bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences and management of physician psychological symptoms during infectious disease outbreaks: a rapid review
Authors: Fiest Kirsten M. , Parsons Leigh Jeanna , Krewulak Karla D. , Plotnikoff Kara M. , Kemp Laryssa G. , Ng-Kamstra Joshua , Stelfox Henry T.
Published: February 2021

Background

Prior to the COVID-19 pandemic, physicians experienced unprecedented levels of burnout. The uncertainty of the ongoing COVID-19 pandemic along with increased workload and difficult medical triage decisions may lead to a further decline in physician psychological health.

Methods

We searched Medline, EMBASE, and PsycINFO for primary research from database inception (Medline [1946], EMBASE [1974], PsycINFO [1806]) to November 17, 2020. Titles and abstracts were screened by one of three reviewers and full-text article screening and data abstraction were conducted independently, and in duplicate, by three reviewers.

Results

From 6223 unique citations, 480 articles were reviewed in full-text, with 193 studies (of 90,499 physicians) included in the final review. Studies reported on physician psychological symptoms and management during seven infectious disease outbreaks (severe acute respiratory syndrome [SARS], three strains of Influenza A virus [H1N1, H5N1, H7N9], Ebola, Middle East respiratory syndrome [MERS], and COVID-19) in 57 countries. Psychological symptoms of anxiety (14.3–92.3%), stress (11.9–93.7%), depression (17–80.5%), post-traumatic stress disorder (13.2–75.2%) and burnout (14.7–76%) were commonly reported among physicians, regardless of infectious disease outbreak or country. Younger, female (vs. male), single (vs. married), early career physicians, and those providing direct care to infected patients were associated with worse psychological symptoms.

Interpretation

Physicians should be aware that psychological symptoms of anxiety, depression, fear and distress are common, manifest differently and self-management strategies to improve psychological well-being exist. Health systems should implement short and long-term psychological supports for physicians caring for patients with COVID-19.
Family income and health in Canada: a longitudinal study of stability and change
Authors: Vanzella-Yang Adam , Veenstra Gerry
Published: February 2021

Background

Extensive research has shown strong associations between income and health. However, the health effects of income dynamics over time are less known. We investigated how stability, volatility and trajectory in family incomes from 2002 to 2011 predicted (1) fair/poor self-rated health and (2) the presence of a longstanding illness or health problem in 2012.

Methods

The data came from the 2012 wave of the Longitudinal and International Study of Adults linked to annual family income data for 2002 to 2011 from the Canada Revenue Agency. We executed a series of binary logistic regressions to examine associations between health and average family income over the decade (Model 1), number of years in the bottom quartile (Model 2) and top quartile (Model 3) of family incomes, standard deviation of family incomes (Model 4), absolute difference between family income at the end and start of the period (Model 5), and number of years in which inflation-adjusted family income went down by more than 1% (Model 6) and up by more than 1% (Model 7) from 1 year to the next. The analyses were conducted separately for women and men.

Results

Average family income over the decade was strongly associated with both self-rated health and the presence of a longstanding illness or health problem. More years spent in the bottom quartile of family incomes corresponded to elevated odds of fair/poor self-rated health and the presence of a longstanding illness or health problem. Steady decreases in family income over the decade corresponded to elevated odds of fair/poor self-rated health for men and more years spent in the top quartile of family incomes over the decade corresponded to elevated odds of fair/poor self-rated health for women.

Conclusion

Previous studies of the association between family income and health in Canada may have overlooked important issues pertaining to family income stability and change that are impactful for health.
Prevalence and correlates of dental service utilisation among a national general adult population sample in Sudan
Authors: Pengpid Supa , Peltzer Karl
Published: February 2021

Background

Prompt dental service utilisation (DSU) is needed for the prevention and treatment of oral diseases, and it is therefore important to determine the facilitators and barriers of DSU. There is, however, scarce information available on DSU in Sudan. Therefore, this study aimed to investigate the prevalence and associated factors of DSU in a general population-based survey among 18–69 year-old persons in Sudan.

Methods

Cross-sectional nationally representative data of 7,722 18–69 year-old persons (36 years median age) from the 2016 Sudan Stepwise approach to surveillance (STEPS) survey were analysed. Using questionnaire, anthropometric and biochemical measures, predisposing, enabling and health and lifestyle factors of DSU were assessed. Multinomial logistic regression was conducted to estimate the predictors of DSU (> 12 months and past 12 months, with never DSU as the reference category).

Results

About two-thirds of the participants (64.6%) had never DSU, 22.0% had more than 12-month DSU, and 13.4% had past 12- month DSU. Among those who had ever DSU, the main reason for the last DSU was pain or trouble with teeth, gums, or mouth (66.9%), treatment or follow-up treatment 22.3%, and routine check-up treatment 5.0%. In adjusted multinomial logistic regression analysis, higher education (p < 0.001), urban residence (p < 0.001), screened for blood pressure (p < 0.001), raised total cholesterol (p < 0.05), poor SROH (p < 0.001), pain in teeth or mouth (p < 0.001), and not working because of teeth or mouth (p < 0.01) were positively and not knowing their household income (p < 0.01), high physical activity (p < 0.05), and having 20 or more teeth (p < 0.001), were negatively associated with both > 12 months and past 12 months DSU. Higher household income (p < 0.001), overweight/obesity (p < 0.05), using tooth paste (p < 0.001), and difficulty chewing (p < 0.001), were positively, and male sex (p < 0.01), and teeth cleaning twice or more times a day (p < 0.05), were negatively associated with > 12 months or past 12 months DSU.

