bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of blood-based biomarkers and subsequent design of bisulfite PCR-LDR-qPCR assay for breast cancer detection
Authors: Bacolod Manny D. , Huang Jianmin , Giardina Sarah F. , Feinberg Philip B. , Mirza Aashiq H. , Swistel Alexander , Soper Steven A. , Barany Francis
Published: January 2020

Background

Interrogation of site-specific CpG methylation in circulating tumor DNAs (ctDNAs) has been employed in a number of studies for early detection of breast cancer (BrCa). In many of these studies, the markers were identified based on known biology of BrCa progression, and interrogated using methyl-specific PCR (MSP), a technique involving bisulfite conversion, PCR, and qPCR.

Methods

In this report, we are demonstrating the development of a novel assay (Multiplex Bisulfite PCR-LDR-qPCR) which can potentially offer improvements to MSP, by integrating additional steps such as ligase detection reaction (LDR), methylated CpG target enrichment, carryover protection (use of uracil DNA glycosylase), and minimization of primer-dimer formation (use of ribose primers and RNAseH2). The assay is designed to for breast cancer-specific CpG markers identified through integrated analyses of publicly available genome-wide methylation datasets for 31 types of primary tumors (including BrCa), as well as matching normal tissues, and peripheral blood.

Results

Our results indicate that the PCR-LDR-qPCR assay is capable of detecting ~ 30 methylated copies of each of 3 BrCa-specific CpG markers, when mixed with excess amount unmethylated CpG markers (~ 3000 copies each), which is a reasonable approximation of BrCa ctDNA overwhelmed with peripheral blood cell-free DNA (cfDNA) when isolated from patient plasma. The bioinformatically-identified CpG markers are located in promoter regions ofNR5A2andPRKCB, and a non-coding region of chromosome 1 (upstream ofEFNA3). Additional bioinformatic analyses would reveal that these methylation markers are independent of patient race and age, and positively associated with signaling pathways associated with BrCa progression (such as those related to retinoid nuclear receptor, PTEN, p53, pRB, and p27).

Conclusion

This report demonstrates the potential utilization of bisulfite PCR-LDR-qPCR assay, along with bioinformatically-driven biomarker discovery, in blood-based BrCa detection.
Simplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutations
Authors: Ruiz-Cordero Roberto , Ma Junsheng , Khanna Abha , Lyons Genevieve , Rinsurongkawong Waree , Bassett Roland , Guo Ming , Routbort Mark J. , Zhang Jianjun , Skoulidis Ferdinandos , Heymach John , Roarty Emily B. , Tang Zhenya , Medeiros L. Jeffrey , Patel Keyur P. , Luthra Rajyalakshmi , Roy-Chowdhuri Sinchita
Published: January 2020

Background

Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification.

Methods

Mutational status of EGFR, KRAS, and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma.

Results

The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival.

Conclusions

The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.
Clinical analysis of posterior segment injury in left-behind children in China
Authors: Sun Zhongcui , Zhuang Xiaonan , Xu Gezhi , Jiang Rui
Published: January 2020

Background

We aimed to evaluate the severity and prognosis of posterior segment injury between left-behind children (LBC) and guarded children (NLBC).

Methods

A retrospective, controlled analysis of a case series was performed. Patients diagnosed with posterior segment injury in Department of vitreous and retinal, the Affiliated Ophthalmology and Otolaryngology Hospital of Fudan University were included in this study. Patients were divided into two groups, including LBC group (n = 48) and NLBC group (n = 44). All the children underwent 25G transconjunctival sutureless pars plana vitrectomy.

Results

Compared with NLBC, LBC had delayed treatment, worse baseline vision and visual prognosis, lower OTS rating, more times of vitrectomies, more complicated surgical procedures, and higher rate of lens removal and silicone oil tamponade.

Conclusions

Due to lack of care and delayed treatment, posterior segment ocular trauma in the LBC was more severe, more common complicated with infectious endophthalmitis, and had worse visual prognosis. It was urgent to enforce the guardianship in LBC.
The Healthy Hawai‘i Initiative: insights from two decades of building a culture of health in a multicultural state
Authors: Agner Joy , Pirkle Catherine M. , Irvin Lola , Maddock Jay E. , Buchthal Opal Vanessa , Yamauchi Jessica , Starr Ranjani , Sentell Tetine
Published: January 2020

Background

The Healthy Hawai‘i Initiative was created in 2000 with tobacco settlement funds as a theory-based statewide effort to promote health-supporting environments through systems and policy change. Still active today, it is imbedded explicitly in a multi-sectoral, social ecological approach, effectively striving to build a culture of health before this was the name for such an ambitious effort.

Methods

From interviews with key informants, we analyze two decades of the Healthy Hawai‘i Initiative (HHI) in the context of the Robert Wood Johnson Foundation (RWJF) Culture of Health Action Framework (CHAF). We list HHI accomplishments and examine how the Initiative achieved notable policy and environmental changes supportive of population health.

