bluuebunny/crossref_metadata_2025 huggingface dataset:
High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial
Authors: Babar Asma , Moore Lynne , Leblanc Vicky , Dudonné Stéphanie , Desjardins Yves , Lemieux Simone , Bochard Valérie , Guyonnet Denis , Dodin Sylvie
Published: March 2021

Purpose

Our objective was to assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection.

Material and methods

We recruited 145 healthy, adult women with a history of recurrent urinary tract infection, defined as ≥ 2 in the past 6 months or ≥ 3 in the past 12 months in this randomized, controlled, double-blind clinical trial. Participants were randomized to receive a high dose of standardized, commercially available cranberry proanthocyanidins (2 × 18.5 mg daily, n = 72) or a control low dose (2 × 1 mg daily, n = 73) for a 24-week period. During follow-up, symptomatic women provided urine samples for detection of pyuria and/or bacteriuria and received an appropriate antibiotic prescription. The primary outcome for the trial was the mean number of new symptomatic urinary tract infections during a 24-week intervention period. Secondary outcomes included symptomatic urinary tract infection with pyuria or bacteriuria.

Results

In response to the intervention, a non-significant 24% decrease in the number of symptomatic urinary tract infections was observed between groups (Incidence rate ratio 0.76, 95%CI 0.51–1.11). Post-hoc analyses indicated that among 97 women who experienced less than 5 infections in the year preceding enrolment, the high dose was associated with a significant decrease in the number of symptomatic urinary tract infections reported compared to the low dose (age-adjusted incidence rate ratio 0.57, 95%CI 0.33–0.99). No major side effects were reported.

Conclusion

High dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year.

Trial registration: Clinicaltrials.gov, identifier NCT02572895
Factors affecting dental self-confidence and satisfaction with dental appearance among adolescents in Saudi Arabia: a cross sectional study
Authors: Ellakany Passent , Fouda Shaimaa M. , Alghamdi Maram , Bakhurji Eman
Published: March 2021

Background

Dental appearance affects facial beauty, social interaction and psychological well-being particularly among adolescents. The aim of the current study was to determine factors affecting adolescent dental self-confidence and satisfaction with dental appearance in Saudi Arabia.

Methods

A cross-sectional study was conducted in the Eastern Province of Saudi Arabia among 3500 students attending intermediate and high schools. Data was collected from 2637 students using the translated Arabic version of the psychosocial impact of dental esthetics questionnaire (PIDAQ) in addition to questions about smile esthetics satisfaction and demographic variables including; gender, age, school grade, and parental level of education. Statistical analysis was performed by using logistic regression to assess the effect of demographical variables on PIDAQ and its domains at 5% significance level.

Results

About 80% of the participants were satisfied or somewhat satisfied with their smiles. Tooth alignment and tooth color were the most cited reasons for adolescents’ dissatisfaction about their smile, 34% and 33% respectively. Females and participants’ fathers’ university education figured in a statistically significant way regarding higher PIDAQ and aesthetic concerns. Females were 70%, and those with fathers’ university education were 22% more likely to have a negative psychological impact. Females expressed aesthetic concerns nearly two times more than males. Participants whose fathers possessed university education had an aesthetic concern 1.25 times more compared to those whose fathers had no school or limited school education. Females and those with mothers who had university education were less likely to have positive dental self-confidence.

Conclusions

Most adolescents exhibited satisfaction with their own smiles. Smile dissatisfaction in the remaining participants was related to teeth alignment, color and shape. Females were more concerned with dental esthetics and smile satisfaction than males. Females and participants whose fathers had a university education exhibited higher psychosocial impact than males and those with or without school education. However, males showed greater self-confidence in their dental aesthetics.
A comparative assessment of oral health-related quality of life of children born with orofacial clefts in Sudan and their caregivers'
Authors: Ali Mecheala Abbas , Abass Shaza K. , Nasir Elwalid Fadul
Published: March 2021

Background

Cleft lip and palate(CL/P)is the most common orofacial malformation affecting one in every 700–1000 newborns worldwide. The aim of the study wasto evaluate the impact of CL/P on health- related quality of life (OHRQoL) in Sudanese children and the level of concordance between caregivers' and children and to investigate correlates of the caregivers' perceptions of OHRQoL with that of their children.

Methods

The sample consisted of 75 children with clefts (age range 8–16 years), (46 male, 29 female) and their caregivers' attending University of Science and Technology Dental Teaching Hospital. The children and their caregivers' were interviewed separately. The interview consisted of 38 questions adopted from the COHIP (Arabic version).The level of concordance between caregivers' and children was compared using paired t-tests and intraclass correlations. Predictive validity was assessed using Pearson correlations and linear regression analyses.

Results

The translated COHIP and its subscales, had Cronbach' alphas score ranged between (0.65 and 0.75) for caregivers' and children with cleft. COHIP scores for children and caregivers' were (89.41 ± 19.97) and (94.34 ± 19.52) respectively. Caregivers' and children differed significantly in the overall COHIP and oral symptoms subscale. There were high correlations between caregivers' and children ranged from (0.63 to 0.87). The correlation between all subscales was statistically significant (p = 0.05).