Conclusion

More than one in ten participants had past 12 months DSU and several factors were detected which could be targeted in intervention activities. Study findings suggest to improve oral health awareness, in particular stressing the relevance of regular dental check-ups, by using different modalities of oral health promotion.
The enzymatic hydrolysates from deer sinew promote MC3T3-E1 cell proliferation and extracellular matrix synthesis by regulating multiple functional genes
Authors: Zhou Zhenwei , Zhao Daqing , Zhang Pengcheng , Zhang Mei , Leng Xiangyang , Yao Baojin
Published: February 2021

Background

Deer Sinew serves as a medicinal food, and has been used for treating skeletal diseases, especially bone diseases in a long history. Thus, it could become an alternative option for the prevention and therapeutic remedy of bone-related diseases. In our previous study, we established an optimal extraction process of the enzymatic hydrolysates from Chinese Sika deer sinews (DSEH), and we demonstrated that DSEH significantly promoted the proliferation of MC3T3-E1 cells (an osteoblast-like cell line) with a certain dose-effect relationship. However, the precise molecular mechanism of deer sinew in regulating bone strength is still largely unknown. The aim of this study was to explore the underlying molecular mechanism of DSEH on MC3T3-E1 cells proliferation and extracellular matrix synthesis.

Methods

Preparation and quality control were performed as previously described. The effect of DSEH at different administrated concentrations on cell proliferation was measured using both CCK-8 and MTT assays, and the capacity of DSEH on extracellular matrix synthesis was detected by Alizarin red staining and quantification. The gene expression pattern change of MC3T3-E1 cells under the treatment of DSEH was investigated by RNA-seq analysis accompanied with validation methods.

Results

We demonstrated that DSEH promoted MC3T3-E1 cell proliferation and extracellular matrix synthesis by regulating multiple functional genes. DSEH significantly increased the expression levels of genes that promoted cell proliferation such as Gstp1, Timp1, Serpine1, Cyr61, Crlf1, Thbs1, Ctgf, P4ha2, Sod3 and Nqo1. However, DSEH significantly decreased the expression levels of genes that inhibited cell proliferation such as Mt1, Cdc20, Gas1, Nrp2, Cmtm3, Dlk2, Sema3a, Rbm25 and Hspb6. Furthermore, DSEH mildly increased the expression levels of osteoblast gene markers.

Conclusions

Our findings suggest that DSEH facilitate MC3T3-E1 cell proliferation and extracellular matrix synthesis to consolidate bone formation and stability, but prevent MC3T3-E1 cells from oxidative stress-induced damage, apoptosis and further differentiation. These findings deepened the current understanding of DSEH on regulating bone development, and provided theoretical support for the discovery of optional prevention and treatment for bone-related diseases.
Dendritic cells transduced with TIPE-2 recombinant adenovirus induces T cells suppression
Authors: Liu Shudong , Wang Jie , Li Wenyan , Shi Hui , Zhou Changlong , Tang Ge , Zhang Jiangwei , Yang Zhao
Published: February 2021

Introduction

TIPE-2 has been identified as a negative regulator of both innate and adaptive immunity and is involved in several inflammatory diseases. However, the role of immune suppression of dendritic cells (DCs) transduced with TIPE-2 has not been well studied.

Methods

In this study, DCs were transduced with TIPE-2 recombinant adenovirus, and then were cocultured with allogeneic CD4+ or CD8 + T cells. The proliferation, cytokine production and activation marker levels of CD4+ or CD8 + T cell were detected.

Results

The data demonstrated that T cell proliferation, cytokine production and activation marker levels were attenuated after treated with TIPE-2 transduced DCs.

Conclusions

These results suggested that TIPE-2 transduced DCs are capable of inducing allogeneic CD4+ or CD8 + T cell immune suppression, which provide a promising way for the therapeutical strategies of transplantation or autoimmune diseases.
Correction to: High dose rate intra-cavitary brachytherapy with cobalt 60 source for locally advanced cervical cancer: the Zimbabwean experience
Authors: Chibonda Shirley , Ndlovu Ntokozo , Tsikai Nomsa , Munangaidzwa Lameck , Ndarukwa Sandra , Nyamhunga Albert , Mazhindu Tinashe
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Mixed phenotype acute leukemia with PML-RARα positive: a case report and literature review
Authors: Zheng Xiaolong , Shen Huafei , Zhu Mingyu , Shi Yuanfei , Wang Huanping , Chen Zhimei , Huang Xin , Wang Yungui , Jin Jie , Xie Wanzhuo
Published: February 2021

