bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative study of Revogene GBS LB assay and GeneXpert GBS LB assay for the detection of group B Streptococcus in prenatal screening samples
Authors: Choera Tsokyi , Jung-Hynes Brittney , Chen Derrick J.
Published: January 2020

Background

Group B Streptococcal (GBS) infections in the United States are a leading cause of meningitis and sepsis in newborns. The CDC therefore recommends GBS screening for all pregnant women at 35–37 weeks of gestation and administration of intrapartum prophylaxis (in those that tested positive) as an effective means of controlling disease transmission. Several FDA approved molecular diagnostic tests are available for rapid and accurate detection of GBS in antepartum women.

Method

In this study, we report a clinical comparison of the Xpert GBS LB assay and a novel FDA-cleared test, Revogene GBS LB assay. A total of 250 vaginal-rectal swabs from women undergoing prenatal screening were submitted to the University of Wisconsin’s clinical microbiology laboratory for GBS testing.

Results

We found 96.8% of samples were concordant between the two tests, while 3.2% were discordant with a positive percent agreement of 98.0% and a negative percent agreement of 96.5% between the Revogene GBS LB assay and the GeneXpert GBS LB assay.

Conclusion

Overall, we report that both assays perform well for the detection of GBS colonization in pregnant women.
Provider volume and maternal complications after Caesarean section: results from a population-based study
Authors: Leonard Philip S. J. , Crouse Dan L. , Boudreau Jonathan G. , Gupta Neeru , McDonald James T.
Published: January 2020

Background

A large literature search suggests a relationship between hospital/surgeon caseload volume and surgical complications. In this study, we describe associations between post-operative maternal complications following Caesarean section and provider caseload volume, provider years since graduation, and provider specialization, while adjusting for hospital volumes and patient characteristics.

Methods

Our analysis is based on population-based discharge abstract data for the period of April 2004 to March 2014, linked to patient and physician universal coverage registry data. We consider all hospital admissions (N = 20,914) in New Brunswick, Canada, where a Caesarean Section surgery was recorded, as identified by a Canadian Classification of Health Intervention code of 5.MD.60.XX. We ran logistic regression models to identify the odds of occurrence of post-surgical complications during the hospital stay.

Results

Roughly 2.6% of admissions had at least one of the following groups of complications: disseminated intravascular coagulation, postpartum sepsis, postpartum hemorrhage, and postpartum infection. The likelihood of complication was negatively associated with provider volume and provider years of experience, and positively associated with having a specialization other than maternal-fetal medicine or obstetrics and gynecology.

Conclusions

Our results suggest that measures of physician training and experience are associated with the likelihood of Caesarean Section complications. In the context of a rural province deciding on the number of rural hospitals to keep open, this suggests a trade off between the benefits of increased volume versus the increased travel time for patients.
Young-onset gastric cancer and Epstein–Barr Virus (EBV) – a major player in the pathogenesis?
Authors: Moore Assaf , Hikri Elad , Goshen-Lago Tal , Barkan Tamar , Morgenstern Sara , Brook Elena , Maderer Annett , Roth Wilfried , Gordon Noa , Kashtan Hanoch , Brenner Baruch , Moehler Markus , Aharon Irit Ben
Published: January 2020

Objective

Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (≤45 years) compared with an average-onset cohort (≥55 years) and characterize the clinicopathologic pattern of young-onset GC.

Methods

Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records.

Results

Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p = 0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p = 0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68 years). MSI-H was found only in the average-onset cohort [0% vs 27%, p = 0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p = 0.002).

Conclusion

Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.
Association of psychosocial and perceived environmental factors with park-based physical activity among elderly in two cities in China and Germany
Authors: Wagner Petra , Duan Yan Ping , Zhang Ru , Wulff Hagen , Brehm Walter
Published: January 2020

Background

Urban parks play an important role in promoting physical activity (PA) among adults and especially among older city residents. According to the socioecological approach the association of physical environments and psychosocial factors in the context of park-based PA of elderly have not been systematically examined until now, let alone the relevance of the city (urban area) on a cross-cultural level. This study investigated selected aspects of (1) the association of psychosocial and park environmental factors with park-based physical activity (PBPA) of older people; and (2) the moderating effect of city on the association of these factors with PBPA.

Methods

A face-to-face survey was conducted of a mixed-culture sample from different urban surroundings in Hong Kong (HK) and Leipzig (L). In six parks of each city physically active elderly (> = 60 years; HK: n = 306; L: n = 311) were recruited. Multiple linear regressions were used to analyse the association between psychosocial factors and perceived environmental factors with PBPA and the moderating effect of city.

