bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deriving neighborhood-level diet and physical activity measurements from anonymized mobile phone location data for enhancing obesity estimation
Authors: Zhou Ryan Zhenqi , Hu Yingjie , Tirabassi Jill N. , Ma Yue , Xu Zhen 
Published: December 2022

Abstract
Background
Obesity is a serious public health problem. Existing research has shown a strong association between obesity and an individual’s diet and physical activity. If we extend such an association to the neighborhood level, information about the diet and physical activity of the residents of a neighborhood may improve the estimate of neighborhood-level obesity prevalence and help identify the neighborhoods that are more likely to suffer from obesity. However, it is challenging to measure neighborhood-level diet and physical activity through surveys and interviews, especially for a large geographic area.

Methods
We propose a method for deriving neighborhood-level diet and physical activity measurements from anonymized mobile phone location data, and examine the extent to which the derived measurements can enhance obesity estimation, in addition to the socioeconomic and demographic variables typically used in the literature. We conduct case studies in three different U.S. cities, which are New York City, Los Angeles, and Buffalo, using anonymized mobile phone location data from the company SafeGraph. We employ five different statistical and machine learning models to test the potential enhancement brought by the derived measurements for obesity estimation.

Results
We find that it is feasible to derive neighborhood-level diet and physical activity measurements from anonymized mobile phone location data. The derived measurements provide only a small enhancement for obesity estimation, compared with using a comprehensive set of socioeconomic and demographic variables. However, using these derived measurements alone can achieve a moderate accuracy for obesity estimation, and they may provide a stronger enhancement when comprehensive socioeconomic and demographic data are not available (e.g., in some developing countries). From a methodological perspective, spatially explicit models overall perform better than non-spatial models for neighborhood-level obesity estimation.

Conclusions
Our proposed method can be used for deriving neighborhood-level diet and physical activity measurements from anonymized mobile phone data. The derived measurements can enhance obesity estimation, and can be especially useful when comprehensive socioeconomic and demographic data are not available. In addition, these derived measurements can be used to study obesity-related health behaviors, such as visit frequency of neighborhood residents to fast-food restaurants, and to identify primary places contributing to obesity-related issues.
Bystander effect of SARS-CoV-2 spike protein on human monocytic THP-1 cell activation and initiation of prothrombogenic stimulus representing severe COVID-19
Authors: Patra Tapas , Ray Ranjit 
Published: December 2022

Abstract
Background
Hypercoagulable state and thromboembolic complications are potential life-threatening events in COVID-19 patients. Our previous studies demonstrated that SARS-CoV-2 infection as well as viral spike protein expressed epithelial cells exhibit senescence with the release of inflammatory molecules, including alarmins.

Findings
We observed extracellular alarmins present in the culture media of SARS-CoV-2 spike expressing cells activate human THP-1 monocytes to secrete pro-inflammatory cytokines to a significant level. The release of THP-1 derived pro-inflammatory cytokine signature correlated with the serum of acute COVID-19 patient, but not in post-COVID-19 state. Our study suggested that the alarmins secreted by spike expressing cells, initiated phagocytosis property of THP-1 cells. The phagocytic monocytes secreted complement component C5a and generated an autocrine signal via C5aR1 receptor. The C5a-C5aR1 signal induced formation of monocyte mediated extracellular trap resulted in the generation of a prothrombogenic stimulus with activating platelets and increased tissue factor activity. We also observed an enhanced C5a level, platelet activating factor, and high tissue factor activity in the serum of acute COVID-19 patients, but not in recovered patients.