Conclusions

Caregivers' had higher perceptions of oral symptoms and overall COHIP compared to their children using the Arabic version of the COHIP. Caregiver's reports have to be considered complementary to the reports of their children themselves.
Association between root/coronal caries and individual factors in institutionalised elderly using ICDAS severity and activity
Authors: Usuga-Vacca Margarita , Marin-Zuluaga Dairo Javier , Castellanos Jaime Eduardo , Martignon Stefania
Published: March 2021

Background

Caries in the elderly has been associated with dependence, oral-health status and -care practices. This cross-sectional study aimed to investigate the association between root/coronal caries and individual factors among institutionalised elderly people in Bogotá, Colombia, using the International Caries Detection and Assessment System severity and activity criteria (ICDAS).

Methods

A total of 226 institutionalised elderly were clinically examined for root and coronal caries in 40 institutions. Caries risk was assessed with Cariogram, and demographics, oral health knowledge and practices, oral health-related quality of life and denture-use habits using a questionnaire.

Results

Participants (mean age: 80.1 ± 9.3 years; 63.7% female) presented a mean number of 10.8 ± 7.3 teeth and 19.4 ± 18.8 exposed root surfaces. Prevalence of Coronal-ICDAS caries experience (C-ICDAS DF) was of 100% and of 54.4% for C-ICDAS D; mean number of C-ICDAS DFS was 16.76 ± 27.36, with 50.9% of subjects having ≥ one active C-ICDAS DS. Prevalence of Root Caries Index was of 49.1% and of R-ICDAS DF of 46%; mean number of R-ICDAS DFS was 2.03 ± 2.78, with 40.3% of subjects having ≥ one active R-ICDAS DS. Most individuals had a systemic condition (94.2%) and required oral-hygiene assistance (58%). Logistic regression analyses showed significant associations (p < 0.05): for coronal active caries when having over six teeth (OR: 2.7), and for root caries, when having coronal caries (OR: 2.41), being a man (OR: 1.95), and having over 14 teeth (OR: 0.30). Those presenting with > eight exposed root surfaces were 4.04 more likely to have root caries and 2.4 times more likely to have active root caries.

Conclusion

In the institutionalised elderly population in Bogotá significant associations were found, both for the presence as for the activity status of root and coronal caries, with individual clinical factors including coronal caries, exposed root surfaces and number of teeth.
Attitudes and educational needs of emergency doctors providing palliative and end-of-life care in Hong Kong: a cross-sectional analysis based on a self-report study
Authors: Wong Kwun Hang , Yang Li Chuan Marc , Woo Kam Wing Raymond , Wong Oi Fung , Kwong Wing Yan , Tse Choi Fung , Lam Shing Kit Tommy , Ma Hing Man , Lit Chau Hung Albert , Ho Hiu Fai , Shih Yau Ngai
Published: March 2021

Background

Due to the ageing population in Hong Kong, the importance and need of palliative care and end-of-life (EOL) care are coming under the spotlight. The objectives of this study were to evaluate the attitudes of emergency doctors in providing palliative and EOL care in Hong Kong, and to investigate the educational needs of emergency doctors in these areas.

Methods

A questionnaire was used to study the attitudes of ED doctors of six different hospitals in Hong Kong. The questionnaire recorded the attitudes of the doctors towards the role of palliative and EOL care in EDs, the specific obstacles faced, their comfort level and further educational needs in providing such care. The attitudes of emergency doctors of EDs with EOL care services were compared with those of EDs without such services.

Results

In total, 145 emergency doctors completed the questionnaire, of which 60 respondents were from EDs with EOL care services. A significant number of participants recognized that the management of the dying process was essential in ED. Providing palliative and EOL care is also accepted as an important competence and responsibility, but the role and priority of palliative and EOL care in ED are uncertain. Lack of time and access to palliative care specialists/ teams were the major barriers. Doctors from EDs with EOL care services are more comfortable in providing such care and discuss it with patients and their relatives. Further educational needs were identified, including the management of physical complaints, communication skills, and EOL care ethics.

Conclusions

The study identified obstacles in promoting palliative and EOL care in the EDs Hong Kong. With the combination of elements of routine ED practice and a basic palliative medicine skill set, it would promote the development of palliative and EOL care in Emergency Medicine in the future.
Determinants of unmet need for family planning in Gambia & Mozambique: implications for women’s health
Authors: Yaya Sanni , Idriss-Wheeler Dina , Uthman Olalekan A. , Bishwajit Ghose
Published: March 2021

Background

In low-middle-income countries, unmet need for family planning (FP) constitutes a major challenge for prevention of unintended pregnancies and associated health and psychological morbidities for women. The factors associated with unmet need for family planning have been studied for several countries in sub-Saharan Africa, but not much is known about the situation in Gambia and Mozambique. The purpose of this study was to perform a comparative analysis of the prevalence of unmet need for FP, and its sociodemographic correlates in Gambia and Mozambique to better inform FP policies and programs aimed at reducing associated negative health outcomes for women and their families.

