bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordinated action of human papillomavirus type 16 E6 and E7 oncoproteins on competitive endogenous RNA (ceRNA) network members in primary human keratinocytes
Authors: László Brigitta , Antal László , Gyöngyösi Eszter , Szalmás Anita , Póliska Szilárd , Veress György , Kónya József
Published: June 2021

Background

miRNAs and lncRNAs can regulate cellular biological processes both under physiological and pathological conditions including tumour initiation and progression. Interactions between differentially expressed diverse RNA species, as a part of a complex intracellular regulatory network (ceRNA network), may contribute also to the pathogenesis of HPV-associated cancer. The purpose of this study was to investigate the global expression changes of miRNAs, lncRNAs and mRNAs driven by the E6 and E7 oncoproteins of HPV16, and construct a corresponding ceRNA regulatory network of coding and non-coding genes to suggest a regulatory network associated with high-risk HPV16 infections. Furthermore, additional GO and KEGG analyses were performed to understand the consequences of mRNA expression alterations on biological processes.

Methods

Small and large RNA deep sequencing were performed to detect expression changes of miRNAs, lncRNAs and mRNAs in primary human keratinocytes expressing HPV16 E6, E7 or both oncoproteins. The relationships between lncRNAs, miRNAs and mRNAs were predicted by using StarBase v2.0, DianaTools-LncBase v.2 and miRTarBase. The lncRNA-miRNA-mRNA regulatory network was visualized with Cytoscape v3.4.0. GO and KEEG pathway enrichment analysis was performed using DAVID v6.8.

Results

We revealed that 85 miRNAs in 21 genomic clusters and 41 lncRNAs were abnormally expressed in HPV E6/E7 expressing cells compared with controls. We constructed a ceRNA network with members of 15 lncRNAs – 43 miRNAs – 358 mRNAs with significantly altered expressions. GO and KEGG functional enrichment analyses identified numerous cancer related genes, furthermore we recognized common miRNAs as key regulatory elements in biological pathways associated with tumorigenesis driven by HPV16.

Conclusions

The multiple molecular changes driven by E6 and E7 oncoproteins resulting in the malignant transformation of HPV16 host cells occur, at least in part, due to the abnormal alteration in expression and function of non-coding RNA molecules through their intracellular competing network.
Disc hemorrhage following peripapillary retinoschisis in glaucoma: a case report
Authors: Lee Won June , Seong Mincheol
Published: June 2021

Background

Disc hemorrhage (DH) is an important factor often associated with the development and especially progression of glaucoma. In contrast, some studies have reported peripapillary retinoschisis in glaucoma, but it is not recognized as a pathognomonic finding, and opinions on the clinical significance of retinoschisis are not consistent. Here,we present the case of DH following peripapillary retinoschisis in the same area within the same glaucomatous eye.

Case presentation

A 70-year-old man with high intraocular pressure (IOP) was referred to the glaucoma clinic. At the time of the baseline study, the IOP was 30mmHg, and peripapillary retinoschisis was discovered at 7 o’clock on the periphery of the optic nerve with swept-source optical coherence tomography. Accompanying retinal nerve fiber layer defect were manifest in the inferotemporal part with red-free fundus photography. Under the impression of open-angle glaucoma, we prescribe latanoprost ophthalmic solution. Eight months later, the IOP was 17mmHg, and the peripapillary retinoschisis had disappeared. DH was observed in the inferotemporal area in the same direction as that of the previous peripapillary retinoschisis.

Conclusions

The case presented here are the first to report on the relationship between peripapillary retinoschisis and DH. Hopefully future studies will reveal the actual connection between peripapillary retinoschisis and DH.
A multicentric study on stigma towards people with mental illness in health sciences students
Authors: Masedo Ana , Grandón Pamela , Saldivia Sandra , Vielma-Aguilera Alexis , Castro-Alzate Elvis S. , Bustos Claudio , Romero-López-Alberca Cristina , Pena-Andreu J. Miguel , Xavier Miguel , Moreno-Küstner Berta
Published: June 2021

Background

There is evidence of negative attitudes among health professionals towards people with mental illness but there is also a knowledge gap on what training must be given to these health professionals during their education. The purpose of this study is to compare the attitudes of students of health sciences: nursing, medical, occupational therapy, and psychology.

Methods

A comparative and cross-sectional study in which 927 final-year students from health sciences university programmes were evaluated using the Mental Illness: Clinicians’ Attitudes (both MICA-2 and MICA-4) scale. The sample was taken in six universities from Chile and Spain.

Results

We found consistent results indicating that stigma varies across university programmes. Medical and nursing students showed more negative attitudes than psychology and occupational therapy students in several stigma-related themes: recovery, dangerousness, uncomfortability, disclosure, and discriminatory behaviour.

