bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 vaccine acceptance among high-risk populations in Uganda
Authors: Bongomin Felix , Olum Ronald , Andia-Biraro Irene , Nakwagala Frederick Nelson , Hassan Khalid Hudow , Nassozi Dianah Rhoda , Kaddumukasa Mark , Byakika-Kibwika Pauline , Kiguli Sarah , Kirenga Bruce J.
Published: June 2021

Background:

Immunization is an important strategy for controlling the COVID-19 pandemic. COVID-19 vaccination was recently launched in Uganda, with prioritization to healthcare workers and high-risk individuals. In this study, we aimed to determine the acceptability of COVID-19 vaccine among persons at high risk of COVID-19 morbidity and mortality in Uganda.

Methods:

Between 29 March and 14 April 2021, we conducted a cross-sectional survey consecutively recruiting persons at high risk of severe COVID-19 (diabetes mellitus, HIV and cardiovascular disease) attending Kiruddu National Referral Hospital outpatient clinics. A trained research nurse administered a semi-structured questionnaire assessing demographics, COVID-19 vaccine related attitudes and acceptability. Descriptive statistics, bivariate and multivariable analyses were performed using STATA 16.

Results:

A total of 317 participants with a mean age 51.5 ± 14.1 years were recruited. Of this, 184 (60.5%) were female. Overall, 216 (70.1%) participants were willing to accept the COVID-19 vaccine. The odds of willingness to accept COVID-19 vaccination were four times greater if a participant was male compared with if a participant was female [adjusted odds ratio (AOR): 4.1, 95% confidence interval (CI): 1.8–9.4, p = 0.00]. Participants who agreed (AOR: 0.04, 95% CI: 0.01–0.38, p = 0.003) or strongly agreed (AOR: 0.04, 95% CI: 0.01–0.59, p = 0.005) that they have some immunity against COVID-19 were also significantly less likely to accept the vaccine. Participants who had a history of vaccination hesitancy for their children were also significantly less likely to accept the COVID-19 vaccine (AOR: 0.1, 95% CI: 0.01–0.58, p = 0.016).

Conclusion:

The willingness to receive a COVID-19 vaccine in this group of high-risk individuals was comparable to the global COVID-19 vaccine acceptance rate. Increased sensitization, myth busting and utilization of opinion leaders to encourage vaccine acceptability is recommended.
Specific detection of high mobility group box 1 degradation product with a novel ELISA
Authors: Totoki Takaaki , Ito Takashi , Yamada Shingo , Honda Goichi , Hattori Tsuyoshi , Maruyama Ikuro
Published: June 2021

Background

During sepsis or sterile tissue injury, the nuclear protein high mobility group box 1 (HMGB1) can be released to the extracellular space and ultimately into systemic circulation, where it mediates systemic inflammation and remote organ failure. The proinflammatory effects of HMGB1 can be suppressed by recombinant thrombomodulin (rTM), in part through a mechanism involving thrombin–rTM-mediated degradation of HMGB1. Given that HMGB1 is proinflammatory but the HMGB1 degradation product (desHMGB1) is not, an analytical method that discriminates between these two molecules may provide a more in-depth understanding of HMGB1-induced pathogenicity as well as rTM-mediated therapeutic efficiency.

Methods

A peptide that has a shared amino-terminal structure with desHMGB1 was synthesized. C3H/lpr mice were immunized with the desHMGB1 peptide conjugate, and antibody-secreting hybridoma cells were developed using conventional methods. The reactivity and specificity of the antibodies were then analyzed using antigen-coated enzyme-linked immunosorbent assay (ELISA) as well as antibody-coated ELISA. Next, plasma desHMGB1 levels were examined in a cecal ligation and puncture (CLP)-induced septic mouse model treated with rTM.

Results

Through a series of screening steps, we obtained a monoclonal antibody that recognized desHMGB1 but did not recognize intact HMGB1. ELISA using this antibody specifically detected desHMGB1, which was significantly increased in CLP-induced septic mice treated with rTM compared with those treated with saline.

Conclusions

In this study, we obtained a desHMGB1-specific monoclonal antibody. ELISA using the novel monoclonal antibody may be an option for the in-depth analysis of HMGB1-induced pathogenicity as well as rTM-mediated therapeutic efficiency.
An Intelligent Fault Diagnosis Method of Multi-Scale Deep Feature Fusion Based on Information Entropy
Authors: Shang Zhiwu , Li Wanxiang , Gao Maosheng , Liu Xia , Yu Yan
Published: June 2021

For a single-structure deep learning fault diagnosis model, its disadvantages are an insufficient feature extraction and weak fault classification capability. This paper proposes a multi-scale deep feature fusion intelligent fault diagnosis method based on information entropy. First, a normal autoencoder, denoising autoencoder, sparse autoencoder, and contractive autoencoder are used in parallel to construct a multi-scale deep neural network feature extraction structure. A deep feature fusion strategy based on information entropy is proposed to obtain low-dimensional features and ensure the robustness of the model and the quality of deep features. Finally, the advantage of the deep belief network probability model is used as the fault classifier to identify the faults. The effectiveness of the proposed method was verified by a gearbox test-bed. Experimental results show that, compared with traditional and existing intelligent fault diagnosis methods, the proposed method can obtain representative information and features from the raw data with higher classification accuracy.
Oil Film Stiffness of Double Involute Gears Based on Thermal EHL Theory
Authors: Yin Zhaoming , Fan Zhimin , Jiang Feng
Published: June 2021