Methods

In this analysis we used nationally representative data from Demographic and Health Surveys in Gambia (2013) and Mozambique (2011). Sample population were 23,978 women (n = 10,037 for Gambia and 13,745 for Mozambique) aged 15–49 years. Women who want to stop or delay childbearing but were not using any contraceptive method were considered to have unmet need for FP. Association between unmet need for FP and the explanatory variables was measured using binary logistic regression models

Results

Prevalence of unmet need for FP was 17.86% and 20.79% for Gambia and Mozambique, respectively. Having employment in professional/technical/managerial position showed an inverse association with unmet need both in Gambia [OR = 0.843, 95% CI 0.730, 0.974] and Mozambique [OR = 0.886, 95% CI 0.786, 0.999]. Education and household wealth level did not show any significant association with unmet need. The only positive association was observed for rural [OR = 1.213, 95% CI 1.022, 1.441] women in the richer households in Gambia. Having access to electronic media [OR = 0.698, 95% CI 0.582, 0.835] showed a negative effect on having unmet need in Mozambique. Women from female headed households in Gambia [OR = 0.780, 95% CI 0.617, 0.986] and Mozambique [OR = 0.865, 95% CI 0.768, 0.973] had lower odds of unmet need for FP.

Conclusion

The situation of unmet need for FP in Gambia and Mozambique was better than the Sub-Saharan African average (25%). Nonetheless, there is room for improvement in both countries. Significant assocations with lower unmet need for family planning and women’s occupational status (more education & higher skilled employment), access to mass media communication, and female-headed households provide possible areas for intervention for improved FP opportunities in the region.
Workplace gender-based violence and associated factors among university women in Enugu, South-East Nigeria: an institutional-based cross-sectional study
Authors: Agbaje Olaoluwa Samson , Arua Chinenye Kalu , Umeifekwem Joshua Emeka , Umoke Prince Christian Iheanachor , Igbokwe Chima Charles , Iwuagwu Tochi Emmanuel , Iweama Cylia Nkechi , Ozoemena Eyuche Lawretta , Obande-Ogbuinya Edith N.
Published: March 2021

Background

Exposure to workplace gender-based violence (GBV) can affect women's mental and physical health and work productivity in higher educational settings. Therefore, this study aimed to examine the prevalence of GBV (workplace incivility, bullying, sexual harassment), and associated factors among Nigerian university women.

Methods

The study was an institutional-based cross-sectional survey. The multi-stage sampling technique was used to select 339 female staff from public and private universities in Enugu, south-east Nigeria. Data was collected using the Workplace Incivility Scale (WIS), Modified Workplace Incivility Scale (MWIS), Negative Acts Questionnaire-Revised (NAQ-R), and Sexual Experiences Questionnaire (SEQ). Descriptive statistics, independent samplest-test, Pearson’s Chi-square test, univariate ANOVA, bivariate, and multivariable logistic regression analyses were conducted at 0.05 level of significance.

Results

The prevalence of workplace incivility, bullying, and sexual harassment (SH) was 63.8%, 53.5%, and 40.5%. The 12-month experience of the supervisor, coworker, and instigated incivilities was 67.4%, 58.8%, and 52.8%, respectively. Also, 47.5% of the participants initiated personal bullying, 62.5% experienced work-related bullying, and 42.2% experienced physical bullying. The 12-month experience of gender harassment, unwanted sexual attention, and sexual coercion were 36.5%, 25.6%, and 26.6%, respectively. Being aged 35–49 years (AOR 0.15; 95% CI (0.06, 0.40), and ≥ 50 years (AOR 0.04; 95% CI (0.01, 0.14) were associated with workplace incivility among female staff. Having a temporary appointment (AOR 7.79, 95% CI (2.26, 26.91) and casual/contract employment status (AOR 29.93, 95% CI (4.57, 192.2) were reported to be associated with workplace bullying. Having a doctoral degree (AOR 3.57, 95% CI (1.24, 10.34), temporary appointment (AOR 91.26, 95% CI (14.27, 583.4) and casual/contract employment status (AOR 73.81, 95% CI (7.26, 750.78) were associated with workplace SH.

Conclusions

The prevalence of GBV was high. There is an urgent need for workplace interventions to eliminate different forms of GBV and address associated factors to reduce the adverse mental, physical, and social health outcomes among university women.
Eye acupuncture for pain conditions: a scoping review of clinical studies
Authors: Chi Yuan , Barth Jürgen , Wang Mei , Robinson Nicola , Li Zan-Hua , Liu Jian-Ping
Published: March 2021

Background

Chinese eye acupuncture, focuses on treating different diseases by applying needle stimulation around the orbit of the eye. Since 1970, it has been used in China for the management of pain-related disorders. This scoping review systematically collected clinical studies on the use of eye acupuncture to treat pain conditions and identify any adverse events.

Methods

Six databases including PubMed, the Cochrane Library, CNKI, VIP, Wan Fang Data and SinoMed were searched from 1970 to March 2019. Randomized controlled trials (RCTs), clinical controlled trials (CCTs) and case series on eye-acupuncture for pain conditions meeting the inclusion criteria were identified. Data were extracted on patients, interventions, details of eye acupuncture, control treatments and outcomes.

