bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular disease events within 5 years after a diagnosis of breast cancer
Authors: Mery Benoîte , Fouilloux Antoine , Rowinski Elise , Catella-Chatron Judith , Guichard Jean-Baptiste , Da Costa Antoine , Tinquaut Fabien , Magné N. , Bertoletti Laurent
Published: May 2020

Background

Concern for cardiovascular disease (particularly atrial fibrillation-AF) among women with breast cancer is becoming a major issue. We aimed at determining the incidence of cardiovascular disease events (AF, arterial and cardiac events, venous-thromboembolism-VTE) in patients diagnosed with breast cancer, and assessing potential risk factors.

Methods

We reviewed medical records of all patients diagnosed with breast cancer from 2010 to 2011 in our cancer center. Baseline characteristics of patients and tumors were collected. The main outcome was the occurrence of cardiovascular disease events (AF, VTE, arterial and cardiac events) during the 5-years follow-up.

Results

Among the 682 breast cancer patients, 22 (3.2%) patients had a history of atrial fibrillation. Thirty-four patients (5%) presented at least one cardiovascular disease event, leading to a cumulative incidence of 5.8% events at 5-years ([3.8–7.7] CI 95%), with most of them occurring in the first 2 years. AF cumulative incidence was 1.1% ([0.1–2.1] CI 95%). Factors associated with the occurrence of cardiovascular disease events (including AF) were an overexpression of HER-2 (HR 2.6 [1.21–5.56] p < 0.011), UICC-stage III tumors or more (HR 5.47 [2.78–10.76] p < 0.001) and pre-existing cardiovascular risk factors (HR 2.91 [1.36–6.23] p < 0.004).

Conclusion

The incidence of cardiovascular disease events was 5.8% ([3.8–7.7] CI 95%), with HER-2 over-expression, UICC-stage III tumors or more and pre-existing cardiovascular diseases being associated with them. These findings call for the development of preventive strategies in patients diagnosed with breast cancer.
PEACE V – Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): a study protocol for a randomized controlled phase II trial
Authors: De Bruycker A. , Spiessens A. , Dirix P. , Koutsouvelis N. , Semac I. , Liefhooghe N. , Gomez-Iturriaga A. , Everaerts W. , Otte F. , Papachristofilou A. , Scorsetti M. , Shelan M. , Siva S. , Ameye F. , Guckenberger M. , Heikkilä R. , Putora P. M. , Zapatero A. , Conde-Moreno A. , Couñago F. , Vanhoutte F. , Goetghebeur E. , Reynders D. , Zilli T. , Ost P.
Published: May 2020

Background

Pelvic nodal recurrences are being increasingly diagnosed with the introduction of new molecular imaging techniques, like choline and PSMA PET-CT, in the restaging of recurrent prostate cancer (PCa). At this moment, there are no specific treatment recommendations for patients with limited nodal recurrences and different locoregional treatment approaches are currently being used, mostly by means of metastasis-directed therapies (MDT): salvage lymph node dissection (sLND) or stereotactic body radiotherapy (SBRT). Since the majority of patients treated with MDT relapse within 2 years in adjacent lymph node regions, with an estimated median time to progression of 12–18 months, combining MDT with whole pelvic radiotherapy (WPRT) may improve oncological outcomes in these patients. The aim of this prospective multicentre randomized controlled phase II trial is to assess the impact of the addition of WPRT to MDT and short-term androgen deprivation therapy (ADT) on metastasis-free survival (MFS) in the setting of oligorecurrent pelvic nodal recurrence.

Methods & design

Patients diagnosed with PET-detected pelvic nodal oligorecurrence (≤5 nodes) following radical local treatment for PCa, will be randomized in a 1:1 ratio between arm A: MDT and 6 months of ADT, or arm B: WPRT added to MDT and 6 months of ADT. Patients will be stratified by type of PET-tracer (choline, FACBC or PSMA) and by type of MDT (sLND or SBRT). The primary endpoint is MFS and the secondary endpoints include clinical and biochemical progression-free survival (PFS), prostate cancer specific survival, quality of life (QoL), toxicity and time to castration-resistant prostate cancer (CRPC) and to palliative ADT. Estimated study completion: December 31, 2023.

Discussion

This is the first prospective multicentre randomized phase II trial assessing the potential of combined WPRT and MDT as compared to MDT alone on MFS for patients with nodal oligorecurrent PCa.

Trial registration

ClinicalTrials.gov Identifier: NCT03569241, registered June 14, 2018, ;

Identifier on Swiss National Clinical Trials Portal (SNCTP): SNCTP000002947, registered June 14, 2018.
The impact of parental psychopathology and sociodemographic factors in selective mutism - a nationwide population-based study
Authors: Koskela Miina , Chudal Roshan , Luntamo Terhi , Suominen Auli , Steinhausen Hans-Christoph , Sourander Andre
Published: May 2020

Background

Selective mutism (SM) is nowadays considered a relatively rare anxiety disorder characterized by children failing to speak in certain situations. Research on risk factors for SM are limited in comparison to other psychiatric disorders. The aim of this study was to examine several potential risk factors for SM in a large nationwide cohort, namely parental psychopathology, parental age, maternal SES, urbanicity, maternal marital status and parental immigration status.

