and peritumoral area (PTA) of nine GBM patients. Results: CD163+ cells were the most common cell type in both the PTA and TC. IDO and PDL-1 were expressed in most of the TC samples, frequently accompanied by TIGIT expression; on the contrary, they were almost absent in the PTA. CD3+ cells were present in both the TC and PTA, to a lesser extent than CD163+ cells; they often were accompanied by PD-1 expression, especially in the TC. FoxP3 was scarcely present. Conclusion: Distinct inhibitory mechanisms can act simultaneously in both the TC and PTA to contribute to the strong immunosuppression observed within the GBM microenvironment. Nevertheless, the PTA shows strongly reduced immunosuppression when compared to the TC, thus representing a potential target for immunotherapies. Moreover, our results support the working hypothesis that immunosuppression and T-cell exhaustion can be simultaneously targeted to rescue anti-tumor immunity in GBM patients.
The Three-Dimensional Morphology and Distribution of CaS Inclusions in Continuous Casting Slab of Ni20Mn6 Steel
Authors: Chen Jing , Zhang Jing , Zheng Shaobo , Zhang Jieyu
Published: September 2020

Calcium sulfide (CaS) inclusion with large and irregular shape is detrimental to the properties of steel. Understanding the shape and distribution of CaS inclusions in a continuous casting (CC) slab is of significance for improving the rolling properties. In this study, CaS inclusions were extracted from CC slab of Ni20Mn6 steel using the electrolytic extraction and investigated by scanning electron microscopy (SEM)-energy dispersive X-ray spectroscopy (EDX). The CaS inclusions morphologies vary with their locations in the CC slab and, thus, are classified into five categories. The thermodynamics calculated results showed that CaS inclusions precipitated at the end of solidification due to the microsegregation of sulfur and calcium in the interdendrite liquid and finally precipitated along the austenite grain boundary. The macrosegregation degree of solutes in different regions is one of the reasons that affect the size of CaS inclusion. The morphologies of CaS inclusion are affected by the solidification structure of slab and austenite grain boundary.
A Simple Approach for Generating Random Aggregate Model of Concrete Based on Laguerre Tessellation and Its Application Analyses
Authors: Guo Yutai , He Jialong , Jiang Hui , Zhou Yuande , Jin Feng , Song Chongmin
Published: September 2020

Generating random aggregate models (RAMs) plays a key role in the mesoscopic modelling of concrete-like composite materials. The arbitrary geometry, wide gradation, and high volume ratio of aggregates pose a great challenge for fast and efficient numerical construction of concrete meso-structures. This paper presents a simple strategy for generating RAMs of concrete based on Laguerre tessellation, which mainly consists of three steps: tessellation, geometric smoothing, and scaling. The computer-assisted design (CAD) file of RAMs obtained by the proposed approach can be directly adopted for the construction of random numerical concrete samples. Combined with the image-based octree meshing algorithm, the scaled boundary finite element method (SBFEM) was adopted for an automatic stress analysis of mass concrete samples, and a parametric study was conducted to investigate the meso-structural effects on concrete elasticity properties. The modelling results successfully reproduced the increasing trend of concrete elastic modulus with the grading of coarse aggregates in literature test data and demonstrate the effectiveness of the proposed strategy.
Grain Growth Kinetics of 0.65Ca0.61La0.26TiO3-0.35Sm(Mg0.5Ti0.5)O3 Dielectric Ceramic
Authors: Liu Jin , Liang Bingliang , Zhang Jianjun , He Wen , Ouyang Sheng , Chen Weihua , Liu Changhong , Ai Yunlong
Published: September 2020

