bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of multiepitope cancer vaccines based on large combinatorial libraries of survivin‐derived mutant epitopes
Authors: Domínguez‐Romero Allan Noé , Martínez‐Cortés Fernando , Munguía María Elena , Odales Josué , Gevorkian Goar , Manoutcharian Karen
Published: July 2020

Immune tolerance is the main challenge in the field of cancer vaccines, so modified peptide sequences or naturally occurring mutated versions of cancer‐related wild‐type (WT) antigens represent a promising pathway. However, the low immunogenicity of mutation‐induced neoantigens and, particularly, their incapacity to activate CD8+ T cells are generating doubts on the success of neoantigen‐based cancer vaccines in clinical trials. We developed a novel vaccine approach based on a new class of vaccine immunogens, called variable epitope libraries (VELs). We used three regions of survivin (SVN), composed of 40, 49 and 51 amino acids, along with the complete SVN protein to generate the VELs as multiepitope vaccines. BALB/c mice, challenged with the aggressive and highly metastatic 4T1 cell line, were vaccinated in a therapeutic setting. We showed significant tumor growth inhibition and, most importantly, strong suppression of lung metastasis after a single immunization using VEL vaccines. We demonstrated vaccine‐induced broad cellular immune responses concomitant with extensive tumor infiltration of T cells, the activation of CD107a+ IFN‐γ+ T cells in the spleen and a significant increase in the number of CD3+ CD8+ Ly6C+ effector T cells. In addition, we observed the presence of interferon‐γ‐, granzyme B‐ and perforin‐producing lymphocytes along with modifications in the amount of CD11b+ Ly6Cint/low Ly6G+ granulocytic myeloid‐derived suppressor cells and CD4+ CD25+ FoxP3+ regulatory T cells in the lungs and tumors of mice. In summary, we showed that the VELs represent a potent new class of cancer immunotherapy and propose the application of the VEL vaccine concept as a true alternative to currently available vaccine platforms.
Protecting prone positioned patients from facial pressure ulcers using prophylactic dressings: A timely biomechanical analysis in the context of the COVID‐19 pandemic
Authors: Peko Lea , Barakat‐Johnson Michelle , Gefen Amit
Published: July 2020

Prone positioning is used for surgical access and recently in exponentially growing numbers of coronavirus disease 2019 patients who are ventilated prone. To reduce their facial pressure ulcer risk, prophylactic dressings can be used; however, the biomechanical efficacy of this intervention has not been studied yet. We, therefore, evaluated facial soft tissue exposures to sustained mechanical loads in a prone position, with versus without multi‐layered silicone foam dressings applied as tissue protectors at the forehead and chin. We used an anatomically realistic validated finite element model of an adult male head to determine the contribution of the dressings to the alleviation of the sustained tissue loads. The application of the dressings considerably relieved the tissue exposures to loading. Specifically, with respect to the forehead, the application of a dressing resulted in 52% and 71% reductions in soft tissue exposures to effective stresses and strain energy densities, respectively. Likewise, a chin dressing lowered the soft tissue exposures to stresses and strain energy densities by 78% and 92%, respectively. While the surgical context is clear and there is a solid, relevant need for biomechanical information regarding prophylaxis for the prone positions, the projected consequences of the coronavirus pandemic make the present work more relevant than ever before.
Mechanism of spontaneous initiation of ventricular fibrillation in patients with implantable defibrillators
Authors: Xie Eric , Mayer Katarina , Capps Melissa F. , Barth Andreas S. , Love Charles J. , Coronel Ruben , Ashikaga Hiroshi
Published: July 2020

Introduction

To improve the mechanistic understanding of spontaneous initiation of ventricular fibrillation (VF), we characterized the patterns of premature ventricular complex (PVC) preceding spontaneous VF in primary and secondary implantable cardioverter‐defibrillator (ICD) recipients.

Methods and Results

A single‐center, cross‐sectional analysis of 1209 patients with primary and secondary prevention ICD identified 190 patients who received ICD therapy (firing or antitachycardia pacing) for VF or monomorphic ventricular tachycardia (MMVT). Initiation was quantified by the coupling interval (CI), the cycle length immediately preceding the CI (CL(−1)), the CI corrected by CL(−1) using Fridericia's formula (CIc), and the prematurity index (PI). In both VF (n = 44; 23%) and MMVT (n = 134; 71%), the most common pattern of initiation was late‐coupled PVC, followed by the short‐long‐short pattern. The parameters such as pre‐initiation median CL, CL(−1), CI, and PI were not significantly different between VF and MMVT for any patterns. At least some events (45% of VF and 63% of MMVT) had extremely long CIs beyond the QTc cut‐off estimated from the CL(−1), suggestive of initiation by a train of multiple PVCs or nonsustained VT instead of a single PVC.

