bluuebunny/crossref_metadata_2025 huggingface dataset:
Mini-Basketball Training Program Improves Social Communication and White Matter Integrity in Children with Autism
Authors: Cai Kelong , Yu Qian , Herold Fabian , Liu Zhimei , Wang Jingui , Zhu Lina , Xiong Xuan , Chen Aiguo , Müller Patrick , Kramer Arthur F. , Müller Notger G. , Zou Liye
Published: November 2020

Impairments in social communication (SC) represent one of the core symptoms of autism spectrum disorder (ASD). While previous studies have demonstrated that exercise intervention improves SC in children with ASD, there is currently no neuroscientific evidence supporting its benefits. Therefore, we evaluated the outcomes of a long-term exercise intervention on SC and white matter integrity (WMI) in children with ASD, and further explored the neural mechanism of exercise intervention on SC in these children. Twenty-nine children aged 3–6 years with ASD were assigned to either exercise group (n = 15) or control group (n = 14). The exercise group received a scheduled mini-basketball training program (5 sessions per week, forty minutes per session) for 12 consecutive weeks, while the control group was instructed to maintain their daily activities. Groups were assessed before and after intervention on SC and WMI. SC scores were lower in the exercise group post-intervention. Compared with the control group, WMI of the exercise group showed higher fractional anisotropy in the body of corpus callosum, fornix, right cerebral peduncle, left posterior limb of internal capsule, right retrolenticular part of internal capsule, left anterior corona radiate and left superior fronto-occipital fasciculus; lower mean diffusivity in the left anterior corona radiate and the bilateral corticospinal tract. Furthermore, increased WMI was associated with lower scores on a measure of social cognition in the overall sample. This study is the first to provide evidence that exercise intervention improves SC and white matter integrity in children with autism.
Physical Activity Amount and Cognitive Impairment in Korean Elderly Population
Authors: Lim Seung-Taek , Jung Yung Zoon , Akama Takao , Lee Eunjae
Published: November 2020

The relationship between physical activity amount and cognitive function in elderly Koreans has received little attention. This study therefore aimed to understand the independent and common link between cognitive function and physical activity levels among elderly Korean adults. This study recruited a total of 2746 elderly adults (1348 males and 1398 females). All participants were assessed for cognitive functioning using the Korean Dementia Screening Questionnaire Cognition (KDSQ-C). The computerized Korean version short form of the International Physical Activity Questionnaire (IPAQ) used in this study was entirely based on the long, self-administered, usual week-long IPAQ found in the IPAQ manual of operation. In the unadjusted model, elderly adults who met the recommended level of moderate-to-vigorous physical activity were more likely to have a sufficient level of cognitive function. Hemoglobin, creatinine, cholesterol (TC), triglycerides (TG), LDL-C, and HDL-C differed significantly between groups. A negative correlation was found between KDSQ-C score and the moderate-to-vigorous physical activity (MVPA) amount per week. Physical activity amount is associated with cognition function in Korean elderly adults. Increasing physical activity may improve hemoglobin and creatinine and be involved in improving serum lipid profiles in elderly adults. Thus, physical activity has been suggesting as a useful tool to reduce the risk of cognitive function associated with aging.
Neurodevelopmental Disorders: Effect of High-Fat Diet on Synaptic Plasticity and Mitochondrial Functions
Authors: Penna Eduardo , Pizzella Amelia , Cimmino Fabiano , Trinchese Giovanna , Cavaliere Gina , Catapano Angela , Allocca Ivana , Chun Jong Tai , Campanozzi Angelo , Messina Giovanni , Precenzano Francesco , Lanzara Valentina , Messina Antonietta , Monda Vincenzo , Monda Marcellino , Perrone-Capano Carla , Mollica Maria Pina , Crispino Marianna
Published: November 2020

Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people’s lifestyles such as diet pattern and physical exercise have significant influence on synaptic plasticity of the brain. Indeed, it has been reported that a high-fat diet (HFD, with 30–50% fat content), which leads to systemic low-grade inflammation, has also a detrimental effect on synaptic efficiency. Interestingly, metabolic alterations associated with obesity in pregnant woman may represent a risk factor for NDDs in the offspring. In this review, we have discussed the potential molecular mechanisms linking the HFD-induced metabolic dysfunctions to altered synaptic plasticity underlying NDDs, with a special emphasis on the roles played by synaptic protein synthesis and mitochondrial functions.
TMS Correlates of Pyramidal Tract Signs and Clinical Motor Status in Patients with Cervical Spondylotic Myelopathy
Authors: Lanza Giuseppe , Puglisi Valentina , Vinciguerra Luisa , Fisicaro Francesco , Vagli Carla , Cantone Mariagiovanna , Pennisi Giovanni , Pennisi Manuela , Bella Rita
Published: November 2020