Results

Searches identified 81 clinical studies and a trend demonstrating an increasing number of published studies. All studies were conducted in China and published in Chinese. These included, 45 (55.6%) RCTs, 5 (6.2%) CCTs, and 31 (38.3%) case series, treating 7113 patients with 44 different pain-related diseases or symptoms. The most frequently reported conditions were headache (18, 16.2%), acute lumbar pain (7, 6.3%) and lumbar disc herniation (7, 6.3%). Treatment using small needles (φ0.25 × 13 mm), retained ≤30 min, needling the horizontal outer orbital edge and the avoidance of manipulation during treatment were the most frequent descriptions of the interventions used. Eye acupuncture was used alone in about half of the studies and of the remaining studies it was combined with other treatment. All studies suggested some beneficial effects including: pain relief, improved quality of life and mental health, and 18 (22.2%) adverse events.

Conclusion

Eye acupuncture, predominantly studied in China, may be a promising intervention for managing diverse pain conditions. However, given the variety of study designs and reported treatment outcomes, conclusions about the evidence for eye acupuncture for specific conditions are not possible at this stage.
Development of the ‘REadiness SElf-assessment (RESEA) guide’ to assist low and middle-income countries with establishing safe and sustainable radiotherapy services: a pragmatic sequential mixed qualitative methods project
Authors: Donkor Andrew , Luckett Tim , Aranda Sanchia , Vanderpuye Verna , Phillips Jane L.
Published: March 2021

Background

Improving access to radiotherapy services in low and middle-income countries (LMICs) is challenging. Many LMICs’ radiotherapy initiatives fail because of multi-faceted barriers leading to significant wastage of scarce resources. Supporting LMICs to self-assess their readiness for establishing radiotherapy services will help to improve cancer outcomes by ensuring safe, effective and sustainable evidenced-based cancer care. The aim of the study was to develop practical guidance for LMICs on self-assessing their readiness to establish safe and sustainable radiotherapy services.

Methods

The Access to Radiotherapy for Cancer treatment (ARC) Project was a pragmatic sequential mixed qualitative methods design underpinned by the World Health Organisation’s ‘Innovative Care for Chronic Conditions Framework’ and ‘Health System Building Blocks Framework for Action’ conceptual frameworks. This paper reports on the process of overall data integration and meta-inference from previously published components comprising a systematic review and two-part qualitative study (semi-structured interviews and a participant validation process). The meta-inferences enabled a series of radiotherapy readiness self-assessment requirements to be generated, formalised as a REadiness SElf-Assessment (RESEA) Guide’ for use by LMICs.

Findings

The meta-inferences identified a large number of factors that acted as facilitators and/or barriers, depending on the situation, which include: awareness and advocacy; political leadership; epidemiological data; financial resources; basic physical infrastructure; radiation safety legislative and regulatory framework; project management; and radiotherapy workforce training and education. ‘Commitment’, ‘cooperation’, ‘capacity’ and ‘catalyst’ were identified as the key domains enabling development of radiotherapy services. Across these four domains, the RESEA Guide included 37 requirements and 120 readiness questions that LMICs need to consider and answer as part of establishing a new radiotherapy service.

Conclusions

The RESEA Guide provides a new resource for LMICs to self-assess their capacity to establish safe and sustainable radiotherapy services. Future evaluation of the acceptability and feasibility of the RESEA Guide is needed to inform its validity. Further work, including field study, is needed to inform further refinements. Exploratory and confirmatory factor analyses are required to reduce the data set and test the fit of the four-factor structure (commitment, cooperation, capacity and catalyst) found in the current study.
Prenatal and postnatal diagnoses and phenotype of 8p23.3p22 duplication in one family
Authors: Shi Panlai , Wang Conghui , Zheng Yuting , Kong Xiangdong
Published: March 2021

Background

Distal 8p duplication is rare but clinically significant. Duplication syndrome results in variable phenotypes, such as developmental delay, intellectual disability, and malformation of the heart. We aimed to provide a better understanding of the phenotypes by studying duplication and its effects in a single family.

Methods

In a family with a previously induced labor (second fetus) at 12 weeks gestation due to increased nuchal translucency (3.5 mm), copy number variation sequencing (CNV-seq) revealed a 16.22 Mb deletion of 8p23.3p22. For their subsequent pregnancy, the family requested a prenatal diagnosis as well as CNV-seq, karyotyping and FISH testing of all family members.

Results

The first and third children were found to have a 16.22 Mb duplication of 8p23.3p22, containing the 8p23.1 duplication syndrome region. The duplication was inherited from their father, a carrier with a translocation of 8p22 and 22q13. We confirmed that the duplication site was located on chromosome 22q13 by combining the results of CNV-seq, karyotype and FISH. The first child is a 7.5-year-old boy. At one month old, he was diagnosed with a ventricular septal defect and treated surgically at age four. His growth and intelligence developed well, and he performed well in school. His primary issue is an inability to distinguish between the blade alveolars and retroflexes in speech. The third fetus had a normal ultrasound index from beginning until birth. The family elected to continue the pregnancy, and the baby was born healthy, providing us the opportunity to evaluate the effects of 8p23.3p22 duplication by comparison with the brother.