Results

The Healthy Hawai‘i Initiative started with an elaborate concept-mapping process that resulted in a common vision about making “the healthy choice the easiest choice.” Early on, the Initiative recognized that making health a shared value beyond the initial stakeholders required coalition and capacity building across a broad range of governmental and nonprofit actors. HHI coalitions were designed to promote grassroots mobilization and to link community leaders across sectors, and at their height, included over 500 members across all main islands of the state. Coalitions were particularly important for mobilizing rural communities. Additionally, the Initiative emphasized accessibility to public health data, published research, and evaluation reports, which strengthened the engagement to meet the shared vision and goals between diverse sector partners and HHI. Over the past two decades, HHI has capitalized on relationship building, data sharing, and storytelling to encourage a shared value of health among lawmakers, efforts which are believed to have led to the development of health policy champions. All of these factors combined, which centered on developing health as a shared value, have been fundamental to the success of the other three action areas of the CHAF over time.

Conclusions

This evidence can provide critical insights for other communities at earlier stages of implementing broad, diverse, multifaceted system change and fills a key evidence gap around building a culture of health from a mature program in a notably multicultural state.
Prevalence and determinants of recent HIV testing among older persons in rural Uganda: a cross-sectional study
Authors: Wandera Stephen Ojiambo , Kwagala Betty , Maniragaba Fred
Published: January 2020

Background

There is limited research on HIV testing among older persons in Uganda. The aim of this study was to investigate the socio-demographic determinants of recent HIV testing among older persons in selected rural districts in Uganda.

Methods

A cross-sectional survey of 649 older men and women age 50 years and older, from central (Masaka district) and western (Hoima district) Uganda was conducted. Frequency distributions, chi-square tests and multivariable logistic regressions were used to examine the association between recent HIV testing and selected explanatory variables.

Results

Nearly six in ten (58%) of older persons had primary education. About 60% of the respondents were in union and 13% of them had two or more spouses. Half of the older people (51%) had sex in the last twelve months. A quarter (25%) of older persons gave or received gifts in exchange for sex in their lifetime. Nearly a third (29%) reported sexually transmitted infections in the last 12 months. Prevalence of lifetime HIV testing was 82% and recent (last 12 months) HIV testing was 53%. HIV testing in the last 12 months was associated with age (OR = 0.50; 95% CI: 0.31–0.79), self-reported sexually transmitted infections (OR = 1.59; 95% CI: 1.00–2.30), male circumcision (OR = 1.71; 95% CI: 1.0–2.93), and sexual activity in the last 12 months (OR = 2.89; 95% CI: 1.83–4.57).

Conclusion

Recent HIV testing among older persons was associated with younger age, self-reported STIs, male circumcision, and sexual activity among older persons in rural Uganda. HIV testing interventions need to target older persons who are 70 years and older, who were less likely to test.
Correlations between opioid mortality increases related to illicit/synthetic opioids and reductions of medical opioid dispensing - exploratory analyses from Canada
Authors: Fischer Benedikt , Jones Wayne , Tyndall Mark , Kurdyak Paul
Published: January 2020

Background

North America has been experiencing a persistent epidemic of opioid-related overdose mortality, which has increasingly been driven by fatalities from illicit, toxic opioids in most recent years. Patterns of synthetic opioid availability and related mortality are heterogeneous across Canada, and differing explanations exist as to their differentiated proliferation. We examined the perspective that heterogeneous province-based variations in prescription opioid availability, facilitated by various control strategies, post-2010 may have created regionally differential supply gaps for non-medical opioid use substituted by synthetic opioid products with differential impacts on mortality risks and outcomes in Canada.

Methods

We examined annual, prescription opioid dispensing rates and changes in the ten Canadian provinces (for the periods of 1) 2011–2018, 2) ‘peak-year’-to-2018) in Defined Daily Doses/1000 population/day, derived from data from a large representative, stratified sample of community pharmacies projected to a Canada total. Annual, provincial opioid-related mortality rates and changes for years 2016–2018 were calculated from federal data. We computed correlation values (Pearson’s R) between respective province-based change rates for prescription opioid dispensing and opioid-related mortality for the two over-time scenarios.

Results

All but one province featured reductions in prescription opioid dispensing 2011–2018; seven of the ten provinces had increases in opioid mortality 2016–2018. The correlation between changes in opioid dispensing (2011–2018) and in opioid-mortality (2016–2018) was r = 0.63 (df = 8, p-value: 0.05); the correlation was r = 0.57 (df = 8, p-value: 0.09) for changes in opioid dispensing ‘peak year’-to-2018, respectively.