Background: While the association between motor-evoked potential (MEP) abnormalities and motor deficit is well established, few studies have reported the correlation between MEPs and signs of pyramidal tract dysfunction without motor weakness. We assessed MEPs in patients with pyramidal signs, including motor deficits, compared to patients with pyramidal signs but without weakness. Methods: Forty-three patients with cervical spondylotic myelopathy (CSM) were dichotomized into 21 with pyramidal signs including motor deficit (Group 1) and 22 with pyramidal signs and normal strength (Group 2), and both groups were compared to 33 healthy controls (Group 0). MEPs were bilaterally recorded from the first dorsal interosseous and tibialis anterior muscle. The central motor conduction time (CMCT) was estimated as the difference between MEP latency and peripheral latency by magnetic stimulation. Peak-to-peak MEP amplitude and right-to-left differences were also measured. Results: Participants were age-, sex-, and height-matched. MEP latency in four limbs and CMCT in the lower limbs were prolonged, and MEP amplitude in the lower limbs decreased in Group 1 compared to the others. Unlike motor deficit, pyramidal signs were not associated with MEP measures, even when considering age, sex, and height as confounding factors. Conclusions: In CSM, isolated pyramidal signs may not be associated, at this stage, with MEP changes.
Multiscale Numerical Analysis of TRM-Reinforced Masonry under Diagonal Compression Tests
Authors: Gulinelli Pietro , Aprile Alessandra , Rizzoni Raffaella , Grunevald Yves-Henri , Lebon Frédéric
Published: November 2020

The present paper reports an experimental study coupled with a numerical modelling approach to simulate masonry walls strengthened with textile-reinforced mortar (TRM). This innovative reinforcing technique is based on high-strength fibre grids embedded into inorganic matrices, and it has recently been promoted for the seismic retrofitting of historical masonry buildings. In the experimental campaign presented here, two different commercial TRM systems are applied to single-leaf clay masonry panels. The specimens are then subjected to diagonal compression tests in order to evaluate the effects of TRM on the structural performance. The proposed finite element (FE) model, based on an original multiscale approach, is employed to simulate the diagonal compression tests. The numerical results show a very good agreement with the experimental data, including in terms of failure mode. In particular, the approach reproduces the macroscopic behaviour of the masonry panels as regards the force-displacement response, and it allows for the possibility of simulating bed joint sliding and TRM layer debonding.
“Open Sesame?”: Biomarker Status of the Human Equilibrative Nucleoside Transporter-1 and Molecular Mechanisms Influencing its Expression and Activity in the Uptake and Cytotoxicity of Gemcitabine in Pancreatic Cancer
Authors: Randazzo Ornella , Papini Filippo , Mantini Giulia , Gregori Alessandro , Parrino Barbara , Liu Daniel S. K. , Cascioferro Stella , Carbone Daniela , Peters Godefridus J. , Frampton Adam E. , Garajova Ingrid , Giovannetti Elisa
Published: November 2020

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive tumor characterized by early invasiveness, rapid progression and resistance to treatment. For more than twenty years, gemcitabine has been the main therapy for PDAC both in the palliative and adjuvant setting. After the introduction of FOLFIRINOX as an upfront treatment for metastatic disease, gemcitabine is still commonly used in combination with nab-paclitaxel as an alternative first-line regimen, as well as a monotherapy in elderly patients unfit for combination chemotherapy. As a hydrophilic nucleoside analogue, gemcitabine requires nucleoside transporters to permeate the plasma membrane, and a major role in the uptake of this drug is played by human equilibrative nucleoside transporter 1 (hENT-1). Several studies have proposed hENT-1 as a biomarker for gemcitabine efficacy in PDAC. A recent comprehensive multimodal analysis of hENT-1 status evaluated its predictive role by both immunohistochemistry (with five different antibodies), and quantitative-PCR, supporting the use of the 10D7G2 antibody. High hENT-1 levels observed with this antibody were associated with prolonged disease-free status and overall-survival in patients receiving gemcitabine adjuvant chemotherapy. This commentary aims to critically discuss this analysis and lists molecular factors influencing hENT-1 expression. Improved knowledge on these factors should help the identification of subgroups of patients who may benefit from specific therapies and overcome the limitations of traditional biomarker studies.
Bone Marrow Transplantation as Therapy for Ataxia-Telangiectasia: A Systematic Review
Authors: Sabino Pinho de Oliveira Bruna , Putti Sabrina , Naro Fabio , Pellegrini Manuela
Published: November 2020

Ataxia-Telangiectasia (A-T) is a rare autosomal recessive disorder, first reported in 1926, caused by a deficiency of ATM (Ataxia-Telangiectasia Mutated) protein. The disease is characterized by progressive cerebellar neurodegeneration, immunodeficiency, leukemia, and lymphoma cancer predisposition. Immunoglobulin replacement, antioxidants, neuroprotective factors, growth, and anti-inflammatory hormones are commonly used for A-T treatment, but, to date, there is no known cure. Bone marrow transplantation (BMT) is a successful therapy for several forms of diseases and it is a valid approach for tumors, hemoglobinopathies, autoimmune diseases, inherited disorders of metabolism, and other pathologies. Some case reports of A-T patients have shown that BMT is becoming a good option, as a correct engraftment of healthy cells can restore some aspects of immunologic capacity. However, due to a high risk of mortality as a result of a clinical and cellular hypersensitivity to ionizing radiation and radiomimetic drugs, a specific non-myeloablative conditioning is required before BMT. Although BMT might be considered as one promising therapy for the treatment of immunological defects and cancer prevention in selected A-T patients, the therapy is currently not recommended or recognized and the eligibility of A-T patients for BMT is a point to deepen and deliberate.
Comorbidity Burden and Presence of Multiple Intracranial Lesions Are Associated with Adverse Events after Surgical Treatment of Patients with Brain Metastases
Authors: Schneider Matthias , Heimann Muriel , Schaub Christina , Eichhorn Lars , Potthoff Anna-Laura , Giordano Frank A. , Güresir Erdem , Ko Yon-Dschun , Landsberg Jennifer , Lehmann Felix , Radbruch Alexander , Schwab Katjana S. , Weinhold Leonie , Weller Johannes , Wispel Christian , Herrlinger Ulrich , Vatter Hartmut , Schäfer Niklas , Schuss Patrick
Published: November 2020