Conclusion
Our present study demonstrated that SARS-CoV-2 spike protein modulates monocyte responses in a paracrine manner for prothrombogenic stimulus by the generation of C5a complement component.
Highly efficacious and safe neutralizing DNA aptamer of SARS-CoV-2 as an emerging therapy for COVID-19 disease
Authors: Ayass Mohamad Ammar , Tripathi Trivendra , Griko Natalya , Pashkov Victor , Dai Jun , Zhang Jin , Herbert Fabian C. , Ramankutty Nair Ramya , Okyay Tutku , Zhu Kevin , Gassensmith Jeremiah J. , Abi-Mosleh Lina 
Published: December 2022

Abstract
Background
The paucity of SARS-CoV-2-specific virulence factors has greatly hampered the therapeutic management of patients with COVID-19 disease. Although available vaccines and approved therapies have shown tremendous benefits, the continuous emergence of new variants of SARS-CoV-2 and side effects of existing treatments continue to challenge therapy, necessitating the development of a novel effective therapy. We have previously shown that our developed novel single-stranded DNA aptamers not only target the trimer S protein of SARS-CoV-2, but also block the interaction between ACE2 receptors and trimer S protein of Wuhan origin, Delta, Delta plus, Alpha, Lambda, Mu, and Omicron variants of SARS-CoV-2. We herein performed in vivo experiments that administer the aptamer to the lungs by intubation as well as in vitro studies utilizing PBMCs to prove the efficacy and safety of our most effective aptamer, AYA2012004_L.

Methods
In vivo studies were conducted in transgenic mice expressing human ACE2 (K18hACE2), C57BL/6J, and Balb/cJ. Flow cytometry was used to check S-protein expressing pseudo-virus-like particles (VLP) uptake by the lung cells and test the immuogenicity of AYA2012004_L. Ames test was used to assess mutagenicity of AYA2012004_L. RT-PCR and histopathology were used to determine the biodistribution and toxicity of AYA2012004_L in vital organs of mice.

Results
We measured the in vivo uptake of VLPs by lung cells by detecting GFP signal using flow cytometry. AYA2012004_L specifically neutralized VLP uptake and also showed no inflammatory response in mice lungs. In addition, AYA2012004_L did not induce inflammatory response in the lungs of Th1 and Th2 mouse models as well as human PBMCs. AYA2012004_L was detectable in mice lungs and noticeable in insignificant amounts in other vital organs. Accumulation of AYA2012004_L in organs decreased over time. AYA2012004_L did not induce degenerative signs in tissues as seen by histopathology and did not cause changes in the body weight of mice. Ames test also certified that AYA2012004_L is non-mutagenic and proved it to be safe for in vivo studies.

Conclusions
Our aptamer is safe, effective, and can neutralize the uptake of VLPs by lung cells when administered locally suggesting that it can be used as a potential therapeutic agent for COVID-19 management.
Studies of parenchymal texture added to mammographic breast density and risk of breast cancer: a systematic review of the methods used in the literature
Authors: Anandarajah Akila , Chen Yongzhen , Colditz Graham A. , Hardi Angela , Stoll Carolyn , Jiang Shu 
Published: December 2022

AbstractThis systematic review aimed to assess the methods used to classify mammographic breast parenchymal features in relation to the prediction of future breast cancer. The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021 to extract published articles in English describing the relationship of parenchymal texture features with the risk of breast cancer. Twenty-eight articles published since 2016 were included in the final review. The identification of parenchymal texture features varied from using a predefined list to machine-driven identification. A reduction in the number of features chosen for subsequent analysis in relation to cancer incidence then varied across statistical approaches and machine learning methods. The variation in approach and number of features identified for inclusion in analysis precluded generating a quantitative summary or meta-analysis of the value of these features to improve predicting risk of future breast cancers. This updated overview of the state of the art revealed research gaps; based on these, we provide recommendations for future studies using parenchymal features for mammogram images to make use of accumulating image data, and external validation of prediction models that extend to 5 and 10 years to guide clinical risk management. Following these recommendations could enhance the applicability of models, helping improve risk classification and risk prediction for women to tailor screening and prevention strategies to the level of risk.
DNA methylation in human gastric epithelial cells defines regional identity without restricting lineage plasticity
Authors: Fritsche Kristin , Boccellato Francesco , Schlaermann Philipp , Koeppel Max , Denecke Christian , Link Alexander , Malfertheiner Peter , Gut Ivo , Meyer Thomas F. , Berger Hilmar 
Published: December 2022

