bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between dietary diversity score and general and abdominal obesity in Iranian children and adolescents
Authors: Golpour-Hamedani Sahar , Rafie Nahid , Pourmasoumi Makan , Saneei Parvane , Safavi Sayyed Morteza
Published: December 2020

Background

To evaluate the association between diet and disease, the consideration of a whole diet has appeared to be more effective than the examination of single-nutrient intake. This study aimed to examine the relationship between dietary diversity score (DDS) and obesity in Iranian children.

Methods

A cross-sectional study was conducted on 456 children aged 11–18 years, who were selected by random cluster sampling. The usual food intake for each participant assessed using a validated Food frequency questionnaire (FFQ). To calculate the dietary diversity score, food items were categorized into 5 broad groups and 23 subgroups based on the US Department of Agriculture Food Guide Pyramid. Participants were categorized based on the DDS tertile cut-off points. Anthropometric measurements were conducted based on standard protocols. Overweight and obesity were defined as 85th ≤ BMI < 95th, and ≥ 95th percentiles of BMI, respectively. Additionally, abdominal obesity was considered as WC ≥ 85th percentile.

Results

Mean and standard deviation (SD) of subjects’ Body Mass Index (BMI) and waist circumference were 20.88 (SD 4.22) kg/m2 and 74.27 (SD 10.31) cm, respectively. The probability of overweight and obesity was increased as tertiles of DDS increased (OR among tertiles: 1.00, 1.82 and 2.13 for overweight and 1.00, 2.60 and 3.45 for obesity; this was the same for abdominal obesity: 1.00, 2.22 and 3.45, P <  0.001 for all). However, no statistically significant results were found after adjustment for energy intake.

Conclusion

Dietary diversity positively affected obesity through higher energy intake. Despite the wide recommendation of having high dietary diversity, public health programs should emphasize to improve dietary diversity only in selective food items.
Peer assessment of professionalism in undergraduate medical education
Authors: Curran Vernon R. , Fairbridge Nicholas A. , Deacon Diana
Published: December 2020

Background

Fostering professional behaviour has become increasingly important in medical education and non-traditional approaches to assessment of professionalism may offer a more holistic representation of students’ professional behaviour development. Emerging evidence suggests peer assessment may offer potential as an alternative method of professionalism assessment. We introduced peer assessment of professionalism in pre-clerkship phases of undergraduate medical education curriculum at our institution and evaluated suitability of adopting a professional behaviour scale for longitudinal tracking of student development, and student comfort and acceptance of peer assessment.

Methods

Peer assessment was introduced using a validated professional behaviours scale. Students conducted repeated, longitudinal assessments of their peers from small-group, clinical skills learning activities. An electronic assessment system was used to collect peer assessments, collate and provide reports to students. Student opinions of peer assessment were initially surveyed before introducing the process, confirmatory analyses were conducted of the adopted scale, and students were surveyed to explore satisfaction with the peer assessment process.

Results

Students across all phases of the curriculum were initially supportive of anonymous peer assessment using small-group learning sessions. Peer scores showed improvement over time, however the magnitude of increase was limited by ceiling effects attributed to the adopted scale. Students agreed that the professional behaviours scale was easy to use and understand, however a majority disagreed that peer assessment improved their understanding of professionalism or was a useful learning experience.

Conclusions

Peer assessment of professional behaviours does expose students to the process of assessing one’s peers, however the value of such processes at early stages of medical education may not be fully recognized nor appreciated by students. Electronic means for administering peer assessment is feasible for collecting and reporting peer feedback. Improvement in peer assessed scores was observed over time, however student opinions of the educational value were mixed and indeterminate.
Barriers in implementing the dying patient law: the Israeli experience - a qualitative study
Authors: Zigdon Avi , Nissanholtz-Gannot Rachel
Published: December 2020

Background

Coping with end-of-life issues is a major challenge for governments and health systems. Despite progress in legislation, many barriers exist to its full implementation. This study is aimed at identifying these end-of-life barriers in relation to Israel.

Methods

Qualitative in-depth interviews using professionals and decision makers in the health-care and related systems (n = 37) were carried out, along with two focus groups based on brainstorming techniques consisting of nurses (n = 10) and social workers (n = 10). Data was managed and analyzed using Naralyzer software.

Results

Qualitative analysis showed identification of six primary barriers: 1) law, procedures, and forms; 2) clinical aspects; 3) human aspects; 4) knowledge and skills of medical teams; 5) communication; and 6) resource allocation. These were further divided into 44 sub area barriers.