Conclusions

Our study presents a relevant description of the attitudes of each university programme for education against stigma in the formative years. Results show that the biomedical understanding of mental disorders can have negative effects on attitudes, and that education based on the psychosocial model allows a more holistic view of the person over the diagnosis.
A quantitative risk assessment to evaluate the efficacy of mitigation strategies to reduce highly pathogenic avian influenza virus, subtype H5N1 (HPAI H5N1) in the Menoufia governorate, Egypt
Authors: Elsobky Yumna , Nganwa David , El Afandi Gamal , Byomi Ahmed , Reddy Gopal , Abdalla Ehsan
Published: June 2021

Background

The poultry industry in Egypt has been suffering from endemic highly pathogenic avian influenza (HPAI) virus, subtype H5N1 since 2006. However, the emergence of H9N2, H5N8, and H5N2 in 2011, 2016, and 2019 respectively, has aggravated the situation. Our objective was to evaluate how effective are the mitigation strategies by a Quantitative Risk Assessment (QRA) model which used daily outbreak data of HPAI-H5N1 subtype in Egypt, stratified by different successive epidemic waves from 2006 to 2016.

Results

By applying the epidemiologic problem-oriented approach methodology, a conceptual scenario tree was drawn based on the knowledgebase. Monte Carlo simulations of QRA parameters based on outbreak data were performed using @Risk software based on a scenario-driven decision tree. In poultry farms, the expected probability of HPAI H5N1 prevalence is 48% due to failure of mitigation strategies in 90% of the time during Monte Carlo simulations. Failure of efficacy of these mitigations will raise prevalence to 70% with missed vaccination, while failure in detection by surveillance activities will raise it to 99%. In backyard poultry farms, the likelihood of still having a high HPAI-H5N1 prevalence in different poultry types due to failure of passive and active surveillance varies between domestic, mixed and reservoir. In mixed poultry, the probability of HPAI-H5N1 not detected by surveillance was the highest with a mean and a SD of 16.8 × 10–3 and 3.26 × 10–01 respectively. The sensitivity analysis ranking for the likelihood of HPAI-H5N1 in poultry farms due to missed vaccination, failure to be detected by passive and active surveillance was examined. Among poultry farms, increasing vaccination by 1 SD will decrease the prevalence by 14%, while active and passive surveillance decreases prevalence by 12, and 6%, respectively. In backyard, the active surveillance had high impact in decreasing the prevalence by 16% in domestic chicken. Whereas the passive surveillance had less impact in decreasing prevalence by 14% in mixed poultry and 3% in domestic chicken.

Conclusion

It could be concluded that the applied strategies were not effective in controlling the spread of the HPAI-H5N1 virus. Public health officials should take into consideration the evaluation of their control strategies in their response.
GNG5 is a novel oncogene associated with cell migration, proliferation, and poor prognosis in glioma
Authors: Zhang Wang , Liu Zhendong , Liu Binchao , Jiang Miaomiao , Yan Shi , Han Xian , Shen Hong , Na Meng , Wang Yanbiao , Ren Zhishuai , Liu Binfeng , Jiang Zhenfeng , Gao Yanzheng , Lin Zhiguo
Published: June 2021

Background

Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified.GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role ofGNG5in glioma has not been studied. Therefore, we aimed to identify the relationship betweenGNG5and glioma prognosis and identify a new biomarker for the diagnosis and treatment of gliomas.

Methods

We used data on more than a thousand gliomas from multiple databases and clinical data to determine the expression ofGNG5in glioma. Based on clinical data and CGGA database, we identified the correlation betweenGNG5and multiple molecular and clinical features and prognosis using various analytical methods. Co-expression analysis and GSEA were performed to detectGNG5-related genes in glioma and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship betweenGNG5and the immune microenvironment. Functional experiments were performed to explore the function ofGNG5in glioma cells.

Results

GNG5is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover,GNG5as an independent risk factor was negatively correlated with the overall survival time. GSEA revealed the potential signaling pathways involved inGNG5function in gliomas, including cell adhesion molecules signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation betweenGNG5expression and various immune cells in glioma. In vivo and in vitro experiments showed thatGNG5could participate in glioma cell proliferation and migration.

Conclusions

Based on the large data platform and the use of different databases to corroborate results obtained using various datasets, as well as in vitro and in vivo experiments, our study reveals for the first time thatGNG5, as an oncogene, is overexpressed in gliomas and can inhibit the proliferation and migration of glioma cells and lead to poor prognosis of patients. Thus,GNG5is a potential novel biomarker for the clinical diagnosis and treatment of gliomas.
Correction to: CTLA4 has a profound impact on the landscape of tumor-infiltrating lymphocytes with a high prognosis value in clear cell renal cell carcinoma (ccRCC)
Authors: Liu Shiyi , Wang Feiyan , Tan Wei , Zhang Li , Dai Fangfang , Wang Yanqing , Fan Yaqi , Yuan Mengqin , Yang Dongyong , Zheng Yajing , Deng Zhimin , Liu Yeqiang , Cheng Yanxiang
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
Policy options to increase motivation for improving evidence-informed health policy-making in Iran
Authors: Sajadi Haniye Sadat , Majdzadeh Reza , Ehsani-Chimeh Elham , Yazdizadeh Bahareh , Nikooee Sima , Pourabbasi Ata , Lavis John
Published: June 2021

Background

Current incentive programmes are not sufficient to motivate researchers and policy-makers to use research evidence in policy-making. We conducted a mixed-methods design to identify context-based policy options for strengthening motivations among health researchers and policy-makers to support evidence-informed health policy-making (EIHP) in Iran.