Methods

This nested case-control study comprised 860 cases with SM, identified from the Finnish Hospital Discharge Register and 3250 controls matched for sex and age from the Finnish Central Population Register. Conditional logistic regression was used to examine the association between the risk factors and SM.

Results

If both parents had any psychiatric disorder, this almost tripled their odds of having a child with SM (OR 2.8, 95% CI 2.0–4.0). There were increased rates of all types of psychiatric disorders in the parents of the children with SM, with a wider range of diagnoses among the mothers than fathers. Fathers over 35 years (OR 1.4, 95% CI 1.1–1.8) were significantly more likely to have children with SM. Offspring of a single mother had a 2-fold (OR = 2.0, 95% CI 1.4–3.0) increased odds of SM than mothers who were married or in a relationship.

Conclusions

Several parental psychiatric disorders were associated with offspring SM. This points towards a shared aetiology of psychiatric disorders. Findings on paternal age and single motherhood help to improve our understanding of risk factors for SM.
Social interactions, experiences with adverse life events and depressive symptoms in individuals with visual impairment: a cross-sectional study
Authors: Brunes Audun , Heir Trond
Published: May 2020

Background

Knowledge about the high rates of depression in people with visual impairment (VI) remains unclear. The study aimed to examine whether depressive symptoms in people with VI were associated with social isolation, perceived social support and lifetime exposure to bullying, physical abuse or sexual abuse.

Methods

An anonymous telephone survey was conducted from January to May 2017 in an age-stratified sample of adults with VI who were members of the Norwegian Association of the Blind and Partially Sighted. Participants were asked questions about social isolation, perceived social support, and past experiences with bullying and abuse. Depressive symptoms were measured by the nine-item Patient Health Questionnaire (PHQ-9). We calculated unadjusted and full-adjusted exponentiated beta-values (Exp(β)) and corresponding 95% confidence intervals (CIs) using generalized linear models.

Results

Overall, 736 (61%) adults participated in the study. The mean depression scores were 5.24 (SD: 5.3, range: 0–27), 4.61 for men and 5.77 for women. Results from the full-adjusted model showed higher levels of depressive symptoms among participants who reported social isolation (Exp(β): 1.89, 95% CI: 1.63–2.20), lower levels of perceived social support (Exp(β): 1.55, 95% CI: 1.31–1.83), and past experiences of abuse (Exp(β): 1.41, 95% CI: 1.17–1.70). The strength of the associations between past exposure to bullying or abuse and depressive symptoms was similar for those with low and high levels of support.

Conclusion

Social isolation, perceived support and experiences of adverse events appear to be independently associated with depressive symptoms. Thus, social integration may be appropriate for the promotion of mental health among people with VI.
Khat use and intimate partner violence in a refugee population: a qualitative study in Dollo Ado, Ethiopia
Authors: Sharma Vandana , Papaefstathiou Stephanos , Tewolde Samuel , Amobi Adaugo , Deyessa Negussie , Relyea Bridget , Scott Jennifer
Published: May 2020

Background

Intimate partner violence (IPV) is the most common form of gender-based violence affecting women and girls worldwide and is exacerbated in humanitarian crises. There is evidence that substance use is associated with male perpetration of IPV. Consumption of khat —a plant containing amphetamines traditionally chewed in the horn of Africa and legal in some countries including Ethiopia—may increase risk of IPV toward women. This analysis aimed to assess perceptions on khat use among Somali refugees in Dollo Ado, Ethiopia and its association with IPV to inform an IPV and HIV prevention intervention.

Methods

A descriptive qualitative study comprising individual interviews (n = 30) and focus group discussions (n = 10) was conducted in Bokolmayo refugee camp in Dollo Ado, Ethiopia in October 2016. A purposive sample of male and female Somali refugees, religious and community leaders, and service providers (n = 110 individuals; 44 women and 66 men) was included. Trained interviewers from the camp conducted the interviews and discussion, which were audio recorded, transcribed and translated. A content analysis was conducted on coded excerpts from the transcripts to identify factors contributing to IPV toward women, including khat use.

Results

Participants reported that displacement has resulted in limited employment opportunities for men and increased idle time, which has led to increased khat use among men as a coping mechanism. Male khat use was perceived to be associated with perpetration of physical and sexual IPV through several mechanisms including increased anger and aggression and enhanced sexual desire. Khat use also contributes to intra-marital conflict as money allocated for a household is spent on purchasing khat.

Conclusion

Khat use should be addressed as part of IPV prevention programming in this context. Livelihood interventions and other strategies to improve economic conditions, should be explored in collaboration with refugee camp authorities and community leaders as a potential avenue to mitigate the impact of khat use on women and families.
The Brazilian Portuguese version of the Exercise Adherence Rating Scale (EARS-Br) showed acceptable reliability, validity and responsiveness in chronic low back pain
Authors: de Lira Mariana Romano , de Oliveira Anamaria Siriani , França Roberta Aniceto , Pereira Ana Claudia , Godfrey Emma L. , Chaves Thais Cristina
Published: May 2020

Background

This study aimed to adapt the Exercise Adherence Rating Scale (EARS) into Brazilian Portuguese and evaluate its measurement properties, given as reliability, validity, and responsiveness in patients with non-specific Chronic Low Back Pain (CLBP).