The 0.65Ca0.61La0.26TiO3-0.35Sm(Mg0.5Ti0.5)O3[0.65CLT-0.35SMT] ceramic was prepared by the solid-state reaction method. The effects of sintering process on its microstructure and grain growth behavior were investigated. The Hillert model and a simplified Sellars model were established by linear regression, and the Sellars-Anelli model with a time index was established by using a nonlinear regression method. The results show that the grain size gradually increases with the increase of sintering temperature and holding time. Meanwhile, the sintering temperature has a more significant effect on the grain growth. The grain sizes of 0.65CLT-0.35SMT ceramic were predicted by the three models and compared with the experimentally measured grain size. The results indicate that for the 0.65CLT-0.35SMT ceramic, the Hillert model has the lowest prediction accuracy and the Sellars-Anelli model, the highest prediction accuracy. In this work, the Sellars-Anelli model can effectively predict the grain growth process of 0.65CLT-0.35SMT ceramic.
Incorporation of Waste Glass as an Activator in Class-C Fly Ash/GGBS Based Alkali Activated Material
Authors: Sasui Sasui , Kim Gyuyong , Nam Jeongsoo , van Riessen Arie , Eu Hamin , Chansomsak Sant , Alam Syed Fakhar , Cho Churl Hee
Published: September 2020

In this study, an alkaline activator was synthesized by dissolving waste glass powder (WGP) in NaOH-4M solution to explore its effects on the formation of alkali-activated material (AAM) generated by Class-C fly ash (FA) and ground granulated blast furnace slag (GGBS). The compressive strength, flexure strength, porosity and water absorption were measured, and X-ray diffraction (XRD) and scanning electron microscopy with energy dispersive X-ray (SEM-EDX) were used to study the crystalline phases, hydration mechanism and microstructure of the resulting composites. Results indicated that the composition of alkali solutions and the ratios of FA/GGBS were significant in enhancing the properties of the obtained AAM. As the amount of dissolved WGP increased in alkaline solution, the silicon concentration increased, causing the accelerated reactivity of FA/GGBS to develop Ca-based hydrate gel as the main reaction product in the system, thereby increasing the strength and lowering the porosity. Further increase in WGP dissolution led to strength loss and increased porosity, which were believed to be due to the excessive water demand of FA/GGBS composites to achieve optimum mixing consistency. Increasing the GGBS proportion in a composite appeared to improve the strength and lower the porosity owing to the reactivity of GGBS being higher than that of FA, which contributed to develop C-S-H-type hydration.
Voltage and Time Required for Irreversible Thermal Damage of Tumor Tissues during Electrochemotherapy under Thomson Effect
Authors: Youssef Hamdy M. , El-Bary Alaa A.
Published: September 2020

The essential target of the tumor’s treatment is how to destroy its tissues. This work is dealing with the thermal damage of the tumor tissue due to the thermoelectrical effect based on the Thomson effect. The governing equation of tumor tissue in concentric spherical space based on the thermal lagging effect is constructed and solved when the surface of the tumor tissue is subjected to a specific electric voltage. Different voltage and resistance effects have been studied and discussed for three different types of tumor tissues. The thermal damage quantity has been calculated with varying values of voltages and times. The voltage has significant effects on the temperature and the amount of the irreversible thermal damage of the tumor. Electrotherapy is a successful treatment. This work introduces a different model to doctors who work in clinical cancer to do experiments using electricity to damage the cancer cells.
Genome Mining, Microbial Interactions, and Molecular Networking Reveals New Dibromoalterochromides from Strains of Pseudoalteromonas of Coiba National Park-Panama
Authors: Atencio Librada A. , Boya P. Cristopher A. , Martin H. Christian , Mejía Luis C. , Dorrestein Pieter C. , Gutiérrez Marcelino
Published: September 2020

The marine bacterial genus Pseudoalteromonas is known for their ability to produce antimicrobial compounds. The metabolite-producing capacity of Pseudoalteromonas has been associated with strain pigmentation; however, the genomic basis of their antimicrobial capacity remains to be explained. In this study, we sequenced the whole genome of six Pseudoalteromonas strains (three pigmented and three non-pigmented), with the purpose of identifying biosynthetic gene clusters (BGCs) associated to compounds we detected via microbial interactions along through MS-based molecular networking. The genomes were assembled and annotated using the SPAdes and RAST pipelines and mined for the identification of gene clusters involved in secondary metabolism using the antiSMASH database. Nineteen BGCs were detected for each non-pigmented strain, while more than thirty BGCs were found for two of the pigmented strains. Among these, the groups of genes of nonribosomal peptide synthetases (NRPS) that code for bromoalterochromides stand out the most. Our results show that all strains possess BGCs for the production of secondary metabolites, and a considerable number of distinct polyketide synthases (PKS) and NRPS clusters are present in pigmented strains. Furthermore, the molecular networking analyses revealed two new molecules produced during microbial interactions: the dibromoalterochromides D/D’ (11–12).
Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment
Authors: Singh Harinder , Miyamoto Satoshi , Darshi Manjula , Torralba Manolito G. , Kwon Keehwan , Sharma Kumar , Pieper Rembert
Published: September 2020