Methods

This study was conducted in 2019 in two phases. In the first phase, we conducted a scoping review to extract interventions implemented or proposed to strengthen motivations to support EIHP. Additionally, we employed a comparative case study design for reviewing the performance evaluation (PE) processes in Iran and other selected countries to determine the current individual and organizational incentives to encourage EIHP. In the second phase, we developed two policy briefs and then convened two policy dialogues, with 12 and 8 key informants, respectively, where the briefs were discussed. Data were analysed using manifest content analysis in order to propose contextualized policy options.

Results

The policy options identified to motivate health researchers and policy-makers to support EIHP in Iran were: revising the criteria of academic PE; designing appropriate incentive programmes for nonacademic researchers; developing an indicator for the evaluation of research impact on policy-making or health outcomes; revising the current policies of scientific journals; revising existing funding mechanisms; presenting the knowledge translation plan when submitting a research proposal, as a mandatory condition; encouraging and supporting mechanisms for increasing interactions between policy-makers and researchers; and revising some administrative processes (e.g. managers and staff PEs; selection, appointment, and changing managers and reward mechanisms).

Conclusions

The current individual or organizational incentives are mainly focused on publications, rather than encouraging researchers and policy-makers to support EIHP. Relying more on incentives that consider the other impacts of research (e.g. impacts on health system and policy, or health outcomes) is recommended. These incentives may encourage individuals and organizations to be more involved in conducting research evidence, resulting in promoting EIHP.

Trial registration

NA.
Determining the sex-specific distributions of average daily alcohol consumption using cluster analysis: is there a separate distribution for people with alcohol dependence?
Authors: Jiang Huan , Lange Shannon , Tran Alexander , Imtiaz Sameer , Rehm Jürgen
Published: June 2021

Background

It remains unclear whether alcohol use disorders (AUDs) can be characterized by specific levels of average daily alcohol consumption. The aim of the current study was to model the distributions of average daily alcohol consumption among those who consume alcohol and those with alcohol dependence, the most severe AUD, using various clustering techniques.

Methods

Data from Wave 1 and Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were used in the current analyses. Clustering algorithms were applied in order to group a set of data points that represent the average daily amount of alcohol consumed. Gaussian Mixture Models (GMMs) were then used to estimate the likelihood of a data point belonging to one of the mixture distributions. Individuals were assigned to the clusters which had the highest posterior probabilities from the GMMs, and their treatment utilization rate was examined for each of the clusters.

Results

Modeling alcohol consumption via clustering techniques was feasible. The clusters identified did not point to alcohol dependence as a separate cluster characterized by a higher level of alcohol consumption. Among both females and males with alcohol dependence, daily alcohol consumption was relatively low.

Conclusions

Overall, we found little evidence for clusters of people with the same drinking distribution, which could be characterized as clinically relevant for people with alcohol use disorders as currently defined.
Generating age-specific mortality statistics from incomplete death registration data: two applications of the empirical completeness method
Authors: Adair Tim , Lopez Alan D
Published: June 2021

Background

The study aims to assess two approaches that apply the empirical completeness method to generate age-specific mortality statistics from incomplete death registration systems.

Methods

We use the empirical completeness method to calculate all-age death registration completeness, which is used with a model life table to generate mortality statistics and age-specific completeness using (1) the conventional method and (2) the equivalent deaths method. The results are compared with a capture-recapture (C-RC) study and three alternative mortality estimates for Brazilian states, and C-RC studies in Thailand, Oman and Vietnam, which independently estimate the level and age pattern of mortality or completeness.

Results

The empirical completeness method produces similar estimates of all-age completeness of registration to the C-RC studies. Compared with C-RC studies, at 15-59 years, the conventional method’s estimates of mortality and completeness are more concordant, while at 60-84 years the equivalent death method’s estimates are closer. Estimates of life expectancy from the two approaches each have similar concordance with the C-RC studies. For male adult mortality in Brazilian states, there is relatively strong average correlation of this study's estimates with three alternative estimates.

Conclusions

The two approaches produce mortality statistics from incomplete data that are mostly concordant with C-RC studies, and can be most usefully applied to subnational populations.
Physical activity and 4-year changes in body weight in 52,498 non-obese people: the Lifelines cohort
Authors: Byambasukh Oyuntugs , Vinke Petra , Kromhout Daan , Navis Gerjan , Corpeleijn Eva
Published: June 2021

Objectives

We investigated associations between leisure-time physical activity (LTPA) at different intensities (moderate and vigorous or moderate-to-vigorous) and prospective weight gain in non-obese people. We also examined whether these associations were independent of other lifestyle factors and changes in muscle mass and whether they were age-dependent and changed over a person’s life course.

Methods

The data were extracted from the Lifelines cohort study (N = 52,498; 43.5% men) and excluded obese individuals (BMI > 30 kg/m2). We used the validated SQUASH questionnaire to estimate moderate-to-vigorous (MVPA; MET≥4), moderate (MPA; MET between 4 and 6.5) and vigorous PA (VPA; MET≥6.5). Body weight was objectively measured, and changes were standardized to a 4-year period. Separate analyses, adjusted for age, educational level, diet, smoking, alcohol consumption and changes in creatinine excretion (a marker of muscle mass), were performed for men and women.

