bluuebunny/crossref_metadata_2025 huggingface dataset:
GenoTypeMapper: graphical genotyping on genetic and sequence-based maps
Authors: Deblieck Mathieu , Fatiukha Andrii , Grundman Norbert , Merchuk-Ovnat Lianne , Saranga Yehoshua , Krugman Tamar , Pillen Klaus , Serfling Albrecht , Makalowski Wojciech , Ordon Frank , Perovic Dragan
Published: September 2020

Background

The rising availability of assemblies of large genomes (e.g. bread and durum wheat, barley) and their annotations deliver the basis to graphically present genome organization of parents and progenies on a physical scale. Genetic maps are a very important tool for breeders but often represent distorted models of the actual chromosomes, e.g., in centromeric and telomeric regions. This biased picture might lead to imprecise assumptions and estimations about the size and complexity of genetic regions and the selection of suitable molecular markers for the incorporation of traits in breeding populations or near-isogenic lines (NILs). Some software packages allow the graphical illustration of genotypic data, but to the best of our knowledge, suitable software packages that allow the comparison of genotypic data on the physical and genetic scale are currently unavailable.

Results

We developed a simple Java-based-software called GenoTypeMapper (GTM) for comparing genotypic data on genetic and physical maps and tested it for effectiveness on data of two NILs that carry QTL-regions for drought stress tolerance from wild emmer on chromosome 2BS and 7AS. Both NILs were more tolerant to drought stress than their recurrent parents but exhibited additional undesirable traits such as delayed heading time.

Conclusions

In this article, we illustrate that the software easily allows users to display and identify additional chromosomal introgressions in both NILs originating from the wild emmer parent. The ability to detect and diminish linkage drag can be of particular interest for pre-breeding purposes and the developed software is a well-suited tool in this respect. The software is based on a simple allele-matching algorithm between the offspring and parents of a crossing scheme. Despite this simple approach, GTM seems to be the only software that allows us to analyse, illustrate and compare genotypic data of offspring of different crossing schemes with up to four parents in two different maps. So far, up to 500 individuals with a maximum number of 50,000 markers can be examined with the software. The main limitation that hampers the performance of the software is the number of markers that are examined in parallel. Since each individual must be analysed separately, a maximum of ten individuals can currently be displayed in a single run. On a computer with an Intel five processor of the 8th generation, GTM can reliably either analyse a single individual with up to 12,000 markers or ten individuals with up to 3,600 markers in less than five seconds. Future work aims to improve the performance of the software so that more complex crossing schemes with more parents and more markers can be analysed.
COVID-19: an update and cardiac involvement
Authors: Alwaqfi Nizar R. , Ibrahim Khalid S.
Published: September 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through angiotensin converting enzyme 2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, and also causing acute cardiac injury and chronic damage to the cardiovascular system. The purpose of this review is primarily reviewing the COVID-19 disease, including pathogen, clinical features, diagnosis, and treatment with particular attention to cardiovascular involvement based on the current evidence. COVID-19 remains a threat to global public health. The associated extra-pulmonary manifestations and their prolonged consequences are frequently overlooked. Pre-existing cardiovascular disease or acute cardiac complications may contribute to adverse early clinical outcome. At the moment, there is no specific treatment for COVID-19, but multiple randomized controlled trials (RCT) are being conducted. New supportive therapies are being evaluated with promising results.
Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer
Authors: Xu Tie , Zeng Yulan , Shi Linli , Yang Qin , Chen Yeshan , Wu Gang , Li Guiling , Xu Shuangbing
Published: September 2020

Background

NEK2, a serine/threonine kinase involved in mitosis, has been found to function in chromosome instability, tumor progression and metastasis, but its role in cervical cancer radioresistance remains unknown.

Methods

We detected the protein levels of NEK2 in cervical carcinoma tissues and paired paracarcinoma tissues by immunohistochemistry. The roles of NEK2 in oncogenesis were examined using cell growth and colony formation assays, EdU assay, apoptosis assay as well as in vivo mouse model. γ-H2AX and Rad51 foci formation, neutral comet assay and clonogenic cell survival assay were applied to determine the radiosensitivity of cervical cancer cells. RNA-seq was performed to identify the downstream effector of NEK2. The gene expression levels were measured by Real-time PCR.

Results

We report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer tissues. Furthermore, we provided evidence that depletion of NEK2 impairs oncogenesis and enhances radiosensitivity in cervical cancer. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/β-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression.

Conclusions

Our results demonstrate that NEK2 activates the Wnt/β-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer.
Consistency and variability in human performance during simulate infant CPR: a reliability study
Authors: Almeida Debora , Clark Carol , Jones Michael , McConnell Phillip , Williams Jonathan
Published: September 2020

Background

Positive outcomes from infant cardiac arrest depend on the effective delivery of resuscitation techniques, including good quality infant cardiopulmonary resuscitation (iCPR) However, it has been established that iCPR skills decay within weeks or months after training. It is not known if the change in performance should be considered true change or inconsistent performance. The aim of this study was to investigate consistency and variability in human performance during iCPR.