Lubrication failure is one of the main failure forms of gear failure. Time varying meshing stiffness is an important factor affecting the dynamic behavior of gears. However, the influence of oil film stiffness is usually ignored in the research process. In this paper, according to the meshing characteristics of double involute gears, based on the non-Newtonian thermal EHL theory, a new calculation method of normal and tangential oil film stiffness for double involute gears is established by the idea of subsection method. The oil film stiffness difference between double involute gears and common involute gears is analyzed, and the influence of tooth waist order parameters, working conditions, and thermal effect on the oil film stiffness are studied. The results reveal that there are some differences between normal and tangential oil film stiffness between double involute gears and common involute gears, but there is little difference. Compared with the torque, rotation speed and initial viscosity of the lubricating oil, the tooth waist order parameters have less influence on the oil film stiffness. Thermal effect has a certain influence on normal and tangential oil film stiffness, which indicates that the influence of thermal effect on the oil film can not be ignored. This research proposes a calculation method of normal and tangential oil film stiffness suitable for double involute gears, which provides a theoretical basis for improving the stability of the transmission.
Global investigation of estrogen-responsive genes regulating lipid metabolism in the liver of laying hens
Authors: Ren Junxiao , Tian Weihua , Jiang Keren , Wang Zhang , Wang Dandan , Li Zhuanjian , Yan Fengbin , Wang Yanbin , Tian Yadong , Ou Kepeng , Wang Hongjun , Kang Xiangtao , Li Hong , Liu Xiaojun
Published: June 2021

Background

Estrogen plays an essential role in female development and reproductive function. In chickens, estrogen is critical for lipid metabolism in the liver. The regulatory molecular network of estrogen in chicken liver is poorly understood. To identify estrogen-responsive genes and estrogen functional sites on a genome-wide scale, we determined expression profiles of mRNAs, lncRNAs, and miRNAs in estrogen-treated ((17β-estradiol)) and control chicken livers using RNA-Sequencing (RNA-Seq) and studied the estrogen receptor α binding sites by ChIP-Sequencing (ChIP-Seq).

Results

We identified a total of 990 estrogen-responsive genes, including 962 protein-coding genes, 11 miRNAs, and 17 lncRNAs. Functional enrichment analyses showed that the estrogen-responsive genes were highly enriched in lipid metabolism and biological processes. Integrated analysis of the data of RNA-Seq and ChIP-Seq, identified 191 genes directly targeted by estrogen, including 185 protein-coding genes, 4 miRNAs, and 2 lncRNAs. In vivo and in vitro experiments showed that estrogen decreased the mRNA expression of PPARGC1B, which had been reported to be linked with lipid metabolism, by directly increasing the expression of miR-144-3p.

Conclusions

These results increase our understanding of the functional network of estrogen in chicken liver and also reveal aspects of the molecular mechanism of estrogen-related lipid metabolism.
Hybridization and introgression in sympatric and allopatric populations of four oak species
Authors: Li Xuan , Wei Gaoming , El-Kassaby Yousry A. , Fang Yanming
Published: June 2021

Background

Hybridization and introgression are vital sources of novel genetic variation driving diversification during reticulated evolution. Quercus is an important model clade, having extraordinary diverse and abundant members in the Northern hemisphere, that are used to studying the introgression of species boundaries and adaptive processes. China is the second-largest distribution center of Quercus, but there are limited studies on introgressive hybridization.

Results

Here, we screened 17 co-dominant nuclear microsatellite markers to investigate the hybridization and introgression of four oaks (Quercus acutissima, Quercus variabilis, Quercus fabri, and Quercus serrata) in 10 populations. We identified 361 alleles in the four-oak species across 17 loci, and all loci were characterized by high genetic variability (HE = 0.844–0.944) and moderate differentiation (FST = 0.037–0.156) levels. A population differentiation analysis revealed the following: allopatric homologous (FST = 0.064) < sympatric heterogeneous (FST = 0.071) < allopatric heterogeneous (FST = 0.084). A Bayesian admixture analysis determined four types of hybrids (Q. acutissima × Q. variabilis, Q. fabri × Q. serrata, Q. acutissima × Q. fabri, and Q. acutissima × Q. variabilis × Q. fabri) and their asymmetric introgression. Our results revealed that interspecific hybridization is commonly observed within the section Quercus, with members having tendency to hybridize.

Conclusions

Our study determined the basic hybridization and introgression states among the studied four oak species and extended our understanding of the evolutionary role of hybridization. The results provide useful theoretical data for formulating conservation strategies.
The provision of dementia care in general practice: practice nurse perceptions of their role
Authors: Gibson Caroline , Goeman Dianne , Hutchinson Alison , Yates Mark , Pond Dimity
Published: June 2021

Background

Primary care nurses can assist General Practitioner’s to identify cognition concerns and support patient health self-management for those experiencing cognitive impairment or dementia. This support may lead to more appropriate care and better health outcomes for this group. Consequently, there is a need to identify the role of the primary care nurse in dementia care provision, nurse perceptions of this role and to also understand the barriers and enablers that may influence any current or potential primary care nurse role in dementia care provision.