Results

The average weight gain was + 0.45 ± 0.03 kg in women. Relative to each reference groups (No-MVPA, No-MPA and No-VPA), MVPA (Beta (95%CI): − 0.34 kg (− 0.56;-0.13)), MPA (− 0.32 kg (− 0.54;-0.10)) and VPA (− 0.30 kg (− 0.43;-0.18)) were associated with less gain in body weight in women after adjusting for potential confounders, described above. These associations were dose-dependent when physically active individuals were divided in tertiles. Beta-coefficients (95%CI) for the lowest, middle, and highest MVPA tertiles relative to the ‘No-MVPA’ were, respectively, − 0.24 (− 0.47;-0.02), − 0.31 (− 0.53;-0.08), and − 0.38 (− 0.61;-0.16) kg. The average weight gain in men was + 0.13 ± 0.03 kg, and only VPA, not MPA was associated with less body weight gain. Beta-coefficients (95%CI) for the VPA tertiles relative to the ‘No-VPA’ group were, respectively, − 0.25 (− 0.42;-0.09), − 0.19 (− 0.38;-0.01) and − 0.20 (− 0.38;-0.02) kg. However, after adjusting for potential confounders, the association was no longer significant in men. The potential benefits of leisure-time PA were age-stratified and mainly observed in younger adults (men < 35 years) or stronger with younger age (women < 55 years).

Conclusion

Higher leisure-time MVPA, MPA, and VPA were associated with less weight gain in women < 55 years. In younger men (< 35 years), only VPA was associated with less weight gain.
Underestimated health risks: polystyrene micro- and nanoplastics jointly induce intestinal barrier dysfunction by ROS-mediated epithelial cell apoptosis
Authors: Liang Boxuan , Zhong Yizhou , Huang Yuji , Lin Xi , Liu Jun , Lin Li , Hu Manjiang , Jiang Junying , Dai Mingzhu , Wang Bo , Zhang Bingli , Meng Hao , Lelaka Jesse Justin J. , Sui Haixia , Yang Xingfen , Huang Zhenlie
Published: June 2021

Background

Micro- and nanoplastic pollution has become a global environmental problem. Nanoplastics in the environment are still hard to detect because of analysis technology limitations. It is believed that when microplastics are found in the environment, more undetected nanoplastics are around. The current “microplastic exposure” is in fact the mixture of micro- and nanoplastic exposures. Therefore, the biological interaction between organisms among different sizes of micro- and nanoplastics should not be neglected.

Results

We measured the biodistribution of three polystyrene (PS) particles (50 nm PS, PS50; 500 nm PS, PS500; 5000 nm PS, PS5000) under single and co-exposure conditions in mice. We explored the underlying mechanisms by investigating the effects on three major components of the intestinal barrier (the mucus layer, tight junctions and the epithelial cells) in four intestine segments (duodenum, jejunum, ileum and colon) of mice. We found that the amounts of both PS500 and PS5000 increased when they were co-exposed with PS50 for 24 h in the mice. These increased amounts were due primarily to the increased permeability in the mouse intestines. We also confirmed there was a combined toxicity of PS50 and PS500 in the mouse intestines. This manifested as the mixture of PS50 and PS500 causing more severe dysfunction of the intestinal barrier than that caused by PS50 or PS500 alone. We found that the combined toxicity of PS micro- and nanoplastics on intestinal barrier dysfunction was caused primarily by reactive oxygen species (ROS)-mediated epithelial cell apoptosis in the mice. These findings were further confirmed by an oxidants or antioxidants pretreatment study. In addition, the combined toxicity of PS micro- and nanoplastics was also found in the mice after a 28-day repeated dose exposure.

Conclusions

There is a combined toxicity of PS50 and PS500 in the mouse intestines, which was caused primarily by ROS-mediated epithelial cell apoptosis in the mice. Considering that most recent studies on PS micro- and nanoplastics have been conducted using a single particle size, the health risks of exposure to PS micro- and nanoplastics on organisms may be underestimated.
Associations between parental alcohol problems in childhood and adversities during childhood and later adulthood: a cross-sectional study of 28047 adults from the general population
Authors: Haugland Siri Håvås , Carvalho Barbara , Stea Tonje Holte , Strandheim Arve , Vederhus John-Kåre
Published: June 2021

Background

Adverse childhood experiences (ACE) are related to adverse physical and mental health outcomes. However, few larger studies based on a general population sample with age groups ranging from young adults to elderly have investigated whether parental alcohol problems increase the risk of offspring subjective reports of ACE both during childhood and current adult adversities. The purpose of this study was to examine the associations between parental alcohol problems and adversities during childhood and later in adulthood.

Methods

The 28,047 respondents were adults (> 18 years old) from the general population who participated in the Norwegian Counties Public Health Survey. The study had a cross-sectional design and included respondents’ evaluations of childhood experiences and current adult adversities. The short version of the Children of Alcoholics Screening Test (CAST-6, cut-off ≥3) measured parental alcohol problems. Multivariable logistic regression was adjusted for gender, age, and education.

Results

Growing up with parental alcohol problems strongly increased the risk of experiencing a dysfunctional family environment during childhood (odds ratio [OR] 6.84; 95% confidence interval [CI] 6.36–7.36), perceiving childhood as difficult (OR 5.01; 95% CI 4.58–5.49), and reporting a lack of support from a trusted adult (OR 3.07; 95% CI 2.86–3.29). Parental alcohol problems were associated with a modestly increased risk of harmful alcohol use (OR 1.38; 95% CI 1.29–1.48), but the association with struggling with bad memories was strong (OR 4.56; 95% CI 4.17–4.98).