Methods

An experimental, prospective, observational study conducted within a university setting with 27 healthcare students (mean (SD) age 32.6 (11.6) years, 74.1% female). On completion of paediatric basic life support (BLS) training, participants performed three trials of 2-min iCPR on a modified infant manikin on two occasions (immediately after training and after 1 week), where performance data were captured. Main outcome measures were within-day and between-day repeated measures reliability estimates, determined using Intraclass Correlation Coefficients (ICCs), Standard Error of Measurement (SEM) and Minimal Detectable Change (MDC95%) for chest compression rate, chest compression depth, residual leaning and duty cycle along with the conversion of these into quality indices according to international guidelines.

Results

A high degree of reliability was found for within-day and between-day for each variable with good to excellent ICCs and narrow confidence intervals. SEM values were low, demonstrating excellent consistency in repeated performance. Within-day MDC values were low for chest compression depth and chest compression rate (6 and 9%) and higher for duty cycle (15%) and residual leaning (22%). Between-day MDC values were low for chest compression depth and chest compression rate (3 and 7%) and higher for duty cycle (21%) and residual leaning (22%). Reliability reduced when metrics were transformed in quality indices.

Conclusion

iCPR skills are highly repeatable and consistent, demonstrating that changes in performance after training can be considered skill decay. However, when the metrics are transformed in quality indices, large changes are required to be confident of real change.
Using qualitative research to explore intervention mechanisms: findings from the trial of the Learning Together whole-school health intervention
Authors: Warren Emily , Melendez-Torres G. J. , Viner Russell , Bonell Chris
Published: September 2020

Background

This study reports on qualitative research conducted within a randomised controlled trial to explore possible intervention mechanisms. It focuses on the ‘Learning Together’ whole-school intervention delivered in secondary schools in England from 2014 to 2017 aiming to prevent bullying and aggression and improve student health. Intervention schools received staff training in restorative practice, a social and emotional learning curriculum, and an external facilitator and manual to convene and run a student/staff action group tasked with coordinating the intervention, focusing this on local needs.

Methods

Informed by realist approaches to evaluation, we analysed qualitative data to explore intervention mechanisms and how these might interact with school contexts to generate outcomes. Qualitative analysis drew on 45 interviews and 21 focus groups across three case-study schools and employed thematic content analysis to explore how intervention resources were taken up and used by local actors, how participants described the intervention mechanisms that then ensued, and how these might have generated beneficial outcomes.

Results

The thematic content analysis identified three social mechanisms that recurred in participant accounts: (1) building student commitment to the school community, (2) building healthy relationships by modelling and teaching pro-social skills, and (3) de-escalating bullying and aggression and enabling re-integration within the school community.

Conclusions

Our analysis provides in-depth exploration of possible mechanisms and the contextual contingencies associated with these, allowing refinement of the initial intervention theory of change.

Trial registration

ISRCTN registry 10751359. Registered on 11 March 2014
Comparative study of composition, antioxidant and antimicrobial activity of two adult edible insects from Tenebrionidae family
Authors: Flores Daniel R. , Casados Luz E. , Velasco Sandra F. , Ramírez Ana C. , Velázquez Gilberto
Published: September 2020

In the case of Tenebrionidae family insects, studies focus on larval stage, leaving a lack of information regarding other stages. Therefore, this study was performed in order to understand the differences between the nutritional composition and the bioactivity of two species of this family in their adult stage, fed with a specific diet. Adult beetles of both species were defatted, lyophilized and protein extracted with buffer. Proximal and phytochemical analysis of the extracts of each insect were performed, along with protein extract and hydrolysis analysis by Tris-Tricine and Tris Glycine SDS PAGE. This analysis showed thatT. molitorcontained more protein and fat thanU. dermestoidesbut contained less crude fiber. The protein extraction was made with PBS, where 130 and 45 kDa bands showed predominant forU. dermestoides,and less protein was present forT. molitor. Antioxidant and antimicrobial activities of the enzymatic protein hydrolysates and protein crude extracts were determined. Presence of protein associated with the antioxidant activity were found in both insects. NonethelessU. dermestoideshad a higher antioxidant activity with the protein extract in contrast with the higher antioxidant activity shown byU. dermestoidesonce the extracts were digested. After proteolysis, protein extracts showed an increasing antioxidant activity, plus, the ability to inhibit microbial growth ofProteus,ShigellaandBacillus. Insect protein hydrolysates with protease open the possibility for the use of these beetles as new sources of encrypted peptides for microbiological control once characterized.
Mechanisms and microbial influences on CTLA-4 and PD-1-based immunotherapy in the treatment of cancer: a narrative review
Authors: Miller Peter L. , Carson Tiffany L.
Published: September 2020

Background

The relationship between gastrointestinal (GI) bacteria and the response to anti-CTLA-4 and anti-PD-1 immunotherapy in the treatment of cancer can potentially be enhanced to allow patients to maximally respond to these treatments. Insight into the complex interaction between gut microbiota and the human adaptive immune system will help guide future immunotherapeutic cancer treatments to allow a more robust clinical response and fewer adverse effects in patients requiring these drugs. This review highlights these interactions as well as the potential for the creation of “oncomicrobiotics” that would selectively tailor one’s GI bacteria to maximally respond to anti-CTLA-4 and anti-PD-1 treatments will fewer adverse effects.