Surgical resection is a key treatment modality for brain metastasis (BM). However, peri- and postoperative adverse events (PAEs) might be associated with a detrimental impact on postoperative outcome. We retrospectively analyzed our institutional database with regard to patient safety indicators (PSIs), hospital-acquired conditions (HACs) and specific cranial surgery-related complications (CSCs) as high-quality metric profiles for PAEs in patients who had undergone surgery for BM in our department between 2013 and 2018. The comorbidity burden was assessed by means of the Charlson comorbidity index (CCI). A multivariate analysis was performed to identify independent predictors for the development of PAEs after surgical resection of BM. In total, 33 patients (8.5%) suffered from PAEs after surgery for BM. Of those, 17 PSI, 5 HAC and 11 CSC events were identified. Multiple brain metastases (p = 0.02) and a higher comorbidity burden (CCI > 10; p = 0.003) were associated with PAEs. In-hospital mortality of patients suffering from a PAE was significantly higher than that of patients without a PAE (24% vs. 0.6%; p < 0.0001). Awareness of risk factors for postoperative complications enables future prevention and optimal response, particularly in vulnerable oncological patients. The present study identified the presence of multiple brain metastases and increased comorbidity burden associated with PAEs in patients suffering from BM.
Co-Delivery of CPT-11 and Panobinostat with Anti-GD2 Antibody Conjugated Immunoliposomes for Targeted Combination Chemotherapy
Authors: Jose Gils , Lu Yu-Jen , Hung Jung-Tung , Yu Alice L. , Chen Jyh-Ping
Published: November 2020

The consistent expression of disialoganglioside GD2 in neuroblastoma tumor cells and its restricted expression in normal tissues open the possibility to use it for molecularly targeted neuroblastoma therapy. On the other hand, immunoliposomes combining antibody-mediated tumor recognition with liposomal delivery of chemotherapeutics have been proved to enhance therapeutic efficacy in brain tumors. Therefore, we develop immunoliposomes (ImmuLipCP) conjugated with anti-GD2 antibody, for targeted co-delivery of CPT-11 and panobinostat in this study. U87MG human glioma cell line and its drug resistant variant (U87DR), which were confirmed to be associated with low and high expression of cell surface GD2, were employed to compare the targeting efficacy. From in vitro cytotoxicity assay, CPT-11 showed synergism drug interaction with panobinostat to support co-delivery of both drugs with ImmuLipCP for targeted synergistic combination chemotherapy. The molecular targeting mechanism was elucidated from intracellular uptake efficacy by confocal microscopy and flow cytometry analysis, where 6-fold increase in liposome and 1.8-fold increase in drug uptake efficiency was found using targeted liposomes. This enhanced intracellular trafficking for drug delivery endows ImmuLipCP with pronounced cytotoxicity toward U87DR cells in vitro, with 1.6-fold increase of apoptosis rate. Using xenograft nude mice model with subcutaneously implanted U87DR cells, we observe similar biodistribution profile but 5.1 times higher accumulation rate of ImmuLip from in vivo imaging system (IVIS) observation of Cy5.5-labelled liposomes. Taking advantage of this highly efficient GD-2 targeting, ImmuLipCP was demonstrated to be an effective cancer treatment modality to significantly enhance the anti-cancer therapeutic efficacy in U87DR tumors, shown from the significant reduced tumor size in and prolonged survival time of experiment animals as well as diminished expression of cell proliferation and enhanced expression of apoptosis marker proteins in tumor section.
The Prognostic Role of Baseline Metabolic Tumor Burden and Systemic Inflammation Biomarkers in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223: A Proof of Concept Study
Authors: Bauckneht Matteo , Rebuzzi Sara Elena , Signori Alessio , Donegani Maria Isabella , Murianni Veronica , Miceli Alberto , Borea Roberto , Raffa Stefano , Damassi Alessandra , Ponzano Marta , Catalano Fabio , Martelli Valentino , Marini Cecilia , Boccardo Francesco , Morbelli Silvia , Sambuceti Gianmario , Fornarini Giuseppe
Published: November 2020

Over the last years has emerged the urgent need for the identification of reliable prognostic biomarkers able to potentially identify metastatic castration-resistant prostate cancer (mCRPC) patients most likely to benefit from Radium-223 (Ra-223) since baseline. In the present monocentric retrospective study, we analyzed the prognostic power of systemic inflammation biomarkers and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET)-derived parameters and their potential interplay in this clinical setting. The following baseline laboratory parameters were collected in 59 mCRPC patients treated with Ra-223: neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), and systemic inflammation index (SII), while maximum Standardized Uptake Value, Metabolic Tumor Volume (MTV), and Total Lesion Glycolysis (TLG) were calculated in the 48 of them submitted to baseline FDG-PET. At the univariate analysis, NLR, dNLR, MTV, and TLG were able to predict the overall survival (OS). However, only NLR and MTV were independent predictors of OS at the multivariate analysis. Additionally, the occurrence of both increased NLR and MTV at baseline identified mCRPC patients at higher risk for lower long-term survival after treatment with Ra-223. In conclusion, the degree of systemic inflammation, the quantification of the metabolically active tumor burden and their combination might represent potentially valuable tools for identifying mCRPC patients who are most likely to benefit from Ra-223. However, further studies are needed to reproduce these findings in larger settings.
The Novel Herbal Cocktail AGA Alleviates Oral Cancer through Inducing Apoptosis, Inhibited Migration and Promotion of Cell Cycle Arrest at SubG1 Phase
Authors: Lu Jui-Hua , Chou Yen-Ru , Deng Yue-Hua , Huang Mao-Suan , Chien Shaw-Ting , Quynh Bach , Wu Chia-Yu , Peláez Achtmann Edlin , Cheng Hsin-Chung , Dubey Navneet , Deng Win-Ping
Published: November 2020