Mixed phenotype acute leukemia (MPAL) is an uncommon type of leukemia. It is one kind of malignant clonal diseases that expresses more than one genealogical specific antigen simultaneously. Most MPAL patients are associated with clonal chromosomal abnormalities and molecular genetic changes, such as t(9;22) (q34;q11) and KMT2A (MLL) rearrangement. These specific abnormalities usually have important guiding significance in MPAL diagnosis, targeted therapy and prognosis judgment. In this paper, we reported a case of MPAL, T/myeloid (M5) with an unfrequent combination of PML-RARα positivity and t(15;17). The treatment was successful with chemotherapy for both AML and ALL with daunorubicin, cytarabine (DA) and vincristine, prednisone (VP). We reported here this suggestive MPAL case of rare disease condition and effective treatment, in order to provide experience for the early diagnosis and treatment of similar patients.
Novel pH-responsive nanohybrid for simultaneous delivery of doxorubicin and paclitaxel: an in-silico insight
Authors: Alimohammadi Ehsan , Maleki Reza , Akbarialiabad Hossein , Dahri Mohammad
Published: February 2021

Background

The distribution of drugs could not be controlled in the conventional delivery systems. This has led to the developing of a specific nanoparticle-based delivery system, called smart drug delivery systems. In cancer therapy, innovative biocompatible nanocarriers have received much attention for various ranges of anti-cancer drugs. In this work, the effect of an interesting and novel copolymer named "dimethyl acrylamide-trimethyl chitosan" was investigated on delivery of paclitaxel and doxorubicin applying carboxylated fullerene nanohybrid. The current study was run via molecular dynamics simulation and quantum calculations based on the acidic pH differences between cancerous microenvironment and normal tissues. Furthermore, hydrogen bonds, radius of gyration, and nanoparticle interaction energies were studied here. Stimulatingly, a simultaneous pH and temperature-responsive system were proposed for paclitaxel and doxorubicin for a co-polymer. A pH-responsive and thermal responsive copolymer were utilized based on trimethyl chitosan and dimethyl acrylamide, respectively. In such a dualistic approach, co-polymer makes an excellent system to possess two simultaneous properties in one bio-polymer.

Results

The simulation results proposed dramatic and indisputable effects of the copolymer in the release of drugs in cancerous tissues, as well as increased biocompatibility and drug uptake in healthy tissues. Repeated simulations of a similar article performed for the validation test. The results are very close to those of the reference paper.

Conclusions

Overall, conjugated modified fullerene and dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) as nanohybrid can be an appropriate proposition for drug loading, drug delivery, and drug release on dual responsive smart drug delivery system.
Epidemiologic profile of viral hepatitis B and C in North of Iran: results from PERSIAN Guilan Cohort Study (PGCS)
Authors: Mansour-Ghanaei Fariborz , Joukar Farahnaz , Naghipour Mohammadreza , Hassanipour Soheil , Yeganeh Sara , Sepehrimanesh Masood , Fathalipour Mohammad
Published: February 2021

Objective

Hepatitis B (HB) and C (HC) are two severe viral infectious diseases with a deleterious impact on global health. This study aimed to evaluate the prevalence of HB and HC in the Prospective Epidemiological Research Studies of the Iranian Adults (PERSIAN) Guilan Cohort Study using immunological and molecular methods.

Results

The blood samples were obtained from 10,520 enrolled participants. Complete biochemical and hematological tests, as well as urine analysis, were assessed. The presence of HBsAg, anti-HBs, anti-HBc, and anti-HCV antibodies for all participant and HBeAg and anti-HBe antibodies for HB-positive patients were evaluated. Moreover, HB genomic DNA and HC genomic RNA were extracted from serum samples of HB-positive patients. The real-time PCR assay was employed to quantify the gene copies of hepatitis B and C viruses. HC genotyping was also performed. The prevalence of HB and HC was 0.24% (95% CI 0.16–0.35) and 0.11% (95% CI 0.06–0.19), respectively. Rural participants were significantly more HB-positive than the urban people (P = 0.045), while males were significantly more HC-positive than the females (P = 0.013). The prevalence of HB and HC in this area were lower than those of other geographical locations of Iran, which may be due to different lifestyles or other unknown reasons.
The use of angiotensin-converting enzyme inhibitors vs. angiotensin receptor blockers and cognitive decline in Alzheimer’s disease: the importance of blood-brain barrier penetration and APOE ε4 carrier status
Authors: Ouk Michael , Wu Che-Yuan , Rabin Jennifer S. , Jackson Aaron , Edwards Jodi D. , Ramirez Joel , Masellis Mario , Swartz Richard H. , Herrmann Nathan , Lanctôt Krista L. , Black Sandra E. , Swardfager Walter
Published: February 2021

Background

The antihypertensive angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACE-Is) have similar indications and mechanisms of action, but prior work suggests divergence in their effects on cognition.

Methods

Participants in the National Alzheimer’s Coordinating Center database with a clinical diagnosis of dementia due to Alzheimer’s disease (AD) using an ACE-I or an ARB at any visit were selected. The primary outcome was delayed recall memory on the Wechsler Memory Scale Revised – Logical Memory IIA. Other cognitive domains were explored, including attention and psychomotor processing speed (Trail Making Test [TMT]-A and Digit Symbol Substitution Test [DSST]), executive function (TMT-B), and language and semantic verbal fluency (Animal Naming, Vegetable Naming, and Boston Naming Tests). Random slopes mixed-effects models with inverse probability of treatment weighting were used, yielding rate ratios (RR) or regression coefficients (B), as appropriate to the distribution of the data. Apolipoprotein (APOE) ε4 status and blood-brain barrier (BBB) penetrance were investigated as effect modifiers.