Main body

CTLA-4 is an antigen on the surface of T cells which, upon stimulation, leads to inhibition of activated T cells to terminate the immune response. However, many types of tumor cells can upregulate CTLA-4 in the tumor microenvironment, allowing these cells to evade targeting and destruction by the body’s immune system by prematurely inhibiting T cells. Increased representation ofBacteroides fragilis,Burkholderia cepaciaand theFaecalibacterium genusin the GI tract of patients receiving CTLA-4-based immunotherapy led to a stronger therapeutic effect while minimizing adverse side effects such as colitis. In addition, by introducing bacteria involved in vitamin B and polyamine transport to the GI tracts of patients treated with anti-CTLA-4 drugs led to increased resistance to colitis while maintaining therapeutic efficacy. PD-1 is another molecule upregulated in many tumor microenvironments which acts in a similar manner to CTLA-4 to tone down the anti-neoplastic actions of T cells. Antibodies to PD-1 have shown promise to help allow the body’s natural immune response to appropriately target and destroy tumor cells. The presence ofBifidobacterium breveandlongum,Akkermansia muciniphilaandFaecalibacterium prausnitziiin the GI tracts of cancer patients has the potential to create a more robust immune response to anti-PD-1 drugs and prolonged survival. The development of “oncomicrobiotics” has the potential to help tailor one’s gut microbiota to allow patients to maximally respond to immunotherapy without sacrificing increases in toxicity. These oncomicrobiotics may possibly include antibiotics, probiotics, postbiotics and/or prebiotics. However, many challenges lie ahead in the creation of oncomicrobiotics.

Conclusion

The creation of oncomicrobiotics may allow many patients receiving anti-CTLA-4 and PD-1 immunotherapy to experience prolonged survival and a better quality of life.
Association of carotid and intracranial stenosis with Alzheimer’s disease biomarkers
Authors: Kang Koung Mi , Byun Min Soo , Lee Jun Ho , Yi Dahyun , Choi Hye Jeong , Lee Eunjung , Lee Younghwa , Lee Jun-Young , Kim Yu Kyeong , Sohn Bo Kyung , Sohn Chul-Ho , Lee Dong Young ,   for the KBASE Research Group
Published: September 2020

Background

To clarify whether atherosclerosis of the carotid and intracranial arteries is related to Alzheimer’s disease (AD) pathology in vivo, we investigated the associations of carotid and intracranial artery stenosis with cerebral beta-amyloid (Aβ) deposition and neurodegeneration in middle- and old-aged individuals. Given different variations of the pathologies between cognitive groups, we focused separately on cognitively normal (CN) and cognitively impaired (CI) groups.

Methods

A total of 281 CN and 199 CI (mild cognitive impairment and AD dementia) subjects underwent comprehensive clinical assessment, [11C] Pittsburgh compound B-positron emission tomography, and magnetic resonance (MR) imaging including MR angiography. We evaluated extracranial carotid and intracranial arteries for the overall presence, severity (i.e., number and degree of narrowing), and location of stenosis.

Results

We found no associations between carotid and intracranial artery stenosis and cerebral Aβ burden in either the CN or the CI group. In terms of neurodegeneration, exploratory univariable analyses showed associations between the presence and severity of stenosis and regional neurodegeneration biomarkers (i.e., reduced hippocampal volume [HV] and cortical thickness in the AD-signature regions) in both the CN and CI groups. In confirmatory multivariable analyses controlling for demographic covariates and diagnosis, the association between number of stenotic intracranial arteries ≥ 2 and reduced HV in the CI group remained significant.

Conclusions

Neither carotid nor intracranial artery stenosis appears to be associated with brain Aβ burden, while intracranial artery stenosis is related to amyloid-independent neurodegeneration, particularly hippocampal atrophy.
Pediatric subset of primary immunodeficiency patients treated with SCIG: post hoc analysis of SHIFT and IBIS pooled data
Authors: Moschese Viviana , Canessa Clementina , Trizzino Antonino , Martire Baldassarre , Boggia Giorgio Maria , Graziani Simona ,   the SHIFT and IBIS Study Groups
Published: September 2020

Background

Primary immunodeficiencies (PID) constitute a heterogeneous group of more than 350 monogenetic diseases. PID patients with antibody impairment require lifelong administration of immunoglobulin G replacement therapy, administered either intravenously (IVIG) or subcutaneously (SCIG). Although the effectiveness of weekly and biweekly (every other week) SCIG administration has been shown in several trials, data on the viability of these two regimens in pediatric PID patients are sparse.