Conclusions

Quasi-significant results indicate that recent increases in opioid-related deaths driven by illicit, synthetic opioids tended to be larger in provinces where reductions in prescription opioid availability have been more extensive. It is a plausible explanation that these reductions created supply gaps for non-medical opioid use increasingly filled by illicit, synthetic opioids differentially contributing to opioid-related deaths, generating un-intended adverse effects for previous interventions. General prevention measures to reduce opioid availability, and targeted prevention for at-risk opioid users exposed to toxic drug supply may be include counteractive effects and require coordinated reconciliation.
Lifestyle risk factor related disparities in oral cancer examination in the U.S: a population-based cross-sectional study
Authors: Akinkugbe Aderonke A. , Garcia Dina T. , Brickhouse Tegwyn H. , Mosavel Maghboeba
Published: January 2020

Background

Oral cancers account for 3% of annual U.S. cancer diagnosis, 2 in 5 of which are diagnosed late when prognosis is poor. The purpose of this study was to report the population-level prevalence of oral cancer examination among adult smokers and alcohol drinkers and assess if these modifiable lifestyle factors are associated with receiving an oral cancer examination.

Methods

Adult participants ≥30 years (n = 9374) of the 2013–2016 cycles of the National Health and Nutrition Examination Survey were included. Oral cancer examination (yes/no), smoking (never, former, current) and alcohol use (abstainers, former, current) were self-reported. Survey-logistic regression estimated odds ratios (OR) and 95% confidence intervals (CIs) of ever and past year oral cancer examination adjusted for age, gender, race/ethnicity, education, income, and time since last dental visit.

Results

One third (33%) reported ever been examined for oral cancer, 66% of whom reported an examination in the past year. Adjusted OR (95% CI) of past year examination comparing current and former smokers to non-smokers were 0.51 (0.29, 0.88) and 0.74 (0.53, 1.04) respectively. Similarly, current and former alcohol drinkers relative to abstainers were less likely to report a past year oral cancer examination, OR (95% CI) = 0.84 (0.53, 1.30) and 0.50 (0.30, 0.83) respectively.

Conclusion

This study showed that smokers and alcohol users were less likely than abstainers to self-report a past year oral cancer examination. Access to affordable and targeted oral cancer examination within the dental care setting might ensure that these high-risk individuals get timely examinations and earlier diagnosis that might improve prognosis and survival.
Decomposing multidimensional child poverty and its drivers in the Mouhoun region of Burkina Faso, West Africa
Authors: Fonta Cynthia L. , Yameogo Thomas B. , Tinto Halidou , van Huysen Tiff , Natama Hamtandi Magloire , Compaore Adelaide , Fonta William M.
Published: January 2020

Background

The global poverty profile shows that Africa and Asia bear the highest burden of multidimensional child poverty. Child survival and development therefore depend on socioeconomic and environmental factors that surround a child.The aim of this paper is to measure multidimensional child poverty and underpin what drives it among children aged 5 to 18 years in a resource poor region of Burkina Faso.

Methods

Using primary data collected from a cross sectional study of 722 households in the Mouhoun region of Burkina Faso, the Alkire–Foster methodology was applied to estimate and decompose child poverty among children aged 5–18 years. Seven broad dimensions guided by the child poverty literature, data availability and the country’s SDGs were used.A binary logistic regression model was applied to identify drivers of multidimensional child poverty in the region.

Results

The highest prevalence of deprivations were recorded in water and sanitation (91%), information and leisure (89%) followed by education (83%). Interestingly, atk = 3 (the sum of weighted indicators that a child must be deprived to be considered multidimensionally poor), about 97% of children are deprived in at least three of the seven dimensions. At k = 4 to k = 6, between 88.7 and 30.9% of children were equally classified as suffering from multidimensional poverty. The odds of multidimensional poverty were reduced in children who belonged to households with a formally educated mother (OR = 0.49) or stable sources of income (OR = 0.31, OR = 0.33). The results equally revealed that being an adolescent (OR = 0.67), residing in the urban area of Boromo (OR = 0.13) and rural area of Safané (OR = 0.61) reduced the odds of child poverty. On the other hand, child poverty was highest among children from the rural area of Yé (OR = 2.74), polygamous households (OR = 1.47, OR = 5.57 and OR = 1.96), households with an adult head suffering from a longstanding illness (OR = 1.61), households with debts (OR = 1.01) and households with above five number of children/woman (OR = 1.49).

Conclusion

Child poverty is best determined by using a multidimensional approach that involves an interplay of indicators and dimensions, bearing in mind its causation.
Suicide among people treated for drug use disorders: a Danish national record-linkage study
Authors: Hesse Morten , Thylstrup Birgitte , Seid Abdu Kedir , Skogen Jens Christoffer
Published: January 2020

Background

Substance use disorders are a major risk factor for suicide. However, less is known about specific risk factors for suicide in people with substance use disorders.

Methods

This population cohort study assessed suicide among people treated for drug use disorders in Denmark 2000–2010, and described risk factors for completed suicide. Data from 27,942 individuals enrolled in treatment were linked to national registers and matched with controls without drug use disorder and with (n = 138,136) or without psychiatric history (n = 1574). Competing risk regression was used to identify risk factors of completed suicide.