Conclusion

Our study makes a significant contribution to the literature because this relatively rare condition can have significant phenotypical consequences, and an understanding of the inheritance and variability of phenotypes caused by this mutation is essential to an increased understanding of the condition.
Impact of diabetes in patients waiting for invasive cardiac procedures during COVID-19 pandemic
Authors: Moreno Raúl , Díez José-Luis , Diarte José-Antonio , Salinas Pablo , de la Torre Hernández José María , Andres-Cordón Juan F. , Trillo Ramiro , Briales Juan Alonso , Amat-Santos Ignacio , Romaguera Rafael , Díaz José-Francisco , Vaquerizo Beatriz , Ojeda Soledad , Cruz-González Ignacio , Morena-Salas Daniel , Pérez de Prado Armando , Sarnago Fernando , Portero Pilar , Gutierrez-Barrios Alejandro , Alfonso Fernando , Bosch Eduard , Pinar Eduardo , Ruiz-Arroyo José-Ramón , Ruiz-Quevedo Valeriano , Jiménez-Mazuecos Jesús , Lozano Fernando , Rumoroso José-Ramón , Novo Enrique , Irazusta Francisco J. , García del Blanco Bruno , Moreu José , Ballesteros-Pradas Sara M. , Frutos Araceli , Villa Manuel , Alegría-Barrero Eduardo , Lázaro Rosa , Paredes Emilio
Published: March 2021

Background

During COVID-19 pandemic, elective invasive cardiac procedures (ICP) have been frequently cancelled or postponed. Consequences may be more evident in patients with diabetes.

Objectives

The objective was to identify the peculiarities of patients with DM among those in whom ICP were cancelled or postponed due to the COVID-19 pandemic, as well as to identify subgroups in which the influence of DM has higher impact on the clinical outcome.

Methods

We included 2,158 patients in whom an elective ICP was cancelled or postponed during COVID-19 pandemic in 37 hospitals in Spain. Among them, 700 (32.4%) were diabetics. Patients with and without diabetes were compared.

Results

Patients with diabetes were older and had a higher prevalence of other cardiovascular risk factors, previous cardiovascular history and co-morbidities. Diabetics had a higher mortality (3.0% vs. 1.0%; p = 0.001) and cardiovascular mortality (1.9% vs. 0.4%; p = 0.001). Differences were especially important in patients with valvular heart disease (mortality 6.9% vs 1.7% [p < 0.001] and cardiovascular mortality 4.9% vs 0.9% [p = 0.002] in patients with and without diabetes, respectively). In the multivariable analysis, diabetes remained as an independent risk factor both for overall and cardiovascular mortality. No significant interaction was found with other clinical variables.

Conclusion

Among patients in whom an elective invasive cardiac procedure is cancelled or postponed during COVID-19 pandemic, mortality and cardiovascular mortality is higher in patients with diabetes, irrespectively on other clinical conditions. These procedures should not be cancelled in patients with diabetes.
LINC00514 upregulates CCDC71L to promote cell proliferation, migration and invasion in triple‐negative breast cancer by sponging miR-6504-5p and miR-3139
Authors: Luo Xiao , Wang Hui
Published: March 2021

Background

Long noncoding RNAs (lncRNAs) have recently identified as essential gene modulators in numerous cancers. Previous studies have confirmed the oncogenic role of long intergenic nonprotein-coding RNA 00514 (LINC00514) in some cancers. Nevertheless, its biological function and mechanism remain unclear in triple-negative breast cancer (TNBC).

Methods

Herein, we detected LINC00514 expression level in TNBC tissues and cells using RT-qPCR. The function of LINC00514 in TNBC cellular activities was assessed by colony formation, EdU, wound healing, transwell assays and flow cytometry analysis.

Results

The binding between miR-6504-5p/miR-3139 and LINC00514/CCDC71L was validated by luciferase reporter assay. The results indicated that LINC00514 expression was upregulated in TNBC tissues and cells. Furthermore, it was manifested that silenced LINC00514 restrained cell proliferative, migratory and invasive abilities and promoted cell apoptosis. In mechanism, LINC00514 was revealed to sequester miR-6504-5p and miR-3139 in TNBC cells. Furthermore, the low level of miR-6504-5p and miR-3139 was identified in TNBC tissues and cells. Overexpression of miR-6504-5p or miR-3139 inhibited cell growth and migration in TNBC. CCDC71L was recognized as a common downstream gene of miR-6504-5p and miR-3139. Rescue assay verified that overexpressed CCDC71L countervailed the anti-tumor influence of LINC00514 knockdown on TNBC cell proliferation, migration, invasion and apoptosis.

Conclusions

LINC00514 promote cell proliferation, migration and invasion in triple-negative breast cancer by targeting the miR-6504-5p/miR-3139/CCDC71L axis in TNBC.
Overexpression of CCNE1 confers a poorer prognosis in triple-negative breast cancer identified by bioinformatic analysis
Authors: Yuan Qianqian , Zheng Lewei , Liao Yiqin , Wu Gaosong
Published: March 2021

Background

Triple-negative breast cancer (TNBC) is a major subtype of breast cancer. Due to the lack of effective therapeutic targets, the prognosis is poor. In order to find an effective target, despite many efforts, the molecular mechanisms of TNBC are still not well understood which remain to be a profound clinical challenge.

Methods

To identify the candidate genes in the carcinogenesis and progression of TNBC, microarray datasets GSE36693 and GSE65216 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and functional and pathway enrichment analyses were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases via DAVID. We constructed the protein-protein interaction network (PPI) and performed the module analysis using STRING and Cytoscape. Then, we reanalyzed the selected DEG genes, and the survival analysis was performed using cBioportal.