AbstractBackgroundEpigenetic modifications in mammalian DNA are commonly manifested by DNA methylation. In the stomach, altered DNA methylation patterns have been observed following chronicHelicobacter pyloriinfections and in gastric cancer. In the context of epigenetic regulation, the regional nature of the stomach has been rarely considered in detail.ResultsHere, we establish gastric mucosa derived primary cell cultures as a reliable source of native human epithelium. We describe the DNA methylation landscape across the phenotypically different regions of the healthy human stomach, i.e., antrum, corpus, fundus together with the corresponding transcriptomes. We show that stable regional DNA methylation differences translate to a limited extent into regulation of the transcriptomic phenotype, indicating a largely permissive epigenetic regulation. We identify a small number of transcription factors with novel region-specific activity and likely epigenetic impact in the stomach, including GATA4, IRX5, IRX2, PDX1 and CDX2. Detailed analysis of the Wnt pathway reveals differential regulation along the craniocaudal axis, which involves non-canonical Wnt signaling in determining cell fate in the proximal stomach. By extending our analysis to pre-neoplastic lesions and gastric cancers, we conclude that epigenetic dysregulation characterizes intestinal metaplasia as a founding basis for functional changes in gastric cancer. We present insights into the dynamics of DNA methylation across anatomical regions of the healthy stomach and patterns of its change in disease. Finally, our study provides a well-defined resource of regional stomach transcription and epigenetics.
Longitudinal profiling in patients undergoing cardiac surgery reveals postoperative changes in DNA methylation
Authors: Fischer Matthew A. , Chapski Douglas J. , Soehalim Elizabeth , Montoya Dennis J. , Grogan Tristan , Pellegrini Matteo , Cai Hua , Shemin Richard J. , Vondriska Thomas M. 
Published: December 2022

AbstractBackgroundCardiac surgery and cardiopulmonary bypass induce a substantial immune and inflammatory response, the overactivation of which is associated with significant pulmonary, cardiovascular, and neurologic complications. Commensurate with the immune and inflammatory response are changes in the heart and vasculature itself, which together drive postoperative complications through mechanisms that are poorly understood. Longitudinal DNA methylation profiling has the potential to identify changes in gene regulatory mechanisms that are secondary to surgery and to identify molecular processes that predict and/or cause postoperative complications. In this study, we measure DNA methylation in preoperative and postoperative whole blood samples from 96 patients undergoing cardiac surgery on cardiopulmonary bypass.ResultsWhile the vast majority of DNA methylation is unchanged by surgery after accounting for changes in cell-type composition, we identify several loci with statistically significant postoperative changes in methylation. Additionally, two of these loci are associated with new-onset postoperative atrial fibrillation, a significant complication after cardiac surgery. Paired statistical analysis, use of FACS data to support sufficient control of cell-type heterogeneity, and measurement of IL6 levels in a subset of patients add rigor to this analysis, allowing us to distinguish cell-type variability from actual changes in methylation.ConclusionsThis study identifies significant changes in DNA methylation that occur immediately after cardiac surgery and demonstrates that these acute alterations in DNA methylation have the granularity to identify processes associated with major postoperative complications. This research also establishes methods for controlling for cell-type variability in a large human cohort that may be useful to deploy in other longitudinal studies of epigenetic marks in the setting of acute and chronic disease.
Physician education on World Asthma Day aids in disease management during the COVID-19
Authors: Cao Angyang , Zhou Yanling , Luo Wenjun , Lv Dan , Shao Zhonghao , Zhu Binbin , Wang Jianhua 
Published: December 2022