Conclusion

Some spontaneous VF events in ICD recipients appear to be initiated by a train of multiple PVC or nonsustained VT rather than a single PVC. This finding indicates that patterns of a single PVC are not an important determinant of VF initiation and thus account for conflicting results in previous studies.
Comprehensive analysis of autophagy‐related prognostic genes in breast cancer
Authors: Lai Jianguo , Chen Bo , Mok Hsiaopei , Zhang Guochun , Ren Chongyang , Liao Ning
Published: July 2020

Accumulating evidence revealed that autophagy played vital roles in breast cancer (BC) progression. Thus, the aim of this study was to investigate the prognostic value of autophagy‐related genes (ARGs) and develop a ARG‐based model to evaluate 5‐year overall survival (OS) in BC patients. We acquired ARG expression profiling in a large BC cohort (N = 1007) from The Cancer Genome Atlas (TCGA) database. The correlation between ARGs and OS was confirmed by the LASSO and Cox regression analyses. A predictive model was established based on independent prognostic variables. Thus, time‐dependent receiver operating curve (ROC), calibration plot, decision curve and subgroup analysis were conducted to determine the predictive performance of ARG‐based model. Four ARGs (ATG4A, IFNG, NRG1 and SERPINA1) were identified using the LASSO and multivariate Cox regression analyses. A ARG‐based model was constructed based on the four ARGs and two clinicopathological risk factors (age and TNM stage), dividing patients into high‐risk and low‐risk groups. The 5‐year OS of patients in the low‐risk group was higher than that in the high‐risk group (P < 0.0001). Time‐dependent ROC at 5 years indicated that the four ARG–based tool had better prognostic accuracy than TNM stage in the training cohort (AUC: 0.731 vs 0.640, P < 0.01) and validation cohort (AUC: 0.804 vs 0.671, P < 0.01). The mutation frequencies of the four ARGs (ATG4A, IFNG, NRG1 and SERPINA1) were 0.9%, 2.8%, 8% and 1.3%, respectively. We built and verified a novel four ARG–based nomogram, a credible approach to predict 5‐year OS in BC, which can assist oncologists in determining effective therapeutic strategies.
Spin in the abstracts of randomized controlled trials in periodontology and oral implantology: A cross‐sectional analysis
Authors: Wu Xinyu , Yan Qi , Fang Xiaolin , Hua Fang , Shi Bin , Tu Yu‐Kang
Published: July 2020

Objectives

To investigate the presence and characteristics of spin (a distorted interpretation to make research findings seem favourable) in abstracts of randomized controlled trials (RCTs) in periodontology and oral implantology, and to explore its associated factors and influence on the subsequent literature.

Materials and methods

PubMed was searched to identify recent RCTs in periodontology and oral implantology, whose primary outcome was non‐significant. Spin in abstracts was assessed and categorized according to pre‐determined spin strategies. The associations between study characteristics and the presence/severity of spin were analysed using multivariable logistic regressions.

Results

196 abstracts were included, 137 (69.9%) of which had spin. 57 (29.1%) abstracts had spin in the Results section, and 126 (64.3%) had spin in the Conclusion section. The main spin strategies in the Results and Conclusion sections were focusing on secondary outcomes (16.3%) and focusing on within‐group comparisons (28.6%), respectively. The presence of spin was associated with number of centres (OR = 0.28, 95% CI: 0.11–0.73; p = .009), while its severity was associated with topic (OR = 0.24, 95% CI: 0.08–0.70; p = .009).

Conclusions

The frequency of spin is relatively high among published RCT abstracts in periodontology and oral implantology. Findings reported in these abstracts need to be interpreted with caution.
Alterations in the epidermis of the carp, Labeo rohita (Cyprinidae: Cypriniformes), infected by the bacteria, Aeromonas hydrophila: A scanning electron microscopic, histopathological and immunohistochemical investigation
Authors: Srivastava Ayan , Mistri Arup , Mittal Swati , Mittal Ajay Kumar
Published: July 2020

This study was carried out to comprehend the pathogenicity of the bacteria in the epidermis of Labeo rohita inoculated with Aeromonas hydrophila. Alterations in the histopathology of the epidermis were examined using scanning electron microscopy, light microscopy and the localization of iNOS and caspase 3 + ve cells by means of immunohistochemical methods. Skin samples obtained from infected fish at different intervals 2, 4, 6, 8 and 10 days showed significant changes in the cellular components of the epidermis. Epithelial cells often appeared hypertrophied with fragmented and loosely arranged microridges, and in the process of exfoliation. Mucous goblet cells increased significantly in density. Club cells showed degenerative changes, often with simultaneous confluence of adjacent cells and release of their contents. Increase in density of iNOS and caspase 3 + ve cells indicates inflammatory response and apoptosis. This study could provide valuable information on the pathogenesis of the disease, and disease outbreaks in farmed fish. Further, it could provide useful guidelines for fish farmers to take preventive measures for the control of the disease.
Soybean AP1 homologs control flowering time and plant height
Authors: Chen Liyu , Nan Haiyang , Kong Lingping , Yue Lin , Yang Hui , Zhao Qingsong , Fang Chao , Li Haiyang , Cheng Qun , Lu Sijia , Kong Fanjiang , Liu Baohui , Dong Lidong
Published: July 2020

Flowering time and plant height are key agronomic traits that directly affect soybean (Glycine max) yield. APETALA1 (AP1) functions as a class A gene in the ABCE model for floral organ development, helping to specify carpel, stamen, petal, and sepal identities. There are four AP1 homologs in soybean, all of which are mainly expressed in the shoot apex. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR) – CRISPR‐associated protein 9 technology to generate a homozygous quadruple mutant, gmap1, with loss‐of‐function mutations in all four GmAP1 genes. Under short‐day (SD) conditions, the gmap1 quadruple mutant exhibited delayed flowering, changes in flower morphology, and increased node number and internode length, resulting in plants that were taller than the wild type. Conversely, overexpression of GmAP1a resulted in early flowering and reduced plant height compared to the wild type under SD conditions. The gmap1 mutant and the overexpression lines also exhibited altered expression of several genes related to flowering and gibberellic acid metabolism, thereby providing insight into the role of GmAP1 in the regulatory networks controlling flowering time and plant height in soybean. Increased node number is the trait with the most promise for enhancing soybean pod number and grain yield. Therefore, the mutant alleles of the four AP1 homologs described here will be invaluable for molecular breeding of improved soybean yield.
Forever Working on the Whiteman: Agency, Vulnerability, and Hope in the Interstices of an Amazonian Frontier
Authors: Mentore Laura
Published: July 2020