Traditional Chinese medicines Antler’s extract (A) and Ganoderma lucidum (G) and Antrodia Camphorata (A) have been known to individually contain a plethora of bioactive factors including triterpenoids, polysaccharides etc., exerting various curative impacts such as anti-inflammatory, anti-oxidative, anti-atherosclerotic and anti-viral activities. However, their combinatorial therapeutic efficacy for oral cancer has not been investigated. Hence, we synthesized a robust cocktail called AGA and investigated its anti-oral cancer potential in vitro and in vivo. An MTT assay revealed the IC50 of AGA to be about 15 mg at 72 h. Therefore, 10 mg and 20 mg doses were selected to study the effect of AGA. The AGA significantly inhibited proliferation of oral cancer cells (HSC3, SAS, and OECM-1) in a dose- and time-dependent manner. AGA retarded cell cycle regulators (CDK4, CDK6, cyclin A, B1, D1 and E2) and apoptosis inhibitory protein Bcl-2, but enhanced pro-apoptotic protein Bax and a higher percentage of cells in Sub-G1 phase. Mechanistically, AGA suppressed all EMT markers; consequently, it decreased the migration ability of cancer cells. AGA significantly reduced xenograft tumor growth in nude mice with no adverse events in liver and renal toxicity. Conclusively, AGA strongly inhibited oral cancer through inducing apoptosis and inhibiting the migration and promotion of cell cycle arrest at subG1 phase, which may be mediated primarily via cocktail-contained triterpenoids and polysaccharides.
Antiplatelet Therapy Improves the Prognosis of Patients with Hepatocellular Carcinoma
Authors: Hayashi Tsuguru , Shibata Michihiko , Oe Shinji , Miyagawa Koichiro , Honma Yuichi , Harada Masaru
Published: November 2020

Aims: Antiplatelet therapy has been reported to reduce liver fibrosis and hepatocellular carcinoma (HCC), and has exhibited antitumor properties in other cancers. However, the effects of antiplatelet therapy after diagnosis of HCC are unknown. We investigated the effects of antiplatelet therapy on prognosis, tumor progression, liver function and safety in HCC patients. Methods: We retrospectively analyzed 772 HCC patients. Antiplatelet therapy was defined as the regular intake of aspirin or clopidogrel from HCC diagnosis through to an endpoint of either overall survival (OS) or liver-related death. Overall survival, liver-related death, tumor progression, Child–Pugh deterioration and hemorrhage were analyzed for patients who either had or had not undertaken antiplatelet therapy. Results: The numbers of patients who did and did not undertake antiplatelet therapy were 111 and 661, respectively. Patients who undertook antiplatelet therapy were older and had better liver function at diagnosis. Antiplatelet therapy resulted in significant improvements in OS (p < 0.01) and lower risk of liver-related death (p < 0.01). Multivariate Cox regression analysis revealed that antiplatelet therapy had a significant negative association with liver-related death (hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.44–0.93, p = 0.02). In patients who underwent transcatheter arterial chemoembolization (TACE) as the first treatment, antiplatelet therapy prevented tumor progression (p < 0.01) and Child–Pugh deterioration (p < 0.01). Antiplatelet therapy did not increase the risk of hemorrhagic events. Conclusions: Antiplatelet therapy reduced liver-related death and improved OS safely in HCC patients.
An Aptamer for Broad Cancer Targeting and Therapy
Authors: Powell Gray Bethany , Song Xirui , Hsu David S. , Kratschmer Christina , Levy Matthew , Barry Ashley P. , Sullenger Bruce A.
Published: November 2020

Recent advances in chemotherapy treatments are increasingly targeted therapies, with the drug conjugated to an antibody able to deliver it directly to the tumor. As high-affinity chemical ligands that are much smaller in size, aptamers are ideal for this type of drug targeting. Aptamer-highly toxic drug conjugates (ApTDCs) based on the E3 aptamer, selected on prostate cancer cells, target and inhibit prostate tumor growth in vivo. Here, we observe that E3 also broadly targets numerous other cancer types, apparently representing a universal aptamer for cancer targeting. Accordingly, ApTDCs formed by conjugation of E3 to the drugs monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF) efficiently target and kill a range of different cancer cells. Notably, this targeting extends to both patient-derived explant (PDX) cancer cell lines and tumors, with the E3 MMAE and MMAF conjugates inhibiting PDX cell growth in vitro and with the E3 aptamer targeting PDX colorectal tumors in vivo.
Past, Present and Future of Oncolytic Reovirus
Authors: Müller Louise , Berkeley Robert , Barr Tyler , Ilett Elizabeth , Errington-Mais Fiona
Published: November 2020