Conclusions

This study highlights the role of the family doctor in end-of-life by training physicians in decision-making workshops and increasing their knowledge in the field of palliative medicine. Effectively channeling resources, knowledge, and support for medical teams, by accounting for the structure and response of the units for home treatment will improve patient’s access to information on and support for end-of-life laws, as well as reduce legislative barriers in other countries that face the same issues.
Can statistical adjustment guided by causal inference improve the accuracy of effect estimation? A simulation and empirical research based on meta-analyses of case–control studies
Authors: Yan Ruohua , Liu Tianyi , Peng Yaguang , Peng Xiaoxia
Published: December 2020

Background

Statistical adjustment is often considered to control confounding bias in observational studies, especially case–control studies. However, different adjustment strategies may affect the estimation of odds ratios (ORs), and in turn affect the results of their pooled analyses. Our study is aimed to investigate how to deal with the statistical adjustment in case–control studies to improve the validity of meta-analyses.

Methods

Three types of adjustment strategies were evaluated including insufficient adjustment (not all preset confounders were adjusted), full adjustment (all confounders were adjusted under the guidance of causal inference), and improper adjustment (covariates other than confounders were adjusted). We carried out a series of Monte Carlo simulation experiments based on predesigned scenarios, and assessed the accuracy of effect estimations from meta-analyses of case–control studies by combining ORs calculated according to different adjustment strategies. Then we used the data from an empirical review to illustrate the replicability of the simulation results.

Results

For all scenarios with different strength of causal relations, combining ORs that were comprehensively adjusted for confounders would get the most precise effect estimation. By contrast, combining ORs that were not sufficiently adjusted for confounders or improperly adjusted for mediators or colliders would easily introduce bias in causal interpretation, especially when the true effect of exposure on outcome was weak or none. The findings of the simulation experiments were further verified by the empirical research.

Conclusions

Statistical adjustment guided by causal inference are recommended for effect estimation. Therefore, when conducting meta-analyses of case–control studies, the causal relationship formulated by exposure, outcome, and covariates should be firstly understood through a directed acyclic graph, and then reasonable original ORs could be extracted and combined by suitable methods.
Dental visits in Medicaid-enrolled youth with mental illness: an analysis of administrative claims data
Authors: Stockbridge Erica L. , Dhakal Eleena , Griner Stacey B. , Loethen Abiah D. , West Joseph F. , Vera Joseph W. , Nandy Karabi
Published: December 2020

Background

State Medicaid plans across the United States provide dental insurance coverage to millions of young persons with mental illness (MI), including those with attention deficit hyperactivity disorder (ADHD), depression, anxiety, bipolar disorder, and schizophrenia. There are significant oral health challenges associated with MI, and providing dental care to persons with MI while they are young provides a foundation for future oral health. However, little is known about the factors associated with the receipt of dental care in young Medicaid enrollees with MI. We aimed to identify mental and physical health and sociodemographic characteristics associated with dental visits among this population.

Methods

We retrospectively analyzed administrative claims data from a Medicaid specialty health plan (September 2014 to December 2015). All enrollees in the plan had MI and were ≥ 7 years of age; data for enrollees aged 7 to 20 years were analyzed. We used two-level, mixed effects regression models to explore the relationships between enrollee characteristics and dental visits during 2015.

Results

Of 6564 Medicaid-enrolled youth with MI, 29.0% (95% CI, 27.9, 30.1%) had one or more visits with a dentist or dental hygienist. Within youth with MI, neither anxiety (Adjusted odds ratio [AOR] = 1.15, p = 0.111), post-traumatic stress disorder (AOR = 1.31, p = 0.075), depression (AOR = 1.02, p = 0.831), bipolar disorder (AOR = 0.97, p = 0.759), nor schizophrenia (AOR = 0.83, p = 0.199) was associated with dental visits in adjusted analyses, although having ADHD was significantly associated with higher odds of dental visits relative to not having this condition (AOR = 1.34, p < 0.001). Age, sex, race/ethnicity, language, and education were also significantly associated with visits (p < 0.05 for all).

Conclusions

Dental utilization as measured by annual dental visits was lower in Medicaid-enrolled youth with MI relative to the general population of Medicaid-enrolled youth. However, utilization varied within the population of Medicaid-enrolled youth with MI, and we identified a number of characteristics significantly associated with the receipt of dental services. By identifying these variations in dental service use this study facilitates the development of targeted strategies to increase the use of dental care in – and consequently improve the current and long-term wellbeing of – the vulnerable population of Medicaid-enrolled youth with MI.
Effectiveness of training interventions to improve quality of medical certification of cause of death: systematic review and meta-analysis
Authors: Gamage U. S. H. , Mahesh Pasyodun Koralage Buddhika , Schnall Jesse , Mikkelsen Lene , Hart John D. , Chowdhury Hafiz , Li Hang , McLaughlin Deirdre , Lopez Alan D.
Published: December 2020

Background

Valid cause of death data are essential for health policy formation. The quality of medical certification of cause of death (MCCOD) by physicians directly affects the utility of cause of death data for public policy and hospital management. Whilst training in correct certification has been provided for physicians and medical students, the impact of training is often unknown. This study was conducted to systematically review and meta-analyse the effectiveness of training interventions to improve the quality of MCCOD.