Este artículo presenta un estudio de caso de término medio entre una comunidad indígena en el sur de Guyana y un grupo de mineros itinerantes de Brasil cuyo jefe era percibido como un hombre blanco. Un elemento central para la aparición de este término medio fue el sentido de agencia creativa de cada parte en relación con la otra, su vulnerabilidad mutua en relación con factores circunstanciales más grandes y su malentendido mutuo de los motivos de compromiso de la otra parte. De este estudio de caso, sostengo que las condiciones que proporcionan un punto medio en los espacios fronterizos de extracción de recursos en la Amazonía son raras, de corta duración y es más probable que surjan en contextos donde una disminución en el valor de mercado de los recursos ha reducido la escala y la intensidad de contacto. El término medio surge en estas condiciones, en parte porque ciertas técnicas indígenas para negociar relaciones de poder florecen cuando la escala de contacto es más interpersonal desde el punto de vista gastronómico.
Benefits of powered standing wheelchair devices for adolescents with Duchenne muscular dystrophy in the first year of use
Authors: Bayley Klair , Parkinson Stephanie , Jacoby Peter , Cross Donna , Morris Sue , Vorster Nitamarie , Schofield Cara , Kava Maina , Siafarikas Aris , Evans Kerry , Gaynor Odette , Chiu Linda , Ryan Monique M , Cairns Anita , Clark Damian , Downs Jenny
Published: July 2020

Aim

Poorer physical and mental health often accompany loss of walking in Duchenne muscular dystrophy. This study assessed the impacts of powered wheelchair standing device (PWSD) use on muscle and joint pain, joint angles when standing and mental health in adolescents with Duchenne muscular dystrophy.

Methods

Fourteen adolescents and parents participated in a stepped wedge design study over 12 months. During a baseline and intervention period, adolescents described pain and mental health, and parents reported their child's mental health. Video data were collected to measure hip, knee and ankle joint angles in the preferred standing position.

Results

Compared with baseline and adjusting for covariates, standing wheelchair use was associated with no change in muscle or joint pain or videoed joint angles in standing. Child‐reported Strengths and Difficulties total scores decreased (coefficient −3.1, 95% confidence interval −4.6, −1.5); and parent‐reported Personal Adjustment and Role Skills Scale total scores increased (coefficient 7.9, 95% confidence interval 3.3–12.5).

Conclusions

PWSD use was associated with maintenance of musculoskeletal status and advantages to mental health. Long‐term observations are necessary to improve understanding of how to support wellbeing in adolescents with Duchenne muscular dystrophy.
Detection of association between periodontitis and polymorphisms of IL‐1β + 3954 and TNF‐α ‐863 in the Korean population after controlling for confounding risk factors
Authors: Kim Hyun‐Joo , Kim Eun‐Hye , Park Ae Kyung , Shin Yerang , Kang Jihoon , Lim Jaesung , Bhak Jong , Lee Ju‐Youn , Kim Byung Chul , Joo Ji‐Young
Published: July 2020

Background and Objective

Interleukin (IL)‐1 and tumor necrosis factor (TNF)‐α are inflammatory cytokines that play an important role in periodontitis, and their genetic variations have been suggested to be associated with increased risk of periodontitis. Focusing on three single nucleotide polymorphisms (SNPs) of IL‐1α + 4845, IL‐1β + 3954, and TNF‐α −863, we aimed to investigate the relationship between periodontitis risk and the polymorphisms of IL‐1 α/β and TNF‐α in Koreans.

Material and Methods

Mouthwash samples from 548 subjects (135 controls without periodontitis, 387 generalized chronic periodontitis patients, and 26 generalized aggressive periodontitis patients) were collected for isolation of genomic DNA. Genotyping of selected SNPs was performed using real‐time PCR. Univariable associations between the polymorphisms and periodontitis were assessed by chi‐squared test or Fisher's exact test. To evaluate the association after controlling for confounding effects of various risk factors, we stratified the subjects according to the presence or absence of self‐reported diseases and employed multiple logistic regression model to adjust for age, smoking status, and oral hygiene indices and behaviors.

Results

Significant association of IL‐1β + 3954 and TNF‐α −863 polymorphisms with periodontitis was observed after adjusting for the confounding risk factors, but not in univariable association analysis. The significant association between genotype CT of IL‐1β + 3954 and increased risk of advanced periodontitis was consistently detected regardless of the status of self‐reported diseases. In the polymorphism of TNF‐α −863, the genotype with minor allele (CA + AA) was significantly associated with periodontitis susceptibility, which was observed only in the subjects with self‐reported diseases.