Results

A total of 140 DEGs were identified, consisting of 69 upregulated genes and 71 downregulated genes. Three hub genes were upregulated among the selected genes from PPI, and biological process analysis uncovered the fact that these genes were mainly enriched in p53 pathway and the pathways in cancer. Survival analysis showed that only CCNE1 may be involved in the carcinogenesis, invasion, or recurrence of TNBC. The expression levels of CCNE1 were significantly higher in TNBC cells than non-TNBC cells that were detected by qRT-PCR (P < 0.05).

Conclusion

CCNE1 could confer a poorer prognosis in TNBC identified by bioinformatic analysis and plays key roles in the progression of TNBC which may contribute potential targets for the diagnosis, treatment, and prognosis assessment of TNBC.
‘Snakes & Ladders’: factors influencing access to appropriate care for children and young people with suspected juvenile idiopathic arthritis – a qualitative study
Authors: Rapley Tim , May Carl , Smith Nicola , Foster Helen E.
Published: March 2021

Background

Many children and young people with juvenile idiopathic arthritis (JIA) experience delay in diagnosis and access to right care. The reasons for delay are multi-factorial and influenced by patient and family, clinician and organisational factors. Our aim was to explore the experiences of care, from initial symptoms to initial referral to paediatric rheumatology.

Methods

We analysed one-to-one and joint qualitative interviews with families of children with JIA (n = 36) presenting to a regional paediatric rheumatology service in the UK. We interviewed 51 family members (including mothers, fathers, patients, grandmothers and an aunt) and 10 health professionals (including orthopaedic surgeons, paediatricians, paediatric immunologist, General Practitioner and nurse) and a teacher involved in the care pathway of these JIA patients. Interviews were audio-recorded and analysed according to the standard procedures of rigorous qualitative analysis - coding, constant comparison, memoing and deviant case analysis.

Results

The median age of the children was 6 years old (range 1–17), with a spread of JIA subtypes. The median reported time to first PRh MDT visit from symptom onset was 22 weeks (range 4-364 weeks). Three key factors emerged in the pathways to appropriate care: (i) the persistence of symptoms (e.g. ‘change’ such as limp or avoidance of previously enjoyed activities); (ii) the persistence of parents help-seeking actions (e.g. repeat visits to primary and hospital care with concern that their child is not ‘normal’; iii) the experience and skills of health professionals resulting in different trajectories (e.g. no-real-concern-at-this-point or further-investigation-is-required). JIA was more likely to be considered amongst health practitioner if they had prior experiences of a child with JIA (moreso with a ‘protracted pathway’) or exposure to paediatric rheumatology in their training. Conversely JIA was more likely to be overlooked if the child had comorbidity such as learning disability or a chronic illness.

Conclusions

Care pathways are often ‘turbulent’ prior to a diagnosis of JIA with physical and emotional distress for families. There is need for greater awareness about JIA amongst health care professionals and observations of change (from family and non-health care professionals such as teachers) are key to trigger referral for paediatric rheumatology opinion.
Clinicopathological features of incidental parotid lesions
Authors: Al-Balas Hassan , Metwalli Zeyad A. , Eberson Sarah , Sada David M.
Published: March 2021

Background

The purpose of this study is to determine the histopathological spectrum and risk of primary malignancy of asymptomatic parotid lesions incidentally discovered on cross-sectional imaging.

Methods

Over a 10-year period, 154 patients underwent 163 ultrasound-guided parotid lesion biopsies at our institution. This retrospective chart review included 89 lesions in 87 patients with asymptomatic parotid lesions discovered on cross-sectional imaging studies performed for unrelated clinical indications. The histopathologic findings of all sampled lesions were reviewed. We evaluated the patient demographics and pathological diagnoses of sampled parotid lesions to determine the histopathological spectrum and risk of malignancy.

Results

The average age was 67.5 years and 92 % were males. 25 % of patients had bilateral lesions. The average size of the parotid lesions was 1.5 cm and 91 % were located in the superficial lobe. 92.1 % of lesions were benign with Warthin tumor being the most common diagnosis followed by pleomorphic adenoma. 2.3 % of lesions were primary parotid malignant neoplasms, while 5.6 % were metastatic lesions in patients with known malignancy.

Conclusions

The incidence of primary parotid malignant neoplasm in asymptomatic incidentally discovered parotid lesions is low. Imaging or clinical follow-up may be considered in patients with incidental parotid lesions who prefer to avoid biopsy.
Dose-escalated radiotherapy with PET/CT based treatment planning in combination with induction and concurrent chemotherapy in locally advanced (uT3/T4) squamous cell cancer of the esophagus: mature results of a phase I/II trial
Authors: Pöttgen C. , Gkika E. , Stahl M. , Abu Jawad J. , Gauler T. , Kasper S. , Trarbach T. , Herrmann K. , Lehmann N. , Jöckel K.-H. , Lax H. , Stuschke M.
Published: March 2021

Background

This prospective phase I/II trial assessed feasibility and efficacy of dose-escalated definitive chemoradiation after induction chemotherapy in locally advanced esophageal cancer. Primary study endpoint was loco-regional progression-free survival at 1 year.