Methods

This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration ID: CRD42020172547) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. CENTRAL, Ovid MEDLINE and Ovid EMBASE databases were searched using pre-defined search strategies covering the eligibility criteria. Studies were selected using four screening questions using the Distiller-SR software. Risk of bias assessments were conducted with GRADE recommendations and ROBINS-I criteria for randomised and non-randomised interventions, respectively. Study selection, data extraction and bias assessments were performed independently by two reviewers with a third reviewer to resolve conflicts. Clinical, methodological and statistical heterogeneity assessments were conducted. Meta-analyses were performed with Review Manager 5.4 software using the ‘generic inverse variance method’ with risk difference as the pooled estimate. A ‘summary of findings’ table was prepared using the ‘GRADEproGDT’ online tool. Sensitivity analyses and narrative synthesis of the findings were also performed.

Results

After de-duplication, 616 articles were identified and 21 subsequently selected for synthesis of findings; four underwent meta-analysis. The meta-analyses indicated that selected training interventions significantly reduced error rates among participants, with pooled risk differences of 15–33%. Robustness was identified with the sensitivity analyses. The findings of the narrative synthesis were similarly suggestive of favourable outcomes for both physicians and medical trainees.

Conclusions

Training physicians in correct certification improves the accuracy and policy utility of cause of death data. Investment in MCCOD training activities should be considered as a key component of strategies to improve vital registration systems given the potential of such training to substantially improve the quality of cause of death data.
Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood
Authors: Tay Chau Thien , Hart Roger J. , Hickey Martha , Moran Lisa J. , Earnest Arul , Doherty Dorota A. , Teede Helena J. , Joham Anju E.
Published: December 2020

Background

Polycystic ovary syndrome (PCOS) is challenging to diagnose. While the 2003 Rotterdam criteria are widely used for adults, the 2018 international PCOS guideline recommended updated Rotterdam criteria with both hyperandrogenism and oligo-anovulation for adolescents based on evidence-informed expert consensus. This study compared the prevalence of PCOS using updated and original Rotterdam criteria in community-based adolescents and explored long-term body mass index (BMI) trajectories across different diagnostic phenotypes.

Methods

Overall, 227 postmenarchal adolescent females from the prospective cohort Raine Study undertook comprehensive PCOS assessment at age 14–16 years. Detailed anthropometric measurements were collected from birth until age 22 years. Cross-sectional and longitudinal BMI were analyzed using t tests and generalized estimating equations.

Results

PCOS was diagnosed in 66 (29.1%) participants using original criteria versus 37 (16.3%) participants using updated Rotterdam criteria. Using updated criteria, participants with PCOS had higher BMI than participants without PCOS from prepubertal. Only the phenotype meeting the updated criteria was significantly associated with higher long-term BMI gain whereas other PCOS phenotypes had similar BMI trajectories to participants without PCOS (p < 0.001).

Conclusions

The use of the 2018 updated Rotterdam criteria reduces over-diagnosis of PCOS in adolescents and identifies those at the greatest risk of long-term weight gain, a key contributor to disease severity and long-term health implications. The BMI trajectories of females with PCOS on updated criteria diverge prepubertally compared to those without PCOS. This work supports targeting adolescents diagnosed with PCOS on the 2018 updated criteria for early lifestyle interventions to prevent long-term health complications.
Changes in oxidation-antioxidation function on the thymus of chickens infected with reticuloendotheliosis virus
Authors: Yang Dahan , Zhao Chenhui , Zhang Meixi , Zhang Shujun , Zhai Jie , Gao XueLi , Liu Chaonan , Lv Xiaoping , Zheng Shimin
Published: December 2020

Background

Reticuloendotheliosis virus (REV) is a retrovirus that causes severe immunosuppression in poultry. Animals grow slowly under conditions of oxidative stress. In addition, long-term oxidative stress can impair immune function, as well as accelerate aging and death. This study aimed to elucidate the pathogenesis of REV from the perspective of changes in oxidative-antioxidative function following REV infection.

Methods

A total of 80 one-day-old specific pathogen free (SPF) chickens were randomly divided into a control group (Group C) and an REV-infected group (Group I). The chickens in Group I received intraperitoneal injections of REV with 104.62/0.1 mL TCID50. Thymus was collected on day 1, 3, 7, 14, 21, 28, 35, and 49 for histopathology and assessed the status of oxidative stress.

Results

In chickens infected with REV, the levels of H2O2 and MDA in the thymus increased, the levels of TAC, SOD, CAT, and GPx1 decreased, and there was a reduction in CAT and Gpx1 mRNA expression compared with the control group. The thymus index was also significantly reduced. Morphological analysis showed that REV infection caused an increase in the thymic reticular endothelial cells, inflammatory cell infiltration, mitochondrial swelling, and nuclear damage.