Conclusions

Parental alcohol problems increased the risk of offspring experiencing adversities during both childhood and adulthood. Providing supportive services to these children and their families and addressing this issue as part of treatment is important to prevent alcohol related harm.
The effect of aqueous extract of Prunus dulcis on tibial bone healing in the rabbit
Authors: Anaraki Nima , Beyraghi Amir Hossein , Raisi Abbas , Davoodi Farshid , Farjanikish Ghasem , Sadegh Amin Bigham
Published: June 2021

Background

Bone fractures are medical emergencies that require prompt intervention to help return bone to its normal function. Various methods and treatments have been utilized to increase the speed and efficiency of bone repair. This study aimed to investigate the treatment effects of Prunus dulcis aqueous extract on tibial bone healing in rabbits.

Methods

All animals were distributed in five groups with six rats in each group, including the sham group, the control group in which tibial lesion was made and received distilled water, treatment groups with 150 mg kg−1, 300 mg kg−1 doses of Prunus dulcis extract, and osteocare treated group. Biochemical blood factors including calcium, phosphorus, and alkaline phosphatase (on days 0, 10, 30, and 50), biomarkers of oxidative stress such as GPx, CAT, and MDA (on days 10 and 30), radiological evaluation, histopathological parameters, and osteocalcin immunohistochemical expression were assessed.

Results

The data showed calcium levels in the treatment groups increased significantly from day 10 to day 50, respectively, and blood phosphorus levels decreased from day 10 to day 50 in the treatment groups. Alkaline phosphatase initially increased and then decreased in treatment groups. In the treatment groups, GPx and CAT levels significantly increased, and the serum amount of MDA reduced. The best antioxidant results were related to the extract-treated group with a higher dose. Radiographic score was significantly higher in the treatment groups than the control group on day 30. Based on the pathological findings, the healing occurred faster in the extract-treated group with a higher dose. Osteocalcin expression was significantly higher in the control group than that in the treatment groups.

Conclusions

Treatment with Prunus dulcis extract with a dosage of 300 mg/kg accelerated tibial bone healing in rabbits.

Graphical abstract
NDRG1 regulates osteosarcoma cells via mediating the mitochondrial function and CSCs differentiation
Authors: Zhao Tong , Meng Ying , Wang Yongping , Wang Wenji
Published: June 2021

Background

Cancer stem cells (CSCs) are mainly contributed to malignancy metastatic potential and resistant therapy of osteosarcoma (OS). The mitochondria-related apoptosis was generally accepted as the target of tumor therapy. However, the effect of N-myc downstream-regulated gene 1 (NDRG1) on CSCs and mitochondrial health in OS is still unknown.

Methods

In OS cells, MG63 and U2OS, the siRNA of NDRG1 were conducted. Transwell, western blot, RT-qPCR, and mitochondria isolation were used to identify the effect of NDRG on OS cells and mitochondria. Moreover, the differentiation-related factors of CSCs were determined.

Results

After downregulation of NDRG1, the cell viability, invasion ability decreased whereas cell apoptosis increased. The expressions profiles of fibronectin, vimentin, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP) 2, MMP9, and MMP13 were downregulated, but E-cadherin expression level was upregulated by NDRG1 siRNA. At the same time, cytochrome (Cyt) C levels were increased in cytosol with the decreasing in mitochondria after siRNA treatment. The mitochondrial membrane potential (MMPs) was declined, and the function of mitochondria was impeded. The expressions of uncoupling proteins (UCP) 2, voltage dependent anion channel (VDAC), peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α, and cyclooxygenase (COX) 2 were downregulated by NDRG1 silencing. Moreover, NDRG performed its function primarily through the Wnt pathway and could regulate the differentiation of osteosarcoma stem cells.

Conclusion

Silencing of NDRG1 could damage the function of mitochondria, promote the CSCs differentiation, alleviating OS progression.
Incidence of valvular regurgitation and leaflet perforation by using automated titanium fasteners (CORKNOT®) in heart valve repair or replacement: less usual than reported
Authors: Sazzad Faizus , Xian Ong Zhi , Ler Ashlynn , Guohao Chang , Swee Kang Giap , Kofidis Theo
Published: June 2021

Background

CORKNOT® facilitates a reduction in cardiopulmonary bypass (CPB) time, aortic cross clamp (ACC) time and operative time, but reported to be associated with other complications. We aim to quantify the incidence of valvular complications related to CORKNOT® and determine the feasibility of its use between different valvular surgeries.

Methods

Patients who underwent heart valve repair or replacement surgery via the use of automated titanium suture fasteners (CORKNOT®) in a tertiary care hospital were included in the study. This single-centre retrospective study was conducted on 132 patients between January 2016 and June 2018.