Methods

Eight focus groups were conducted with a total of 36 primary care nurses. Data was transcribed verbatim and thematically analysed.

Results

There was a high level of agreement between primary care nurses that they had a role in provision of dementia care. This role was largely attributed to the strong therapeutic relationship between nurses and patients. However, dementia care provision was not without its challenges, including a perceived lack of knowledge, limited resources and the hierarchical nature of general practice. Three main themes were identified: personal attributes of the primary care nurse; professional attributes of the primary care nurse role and the context of practice. Six sub-themes were identified: knowing the person; overcoming stigma; providing holistic care; knowing what to do; team culture and working in the system.

Conclusions

The findings of this study suggest primary care nurses have a role in dementia care provision and, there is a need to provide support for the nurse to deliver person-centred health care in the context of cognitive impairment. As the demand for good quality primary care for people living with dementia increases, the role of the primary care nurse should be considered in primary care policy discussions. The knowledge gained from this study could be useful in informing dementia training content, to provide better prompts in the health assessment and care planning templates used by primary care nurses to better identify the care needs of people with a cognitive impairment and to develop dementia care guidelines for primary care nurses.
The association of breastfeeding self-efficacy with breastfeeding duration and exclusivity: longitudinal assessment of the predictive validity of the Greek version of the BSES-SF tool
Authors: Economou Mary , Kolokotroni Ourania , Paphiti-Demetriou Irene , Kouta Christiana , Lambrinou Ekaterini , Hadjigeorgiou Eleni , Hadjiona Vasiliki , Middleton Nicos
Published: June 2021

Introduction

While breastfeeding self-efficacy (BSES) is an important modifiable determinant of breastfeeding, a structured assessment is not standard practice in Cyprus. We assessed the Greek version of the Breastfeeding Self-Efficacy Scale (BSES-SF), including its predictive validity in terms of Breastfeeding (BF) and Exclusive Breastfeeding (EBF) up to the sixth month.

Methods

A methodological study with longitudinal design among 586 mother-infant dyads, as part of the “BrEaST Start in Life” project. BSES was assessed 24–48 h after birth and at the first month. Breastfeeding status was assessed at the clinic, the 1st, 4th and 6th month. The association between BSES and breastfeeding was estimated in logistic regression models and its diagnostic ability in ROC analysis.

Results

With Mean = 3.55 (SD = 0.85), BSES was moderate, and lower among Cypriot women, primiparas and those who delivered by Cesarean Section (C/S). There was good internal consistency across the 14 items (Cronbach’s α = 0.94) while factor analysis revealed a two-factor structure. BSES scores were higher among mothers who initiated exclusive breastfeeding (M = 3.92, SD = 0.80) compared to breastfeeding not exclusively (M = 3.29, SD = 0.84) and not breastfeeding (M = 3.04, SD = 1.09;p-value < 0.001). There was a stepwise association with exclusivity (40.5% in the highest vs 7.9% lowest quartile of self-efficacy). The association between in-hospital BSES and long-term EBF persisted in multivariable models. Women in the upper quartile of BSES at 48 h were more likely to breastfeed exclusively by adjOR = 5.3 (95% CI 1.7–17.1) at the 1st and adjOR = 13.7 (95% CI 2.7–68.6) at the 4th month. Similar associations were observed between self-efficacy at the 1st month and BF at subsequent time-points. High first month BSES (> 3.96 as per ROC) had 58.9% positive and 79.6% negative predictive value for breastfeeding at 6 months which reflects higher sensitivity but lower specificity.

Conclusions

The Greek version of BSES-SF showed good metric properties (construct, know-group, concurrent and predictive validity). In the absence of community support structures or programmes in Cyprus, prevalence of breastfeeding remains low. This suggests a need for policy, educational and community support interventions, including the systematic use of BSES scale as a screening tool to identify those at higher risk for premature BF discontinuation.
Clinical outcomes of arthroscopic and navigation-assisted two tunnel technique for coracoclavicular ligament augmentation of acute acromioclavicular joint dislocations
Authors: Theopold Jan , Henkelmann Ralf , Zhang Claus , Schöbel Tobias , Osterhoff Georg , Hepp Pierre
Published: June 2021

Background

The purpose of this study was to present a navigated image-free augmentation technique for the acromioclavicular joint (ACJ) and coracoclavicular (CC) ligaments and to report the clinical and radiological outcomes.

Methods

From 2013 to 2018, 35 eligible patients were treated with our navigated image-free ACJ- and CC-augmentation technique. The average follow-up was 3 years. Follow-up evaluations included the Constant-Murley Score, subjective shoulder value, Taft score, and the acromioclavicular joint instability (ACJI) score. The patients’ quality of life was assessed using the EuroQol-5D (EQ-5D) questionnaire. In addition, in accordance with the instability criteria, radiographs were evaluated before surgery, after surgery, and during follow-up.