Results

Among 1689 participants with AD, ARB use (n = 578) was associated with 9.4% slower decline in delayed recall performance over a mean follow-up of 2.28 years compared with ACE-I use (n = 1111) [RR = 1.094, p = 0.0327]; specifically, users of BBB-crossing ARBs (RR = 1.25, p = 0.002), BBB-crossing ACE-Is (RR = 1.16, p = 0.010), and non-BBB-crossing ARBs (RR = 1.20, p = 0.005) had better delayed recall performance over time compared with non-BBB-crossing ACE-I users. An interaction with APOE ε4 status (drug × APOE × time RR = 1.196, p = 0.033) emerged; ARBs were associated with better delayed recall scores over time than ACE-Is in non-carriers (RR = 1.200, p = 0.003), but not in carriers (RR = 1.003, p = 0.957). ARB use was also associated with better performance over time on the TMT-A (B = 2.023 s, p = 0.0004) and the DSST (B = 0.573 symbols, p = 0.0485), and these differences were significant among APOE ε4 non-carriers (B = 4.066 s, p = 0.0004; and B = 0.982 symbols, p = 0.0230; respectively). Some differences were seen also in language and verbal fluency among APOE ε4 non-carriers.

Conclusions

Among APOE ε4 non-carriers with AD, ARB use was associated with greater preservation of memory and attention/psychomotor processing speed, particularly compared to ACE-Is that do not cross the blood-brain-barrier.
Estrogen receptors in pain modulation: cellular signaling
Authors: Chen Qing , Zhang Wenxin , Sadana Neeti , Chen Xinzhong
Published: February 2021

Sensory perception and emotional disorders are disproportionally represented in men and women and are thus thought to be modulated by different sex hormones in various conditions. Among the most important hormones perceived to affect sensory processing and transduction is estrogen. Numerous previous researchers have endeavored to demonstrate that estrogen is capable of modulating the activity of sensory neurons in peripheral and central sites in female, male, or castrated animals. However, the underlying mechanisms of its modulation of neuronal activity are somewhat unclear. In the present review, we discuss the possible cellular and molecular mechanisms involved in the modulation of nociception by estrogen.
ChemSpectra: a web-based spectra editor for analytical data
Authors: Huang Yu-Chieh , Tremouilhac Pierre , Nguyen An , Jung Nicole , Bräse Stefan
Published: February 2021

ChemSpectra, a web-based software to visualize and analyze spectroscopic data, integrating solutions for infrared spectroscopy (IR), mass spectrometry (MS), and one-dimensional 1H and 13C NMR (proton and carbon nuclear magnetic resonance) spectroscopy, is described. ChemSpectra serves as web-based tool for the analysis of the most often used types of one-dimensional spectroscopic data in synthetic (organic) chemistry research. It was developed to support in particular processes for the use of open file formats which enable the work according to the FAIR data principles. The software can deal with the open file formats JCAMP-DX (IR, MS, NMR) and mzML (MS) proposing these data file types to gain interoperable data. ChemSpectra can be extended to read also other formats as exemplified by selected proprietary mass spectrometry data files of type RAW and NMR spectra files of type FID. The JavaScript-based editor can be integrated with other software, as demonstrated by integration into the Chemotion electronic lab notebook (ELN) and Chemotion repository, demonstrating the implementation into a digital work environment that offers additional functionality and sustainable research data management options. ChemSpectra supports different functions for working with spectroscopic data such as zoom functions, peak picking and automatic peak detection according to a default or manually defined threshold. NMR specific functions include the definition of a reference signal, the integration of signals, coupling constant calculation and multiplicity assignment. Embedded into a web application such as an ELN or a repository, the editor can also be used to generate an association of spectra to a sample and a file management. The file management supports the storage of the original spectra along with the last edited version and an automatically generated image of the spectra in png format. To maximize the benefit of the spectra editor for e.g. ELN users, an automated procedure for the transfer of the detected or manually chosen signals to the ELN was implemented. ChemSpectra is released under the AGPL license to encourage its re-use and further developments by the community.
Laboratory studies of the algaecide GreenTD: stability, algaecidal activity and reduction of microcystin production
Authors: Cho Il Kyu , Seol Jae Ung , Rahman Md. Musfiqur , Lee Dong-Gi , Son Hyeongkyu , Cho Hoon
Published: February 2021