Results

There were 163 suicides among patients with a history of drug treatment (0.6% of patients). Increased risk was associated with younger age at enrolment (hazard ratio [HR] = 0.97, 95% confidence interval (CI): 0.95, 0.98), history of psychiatric care (HR = 1.96, CI 95%: 1.39, 2.77), opioid use (HR = 1.81, 95% CI: 1.23, 2.68), and alcohol use (HR = 1.56, 95% CI: 1.09, 2.23). Lower risk was associated with cannabis use (HR = 0.69, 95% CI: 0.50, 0.96). Compared with age- and gender-matched controls without a history of treatment for substance use disorders or recent psychiatric care, the standardized mortality ratio due to suicide was 7.13 for people with drug use disorder without a history of psychiatric care (95% CI: 5.81, 8.44), 13.48 for people with drug use disorder and psychiatric history (95% CI: 9.75, 17.22), and 13.61 for people with psychiatric history only (95% CI: 6.72, 20.50).

Conclusions

Risk of suicide is increased among people with drug use disorders. Access to treatment for co-morbid mental health problems for people with drug use disorders could potentially reduce risk of suicide.
Physical education environment and student physical activity levels in low-income communities
Authors: Kwon Soyang , Welch Sarah , Mason Maryann
Published: January 2020

Background

The purpose of this study was to examine the association of physical education (PE) class characteristics, such as lesson context, teacher’s physical activity (PA) promotion behavior, and lesson location, with student engagement in moderate- and vigorous-intensity physical activity (MVPA) during PE lessons in elementary school (ES), middle school (MS), and high school (HS).

Methods

The study sample included 2106 PE classes from 40 schools located in low-income communities. The System for Observing Fitness Instruction Time (SOFIT) was used to assess lesson context, teacher’s behavior, and student PA during PE lessons. Mixed models were used to examine the association between PE class characteristics and the probability of meeting the recommended level of MVPA during PE lessons (MVPA ≥50%), accounting for within-school random effects and school characteristics.

Results

Almost all PE classes (90%) with ≥60–70% of lesson time spent in motor content and ≥ 10–20% in teacher’s in-class PA promotion met the recommended level of MVPA across the school levels. More specifically, among the sub-categories of motor content, more lesson time spent in fitness was significantly associated with MVPA ≥50% in all school levels. However, more lesson time spent in game play was a significant factor only in ES (OR = 2.1; 95% CI = 1.4–3.0). Outdoor lessons were a significant factor in ES (OR = 5.3; 95% CI = 3.1–9.0) and MS (OR = 21.0; 95% CI = 6.3–69.4), but not HS (OR = 1.4; 95% CI = 0.6, 3.2).

Conclusions

PE lessons with higher motor content and higher teacher’s in-class PA promotion are more likely to meet the recommended level of MVPA in all school levels. However, the sub-categories of motor content and lesson location could impact student MVPA differently by school levels.
Does urethral length affect continence outcomes following robot assisted laparoscopic radical prostatectomy (RALP)?
Authors: Lin Diwei , O’Callaghan Michael , David Rowan , Fuller Andrew , Wells Richard , Sutherland Peter , Foreman Darren
Published: January 2020

Background

Post-operative urinary incontinence is a significant concern for patients choosing to undergo a radical prostatectomy (RP) for treatment of prostate cancer. The aim of our study was to determine the effect of pre-operative MUL on 12 month continence outcomes in men having robot-assisted laparoscopic prostatectomy (RALP).

Methods

We use the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database, to identify 602 patients who had undergone RALP by a high volume surgeon. Only patients who received an assessment and education by a specialist pelvic floor physiotherapist, had completed EPIC questionnaires before treatment and did not have radiotherapy treatment within 12 months of surgery were included. MUL measurements were taken from pre-operative magnetic resonance imaging (MRI) scans. The short-form version of the Expanded Prostate Cancer Index Composite (EPIC-26) was used to measure continence outcomes. Continence was defined as 100/100 in the EPIC-26 Urinary Continence domain score.

Results

The observed median MUL in this study was 14.6 mm. There was no association between MUL and baseline continence. MUL was associated with continence at 12 months post RALP (OR 1.13, 95% CI 1.03–1.21, p = 0.0098). In men who were continent before surgery, MUL was associated with return to continence at 12 months after RALP (OR 1.15, 1.05–1.28, p = 0.006). MUL was also associated with change in continence after surgery (β = 1.22, p = 0.002).

Conclusions

MUL had no effect on baseline continence but had a positive and significant association with continence outcomes over 12 months post RALP.
A cross-sectional study of current work ability after radical prostatectomy
Authors: Dahl Alv A. , Brennhovd Bjørn , Fosså Sophie D. , Axcrona Karol
Published: January 2020

Background

Work ability represents a person’s subjective assessment of current ability to work compared to his lifetime best. Since many men with prostate cancer are retired, work ability represents a more relevant work measure than employment status. The primary aim was to examine the prevalence of men who had high versus moderate/poor current work ability compared to their lifetime best work ability at a mean of 3.0 years after robot-assisted laparoscopic prostatectomy. The secondary aim was to study variables associated with moderate/poor work ability at survey.