Results

Overall, 25 patients (71%) suffered an acute type V disruption, 5 (14%) had a type IV disruption, and 5 (14%) had an acute Rockwood type IIIb injury. The mean Constant-Murley Score was 90 (range: 56–100; p = 0.53) on the injured side, and the mean subjective shoulder value was 92% (range: 80–100%). The mean Taft and ACJI scores were 10 (range: 4–12) and 86 (range: 34–100), respectively and the mean EQ-5D was 86 (range: 2–100). The mean CC difference of the injured side was 4 mm (range: 1.9–9.1 mm) at follow-up, which was not significantly different than that of the healthy side (p = 0.06). No fractures in the area of the clavicle or the coracoid were reported.

Conclusions

The arthroscopic- and navigation-assisted treatment of high-grade ACJ injuries in an anatomical double-tunnel configuration yields similar clinical and radiological outcomes as the conventional technique using an aiming device. Precise positioning of the navigation system prevents multiple drillings, which avoids fractures.
The associations between coping strategies, psychological health, and career indecision among medical students: a cross-sectional study in China
Authors: Zhu Yaxin , Zuo Tianming , Lai Yanni , Zhao Shenglin , Qu Bo
Published: June 2021

Background

Medical students experience difficulties in the process of making decisions about their careers, which is referred to as career indecision. This study aimed to examine the difficulties in the career decision-making processes of medical students and to explore the association of coping strategies and psychological health with career indecision. The findings may provide a reference for designing interventions to advance satisfying career decisions for medical students.

Methods

A cross-sectional survey of 359 medical students was conducted in 5 Chinese medical schools. Students completed an anonymous self-administered questionnaire measuring their career indecision, coping strategies, and psychological health. Independent t-test, F-test, bivariate Pearson’s correlation analysis, and linear regression analysis were applied to test the relation between career indecision and the associated factors. Data were analyzed using SPSS V.22 for Windows. A p-value < 0.05 was considered to be statistically significant.

Results

Difficulties regarding lack of readiness frequently occurred in medical students when making career decisions, with the highest score of 2.48 ± 0.58. Among all the associated factors in this study, career indecision was positively associated with psychological distress problem (β = 0.20, p < 0.05). This study also proved that being at a higher level of career indecision is negatively associated with using problem-focused coping strategies (β = − 0.14, p < 0.05). For the maladaptive coping strategies, applying dysfunctional coping strategies showed a significantly positive association with career indecision among medical students (β = 0.25, p < 0.05).

Conclusions

Medical students experienced difficulties regarding lack of readiness frequently when making career decisions. Both coping strategies and psychological health were associated with career indecision among medical students. To prevent career indecision, it is necessary to promote earlier career awareness to medical students. Specifically, psychological health should be addressed in career intervention programs for medical students. Additionally, when helping medical students to cope with career indecision, cognitive techniques that reduce the use of maladaptive coping strategies and enhance the use of adaptive coping strategies should be adopted.
Personal barriers to addressing intimate partner abuse: a qualitative meta-synthesis of healthcare practitioners’ experiences
Authors: Tarzia Laura , Cameron Jacqui , Watson Jotara , Fiolet Renee , Baloch Surriya , Robertson Rebecca , Kyei-Onanjiri Minerva , McKibbin Gemma , Hegarty Kelsey
Published: June 2021

Background

Healthcare practitioners (HCPs) play a crucial role in recognising, responding to, and supporting female patients experiencing intimate partner abuse (IPA). However, research consistently identifies barriers they perceive prevent them from doing this work effectively. These barriers can be system-based (e.g. lack of time or training) or personal/individual. This review of qualitative evidence aims to synthesise the personal barriers that impact HCPs’ responses to IPA.

Methods

Five databases were searched in March 2020. Studies needed to utilise qualitative methods for both data collection and analysis and be published between 2010 and 2020 in order to qualify for inclusion; however, we considered any type of healthcare setting in any country. Article screening, data extraction and methodological appraisal using a modified version of the Critical Appraisal Skills Program checklist for qualitative studies were undertaken by at least two independent reviewers. Data analysis drew on Thomas and Harden’s thematic synthesis approach.

Results

Twenty-nine studies conducted in 20 countries informed the final review. A variety of HCPs and settings were represented. Three themes were developed that describe the personal barriers experienced by HCPs:I can’t interfere(which describes the belief that IPA is a “private matter” and HCPs’ fears of causing harm by intervening); I don’t have control(highlighting HCPs’ frustration when women do not follow their advice); and I won’t take responsibility(which illuminates beliefs that addressing IPA should be someone else’s job).

Conclusion

This review highlights the need for training to address personal issues in addition to structural or organisational barriers. Education and training for HCPs needs to: encourage reflection on their own values to reinforce their commitment to addressing IPA; teach HCPs to relinquish the need to control outcomes so that they can adopt an advocacy approach; and support HCPs’ trust in the critical role they can play in responding. Future research should explore effective ways to do this within the context of complex healthcare organisations.
Sex-specific recombination patterns predict parent of origin for recurrent genomic disorders
Authors: Mosley Trenell J. , Johnston H. Richard , Cutler David J. , Zwick Michael E. , Mulle Jennifer G.
Published: June 2021

Background

Structural rearrangements of the genome, which generally occur during meiosis and result in large-scale (> 1 kb) copy number variants (CNV; deletions or duplications ≥ 1 kb), underlie genomic disorders. Recurrent pathogenic CNVs harbor similar breakpoints in multiple unrelated individuals and are primarily formed via non-allelic homologous recombination (NAHR). Several pathogenic NAHR-mediated recurrent CNV loci demonstrate biases for parental origin of de novo CNVs. However, the mechanism underlying these biases is not well understood.