Results

In our study, the overall mean operative time was 320.0 ± 97.0 min, mean CPB time was 171.4 ± 76.0 min and the calculated mean ACC time was 105.9 ± 54.0 min. Fifty-eight patients (43.9%) underwent minimally invasive valve replacement or repair surgery and 66 patients (50.0%) underwent concomitant procedures. A total of 157 valves were operated on, with 112 (84.8%) single valve surgeries, 15 (11.4%) double valve surgeries and 5 (3.8%) triple valve surgeries. After reviewed by the cardiologist blinded towards the study, we report trivial and/or mild paravalvular leak (PVL) in immediate post-operative echocardiography was found in 1 (1.01%) patients. There were no reported cases of valvular thrombosis, leaflet perforation, device dislodgement or embolization, moderate and/or severe PVL during hospitalization and follow-up echocardiography within 1 year. Single mitral valve and aortic surgeries had comparable incidences of post surgical complications.

Conclusion

We conclude the feasibility of CORKNOT® utilisation in mitral and aortic valve surgeries. Additionally, incidence of CORKNOT® related complications in heart valve repair or replacement surgery is less usual in our setting than previously reported. These results motivate the use of CORKNOT® as a valid alternative with complete commitment.
Comparison of the clinical effect between the lower sternal incision and the left parasternal fourth intercostal incision in the transthoracic closure of ventricular septal defect
Authors: Ma Jun , Shangguan Wenlin , Chen Liang-Wan , Liao Dong-shan
Published: June 2021

Background

To analyze the clinical effect of two different ways of minimally invasive transthoracic closure in children with ventricular septal defect (VSD).

Methods

From January 2015 to July 2019, 294 children with VSD were enrolled in the Fujian Medical University Union Hospital. Patients were divided into two groups – those who underwent VSD closure through the left sternal fourth intercostal incision (group A: n = 95) and the lower sternal incision (group B: n = 129).

Results

The operation time, bleeding volume, postoperative mechanical ventilation time, postoperative intensive care unit (ICU) monitoring time, postoperative hospitalization time and complication rate in group A were significantly lower than those in group B (P < 0.05). There was no significant difference between the two groups in the operation success rate, mechanical ventilation time and total hospitalization cost (P > 0.05).

Conclusion

The transthoracic closure of ventricular septal defect through the left sternal fourth intercostal incision is feasible, safe, cosmetic, and worth popularizing.
Analysis of copy number variations of WNT4 gene in a Chinese population with Müllerian anomalies
Authors: Zhu Ying , Wang Ruyi , Cheng Yun , Han Yang , Li Tengyan , Cao Yunxia , Wang Binbin
Published: June 2021

Background

To investigate the genetic contribution of copy number variations (CNVs) in Wingless-type MMTV integration site family, member 4 (WNT4), in a Chinese population with Müllerian anomalies (MA), copy number analysis of WNT4 by Multiplex ligation‐dependent probe amplification (MLPA) was performed on 248 female patients. Some studies have shown that heterozygous missense mutation of WNT4 can lead to MA. However, few studies on the relationship between WNT4 CNVs and MA have been performed.

Results

Among the 248 Chinese women affected by MA in this study, heterozygous deletion of WNT4 was detected in a single patient.

Conclusions

MLPA identified one heterozygous deletion in WNT4 in a single female patient among 248 Chinese women affected by MA. This study firstly reports CNVs of WNT4 in a large sample of MA patients from the Chinese population, which suggests that CNVs of WNT4 cannot be excluded in the occurrence of MA. This provides a genetic basis for precise treatment in the future.
Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma
Authors: Sharma Revati , Kadife Elif , Myers Mark , Kannourakis George , Prithviraj Prashanth , Ahmed Nuzhat
Published: June 2021

Vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC). Despite its early promising results in decreasing or delaying the progression of RCC in patients, VEGF-TKIs have provided modest benefits in terms of disease-free progression, as 70% of the patients who initially respond to the treatment later develop drug resistance, with 30% of the patients innately resistant to VEGF-TKIs. In the past decade, several molecular and genetic mechanisms of VEGF-TKI resistance have been reported. One of the mechanisms of VEGF-TKIs is inhibition of the classical angiogenesis pathway. However, recent studies have shown the restoration of an alternative angiogenesis pathway in modulating resistance. Further, in the last 5 years, immune checkpoint inhibitors (ICIs) have revolutionized RCC treatment. Although some patients exhibit potent responses, a non-negligible number of patients are innately resistant or develop resistance within a few months to ICI therapy. Hence, an understanding of the mechanisms of VEGF-TKI and ICI resistance will help in formulating useful knowledge about developing effective treatment strategies for patients with advanced RCC. In this article, we review recent findings on the emerging understanding of RCC pathology, VEGF-TKI and ICI resistance mechanisms, and potential avenues to overcome these resistance mechanisms through rationally designed combination therapies.
Prophylaxis for patients at Risk to Eliminate Post-operative Atrial Fibrillation (PREP-AF trial): a protocol for a feasibility randomized controlled study
Authors: Smith Heather A. , Kanji Salmaan , Tran Diem T. T. , Redpath Calum , Ferguson Dean , Lenet Tori , Sigler Greg , Gilbert Sebastien , Maziak Donna , Villeneuve Patrick , Sundaresan Sudhir , Seely Andrew J. E.
Published: June 2021

Background

Postoperative atrial fibrillation (POAF) is a frequent adverse event after thoracic surgery with associated morbidity, mortality, and healthcare costs. It has been shown to be preventable with prophylactic amiodarone, which is only recommended in high-risk individuals due to the potential associated side effects. Risk factors for POAF have been identified and incorporated into a prediction model to identify high-risk patients. Further evaluation in the form of a multicenter clinical trial is required to assess the effectiveness of prophylaxis specifically in this high-risk population. The feasibility of such a trial first needs to be assessed.