Methods

This is a questionnaire-based study of men who had robot-assisted laparoscopic prostatectomy at Oslo University Hospital, Radiumhospitalet between January 2005 and August 2010. Among them 777 responded (79%), 730 reported on current work ability, socio-demographic data, somatic and mental health, and typical adverse effects (the EPIC-26) after prostatectomy. High versus moderate/poor work ability was the primary outcome. Descriptive statistics and logistic regression analyses were applied.

Results

The mean age of the sample at survey was 65.5 years (SD 5.9). At survey 42% of the sample reported moderate/poor current work ability and 58% reported high work ability. In multivariable analysis older age at survey, low basic education, comorbidity, poor self-rated health, presence of depression and low EPIC-26 hormonal domain score remained significantly associated with moderate/poor work ability.

Conclusions

Current work ability is a useful measure for the working capacity particularly of retired men. Socio-demographic, cancer-related, health, psychological and typical adverse effect variables were significantly associated with moderate/poor current work ability after robot-assisted laparoscopic prostatectomy, and several health and psychological variables are amenable to identification and treatment by health care providers.
Trauma induced tissue survival in vitro with a muscle-biomaterial based osteogenic organoid system: a proof of concept study
Authors: He Tao , Hausdorf Jörg , Chevalier Yan , Klar Roland M.
Published: January 2020

Background

The translation from animal research into the clinical environment remains problematic, as animal systems do not adequately replicate the human in vivo environment. Bioreactors have emerged as a good alternative that can reproduce part of the human in vivo processes at an in vitro level. However, in vitro bone formation platforms primarily utilize stem cells only, with tissue based in vitro systems remaining poorly investigated. As such, the present pilot study explored the tissue behavior and cell survival capability within a new in vitro skeletal muscle tissue-based biomaterial organoid bioreactor system to maximize future bone tissue engineering prospects.

Results

Three dimensional printed β-tricalcium phosphate/hydroxyapatite devices were either wrapped in a sheet of rat muscle tissue or first implanted in a heterotopic muscle pouch that was then excised and cultured in vitro for up to 30 days. Devices wrapped in muscle tissue showed cell death by day 15. Contrarily, devices in muscle pouches showed angiogenic and limited osteogenic gene expression tendencies with consistent TGF-ß1, COL4A1, VEGF-A, RUNX-2, and BMP-2 up-regulation, respectively. Histologically, muscle tissue degradation and fibrin release was seen being absorbed by devices acting possibly as a support for new tissue formation in the bioceramic scaffold that supports progenitor stem cell osteogenic differentiation.

Conclusions

These results therefore demonstrate that the skeletal muscle pouch-based biomaterial culturing system can support tissue survival over a prolonged culture period and represents a novel organoid tissue model that with further adjustments could generate bone tissue for direct clinical transplantations.
Simulation of three intraoral radiographic techniques in pediatric dental patients: subjective comfort assessment using the VAS and Wong-Baker FACES Pain Raiting Scale
Authors: Ozdemir Serife , Parlakyıldız Gokce Aysenur , Unver Tugba
Published: January 2020

Background

Perception of pain associated with intraoral radiography in pediatric patients was evaluated through statistical comparisons of data obtained using the Wong-Baker FACES Pain Raiting Scale (WBFPRS) and visual analog scale (VAS) scoring.

Methods

A total of 75 pediatric patients aged 6–12 years were included in this study. Simulations of each of three radiological methods (analog films, CCD sensor and phosphorus plates) were performed on 25 pediatric patients. Following the simulations, the meaning of each facial expression on the WBFPRS and the numbers on the VAS were explained to each child. For the comparison between groups, the homogeneity of the variances was tested with Levene’s test; because the variances were not homogeneous, Welch’s test was used. Tamhane’s T2 test was used because the homogeneity assumption was not provided to determine the source of the difference between the groups.

Results

When the conventional method was compared to the PSPL (photostimulable phosphor luminescence) method, no significant differences were noted in either the WBFPRS or VAS results (p >0.05). The results obtained from both of the scales were significantly different between the conventional method and the CCD sensor method (p < 0.05). When the PSPL and CCD sensors were compared, a significant difference was observed for the WBFPRS (p < 0.05). It was found the highest level of pain scores when used the CCD sensor method than the analog film and PSPL methods (p < 0.05).

Conclusions

It is expected that digital radiographic techniques will be improved in the future and that their disadvantages will be eliminated, resulting in imaging devices that are more comfortable for pediatric patients.
Point-of-care ultrasound curriculum for internal medicine residents: what do you desire? A national survey
Authors: Olgers Tycho J. , ter Maaten Jan C.
Published: January 2020

Background

Point-of-care Ultrasound is a relative new diagnostic tool for internists. Since 2019, it is a mandatory skill for internal medicine residents in the Netherlands but an ultrasound curriculum still has to be developed. In this study we explored the current ultrasound training program and educational wishes from internal medicine residents.