Methods

We performed a systematic, comprehensive literature search to curate parent of origin data for multiple pathogenic CNV loci. Using a regression framework, we assessed the relationship between parental CNV origin and the male to female recombination rate ratio.

Results

We demonstrate significant association between sex-specific differences in meiotic recombination and parental origin biases at these loci (p = 1.07 × 10–14).

Conclusions

Our results suggest that parental origin of CNVs is largely influenced by sex-specific recombination rates and highlight the need to consider these differences when investigating mechanisms that cause structural variation.
Genome-wide analysis of retinal transcriptome reveals common genetic network underlying perception of contrast and optical defocus detection
Authors: Tkatchenko Tatiana V. , Tkatchenko Andrei V.
Published: June 2021

Background

Refractive eye development is regulated by optical defocus in a process of emmetropization. Excessive exposure to negative optical defocus often leads to the development of myopia. However, it is still largely unknown how optical defocus is detected by the retina.

Methods

Here, we used genome-wide RNA-sequencing to conduct analysis of the retinal gene expression network underlying contrast perception and refractive eye development.

Results

We report that the genetic network subserving contrast perception plays an important role in optical defocus detection and emmetropization. Our results demonstrate an interaction between contrast perception, the retinal circadian clock pathway and the signaling pathway underlying optical defocus detection. We also observe that the relative majority of genes causing human myopia are involved in the processing of optical defocus.

Conclusions

Together, our results support the hypothesis that optical defocus is perceived by the retina using contrast as a proxy and provide new insights into molecular signaling underlying refractive eye development.
Alcohol use and associated factors among adolescent boys and young men in Kampala, Uganda
Authors: Kabwama Steven Ndugwa , Matovu Joseph KB , Ssenkusu John M , Ssekamatte Tonny , Wanyenze Rhoda K.
Published: June 2021

Background

Alcohol use leads to about 3 million deaths globally. The alcohol industry employs marketing strategies to establish their brands in the lives of young people at a time when addictive behaviors are initiated and reinforced. We conducted a survey among adolescent boys and young men (ABYM) to estimate the prevalence of alcohol use and associated factors using the Health Belief Model as the guiding framework.

Methods

The study was conducted among ABYM in- or out-of-school aged 10–24 years in Kampala, Uganda. We used questions adopted from the Global School-based Student Health Survey and the WHO STEPwise approach to Surveillance questionnaire to collect data. The outcome of interest was alcohol use within 30 days before the interview. We also asked about characteristics such as alcohol use by siblings, parents/ guardians, school status among others. We used odds ratios obtained via a logistic regression model as the measure of association.

Results

A total of 2500 ABYM participated, of which 262 (10.5 %, 95 %CI 9.3–11.7) had consumed alcohol within 30 days before the interview. Out-of-school ABYM had higher odds of consuming alcohol compared with their in-school counterparts AOR 1.55 (95 %CI 1.09–2.20). Compared with ABYM whose parents/ guardians did not drink alcohol, ABYM whose both parents consumed alcohol had higher odds of consuming alcohol AOR 2.24 (95 %CI 1.38–3.64) as were those with only a mother or female guardian who consumed alcohol AOR 1.95 (95 %CI 1.11–3.41). ABYM with siblings that drink alcohol had higher odds of consuming alcohol AOR 2.25 (95 %CI 1.80–3.52). ABYM who possessed items with an alcohol brand logo had higher odds of consuming alcohol AOR 2.00 (95 %CI 1.33–3.01).

Conclusions

There are significant levels of alcohol consumption among ABYM which calls for evidence-based measures targeting this age group to reduce consumption and recognizing the role of the family, school and community in prevention and promotion of use. There is need to regulate alcohol marketing and ensuring availability of alcohol dependence treatment services that build confidence among youth.
Development and content validity of the Barth Syndrome Symptom Assessment (BTHS-SA) for adolescents and adults
Authors: Gwaltney Chad , Stokes Jonathan , Aiudi Anthony , Mazar Iyar , Ollis Sarah , Love Emily , Shields Alan
Published: June 2021

Background

Barth Syndrome (BTHS) is a rare genetic disorder that presents as a complex of debilitating symptoms and reduced life expectancy. Well-developed, BTHS-specific assessments measuring primary signs and symptoms of BTHS are not currently available, making it difficult to evaluate treatment effects in BTHS clinical studies. The objective of this research was to develop symptom-focused patient-reported outcome (PRO) measures for use in clinical studies with adolescents and adults with BTHS.