Methods

A total of 108 patients with a mean age of 46.62 years (SD = 9.98) and CLBP participated in this longitudinal study. Participants were oriented on undertaking the prescribed exercises in the first session, and adherence behavior was assessed after 1 week, and finally reassessed after 2 weeks (test-retest reliability). Three weeks after the first assessment, they were invited again to full fill the EARS (responsiveness). The intraclass correlation coefficient (ICC2,1) and Cronbach’s α were used to assess test-retest reliability and internal consistency, respectively. Spearman’s correlation and confirmatory factor analysis (CFA) were used to assess construct validity, and the Receiver operating characteristic curve and area under the curve (AUC) were used to analyze responsiveness.

Results

The one-factor EARS-Br (adherence behavior) structure with 6 items showed acceptable fit indexes (comparative fit index and goodness of fit index> 0.90 and root-mean-square error of approximation< 0.08). The EARS-Br scale showed acceptable internal consistency (α = 0.88) and excellent reliability (ICC = 0.91 [95% CI 0.86–0.94]). Mild to moderate correlations were observed between EARS-Br total score vs. disability, pain catastrophizing, depression/anxiety, fear-avoidance and pain intensity. A Minimally Important Change (MIC) of 5.5 in the EARS-Br total score was considered as a meaningful change in the adherence behavior (AUC = 0.82). Moderate accuracy (AUC = 0.89) was obtained for a 17/24 total EARS cutoff score after home exercise was prescribed. The sensitivity and specificity were also acceptable (greater than 80%).

Conclusion

Our results demonstrated acceptable EARS-Br reliability, validity, and responsiveness for patients with CLBP. A final score of 17/24 on EARS after the prescription of home-exercise could be used as a cut-off for an acceptable adherence behavior associated with improvement in patient outcomes.
The required competencies of physicians within palliative care from the perspectives of multi-professional expert groups: a qualitative study
Authors: Melender Hanna-Leena , Hökkä Minna , Saarto Tiina , Lehto Juho T.
Published: May 2020

Background

Although statements on the competencies required from physicians working within palliative care exist, these requirements have not been described within different levels of palliative care provision by multi-professional workshops, comprising representatives from working life. Therefore, the aim of this study was to describe the competencies required from physicians working within palliative care from the perspectives of multi-professional groups of representatives from working life.

Methods

A qualitative approach, using a workshop method, was conducted, wherein the participating professionals and representatives of patient organizations discussed the competencies that are required in palliative care, before reaching and documenting a consensus. The data (n = 222) was collected at workshops held in different parts of Finland and it was analyzed using a qualitative content analysis method.

Results

The description of the competencies required of every physician working within palliative care at the general level included 13 main categories and 50 subcategories in total. ‘Competence in advanced care planning and decision-making’ was the main category which was obtained from the highest number of reduced expressions from the original data (f = 125). Competence in social interactions was another strong main category (f = 107). In specialist level data, six main categories with 22 subcategories in total were found. ‘Competence in complex symptom management’ was the main category which was obtained from the biggest number of reduced expressions (f = 46). A notable association between general level and specialist level data was related to networking, since one of the general level categories was ‘Competence in consultations and networking’ (f = 34) and one of the specialist level categories was ‘Competence to offer consultative and educational support to other professionals’ (f = 30). Moreover, part of the specialist level results were subcategories which belonged to the main categories produced from the general level data.

Conclusions

The competencies described in this study emphasize decision-making, social interactions and networking. It is important to listen to the voices of the working-life representatives when planning curricula. Moreover, the views of the working-life representatives inform how the competencies gained during their education meet the challenges of the ordinary work.
How stable is lung function in patients with stable chronic obstructive pulmonary disease when monitored using a telehealth system? A longitudinal and home-based study
Authors: Holmner Åsa , Öhberg Fredrik , Wiklund Urban , Bergmann Eva , Blomberg Anders , Wadell Karin
Published: May 2020

Background

Many telehealth systems have been designed to identify signs of exacerbations in patients with chronic obstructive pulmonary disease (COPD), but few previous studies have reported the nature of recorded lung function data and what variations to expect in this group of individuals. The aim of the study was to evaluate the nature of individual diurnal, day-to-day and long-term variation in important prognostic markers of COPD exacerbations by employing a telehealth system developed in-house.

Methods

Eight women and five men with COPD performed measurements (spirometry, pulse oximetry and the COPD assessment test (CAT)) three times per week for 4–6 months using the telehealth system. Short-term and long-term individual variations were assessed using the relative density and weekly means respectively. Quality of the spirometry measurements (forced expiratory volume in one second (FEV1) and inspiratory capacity (IC)) was assessed employing the criteria of American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.

Results

Close to 1100 measurements of both FEV1and IC were performed during a total of 240 patient weeks. The two standard deviation ranges for intra-individual short-term variation were approximately ±210 mL and ± 350 mL for FEV1and IC respectively. In long-term, spirometry values increased and decreased without notable changes in symptoms as reported by CAT, although it was unusual with a decrease of more than 50 mL per measurement of FEV1between three consecutive measurement days. No exacerbation occurred. There was a moderate to strong positive correlation between FEV1and IC, but weak or absent correlation with the other prognostic markers in the majority of the participants.