Methods

We have undertaken a national study in March 2019 using an online questionnaire. All internal medicine residents in the Netherlands were invited to respond.

Results

A total of 247 from 959 (26%) residents completed the questionnaire. The majority of residents (78.6%) received less than 10 h of ultrasound training and 40% has never made an ultrasound at all. Almost all residents (92%) indicate that ultrasound is a useful skill for the internist. They report that the most useful applications are ultrasound of the inferior vena cava, kidneys, abdominal free fluid, deep vein thrombosis, heart and lungs. The main perceived barrier to perform ultrasound is the lack of availability of experts for bedside supervision.

Conclusion

This study confirms the need for a national ultrasound curriculum for internal medicine residents and may contribute to the development of an ultrasound curriculum in line with residents educational needs. We should begin the curriculum with the previously mentioned applications, perceived by internal residents as most useful. Additional applications can be appended in the future. Finally it is necessary to expand the number of experts to supervise the residents.
Why genomics researchers are sometimes morally required to hunt for secondary findings
Authors: Koplin Julian J. , Savulescu Julian , Vears Danya F.
Published: January 2020

Background

Genomic research can reveal ‘unsolicited’ or ‘incidental’ findings that are of potential health or reproductive significance to participants. It is widely thought that researchers have a moral obligation, grounded in the duty of easy rescue, to return certain kinds of unsolicited findings to research participants. It is less widely thought that researchers have a moral obligation to actively look for health-related findings (for example, by conducting additional analyses to search for findings outside the scope of the research question).

Main text

This paper examines whether there is a moral obligation, grounded in the duty of easy rescue, to actively hunt for genomic secondary findings. We begin by showing how the duty to disclose individual research findings can be grounded in the duty of easy rescue. Next, we describe a parallel moral duty, also grounded in the duty of easy rescue, to actively hunt for such information. We then consider six possible objections to our argument, each of which we find unsuccessful. Some of these objections provide reason to limit the scope of the duty to look for secondary findings, but none provide reason to reject this duty outright.

Conclusions

We argue that under a certain range of circumstances, researchers are morally required to hunt for these kinds of secondary findings. Although these circumstances may not currently obtain, genomic researchers will likely acquire an obligation to hunt for secondary findings as the field of genomics continues to evolve.
Continuity of care and its associations with self-reported health, clinical characteristics and follow-up services after percutaneous coronary intervention
Authors: Valaker Irene , Fridlund Bengt , Wentzel-Larsen Tore , Nordrehaug Jan Erik , Rotevatn Svein , Råholm Maj-Britt , Norekvål Tone M.
Published: January 2020

Aims

Complexity of care in patients with coronary artery disease is increasing, due to ageing, improved treatment, and more specialised care. Patients receive care from various healthcare providers in many settings. Still, few studies have evaluated continuity of care across primary and secondary care levels for patients after percutaneous coronary intervention (PCI). This study aimed to determine multifaceted aspects of continuity of care and associations with socio-demographic characteristics, self-reported health, clinical characteristics and follow-up services for patients after PCI.

Methods

This multi-centre prospective cohort study collected data at baseline and two-month follow-up from medical records, national registries and patient self-reports. Univariable and hierarchical regressions were performed using the Heart Continuity of Care Questionnaire total score as the dependent variable.

Results

In total, 1695 patients were included at baseline, and 1318 (78%) completed the two-month follow-up. Patients stated not being adequately informed about lifestyle changes, medication and follow-up care. Those experiencing poorer health status after PCI scored significantly worse on continuity of care. Patients with ST-segment elevation myocardial infarction scored significantly better on informational and management continuity than those with other cardiac diagnoses. The regression analyses showed significantly better continuity (P ≤ 0.034) in patients who were male, received written information from hospital, were transferred to another hospital before discharge, received follow-up from their general practitioner or had sufficient consultation time after discharge from hospital.

Conclusion

Risk factors for sub-optimal continuity were identified. These factors are important to patients, healthcare providers and policy makers. Action should be taken to educate patients, reconcile discharge plans and organise post-discharge services. Designing pathways with an interdisciplinary approach and shared responsibility between healthcare settings is recommended.
Facilitators and barriers for emergency department clinicians using a rapid chest pain assessment protocol: qualitative interview research
Authors: Crilly Julia , Greenslade Jaimi H. , Berndt Sara , Hawkins Tracey , Cullen Louise
Published: January 2020

Background

Guideline-based processes for the assessment of chest pain are lengthy and resource intensive. The IMProved Assessment of Chest Pain Trial (IMPACT) protocol was introduced in one Australian hospital Emergency Department (ED) to more efficiently risk stratify patients. The theoretical domains framework is a useful approach to assist in identifying barriers and facilitators to the implementation of new guidelines in clinical practice. The aim of this study was to understand clinicians’ perceptions of facilitators and barriers to the use of the IMPACT protocol.