Methods

Eligible patients received 2 cycles of induction chemotherapy with irinotecan, folinic acid and 5-fluorouracil weekly and cisplatin every 2 weeks (weeks 1–6, 8–13) followed by concurrent chemoradiation with cisplatin and irinotecan (weeks 14, 15, 17, 18, 20). Radiotherapy dose escalation was performed in three steps (60 Gy, 66 Gy, 72 Gy) using conventional fractionation, planning target volumes were delineated with the aid of 18F-FDG-PET/CT scans. During follow-up, endoscopic examinations were performed at regular intervals.

Results

Between 09/2006 and 02/2010, 17 patients were enrolled (male/female:13/4, median age: 59 [range 48–66] years, stage uT3N0/T3N1/T4N1: 4/12/1). One patient progressed during induction chemotherapy and underwent surgery. Of 16 patients treated with definitive chemoradiotherapy, 9 (56%) achieved complete response after completion of chemoradiation. One-, 2-, 3- and 5-year overall survival rates (OS) were 77% [95%CI: 59–100], 53% [34–83], 41% [23–73], and 29% [14–61], respectively. Loco-regional progression-free survival at 1, 3, and 5 years was 59% [40–88], 35% [19–67], and 29% [14–61], corresponding cumulative incidences of loco-regional progressions were 18% [4–39%], 35% [14–58%], and 41% [17–64%]. No treatment related deaths occurred. Grade 3 toxicities during induction therapy were: neutropenia (41%), diarrhoea (41%), during combined treatment: neutropenia (62%) and thrombocytopenia (25%).

Conclusions

Dose-escalated radiotherapy and concurrent cisplatin/irinotecan after cisplatin/irinotecan/5FU induction chemotherapy was tolerable. The hypothesized phase II one-year loco-regional progression free survival rate of 74% was not achieved. Long-term survival compares well with other studies on definitive radiotherapy using irinotecan and cisplatin but is not better than recent trials using conventionally fractionated radiotherapy ad 50 Gy with concurrent paclitaxel or 5FU and platinum compound.

Trial registration The present trial was registered as a phase I/II trial at the EudraCT database: Nr. 2005-006097-10 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-006097-10/DE) and authorized to proceed on 2006-09-25.
Sugammadex is associated with shorter hospital length of stay after open lobectomy for lung cancer: a retrospective observational study
Authors: Song Seung Won , Yoo Kyung Yeon , Ro Yong Sung , Pyeon Taehee , Bae Hong-Beom , Kim Joungmin
Published: March 2021

Background

Sugammadex is associated with few postoperative complications. Postoperative pulmonary complications (PPC) are related to prolonged hospitalizations. Present study explored whether the use of sugammadex could reduce PPCs and thereby reduce hospital length of stay (LOS) after lung surgery.

Methods

We reviewed the medical records of patients who underwent elective open lobectomy for lung cancer from January 2010 to December 2015. Patients were divided into the sugammadex group and pyridostigmine group.

The primary outcome was hospital LOS and secondary outcomes were postoperative complications and overall survival at 1 year. The cohort was subdivided into patients with and without prolonged LOS to explore the effects of sugammadex on outcomes in each group. Risk factors for LOS were determined via multivariate analyses. After propensity score matching, 127 patients were assigned to each group.

Results

Median hospital LOS was shorter (10.0 vs. 12.0 days) and the incidence of postoperative atelectasis was lower (18.1 vs. 29.9%) in the sugammadex group. However, no significant difference in overall survival between the groups was seen over 1 year (hazard ratio, 0.967; 95% confidence interval, 0.363 to 2.577). Sugammadex was a predictor related to LOS (exponential coefficient 0.88; 95% CI 0.82–0.95).

Conclusions

Our data suggest that sugammadex is a preferable agent for neuromuscular blockade (NMB) reversal than cholinesterase inhibitors in this patient population.

Trial registration

This study registered in the Clinical Research Information Service of the Korea National Institute of Health (approval number: KCT0004735, Date of registration: 21 January 2020, Retrospectively registered).
Establishment of an in vitro model for analyzing mitochondrial ultrastructure in PRKN-mutated patient iPSC-derived dopaminergic neurons
Authors: Yokota Mutsumi , Kakuta Soichiro , Shiga Takahiro , Ishikawa Kei-ichi , Okano Hideyuki , Hattori Nobutaka , Akamatsu Wado , Koike Masato
Published: March 2021