Methods

The PREP-AF trial is a double-blind randomized controlled feasibility trial. Individuals undergoing major thoracic surgery who are identified to be high-risk by the POAF prediction model will be randomized 1:1 to receive a short course of amiodarone vs. placebo in the immediate postoperative period. The primary outcome is feasibility, which will be measured by the number of eligible patients identified, consented, and randomized; intervention adherence; and measurement of future outcomes of a full trial.

Discussion

This study will determine the feasibility of a randomized controlled trial to assess the effectiveness of prophylactic amiodarone, in high-risk patients undergoing major thoracic surgery. This will inform the development of a multi-center trial to establish if prophylactic amiodarone is safe and effective at reducing the incidence of POAF. Preventing this adverse event will not only improve outcomes for patients but also reduce the associated health resource utilization and costs.

Trial registration

ClinicalTrials.gov NCT04392921. Registered on 19 May 2020.
Auricular acupressure for myopia prevention and control in children and its effect on choroid and retina: a randomized controlled trial protocol
Authors: Han Rong , Kong Xie-he , Zhao Feng , Yang Yan-ting , Dong Xiao-qing , Zeng Li , Chen Zhi , Zhao Yue , Yang Guang , Hong Jue , Zhou Xing-tao , Ma Xiao-peng
Published: June 2021

Background

Nowadays, because of the increasing incidence, the prevention and control of myopia has become an urgent issue. In China, auricular acupressure has been commonly used in the clinical treatment of myopia in children, but the exact effectiveness remains unproven. The purpose of this trial is to observe the efficacy of auricular acupressure in myopia prevention and control, as well as its effect on the choroidal and retinal thickness.

Method/design

A total of 480 subjects at 8–9 years old will be randomized in a 1:1 ratio to an intervention group versus a control group. The intervention group will receive auricular acupressure for 12 months, while the control group will be taken as a blank control. The primary and secondary outcomes will be measured at baseline, and again at 3, 6, 9, and 12 months after recruitment. The myopia incidence (spherical equivalent ≤ − 0.50 D) and the mean change of spherical equivalent will be taken as the primary variables; the secondary outcome measures include axial length, uncorrected visual acuity, and choroidal and retinal thickness.

Discussion

This trial aims to evaluate the effectiveness of auricular acupressure for myopia prevention and control with objective evidence and to preliminarily explore the plausible mechanism and provide reference for adopting this approach to retard the onset and control the progression of myopia.

Trial registration

Chinese Clinical Trial Registry ChiCTR2000038456. Registered on September 23, 2020.
Maternal low-intensity psychosocial telemental interventions in response to COVID-19 in Qatar: study protocol for a randomized controlled trial
Authors: Naja Sarah , Elyamani Rowaida , Chehab Mohamad , Siddig Mohamed , Al Ibrahim Abdullah , Mohamad Tagreed , Singh Rajvir , Bougmiza Iheb
Published: June 2021

Introduction

As COVID-19 is spreading, new psychological health problems are suspected to be emerging among pregnant women. Higher maternal mental health distress, including perinatal anxiety, depression, and COVID-19-specific phobia, is supposed to be increasing during the pandemic, which impacts pregnant women’s health and their infants and calls for intervention. Due to the social distancing protocols posed by the pandemic, telemental health interventions have fast become the most common form of psychosocial support for maternal mental health. However, there is no evidence of the effectiveness of maternal low-intensity psychosocial telemental interventions in improving mental health outcomes. The trial’s objective is to evaluate the clinical efficacy of telemental low-intensity psychosocial interventions in pregnant and postpartum women attending the Women Wellness and Research Centre in Qatar in the era of the COVID-19 pandemic.

Methods and analysis

The clinical trial is randomized in which pregnant women will be assigned equally through block randomization between two arms: (1) a control group and (2) an intervention group. The primary endpoint is the perinatal psychological distress, including perinatal depression, anxiety, and COVID-19 phobia in their third trimester; the secondary, tertiary, fourth, and fifth endpoints will be in the postnatal period (3–5 weeks, 2–4 months, 5–7 months, and 8–10 months). This trial involves pregnant women in their second trimester with no mental health illness history who communicate in English and Arabic and consent to participate. A sample size of 58 (29 participants per arm) is targeted.

Discussion

This study will provide recommendations about the efficacy of low-intensity psychosocial maternal telemental interventions to be implemented as a preventive service.

Trial registration

2a-ClinicalTrials.gov NCT04594525. Registered on October 20, 2020.
The quality of intervention reporting in trials of therapeutic exercise for hip osteoarthritis: a secondary analysis of a systematic review
Authors: Burgess Louise C. , Wainwright Thomas W. , James Khara A. , von Heideken Johan , Iversen Maura D.
Published: June 2021

Background

Therapeutic exercise is recommended as a core treatment for hip osteoarthritis (HOA). Whilst it is widely accepted that exercise can improve pain and disability, optimal type and dose of exercise are yet to be agreed upon. This may, in part, be attributed to the wide variation and inadequate reporting of interventions within the literature. This study evaluates the quality of intervention reporting among trials of therapeutic exercise in HOA.