Methods

Data on the pediatric subsets of PID patients enrolled in SHIFT (weekly) and IBIS (biweekly) studies were pooled and analyzed to indirectly compare two different 20%-concentrated SCIG (Hizentra®) regimens. The primary endpoints were to evaluate trough IgG levels and cumulative monthly doses; the secondary endpoint was to analyze incidence of infections.

Results

Fifteen and 13 children from the SHIFT and IBIS studies were included, respectively. Cumulative 20%-concentrated SCIG monthly dose was slight lower for the biweekly regimen (Δ = − 2.04, 90% CI − 8.3 to 4.23). However, the trough IgG levels were similar between the two groups (Δ = 0.28, 90% CI − 0.51 to 1.07) and constantly above the threshold of 5 g/L. After adjusting for potential confounders, the annualized rate of infections was similar between SHIFT and IBIS patients (incidence rate ratio = 1.09, 90% CI 0.72–1.67); only 1 serious bacterial infection was experienced by a patient in the IBIS group.

Conclusion

In pediatric PID patients, weekly and biweekly Hizentra® administrations appeared equally effective treatment options.
Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology
Authors: Cheroni Cristina , Caporale Nicolò , Testa Giuseppe
Published: September 2020

The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. On the other hand, exposure to chemicals that are widespread in the environment, such as endocrine disruptors, has been associated with adverse effects on human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. The pervasive nature of chemical exposure poses pivotal challenges for neurotoxicological studies, regulatory agencies, and policy makers. This highlights an emerging need of developing new integrative models, including biomonitoring, epidemiology, experimental, and computational tools, able to capture real-life scenarios encompassing the interaction between chronic exposure to mixture of substances and individuals’ genetic backgrounds. In this review, we address the intertwined roles of genetic lesions and environmental insults. Specifically, we outline the transformative potential of stem cell models, coupled with omics analytical approaches at increasingly single cell resolution, as converging tools to experimentally dissect the pathogenic mechanisms underlying neurodevelopmental disorders, as well as to improve developmental neurotoxicology risk assessment.
CRISPR-mediated gene modification of hematopoietic stem cells with beta-thalassemia IVS-1-110 mutation
Authors: Gabr Hala , El Ghamrawy Mona Kamal , Almaeen Abdulrahman H. , Abdelhafiz Ahmed Samir , Hassan Aya Osama Saad , El Sissy Maha Hamdi
Published: September 2020

Background

β-Thalassemias represent a group of genetic disorders caused by human hemoglobin beta (HBB) gene mutations. The radical curative approach is to correct the mutations causing the disease. CRISPR-CAS9 is a novel gene-editing technology that can be used auspiciously for the treatment of these disorders. The study aimed to investigate the utility of CRISPR-CAS9 for gene modification of hematopoietic stem cells in β-thalassemia with IVS-1-110 mutation.

Methods and results

We successfully isolated CD34+ cells from peripheral blood of β-thalassemia patients with IVS-1-110 mutation. The cells were transfected with Cas9 endonuclease together with guide RNA to create double-strand breaks and knock out the mutation. The mutation-corrected CD34+ cells were subjected to erythroid differentiation by culturing in complete media containing erythropoietin.

Conclusion

CRISPR/Cas-9 is an effective tool for gene therapy that will broaden the spectrum of therapy and potentially improve the outcomes of β-thalassemia.
Identification of the natural product berberine as an antiviral drug
Authors: Shao Jiping , Zeng Debin , Tian Shuhong , Liu Gezhi , Fu Jian
Published: September 2020

Drugs targeting the fusion process of viral entry into host cells have been approved for clinical use in the treatment of AIDS. There remains a great need to improve the use of existing drugs for HIV therapy. Berberine is traditionally used to treat diarrhea, bacillary dysentery, and gastroenteritis in clinics, here our research shows that berberine is effective in inhibiting HIV-1 entry. Native polyacrylamide gel electrophoresis studies reveal that berberine can directly bind to both N36 and C34 to form a novel N36-berberine-C34 complex and effectively block the six-helix bundle formation between the N-terminal heptad repeat peptide N36 and the C-terminal heptad repeat peptide C34. Circular dichroism experiments show that binding of berberine produces conformational changes that damages the secondary structures of 6-HB. Computer-aided molecular docking studies suggest a hydrogen bond with T-639 and two polar bonds with Q-563 and T-639 are established, involving the oxygen atom and the C=O group of the indole ring. Berberine completely inhibits six HIV-1 clade B isolates and exhibits antiviral activities in a concentration-dependent manner with IC50 values varying from 5.5 to 10.25 µg/ml. This compound-peptide interaction may represent a mechanism of action of antiviral activities of berberine. As a summary, these studies successfully identify compound berberine as a potential candidate drug for HIV-1 treatment. As a summary, antiviral activity of berberine in combination with its use in clinical practice, this medicine can be used as a potential clinically anti-HIV drug.
Conditional ablation of MAPK7 expression in chondrocytes impairs endochondral bone formation in limbs and adaptation of chondrocytes to hypoxia
Authors: Yang Xiaoming , Zhong Dongmei , Gao Wenjie , Liao Zhiheng , Chen Yuyu , Zhang Shun , Zhou Hang , Su Peiqiang , Xu Caixia
Published: September 2020

Background

Long bones of limbs are formed through endochondral bone formation, which depends on the coordinated development of growth plates. Our previous studies have demonstrated that dysfunction of mitogen-activated protein kinase 7 (MAPK7) can cause skeletal dysplasia. However, little is known about the role of MAPK7 in the regulation of proliferation and differentiation of chondrocytes during growth plate development.