Results

Controlled for demographic variables, all other psychosocial factors were significantly related to PBPA, except social support. In terms of environmental factors, PBPA was positively associated with safety, attractiveness, features and negatively associated with park time distance. Controlled for demographic variables, psychosocial and environmental factors, the moderating effect of city on the associations of park features and park time distance with PBPA was not significant in HK. In contrast, there was a significant positive relationship for park features and a negative relationship for park time distance with PBPA in L.

Conclusions

Psychosocial and perceived environmental factors significantly influence PBPA of older people. City moderates the associations of these factors and independently contributes to park-based PA of the elderly. The different interactions of environmental factors and urban area for PBPA of elderly can support policy makers on the municipal level in choosing adequate strategies for promoting PA of older people in parks.
A systematic review and meta-analysis of the prevalence of hepatitis C virus infection in people who inject drugs in Iran
Authors: Behzadifar Masoud , Behzadifar Meysam , Bragazzi Nicola Luigi
Published: January 2020

Background

Hepatitis C virus (HCV) infection is one of the major public health challenges generating a relevant burden. High-risk groups, including people who inject drugs (PWID), are at serious risk for developing HCV. In recent years, several investigations have been conducted in Iran to assess the prevalence e of HCV among PWID. The aim of the present study was to synthesize the literature performing a comprehensive search and meta-analysis.

Methods

A comprehensive literature search was carried out from January 2000 to September 2019. Several international databases, namely Scopus, PubMed/MEDLINE, Embase, ISI/Web of Science, PsycINFO, CINAHL, the Cochrane Library and the Directory of Open Access Journals (DOAJ), as well as Iranian databases (Barakathns, SID and MagIran), were consulted. Eligible studies were identified according to the following PECOS (population, exposure, comparison/comparator, outcome and study type) criteria: i) population: Iranian population; ii) exposure: injection drug users; iii) comparison/comparator: type of substance injected and level of substance use, iv) outcome: HCV prevalence; and v) study type: cross-sectional study. After finding potentially related studies, authors extracted relevant data and information based on an ad hoc Excel spreadsheet. Extracted data included the surname of the first author, the study journal, the year of publication, the number of participants examined, the type of diagnostic test performed, the number of positive HCV patients, the number of participants stratified by gender, the reported prevalence, the duration of drug injection practice and the history of using a shared syringe.

Results

Forty-two studies were included. 15,072 PWID were assessed for determining the prevalence of HCV. The overall prevalence of HCV among PWID in Iran was computed to be 47% (CI 95: 39–56). The prevalence ranged between 7 and 96%. Men and subjects using a common/shared syringe were 1.46 and 3.95 times more likely to be at risk, respectively.

Conclusion

The findings of the present study showed that the prevalence of HCV among PWIDs in Iran is high. The support and implementation of ad hoc health-related policies and programs that reduce this should be put into action.
Risk factors for subsidence of titanium mesh cage following single-level anterior cervical corpectomy and fusion
Authors: Ji Chengyue , Yu Shunzhi , Yan Ning , Wang Jiaxing , Hou Fang , Hou Tiesheng , Cai Weihua
Published: January 2020

Background

To clarify the risk factors for subsidence of titanium mesh cage (TMC) following single-level anterior cervical corpectomy and fusion (ACCF) to reduce subsidence.

Methods

The present retrospective cohort study included 73 consecutive patients who underwent single-level ACCF. Patients were divided into subsidence (n = 31) and non-subsidence groups (n = 42). Medical records and radiological parameters such as age, sex, operation level, segmental angle (SA), cervical sagittal angle (CSA), height of anterior (HAE) and posterior endplate (HPE), ratio of anterior (RAE) and posterior endplate (RPE), the alignment of TMC, the global cervical Hounsfield Units (HU) were analyzed. Clinical results were evaluated using the Japanese Orthopedic Association (JOA) scoring system and the Visual Analog Scale (VAS).

Results

Subsidence occurred in 31 of 73 (42.5%) patients. Comparison between the groups showed significant differences in the value of RAE, the alignment of TMC and the global cervical HU value (p < 0.001, p = 0.002, p < 0.001). In multivariate logistic regression analysis, RAE > 1.18 (OR = 6.116, 95%CI = 1.613–23.192, p = 0.008), alignment of TMC > 3° (OR = 5.355, 95%CI = 1.474–19.454, p = 0.011) and the global cervical HU value< 333 (OR = 11.238, 95%CI = 2.844–44.413, p = 0.001) were independently associated with subsidence. Linear regression analysis revealed that RAE is significantly positive related to the extent of subsidence (r = − 0.502, p = 0.006).