Conclusions

Although FEV1and IC varied within a noticeable range, no corresponding change in symptoms occurred. Therefore, this study reveals important and, to our knowledge, previously not reported information about short and long-term variability in prognostic markers in stable patients with COPD. The present data are of significance when defining criteria for detecting exacerbations using telehealth strategies.
N6-methyladenosine methyltransferase METTL3 affects the phenotype of cerebral arteriovenous malformation via modulating Notch signaling pathway
Authors: Wang Lin-jian , Xue Yimeng , Huo Ran , Yan Zihan , Xu Hongyuan , Li Hao , Wang Jia , Zhang Qian , Cao Yong , Zhao Ji-zong
Published: May 2020

Background

Cerebral arteriovenous malformation (AVM) is a serious life-threatening congenital cerebrovascular disease. Specific anatomical features, such as nidus size, location, and venous drainage, have been validated to affect treatment outcomes. Until recently, molecular biomarkers and corresponding molecular mechanism related to anatomical features and treatment outcomes remain unknown.

Methods

RNA N6-methyladenosine (m6A) Methyltransferase METTL3 was identified as a differentially expressed gene in groups with different lesion sizes by analyzing the transcriptome sequencing (RNA-seq) data. Tube formation and wound healing assays were performed to investigate the effect of METTL3 on angiogenesis. In addition, Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq) was performed to screen downstream targets of METTL3 in endothelial cells and to fully clarify the specific underlying molecular mechanisms affecting the phenotype of cerebral AVM.

Results

In the current study, we found that the expression level of METTL3 was reduced in the larger pathological tissues of cerebral AVMs. Moreover, knockdown of METTL3 significantly affected angiogenesis of the human endothelial cells. Mechanistically, down-regulation of METTL3 reduced the level of heterodimeric Notch E3 ubiquitin ligase formed by DTX1 and DTX3L, thereby continuously activating the Notch signaling pathway. Ultimately, the up-regulated downstream genes of Notch signaling pathway dramatically affected the angiogenesis of endothelial cells. In addition, we demonstrated that blocking Notch pathway with DAPT could restore the phenotype of METTL3 deficient endothelial cells.

Conclusions

Our findings revealed the mechanism by which m6A modification regulated the angiogenesis and might provide potential biomarkers to predict the outcome of treatment, as well as provide suitable pharmacological targets for preventing the formation and progression of cerebral AVM.
In vitro and in vivo recombination of heterologous modules for improving biosynthesis of astaxanthin in yeast
Authors: Qi Dan-Dan , Jin Jin , Liu Duo , Jia Bin , Yuan Ying-Jin
Published: May 2020

Background

Astaxanthin is a kind of tetraterpene and has strong antioxygenic property. The biosynthesis of astaxanthin in engineered microbial chassis has greater potential than its chemical synthesis and extraction from natural producers in an environmental-friendly way. However, the cost-offsetting production of astaxanthin in engineered microbes is still constrained by the poor efficiency of astaxanthin synthesis pathway as a heterologous pathway.

Results

To address the bottleneck of limited production of astaxanthin in microbes, we developed in vitro and in vivo recombination methods respectively in engineered yeast chassis to optimize the combination of heterologous β-carotene ketolase (crtW) and hydroxylase (crtZ) modules that were selected from different species. As a result, the in vitro and in vivo recombination methods enhanced the astaxanthin yield respectively to 2.11–8.51 folds and 3.0–9.71 folds compared to the initial astaxanthin pathway, according to the different combination of particular genes. The highest astaxanthin producing strain yQDD022 was constructed by in vivo method and produced 6.05 mg g−1 DCW of astaxanthin. Moreover, it was proved that the in vivo recombination method showed higher DNA-assembling efficiency than the in vitro method and contributed to higher stability to the engineered yeast strains.

Conclusions

The in vitro and in vivo recombination methods of heterologous modules provide simple and efficient ways to improve the astaxanthin yield in yeast. Both the two methods enable high-throughput screening of heterologous pathways through recombination of certain crtW and crtZ derived from different species. This study not only exploited the underlying optimal combination of crtZ and crtW for astaxanthin synthesis, but also provided a general approach to evolve a heterologous pathway for the enhanced accumulation of desired biochemical products.
Circ_100565 promotes proliferation, migration and invasion in non-small cell lung cancer through upregulating HMGA2 via sponging miR-506-3p
Authors: Li Li , Wei Haitao , Zhang Haifeng , Xu Feng , Che Guowei
Published: May 2020

Background

Circular RNAs (circRNAs) play a vital role in the development of various cancers. Circ_100565 was found to be a highly expressed circRNA in non-small cell lung cancer (NSCLC) tissues screened by microarray profiles of circRNAs. However, the role of circ_100565 in NSCLC still remains unknown.

Methods

Microarray analysis was used to screen for differentially expressed circRNAs in NSCLC tissues. The expression levels of circ_100565, microRNA-506-3p (miR-506-3p) and high mobility group AT-hook 2 (HMGA2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. Transwell assay was used to determine the migration and invasion of cells. Besides, Western blot (WB) analysis was performed to assess the levels of proliferation and metastasis-related proteins and HMGA2 protein. Moreover, animal experiments were used to confirm the effect of circ_100565 on NSCLC tumor growth in vivo. In addition, the interaction between miR-506-3p and circ_100565 or HMGA2 was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) assay or biotin-labeled pull-down assay.

Results

Circ_100565 was upregulated in NSCLC, and its high expression was positively associated with the poor overall survival of NSCLC patients. Silencing of circ_100565 suppressed the proliferation, migration and invasion of NSCLC cells in vitro and reduced the tumor growth of NSCLC in vivo. Circ_100565 could sponge miR-506-3p, and miR-506-3p could target HMGA2. Moreover, miR-506-3p inhibitor or HMGA2 overexpression could reverse the inhibition effect of circ_100565 knockdown on NSCLC progression.