Results

Ablation of MAPK7 expression in chondrocytes led to growth restriction, short limbs and bone mass loss in postnatal mice. Histological studies revealed that MAPK7 deficiency increased the apoptosis and decreased the proliferation of chondrocytes in the center of the proliferative layer, where the most highly hypoxic chondrocytes are located. Accordingly, hypertrophic differentiation markers were downregulated in the central hypertrophic layer, beneath the site where abnormal apoptosis was observed. Simultaneously, we demonstrated that hypoxic adaptation and hypoxia-induced activation of hypoxia-inducible factor 1 subunit α (HIF1α) were impaired when MAPK7 could not be activated normally in primary chondrocytes. Concomitantly, vascular invasion into epiphyseal cartilage was inhibited whenMapk7was deleted.

Conclusions

We demonstrated that MAPK7 is necessary for maintaining proliferation, survival, and differentiation of chondrocytes during postnatal growth plate development, possibly through modulating HIF1α signaling for adaptation to hypoxia. These results indicate that MAPK7 signaling might be a target for treatment of chondrodysplasia.
MSC-based therapy in female pelvic floor disorders
Authors: Sima Yizhen , Chen Yisong
Published: September 2020

Mesenchymal stem cells (MSCs), also referred to as multipotent stromal cells or mesenchymal stromal cells, are present in multiple tissues and capable of differentiating into diverse cell lineages, holding a great promise in developing cell-based therapy for a wide range of conditions. Pelvic floor disorders (PFDs) is a common degenerative disease in women and may diminish a woman’s quality of life at any age. Since the treatments for this disease are limited by the high rates of recurrence and surgical complications, seeking an ideal therapy in the restoration of pelvic floor function is an urgent issue at present. Herein, we summarize the cell sources of MSCs used for PFDs and discuss the potential mechanisms of MSCs in treating PFDs. Specifically, we also provide a comprehensive review of current preclinical and clinical trials dedicated to investigating MSC-based therapy for PFDs. The novel therapy has presented promising therapeutic effects which include relieving the symptoms of urinary or fecal incontinence, improving the biological properties of implanted meshes and promoting the injured tissue repair. Nevertheless, MSC-based therapies for PFDs are still experimental and the unstated issues on their safety and efficacy should be carefully addressed before their clinical applications.
High-dimensional neural feature design for layer-wise reduction of training cost
Authors: Javid Alireza M. , Venkitaraman Arun , Skoglund Mikael , Chatterjee Saikat
Published: September 2020

We design a rectified linear unit-based multilayer neural network by mapping the feature vectors to a higher dimensional space in every layer. We design the weight matrices in every layer to ensure a reduction of the training cost as the number of layers increases. Linear projection to the target in the higher dimensional space leads to a lower training cost if a convex cost is minimized. An ℓ2-norm convex constraint is used in the minimization to reduce the generalization error and avoid overfitting. The regularization hyperparameters of the network are derived analytically to guarantee a monotonic decrement of the training cost, and therefore, it eliminates the need for cross-validation to find the regularization hyperparameter in each layer. We show that the proposed architecture is norm-preserving and provides an invertible feature vector and, therefore, can be used to reduce the training cost of any other learning method which employs linear projection to estimate the target.
Existence and uniqueness criteria for the higher-order Hilfer fractional boundary value problems at resonance
Authors: Gholami Yousef
Published: September 2020

This investigation is devoted to the study of a certain class of coupled systems of higher-order Hilfer fractional boundary value problems at resonance. Combining the coincidence degree theory with the Lipschitz-type continuity conditions on nonlinearities, we present some existence and uniqueness criteria. Finally, to practically implement the obtained theoretical criteria, we give an illustrative application.
Effect of sequential presoaking and chlorine dioxide treatment on the inactivation of pathogenic Escherichia coli and Salmonella spp. on sprout seeds
Authors: Hung Nguyen Bao , Park Woon-Ra , Yun Bohyun , Seo Dong Cheol , Kim Won-Il , Kim Hyun-Ju , Han Sanghyun , Kim Se-Ri
Published: September 2020