Conclusion

Our findings suggest that the value of RAE more than 1.18, alignment of TMC and poor bone mineral density are the risk factors for subsidence. TMC subsidence does not negatively affect the clinical outcomes after operation. Avoiding over expansion of intervertebral height, optimizing placing of TMC and initiation of anti-osteoporosis treatments 6 months prior to surgery might help surgeons to reduce subsidence after ACCF.
Patients’ experiences of discontentment one year after total knee arthroplasty- a qualitative study
Authors: Mahdi Aamir , Svantesson Mia , Wretenberg Per , Hälleberg-Nyman Maria
Published: January 2020

Background

Total knee arthroplasty is a common procedure with generally good results. However, there are still patients who are dissatisfied without known explanation. Satisfaction and dissatisfaction have previously been captured by quantitative designs, but there is a lack of qualitative studies regarding these patients’ experiences. Qualitative knowledge might be useful in creating strategies to decrease the dissatisfaction rate.

Methods

Of the 348 patients who responded to a letter asking if they were satisfied or dissatisfied with their surgery, 61 (18%) reported discontent. After excluding patients with documented complications and those who declined to participate, semi-structured interviews were conducted with 44 patients. The interviews were analyzed according to qualitative content analysis. The purpose was to describe patients’ experiences of discontentment 1 year after total knee arthroplasty.

Results

The patients experienced unfulfilled expectations and needs regarding unresolved and new problems, limited independence, and lacking of relational supports. They were bothered by pain and stiffness, and worried that changes were complications as a result of surgery. They described inability to perform daily activities and valued activities. They also felt a lack of relational supports, and a lack of respect and continuity, support from health care, and information adapted to their needs.

Conclusion

Patient expectation seems to be the major contributing factor in patient discontentment after knee replacement surgery. This qualitative study sheds light on the on the meaning of unfulfilled expectations, in contrast to previous quantitative studies. The elements of unfulfilled expectations need to be dealt with both on the individual staff level and on the organizational level. For instance, increased continuity of healthcare staff and facilities may help to improve patient satisfaction after surgery.
Implementing a collaborative model in health education practice: a process evaluation of a health education programme targeting users with mental health problems
Authors: Pals Regitze Anne Saurbrey , Drejer Sabina , Laursen Rikke Hjort , Oest Lone , Levisen Vinie Diana Hvidbak , Krogh Naja Ramskov , Hempler Nana Folmann
Published: January 2020

Background

Users with mental health problems (users) have a substantially higher risk of developing type 2 diabetes than the general population. Recent studies show that traditional lifestyle interventions focusing solely on exercise and diet among users have limited effect. Studies suggest collaborative models as a starting point for health behaviour change are more beneficial, but implementation in practice is a challenge. Using the Medical Research Council’s guidance for process evaluation, we explored implementation of a collaborative model in health education activities targeting users. The collaborative model focused on involving users in agenda setting and reflection about readiness to change health behaviour and was supported by dialogue tools (e.g., quotes and games). Educators received 3 days of training in applying the model.

Methods

Collected data included questionnaires for users (n = 154) and professionals (n = 158), interviews with users (n = 14), and observations of health education activities (n = 37) and the professional development programme (n = 9). Data were analysed using descriptive statistics and systematic text condensation.

Results

Ninetysix percent (152) of professionals tested the model in practice and tried at least one tool. Users reported that the model supported them in expressing their thoughts about their health and focused on their needs rather than the agenda of the professional. Ninetythree percent (143) of users strongly agreed that professionals were open-minded and responsive. However, observations showed that some professionals overlooked cues from users about motivation for health behaviour change. Furthermore, professionals identified lack of involvement from their managers as a barrier to implementation.

Conclusions

Implementation of a collaborative model was feasible in practice. Training of professionals in active listening and involvement of managers prior to implementation is crucial.
Vaccinating children against influenza: overall cost-effective with potential for undesirable outcomes
Authors: de Boer Pieter T. , Backer Jantien A. , van Hoek Albert Jan , Wallinga Jacco
Published: January 2020

Background

The present study aims to assess the cost-effectiveness of an influenza vaccination program for children in the Netherlands. This requires an evaluation of the long-term impact of such a program on the burden of influenza across all age groups, using a transmission model that accounts for the seasonal variability in vaccine effectiveness and the shorter duration of protection following vaccination as compared to natural infection.

Methods

We performed a cost-effectiveness analysis based on a stochastic dynamic transmission model that has been calibrated to reported GP visits with influenza-like illness in the Netherlands over 11 seasons (2003/2004 to 2014/2015). We analyzed the costs and effects of extending the current program with vaccination of children aged 2–16 years at 50% coverage over 20 consecutive seasons. We measured the effects in quality-adjusted life-years (QALYs) and we adopted a societal perspective.