GreenTD (Dichlorobenzyl derivative, MW 362.17) is a new dichlorobenzyl derivative algaecide. It is effective and selective against harmful algal blooms (HABs). HABs cause serious problems for public health and fishery industries. Algae that cause HABs include Microcystis spp., Anabaena spp., and Aphanizomenon spp. Blooms of toxin-producing Microcystis aeruginosa occur regularly in fresh water where is rich in nitrogen and phosphorus nutrients. Environmental fate studies are needed to investigate the degradation of GreenTD. In the present study, we studied the persistence of GreenTD (90% aqueous solution) in water and toxic effects GreenTD on M. aeruginosa and reduction of microcystin production in the culture media. GreenTD was added in the water pots and microcystis media tubes at levels of 25 g/0.1 ha (0.5 mg/kg) and 50 g/0.1 ha (1.0 mg/kg). Samples were collected after 1, 3, 5, 7 and 14 days. The residues of GreenTD and microcystins in water and the media were determined using high performance liquid chromatography-diode array detection and ultra-performance liquid chromatography-tandem mass spectrometry, respectively. The half-life of GreenTD at concentrations of 0.5 and 1.0 mg/kg was 4.5 and 3.6 days, respectively. This result presents a safety level suitable for the acceptable guideline of water residue. The average recoveries of microcystins RR, YR, LR, and LA were 106–115%, 103–110%, 96–105% and 89–113% in the microcystis media, respectively. The limit of detection of (LOD) the microcystins was 0.1 µg/kg. No microcystins in the media were detected at the LOD (0.1 µg/kg). GreenTD at concentrations of 0.2 and 0.5 µg/kg had a 100% of control efficacy of M. aeruginosa. No growth of the blue-green algae was observed after 14 days of GreenTD application.
Treatment of compulsive exercise in eating disorders and muscle dysmorphia: protocol for a systematic review
Authors: Martenstyn Jordan Andre , Touyz Stephen , Maguire Sarah
Published: February 2021

Background

Compulsive exercise is a core feature of both eating disorders and muscle dysmorphia. Earlier models of treatment recommended complete abstinence from exercise in eating disorder populations, but recent guidelines advocate for the gradual inclusion of healthier forms of exercise into an overall treatment plan where appropriate. Given the association between problematic exercise behaviour and poorer prognosis, there has been a recent upsurge in the number of treatment interventions for compulsive exercise in eating disorders. However, no systematic review has been published summarising this existing treatment literature. The aim of this review is to determine the efficacy of existing treatments for compulsive exercise in eating disorders and muscle dysmorphia.

Methods

A systematic review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases (PsycInfo, MEDLINE, Embase, Web of Science, and Scopus) will be searched from database inception until November 2020. We will include studies that: (a) sampled adolescents and/or adults with either an eating disorder or muscle dysmorphia; (b) assessed changes in compulsive exercise from pre- to post-intervention; and (c) used a standardised instrument to measure compulsive exercise or related constructs. We will include studies with a comparison group (e.g., randomised controlled trials) and without a comparison group (e.g., pilot studies and case studies) to provide a comprehensive overview of the literature. One reviewer will screen all titles and abstracts against eligibility criteria, with 20% of excluded articles cross-referenced by another reviewer. Full texts will be obtained for articles deemed relevant or where inclusion was uncertain, and will be screened by both reviewers. We will also evaluate the quality of the included studies using a modified Downs and Black (J Epidemiol Community Health 52:377–384, 1998) assessment checklist.

Discussion

Results from this review will help to determine the most efficacious treatment components for compulsive exercise in eating disorders and muscle dysmorphia. We hope that our results will help inform clinical practice guidelines in recommending targeted interventions for the treatment of compulsive exercise.
Early termination of vocational training: dropout or stopout?
Authors: Wydra-Somaggio Gabriele
Published: February 2021

Dropping out of the educational system has marked negative consequences in the labour market. Dropping out is followed by an early termination that does not necessarily mean leaving the educational system without graduating. Trainees may reassess their initial choice by starting another vocational education and training (VET) programme and preserve their labour market chances when graduating. This paper examines the factors that drive the decision to stop out (start new vocational training) after an early termination. The analysis is based on a data set for VET in Germany (Ausbildungspanel Saarland) that contains detailed information on the VET careers and labour market outcomes of almost 3000 apprentices who terminated their education early. The results show that approximately 71 percent of apprentices continue with another VET programme after a termination. Termination at an early stage of VET and training in a small establishment are more likely to lead to stopping out than to dropping out. Stopouts who terminate their contracts during an early stage of their VET programme are more likely to change their occupation and obtain a formal VET degree. The results suggest that dissatisfaction with VET must be recognized at an early stage in order for students to take appropriate measures with the aim of graduation.
Evaluation of candidate models for the 13th generation International Geomagnetic Reference Field
Authors: Alken P. , Thébault E. , Beggan C. D. , Aubert J. , Baerenzung J. , Brown W. J. , Califf S. , Chulliat A. , Cox G. A. , Finlay C. C. , Fournier A. , Gillet N. , Hammer M. D. , Holschneider M. , Hulot G. , Korte M. , Lesur V. , Livermore P. W. , Lowes F. J. , Macmillan S. , Nair M. , Olsen N. , Ropp G. , Rother M. , Schnepf N. R. , Stolle C. , Toh H. , Vervelidou F. , Vigneron P. , Wardinski I.
Published: February 2021