Methods

Concept elicitation interviews (CEIs) with pediatric (n = 18, age < 16 years) and adult (n = 15, age ≥ 16 years) individuals with BTHS and/or their caregivers were conducted to identify signs and symptoms relevant to BTHS and important to individuals with the condition. Based on CEI results, questionnaire construction activities were conducted to create unique adolescent and adult versions of the Barth Syndrome-Symptom Assessment (BTHS-SA). The questionnaires were evaluated in cognitive debriefing interviews (CDIs) with adolescents (n = 12; age 12- < 16 years) and adults (n = 12; age ≥ 16 years) with BTHS to assess relevance and readability of the tools.

Results

During the CEIs, a total of 48 and 40 signs and symptoms were reported by the pediatric and adult groups, respectively; 31 were reported by both age groups. Fatigue/tiredness and muscle weakness were the symptoms most frequently reported by both pediatric and adult patients with BTHS as important to improve with an effective treatment. The CEI results informed construction of a nine-item version of the BTHS-SA for adolescents and an eight-item version for adults. Developed for daily administration, each version asks respondents to rate symptom severity “at its worst” over the 24 h prior to administration. CDIs with both adolescents and adults with BTHS demonstrated that each BTHS-SA version was reflective of the disease experience and that respondents could interpret the questionnaire as intended and provide responses that accurately reflected their symptom experience.

Conclusions

The BTHS-SA adolescent and adult versions are content-valid PRO measures that can be used to evaluate severity of disease-specific symptoms in future clinical trials. Given the lack of available and well-developed assessments in this underserved therapeutic area, these tools fulfill a need for clinical researchers developing treatments for individuals with BTHS.
Simultaneous determination of five diuretic drugs using quantitative analysis of multiple components by a single marker
Authors: Chen Fuchao , Fang Baoxia , Li Peng , Wang Sicen
Published: June 2021

Background

Loop diuretics are commonly used in clinical practice to manage high fluid loads and to control fluid balance. In this paper, a novel quantitative analysis method for multiple components with a single marker (QAMS) was developed for the simultaneous determination of 5 diuretic drugs furosemide, torasemide, azosemide, etacrynic acid, and bumetanide, by HPLC. Qualitative analysis was performed using relative retention time and ultraviolet (UV) spectral similarity as the double indicator. The QAMS method was conducted with etacrynic acid as an internal reference substance. The quantities of the other four diuretics were calculated by using the relative correction factors for etacrynic acid. The quantities of the 5 diuretic drugs were also determined by the external standard method (ESM). Chromatographic separation was achieved on a Shimadzu HC-C18column (150 mm × 4.6 mm, 5 µm) using 50 mM potassium dihydrogen phosphate (pH adjusted to 4.0 with phosphoric acid) with acetonitrile (64:36, v/v) as the mobile phase at a flow rate of 1.0 mL/min and a column temperature of 30 ℃.

Results

Under these conditions, the 5 diuretic drugs were well separated, showing linear relationships within certain ranges. The quantitative results showed that there was no significant difference between the QAMS and ESM methods.

Conclusions

Overall, the HPLC-QAMS analytical scheme established in this study is a simple, efficient, economical, and accurate method for the quantitative evaluation of 5 diuretic drugs.
The effects of DENV serotype competition and co-infection on viral kinetics in Wolbachia-infected and uninfected Aedes aegypti mosquitoes
Authors: Novelo M. , Audsley M. D. , McGraw E. A.
Published: June 2021

Background

The Aedes aegypti mosquito is responsible for the transmission of several medically important arthropod-borne viruses, including multiple serotypes of dengue virus (DENV-1, -2, -3, and -4). Competition within the mosquito between DENV serotypes can affect viral infection dynamics, modulating the transmission potential of the pathogen. Vector control remains the main method for limiting dengue fever. The insect endosymbiont Wolbachia pipientis is currently being trialed in field releases globally as a means of biological control because it reduces virus replication inside the mosquito. It is not clear how co-infection between DENV serotypes in the same mosquito might alter the pathogen-blocking phenotype elicited by Wolbachia in Ae. aegypti.

Methods

Five- to 7-day-old female Ae. aegypti from two lines, namely, with (wMel) and without Wolbachia infection (WT), were fed virus-laden blood through an artificial membrane with either a mix of DENV-2 and DENV-3 or the same DENV serotypes singly. Mosquitoes were subsequently incubated inside environmental chambers and collected on the following days post-infection: 3, 4, 5, 7, 8, 9, 11, 12, and 13. Midgut, carcass, and salivary glands were collected from each mosquito at each timepoint and individually analyzed to determine the percentage of DENV infection and viral RNA load via RT-qPCR.

Results

We saw that for WT mosquitoes DENV-3 grew to higher viral RNA loads across multiple tissues when co-infected with DENV-2 than when it was in a mono-infection. Additionally, we saw a strong pathogen-blocking phenotype in wMel mosquitoes independent of co-infection status.

Conclusion

In this study, we demonstrated that the wMel mosquito line is capable of blocking DENV serotype co-infection in a systemic way across the mosquito body. Moreover, we showed that for WT mosquitoes, serotype co-infection can affect infection frequency in a tissue- and time-specific manner and that both viruses have the potential of being transmitted simultaneously. Our findings suggest that the long-term efficacy of Wolbachia pathogen blocking is not compromised by arthropod-borne virus co-infection.