Results

The childhood vaccination program is estimated to have an average incremental cost-effectiveness ratio (ICER) of €3944 per QALY gained and is cost-effective in the general population (across 1000 simulations; conventional Dutch threshold of €20,000 per QALY gained). The childhood vaccination program is not estimated to be cost-effective for the target-group itself with an average ICER of €57,054 per QALY gained. Uncertainty analyses reveal that these ICERs hide a wide range of outcomes. Even though introduction of a childhood vaccination program decreases the number of infections, it tends to lead to larger epidemics: in 23.3% of 1000 simulations, the childhood vaccination program results in an increase in seasons with a symptomatic attack rate larger than 5%, which is expected to cause serious strain on the health care system. In 6.4% of 1000 simulations, the childhood vaccination program leads to a net loss of QALYs. These findings are robust across different targeted age groups and vaccination coverages.

Conclusions

Modeling indicates that childhood influenza vaccination is cost-effective in the Netherlands. However, childhood influenza vaccination is not cost-effective when only outcomes for the children themselves are considered. In approximately a quarter of the simulations, the introduction of a childhood vaccination program increases the frequency of seasons with a symptomatic attack rate larger than 5%. The possibility of an overall health loss cannot be excluded.
A neutralizing monoclonal antibody-based competitive ELISA for classical swine fever C-strain post–vaccination monitoring
Authors: Wang Lihua , Mi Shijiang , Madera Rachel , Ganges Llilianne , Borca Manuel V. , Ren Jingqiang , Cunningham Chase , Cino-Ozuna Ada G. , Li Hongwei , Tu Changchun , Gong Wenjie , Shi Jishu
Published: January 2020

Background

Virus neutralization test (VNT) is widely used for serological survey of classical swine fever (CSF) and efficacy evaluation of CSF vaccines. However, VNT is a time consuming procedure that requires cell culture and live virus manipulation. C-strain CSF vaccine is the most frequently used vaccine for CSF control and prevention. In this study, we presented a neutralizing monoclonal antibody (mAb) based competitive enzyme-linked immunosorbent assay (cELISA) with the emphasis on the replacement of VNT for C-strain post–vaccination monitoring.

Results

One monoclonal antibody (6B211) which has potent neutralizing activity against C-strain was generated. A novel cELISA was established and optimized based on the strategy that 6B211 can compete with C-strain induced neutralizing antibodies in pig serum to bind capture antigen C-strain E2. By testing C-strain VNT negative pig sera (n = 445) and C-strain VNT positive pig sera (n = 70), the 6B211 based cELISA showed 100% sensitivity (95% confidence interval: 94.87 to 100%) and 100% specificity (95% confidence interval: 100 to 100%). The C-strain antibody can be tested in pigs as early as 7 days post vaccination with the cELISA. By testing pig sera (n = 139) in parallel, the cELISA showed excellent agreement (Kappa = 0.957) with VNT. The inhibition rate of serum samples in the cELISA is highly correlated with their titers in VNT (r2 = 0.903, p < 0.001). In addition, intra- and inter-assays of the cELISA exhibited acceptable repeatability with low coefficient of variations (CVs).

Conclusions

This novel cELISA demonstrated excellent agreement and high level correlation with VNT. It is a reliable tool for sero-monitoring of C-strain vaccination campaign because it is a rapid, simple, safe and cost effective assay that can be used to monitor vaccination-induced immune response at the population level.
Testing possible causes of gametocyte reduction in temporally out-of-synch malaria infections
Authors: Westwood Mary L. , O’Donnell Aidan J. , Schneider Petra , Albery Gregory F. , Prior Kimberley F. , Reece Sarah E.
Published: January 2020

Background

The intraerythrocytic development cycle (IDC) of the rodent malaria Plasmodium chabaudi is coordinated with host circadian rhythms. When this coordination is disrupted, parasites suffer a 50% reduction in both asexual stages and sexual stage gametocytes over the acute phase of infection. Reduced gametocyte density may not simply follow from a loss of asexuals because investment into gametocytes (“conversion rate”) is a plastic trait; furthermore, the densities of both asexuals and gametocytes are highly dynamic during infection. Hence, the reasons for the reduction of gametocytes in infections that are out-of-synch with host circadian rhythms remain unclear. Here, two explanations are tested: first, whether out-of-synch parasites reduce their conversion rate to prioritize asexual replication via reproductive restraint; second, whether out-of-synch gametocytes experience elevated clearance by the host’s circadian immune responses.