Conclusion

Circ_100565 increased HMGA2 expression to promote proliferation, migration and invasion in NSCLC via absorbing miR-506-3p. Our findings provided a new biomarker for NSCLC therapy.
Insecticide resistance in Anopheles stephensi in Somali Region, eastern Ethiopia
Authors: Yared Solomon , Gebressielasie Araya , Damodaran Lambodhar , Bonnell Victoria , Lopez Karen , Janies Daniel , Carter Tamar E.
Published: May 2020

Background

The movement of malaria vectors into new areas is a growing concern in the efforts to control malaria. The recent report of Anopheles stephensi in eastern Ethiopia has raised the necessity to understand the insecticide resistance status of the vector in the region to better inform vector-based interventions. The aim of this study was to evaluate insecticide resistance in An. stephensi in eastern Ethiopia using two approaches: (1) World Health Organization (WHO) bioassay tests in An. stephensi; and (2) genetic analysis of insecticide resistance genes in An. stephensi in eastern Ethiopia.

Methods

Mosquito larvae and pupae were collected from Kebri Dehar. Insecticide susceptibility of An. stephensi was tested with malathion 5%, bendiocarb 0.1%, propoxur 0.1%, deltamethrin 0.05%, permethrin 0.75%, pirimiphos-methyl 0.25% and DDT 4%, according to WHO standard protocols. In this study, the knockdown resistance locus (kdr) in the voltage gated sodium channel (vgsc) and ace1R locus in the acetylcholinesterase gene (ace-1) were analysed in An. stephensi.

Results

All An. stephensi samples were resistant to carbamates, with mortality rates of 23% and 21% for bendiocarb and propoxur, respectively. Adult An. stephensi was also resistant to pyrethroid insecticides with mortality rates 67% for deltamethrin and 53% for permethrin. Resistance to DDT and malathion was detected in An. stephensi with mortality rates of 32% as well as An. stephensi was resistance to pirimiphos-methyl with mortality rates 14%. Analysis of the insecticide resistance loci revealed the absence of kdr L1014F and L1014S mutations and the ace1R G119S mutation.

Conclusion

Overall, these findings support that An. stephensi is resistant to several classes of insecticides, most notably pyrethroids. However, the absence of the kdr L1014 gene may suggest non-target site resistance mechanisms. Continuous insecticide resistance monitoring should be carried out in the region to confirm the documented resistance and exploring mechanisms conferring resistance in An. stephensi in Ethiopia.
Circular RNA circCCDC9 acts as a miR-6792-3p sponge to suppress the progression of gastric cancer through regulating CAV1 expression
Authors: Luo Zai , Rong Zeyin , Zhang Jianming , Zhu Zhonglin , Yu Zhilong , Li Tengfei , Fu Zhongmao , Qiu Zhengjun , Huang Chen
Published: May 2020

Background

As a novel type of noncoding RNAs, covalently closed circular RNAs (circRNAs) are ubiquitously expressed in eukaryotes. Emerging studies have related dysregulation of circRNAs to tumorigenesis. However, the biogenesis, regulation, function and mechanism of circRNAs in gastric cancer (GC) remain largely unclear.

Methods

The expression profile of circRNAs in 6 pairs of GC tissues and adjacent non-tumor tissues was analyzed by RNA-sequencing. Quantitative real-time PCR was used to determine the expression level of circCCDC9 in GC tissues and cell lines. Then, functional experiments in vitro and in vivo were employed to explore the effects of circCCDC9 on tumor growth and metastasis in GC. Mechanistically, dual luciferase reporter, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to confirm that circCCDC9 directly sponged miR-6792-3p and alleviated suppression on target CAV1 expression.

Results

Evidently down-regulated expression of circCCDC9 was observed in both GC tissues and cell lines. Expression of circCCDC9 was negatively correlated with tumor size, lymph node invasion, advanced clinical stage and overall survival in GC patients. Functionally, overexpression of circCCDC9 significantly inhibited the proliferation, migration and invasion of GC cell lines in vitro and tumor growth and metastasis in vivo, whereas miR-6792-3p mimics counteracted these effects. Mechanistic analysis demonstrated that circCCDC9 acted as a “ceRNA” of miR-6792-3p to relieve the repressive effect of miR-6792-3p on its target CAV1, then suppressed the tumorigenesis of GC.

Conclusions

CircCCDC9 functions as a tumor suppressor in inhibiting the progression of GC through miR-6792-3p/CAV1 axis, which has provided an exploitable biomarker and therapeutic target for patients with GC.
Exploring the experience of inpatients with severe alcohol use disorder on a managed alcohol program (MAP) at St. Paul’s Hospital
Authors: Parappilly Beena P. , Garrod Emma , Longoz Ryan , Eligh Eric , van Heukelom Holly , Fairgrieve Christopher Kit , Pauly Bernadette
Published: May 2020

Background

Managed alcohol programs are a harm reduction approach for people with severe alcohol use disorder that provide alcohol in a structured setting. We examined the patient experience of receiving alcohol after the implementation of a hospital-based managed alcohol program.