Methods

Randomised controlled trials (RCTs) were sourced in a systematic review, completed in August 2020. Two raters independently used the Template for Intervention Description and Replication (TIDieR) and Consensus on Exercise Reporting Template (CERT) to evaluate intervention reporting. Correlations between quality assessment scores and CERT and TIDieR scores evaluated the relationship between internal validity and external applicability. The year of publication was compared to the quality of reporting scores.

Results

Fourteen RCTs were included in the analysis. On average, studies were awarded 9.43 ± 1.95 out of 12 points for the TIDieR checklist (range 4–12) and 13.57 ± 4.01 out of 19 points for the CERT (range 5–19). Pearson’s correlation coefficient suggested that the quality of reporting had improved over time and that there was a fair, positive relationship between internal validity and external applicability.

Discussion

Whilst the quality of intervention reporting is improving, many RCTs of therapeutic exercise in HOA lack the detail necessary to allow accurate evaluation and replication. Researchers are encouraged to utilise the standardised reporting guidelines to increase the translation of effective interventions into clinical practice.
Extensions of Hermite–Hadamard inequalities for harmonically convex functions via generalized fractional integrals
Authors: You Xue-Xiao , Ali Muhammad Aamir , Budak Hüseyin , Agarwal Praveen , Chu Yu-Ming
Published: June 2021

In the paper, the authors establish some new Hermite–Hadamard type inequalities for harmonically convex functions via generalized fractional integrals. Moreover, the authors prove extensions of the Hermite–Hadamard inequality for harmonically convex functions via generalized fractional integrals without using the harmonic convexity property for the functions. The results offered here are the refinements of the existing results for harmonically convex functions.
Dynamics of a lake-eutrophication model with nontransient/transient impulsive dredging and pulse inputting
Authors: Jiao Jianjun , Tang Wenyan
Published: June 2021

In this work, we present a lake-eutrophication model with nontransient/transient impulsive dredging and pulse inputting. We obtain globally asymptotically stable conditions for the phytoplankton-extinction periodic solution of system (2.1). Furthermore, we gain the permanent conditions for system (2.1). Finally, we employ computer simulations to illustrate the results. Our results indicate the effective controlling strategy for water resource management.
Introducing 3D printed models of the upper urinary tract for high-fidelity simulation of retrograde intrarenal surgery
Authors: Orecchia Luca , Manfrin Diego , Germani Stefano , Del Fabbro Dario , Asimakopoulos Anastasios D. , Finazzi Agrò Enrico , Miano Roberto
Published: June 2021

Purpose

Training in retrograde intrarenal surgery for the treatment of renal stone disease is a challenging task due to the unique complexity of the procedure. This study introduces a series of 3D printed models of upper urinary tract and stones designed to improve the training process.

Methods

Six different models of upper urinary tract were algorithmically isolated, digitally optimized and 3D printed from real-life cases. Soft and hard stones in different sizes were produced from 3D printed moulds. The models were fitted onto a commercially available part-task trainer and tested for retrograde intrarenal surgery.

Results

Each step of the procedure was simulated with extraordinary resemblance to real-life cases. The unique anatomical intricacy of each model and type of stones allowed us to reproduce surgeries of increasing difficulty. As the case-load required to achieve proficiency in retrograde intrarenal surgery is high, benchtop simulation could be integrated in training programs to reach good outcomes and low complication rates faster. Our models match incredible anatomical resemblance with low production cost and high reusability. Validation studies and objective skills assessment during simulations would allow comparison with other available benchtop trainers and the design of stepwise training programs.

Conclusions

3D printing is gaining a significant importance in surgical training. Our 3D printed models of the upper urinary tract might represent a risk-free training option to hasten the achievement of proficiency in endourology.
Depression and anxiety among hyperthyroid female patients and impact of treatment
Authors: Shoib Sheikh , Ahmad Javid , Wani Manzoor Ahmed , Ullah Irfan , Tarfarosh Shah Faisal Ahmad , Masoodi Shariq Rashid , Ramalho Rodrigo
Published: June 2021

Background

The aim of the present study was to compare the presence of psychiatric disorders in people with hyperthyroidism and euthyroid patients attending the Endocrinology Outpatient Department at the Shri Maharaja Hari Singh Hospital in Kashmir, India. Seventy-five patients with hyperthyroidism and an equal number of euthyroid patients participated in the study. Participants were selected using stratified random sampling. All patients were female. There was no significant difference between the two groups in terms of demographic features. Hormonal screening was performed by immunoassay and haemagglutination method. For the mental health assessment, the Mini-International Neuropsychiatric Interview (MINI), Hamilton Depression Rating Scale [HAM-D], and Hamilton Anxiety Rating Scale [HAM-A] were used.

Results

There was a higher prevalence of psychiatric disorders among the hyperthyroidism group (60% versus 34.7%). In particular, there was a higher prevalence of major depressive disorder, suicidality, generalised anxiety disorder, panic attacks, and agoraphobia. In some cases, the prevalence of a psychiatric disorder diminished after endocrinological treatment.

Conclusions

Screening patients with hyperthyroid disorders for psychiatric symptoms and disorders, and providing timely care when necessary, can go a long way in improving the quality of life of this population. It is imperative to establish routine screening and timely care of mental health symptoms and disorders in patients with hyperthyroidism.