In December 2019, the 13th revision of the International Geomagnetic Reference Field (IGRF) was released by the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group V-MOD. This revision comprises two new spherical harmonic main field models for epochs 2015.0 (DGRF-2015) and 2020.0 (IGRF-2020) and a model of the predicted secular variation for the interval 2020.0 to 2025.0 (SV-2020-2025). The models were produced from candidates submitted by fifteen international teams. These teams were led by the British Geological Survey (UK), China Earthquake Administration (China), Universidad Complutense de Madrid (Spain), University of Colorado Boulder (USA), Technical University of Denmark (Denmark), GFZ German Research Centre for Geosciences (Germany), Institut de physique du globe de Paris (France), Institut des Sciences de la Terre (France), Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation (Russia), Kyoto University (Japan), University of Leeds (UK), Max Planck Institute for Solar System Research (Germany), NASA Goddard Space Flight Center (USA), University of Potsdam (Germany), and Université de Strasbourg (France). The candidate models were evaluated individually and compared to all other candidates as well to the mean, median and a robust Huber-weighted model of all candidates. These analyses were used to identify, for example, the variation between the Gauss coefficients or the geographical regions where the candidate models strongly differed. The majority of candidates were sufficiently close that the differences can be explained primarily by individual modeling methodologies and data selection strategies. None of the candidates were so different as to warrant their exclusion from the final IGRF-13. The IAGA V-MOD task force thus voted for two approaches: the median of the Gauss coefficients of the candidates for the DGRF-2015 and IGRF-2020 models and the robust Huber-weighted model for the predictive SV-2020-2025. In this paper, we document the evaluation of the candidate models and provide details of the approach used to derive the final IGRF-13 products. We also perform a retrospective analysis of the IGRF-12 SV candidates over their performance period (2015–2020). Our findings suggest that forecasting secular variation can benefit from combining physics-based core modeling with satellite observations.
The views of New Zealand general practitioners and patients on a proposed risk assessment and communication tool: a qualitative study using Normalisation Process Theory
Authors: Leitch Sharon , Smith Alesha , Crengle Sue , Stokes Tim
Published: February 2021

Background

Communicating risks of medication harm and obtaining informed consent is difficult due to structural barriers, language and cultural practices, bias and a lack of resources appropriately tailored for the health literacy of most patients. A decision support tool was proposed to alert prescribers of risk and provide tailored information for patients to facilitate informed decision-making with patients and their whānau (family) around medication use. Patient and prescriber co-design was used to ensure the tool was designed to best meet the needs of end-users and avoid increasing health inequity. This paper describes the first stage of the co-design process.

Method

Normalisation Process Theory (NPT) was used to prospectively evaluate the tool. Semi-structured interviews were held with fifteen patients (five Māori, five Pasifika and five NZ European) and nine general practitioners (two Māori and seven European).

Results

Three themes were identified, which related to the three NPT concepts most relevant to developing the tool. Theme 1 (coherence: meaning and sense making by participants) explored participants’ understanding of prescribing safety, medication harm and risk, which is based on experience. Patients want as much information as possible about their medications and risk, but doctors find it difficult to communicate that information. Theme 2 related to the NPT concept of cognitive participation (commitment and engagement by participants) explored what participants thought about a prescribing decision support tool. Participants were cautiously optimistic, but worried about potential harm arising from its use. They also identified requirements for the tool and features to avoid. Theme 3 describes the collective action required for successful implementation of the tool; namely, culturally safe and trustworthy doctor-patient relationships.

Conclusion

Patients and general practitioners provided different perspectives when prospectively evaluating the proposed risk assessment and communication tool. This co-design research identified important pre-requisites for the tool and features to avoid and novel ideas for the proposed tool. Overall participants supported the development of the proposed risk assessment and communication tool, but identified the important role that doctor-patient relationships would play to ensure successful implementation. The use of Māori and Pacific languages in the proposed tool may enhance engagement and understanding.
HDL Particle Subspecies and Their Association With Incident Type 2 Diabetes: The PREVEND Study
Authors: Sokooti Sara , Flores-Guerrero Jose L , Kieneker Lyanne M , Heerspink Hiddo J L , Connelly Margery A , Bakker Stephan J L , Dullaart Robin P F
Published: February 2021

Context

High-density lipoproteins (HDL) may be protective against type 2 diabetes (T2D) development, but HDL particles vary in size and function, which could lead to differential associations with incident T2D. A newly developed nuclear magnetic resonance (NMR)-derived algorithm provides concentrations for 7 HDL subspecies.

Objective

We aimed to investigate the association of HDL particle subspecies with incident T2D in the general population.

Methods

Among 4828 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline, HDL subspecies with increasing size from H1P to H7P were measured by NMR (LP4 algorithm of the Vantera NMR platform).

Results

A total of 265 individuals developed T2D (median follow-up of 7.3 years). In Cox regression models, HDL size and H4P (hazard ratio [HR] per 1 SD increase 0.83 [95% CI, 0.69-0.99] and 0.85 [95% CI, 0.75-0.95], respectively) were inversely associated with incident T2D, after adjustment for relevant covariates. In contrast, levels of H2P were positively associated with incident T2D (HR 1.15 [95% CI, 1.01-1.32]). In secondary analyses, associations with large HDL particles and H6P were modified by body mass index (BMI) in such a way that they were particularly associated with a lower risk of incident T2D, in subjects with BMI < 30 kg/m2.