This study was conducted to evaluate the effect of sequential presoaking and chlorine dioxide (ClO2) on the reduction of pathogenic Escherichia coli and Salmonella spp. in alfalfa. When unsoaked and presoaked alfalfa were exposed to 200 ppm ClO2 for 15 min, the population of E. coli and Salmonella spp. on presoaked seeds reduced more than those on unsoaked seeds by 2.07 and 1.43 log CFU g−1 (p < 0.05), respectively. To determine the optimal concentration and treatment time to reduce pathogenic E. coli and Salmonella spp. in alfalfa seeds immersed in water for 5 h, presoaked seeds were exposed to four different concentrations of ClO2 (50, 100, 150, and 200 ppm) for 15, 30, 45, and 60 min. The most effective condition to eliminate E. coli and Salmonella spp. from alfalfa seeds was sequential immersion in water for 5 h and 200 ppm ClO2 treatment for 1 h. After the optimal condition was applied to eight kinds of sprout seeds, the pathogens were completely inactivated in all seeds, except radish seeds. Growth of pathogenic E. coli and Salmonella spp. during sprouting after ClO2 treatment of alfalfa seeds was also completely inactivated. However, the germination rate of seeds did not significantly decrease after ClO2 treatment. In addition, ClO2 residues were not present in any sprout during 3 days of cultivation. These results demonstrated that sequential presoaking and 200 ppm ClO2 treatment is the optimal seed disinfection treatment to prevent foodborne diseases associated with sprout consumption.
A modular multi-agent framework for innovation diffusion in changing business environments: conceptualization, formalization and implementation
Authors: Johanning Simon , Scheller Fabian , Abitz Daniel , Wehner Claudius , Bruckner Thomas
Published: September 2020

Understanding how innovations are accepted in a dynamic and complex market environment is a crucial factor for competitive advantage. To understand the relevant factors for this diffusion and to predict success, empirically grounded agent-based models have become increasingly popular in recent years. Despite the popularity of these innovation diffusion models, no common framework that integrates their diversity exists. This article presents a flexible, modular and extensible common description and implementation framework that allows to depict the large variety of model components found in existing models. The framework aims to provide a theoretically grounded description and implementation framework for empirically grounded agent-based models of innovation diffusion. It identifies 30 component requirements to conceptualize an integrated formal framework description. Based on this formal description, a java-based implementation allowing for flexible configuration of existing and future models of innovation diffusion is developed. As a variable decision support tool in decision-making processes on the adoption of innovations the framework is valuable for the investigation of a range of research questions on innovation diffusion, business model evaluation and infrastructure transformation.
LncRNA SNHG16 as a potential biomarker and therapeutic target in human cancers
Authors: Xiao Yuhang , Xiao Ta , Ou Wei , Wu Zhining , Wu Jie , Tang Jinming , Tian Bo , Zhou Yong , Su Min , Wang Wenxiang
Published: September 2020

Long non-coding RNAs (lncRNAs) represent an important class of RNAs comprising more than 200 nucleotides, which are produced by RNA polymerase II. Although lacking an open reading framework and protein-encoding activity, lncRNAs can mediate endogenous gene expression by serving as chromatin remodeler, transcriptional or post-transcriptional modulator, and splicing regulator during gene modification. In recent years, increasing evidence shows the significance of lncRNAs in many malignancies, with vital roles in tumorigenesis and cancer progression. Moreover, lncRNAs were also considered potential diagnostic and prognostic markers in cancer. The lncRNA small nuclear RNA host gene 16 (SNHG16), found on chromosome 17q25.1, represents a novel tumor-associated lncRNA. SNHG16 was recently found to exhibit dysregulated expression in a variety of malignancies. There are growing evidence of SNHG16’s involvement in characteristics of cancer, including proliferation, apoptosis, together with its involvement in chemoresistance. In addition, SNHG16 has been described as a promising diagnostic and prognostic biomarker in cancer patients. The current review briefly summarizes recently reported findings about SNHG16 and discuss its expression, roles, mechanisms, and diagnostic and prognostic values in human cancers.
Activation of Toll-like receptor 5 in microglia modulates their function and triggers neuronal injury
Authors: Ifuku Masataka , Hinkelmann Lukas , Kuhrt Leonard D. , Efe Ibrahim E. , Kumbol Victor , Buonfiglioli Alice , Krüger Christina , Jordan Philipp , Fulde Marcus , Noda Mami , Kettenmann Helmut , Lehnardt Seija
Published: September 2020

Microglia are the primary immune-competent cells of the central nervous system (CNS) and sense both pathogen- and host-derived factors through several receptor systems including the Toll-like receptor (TLR) family. Although TLR5 has previously been implicated in different CNS disorders including neurodegenerative diseases, its mode of action in the brain remained largely unexplored. We sought to determine the expression and functional consequences of TLR5 activation in the CNS. Quantitative real-time PCR and immunocytochemical analysis revealed that microglia is the major CNS cell type that constitutively expresses TLR5. Using Tlr5−/− mice and inhibitory TLR5 antibody we found that activation of TLR5 in microglial cells by its agonist flagellin, a principal protein component of bacterial flagella, triggers their release of distinct inflammatory molecules, regulates chemotaxis, and increases their phagocytic activity. Furthermore, while TLR5 activation does not affect tumor growth in an ex vivo GL261 glioma mouse model, it triggers microglial accumulation and neuronal apoptosis in the cerebral cortex in vivo. TLR5-mediated microglial function involves the PI3K/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway, as specific inhibitors of this signaling pathway abolish microglial activation. Taken together, our findings establish TLR5 as a modulator of microglial function and indicate its contribution to inflammatory and injurious processes in the CNS.
Regulatory inspection of registered private drug shops in East-Central Uganda—what it is versus what it should be: a qualitative study
Authors: Bagonza Arthur , Peterson Stefan , Mårtensson Andreas , Wamani Henry , Awor Phyllis , Mutto Milton , Musoke David , Gibson Linda , Kitutu Freddy Eric
Published: September 2020