Oncolytic virotherapy (OVT) has received significant attention in recent years, especially since the approval of talimogene Laherparepvec (T-VEC) in 2015 by the Food and Drug administration (FDA). Mechanistic studies of oncolytic viruses (OVs) have revealed that most, if not all, OVs induce direct oncolysis and stimulate innate and adaptive anti-tumour immunity. With the advancement of tumour modelling, allowing characterisation of the effects of tumour microenvironment (TME) components and identification of the cellular mechanisms required for cell death (both direct oncolysis and anti-tumour immune responses), it is clear that a “one size fits all” approach is not applicable to all OVs, or indeed the same OV across different tumour types and disease locations. This article will provide an unbiased review of oncolytic reovirus (clinically formulated as pelareorep), including the molecular and cellular requirements for reovirus oncolysis and anti-tumour immunity, reports of pre-clinical efficacy and its overall clinical trajectory. Moreover, as it is now abundantly clear that the true potential of all OVs, including reovirus, will only be reached upon the development of synergistic combination strategies, reovirus combination therapeutics will be discussed, including the limitations and challenges that remain to harness the full potential of this promising therapeutic agent.
LncRNAs in Cancer: From garbage to Junk
Authors: Aprile Marianna , Katopodi Vicky , Leucci Eleonora , Costa Valerio
Published: November 2020

Sequencing-based transcriptomics has significantly redefined the concept of genome complexity, leading to the identification of thousands of lncRNA genes identification of thousands of lncRNA genes whose products possess transcriptional and/or post-transcriptional regulatory functions that help to shape cell functionality and fate. Indeed, it is well-established now that lncRNAs play a key role in the regulation of gene expression through epigenetic and posttranscriptional mechanims. The rapid increase of studies reporting lncRNAs alteration in cancers has also highlighted their relevance for tumorigenesis. Herein we describe the most prominent examples of well-established lncRNAs having oncogenic and/or tumor suppressive activity. We also discuss how technical advances have provided new therapeutic strategies based on their targeting, and also report the challenges towards their use in the clinical settings.
Environmental Applications of Photocatalytic Processes
Authors: Rizzo Luigi , Silva Adrián M.T.
Published: November 2020

Photocatalytic processes have been investigated in different environmental fields, but their applications at full scale are still scarce [...]
Rab11A Functions as a Negative Regulator of Osteoclastogenesis through Dictating Lysosome-Induced Proteolysis of c-fms and RANK Surface Receptors
Authors: Okusha Yuka , Tran Manh Tien , Itagaki Mami , Sogawa Chiharu , Eguchi Takanori , Okui Tatsuo , Kadowaki Tomoko , Sakai Eiko , Tsukuba Takayuki , Okamoto Kuniaki
Published: November 2020

Osteoclast differentiation and activity are controlled by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-κB ligand (RANKL). Rab11A GTPase, belonging to Rab11 subfamily representing the largest branch of Ras superfamily of small GTPases, has been identified as one of the crucial regulators of cell surface receptor recycling. Nevertheless, the regulatory role of Rab11A in osteoclast differentiation has been completely unknown. In this study, we found that Rab11A was strongly upregulated at a late stage of osteoclast differentiation derived from bone marrow-derived macrophages (BMMs) or RAW-D murine osteoclast precursor cells. Rab11A silencing promoted osteoclast formation and significantly increased the surface levels of c-fms and receptor activator of nuclear factor-κB (RANK) while its overexpression attenuated osteoclast formation and the surface levels of c-fms and RANK. Using immunocytochemical staining for tracking Rab11A vesicular localization, we observed that Rab11A was localized in early and late endosomes, but not lysosomes. Intriguingly, Rab11A overexpression caused the enhancement of fluorescent intensity and size-based enlargement of early endosomes. Besides, Rab11A overexpression promoted lysosomal activity via elevating the endogenous levels of a specific lysosomal protein, LAMP1, and two key lysosomal enzymes, cathepsins B and D in osteoclasts. More importantly, inhibition of the lysosomal activity by chloroquine, we found that the endogenous levels of c-fms and RANK proteins were enhanced in osteoclasts. From these observations, we suggest a novel function of Rab11A as a negative regulator of osteoclastogenesis mainly through (i) abolishing the surface abundance of c-fms and RANK receptors, and (ii) upregulating lysosomal activity, subsequently augmenting the degradation of c-fms and RANK receptors, probably via the axis of early endosomes–late endosomes–lysosomes in osteoclasts.
Secreted Factors from Stem Cells of Human Exfoliated Deciduous Teeth Directly Activate Endothelial Cells to Promote All Processes of Angiogenesis
Authors: Kato Makoto , Tsunekawa Shin , Nakamura Nobuhisa , Miura-Yura Emiri , Yamada Yuichiro , Hayashi Yusuke , Nakai-Shimoda Hiromi , Asano Saeko , Hayami Tomohide , Motegi Mikio , Asano-Hayami Emi , Sasajima Sachiko , Morishita Yoshiaki , Himeno Tatsuhito , Kondo Masaki , Kato Yoshiro , Izumoto-Akita Takako , Yamamoto Akihito , Naruse Keiko , Nakamura Jiro , Kamiya Hideki
Published: November 2020