Conclusion

Greater HDL size and lower levels of H4P were associated with a lower risk, whereas higher levels of H2P were associated with a higher risk of developing T2D. In addition, large HDL particles and H6P were inversely associated with T2D in nonobese subjects.
Low-dose whole-body CT using deep learning image reconstruction: image quality and lesion detection
Authors: Noda Yoshifumi , Kaga Tetsuro , Kawai Nobuyuki , Miyoshi Toshiharu , Kawada Hiroshi , Hyodo Fuminori , Kambadakone Avinash , Matsuo Masayuki
Published: February 2021

Objectives:

To evaluate image quality and lesion detection capabilities of low-dose (LD) portal venous phase whole-body computed tomography (CT) using deep learning image reconstruction (DLIR).

Methods:

The study cohort of 59 consecutive patients (mean age, 67.2 years) who underwent whole-body LD CT and a prior standard-dose (SD) CT reconstructed with hybrid iterative reconstruction (SD-IR) within one year for surveillance of malignancy were assessed. The LD CT images were reconstructed with hybrid iterative reconstruction of 40% (LD-IR) and DLIR (LD-DLIR). The radiologists independently evaluated image quality (5-point scale) and lesion detection. Attenuation values in Hounsfield units (HU) of the liver, pancreas, spleen, abdominal aorta, and portal vein; the background noise and signal-to-noise ratio (SNR) of the liver, pancreas, and spleen were calculated. Qualitative and quantitative parameters were compared between the SD-IR, LD-IR, and LD-DLIR images. The CT dose-index volumes (CTDIvol) and dose-length product (DLP) were compared between SD and LD scans.

Results:

The image quality and lesion detection rate of the LD-DLIR was comparable to the SD-IR. The image quality was significantly better in SD-IR than in LD-IR (p < 0.017). The attenuation values of all anatomical structures were comparable between the SD-IR and LD-DLIR (p = 0.28–0.96). However, background noise was significantly lower in the LD-DLIR (p < 0.001) and resulted in improved SNRs (p < 0.001) compared to the SD-IR and LD-IR images. The mean CTDIvol and DLP were significantly lower in the LD (2.9 mGy and 216.2 mGy•cm) than in the SD (13.5 mGy and 1011.6 mGy•cm) (p < 0.0001).

Conclusion:

LD CT images reconstructed with DLIR enable radiation dose reduction of >75% while maintaining image quality and lesion detection rate and superior SNR in comparison to SD-IR.

Advances in knowledge:

Deep learning image reconstruction algorithm enables around 80% reduction in radiation dose while maintaining the image quality and lesion detection compared to standard-dose whole-body CT.
CompoundHetVIP: Compound Heterozygous Variant Identification Pipeline
Authors: Miller Dustin B. , Piccolo Stephen R.
Published: February 2021

Compound Heterozygous (CH) variant identification requires distinguishing maternally from paternally derived nucleotides, a process that requires numerous computational tools. Using such tools often introduces unforeseen challenges such as installation procedures that are operating-system specific, software dependencies that must be installed, and formatting requirements for input files. To overcome these challenges, we developed Compound Heterozygous Variant Identification Pipeline (CompoundHetVIP), which uses a single Docker image to encapsulate commonly used software tools for file aggregation (BCFtools or GATK4), VCF liftover (Picard Tools), joint-genotyping (GATK4), file conversion (Plink2), phasing (SHAPEIT2, Beagle, and/or Eagle2), variant normalization (vt tools), annotation (SnpEff), relational database generation (GEMINI), and identification of CH, homozygous alternate, and de novo variants in a series of 13 steps. To begin using our tool, researchers need only install the Docker engine and download the CompoundHetVIP Docker image. The tools provided in CompoundHetVIP, subject to the limitations of the underlying software, can be applied to whole-genome, whole-exome, or targeted exome sequencing data of individual samples or trios (a child and both parents), using VCF or gVCF files as initial input. Each step of the pipeline produces an analysis-ready output file that can be further evaluated. To illustrate its use, we applied CompoundHetVIP to data from a publicly available Ashkenazim trio and identified two genes with a candidate CH variant and two genes with a candidate homozygous alternate variant after filtering based on user-set thresholds for global minor allele frequency, Combined Annotation Dependent Depletion, and Gene Damage Index. While this example uses genomic data from a healthy child, we anticipate that most researchers will use CompoundHetVIP to uncover missing heritability in human diseases and other phenotypes. CompoundHetVIP is open-source software and can be found at https://github.com/dmiller903/CompoundHetVIP; this repository also provides detailed, step-by-step examples.
Limited containment options of COVID-19 outbreak revealed by regional agent-based simulations for South Africa
Authors: Bossert Andreas , Kersting Moritz , Timme Marc , Schröder Malte , Feki Azza , Coetzee Justin , Schlüter Jan
Published: February 2021

Background: COVID-19 has spread from China across Europe and the United States and has become a global pandemic. In countries of the Global South, due to often weaker socioeconomic options and health care systems, effective local countermeasures remain debated. 

Methods: We combine large-scale socioeconomic and traffic survey data with detailed agent-based simulations of local transportation to analyze COVID-19 spreading in a regional model for the Nelson Mandela Bay Municipality in South Africa under a range of countermeasure scenarios.