Background

Regulatory inspection of private drug shops in Uganda is a mandate of the Ministry of Health carried out by the National Drug Authority. This study evaluated how this mandate is being carried out at national, district, and drug shop levels. Specifically, perspectives on how the inspection is done, who does it, and challenges faced were sought from inspectors and drug sellers.

Methods

Six key informant interviews (KIIs) were held with inspectors at the national and district level, while eight focus group discussions (FGDs) were conducted among nursing assistants, and two FGDs were held with nurses. The study appraised current methods of inspecting drug sellers against national professional guidelines for licensing and renewal of class C drug shops in Uganda. Transcripts were managed using Atlas ti version 7 (ATLAS.ti GmbH, Berlin) data management software where the thematic content analysis was done.

Results

Five themes emerged from the study: authoritarian inspection, delegated inspection, licensing, training, and bribes. Under authoritarian inspection, drug sellers decried the high handedness used by inspectors when found with expired or no license at all. For delegated inspection, drug sellers said that sometimes, inspectors send health assistants and sub-county chiefs for inspection visits. This cadre of people is not recognized by law as inspectors. Inspectors trained drug sellers on how to organize their drug shops better and how to use new technologies such as rapid diagnostic tests (RDTs) in diagnosing malaria. Bribes were talked about mostly by nursing assistants who purported that inspectors were not interested in inspection per se but collecting illicit payments from them. Inspectors said that the facilitation they received from the central government were inadequate for a routine inspection.

Conclusion

The current method of inspecting drug sellers is harsh and instills fear among drug sellers. There is a need to establish a well-recognized structure of inspection as well as establish channels of dialogue between inspectors and drug sellers if meaningful compliance is to be achieved. The government also needs to enhance both human and financial resources if meaningful inspection of drug sellers is to take place.
Detection of deep low-frequency earthquakes in the Nankai subduction zone over 11 years using a matched filter technique
Authors: Kato Aitaro , Nakagawa Shigeki
Published: September 2020

To improve our understanding of the long-term behavior of low-frequency earthquakes (LFEs) along the tremor belt of the Nankai subduction zone, we applied a matched filter technique to continuous seismic data recorded by a dense and highly sensitive seismic network over an 11-year window, April 2004 to August 2015. We detected a total of ~ 510,000 LFEs, or ~ 23 × the number of LFEs in the JMA catalog for the same period. During long-term slow slip events (SSEs) in the Bungo Channel, a series of migrating LFE bursts intermittently occurred along the fault-strike direction, with slow hypocenter propagation. Elastic energy released by long-term SSEs appears to control the extent of LFE activity. We identify slowly migrating fronts of LFEs during major episodic tremor and slip (ETS) events, which extend over distances of up to 100 km and follow diffusion-like patterns of spatial evolution with a diffusion coefficient of ~ 104 m2/s. This migration pattern closely matches the spatio-temporal evolution of tectonic tremors reported by previous studies. At shorter distances, up to 15 km, we discovered rapid diffusion-like migration of LFEs with a coefficient of ~ 105 m2/s. We also recognize that rapid migration of LFEs occurred intermittently in many streaks during major ETS episodes. These observations suggest that slow slip transients contain a multitude of smaller, temporally clustered fault slip events whose evolution is controlled by a diffusional process.
L-shell and energy dependence of magnetic mirror point of charged particles trapped in Earth’s magnetosphere
Authors: Soni Pankaj K. , Kakad Bharati , Kakad Amar
Published: September 2020