Diabetes is a major risk factor for atherosclerosis and ischemic vascular diseases. Recently, regenerative medicine is expected to be a novel therapy for ischemic diseases. Our previous studies have reported that transplantation of stem cells promoted therapeutic angiogenesis for diabetic neuropathy and ischemic vascular disease in a paracrine manner, but the precise mechanism is unclear. Therefore, we examined whether secreted factors from stem cells had direct beneficial effects on endothelial cells to promote angiogenesis. The soluble factors were collected as conditioned medium (CM) 48 h after culturing stem cells from human exfoliated deciduous teeth (SHED) in serum-free DMEM. SHED-CM significantly increased cell viability of human umbilical vein endothelial cells (HUVECs) in MTT assays and accelerated HUVECs migration in wound healing and Boyden chamber assays. In a Matrigel plug assay of mice, the migrated number of primary endothelial cells was markedly increased in the plug containing SHED-CM or SHED suspension. SHED-CM induced complex tubular structures of HUVECs in a tube formation assay. Furthermore, SHED-CM significantly increased neovascularization from the primary rat aorta, indicating that SHED-CM stimulated primary endothelial cells to promote comprehensive angiogenesis processes. The angiogenic effects of SHED-CM were the same or greater than the effective concentration of VEGF. In conclusion, SHED-CM directly stimulates vascular endothelial cells to promote angiogenesis and is promising for future clinical application.
Snake W Sex Chromosome: The Shadow of Ancestral Amniote Super-Sex Chromosome
Authors: Singchat Worapong , Ahmad Syed Farhan , Laopichienpong Nararat , Suntronpong Aorarat , Panthum Thitipong , Griffin Darren K. , Srikulnath Kornsorn
Published: November 2020

Heteromorphic sex chromosomes, particularly the ZZ/ZW sex chromosome system of birds and some reptiles, undergo evolutionary dynamics distinct from those of autosomes. The W sex chromosome is a unique karyological member of this heteromorphic pair, which has been extensively studied in snakes to explore the origin, evolution, and genetic diversity of amniote sex chromosomes. The snake W sex chromosome offers a fascinating model system to elucidate ancestral trajectories that have resulted in genetic divergence of amniote sex chromosomes. Although the principal mechanism driving evolution of the amniote sex chromosome remains obscure, an emerging hypothesis, supported by studies of W sex chromosomes of squamate reptiles and snakes, suggests that sex chromosomes share varied genomic blocks across several amniote lineages. This implies the possible split of an ancestral super-sex chromosome via chromosomal rearrangements. We review the major findings pertaining to sex chromosomal profiles in amniotes and discuss the evolution of an ancestral super-sex chromosome by collating recent evidence sourced mainly from the snake W sex chromosome analysis. We highlight the role of repeat-mediated sex chromosome conformation and present a genomic landscape of snake Z and W chromosomes, which reveals the relative abundance of major repeats, and identifies the expansion of certain transposable elements. The latest revolution in chromosomics, i.e., complete telomere-to-telomere assembly, offers mechanistic insights into the evolutionary origin of sex chromosomes.
Characterization of the Polysialylation Status in Ovaries of the Salmonid Fish Coregonus maraena and the Percid Fish Sander lucioperca
Authors: Venuto Marzia Tindara , Martorell-Ribera Joan , Bochert Ralf , Harduin-Lepers Anne , Rebl Alexander , Galuska Sebastian Peter
Published: November 2020

In vertebrates, the carbohydrate polymer polysialic acid (polySia) is especially well known for its essential role during neuronal development, regulating the migration and proliferation of neural precursor cells, for instance. Nevertheless, sialic acid polymers seem to be regulatory elements in other physiological systems, such as the reproductive tract. Interestingly, trout fish eggs have polySia, but we know little of its cellular distribution and role during oogenesis. Therefore, we localized α2,8-linked N-acetylneuraminic acid polymers in the ovaries of Coregonus maraena by immunohistochemistry and found that prevalent clusters of oogonia showed polySia signals on their surfaces. Remarkably, the genome of this salmonid fish contains two st8sia2 genes and one st8sia4 gene, that is, three polysialyltransferases. The expression analysis revealed that for st8sia2-r2, 60 times more mRNA was present than st8sia2-r1 and st8sia4. To compare polysialylation status regarding various polySiaT configurations, we performed a comparable analysis in Sander lucioperca. The genome of this perciform fish contains only one st8sia2 and no st8sia4 gene. Here, too, clusters of oogonia showed polysialylated cell surfaces, and we detected high mRNA values for st8sia2. These results suggest that in teleosts, polySia is involved in the cellular processes of oogonia during oogenesis.
Hyperthrombotic Milieu in COVID-19 Patients
Authors: Kamel Mohamed Hassan , Yin Wenqing , Zavaro Chris , Francis Jean M. , Chitalia Vipul C.
Published: November 2020

COVID-19 infection has protean systemic manifestations. Experience from previous coronavirus outbreaks, including the current SARS-CoV-2, has shown an augmented risk of thrombosis of both macrovasculature and microvasculature. The former involves both arterial and venous beds manifesting as stroke, acute coronary syndrome and venous thromboembolic events. The microvascular thrombosis is an underappreciated complication of SARS-CoV-2 infection with profound implications on the development of multisystem organ failure. The telltale signs of perpetual on-going coagulation and fibrinolytic cascades underscore the presence of diffuse endothelial damage in the patients with COVID-19. These parameters serve as strong predictors of mortality. While summarizing the alterations of various components of thrombosis in patients with COVID-19, this review points to the emerging evidence that implicates the prominent role of the extrinsic coagulation cascade in COVID-19-related coagulopathy. These mechanisms are triggered by widespread endothelial cell damage (endotheliopathy), the dominant driver of macro- and micro-vascular thrombosis in these patients. We also summarize other mediators of thrombosis, clinically relevant nuances such as the occurrence of thromboembolic events despite thromboprophylaxis (breakthrough thrombosis), current understanding of systemic anticoagulation therapy and its risk–benefit ratio. We conclude by emphasizing a need to probe COVID-19-specific mechanisms of thrombosis to develop better risk markers and safer therapeutic targets.
Statistical Evaluation of the Perpendicularity of Boreholes in Concrete for Post-Installed Fasteners
Authors: Zeman Oliver , Schwenn Michael , Schorn Josef , Bergmeister Konrad
Published: November 2020