Methods

First, conversion rate data were analysed from a previous experiment comparing infections of P. chabaudi that were in-synch or 12 h out-of-synch with host circadian rhythms. Second, three new experiments examined whether the inflammatory cytokine TNF varies in its gametocytocidal efficacy according to host time-of-day and gametocyte age.

Results

There was no evidence that parasites reduce conversion or that their gametocytes become more vulnerable to TNF when out-of-synch with host circadian rhythms.

Conclusions

The factors causing the reduction of gametocytes in out-of-synch infections remain mysterious. Candidates for future investigation include alternative rhythmic factors involved in innate immune responses and the rhythmicity in essential resources required for gametocyte development. Explaining why it matters for gametocytes to be synchronized to host circadian rhythms might suggest novel approaches to blocking transmission.
A method for measuring spatial effects on socioeconomic inequalities using the concentration index
Authors: Kim Sung Wook , Haghparast-Bidgoli Hassan , Skordis-Worrall Jolene , Batura Neha , Petrou Stavros
Published: January 2020

Background

Although spatial effects contribute to inequalities in health care service utilisation and other health outcomes in low and middle income countries, there have been no attempts to incorporate the impact of neighbourhood effects into equity analyses based on concentration indices. This study aimed to decompose and estimate the contribution of spatial effects on inequalities in uptake of HIV tests in Malawi.

Methods

We developed a new method of reflecting spatial effects within the concentration index using a spatial weight matrix. Spatial autocorrelation is presented using a spatial lag model. We use data from the Malawi Demographic Health Survey (n = 24,562) to illustrate the new methodology. Need variables such as ‘Any STI last 12 month’, ‘Genital sore/ulcer’, ‘Genital discharge’ and non need variables such as Education, Literacy, Wealth, Marriage, and education were used in the concentration index. Using our modified concentration index that incorporates spatial effects, we estimate inequalities in uptake of HIV testing amongst both women and men living in Malawi in 2015–2016, controlling for need and non-need variables.

Results

For women, inequalities due to need variables were estimated at − 0.001 and − 0.0009 (pro-poor) using the probit and new spatial probit estimators, respectively, whereas inequalities due to non-need variables were estimated at 0.01 and 0.0068 (pro-rich) using the probit and new spatial probit estimators. The results suggest that spatial effects increase estimated inequalities in HIV uptake amongst women. Horizontal inequity was almost identical (0.0103 vs 0.0102) after applying the spatial lag model. For men, inequalities due to need variables were estimated at − 0.0002 using both the probit and new spatial probit estimators; however, inequalities due to non-need variables were estimated at − 0.006 and − 0.0074 for the probit and new spatial probit models. Horizontal inequity was the same for both models (− 0.0057).

Conclusion

Our findings suggest that men from lower socioeconomic groups are more likely to receive an HIV test after adjustment for spatial effects. This study develops a novel methodological approach that incorporates estimation of spatial effects into a common approach to equity analysis. We find that a significant component of inequalities in HIV uptake in Malawi driven by non-need factors can be explained by spatial effects. When the spatial model was applied, the inequality due to non need in Lilongwe for men and horizontal inequity in Salima for women changed the sign.

This approach can be used to explore inequalities in other contexts and settings to better understand the impact of spatial effects on health service use or other health outcomes, impacting on recommendations for service delivery.
The impact of vaccination on gender equity: conceptual framework and human papillomavirus (HPV) vaccine case study
Authors: Portnoy Allison , Clark Samantha , Ozawa Sachiko , Jit Mark
Published: January 2020

Background

Although the beneficial effects of vaccines on equity by socioeconomic status and geography are increasingly well-documented, little has been done to extend these analyses to examine the linkage between vaccination and gender equity. In this paper, evidence from the published literature is used to develop a conceptual framework demonstrating the potential impact of vaccination on measures of gender equity. This framework is then applied to human papillomavirus (HPV) vaccination in three countries with different economic and disease burden profiles to establish a proof of concept in a variety of contexts.

Methods

We conducted a literature review examining evidence on the linkage between health outcomes and dimensions of gender equity. We utilized the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to estimate cervical cancer incidence and deaths due to HPV types 16/18 by age in each country. We estimated labor force participation and fertility effects from improvements in health, and converted these into inputs consistent with those used to calculate the United Nations Gender Inequality Index to assess gender equity.

Results

In our case study, we found that HPV vaccination among girls could help narrow socioeconomic gender disparities by quantifying the main pathways by which HPV vaccination improves health, which enables improvement in gender equity indicators such as labor force participation and maternal mortality ratios. While these improvements are small when averaged over the entire population, the components measured – labor force participation and maternal mortality ratio – account for 50% of the index scores.