Graphical Abstract
The derepression of transposable elements in lung cells is associated with the inflammatory response and gene activation in idiopathic pulmonary fibrosis
Authors: Rostami Mahboubeh R. , Bradic Martina
Published: June 2021

Background

Transposable elements (TEs) are repetitive sequences of viral origin that compose almost half of the human genome. These elements are tightly controlled within cells, and if activated, they can cause changes in both gene regulation and immune viral responses that have been associated with several chronic inflammatory diseases in humans. As oxidants are potent activators of TEs, and because oxidative injury is a major risk factor in relation to idiopathic pulmonary fibrosis (IPF), we hypothesized that TEs might be involved in the regulation of gene expression and so contribute to inflammation in cases of IPF. IPF is a fatal lung disease that involves the gradual replacement of the alveolar tissue with fibrotic scars as well as the accumulation of inflammatory cells in the lower respiratory tract. Although IPF is known to occur as a result of the complex interaction between age, environmental risk factors (i.e., oxidative stress) and genetics, the relative contributions of these factors to the disease remain unclear. To determine whether TEs are associated with IPF, we compared the transcriptional profiles of the genes and TEs of lung cells obtained from both healthy donors and IPF patients.

Results

We quantified TE and gene expression levels using a published bulk RNA-seq dataset containing 24 subjects (16 donors and eight IPF patients), including three lung-cell types per subject, as well as an scRNA-seq dataset concerning 16 subjects (eight donors and eight IPF patients).

We found evidence of TE dysregulation in the alveolar type II lung cells and alveolar macrophages of the IPF patients. In addition, the activation of the LINE1 family of elements in IPF is associated with the increased expression of TE cellular regulators (MOV10, IFI16, SAMHD1, and APOBECG3), interferon-stimulating genes (ISG15, IFI6, IFI27, IFI44, and OAS1), chemokines (CX3CL1 and CXCL9), and interleukins (IL15RA). We also propose that TE derepression might be involved in the regulation of previously reported IPF candidate genes (MUC5B, CHL1, SPP1, and MMP7).

Conclusion

Based on our findings, we propose that TE derepression plays an important role in the regulation of gene expression and can also prompt both the recruitment of inflammatory processes and the disruption of the immunological balance, which can lead to chronic inflammation in IPF.
Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment
Authors: Zhou Yadi , Xu Jielin , Hou Yuan , Leverenz James B. , Kallianpur Asha , Mehra Reena , Liu Yunlong , Yu Haiyuan , Pieper Andrew A. , Jehi Lara , Cheng Feixiong
Published: June 2021

Background

Dementia-like cognitive impairment is an increasingly reported complication of SARS-CoV-2 infection. However, the underlying mechanisms responsible for this complication remain unclear. A better understanding of causative processes by which COVID-19 may lead to cognitive impairment is essential for developing preventive and therapeutic interventions.

Methods

In this study, we conducted a network-based, multimodal omics comparison of COVID-19 and neurologic complications. We constructed the SARS-CoV-2 virus-host interactome from protein-protein interaction assay and CRISPR-Cas9-based genetic assay results and compared network-based relationships therein with those of known neurological manifestations using network proximity measures. We also investigated the transcriptomic profiles (including single-cell/nuclei RNA-sequencing) of Alzheimer’s disease (AD) marker genes from patients infected with COVID-19, as well as the prevalence of SARS-CoV-2 entry factors in the brains of AD patients not infected with SARS-CoV-2.

Results

We found significant network-based relationships between COVID-19 and neuroinflammation and brain microvascular injury pathways and processes which are implicated in AD. We also detected aberrant expression of AD biomarkers in the cerebrospinal fluid and blood of patients with COVID-19. While transcriptomic analyses showed relatively low expression of SARS-CoV-2 entry factors in human brain, neuroinflammatory changes were pronounced. In addition, single-nucleus transcriptomic analyses showed that expression of SARS-CoV-2 host factors (BSGandFURIN) and antiviral defense genes (LY6E,IFITM2,IFITM3, andIFNAR1) was elevated in brain endothelial cells of AD patients and healthy controls relative to neurons and other cell types, suggesting a possible role for brain microvascular injury in COVID-19-mediated cognitive impairment. Overall, individuals with the AD risk alleleAPOEE4/E4 displayed reduced expression of antiviral defense genes compared toAPOEE3/E3 individuals.

Conclusion

Our results suggest significant mechanistic overlap between AD and COVID-19, centered on neuroinflammation and microvascular injury. These results help improve our understanding of COVID-19-associated neurological manifestations and provide guidance for future development of preventive or treatment interventions, although causal relationship and mechanistic pathways between COVID-19 and AD need future investigations.
Healthcare provider characteristics that influence the implementation of individual-level patient-centered outcome measure (PROM) and patient-reported experience measure (PREM) data across practice settings: a protocol for a mixed methods systematic review with a narrative synthesis
Authors: Wolff Angela C. , Dresselhuis Andrea , Hejazi Samar , Dixon Duncan , Gibson Deborah , Howard A. Fuchsia , Liva Sarah , Astle Barbara , Reimer-Kirkham Sheryl , Noonan Vanessa K. , Edwards Lisa
Published: June 2021

Background

Substantial literature has highlighted the importance of patient-reported outcome and experience measures (PROMs and PREMs, respectively) to collect clinically relevant information to better understand and address what matters to patients. The purpose of this systematic review is to synthesize the evidence about how healthcare providers implement individual-level PROMs and PREMs data into daily practice.