In the Earth’s inner magnetosphere, there exist regions like plasmasphere, ring current, and radiation belts, where the population of charged particles trapped along the magnetic field lines is more. These particles keep performing gyration, bounce and drift motions until they enter the loss cone and get precipitated to the neutral atmosphere. Theoretically, the mirror point latitude of a particle performing bounce motion is decided only by its equatorial pitch angle. This theoretical manifestation is based on the conservation of the first adiabatic invariant, which assumes that the magnetic field varies slowly relative to the gyro-period and gyro-radius. However, the effects of gyro-motion cannot be neglected when gyro-period and gyro-radius are large. In such a scenario, the theoretically estimated mirror point latitudes of electrons are likely to be in agreement with the actual trajectories due to their small gyro-radius. Nevertheless, for protons and other heavier charged particles like oxygen, the gyro-radius is relatively large, and the actual latitude of the mirror point may not be the same as estimated from the theory. In this context, we have carried out test particle simulations and found that the L-shell, energy, and gyro-phase of the particles do affect their mirror points. Our simulations demonstrate that the existing theoretical expression sometimes overestimates or underestimates the magnetic mirror point latitude depending on the value of L-shell, energy and gyro-phase due to underlying guiding centre approximation. For heavier particles like proton and oxygen, the location of the mirror point obtained from the simulation deviates considerably (∼ 10°–16°) from their theoretical values when energy and L-shell of the particle are higher. Furthermore, the simulations show that the particles with lower equatorial pitch angles have their mirror points inside the high or mid-latitude ionosphere.
Repeated measures of Heparin-binding protein (HBP) and procalcitonin during septic shock: biomarker kinetics and association with cardiovascular organ dysfunction
Authors: Tverring Jonas , Nielsen Niklas , Dankiewicz Josef , Linder Adam , Kahn Fredrik , Åkesson Per
Published: September 2020

Background

Heparin-binding protein (HBP) is a neutrophil-derived pro-inflammatory protein, an inducer of endothelial dysfunction and vascular permeability and a promising prognostic biomarker in sepsis. This exploratory study aims to describe the kinetics of plasma HBP during septic shock and investigate an association between repeated measures of HBP concentration and cardiovascular organ dysfunction severity.

Methods

We included patients at or above 18 years with suspected septic shock on admission to the intensive care unit (ICU) during 2014 and 2016 to 2018. Plasma samples were collected from ICU admission and every 4 h for 72 h or until death or ICU discharge and batch analysed for HBP. Mean arterial blood pressure (MAP) and noradrenaline dose (NA dose) were recorded at each sampling time point, and systemic vascular resistance index (SVRI) was recorded when available from non-invasive monitoring. The association between HBP, NA dose, MAP and SVRI was assessed respectively using mixed-effects linear regression models. Procalcitonin (PCT) was used as a comparator.

Results

A total of 24 patients were included. The kinetics of plasma HBP was highly variable over time, with occasional >2-fold increases and decreases in between 4-h measurements. Every 100 ng/mL increase in HBP corresponded to a 30% increase in NA dose in a crude model (95% CI 3 to 60%, p = 0.03, nobs = 340), a 1.4-mmHg decrease in MAP in an adjusted model (95% CI − 1 to − 2.3 mmHg, p = 0.04) or a 99 dyne s cm−5 m−2 decrease in SVRI in another adjusted model (95% CI − 36 to − 162, p = 0.002, npat = 13). PCT had a stronger association to NA dose than HBP in a crude model but was not significantly associated to NA dose, MAP or SVRI in any time-adjusted model.

Conclusions

Plasma HBP displayed a highly variable kinetic pattern during septic shock and was significantly associated to cardiovascular organ dysfunction severity over time.
Innovative strategies for the reception of asylum seekers and refugees in European cities: multi-level governance, multi-sector urban networks and local engagement
Authors: Oliver Caroline , Dekker Rianne , Geuijen Karin , Broadhead Jacqueline
Published: September 2020

Cities are taking a prominent role in solving global challenges, with a ‘new localism’ inviting a reorientation of power from nation-states downwards, outwards and globally. This special issue explores this phenomenon through extending the existing analyses of multi-level governance and the ‘local turn’ to the underexplored area of asylum seeker and refugee reception in European cities. The special issue draws on research in European cities where new strategies were piloted especially in the wake of ‘the refugee crisis’ from 2015, consolidating the ‘local turn’ evident in immigration and integration policy-making. The collection is in two parts: the first part explores innovation in local governance of asylum seeker reception. Here, case studies demonstrate how cities responded through forging new alliances both vertically and (especially) horizontally in networks within and between cities. The second part explores innovation in practice, analysing novel initiatives premised on local engagement and inclusivity of newcomers within the social fabric of the city. This editorial paper draws out the wider lessons of efforts from this comparative exploration of attempts to rethink asylum seeker and refugee reception at the local level.
A reflection on economic uncertainty and fertility in Europe: The Narrative Framework
Authors: Vignoli Daniele , Guetto Raffaele , Bazzani Giacomo , Pirani Elena , Minello Alessandra
Published: September 2020

The generalized and relatively homogeneous fertility decline across European countries in the aftermath of the Great Recession poses serious challenges to our knowledge of contemporary low fertility patterns. In this paper, we argue that fertility decisions are not a mere “statistical shadow of the past”, and advance the Narrative Framework, a new approach to the relationship between economic uncertainty and fertility. This framework proffers that individuals actaccording toordespiteuncertainty based on their “narrative of the future” – imagined futures embedded in social elements and their interactions. We also posit that personal narratives of the future are shaped by the “shared narratives” produced by socialization agents, including parents and peers, as well as by the narratives produced by the media and other powerful opinion formers. Finally, within this framework, we propose several empirical strategies, from both a qualitative and a quantitative perspective, including an experimental approach, for assessing the role of narratives of the future in fertility decisions.