Methods

Using an interpretative descriptive methodology, we conducted interviews with five patients. The criteria for enrollment included continuation of community managed alcohol program or provision of alcohol for stabilization in hospital and ability to provide consent.

Results

Five themes emerged in the analysis: (1) Reasons for alcohol use highlighting factors leading to alcohol consumption; (2) I’m very appreciative indicating participant’s perception of hospital-based managed alcohol program; (3) From just vibrating to calm and It’s kinda like a pacifier for me recognizing the impact of hospital-based managed alcohol program on managing withdrawal and on psychological health; (4) I have no need to go anywhere at all demonstrating engagement in healthcare; and (5) Might be nice to have a selection for other people indicating the need for a broader selection of alcohol.

Conclusions

This study helped to explore the effectiveness of a hospital-based managed alcohol program as experienced by the patients. Overall, participants had a positive experience on hospital-based managed alcohol program. Their perceptions can be used to inform implementation of managed alcohol programs in other hospital settings.
Hospital admissions among people who inject opioids following syringe services program implementation
Authors: Bornstein K. J. , Coye A. E. , St. Onge J. E. , Li H. , Muller A. , Bartholomew T. S. , Tookes H. E.
Published: May 2020

Background

Syringe services programs (SSPs) are an evidence-based harm reduction strategy that reduces dangerous sequelae of injection drug use among people who inject drugs (PWID) such as overdose. SSP services include safer injection education and community-based naloxone distribution programs. This study evaluates differences in overdose-associated hospital admissions following the implementation of the first legal SSP in Florida, based in Miami-Dade County.

Methods

We performed a retrospective analysis of hospitalizations for injection drug-related sequelae at a county hospital before and after the implementation of the SSP. An algorithm utilizing ICD-10 codes for opioid use and sequelae was used to identify people who inject opioids (PWIO). Florida Department of Law Enforcement Medical Examiners Commission Report data was used to analyze concurrent overdose death trends in Florida counties.

Results

Over the 25-month study period, 302 PWIO admissions were identified: 146 in the pre-index period vs. 156 in the post-index period. A total of 26 admissions with PWIO overdose were found: 20 pre-index and 6 post-index (p = 0.0034).

Conclusions

Declining overdose-associated admissions among PWIO suggests early impacts following SSP implementation. These results indicate a potential early benefit of SSP that should be further explored for its effects on future hospital admission and mortality.
The impact of type 1 diabetes on young adults’ health-related quality of life
Authors: Bronner Madelon B. , Peeters Mariëlle A. C. , Sattoe Jane N. T. , van Staa AnneLoes
Published: May 2020

Background

Young adulthood is a challenging period for people with diabetes mellitus type 1 (T1DM) as they are facing multiple life transitions while managing a demanding disease. This poses a risk for impaired health-related quality of life (HRQOL). We assessed HRQOL in a cohort of young adults with T1DM in the Netherlands, and compared outcomes with those of Dutch norm groups of healthy young adults and young adults with a chronic disease.

Methods

We analyzed data collected in a larger evaluation study on transitional care for young adults with T1DM in a nationwide sample in the Netherlands, including twelve participating hospitals. These data had been obtained from online questionnaires completed by young adults with T1DM after they had transferred to adult care. HRQOL was self-reported with the Pediatric Quality of Life Inventory for young adults (PedsQL-YA).

Results

One hundred and sixty-five young adults with T1DM participated (44.2% response); and they scored significantly worse than did healthy peers on all domains of HRQOL, except social functioning. Particularly, functioning at school or work was worse than that of the norm group. The study group’s HRQOL-scores were comparable to norm scores of young adults with chronic diseases, although the physical and social functioning of young people with T1DM was better. One quarter (26.1%) of all young adults with T1DM reported fatigue.

Conclusions

During transition to adulthood, young adults with T1DM struggle to maintain a balance between the demands of managing a disease and their life. Many of them encounter problems at work or school, and suffer from fatigue. These findings underscore the need to regularly assess HRQOL, and to discuss work- and education-related issues in clinical practice.
Association between the quality of inner cell mass and first trimester miscarriage after single blastocyst transfer
Authors: Shi Dayuan , Xu Jiawei , Zhang Meixiang , Niu Wenbin , Shi Hao , Yao Guidong , Li Ying , Zhang Nan , Sun Yingpu
Published: May 2020

Background

The blastocyst morphology provided valuable roles for predicting pregnancy and live birth, but was still not fully understood for evaluating miscarriage. The aim of this study was to explore the association between blastocyst morphologic evaluation and first trimester miscarriage combined with karyotype of miscarried conceptus.

Methods

This retrospective cohort study included a total of 2873 clinical pregnancy cycles with single blastocyst transfer performed from January 2013 to April 2019. Chromosome karyotype of miscarried conceptus was analyzed via single nucleotide polymorphism array analysis. Miscarriage and karyotype of miscarried conceptus associated with blastocyst morphology were analyzed by chi-square and logistic regression analysis.

Results

A total of 354 (12.3%) cycles resulted in first trimester miscarriage. Miscarriage rates increased with trophectoderm (TE) grade from A to C (P = 0.012), while three morphologic parameters (blastocoele expansion degree, inner cell mass (ICM) and TE) showed no statistical significance with miscarriage after multivariable analysis. The rate of aneuploidy was 47.7% (83 of 174) in total miscarried conceptuses. For euploid miscarriages, the grade B of ICM occupied a higher proportion compared with aneuploidy, with OR of 2.474, (95% CI, 1.311–4.699), P = 0.005.