Conclusions

These results indicate that an increase in oxidative stress enhanced lipid peroxidation, markedly decreased antioxidant function, caused thymus atrophy, and immunosuppression in REV-infected chickens.
Identification of LINC02310 as an enhancer in lung adenocarcinoma and investigation of its regulatory network via comprehensive analyses
Authors: Zhao Wenyuan , Wang Jun , Luo Qingxi , Peng Wei , Li Bin , Wang Lei , Zhang Chunfang , Duan Chaojun
Published: December 2020

Background

Lung adenocarcinoma (LADC) is a major subtype of non-small cell lung cancer and has one of the highest mortality rates. An increasing number of long non-coding RNAs (LncRNAs) were reported to be associated with the occurrence and progression of LADC. Thus, it is necessary and reasonable to find new prognostic biomarkers for LADC among LncRNAs.

Methods

Differential expression analysis, survival analysis, PCR experiments and clinical feature analysis were performed to screen out the LncRNA which was significantly related to LADC. Its role in LADC was verified by CCK-8 assay and colony. Furthermore, competing endogenous RNA (ceRNA) regulatory network construction, enrichment analysis and protein–protein interaction (PPI) network construction were performed to investigate the downstream regulatory network of the selected LncRNA.

Results

A total of 2431 differentially expressed LncRNAs (DELncRNAs) and 2227 differentially expressed mRNAs (DEmRNAs) were from The Cancer Genome Atlas database. Survival analysis results indicated that lnc-YARS2-5, lnc-NPR3-2 and LINC02310 were significantly related to overall survival. Their overexpression indicated poor prognostic. PCR experiments and clinical feature analysis suggested that LINC02310 was significantly correlated with TNM-stage and T-stage. CCK-8 assay and colony formation assay demonstrated that LINC02310 acted as an enhancer in LADC. In addition, 3 targeted miRNAs of LINC02310 and 414 downstream DEmRNAs were predicted. The downstream DEmRNAs were then enriched in 405 Gene Ontology terms and 11 Kyoto Encyclopedia of Genes and Genomes pathways, which revealed their potential functions and mechanisms. The PPI network showed the interactions among the downstream DEmRNAs.

Conclusions

This study verified LINC02310 as an enhancer in LADC and performed comprehensive analyses on its downstream regulatory network, which might benefit LADC prognoses and therapies.
Genetic and clinical phenotypic analysis of familial stapes sclerosis caused by an NOG mutation
Authors: Yu Rong , Jiang Hongqun , Liao Huihuang , Luo Wugen
Published: December 2020

Background

The noggin protein encoded by the NOG gene can interfere with the binding of bone morphogenetic protein to its receptor, thus affecting bone and joint development. The symptoms include abnormal skeletal development and conductive deafness.

Methods

In a retrospective study, clinical data of the proband and her family members, including 8 people and 50 healthy normal controls, were collected. Second-generation sequencing was performed on peripheral blood samples from them.

Results

The sequencing analysis indicated that in the proband, theNOGgene had a c.532T > C, p.C178R (cytosine deletion, NM_005450.6:c.532T > C), leading to an amino acid change. The proband's father, grandmother, second sister, and third sister also had this mutation, whereas family members with normal phenotypes did not have the mutation.

Conclusion

Analysis of this family showed that the novel presentation of the c.532T > C, p.C178R mutation in theNOGgene resulted in syndrome-type autosomal dominant inheritance reflected in a mild clinical phenotype, which is of great importance for further studies of the clinical phenotype and pathogenesis of stapes sclerosis.
Designing next generation recombinant protein expression platforms by modulating the cellular stress response in Escherichia coli
Authors: Guleria Richa , Jain Priyanka , Verma Madhulika , Mukherjee Krishna J.
Published: December 2020

Background

A cellular stress response (CSR) is triggered upon recombinant protein synthesis which acts as a global feedback regulator of protein expression. To remove this key regulatory bottleneck, we had previously proposed that genes that are up-regulated post induction could be part of the signaling pathways which activate the CSR. Knocking out some of these genes which were non-essential and belonged to the bottom of the E. coli regulatory network had provided higher expression of GFP and L-asparaginase.

Results

We chose the best performing double knockout E. coli BW25113ΔelaAΔcysW and demonstrated its ability to enhance the expression of the toxic Rubella E1 glycoprotein by 2.5-fold by tagging it with sfGFP at the C-terminal end to better quantify expression levels. Transcriptomic analysis of this hyper-expressing mutant showed that a significantly lower proportion of genes got down-regulated post induction, which included genes for transcription, translation, protein folding and sorting, ribosome biogenesis, carbon metabolism, amino acid and ATP synthesis. This down-regulation which is a typical feature of the CSR was clearly blocked in the double knockout strain leading to its enhanced expression capability. Finally, we supplemented the expression of substrate uptake genes glpK and glpD whose down-regulation was not prevented in the double knockout, thus ameliorating almost all the negative effects of the CSR and obtained a further doubling in recombinant protein yields.