Conclusions

This proof of concept model is a starting point to inform future health and economic analyses that might incorporate the impact of gender equity as an additional impact of vaccination in improving the health and well-being of the population.
Circular RNAs in the tumour microenvironment
Authors: Ma Zhonghua , Shuai You , Gao Xiangyu , Wen Xianzi , Ji Jiafu
Published: January 2020

Background

Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs (ncRNAs) widely expressed in eukaryotic cells. Mounting evidence has highlighted circRNAs as critical regulators of various tumours. More importantly, circRNAs have been revealed to recruit and reprogram key components involved in the tumour microenvironment (TME), and mediate various signaling pathways, thus affecting tumourigenesis, angiogenesis, immune response, and metastatic progression.

Main body of the abstract

In this review, we briefly introduce the biogenesis, characteristics and classification of circRNAs, and describe various mechanistic models of circRNAs. Further, we provide the first systematic overview of the interplay between circRNAs and cellular/non-cellular counterparts of the TME and highlight the potential of circRNAs as prospective biomarkers or targets in cancer clinics. Finally, we discuss the biological mechanisms through which the circRNAs drive development of resistance, revealing the mystery of circRNAs in drug resistance of tumours.

Short conclusion

Deep understanding the emerging role of circRNAs and their involvements in the TME may provide potential biomarkers and therapeutic targets for cancer patients. The combined targeting of circRNAs and co-activated components in the TME may achieve higher therapeutic efficiency and become a new mode of tumour therapy in the future.
Triglyceride glucose index is a useful marker for predicting subclinical coronary artery disease in the absence of traditional risk factors
Authors: Park Gyung-Min , Cho Young-Rak , Won Ki-Bum , Yang Yu Jin , Park Sangwoo , Ann Soe Hee , Kim Yong-Giun , Park Eun Ji , Kim Shin-Jae , Lee Sang-Gon , Yang Dong Hyun , Kang Joon-Won , Lim Tae-Hwan , Kim Hong-Kyu , Choe Jaewon , Lee Seung-Whan , Kim Young-Hak
Published: January 2020

Background

Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden. This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs).

Methods

This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m2; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia). CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography. The participants were divided into three groups based on TyG index tertiles.

Results

The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P < 0.001). Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026–2.166); especially non-calcified (OR 1.581, 95% CI 1.002–2.493) and mixed plaques (OR 2.419, 95% CI 1.051–5.569) (all P < 0.05). The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P < 0.001). The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex.

Conclusions

TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy.
Assessment of outcomes and novel immune biomarkers in metaplastic breast cancer: a single institution retrospective study
Authors: Morgan Evan , Suresh Anupama , Ganju Akaansha , Stover Daniel G. , Wesolowski Robert , Sardesai Sagar , Noonan Anne , Reinbolt Raquel , VanDeusen Jeffrey , Williams Nicole , Cherian Mathew A. , Li Zaibo , Young Gregory , Palettas Marilly , Stephens Julie , Liu Joseph , Luff Amanda , Ramaswamy Bhuvaneswari , Lustberg Maryam
Published: January 2020

Background

Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear.

Methods

We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples.

Results

Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1–19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02).

Conclusions

Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.
Targeting the orphan nuclear receptor NR2F6 in T cells primes tumors for immune checkpoint therapy
Authors: Klepsch Victoria , Pommermayr Maria , Humer Dominik , Brigo Natascha , Hermann-Kleiter Natascha , Baier Gottfried
Published: January 2020

Background

NR2F6 has been proposed as an alternative cancer immune checkpoint in the effector T cell compartment. However, a realistic assessment of the in vivo therapeutic potential of NR2F6 requires acute depletion.

Methods

Employing primary T cells isolated from Cas9-transgenic mice for electroporation of chemically synthesized sgRNA, we established a CRISPR/Cas9-mediated acute knockout protocol of Nr2f6 in primary mouse T cells.

Results

Analyzing these Nr2f6CRISPR/Cas9 knockout T cells, we reproducibly observed a hyper-reactive effector phenotype upon CD3/CD28 stimulation in vitro, highly reminiscent to Nr2f6−/− T cells. Importantly, CRISPR/Cas9-mediated Nr2f6 ablation prior to adoptive cell therapy (ACT) of autologous polyclonal T cells into wild-type tumor-bearing recipient mice in combination with PD-L1 or CTLA-4 tumor immune checkpoint blockade significantly delayed MC38 tumor progression and induced superior survival, thus further validating a T cell-inhibitory function of NR2F6 during tumor progression.