The form and the perpendicularity of boreholes influence the ultimate behaviour of post-installed fasteners and are restricted with regard to the concrete surface to 5° in Europe and to 6° in the United States in various regulations (e.g., EAD 330232-00-0601 resp. ACI 355.2-19). It is assumed that the deviation of the borehole from the vertical axis has an effect on the load transfer behaviour of an anchorage. This article investigates on the perpendicularity of vertically downward drilled boreholes using different drilling tools considering hammer drilling, hollow drilling and diamond core drilling. It can be shown that the requirements of e.g., EAD 330232-00-0601 of a maximum deviation to the concrete surface of 5° can be fulfilled for approximately 95% of the determined values for different drilling methods. This is based on a considerable number of measurements (generated from drilled boreholes) in different concrete types. As a result, a detailed statistical evaluation is provided to describe the borehole perpendicularity by means of statistical methods.
Nonthermal Plasma Treatment Improves Uniformity and Adherence of Cyclodextrin-Based Coatings on Hydrophobic Polymer Substrates
Authors: Learn Greg D. , Lai Emerson J. , von Recum Horst A.
Published: November 2020

Low surface energy substrates, which include many plastics and polymers, present challenges toward achieving uniform, adherent coatings, thus limiting intended coating function. These inert materials are common in various applications due to favorable bulk, despite suboptimal surface, properties. The ability to functionally coat low surface energy substrates holds broad value for uses across medicine and industry. Cyclodextrin-based materials represent an emerging, widely useful class of coatings, which have previously been explored for numerous purposes involving sustained release, enhanced sorption, and reversible reuse thereof. In this study, substrate exposure to nonthermal plasma was explored as a novel means to improve uniformity and adherence of cyclodextrin-based polyurethane coatings upon unreceptive polypropylene substrates. Plasma effects on substrates were investigated using contact angle goniometry and X-ray photoelectron spectroscopy (XPS). Plasma impact on coating uniformity was assessed through visualization directly and microscopically. Plasma effects on coating adhesion and bonding were studied with mechanical lap-shear testing and XPS, respectively. Substrate surface wettability and oxygen content increased with plasma exposure, and these modifications were associated with improved coating uniformity, adhesion, and interfacial covalent bonding. Findings demonstrate utility of, and elucidate mechanisms behind, plasma-based surface activation for improving coating uniformity, adherence, and performance on inert polymeric substrates.
Effects of Various Polishing Techniques on the Surface Characteristics of the Ti-6Al-4V Alloy and on Bacterial Adhesion
Authors: Jhong Yu-Ting , Chao Chih-Yeh , Hung Wei-Chun , Du Je-Kang
Published: November 2020

Ti-6Al-4V, although widely used in dental materials, causes peri-implant inflammation due to the long-term accumulation of bacteria around the implant, resulting in bone loss and eventual failure of the implant. This study aims to overcome the problem of dental implant infection by analyzing the influence of Ti-6Al-4V surface characteristics on the quantity of accumulated bacteria. Ti-6Al-4V specimens, each with different surface roughness are produced by mechanical, chemical, and electrolytic polishing. The surface roughness, surface contact angle, surface oxygen content, and surface structure were measured via atomic force microscopy (AFM), laser scanning confocal microscopy (LSCM), drop shape analysis (using sessile drop), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The micro and macro surface roughness are 10.33–120.05 nm and 0.68–2.34 μm, respectively. The surface X direction and Y direction contact angle are 21.38°–96.44° and 18.37°–92.72°, respectively. The surface oxygen content is 47.36–59.89 at.%. The number of colonies and the optical density (OD) are 7.87 × 106–17.73 × 106 CFU/mL and 0.189–0.245, respectively. The bacterial inhibition were the most effective under the electrolytic polishing of Ti-6Al-4V. The electrolytic polishing of Ti-6Al-4V exhibited the best surface characteristics: the surface roughness of 10 nm, surface contact angle of 92°, and surface oxygen content of 54 at.%, respectively. This provides the best surface treatment of Ti-6Al-4V in dental implants.
Electromagnetic and Power Side-Channel Analysis: Advanced Attacks and Low-Overhead Generic Countermeasures through White-Box Approach
Authors: Das Debayan , Sen Shreyas
Published: November 2020

Electromagnetic and power side-channel analysis (SCA) provides attackers a prominent tool to extract the secret key from the cryptographic engine. In this article, we present our cross-device deep learning (DL)-based side-channel attack (X-DeepSCA) which reduces the time to attack on embedded devices, thereby increasing the threat surface significantly. Consequently, with the knowledge of such advanced attacks, we performed a ground-up white-box analysis of the crypto IC to root-cause the source of the electromagnetic (EM) side-channel leakage. Equipped with the understanding that the higher-level metals significantly contribute to the EM leakage, we present STELLAR, which proposes to route the crypto core within the lower metals and then embed it within a current-domain signature attenuation (CDSA) hardware to ensure that the critical correlated signature gets suppressed before it reaches the top-level metal layers. CDSA-AES256 with local lower metal routing was fabricated in a TSMC 65 nm process and evaluated against different profiled and non-profiled attacks, showing protection beyond 1B encryptions, compared to ∼10K for the unprotected AES. Overall, the presented countermeasure achieved a 100× improvement over the state-of-the-art countermeasures available, with comparable power/area overheads and without any performance degradation. Moreover, it is a generic countermeasure and can be used to protect any crypto cores while preserving the legacy of the existing implementations.
Enhancing the Solubility and Dissolution Performance of Safinamide Using Salts
Authors: Gao Lei , Liu Qian , Zhang Xian-Rui
Published: November 2020