AbstractAnxiety and depression can negatively affect the management of asthma. The study aimed to assess the psychosocial effects of asthma patients during COVID-19 and analyze potential risk factors and interventions.In June 2022, the “Questionnaire Star” electronic questionnaire system was used to collect data. A total of 98 asthma patients from the affiliated hospital of the medical school of Ningbo University were invited to complete the questionnaires. According to our study, the prevalence of symptoms of anxiety and depression in the asthma patients in the institution was 91.8 and 77.6%, respectively. Patients who had an asthma exacerbation in the previous two months were more likely to have anxiety symptoms (OR = 0.142 95%CI 0.025–0.820), while patients who did not participate in asthma day activities were more likely to have anxiety symptoms than those who did (OR = 0.130 95%CI 0.022–0.762).This study found that routine disease educational lectures on asthma day can successfully alleviate asthma sufferers' anxiety and depression.
Inhibition of PI3 kinase isoform p110α suppresses neuroblastoma growth and induces the reduction of Anaplastic Lymphoma Kinase
Authors: Guo Yue , Guo Donghao , Zhang Shaoting , Zhang Yuan , He Xiaoyan , Jiang Xiaohua , Chan Andrew Man-Lok , Zou Lin , Sun Jianmin , Zhao Hui 
Published: December 2022

Abstract
Background
In neuroblastoma, hyperactivation of the PI3K signaling pathway has been correlated with aggressive neuroblastomas, suggesting PI3Ks as promising targets for the treatment of neuroblastoma. However, the oncogenic roles of individual PI3K isoforms in neuroblastoma remain elusive.

Results
We found that PI3K isoform p110α was expressed at higher levels in neuroblastoma tissues compared with normal tissues, and its high expression was correlated with an unfavorable prognosis of neuroblastoma. Accordingly, PI3K activation in neuroblastoma cells was predominantly mediated by p110α but not by p110β or p110δ. Suppression of p110α inhibited the growth of neuroblastoma cells both in vitro and in vivo, suggesting a crucial role of p110α in the tumorigenesis of neuroblastoma. Mechanistically, inhibition of p110α decreased anaplastic lymphoma kinase (ALK) in neuroblastoma cells by decreasing its protein stability.

Conclusions
In this study, we investigated the oncogenic roles of PI3K isoforms in neuroblastoma. Our data shed light on PI3K isoform p110α in the tumorigenesis of neuroblastoma, and strongly suggest the p110α inhibitors as potential drugs in treating neuroblastoma.
Protocol for a scoping review of potential vaccine candidates predicted by VaxiJen for different viral pathogens between 2017–2021
Authors: Salod Zakia , Mahomed Ozayr 
Published: December 2022

Abstract

Background
Vaccination is essential for the prevention of infectious diseases and has helped to reduce disease-related mortality, such as pneumonia. However, traditional vaccine development is time-consuming and risky. Reverse vaccinology (RV) is a promising alternative to developing vaccines based on the in silico discovery of antigens, often termed ‘potential vaccine candidates’ (PVCs), using a pathogen’s proteome. RV prediction technologies, such as VaxiJen (founded in 2007), are used to take the first step toward vaccine development. VaxiJen is used by researchers to identify PVCs for various diseases. A 10-year review of these PVCs was published in 2017. There has since been no review of viral PVCs predicted by VaxiJen from 2017 to 2021. The proposed scoping review aims to address this gap.

Methods
This protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 checklist. The review will employ Arksey and O’Malley’s five-stage methodological framework, which was later enhanced by Levac et al. and the Joanna Briggs Institute (JBI). The PRISMA extension for Scoping Reviews (PRISMA-ScR) reporting guideline will be utilized with this framework. PubMed, Scopus, Web of Science, EBSCOhost, and ProQuest One Academic will be searched using the term ‘vaxijen’. The inclusion criteria will be English-only full-text original articles published in peer-reviewed journals and unpublished papers from 2017 to 2021. Rayyan will be used to deduplicate, screen titles and abstracts of articles. The articles’ full texts will be examined. The data will be extracted using Microsoft Excel. Using a data charting form, data will be sifted and organized by key categories and themes.

Discussion
This protocol was submitted for publication and went through an extensive peer review process. The review has implications for novel vaccine development against various viruses. The key limitation of this study is language bias due to the selection of English-only papers because of limited resources. This study will not require ethical clearance since it will use secondary data and will not include patients. Nevertheless, this research is part of a larger project that was submitted for ethical consideration to the Biomedical Research Ethics Committee of the University of KwaZulu-Natal in South Africa. This study’s findings will be published in a peer-reviewed journal and provided to relevant stakeholders.