Conclusion

The results suggest that genetic variations of IL‐1β + 3954 and TNF‐α −863 are associated with increased risk of periodontitis in Koreans. In addition, our findings underscore the importance of controlling for confounding risk factors to detect significant association between genetic factors and risk of periodontitis. A further well‐designed large‐scale study is needed to warrant our results.
Kinetics of single and dual simultaneous infection of pigs with swine influenza A virus and porcine reproductive and respiratory syndrome virus
Authors: Pomorska‐Mól Małgorzata , Podgórska Katarzyna , Czyżewska‐Dors Ewelina , Turlewicz‐Podbielska Hanna , Gogulski Maciej , Włodarek Jan , Łukomska Anna
Published: July 2020

Background

Simultaneous viral infections exhibit the phenomenon of viral interference, but understanding of the effect of one virus on another is limited.

Objective

Evaluate and compare clinical characteristics, immune and acute phase response, viral shedding and viral load in pigs singly and doubly inoculated with swine influenza A virus (swIAV) and porcine reproductive and respiratory syndrome virus (PRRSV).

Animals

Fifty‐four 7‐week‐old piglets.

Methods

Clinical status and gross lung lesions were scored. Titration of swIAV was carried out in Madin‐Darby canine kidney cells. The PRRSV RNA was quantified using a commercial qPCR kit. Antibodies were detected by hemagglutination inhibition assay and commercial ELISA. A lymphocyte proliferation assay was used to measure antigen‐specific T‐cell responses. Acute phase proteins were determined using ELISA.

Results

No differences were found between mean clinical scores, swIAV and PRRSV shedding, and magnitude of the humoral and T‐cell response between single‐inoculated and dual‐inoculated groups. Concentrations of C‐reactive protein and haptoglobin increased in PRRSV‐inoculated and coinoculated groups, whereas serum amyloid A concentration was increased in groups inoculated or coinoculated with swIAV. Mean swIAV TCID50titers in the lungs did not differ significantly between coinoculated and swIAV single‐inoculated pigs. A significantly higher mean copy number of PRRSV was found in the lungs of PRRSV only‐inoculated pigs at 2 day postinoculation (DPI). From 4 DPI, no significant differences in PRRSV load were identified.

Conclusions and Clinical Importance

Coinfection of pigs with swIAV and PRRSV did not potentiate clinical signs, lung lesions, immune response, and replication of the viruses in the respiratory tract.
Ciliate diversity and distribution across horizontal and vertical scales in the open ocean
Authors: Canals Oriol , Obiol Aleix , Muhovic Imer , Vaqué Dolors , Massana Ramon
Published: July 2020

Ciliates are globally distributed eukaryotic organisms inhabiting virtually all environments on Earth. Although ciliates range from 10 µm to a few millimetres in cell size, they are repeatedly reported in the pico‐sized fraction (<2–3 µm) of molecular surveys. Here, we used existing data sets (BioMarKs and Tara Oceans) with different size fractions to demonstrate that the ciliate pico‐sized signal, probably derived from cell breakage during filtration, is informative and reliable to study marine ciliate biodiversity and biogeography. We then used sequences from the pico‐eukaryotic fraction of two circumnavigation expeditions, Malaspina‐2010 and Tara Oceans, to give insights into the taxonomic composition and horizontal and vertical distribution of ciliates in the global ocean. The results suggested a high homogeneity of ciliate communities along the ocean surface from temperate to tropical waters, with ciliate assemblages dominated by a few abundant and widely distributed taxa. Very few taxa were found in a single oceanic region, therefore suggesting a high level of ciliate cosmopolitanism in the global ocean. In vertical profiles, ciliates were detected up to 4,000 m depth, and a clear vertical community structuring was observed. Our results provided evidence supporting ciliates as deeply integrated organisms in the deep‐sea trophic web, where they may play a relevant role as symbionts of metazoans and grazers of prokaryotes and small eukaryotes in the water column and in aggregates.
Phylogenetic signals and predictability in plant–soil feedbacks
Authors: Wandrag Elizabeth M. , Bates Sarah E. , Barrett Luke G. , Catford Jane A. , Thrall Peter H. , van der Putten Wim H. , Duncan Richard P.
Published: July 2020

There is strong evidence for a phylogenetic signal in the degree to which species share co‐evolved biotic partners and in the outcomes of biotic interactions. This implies there should be a phylogenetic signal in the outcome of feedbacks between plants and the soil microbiota they cultivate. However, attempts to identify a phylogenetic signal in plant–soil feedbacks have produced mixed results.

Here we clarify how phylogenetic signals could arise in plant–soil feedbacks and use a recent compilation of data from feedback experiments to identify: whether there is a phylogenetic signal in the outcome of plant–soil feedbacks; and whether any signal arises through directional or divergent changes in feedback outcomes with evolutionary time.

We find strong evidence for a divergent phylogenetic signal in feedback outcomes. Distantly related plant species show more divergent responses to each other’s soil microbiota compared with closely related plant species. The pattern of divergence implies occasional co‐evolutionary shifts in how plants interact with soil microbiota, with strongly contrasting feedback responses among some plant lineages.

Our results highlight that it is difficult to predict feedback outcomes from phylogeny alone, other than to say that more closely related species tend to have more similar responses.
CDK8 is associated with RAP2.6 and SnRK2.6 and positively modulates abscisic acid signaling and drought response in Arabidopsis
Authors: Zhu Yingfang , Huang Pengcheng , Guo Pengcheng , Chong Leelyn , Yu Gaobo , Sun Xiaoli , Hu Tao , Li Yuan , Hsu Chuan‐Chih , Tang Kai , Zhou Yun , Zhao Chunzhao , Gao Wei , Tao W. Andy , Mengiste Tesfaye , Zhu Jian‐Kang
Published: July 2020

CDK8 is a key subunit of Mediator complex, a large multiprotein complex that is a fundamental part of the conserved eukaryotic transcriptional machinery. However, the biological functions of CDK8 in plant abiotic stress responses remain largely unexplored.