Results: The simulations indicate that any realistic containment strategy, including those similar to the one ongoing in South Africa, may yield a manifold overload of available intensive care units. Only immediate and the most severe countermeasures, up to a complete lock-down that essentially inhibits all joint human activities, can contain the epidemic effectively. 

Conclusions: As South Africa exhibits rather favorable conditions compared to many other countries of the Global South, our findings constitute rough conservative estimates and may support identifying strategies towards containing COVID-19 as well as any major future pandemics in these countries.
Guidance for ensuring fair and ethical broad consent for future use. A scoping review protocol.
Authors: Maxwell Lauren , Gilyan Regina , Chavan Sayali Arvind , Merson Laura , Saxena Abha , Terry Rob
Published: February 2021

Introduction: Broad consent for future use is the reuse of data and/or samples collected by a study by researchers who may not be affiliated with the original study team for purposes that may differ from the objectives of the original study. Sharing participant-level data and samples collected from research participants facilitates reuse and transparency and can accelerate drug or vaccine development, research findings, and translation. Data reuse and synthesis help prevent unnecessary research, thereby respecting research participants time and efforts and building their trust in the research process. Despite these myriad benefits, data and sample sharing represent a significant investment of time for the team that collected the data or samples, and may present additional risks for research participants, including that of re-identifiability and incidental findings, or for the source community. This scoping review will summarize existing guidance on broad consent for future use and highlight evidence gaps related to the ethical, equitable implementation of broad consent for future use.

Methods and analysis: We will apply the Arskey and O’Malley scoping review methodology and best practice as outlined in the Joanna Briggs scoping review guidelines.  The research questions have been identified through a literature review and consultation with subject-matter experts. The systematic search will be conducted in three databases using a tailored search strategy. We will search the reference lists of included articles or related systematic reviews for additional citations. The title-abstract and full text screening and charting the data will be conducted independently by two reviewers. Discrepancies will be resolved by a third reviewer. Results will be summarized in narrative form.

Ethics and dissemination: This scoping review summarizes findings from existing publications and grey literature rather than primary data and, as such, does not require ethics review. Findings will be disseminated through an open access publication and webinar.
The barriers and facilitators to implementing screening in emergency departments: a qualitative evidence synthesis (QES) protocol exploring the experiences of healthcare workers
Authors: Barry Louise , Galvin Rose , Murphy Tighe Sylvia , O'Connor Margaret , Ryan Damian , Meskell Pauline
Published: February 2021

Background: Screening in the emergency department (ED) can identify individuals in need of targeted assessment and early intervention in the hospital or community setting. Time pressures, inadequate resources, poor integration of screening tools into clinical workflow and lack of staff training are barriers to successfully implementing screening in the ED. Tailored implementation processes and education programmes were identified as facilitators. The aim of this QES is to synthesise evidence pertaining to the barriers and facilitators to implementing screening in the ED. This review will focus on the experience of healthcare workers (HCWs) who are involved in this process.

Methods: A comprehensive literature search will be completed in Scopus, CINAHL, Medline, Embase, Pubmed and Cochrane library. Grey literature sources will be searched and include Open Grey, Google Scholar, Lenus Irish Health Repository, Science.Gov and Embase Grey Literature. Qualitative or mixed methods studies that include qualitative data on the experiences of HCWs will be included. “Best fit” framework synthesis will be utilised to produce a context specific conceptual model to describe and explain how these barriers and facilitators may impact on implementation. An a priori framework of themes, formed from the existing evidence base, will inform the ultimate thematic analysis and assist in the organisation and interpretation of search results, ensuring the QES is built upon current findings. CASP will be utilised to quality appraise articles and GRADE CERQual will assess confidence in the QES findings. The screening, quality appraisal, data extraction and assessment of confidence in findings will be completed by two reviewers independently and in duplicate. Contingencies for conflict management during these processes will be outlined.  

Conclusions: This synthesis, will offer a new conceptual model for describing healthcare workers’ experience of the barriers and facilitators that impact on the implementation of screening tools in the ED.  

Registration: PROSPERO CRD42020188712 05/07/20
Generation of human midbrain organoids from induced pluripotent stem cells
Authors: Mohamed Nguyen-Vi , Mathur Meghna , da Silva Ronan V. , Thomas Rhalena A. , Lepine Paula , Beitel Lenore K. , Fon Edward A. , Durcan Thomas M.
Published: February 2021

The development of brain organoids represents a major technological advance in the stem cell field, a novel bridge between traditional 2D cultures and in vivo animal models. In particular, the development of midbrain organoids containing functional dopaminergic neurons producing neuromelanin granules, a by-product of dopamine synthesis, represents a potential new model for Parkinson’s disease. To generate human midbrain organoids, we introduce specific inductive cues, at defined timepoints, during the 3D culture process to drive the stem cells towards a midbrain fate. In this method paper, we describe a standardized protocol to generate human midbrain organoids (hMOs) from induced pluripotent stem cells (iPSCs). This protocol was developed to demonstrate how human iPSCs can be successfully differentiated into numerous, high quality midbrain organoids in one batch. We also describe adaptations for cryosectioning of fixed organoids for subsequent histological analysis.