Conclusion

The study validated the hypothesis that these up-regulated genes act as signaling messengers which activate the CSR and thus, despite having no casual connection with recombinant protein synthesis, can improve cellular health and protein expression capabilities. Combining gene knockouts with supplementing the expression of key down-regulated genes can counter the harmful effects of CSR and help in the design of a truly superior host platform for recombinant protein expression.
The Gαi protein subclass selectivity to the dopamine D2 receptor is also decided by their location at the cell membrane
Authors: Polit Agnieszka , Rysiewicz Beata , Mystek Paweł , Błasiak Ewa , Dziedzicka-Wasylewska Marta
Published: December 2020

Background

G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins plays an important role in the cellular regulation of responses to external stimuli. Despite intensive structural research, the mechanism underlying the receptor–G protein coupling of closely related subtypes of Gαi remains unclear. In addition to the structural changes of interacting proteins, the interactions between lipids and proteins seem to be crucial in GPCR-dependent cell signaling due to their functional organization in specific membrane domains. In previous works, we found that Gαs and Gαi3 subunits prefer distinct types of membrane-anchor lipid domains that also modulate the G protein trimer localization. In the present study, we investigated the functional selectivity of dopamine D2 long receptor isoform (D2R) toward the Gαi1, Gαi2, and Gαi3 subunits, and analyzed whether the organization of Gαi heterotrimers at the plasma membrane affects the signal transduction.

Methods

We characterized the lateral diffusion and the receptor–G protein spatial distribution in living cells using two assays: fluorescence recovery after photobleaching microscopy and fluorescence resonance energy transfer detected by fluorescence-lifetime imaging microscopy. Depending on distribution of data differences between Gα subunits were investigated using parametric approach–unpaired T-test or nonparametric–Mann–Whitney U test.

Results

Despite the similarities between the examined subunits, the experiments conducted in the study revealed a significantly faster lateral diffusion of the Gαi2 subunit and the singular distribution of the Gαi1 subunit in the plasma membrane. The cell membrane partitioning of distinct Gαi heterotrimers with dopamine receptor correlated very well with the efficiency of D2R-mediated inhibition the formation of cAMP.

Conclusions

This study showed that even closely related subunits of Gαi differ in their membrane-trafficking properties that impact on their signaling. The interactions between lipids and proteins seem to be crucial in GPCR-dependent cell signaling due to their functional organization in specific membrane domains, and should therefore be taken into account as one of the selectivity determinants of G protein coupling.
Circular RNA expression profiles and features in NAFLD mice: a study using RNA-seq data
Authors: Yuan Xinlu , Diao Jianjun , Du Anqing , Wen Song , Zhou Ligang , Pan Yangbin
Published: December 2020

Background

Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously.

Methods

A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).

Results

The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development.

Conclusions

Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.
A systematic literature review and meta-analysis of characterization of canine parvoviruses 2 prevalent in mainland China
Authors: Dong Bo , Zhang Gaoqiang , Zhang Jiajia , Bai Junyu , Lin Weiming
Published: December 2020

Background

Canine parvovirus 2 (CPV-2) is a pathogenic virus that infects dogs, causing a highly infectious disease. Monitoring CPV-2 spread is an important part of prevention; however, the prevalence and epidemiological characteristics of CPV-2 have not been systematically evaluated and analyzed in mainland China. Therefore, a systematic review and meta-analysis were performed to assess prevalence and epidemiological characteristics of CPV-2 in domestic dogs in mainland China.

Methods

In this study, Chinese and English literature on CPV-2 epidemiology published between January 2006 and December 2019 was evaluated. Regarding meta-analysis, the random-effect model was employed by forest plot with 95% of confidence interval. The number of CPV-2 infections was identified and the pooled prevalence of infection, as well as the epidemiological characteristics, was calculated using meta-analysis.

Results

A total of 39 studies (data from 137,844 dogs) met the evaluation criteria and were used in our study. The pooled prevalence of CPV-2 infection in mainland China was 36%. CPV-2 infection were associated with age, breed, sampling season and immunization status, but not with gender, publication time and diagnostic methods.

Conclusions

Our results indicated that CPV-2 is prevalent among dogs in China. It is therefore necessary to carry out continuous surveillance and epidemiological studies of CPV-2. In addition, accordingly, effective measures should be taken to prevent the transmission and spread of CPV-2 among the Chinese dog population.
Arabic version of the Hayling sentence completion test: scale validation, normative data and factors associated with executive functions in a sample of the Lebanese adults
Authors: Boutros Sarah , El Hachem Emilio , Mattar Joseph , Hallit Souheil , Mattar Hanna
Published: December 2020

Background

This study was conducted for several reasons, primarily because of the lack of an Arabic version of the HSCT that could be beneficial in our clinical practice. Another reason is the need to find potential relationships between various factors with executive functions, especially problematic mobile phone use as suggested by many previous studies, since smartphones have become, nowadays, a daily companion of people from all generations. Thus, it is important to conduct this study in Lebanon to be adapted to the ideas, customs and social behavior of the Lebanese citizens. Hence, the objectives of the current study are to use the Arabic version of the HSCT in healthy community-dwelling Arabic-speaking adults in Lebanon, to check its validity compared to other versions of the test, as well as to identify risk factors that might affect the executive functions in these adults.