Here, we demonstrated CDK8 as a critical regulator in the abscisic acid (ABA) signaling and drought response pathways in Arabidopsis. Compared to wild‐type, cdk8 mutants showed reduced sensitivity to ABA, impaired stomatal apertures and hypersensitivity to drought stress. Transcriptomic and chromatin immunoprecipitation analysis revealed that CDK8 positively regulates the transcription of several ABA‐responsive genes, probably through promoting the recruitment of RNA polymerase II to their promoters.

We discovered that both CDK8 and SnRK2.6 interact physically with an ERF/AP2 transcription factor RAP2.6, which can directly bind to the promoters of RD29A and COLD‐REGULATED 15A (COR15A) with GCC or DRE elements, thereby promoting their expression. Importantly, we also showed that CDK8 is essential for the ABA‐induced expression of RAP2.6 and RAP2.6‐mediated upregulation of ABA‐responsive genes, indicating that CDK8 could link the SnRK2.6‐mediated ABA signaling to RNA polymerase II to promote immediate transcriptional response to ABA and drought signals.

Overall, our data provide new insights into the roles of CDK8 in modulating ABA signaling and drought responses.
Analysis of lncRNAs‐miRNAs‐mRNAs networks in periodontal ligament stem cells under mechanical force
Authors: Wang Hong , Feng Cheng , Li Mengying , Zhang Zijie , Liu Jiani , Wei Fulan
Published: July 2020

Objectives

Our study aims to analyze the expression profiles of long non‐coding RNAs (lncRNAs) and investigate the potential regulatory networks among lncRNAs, microRNAs (miRNAs), and mRNAs in periodontal ligament stem cells (PDLSCs) under mechanical force (MF).

Materials and Methods

PDLSCs were isolated from human periodontal ligament tissues and identified by flow cytometry analysis. Multidirectional differentiation potential of PDLSCs was obtained by osteogenic and adipogenic induction. High‐throughput RNA sequencing was used to identify the expression patterns of lncRNAs and mRNAs in PDLSCs under MF. MF‐responsive miRNAs were obtained from the previous microarray data. LncRNAs‐miRNAs‐mRNAs networks were constructed by Cytoscape.

Results

PDLSCs cultured from the periodontal ligament tissues were positive for STRO‐1, CD146 and negative for CD45, CD34. Alizarin red staining and Oil Red O staining showed that PDLSCs had the ability of osteogenic and adipogenic differentiation. Then, a total of 1,339 and 1,426 differentially expressed lncRNAs and mRNAs were identified, respectively, in PDLSCs under MF. Based on the previous miRNA microarray analysis, the potential interaction networks of lncRNAs‐miRNAs‐mRNAs were constructed. It was found that lncRNAs and mRNAs could competitively interact with the same miRNA.

Conclusions

LncRNAs‐miRNAs‐mRNAs networks were involved in PDLSCs under MF, which might provide a novel mechanism in the regulation of clinical orthodontic tooth movement process.
Intra‐gastrointestinal amyloid‐β1–42 oligomers perturb enteric function and induce Alzheimer's disease pathology
Authors: Sun Yayi , Sommerville Nerina R. , Liu Julia Yuen Hang , Ngan Man Piu , Poon Daniel , Ponomarev Eugene D. , Lu Zengbing , Kung Jeng S. C. , Rudd John A.
Published: July 2020

Key points

Alzheimer's disease (AD) patients and transgenic mice have beta‐amyloid (Aβ) aggregation in the gastrointestinal (GI) tract.

It is possible that Aβ from the periphery contributes to the load of Aβ in the brain, as Aβ has prion‐like properties.

The present investigations demonstrate that Aβ injected into the GI tract of ICR mice is internalised into enteric cholinergic neurons; at 1 month, administration of Aβ into the body of the stomach and the proximal colon was observed to partly redistribute to the fundus and jejunum; at 1 year, vagal and cerebral β‐amyloidosis was present, and mice exhibited GI dysfunction and cognitive deficits.

These data reveal a previously undiscovered mechanism that potentially contributes to the development of AD.

Alzheimer's disease (AD) is the most common age‐related cause of dementia, characterised by extracellular beta‐amyloid (Aβ) plaques and intracellular phosphorylated tau tangles in the brain. Aβ deposits have also been observed in the gastrointestinal (GI) tract of AD patients and transgenic mice, with overexpression of amyloid precursor protein. In the present studies, we investigate whether intra‐GI administration of Aβ can potentially induce amyloidosis in the central nervous system (CNS) and AD‐related pathology such as dementia. We micro‐injected Aβ1–42 oligomers (4 μg per site, five sites) or vehicle (saline, 5 μl) into the gastric wall of ICR mice under general anaesthesia. Immunofluorescence staining and in vivo imaging showed that HiLyte Fluor 555‐labelled Aβ1–42 had migrated within 3 h via the submucosa to nearby areas and was internalised into cholinergic neurons. At 1 month, HiLyte Fluor 555‐labelled Aβ1–42 in the body of the stomach and proximal colon had partly re‐distributed to the fundus and jejunum. At 1 year, the jejunum showed functional alterations in neuromuscular coupling (P < 0.001), and Aβ deposits were present in the vagus and brain, with animals exhibiting cognitive impairments in the Y‐maze spontaneous alteration test (P < 0.001) and the novel object recognition test (P < 0.001). We found that enteric Aβ oligomers induce an alteration in gastric function, amyloidosis in the CNS, and AD‐like dementia via vagal mechanisms. Our results suggest that Aβ load is likely to occur initially in the GI tract and may translocate to the brain, opening the possibility of new strategies for the early diagnosis and prevention of AD.
The Role of Flow Structures on the Thermal Performance of Microchannels With Wall Features
Authors: Datta Aparesh , Debbarma Dipak , Biswas Nirmalendu , Sanyal Dipankar , Das Ajoy Kumar
Published: July 2020