Methods

Guided by the theoretical domains framework, semi-structured interviews with nine ED clinical staff (medical and nursing) were undertaken in 2016. Content analysis was conducted independently by two researchers to identify those theoretical domains that facilitated or hindered protocol use.

Results

Domains most often reported as fundamental to the use of the IMPACT protocol included ‘social/professional role and identity’, ‘environmental context and resources’ and ‘social influences’. These factors seemingly influenced professional confidence, with participants noting ‘goals’ that included standardisation of practice, enhanced patient safety, and reduced need for unnecessary testing. The domain ‘environmental context and resources’ also contained the most noted barrier - the need to inform new members of staff regarding protocol use. Opportunities to overcome this barrier included modelling of protocol use by staff at all levels and education – both formal and informal.

Conclusions

A range of domains were identified by ED staff as influencing their chest pain management behaviour. Fundamental to its use were champions/leaders that were trusted and accessible, as well as social influences (other staff within ED and other specialty areas) that enabled and supported protocol use. Research investigating the implementation and perceived use of the protocol at other sites, of varied geographical locations, is warranted.
TRIM21–SERPINB5 aids GMPS repression to protect nasopharyngeal carcinoma cells from radiation-induced apoptosis
Authors: Zhang Panpan , Li Xiaomin , He Qiuping , Zhang Lulu , Song Keqing , Yang Xiaojing , He Qingmei , Wang Yaqin , Hong Xiaohong , Ma Jun , Liu Na
Published: January 2020

Background

The main strategy against nasopharyngeal carcinoma (NPC) is radiotherapy. However, radioresistance mediated recurrence is a leading clinical bottleneck in NPC. Revealing the mechanism of NPC radioresistance will help improve the therapeutic effect.

Methods

In this study, the role of TRIM21 (tripartite motif–containing 21) in NPC receiving ionizing radiation was firstly examined both in vivo and in vitro. Mass spectrometry analysis was performed to identify the downstream targets of TRIM21. NPC cells with TRIM21 or SERPINB5 (serpin family B member 5) overexpression or knockout were used to determine the epistatic relationship among SERPINB5, GMPS (guanine monophosphate synthase) and TRIM21. Flow cytometry, co-immunoprecipitation, western blot and immunofluorescence were employed to strengthen the results. Finally, immunohistochemistry using 4 radiosensitive and 8 radioresistent NPC patient samples was perform to examine the association between SERPINB5 or GMPS expression and patient radio-sensitivity.

Results

As an E3 ligase, TRIM21 was highly expressed in NPC. After ionizing radiation, TRIM21 repressed TP53 expression by mediating GMPS ubiquitination and degradation. Overexpression of TRIM21 protected NPC cells from radiation mediated cell apoptosis in vitro and in vivo. Further analysis revealed that TRIM21 mediated GMPS repression was dependent on SERPINB5, and SERPINB5 served as an adaptor which prevented GMPS from entering into the nucleus and introduced TRIM21 for GMPS ubiquitination. Moreover, the in vitro and in vivo results validated the finding that SERPINB5 promoted NPC cell radioresistance, and the radioresistant patients had higher SERPINB5 expression.

Conclusions

Overall, our data showed that TRIM21–SERPINB5-mediated GMPS degradation facilitated TP53 repression, which promoted the radioresistance of NPC cells. This novel working model related to TP53 suppression provided new insight into NPC radioresistence clinically.
The extended recovery ring-stage survival assay provides a superior association with patient clearance half-life and increases throughput
Authors: Davis Sage Z. , Singh Puspendra P. , Vendrely Katelyn M. , Shoue Douglas A. , Checkley Lisa A. , McDew-White Marina , Button-Simons Katrina A. , Cassady Zione , Sievert Mackenzie A. C. , Foster Gabriel J. , Nosten François H. , Anderson Timothy J. C. , Ferdig Michael T.
Published: January 2020

Background

Tracking and understanding artemisinin resistance is key for preventing global setbacks in malaria eradication efforts. The ring-stage survival assay (RSA) is the current gold standard for in vitro artemisinin resistance phenotyping. However, the RSA has several drawbacks: it is relatively low throughput, has high variance due to microscopy readout, and correlates poorly with the current benchmark for in vivo resistance, patient clearance half-life post-artemisinin treatment. Here a modified RSA is presented, the extended Recovery Ring-stage Survival Assay (eRRSA), using 15 cloned patient isolates from Southeast Asia with a range of patient clearance half-lives, including parasite isolates with and without kelch13 mutations.

Methods

Plasmodium falciparum cultures were synchronized with single layer Percoll during the schizont stage of the intraerythrocytic development cycle. Cultures were left to reinvade to early ring-stage and parasitaemia was quantified using flow cytometry. Cultures were diluted to 2% haematocrit and 0.5% parasitaemia in a 96-well plate to start the assay, allowing for increased throughput and decreased variability between biological replicates. Parasites were treated with 700 nM of dihydroartemisinin or 0.02% dimethyl sulfoxide (DMSO) for 6 h, washed three times in drug-free media, and incubated for 66 or 114 h, when samples were collected and frozen for PCR amplification. A SYBR Green-based quantitative PCR method was used to quantify the fold-change between treated and untreated samples.