Methods

This mixed methods systematic review protocol describes the design of our synthesis of the peer-reviewed research evidence (i.e., qualitative, quantitative, and mixed methods), systematic reviews, organizational implementation projects, expert opinion, and grey literature. Keyword synonyms for “PROMs,” PREMs,” and “implementation” will be used to search eight databases (i.e., MEDLINE, CINAHL, PsycINFO, Web of Science, Embase, SPORTDiscus, Evidence-based Medicine Reviews, and ProQuest (Dissertation and Theses)) with limiters of English from 2009 onwards. Study selection criteria include implementation at the point-of-care by healthcare providers in any practice setting. Eligible studies will be critically appraised using validated tools (e.g., Joanna Briggs Institute). Guided by the review questions, data extraction and synthesis will occur simultaneously to identify biographical information and methodological characteristics as well as classify study findings related to implementation processes and strategies. As part of the narrative synthesis approach, two frameworks will be utilized: (a) Consolidated Framework for Implementation Research (CFIR) to identify influential factors of PROMs and PREMs implementation and (b) Expert Recommendations for Implementing Change (ERIC) to illicit strategies. Data management will be undertaken using NVivo 12TM.

Discussion

Data from PROMs and PREMs are critical to adopt a person-centered approach to healthcare. Findings from this review will guide subsequent phases of a larger project that includes interviews and a consensus-building forum with end users to create guidelines for implementing PROMs and PREMs at the point of care.

Systematic review registration

PROSPERO CRD42020182904.
Post-abortion family planning use, method preference, and its determinant factors in Eastern Africa: a systematic review and meta-analysis
Authors: Bizuneh Asmamaw Demis , Azeze Getnet Gedefaw
Published: June 2021

Background

Utilization of post-abortion family planning is very critical to reduce high levels of unintended pregnancy, which is the root cause of induced abortion. In Eastern Africa, it is estimated that as many as 95% of unintended pregnancies occurred among women who do not practice contraception at all. Therefore, this meta-analysis aimed to assess post-abortion family planning utilization and its determinant factors in Eastern Africa.

Methods

Published papers from Scopus, HINARI, PubMed, Google Scholar, and Web of Science electronic databases and grey literature repository were searched from database inception to January 30, 2020, with no restriction by design and date of publishing. We screened records, extracted data, and assessed risk of bias in duplicate. Cochrane I2statistics were used to check the heterogeneity of the studies. Publication bias was assessed by Egger and Biggs test with a funnel plot. A random-effects model was calculated to estimate the pooled prevalence of post-abortion family planning utilization.

Results

A total of twenty-nine cross-sectional studies with 70,037 study participants were included. The overall pooled prevalence of post-abortion family planning utilization was 67.86% (95% CI 63.59–72.12). The most widely utilized post-abortion family methods were injectable 33.23% (95% CI 22.12–44.34), followed by implants 24.71% (95% CI 13.53–35.89) and oral contraceptive pills 23.42% (95% CI 19.95–26.89). Married marital status (AOR=3.20; 95% CI 2.02–5.05), multiparity (AOR=3.84; 95% CI 1.43–10.33), having a history of abortion (AOR=2.33; 95% CI 1.44–3.75), getting counselling on post-abortion family planning (AOR=4.63; 95% CI 3.27–6.56), and ever use of contraceptives (AOR=4.63; 95% CI 2.27–5.21) were factors associated with post-abortion family planning utilization in Eastern Africa.

Conclusions

This study revealed that the marital status of the women, multiparity, having a history of abortion, getting counselling on post-abortion family planning, and ever used contraceptives were found to be significantly associated with post-abortion family planning utilization.
On interpolative F-contractions with shrink map
Authors: Alansari Monairah , Ali Muhammad Usman
Published: June 2021

In this article, we introduce two notions of interpolative F-contractions with shrink map and F-contractions with shrink map. We also study the existence of E-fixed points by using these notations on a metric space endowed with a binary relation. As an application and consequence of the main results, we also get some other interesting results like a common fixed point result, an E-fixed point result on a metric space equipped with graph, and an existence theorem for a solution of integral equations.
First-order impulsive differential systems: sufficient and necessary conditions for oscillatory or asymptotic behavior
Authors: Santra Shyam Sundar , Baleanu Dumitru , Khedher Khaled Mohamed , Moaaz Osama
Published: June 2021

In this paper, we study the oscillatory and asymptotic behavior of a class of first-order neutral delay impulsive differential systems and establish some new sufficient conditions for oscillation and sufficient and necessary conditions for the asymptotic behavior of the same impulsive differential system. To prove the necessary part of the theorem for asymptotic behavior, we use the Banach fixed point theorem and the Knaster–Tarski fixed point theorem. In the conclusion section, we mention the future scope of this study. Finally, two examples are provided to show the defectiveness and feasibility of the main results.