Innovative design of microchannel heat sinks (MCHS) remains a contemporary research need to meet the increasing cooling demand of modern electronic industries. A transient three-dimensional conjugate heat transfer study has been carried out here for different combinations of constrictors like ribs or protrusions along with cavities on the sidewalls of a microchannel (MC). A facing pair of cavities with circular arc sections, together called a fan-shaped cavity (FC), has been considered. Each in the facing pair of ribs (R) or protrusions (P) is in the form of a part of cylinder or sphere, respectively. The results include the variations of Nusselt number, friction factor, and thermal performance over a range of Reynolds numbers from 140 to 605 in microchannels with rib (MCR), protrusion (MCP), or cavity pairs alone (MCFC), as well as with cavity-rib pairs (MCFCR) or cavity–protrusion pairs (MCFCP). Contrasting the highest thermal performance of 1.6 reported in an earlier study on MCFCR, a value as high as 1.76 has been obtained around Re of 550 for MCFCP with the relative values of cavity length, width, and pitch of 0.015, 0.5, and 0.0625, respectively, along with protrusion length and width of 0.01 and 0.4, respectively. The mechanisms leading to spiraling transverse streamlines in both MCFCR and MCFCP have been explained. The superior performance of MCFCP has presumably arisen from the vortex structure with no interference with the boundary layers at the top and bottom walls.
Developments in Tribology of Manufacturing Processes
Authors: Schmid S. R. , Saha P. K. , Wang J. , Schmitz T.
Published: July 2020

Tribology in manufacturing has seen tremendous development in the past 100 years and essentially was transformed from a known and unavoidable nuisance to a sophisticated discipline. This is demonstrated by the reliability and quality of products that result in modern metal forming and cutting. This paper provides a brief summary of the state-of-the-art in manufacturing tribology, discussing some of the important developments in the field.
The Effect of a Team Building Program on the Self-Conceptions of Grade 6 and 7 Physical Education Students
Authors: Ebbeck Vicki , Gibbons Sandra L.
Published: July 2020

This study investigated the effectiveness of a Team Building Through Physical Challenges (TBPC; Glover and Midura, 1992) program on the self-conceptions of physical education students in Grades 6 and 7. The treatment group was exposed to one TBPC activity every second week for 8 months, while the second group completed the regular physical education curriculum without any TBPC activities. Data were analyzed using 2 (treatment/control) x 2 (preintervention/postintervention) x 2 (male/female) repeated measures analysis. Results at postintervention revealed that both male and female students in the treatment group were significantly higher on perceptions of global self-worth, athletic competence, physical appearance, and social acceptance than the control group. Female students in the treatment group were also significantly higher on perceptions of scholastic competence and behavioral conduct than female students in the control group. Effect sizes indicated that meaningful as well as significant differences in self-conceptions were created by the TBPC program.
Discovery of diffuse optical emission lines from the inner Galaxy: Evidence for LI(N)ER-like gas
Authors: Krishnarao D. , Benjamin R. A. , Haffner L. M.
Published: July 2020

Optical emission line observations from the inner Galaxy show that the Milky Way hosts the closest known example of a LI(N)ER.
Paleoindian ochre mines in the submerged caves of the Yucatán Peninsula, Quintana Roo, Mexico
Authors: MacDonald Brandi L. , Chatters James C. , Reinhardt Eduard G. , Devos Fred , Meacham Sam , Rissolo Dominique , Rock Barry , Le Maillot Chris , Stalla David , Marino Marc D. , Lo Eric , Erreguerena Pilar Luna
Published: July 2020

Cave divers discover La Mina, a pristine Paleoindian-age subterranean ochre mine, deep in the now-submerged caves of Quintana Roo.
Aggregative Adherence Fimbriae II of Enteroaggregative Escherichia coli Are Required for Adherence and Barrier Disruption during Infection of Human Colonoids
Authors: Gonyar Laura A. , Smith Rachel M. , Giron Jorge A. , Zachos Nicholas C. , Ruiz-Perez Fernando , Nataro James P.
Published: July 2020

Symptomatic and asymptomatic infection with the diarrheal pathogen enteroaggregative
Escherichia coli
(EAEC) is associated with growth faltering in children in developing settings. The mechanism of this association is unknown, emphasizing a need for better understanding of the interactions between EAEC and the human gastrointestinal mucosa. In this study, we investigated the role of the aggregative adherence fimbriae II (AAF/II) in EAEC adherence and pathogenesis using human colonoids and duodenal enteroids.
H9N2 Influenza Virus Infections in Human Cells Require a Balance between Neuraminidase Sialidase Activity and Hemagglutinin Receptor Affinity
Authors: Arai Yasuha , Elgendy Emad Mohamed , Daidoji Tomo , Ibrahim Madiha Salah , Ono Takao , Sriwilaijaroen Nongluk , Suzuki Yasuo , Nakaya Takaaki , Matsumoto Kazuhiko , Watanabe Yohei
Published: July 2020