Results

15 cloned patient isolates from Southeast Asia with a range of patient clearance half-lives were assayed using the eRRSA. Due to the large number of pyknotic and dying parasites at 66 h post-exposure (72 h sample), parasites were grown for an additional cell cycle (114 h post-exposure, 120 h sample), which drastically improved correlation with patient clearance half-life compared to the 66 h post-exposure sample. A Spearman correlation of − 0.8393 between fold change and patient clearance half-life was identified in these 15 isolates from Southeast Asia, which is the strongest correlation reported to date.

Conclusions

eRRSA drastically increases the efficiency and accuracy of in vitro artemisinin resistance phenotyping compared to the traditional RSA, which paves the way for extensive in vitro phenotyping of hundreds of artemisinin resistant parasites.
Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340
Authors: Jian Xiangyu , He Han , Zhu Jiehong , Zhang Qi , Zheng Zhongxin , Liang Xiangjing , Chen Liuyan , Yang Meiling , Peng Kaiyue , Zhang Zhaowen , Liu Tengfei , Ye Yaping , Jiao Hongli , Wang Shuyang , Zhou Weijie , Ding Yanqing , Li Tingting
Published: January 2020

Background

Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown.

Methods

qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells.

Results

Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1.

Conclusions

Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.
Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells
Authors: Oono Keiichi , Ohtake Kazuo , Watanabe Chie , Shiba Sachiko , Sekiya Takashi , Kasono Keizo
Published: January 2020

Background

n-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are thought to exert protective effects in cardiovascular diseases. In addition, n-3 PUFAs have demonstrated anti-cancer effects in vitro and in vivo.

Objective

We investigated the anti-cancer effects and mechanism of action of EPA on PC3 prostate cancer cells in vitro.

Methods

PC3 cells were treated with various concentrations of EPA, and cell survival and the abilities of migration and invasion were evaluated. The time course of the growth inhibitory effect of EPA on PC3 cells was also assessed. The mechanism underlying the anti-cancer effects of EPA was investigated by human phosphokinase and human apoptosis antibody arrays, and confirmed by western blot analysis. We also examined the contribution of reactive oxygen species (ROS) to the effects of EPA using the ROS inhibitor N-acetyl cysteine.

Results

EPA decreased the survival of PC3 cells in a dose-dependent manner within 3 h of application, with an effective concentration of 500 μmol/L. EPA inhibited proline-rich tyrosine kinase (Pyk)2 and extracellular signal-regulated kinase 1/2 phosphorylation as determined by western blotting and the antibody arrays. The growth of PC3 cells was inhibited by EPA, which was dependent on ROS induction, while EPA inhibited Pyk2 phosphorylation independent of ROS production.

Conclusions

Inhibition of Pyk2 phosphorylation and ROS production contribute to the anticancer effects of EPA on PC3 cells.
Reference values for lipid profile in Iranian children and adolescents: the CASPIAN-V study
Authors: Azizi-Soleiman Fatemeh , Khoramdad Maliheh , Heshmat Ramin , Ejtahed Hanieh-Sadat , Motlagh Mohammad Esmaeil , Daniali Seyede Shahrbanoo , Qorbani Mostafa , Kelishadi Roya
Published: January 2020

Background

We aimed to develop the age- and sex-specific reference values for lipid profile of Iranian pediatric population.

Methods

Fasting lipid profiles of 3843 participants, aged 7 to 18 years, were extracted from a surveillance survey on Iranian children and adolescents living in 30 provinces across the country.

Results

The mean (SD) age of participants was 12.3(3.1) years, and 52.3% of them were boys. Significant differences were observed between genders comparing the levels of triglyceride (TG) (P = 0.04), total cholesterol (TC) (P = 0.02), low-density lipoprotein- cholesterol (LDL-C) (P = 0.01), and non-high-density lipoprotein cholesterol (non-HDL-C) (P = 0.03). In both genders, TG levels increased with age in the 75th and higher percentiles. Among boys, TC showed a decreasing trend at all percentiles and all age groups. In girls, TC levels increased with age at all percentiles except for the 75th and 90th percentiles. Among boys, the levels of LDL-C and HDL-C decreased with age in all percentiles. However, LDL-C and HDL-C concentrations increased up to the 50th percentile in girls and then decreased with age. The non-HDL-C level decreased in the 50th and higher percentiles among boys and in the 90th and 95th percentiles among girls. The TG/HDL-C ratio increased with age at all percentiles in boys. In girls, TG/HDL-C ratio increased with age in the 50th and higher percentiles.

Conclusions

Based on the observed differences, it seems necessary to determine age- and sex-specific cut-off values for lipid parameters of children and adolescents in different populations.