Conclusions

Chromosomal aberration of embryo is an important genetic factor for first trimester miscarriage, and the quality of ICM is a potential indicator for euploid miscarriage. Blastocysts with grade A of ICM should be given priority during single blastocyst transfer to reduce potential miscarriage.
Cryopreservation of single-sperm: where are we today?
Authors: Liu Shasha , Li Fuping
Published: May 2020

Background

Patients with severe oligospermia and nonobstructive azoospermia have very limited numbers of viable sperm in their epididymal and testicular samples. Thus, cryopreservation of their sperm is performed to avoid repeated sperm retrievals and to preserve their sperm from any side effects of any treatment regimens.

Main body

The development of intracytoplasmic sperm injection technology has extended the therapeutic capacity of assisted reproductive technology for men with azoospermia via the surgical or percutaneous isolation of sperm from the testis/epididymis. The conventional cryopreservation techniques are inadequate for preserving individually selected sperm. The technique for freezing single sperm was first developed in 1997 and has been explored from the perspective of frozen carriers, freezing programs, and cryoprotectant formulations. Among these methods, advances in frozen carriers have directly improved single-sperm freezing technology. In this review, we evaluate the different technologies for the cryopreservation of single sperm by discussing the advantages and disadvantages of different freezing methods, their clinical applications, and the outcomes for a range of frozen carriers.

Conclusion

Our review article describes the latest and current technologies implemented for the cryopreservation of single sperm that could potentially benefit patients with severe oligospermia and who rarely have any sperm in their ejaculate. This review provides a platform to understand the process and pitfalls of single-sperm cryopreservation to ensure further improvements in the cryopreservation technology in future studies.
Immuno-metabolic impact of the multiple sclerosis patients’ sera on endothelial cells of the blood-brain barrier
Authors: Sheikh M. H. , Henson S. M. , Loiola R. A. , Mercurio S. , Colamatteo A. , Maniscalco G. T. , De Rosa V. , McArthur S. , Solito E.
Published: May 2020

Background

Multiple sclerosis (MS) is an autoimmune disease which results from the invasion of the brain by activated immune cells across the endothelial cells (ECs) of the blood-brain barrier (BBB), due to loss of immune self-tolerance. Many reports define the metabolic profile of immune cells in MS, however little is known about the metabolism of the BBB ECs during the disease. We aim to determine whether circulating factors in MS induce metabolic alterations of the BBB ECs compared to a healthy state, which can be linked with disruption of BBB integrity and subsequent immune cell extravasation.

Methods and results

In this report, we used an in vitro model to study the effect of sera from naïve-to-treatment, relapsing-remitting MS (RRMS) patients on the human brain microvascular endothelium, comparing effects to age/sex-matched healthy donor (HD) sera. Our data show that RRMS serum components affect brain endothelial cells by impairing intercellular tightness through the down-modulation of occludin and VE-cadherin, and facilitating immune cell extravasation through upregulation of intercellular adhesion molecules (ICAM-1) and P-glycoprotein (P-gp). At a metabolic level, the treatment of the endothelial cells with RRMS sera reduced their glycolytic activity (measured through the extracellular acidification rate-ECAR) and oxygen consumption rate (oxidative phosphorylation rate-OCR). Such changes were associated with the down-modulation of endothelial glucose transporter 1 (GLUT-1) expression and by altered mitochondrial membrane potential. Higher level of reactive oxygen species released from the endothelial cells treated with RRMS sera indicate a pro-inflammatory status of the cells together with the higher expression of ICAM-1, endothelial cell cytoskeleton perturbation (stress fibres) as well as disruption of the cytoskeleton signal transduction MSK1/2 and β-catenin phosphorylation.

Conclusions

Our data suggest that circulating factors present in RRMS patient serum induce physiological and biochemical alterations to the BBB, namely reducing expression of essential tightness regulators, as well as reduced engagement of glycolysis and alteration of mitochondrial potential. As these last changes have been linked with alterations in nutrient usage and metabolic function in immune cells; we propose that the BBB endothelium of MS patients may similarly undergo metabolic dysregulation, leading to enhanced permeability and increased disease susceptibility.
How obsessive–compulsive and bipolar disorders meet each other? An integrative gene-based enrichment approach
Authors: Hamidian Sajedeh , Pourshahbaz Abbas , Bozorgmehr Ali , Ananloo Esmaeil Shahsavand , Dolatshahi Behrooz , Ohadi Mina
Published: May 2020

Background

The novel approaches to psychiatric classification assume that disorders, contrary to what was previously thought, are not completely separate phenomena. In this regard, in addition to symptom-based criteria, disturbances are also considered on the basis of lower level components. With this viewpoint, identifying common biochemical markers would be beneficial in adopting a comprehensive strategy for prevention, diagnosis and treatment.

Main body

One of the problematic areas in clinical settings is the coexistence of both obsessive–compulsive disorder (OCD) and bipolar disorder (BD) that is challenging and difficult to manage. In this study, using a system biologic approach we aimed to assess the interconnectedness of OCD and BD at different levels. Gene Set Enrichment Analysis (GSEA) method was used to identify the shared biological network between the two disorders. The results of the analysis revealed 34 common genes between the two disorders, the most important of which were CACNA1C, GRIA1, DRD2, NOS1, SLC18A1, HTR2A and DRD1. Dopaminergic synapse and cAMP signaling pathway as the pathways, dopamine binding and dopamine neurotransmitter receptor activity as the molecular functions, dendrite and axon part as the cellular component and cortex and striatum as the brain regions were the most significant commonalities.