H9N2 avian influenza (AI) virus, one of the most prevalent AI viruses, has caused repeated poultry and human infections, posing a huge public health risk. The H9N2 virus has diversified into multiple lineages, with the G1 lineage being the most prevalent worldwide. In this study, we isolated G1 variants carrying an 8-amino-acid deletion in their NA stalk, which is, to our knowledge, the longest deletion found in H9N2 viruses in the field. The NA stalk length was found to modulate G1 virus entry into host cells, with the effects being species specific and dependent on the corresponding HA binding affinity. Our results suggest that, in nature, H9N2 G1 viruses balance their HA and NA functions by the NA stalk length, leading to the possible association of host range and virulence in poultry and mammals during the evolution of G1 lineage viruses.
Metformin and statin use associate with plasma proteinN-glycosylation in people with type 2 diabetes
Authors: Singh Sunny S , Naber Annemieke , Dotz Viktoria , Schoep Emma , Memarian Elham , Slieker Roderick C , Elders Petra J M , Vreeker Gerda , Nicolardi Simone , Wuhrer Manfred , Sijbrands Eric J G , Lieverse Aloysius G , 't Hart Leen M , van Hoek Mandy
Published: July 2020

Introduction

Recent studies revealedN-glycosylation signatures of type 2 diabetes, inflammation and cardiovascular risk factors. Most people with diabetes use medication to reduce cardiovascular risk. The association of these medications with the plasmaN-glycome is largely unknown. We investigated the associations of metformin, statin, ACE inhibitor/angiotensin II receptor blocker (ARB), sulfonylurea (SU) derivatives and insulin use with the total plasmaN-glycome in type 2 diabetes.

Research design and methods

After enzymatic release from glycoproteins,N-glycans were measured by matrix-assisted laser desorption/ionization mass spectrometry in the DiaGene (n=1815) and Hoorn Diabetes Care System (n=1518) cohorts. Multiple linear regression was used to investigate associations with medication, adjusted for clinical characteristics. Results were meta-analyzed and corrected for multiple comparisons.

Results

Metformin and statins were associated with decreased fucosylation and increased galactosylation and sialylation in glycans unrelated to immunoglobulin G. Bisection was increased within diantennary fucosylated non-sialylated glycans, but decreased within diantennary fucosylated sialylated glycans. Only few glycans were associated with ACE inhibitor/ARBs, while none associated with insulin and SU derivative use.

Conclusions

We conclude that metformin and statins associate with a total plasmaN-glycome signature in type 2 diabetes. Further studies are needed to determine the causality of these relations, and futureN-glycomic research should consider medication a potential confounder.
Using the ‘shit’ of the current COVID-19 crisis as fertiliser for the soil to lay the foundations of a new and sustainable era: lessons from past crises to improve the future
Authors: Roseboom Tessa
Published: July 2020

Studies of past crises have demonstrated that adverse experiences during critical periods of human development hamper the individual’s ability to reach its full potential and leaves lasting marks on health, behaviour, productivity and society as a whole. The COVID-19 crisis has severely worsened the environment in which we live and in which our future generations are being shaped, and will lead to loss of future human potential and capital. It is clear that the COVID-19 pandemic does not only harm the current world population, but also affects our future, as well as that of future generations. The science of transgenerational plasticity demonstrates that investments in early life hold the promise of having beneficial effects across multiple generations. As governments are reopening societies and prioritising policies, their overarching goal should be to improve the environment in which future generations grow and develop, learn and live. This will change the lifetime trajectories of children for the better and affect future health, school success, behaviour, productivity and well-being. This prioritisation will prove to be the most effective intervention to build sustainable futures but will also yield returns many times the original investment. It is a promising way to break the intergenerational cycle of adversity and accelerate progress on achieving the Sustainable Development Goals.
Advanced imaging of right ventricular anatomy and function
Authors: Badano Luigi P , Addetia Karima , Pontone Gianluca , Torlasco Camilla , Lang Roberto M , Parati Gianfranco , Muraru Denisa
Published: July 2020

Right ventricular (RV) size and function are important predictors of cardiovascular morbidity and mortality in patients with various conditions. However, non-invasive assessment of the RV is a challenging task due to its complex anatomy and location in the chest. Although conventional echocardiography is widely used, its limitations in RV assessment are well recognised. New techniques such as three-dimensional and speckle tracking echocardiography have overcome the limitations of conventional echocardiography allowing a comprehensive, quantitative assessment of RV geometry and function without geometric assumptions. Cardiac magnetic resonance (CMR) and CT provide accurate assessment of RV geometry and function, too. In addition, tissue characterisation imaging for myocardial scar and fat using CMR and CT provides important information regarding the RV that has clinical applications for diagnosis and prognosis in a broad range of cardiac conditions. Limitations also exist for these two advanced modalities including availability and patient suitability for CMR and need for contrast and radiation exposure for CT. Hybrid imaging, which is able to integrate anatomical information (usually obtained by CT or CMR) with physiological and molecular data (usually obtained with positron emission tomography), can provide optimal in vivo evaluation of Rv functional impairment. This review summarises the clinically useful applications of advanced echocardiography techniques, CMR and CT for comprehensive assessment of RV size, function and mechanics.
Mir-3150B-3P Inhibits the Proliferation and Invasion of Cervical Cancer Cells by Targeting Tnfrsf11A
Authors: Yu Zhijuan , Wang Liguo , Li Xiujuan
Published: July 2020