The leptin receptor-deficient db/db mouse model is an accepted in vivo model to study obesity, type 2 diabetes, and diabetic kidney disease. Healthy gastrointestinal (GI) microbiota has been linked to weight loss, improved glycemic control, and physiological benefits. We investigated the effect of various drugs on the GI microbiota of db/db mice as compared to control db/m mice. Treatment with long-acting pirfenidone (PFD) increased gut microbial diversity in diabetic db/db mice. Firmicutes, the most abundant phylum in db/m mice, decreased significantly in abundance in db/db mice but showed increased abundance with long-acting PFD treatment. Several bacterial taxa, including Lactobacillus and some Bacteroides, were less abundant in db/db mice and more abundant in long-acting-PFD-treated db/db mice. Long-acting PFD treatment reduced the abundance of Akkermansia muciniphila (5%) as compared to db/db mice (~15%). We conclude that gut microbial dysbiosis observed in db/db mice was partially reversed by long-acting PFD treatment and hypothesize that PFD has beneficial effects, in part, via its influence on the gut microbial metabolite profile. In quantitatively assessing urine metabolites, we observed a high abundance of diabetic ketoacidosis biomarkers, including 3-hydroxybutyric acid and acetoacetic acid in db/db mice, which were less abundant in the long-acting-PFD-treated db/db mice.
Nutrition for Gestational Diabetes—Progress and Potential
Authors: Petry Clive J.
Published: September 2020

Gestational diabetes (GDM), traditionally defined as any form of glucose intolerance first detected in pregnancy [...]
The Association of Dietary Macronutrients with Lung Function in Healthy Adults Using the Ansan-Ansung Cohort Study
Authors: Lee Sang-Ah , Joshi Pankaj , Kim Yeonjin , Kang Daehee , Kim Woo Jin
Published: September 2020

This study is aimed to examine the association between macronutrient intake and lung function in healthy adults (n = 5880) using the Ansan-Ansung cohort study. To identify the index of lung function, we used the percentage difference of predicted Forced Expiratory Volume (%FEV1_diff) between baseline and follow-up. Based on the median %FEV1_diff, subjects were classified by two groups as “decreased vs. unchanged/improved”. The dietary macronutrients were estimated and validated using the food-frequency questionnaire. Multiple logistic regression models were used to evaluate the association after adjusting for confounders. Advanced analysis examined the association after stratifying by age and obesity. The average of %FEV1 is 114.1 and 112.5 at baseline and follow-up, respectively. The positive association of protein and fiber intake with lung function was observed in men. Low fat and high carbohydrate intake decreased the lung function in women only. After stratification by age, the association of protein, fat, and carbohydrate intake with lung function was observed in young men and old women only. Otherwise, the association of protein and fiber with lung function was influenced by abdominal obesity. In conclusion, the lung function was positively associated with high protein and fat intake, but was negatively associated with high carbohydrate intake, which could be influenced by age and obesity.
Antimatter Gravity: Second Quantization and Lagrangian Formalism
Authors: Jentschura Ulrich D.
Published: September 2020