Short conclusion

The results of this study highlight the role of multiple systems, especially the dopaminergic system in linking OCD and BD. The results can be used to estimate the disease course, prognosis, and treatment choice, particularly in the cases of comorbidity. Such perspectives, going beyond symptomatic level, help to identify common endophenotypes between the disorders and provide diagnostic and therapeutic approaches based on biological in addition to the symptomatic level.
“Left ventricular lipoma….. a rare case”, case report
Authors: Shamsi Fahad , Bajwa Gurjyot , Ghalib Hussam
Published: May 2020

Background

A cardiac lipoma is a rare primary cardiac tumor. They are usually asymptomatic and carry a good prognosis. Cardiac Magnetic Resonance Imaging (CMR) is the confirmatory investigation of choice.

Case presentation

We present a case of left ventricular lipoma in an asymptomatic patient, which was successfully treated with surgical resection.

Conclusion

Cardiac lipomas are rare and are usually benign. There is no guideline on the management of cardiac lipomas and treatment is individualized.
A case of giant main pulmonary artery aneurysm associated with complicated congenital heart disease and simultaneous chronic pulmonary artery dissection
Authors: Wang Yue-bo , Chen Guang-wen , Pu Hong , Li Hang
Published: May 2020

Background

Pulmonary artery aneurysm (PAA), usually associated with congenital heart disease (CHD), is a very rare clinical condition. Pulmonary artery dissection (PAD) is considered the most life-threatening complication of PAA, and patients can progress from being asymptomatic to sudden death. We report the following case of PAA associated with complicated congenital heart disease and simultaneous chronic PAD. To our knowledge, few such complicated cases have ever been reported.

Case presentation

A 36-year-old male presented to our hospital with a 10-year history of heart fatigue after activities and aggravated for 2 years. Computed tomography angiography (CTA) and echocardiogram showed a giant main pulmonary artery aneurysm (14 cm) with complicated congenital heart disease (a small patent ductus arteriosus, ventricular septal defects, aortic coarctation). Chronic PAD, which was mistaken for a pulmonary valve before operation, was detected during surgery.

Conclusions

PAA associated with complicated CHD and simultaneous PAD is very rare, and its clinical symptoms are varied. Radiologists and surgeons should pay attention to determining whether this patient simultaneously had PAD when PAA was detected on preoperative CTA imaging.
APEC: an accesson-based method for single-cell chromatin accessibility analysis
Authors: Li Bin , Li Young , Li Kun , Zhu Lianbang , Yu Qiaoni , Cai Pengfei , Fang Jingwen , Zhang Wen , Du Pengcheng , Jiang Chen , Lin Jun , Qu Kun
Published: May 2020

The development of sequencing technologies has promoted the survey of genome-wide chromatin accessibility at single-cell resolution. However, comprehensive analysis of single-cell epigenomic profiles remains a challenge. Here, we introduce an accessibility pattern-based epigenomic clustering (APEC) method, which classifies each cell by groups of accessible regions with synergistic signal patterns termed “accessons”. This python-based package greatly improves the accuracy of unsupervised single-cell clustering for many public datasets. It also predicts gene expression, identifies enriched motifs, discovers super-enhancers, and projects pseudotime trajectories. APEC is available athttps://github.com/QuKunLab/APEC.
The effect of supplemental oxygen on perioperative brain natriuretic peptide concentration in cardiac risk patients – a protocol for a prosprective randomized clinical trial
Authors: Reiterer Christian , Kabon Barbara , von Sonnenburg Markus Falkner , Starlinger Patrick , Taschner Alexander , Zotti Oliver , Goshin Julius , Drlicek Gregor , Fleischmann Edith
Published: May 2020

Background

Elevated postoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are predictive for cardiac adverse events in noncardiac surgery. Studies indicate that supplemental oxygen decreases sympathetic nerve activity and might, therefore, improve cardiovascular function. Thus, we will test the effect of perioperative supplemental oxygen administration on NT-proBNP release after surgery.

Methods/design

We will conduct a single-center, double-blinded, randomized trial at the Medical University of Vienna, including 260 patients with increased cardiac risk factors undergoing moderate- to high-risk noncardiac surgery. Patients will be randomly assigned to receive 80% versus 30% oxygen during surgery and for 2 h postoperatively. The primary outcome will be the difference in maximum NT-proBNP release after surgery.

As secondary outcomes we will assess the effect of supplemental oxygen on postoperative maximum troponin T concentration, oxidation-reduction potential, von Willebrand factor concentration and perioperative fluid requirements. We will perform outcome measurements 2 h after surgery, on postoperative day 1 and on postoperative day 3. The NT-proBNP concentration and the oxidation-reduction potential will also be measured within 72 h before discharge.

Discussion

Our trial should determine whether perioperative supplemental oxygen administration will reduce the postoperative release of NT-proBNP in patients with preoperative increased cardiovascular risk factors undergoing noncardiac surgery.

Trial registration

ClinicalTrials.gov, ID: NCT03366857. Registered on 8th December 2017.