The objective of this study was to determine the role of miR-3150b-3p in the cervical cancer (CC) progression. Real-time PCR and western blot analysis were conducted to test the expression of miR-3150b-3p, TNFRSF11a and p38 mitogen-activated protein kinase (MAPK) signaling pathway. The interaction between miR-3150b-3p and TNFRSF11a was verified by luciferase assay. Cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. In this study, we showed that miR-3150b-3p was significantly downregulated in CC cell lines. Additionally, miR-3150b-3p markedly attenuated the proliferation, migration and invasion of HeLa and SiHa cells. Moreover, we identified TNFRSF11a to be a novel target of miR-3150b-3p in CC cells. Enforced expression of TNFRSF11a abolished the antitumor effect of miR-3150b-3p. Besides, miR-3150b-3p was involved in the regulation of the p38 MAPK signaling pathway. In conclusion, our data suggested that miR-3150b-3p directly targets TNFRSF11a to inactivate the p38 MAPK signaling pathway, thus implicating miR-3150b-3p in the regulation of CC cell growth.
Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study
Authors: Li Yanan , Li Man , Wang Mengdie , Zhou Yifan , Chang Jiang , Xian Ying , Wang David , Mao Ling , Jin Huijuan , Hu Bo
Published: July 2020

Background and purpose

COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19. Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection.

Materials and methods

Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed. Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.

Results

Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage. COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05). In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3–127.9) vs 12.1 (0.1–212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3–20.0) vs 0.5 (0.1–20.0) mg/L, p<0.001). Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died. The other four patients received anticoagulant treatment with enoxaparin and 2 of them died. As of 24 March 2020, six patients with CVD died (54.5%).

Conclusion

Acute CVD is not uncommon in COVID-19. Our findings suggest that older patients with risk factors are more likely to develop CVD. The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.
Endometrial mineralisation in a bitch with ovarian granulosa cell tumour and cystic endometrial hyperplasia‐pyometra complex
Authors: Rodenas Carmen , Agut Amalia , Bernabe Antonio , Gómez Miguel Angel , Lucas Xiomara
Published: July 2020

Granulosa cell tumour is a common ovarian pathology in bitches. Depending on its hormonal production, this tumour often induces persistent oestrus signs and uterine disorders. Chronic treatment with progesterone contraceptives has been associated with endometrial mineralisation in bitches. The authors describe the case of a three‐year‐old female entire mastiff dog with a one‐year history of chronic hyperoestrogenism signs and anorexia. Serum biochemistry and haematology revealed moderate leucocytosis. Abdominal ultrasound showed dilated uterine horns with anechoic fluid in the lumen, small cystic structures, and multiple stippled hyperechoic lesions with mild acoustic shadowing and comet tail artefact along the endometrial wall. Furthermore, cystic structures were observed in the right ovary. After surgery, histopathological study revealed the presence of endometrial hyperplasia‐pyometra complex, endometrial mineralisation and a granulosa cell tumour. To the best of the authors’ knowledge, this is the first report of endometrial mineralisation associated with ovarian granulosa cell tumour in a bitch.
Applications and prospects of targeted therapy for neuroblastoma
Authors: Wang Jing , Yao Wei , Li Kai
Published: July 2020

Background

Neuroblastoma is an extremely malignant tumor in children. For advanced or recurrent cases, existing treatment modalities are limited and efficacy remains disappointing. With the improvement in understanding of molecular biology of neuroblastoma and the development of clinical trials of targeted drug therapy, a variety of targeted therapies for neuroblastoma have appeared.

Data sources

All the recent literatures on targeted therapies of neuroblastoma on PubMed were searched and reviewed.

Results

This article reviewed targeted therapies of neuroblastoma going through clinical trials and obtained preliminary results. The features, advantages and disadvantages of targeted radiation therapy,

immunotherapy, gene and pathway molecular inhibitor and angiogenesis inhibitor were discussed.

Conclusion

This study provides references for better understanding the current progress of targeted therapies for neuroblastoma.
Spatiotemporal variation in maturation: a case study with American plaice (Hippoglossoides platessoides) on the Grand Bank off Newfoundland
Authors: Zheng Nan , Robertson Matthew , Cadigan Noel , Zhang Fan , Morgan Joanne , Wheel Laura
Published: July 2020

Fisheries management usually does not explicitly account for spatial variation in life history traits within populations. However, for some stocks this spatial variation may be substantial. We develop a spatiotemporal generalized linear model and fit the model to a long time series of maturation data for American plaice (Hippoglossoides platessoides) on the Grand Bank off Newfoundland and Labrador. The spatiotemporal correlation structure improves estimation of small-scale spatiotemporal variation in maturity across locations and times with limited or few samples. We test how American plaice maturity varies at three different spatial resolutions. We find improvements in model fit when decreasing spatial scales for higher spatial resolution due to high levels of spatial heterogeneity in American plaice maturity at age and size. Modeling variation in life history traits at the appropriate spatial and temporal scales is necessary for understanding population dynamics and developing appropriate fisheries management strategies.