Conclusions

These findings indicate that Nr2f6CRISPR/Cas9 knockout T cells are comparable to germline Nr2f6−/− T cells, a result providing an independent confirmation of the immune checkpoint function of lymphatic NR2F6. Taken together, CRISPR/Cas9-mediated acute Nr2f6 gene ablation in primary mouse T cells prior to ACT appeared feasible for potentiating established PD-L1 and CTLA-4 blockade therapies, thereby pioneering NR2F6 inhibition as a sensitizing target for augmented tumor regression.

Graphical abstract
‘Social screens’ and ‘the mainstream’: longitudinal competitors of non-organized physical activity in the transition from childhood to adolescence
Authors: Kemp Byron J. , Parrish Anne-Maree , Cliff Dylan P.
Published: January 2020

Background

Physical activity (PA) tends to decline during late childhood and adolescence. In Australia, this decline has been shown to occur particularly in non-organized PA (e.g. active play and informal sport). Using a social marketing approach, segments of youth may be identified and targeted based on their profile of alternative activities that compete with non-organized PA during the transition to adolescence. The objectives of this study were to identify and describe segments of youth whose participation in non-organized PA declined between 11 and 13 years, based on changes in other potential competing activities during this period.

Methods

Data were sourced from Waves 4 and 5 of the Longitudinal Study of Australian Children. Participation in non-organized PA and thirteen alternative activities (e.g. video games, homework, sleep) were measured using 24-h time-use diaries. Analyses were limited to participants whose non-organized PA had declined between 11 and 13 years (n = 1043). Two-stage cluster analysis was conducted and segments were described using chi-square and t-tests.

Results

Among the analytic sample, average non-organized PA participation declined by 87 min/day between 11y and 13y (p < 0.001). Two segments were identified (κ = 0.66). The ‘Social Screens’ segment (n = 143) had large increases in texting, emailing and social media use (+ 56 min/day, p < 0.001) and other internet use (+ 32 min/day, p < 0.001). Conversely, ‘the Mainstream’ segment (n = 900) had smaller increases in a wider range of activities, including other PA (organized PA, active transport, active chores/work) (+ 16.0 min/day, p < 0.001), homework/study (+ 9.5 min/day, p < 0.001) and electronic gaming (+ 6.7 min/day, p < 0.05). ‘Social Screens’ were more likely to attend public school, live in urban areas and have more advanced pubertal development (girls only). ‘The Mainstream’ were more likely to participate in PA and out-of-school activities.

Conclusions

The ‘Social Screens’ segment had a much larger increase in texting, emailing, social media and other internet use, and lower participation in overall PA and out-of-school activities, compared with ‘the Mainstream’. Future research may trial PA promotion strategies to replace benefits that this segment may seek in competing activities (e.g. social PA apps).
Phase I and registry study of autologous bone marrow concentrate evaluated in PDE5 inhibitor refractory erectile dysfunction
Authors: Bieri Mark , Said Elias , Antonini Gabrielle , Dickerson Donald , Tuma Jorge , Bartlett Courtney E. , Patel Amit N. , Gershman Alexander
Published: January 2020

Background

Bone marrow mononuclear cells have been successfully utilized for numerous regenerative purposes. In the current study, patients suffering from erectile dysfunction (ED) unresponsive to phosphodiesterase 5 inhibitors were administered autologous bone marrow concentrate delivered intracavernously utilizing a point of care FDA cleared medical device.

Methods

A total of 40 patients were treated in the primary trial and 100 in the clinical registry, with the longest follow up of 12 months.

Results

Minimal treatment associated adverse effects where observed related to short term bruising at the site of harvest or injection. No long-term adverse events were noted related to the intervention. Mean improvements in IIEF-5 score were 2 in the Caverstem 1.0 low dose group, 3 in the high dose Caverstem 1.0 group and 9 in the Caverstem 2.0 group. Furthermore, improvements peaked by 3 months and maintained at 6 months follow-up.

Conclusion

These data support the safety and efficacy of point of care, minimally to non-manipulated, non-expanded bone marrow concentrate for the treatment of ED.

Trial registration Funded by Creative Medical Health, Inc.; Clinicaltrials.gov number: NCT03699943; https://clinicaltrials.gov/ct2/show/NCT03699943?term=caverstem&rank=1; initially registered December 12, 2015.
Body image perception and body composition: assessment of perception inconsistency by a new index
Authors: Zaccagni Luciana , Rinaldo Natascia , Bramanti Barbara , Mongillo Jessica , Gualdi-Russo Emanuela
Published: January 2020

Background

A correct perception of the body image, as defined by comparison with actual anthropometric analyses, is crucial to ensure the best possible nutritional status of each individual. Bioimpedance analysis (BIA) represents a leading technique to assess body composition parameters and, in particular, the fat mass. This study examined the self-perception of body image at various levels of adiposity proposing a new index.