Systematic review registration
Open Science Framework (OSF): https://osf.io/ht8wr
Fertilisation with compost mitigates salt stress in tomato by affecting plant metabolomics and nutritional profiles
Authors: Savy Davide , Cozzolino Vincenza , Vinci Giovanni , Verrillo Mariavittoria , Aliberti Antonietta , Maggio Albino , Barone Amalia , Piccolo Alessandro 
Published: December 2022

Abstract
Background
Salinity is one of the major threats for crop growth and yield and its rate of expansion is expected to increase. We conducted a pot experiment to evaluate and compare the effect of a green compost addition and mineral fertilisation, on growth, nutrition and metabolites of tomato plants, exposed to increasing doses of NaCl.

Results
Although the development of stressed plants was lower than the corresponding controls, compost-treated plants performed better than mineral-amended plants watered with the same amount of salt. The different plant growth was related to an increased nutritional status. Namely, compost-treated plants showed a larger content of macro- and micronutrients, and a greater accumulation of osmoprotectants, such as soluble sugars and amino acids. Moreover, compost-treated plants showed a larger content of metabolites involved in modulating the response to salt stress, such as molecules related to energy transfer in plants and precursors of Reactive Oxygen Species scavenging compounds. Overall, the better performance of compost-added plants may be attributed to a greater availability of the organic forms of nutrients and to the positive bioactivity of compost-derived humic substances.

Conclusions
Compost application efficiently mitigated salt stress in tomato plants in respect to mineral fertilisation. This alleviating role was associated to the induction of a more efficient metabolic response that increased accumulation of metabolites involved in modulating the salinity stress. Therefore, fertilising with composted agricultural residue may represent a convenient alternative to mineral fertilisers to grow tomato plants in the presence of salt stress.

Graphical Abstract
Assessment of knowledge, attitude, and practice regarding the disposal of expired and unused medications among the Lebanese population
Authors: Hajj Aline , Domiati Souraya , Haddad Chadia , Sacre Hala , Akl Maria , Akel Marwan , Tawil Samah , Abramian Soula , Zeenny Rony M. , Hodeib Fadi , Salameh Pascale 
Published: December 2022

Abstract
Background
Medication waste is a public health problem affecting developed and developing countries. In Lebanon, a developing country in the Middle East, efforts are being deployed in hospitals but not in the community.

Objective
This study aimed to validate a questionnaire to explore the knowledge, attitude, and practice (KAP) towards the disposal of unused and expired medicines among the Lebanese population and then identify the factors associated with these variables comparatively between the general population and healthcare professionals.

Methods
A cross-sectional study was conducted among the general Lebanese population in May–June 2022 using a standardized questionnaire. The validity and reliability of the KAP scales were assessed, then a thorough statistical analysis was done to explore the factors associated with these scales.

Results
The KAP scales generated by this study were valid and reliable. Using these scales, 24.5%, 22.6%, and 21% of participants demonstrated proper knowledge, attitude, and practice, respectively. Higher knowledge scores were significantly associated with female gender (Beta = 0.97), a high monthly income (Beta = 1.68), a secondary (Beta = 6.11) or university (Beta = 6.80) education level, and postgraduate education (Beta = 7.13). However, older age (Beta = − 0.06) and a low monthly income (Beta = − 3.06) were significantly associated with lower knowledge scores. A higher knowledge score (Beta = 0.06) was significantly associated with a more positive attitude regarding unused or expired medication disposal. Being a healthcare professional (Beta = 0.72) was significantly associated with a higher practice score, while being a female (Beta = − 0.32) and living in a rural area (Beta = − 0.37) were significantly associated with lower practice scores.

Conclusion
This study validated KAP scales regarding medication waste in Lebanon and showed low KAP scores in the majority of respondents. Factors associated with higher KAP scores in various aspects of medication disposal, including gender, age, education level, and profession (healthcare professionals), suggest the need to consider those when implementing targeted corrective measures. Although further studies are required to confirm our findings, this study could be the ground for a medication waste management national strategy in Lebanon.