The application of the CPT (charge-conjugation, parity, and time reversal) theorem to an apple falling on Earth leads to the description of an anti-apple falling on anti–Earth (not on Earth). On the microscopic level, the Dirac equation in curved space-time simultaneously describes spin-1/2 particles and their antiparticles coupled to the same curved space-time metric (e.g., the metric describing the gravitational field of the Earth). On the macroscopic level, the electromagnetically and gravitationally coupled Dirac equation therefore describes apples and anti-apples, falling on Earth, simultaneously. A particle-to-antiparticle transformation of the gravitationally coupled Dirac equation therefore yields information on the behavior of “anti-apples on Earth”. However, the problem is exacerbated by the fact that the operation of charge conjugation is much more complicated in curved, as opposed to flat, space-time. Our treatment is based on second-quantized field operators and uses the Lagrangian formalism. As an additional helpful result, prerequisite to our calculations, we establish the general form of the Dirac adjoint in curved space-time. On the basis of a theorem, we refute the existence of tiny, but potentially important, particle-antiparticle symmetry breaking terms in which possible existence has been investigated in the literature. Consequences for antimatter gravity experiments are discussed.
Genetic Diversity and Combining Ability of White Maize Inbred Lines under Different Plant Densities
Authors: Kamara Mohamed M. , Rehan Medhat , Ibrahim Khaled M. , Alsohim Abdullah S. , Elsharkawy Mohsen M. , Kheir Ahmed M. S. , Hafez Emad M. , El-Esawi Mohamed A.
Published: September 2020

Knowledge of combining ability and genetic diversity are important prerequisites for the development of outstanding hybrids that are tolerant to high plant density. This work was carried out to assess general combining ability (GCA) and specific combining ability (SCA), identify promising hybrids, estimate genetic diversity among the inbred lines and correlate genetic distance to hybrid performance and SCA across different plant densities. A total of 28 F1 hybrids obtained by crossing eight adverse inbred lines (four local and four exotic) were evaluated under three plant densities 59,500 (D1), 71,400 (D2) and 83,300 (D3) plants ha−1 using spilt plot design with three replications at two locations during 2018 season. Increasing plant density from D1 to D3 significantly decreased leaf angle (LANG), chlorophyll content (CHLC), all ear characteristics and grain yield per plant (GYPP). Contrarily, days to silking (DTS), anthesis–silking interval (ASI), plant height (PLHT), ear height (EHT), and grain yield per hectare (GYPH) were significantly increased. Both additive and non-additive gene actions were involved in the inheritance of all the evaluated traits, but additive gene action was predominant for most traits. Inbred lines L1, L2, and L5 were the best general combiners for increasing grain yield and other desirable traits across research environments. Two hybrids L2 × L5 and L2 × L8 were found to be good specific combiners for ASI, LANG, GYPP and GYPH. Furthermore, these hybrids are ideal for further testing and promotion for commercialization under high plant density. Genetic distance (GD) among pairs of inbred lines ranged from 0.31 to 0.78, with an average of 0.61. Clustering based on molecular GD has effectively grouped the inbred lines according to their origin. No significant correlation was found between GD and both hybrid performance and SCA for grain yield and other traits and proved to be of no predictive value. Nevertheless, SCA could be used to predict the hybrid performance across all plant densities. Overall, this work presents useful information regarding the inheritance of maize grain yield and other important traits under high plant density.
Intra- and Inter-Specific Crosses among Centaurea aspera L. (Asteraceae) Polyploid Relatives—Influences on Distribution and Polyploid Establishment
Authors: Garmendia Alfonso , Ferriol María , Benavent David , Ferrer-Gallego P. Pablo , Merle Hugo
Published: September 2020

How polyploids become established is a long-debated question, especially for autopolyploids that seem to have no evolutionary advantage over their progenitors. The Centaurea aspera polyploid complex includes diploid C. aspera and two related tetraploids C. seridis and C. gentilii. Our purpose was to study the mating system among these three taxa and to analyze its influence on polyploid establishment. The distribution and ploidy level of the Moroccan populations, and forced intra- and inter-specific crosses were assessed. Allotetraploid C. seridis produced more cypselae per capitulum in the intra-specific crosses. It is a bigger plant and autogamous, and previous studies indicated that selfing forces the asymmetric formation of sterile hybrids. All these characteristics help C. seridis to avoid the minority-cytotype-exclusion effect and become established. Inter-specific hybridization was possible between C. aspera and C. gentilii, and with the symmetric formation of hybrids. However, 49% of the hybrid cypselae were empty, which probably reveals postzygotic barriers. Autotetraploid C. gentilii produced the same number of cypselae per capitulum as those of the diploid parental, has an indistinguishable field phenotype, is allogamous, and symmetrically produces hybrids. Therefore, C. gentilii does not seem to have the same competitive advantages as those of C. seridis.