Methods

Between August–December 2019, 350 participants were randomly selected. The Arabic version of the HSCT, divided into automatic and inhibition conditions, was used; in each condition, participants’ response-time and number of errors committed were recorded.

Results

None of the scale items was removed. For the automatic condition, response-time items converged over one factor (αCronbach = 0.905) and number of errors converged over seven factors (αCronbach = 0.334). For the inhibition condition, response-time converged over one factor (αCronbach = 0.943) and number of errors converged over four factors (αCronbach = 0.728). Using electricity as a heating method inside the house was significantly associated with a lower response-time, whereas higher problematic mobile phone use was associated with higher response-time. Using wood as a heating system inside the house and higher problematic mobile phone use were associated with higher number of errors, while using Arabian incense (bakhour) inside the house was associated with lower number of errors.

Conclusion

We were able to set normative data for the HSCT Arabic version for use in the Lebanese population. Problematic mobile phone use was associated with lower inhibitory control in terms of response-time and errors number.
Coincidence analysis: a new method for causal inference in implementation science
Authors: Whitaker Rebecca Garr , Sperber Nina , Baumgartner Michael , Thiem Alrik , Cragun Deborah , Damschroder Laura , Miech Edward J. , Slade Alecia , Birken Sarah
Published: December 2020

Background

Implementation of multifaceted interventions typically involves many diverse elements working together in interrelated ways, including intervention components, implementation strategies, and features of local context. Given this real-world complexity, implementation researchers may be interested in a new mathematical, cross-case method called Coincidence Analysis (CNA) that has been designed explicitly to support causal inference, answer research questions about combinations of conditions that are minimally necessary or sufficient for an outcome, and identify the possible presence of multiple causal paths to an outcome. CNA can be applied as a standalone method or in conjunction with other approaches and can reveal new empirical findings related to implementation that might otherwise have gone undetected.

Methods

We applied CNA to a publicly available dataset from Sweden with county-level data on human papillomavirus (HPV) vaccination campaigns and vaccination uptake in 2012 and 2014 and then compared CNA results to the published regression findings.

Results

The original regression analysis found vaccination uptake was positively associated only with the availability of vaccines in schools. CNA produced different findings and uncovered an additional solution path: high vaccination rates were achieved by either (1) offering the vaccine in all schools or (2) a combination of offering the vaccine in some schools and media coverage.

Conclusions

CNA offers a new comparative approach for researchers seeking to understand how implementation conditions work together and link to outcomes.
Surveillance ultrasonography for conservative treatment of femoral shaft fractures in young children
Authors: Gao Hui , Wang Zhaoxia , Su Yuxi
Published: December 2020

Background

The treatment for femoral shaft fracture (FSF) depends on the age of the patient. While the Pavlik harness is the first choice for patients under 6 months of age, spica casting is preferred for patients over 6 months and under preschool age. Minimally-invasive surgery using elastic stable intramedullary nails is also used in some cases. Skin traction is another treatment choice for some patients who are not candidates for the above methods. This study aimed to evaluate the feasibility of surveillance ultrasonography (US) for the conservative treatment of FSFs in young children.

Materials and methods

This retrospective study included 92 children who were diagnosed with FSF in our hospital from April 2017 to May 2019. After applying the inclusion and exclusion criteria, they were divided into US surveillance (A) and control (B) groups. All patients received conservative treatment by skin traction. For group A, US was used to assess the femur fractures and adjust its reduction on days 1, 3, 5, 7, 10, and 14 until the fracture stabilized. For group B, the fractures were checked by radiographs on days 1, 3, 5, 7, 10, and 14 until the callus appeared. The FSF angle was measured using anteroposterior and lateral radiographs.

Results

All patients were followed up for 18 months. The radiographic evaluation of both groups at the final follow-up showed a significant difference in the FSF angle. The radiograph times and accumulated radiation also showed significant differences between the two groups. However, there was no significant difference in the incidence of complications.

Conclusions

For FSF closed reduction, surveillance US is a better option compared to radiographs in children treated by skin traction. This approach can significantly decrease exposure to X-ray radiation and improve the reduction.

Level of evidence

III
Novel gene variants in Polish patients with Leber congenital amaurosis (LCA)
Authors: Skorczyk-Werner Anna , Niedziela Zuzanna , Stopa Marcin , Krawczyński Maciej Robert
Published: December 2020

Background

Leber congenital amaurosis (LCA) is a rare retinal disease that is the most frequent cause of congenital blindness in children and the most severe form of inherited retinal dystrophies. To date, 25 genes have been implicated in the pathogenesis of LCA. As gene therapy is becoming available, the identification of potential treatment candidates is crucial. The aim of the study was to report the molecular basis of Leber congenital amaurosis in 22 Polish families.