Mitochondrial structural changes are associated with the regulation of mitochondrial function, apoptosis, and neurodegenerative diseases. PRKN is known to be involved with various mechanisms of mitochondrial quality control including mitochondrial structural changes. Parkinson’s disease (PD) with PRKN mutations is characterized by the preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta, which has been suggested to result from the accumulation of damaged mitochondria. However, ultrastructural changes of mitochondria specifically in dopaminergic neurons derived from iPSC have rarely been analyzed. The main reason for this would be that the dopaminergic neurons cannot be distinguished directly among a mixture of iPSC-derived differentiated cells under electron microscopy. To selectively label dopaminergic neurons and analyze mitochondrial morphology at the ultrastructural level, we generated control and PRKN-mutated patient tyrosine hydroxylase reporter (TH-GFP) induced pluripotent stem cell (iPSC) lines. Correlative light-electron microscopy analysis and live cell imaging of GFP-expressing dopaminergic neurons indicated that iPSC-derived dopaminergic neurons had smaller and less functional mitochondria than those in non-dopaminergic neurons. Furthermore, the formation of spheroid-shaped mitochondria, which was induced in control dopaminergic neurons by a mitochondrial uncoupler, was inhibited in the PRKN-mutated dopaminergic neurons. These results indicate that our established TH-GFP iPSC lines are useful for characterizing mitochondrial morphology, such as spheroid-shaped mitochondria, in dopaminergic neurons among a mixture of various cell types. Our in vitro model would provide insights into the vulnerability of dopaminergic neurons and the processes leading to the preferential loss of dopaminergic neurons in patients with PRKN mutations.
ATAD2 interacts with C/EBPβ to promote esophageal squamous cell carcinoma metastasis via TGF-β1/Smad3 signaling
Authors: Cao Lian-Jing , Zhang Yi-Jun , Dong Si-Qi , Li Xi-Zhao , Tong Xia-Ting , Chen Dong , Wu Zi-Yi , Zheng Xiao-Hui , Xue Wen-Qiong , Jia Wei-Hua , Zhang Jiang-Bo
Published: March 2021

Background

Distant metastasis is the leading cause of death for esophageal squamous cell carcinoma (ESCC) with limited treatment options and unsatisfactory effectiveness. Bromodomain (BRD) containing proteins are emerging targets for cancer therapy with promising effects. As a unique member of BRD family, the function and molecular mechanism of ATAD2 in cancer development is seldomly investigated.

Methods

The clinical impact of ATAD2 was assessed both at RNA and protein level in 75 and 112 ESCC patients separately. The biological function of ATAD2 was investigated in vitro and in vivo. Signaling pathway and downstream effectors of ATAD2 were identified by RNA sequencing, luciferase reporter, co-immunoprecipitation, chromatin immunoprecipitation, immunofluorescence and western blot assay.

Results

We found that elevated ATAD2 expression was significantly associated with lymph node metastasis, advanced clinical stage as well as poor survival of ESCC patients. Silencing ATAD2 significantly suppressed ESCC cell migration and invasion in vitro, and inhibited tumor growth and lung metastasis in vivo. Mechanically, we identified a new cofactor, C/EBPβ. ATAD2 directly interacted with C/EBPβ and promoted its nuclear translocation, which directly bound to the promoter region of TGF-β1 and activated its expression. Further, we demonstrated that TGF-β1 activated its downstream effectors in a Smad3 dependent manner. In addition, we further found that ATAD2 promoted ESCC metastasis through TGF-β signaling induced Snail expression and the subsequent epithelial-mesenchymal transition.

Conclusion

Our findings demonstrated the pro-metastatic function of ATAD2 and uncovered the new molecular mechanism by regulating C/EBPβ/TGF-β1/Smad3/Snail signaling pathway, thus providing a potential target for the treatment of ESCC metastasis.
Urinary metabolites predict mortality or need for renal replacement therapy after combat injury
Authors: Gisewhite Sarah , Stewart Ian J. , Beilman Greg , Lusczek Elizabeth
Published: March 2021

Background

Traditionally, patient risk scoring is done by evaluating vital signs and clinical severity scores with clinical intuition. Urinary biomarkers can add objectivity to these models to make risk prediction more accurate. We used metabolomics to identify prognostic urinary biomarkers of mortality or need for renal replacement therapy (RRT). Additionally, we assessed acute kidney injury (AKI) diagnosis, injury severity score (ISS), and AKI stage.

Methods

Urine samples (n = 82) from a previous study of combat casualties were evaluated using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Chenomx software was used to identify and quantify urinary metabolites. Metabolite concentrations were normalized by urine output, autoscaled, and log-transformed. Partial least squares discriminant analysis (PLS-DA) and statistical analysis were performed. Receiver operating characteristic (ROC) curves were used to assess prognostic utility of biomarkers for mortality and RRT.

Results

Eighty-four (84) metabolites were identified and quantified in each urine sample. Of these, 11 were identified as drugs or drug metabolites and excluded. The PLS-DA models for ISS and AKI diagnosis did not have acceptable model statistics. Therefore, only mortality/RRT and AKI stage were analyzed further. Of 73 analyzed metabolites, 9 were significantly associated with mortality/RRT (p < 0.05) and 11 were significantly associated with AKI stage (p < 0.05). 1-Methylnicotinamide was the only metabolite to be significantly associated (p < 0.05) with all outcomes and was significantly higher (p < 0.05) in patients with adverse outcomes. Elevated lactate and 1-methylnicotinamide levels were associated with higher AKI stage and mortality and RRT, whereas elevated glycine levels were associated with patients who survived and did not require RRT, or had less severe AKI. ROC curves for each of these metabolites and the combined panel had good predictive value (lactate AUC = 0.901, 1-methylnicotinamide AUC = 0.864, glycine AUC = 0.735, panel AUC = 0.858).

Conclusions

We identified urinary metabolites associated with AKI stage and the primary outcome of mortality or need for RRT. Lactate, 1-methylnicotinamide, and glycine may be used as a panel of predictive biomarkers for mortality and RRT. 1-Methylnicotinamide is a novel biomarker associated with adverse outcomes. Additional studies are necessary to determine how these metabolites can be utilized in clinically-relevant risk prediction models.