bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractIn 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

AbstractBackgroundThe 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 bodyCTLA-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.ConclusionThe 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

AbstractBackgroundTo 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.MethodsA 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.ResultsWe 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.ConclusionsNeither 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

Abstract
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

AbstractThe 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

Abstract
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

AbstractDrugs 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

AbstractBackgroundLong 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.ResultsAblation 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.ConclusionsWe 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

AbstractMesenchymal 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

AbstractWe 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

AbstractThis 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

AbstractThis 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

AbstractUnderstanding 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.