Methods

Single Nucleotide Polymorphism-microarray for LCA genes or Next Generation Sequencing diagnostic panel for LCA genes (or both tests) were performed to identify potentially pathogenic variants. Bidirectional Sanger sequencing was carried out for validation and segregation analysis of the variants identified within the families.

Results

The molecular background was established in 22 families. From a total of 24 identified variants, 23 were predicted to affect protein-coding or splicing, including 10 novel variants. The variants were identified in 7 genes: CEP290, GUCY2D, RPE65, NMNAT1, CRB1, RPGRIP1, and CRX. More than one-third of the patients, with clinical LCA diagnosis confirmed by the results of molecular analysis, appeared to be affected with a severe form of the disease: LCA10 caused by the CEP290 gene variants. Intronic mutation c.2991+1655A>G in the CEP290 gene was the most frequent variant identified in the studied group.

Conclusions

This study provides the first molecular genetic characteristics of patients with Leber congenital amaurosis from the previously unexplored Polish population. Our study expands the mutational spectrum as we report 10 novel variants identified in LCA genes. The fact that the most frequent causes of the disease in the studied group of Polish patients are mutations in one out of three genes that are currently the targets for gene therapy (CEP290, GUCY2D, and RPE65) strongly emphasizes the importance of the molecular background analyses of LCA in Polish patients.
MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents
Authors: Bolomsky Arnold , Vogler Meike , Köse Murat Cem , Heckman Caroline A. , Ehx Grégory , Ludwig Heinz , Caers Jo
Published: December 2020

Cell death escape is one of the most prominent features of tumor cells and closely linked to the dysregulation of members of the Bcl-2 family of proteins. Among those, the anti-apoptotic family member myeloid cell leukemia-1 (MCL-1) acts as a master regulator of apoptosis in various human malignancies. Irrespective of its unfavorable structure profile, independent research efforts recently led to the generation of highly potent MCL-1 inhibitors that are currently evaluated in clinical trials. This offers new perspectives to target a so far undruggable cancer cell dependency. However, a detailed understanding about the tumor and tissue type specific implications of MCL-1 are a prerequisite for the optimal (i.e., precision medicine guided) use of this novel drug class. In this review, we summarize the major functions of MCL-1 with a special focus on cancer, provide insights into its different roles in solid vs. hematological tumors and give an update about the (pre)clinical development program of state-of-the-art MCL-1 targeting compounds. We aim to raise the awareness about the heterogeneous role of MCL-1 as drug target between, but also within tumor entities and to highlight the importance of rationale treatment decisions on a case by case basis.
RETRACTED ARTICLE: Circular RNA hsa_circ_0001829 promotes gastric cancer progression through miR-155-5p/SMAD2 axis
Authors: Niu Qiuling , Dong Zhijie , Liang Min , Luo Yuanwei , Lin Hai , Lin Mingzhen , Zhong Xiu , Yao Wenxia , Weng Jinsheng , Zhou Xinke
Published: December 2020

Background

Accumulating evidences have shown that circular RNAs (circRNAs) play important roles in regulating the pathogenesis of cancer. However, the role of circRNAs in gastric cancer (GC) remains largely unclear.

Methods

In this study, we identified a novel upregulated circRNA, hsa_circ_0001829, in chemically induced malignant transformed human gastric epithelial cells using RNA-seq. Subsequent qRT-PCR and ISH assays were performed to detect the expression level of hsa_circ_0001829 in GC cell lines and tissues. Functional roles of hsa_circ_0001829 in GC were then explored by loss- and gain-of- function assays. Bioinformatic prediction and luciferase assay were used to investigate potential mechanisms of hsa_circ_0001829. Finally, the mice xenograft and metastasis models were constructed to assess the function of hsa_circ_0001829 in vivo.

Results

We found that hsa_circ_0001829 was significantly upregulated in GC tissues and cell lines. Loss- and gain-of- function assays showed that hsa_circ_0001829 promotes GC cells proliferation, migration and invasion, and the affected cell cycle progression and apoptosis rates may account for the effect of hsa_circ_0001829 on GC proliferation. In addition, bioinformatic prediction and luciferase assay showed that hsa_circ_0001829 acts as a molecular sponge for miR-155-5p and that SMAD2 was a target gene of miR-155-5p; moreover, hsa_circ_0001829 sponges miR-155-5p to regulate SMAD2 expression and hsa_circ_0001829 promotes GC progression through the miR-155-5p–SMAD2 pathway. Finally, suppression of hsa_circ_0001829 expression inhibited tumor growth and aggressiveness in vivo.