Methods

We investigated 487 young Italian adults (mean age of males: 21.9 ± 2.4 years; mean age of females: 21.0 ± 2.2 years). Each subject could choose, on the Contour Drawing Rating Scale, the silhouette that he/she considered most resembling his/her perceived body image as well as his/her ideal body image. On each subject, we performed anthropometric measurements and determined the values of Fat mass and  %Fat with BIA. A new index, FAIFAT (Feel fat status minus Actual fat status Inconsistency), was developed to evaluate possible fat status perception inconsistencies by BIA.

Results

Based on ideal and feel body image comparison, women showed higher dissatisfaction than men and preferred slimmer silhouettes. FAIFAT values indicated that the fat status perception was correct in the majority of the examined individuals and only three subjects showed a serious misperception.

Conclusions

Our findings suggest that FAIFAT is an appropriate index for assessing the perceived fat status from the body image when compared with data obtained by BIA. In a population, the use of this index will allow the correct identification of groups at risk for eating disorders.
IL-23 and PSMA-targeted duo-CAR T cells in Prostate Cancer Eradication in a preclinical model
Authors: Wang Dawei , Shao Yuan , Zhang Xiang , Lu Guoliang , Liu Boke
Published: January 2020

Background

Prostate cancer is one of the most common adult malignancies in men, and nearly all patients with metastatic prostate cancer can develop and receive resistance to primary androgen deprivation therapy (ADT), a state known as metastatic castration-resistant prostate cancer (mCRPC). Recent reports demonstrated the great breakthroughs made by the chimeric antigen receptor T (CAR-T) cell therapy, which is significantly different from traditional T cells therapies. In spite of the progress of CAR-T technology in the treatment of lymphoma, leukemia, and other blood system tumor, there are still many difficulties in the treatment of solid tumors by CAR-T technology.

Methods

In this report, we designed a panel of IL23mAb-PSMA-CARs, including PSMA-CAR, IL23mAb-T2A-PSMA-CAR, IL23mAb-PSMA-CAR, and PSMA-CAR (soluble IL23mAb). And we studied the function of these CARs in mice model.

Results

Co-culture experiments with different CAR T cells have normal lysis function in vitro. The duo-CAR T cells co-expressing the IL-23mAb and PSMA-mAb had a significant higher population than the rest three different CAR T cells in co-culturing experiments at day 28, 35 and 42. A panel of cytokines were differentially secreted at higher amounts in IL23mAb-T2A-PSMA-CAR T cells than CAR T cells in other groups. In NOD/SCID IL-2 gamma (NSG) mice model, IL23mAb-T2A-PSMA-CAR T cells functioned significantly better than CAR T cells from the other groups and eradicated the tumor from these mice starting at day 14 post T cells injection and regained the body weight immediately. In IL23mAb-T2A-PSMA-CAR mice, CD45RO+ CD8+ T cells and CD127+ CD4+ CAR T cells were significantly increased. RNA sequencing revealed a difference expression pattern of genes in IL23mAb-T2A-PSMA-CAR mice. A reverse infusion experiment under the same model further proved the tumor eradication function of IL23mAb-T2A-PSMA-CAR T cells.

Conclusions

We found that IL-23mAb combined PSMA CARs worked better than PSMA CAR only in Prostate Cancer Eradication, and we further discussed the mechanisms among different IL-23mAb combined PSMA CARs in Prostate Cancer Eradication.
Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients
Authors: Celarain Naiara , Tomas-Roig Jordi
Published: January 2020

Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system characterised by incoordination, sensory loss, weakness, changes in bladder capacity and bowel function, fatigue and cognitive impairment, creating a significant socioeconomic burden. The pathogenesis of MS involves both genetic susceptibility and exposure to distinct environmental risk factors. The gene x environment interaction is regulated by epigenetic mechanisms. Epigenetics refers to a complex system that modifies gene expression without altering the DNA sequence. The most studied epigenetic mechanism is DNA methylation. This epigenetic mark participates in distinct MS pathophysiological processes, including blood–brain barrier breakdown, inflammatory response, demyelination, remyelination failure and neurodegeneration. In this study, we also accurately summarised a list of environmental factors involved in the MS pathogenesis and its clinical course. A literature search was conducted using MEDLINE through PubMED and Scopus. In conclusion, an exhaustive study of DNA methylation might contribute towards new pharmacological interventions in MS by use of epigenetic drugs.