Safinamide (SAF) is an anti-Parkinson’s disease (PD) drug that has selective monoamine oxidase type-B (MAO-B) inhibition activity. In 2017, SAF was approved by the U.S. Food and Drug Administration (FDA) as safinamide mesylate (SAF-MS, marketed as Xadago). Owing to its poor solubility in water, SAF is a Biopharmaceutics Classification System BCS Class II compound. In this study, four salts of safinamide (with hydrochloric acid (HCl), hydrobromic acid (HBr), and maleic acid (MA)) were obtained and characterized using single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and thermogravimetry (TG). The solubility and dissolution rate of all salts were systematically studied in water and phosphate buffer (pH 6.86) solutions. The accelerated stability tests indicated that all salts, except SAF-MA, had good stability under high humidity conditions.
Lithium Niobate Single Crystals and Powders Reviewed—Part II
Authors: Sánchez-Dena Oswaldo , Villalobos-Mendoza Sergio David , Farías Rurik , Fierro-Ruiz Cesar David
Published: November 2020

A review on lithium niobate single crystals and polycrystals has been prepared. Both the classical and recent literature on this topic is revisited. It is composed of two parts with several sections. The current part discusses the available defect models (intrinsic), the trends found in ion-doped crystals and polycrystals (extrinsic defects), the fundamentals on dilute magnetic oxides, and their connection to ferromagnetic behavior in lithium niobate.
A Five-Coordinate Copper(II) Complex Constructed from Sterically Hindered 4-Chlorobenzoate and Benzimidazole: Synthesis, Crystal Structure, Hirshfeld Surface Analysis, DFT, Docking Studies and Antibacterial Activity
Authors: Ajibola Abiodun A. , Perveen Fouzia , Jan Kalsoom , Anibijuwon Ibikunle I. , Shaibu Solomon E. , Sieroń Lesław , Maniukiewicz Waldemar
Published: November 2020

A new CuII complex (1) was synthesized by reacting 4-chlorobenzoic acid, benzimidazole and metal salt using ethanol–water (1:1 v/v) as a solvent at room temperature. The complex was characterized by single-crystal X-ray analysis, FTIR and UV—vis spectroscopy. A distorted square pyramidal geometry of the CuII center was observed from the single-crystal X-ray study, which also revealed that the uncoordinated oxygen atom of the carboxylate anions forms intermolecular hydrogen bonds with the N–H groups of the benzimidazole ligands. The Hirshfeld analysis results revealed that the molecular packing of 1 is mainly controlled by O...H (12.7%), Cl...H (16.4%), C...H (24.4%) and H...H (31.1%) contacts. Density functional theory (DFT) calculations were performed to compute the HOMO–LUMO energy gap and electrostatic potential map for the charge transfer regions within the molecule and identify the possible electrophilic and nucleophilic regions of the molecule. A number of reactivity parameters calculated on the basis of EHOMO and ELUMO show its significant polarizability and reactive nature. Complex 1 was also examined and screened for its potential antibacterial effect using the agar well diffusion method. The newly synthesized complex showed an effective and higher killing rate of the microbes in antibacterial testing compared to the parent ligand. The CuII complex (1) showed an enhanced inhibitory activity against P. aeruginosa and equally demonstrated greater binding affinity with DNA gyrase (1KIJ) compared to its ligands according to the molecular docking studies.
Predators as Agents of Selection and Diversification
Authors: Johnson Jerald B. , Belk Mark C.
Published: November 2020

Predation is ubiquitous in nature and can be an important component of both ecological and evolutionary interactions. One of the most striking features of predators is how often they cause evolutionary diversification in natural systems. Here, we review several ways that this can occur, exploring empirical evidence and suggesting promising areas for future work. We also introduce several papers recently accepted in Diversity that demonstrate just how important and varied predation can be as an agent of natural selection. We conclude that there is still much to be done in this field, especially in areas where multiple predator species prey upon common prey, in certain taxonomic groups where we still know very little, and in an overall effort to actually quantify mortality rates and the strength of natural selection in the wild.
Comparison of 3D Point Clouds Obtained by Terrestrial Laser Scanning and Personal Laser Scanning on Forest Inventory Sample Plots
Authors: Gollob Christoph , Ritter Tim , Nothdurft Arne
Published: November 2020

In forest inventory, trees are usually measured using handheld instruments; among the most relevant are calipers, inclinometers, ultrasonic devices, and laser range finders. Traditional forest inventory has been redesigned since modern laser scanner technology became available. Laser scanners generate massive data in the form of 3D point clouds. We have developed a novel methodology to provide estimates of the tree positions, stem diameters, and tree heights from these 3D point clouds. This dataset was made publicly accessible to test new software routines for the automatic measurement of forest trees using laser scanner data. Benchmark studies with performance tests of different algorithms are welcome. The dataset contains co-registered raw 3D point-cloud data collected on 20 forest inventory sample plots in Austria. The data were collected by two different laser scanning systems: (1) A mobile personal laser scanner (PLS) (ZEB Horizon, GeoSLAM Ltd., Nottingham, UK) and (2) a static terrestrial laser scanner (TLS) (Focus3D X330, Faro Technologies Inc., Lake Mary, FL, USA). The data also contain digital terrain models (DTMs), field measurements as reference data (ground-truth), and the output of recent software routines for the automatic tree detection and the automatic stem diameter measurement.