Conclusion

Taken together, our findings firstly demonstrated a novel oncogenic role of hsa_circ_0001829 in GC progression through miR-155-5p–SMAD2 axis, and our study may offer novel biomarkers and therapeutic targets for GC.
CircCDKN2B-AS1 interacts with IMP3 to stabilize hexokinase 2 mRNA and facilitate cervical squamous cell carcinoma aerobic glycolysis progression
Authors: Zhang Yanan , Zhao Lu , Yang Shizhou , Cen Yixuan , Zhu Tingjia , Wang Lingfang , Xia Lili , Liu Yuwan , Zou Jian , Xu Junfen , Li Yang , Cheng Xiaodong , Lu Weiguo , Wang Xinyu , Xie Xing
Published: December 2020

Background

Circular RNAs (circRNAs) have been reported to play key roles in the development of various cancers. However, the biological functions and clinical significance of most circRNAs are still elusive. The purpose of this study was to explore the function and mechanism of a certain circRNA named circCDKN2B-AS1 in cervical cancer development and its potential value in the clinic.

Methods

qRT-PCR was used to verify the expression level of circCDKN2B-AS1. CCK-8, Transwell, and flow cytometry (FCM) assays were performed to detect cellular proliferation, migration, and apoptosis, respectively. A Seahorse XFe96 Analyzer was used to measure glycolysis metabolism level. RNA pull-down, RNA immunoprecipitation (RIP), actinomycin-D addition assays and Western blotting were used to screen and elucidate the potential mechanisms involved. BALB/c nude mice and zebrafish embryos (AB, WT) were used as animal models to investigate tumorigenesis capability.18FDG-microPET/CT imaging and lactic acid (LA) and pyruvic acid (PA) content detection assays were used to detect the level of glucose metabolism in subcutaneous tumors from nude mice.

Results

CircCDKN2B-AS1, a circular isoform of the long noncoding RNA (lncRNA) CDKN2B-AS1, was upregulated in cervical cancer and precancerous tissues. We found that circCDKN2B-AS1 associated with the IMP3 protein depending on a specific binding site and regulated the stability of Hexokinase 2 (HK2) mRNA, the rate-limiting enzyme of the aerobic glycolysis pathway. The expression level of circCDKN2B-AS1 fated the binding of IMP3 to the 3′ untranslated region (UTR) of HK2 mRNA, consequently affecting the malignant cell phenotype and aerobic glycolysis in cervical cancer in vitro and in vivo. Mutant circCDKN2B-AS1, lacking the IMP3 binding site, did not have such effects. Utilization of an inhibitory peptide to block the interaction between circCDKN2B-AS1 and the IMP3 protein impeded the binding of IMP3 to the 3’UTR of HK2 mRNA and suppressed aerobic glycolysis in cervical cancer cells.

Conclusions

Our findings demonstrate that circCDKN2B-AS1 facilitates aerobic glycolysis by sponging the IMP3 protein to stabilize HK2 mRNA, consequently promoting the malignant phenotype in cervical cancer, which may provide a potential approach for cervical cancer therapeutics.
Death Cafés for prevention of burnout in intensive care unit employees: study protocol for a randomized controlled trial (STOPTHEBURN)
Authors: Bateman Marjorie E. , Hammer Rachel , Byrne Abigail , Ravindran Nithya , Chiurco Jennifer , Lasky Sasha , Denson Rebecca , Brown Margo , Myers Leann , Zu Yuanhao , Denson Joshua L.
Published: December 2020

Background

Burnout is an occupational syndrome that leads to mental health problems, job turnover, and patient safety events. Those caring for critically ill patients are especially susceptible due to high patient mortality, long hours, and regular encounters with trauma and ethical issues. Interventions to prevent burnout in this population are needed. Preliminary studies suggest debriefing sessions may reduce burnout. This study aims to assess whether participation in regular debriefing can prevent burnout in intensive care unit (ICU) clinicians.

Methods

A randomized controlled trial will be conducted in two large academic medical centers. Two hundred ICU clinicians will be recruited with target enrollment of 100 physicians and 100 non-physicians (nurses, pharmacists, therapists). Participants must have worked in the ICU for the equivalent of at least 1 full time work week in the preceding 4 weeks. Enrolled subjects will be randomized to virtually attend biweekly debriefing sessions facilitated by a psychotherapist for 3 months or to a control arm without sessions. Our debriefs are modeled after Death Cafés, which are informal discussions focusing on death, dying, loss, grief, and illness. These sessions allow for reflection on distressing events and offer community and collaboration among hospital employees outside of work.

The primary outcome is clinician burnout as measured by the Maslach Burnout Inventory (MBI) Score. Secondary outcomes include depression and anxiety, as measured by the Patient Health Questionnaire 8 (PHQ-8) and Generalized Anxiety Disorder 7-item scale (GAD-7), respectively. Questionnaires will be administered prior to the intervention, at 1 month, at 3 months, and at 6 months after enrollment. These values will be compared between groups temporally. Qualitative feedback will also be collected and analyzed.

Discussion

With ICU clinician burnout rates exceeding 50%, Death Café debriefing sessions may prove to be an effective tool to avert this debilitating syndrome. With COVID-19 limiting social interactions and overloading ICUs worldwide, the virtual administration of the Death Café for ICU clinicians provides an innovative strategy to potentially mitigate burnout in this vulnerable population.

Trial registration

ClinicalTrials.gov NCT04347811. Registered on 15 April 2020