bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of high drinking water nitrate levels on the endogenous formation of apparent N-nitroso compounds in combination with meat intake in healthy volunteers
Authors: van Breda Simone G. , Mathijs Karen , Sági-Kiss Virág , Kuhnle Gunter G. , van der Veer Ben , Jones Rena R. , Sinha Rashmi , Ward Mary H. , de Kok Theo M. 
Published: October 2019

Abstract

Background
Nitrate is converted to nitrite in the human body and subsequently can react with amines and amides in the gastrointestinal tract to form N-nitroso compounds (NOCs), which are known to be carcinogenic in animals. Humans can be exposed to nitrate via consumption of drinking water and diet, especially green leafy vegetables and cured meat. The contribution of nitrate from drinking water in combination with meat intake has not been investigated thoroughly. Therefore, in the present pilot study, we examined the effect of nitrate from drinking water, and its interaction with the consumption of white and processed red meat, on the endogenous formation of NOCs, taking into account the intake of vitamin C, a nitrosation inhibitor.

Methods
Twenty healthy subjects were randomly assigned to two groups consuming either 3.75 g/kg body weight (maximum 300 g per day) processed red meat or unprocessed white meat per day for two weeks. Drinking water nitrate levels were kept low during the first week (< 1.5 mg/L), whereas in week 2, nitrate levels in drinking water were adjusted to the acceptable daily intake level of 3.7 mg/kg bodyweight. At baseline, after 1 and 2 weeks, faeces and 24 h urine samples were collected for analyses of nitrate, apparent total N-nitroso compounds (ATNC), compliance markers, and genotoxic potential in human colonic Caco-2 cells.

Results
Urinary nitrate excretion was significantly increased during the high drinking water nitrate period for both meat types. Furthermore, levels of compliance markers for meat intake were significantly increased in urine from subjects consuming processed red meat (i.e. 1-Methylhistidine levels), or unprocessed white meat (i.e. 3-Methylhistidine). ATNC levels significantly increased during the high drinking water nitrate period, which was more pronounced in the processed red meat group. Genotoxicity in Caco-2 cells exposed to faecal water resulted in increased genotoxicity after the interventions, but results were only significant in the low drinking water nitrate period in subjects consuming processed red meat. Furthermore, a positive correlation was found between the ratio of nitrate/vitamin C intake (including drinking water) and the level of ATNC in faecal water of subjects in the processed red meat group, but this was not statistically significant.

Conclusions
Drinking water nitrate significantly contributed to the endogenous formation of NOC, independent of the meat type consumed. This implies that drinking water nitrate levels should be taken into account when evaluating the effect of meat consumption on endogenous formation of NOC.

Trial registration
Dutch Trialregister: 29707. Registered 19th of October 2018. Retrospectively registered.
Prevalence and risk factors of HIV infection among people who inject drugs in Cambodia: findings from a national survey
Authors: Mburu Gitau , Chhoun Pheak , Chann Navy , Tuot Sovannary , Mun Phalkun , Yi Siyan 
Published: October 2019

Abstract

Background
Globally, people who inject drugs (PWID) continue to be among the most vulnerable populations to acquire infection of human immunodeficiency virus (HIV). The most recent national survey found that nearly a quarter of PWID in Cambodia were infected with HIV in 2012. The aim of this study is to estimate the current prevalence of and factors associated with HIV infection among PWID in Cambodia.

Methods
This national integrated biological and behavioral survey was conducted from June to December 2017. Participants were recruited from the capital city and 11 major provinces using the respondent driven sampling method. Face-to-face interviews were conducted using a structured questionnaire, and blood samples were collected for HIV, syphilis, and hepatitis C virus (HCV) testing. Multiple logistic regression analysis was conducted to identify risk factors for HIV infection. All analyses were estimated with sampling weights that corrected for non-response and sample design.

Results
A total of 310 PWID participated in the study, and the mean age was 31.8 years (SD = 7.8). The prevalence of HIV was 15.2%. More than half (57.4%) of the HIV-positive participants were co-infected with HCV, and 44.7% were not aware of their HIV status prior to this study. After adjustment for other covariates, HIV infection remained positively associated with being female (AOR = 1.88, 95% CI = 1.03–4.04), being in the older age group of ≥35 (AOR = 2.99, 95% CI 1.33–9.22), being widowed, divorced or separated (AOR = 2.57, 95% CI = 1.04–6.67), living on the streets (AOR = 2.86, 95% CI 1.24–4.37), and HCV infection (AOR = 3.89, 95% CI 1.86–1.15). The HIV infection remained negatively associated with having higher level of formal education of ≥10 years (AOR = 0.44, 95% CI 0.13–0.83) and higher average income of ≥US$200 per month (AOR = 0.20, 95% CI = 0.05–0.74).

Conclusions
The prevalence of HIV among PWID in Cambodia remains high, but is reducing compared with the 24.8% reported in the 2012 national survey. Findings from this study provide critical information for tailoring interventions based on identified vulnerabilities and risk factors for HIV. Our findings underline the importance of socio-structural factors in HIV epidemiology among PWID in Cambodia, which require mitigation.
Cortical ensemble activity discriminates auditory attentional states
Authors: Yao Pan-tong , Shen Jia , Chen Liang , Ge Shaoyu , Xiong Qiaojie 
Published: October 2019

Abstract
Selective attention modulates sensory cortical activity. It remains unclear how auditory cortical activity represents stimuli that differ behaviorally. We designed a cross-modality task in which mice made decisions to obtain rewards based on attended visual or auditory stimuli. We recorded auditory cortical activity in behaving mice attending to, ignoring, or passively hearing auditory stimuli. Engaging in the task bidirectionally modulates neuronal responses to the auditory stimuli in both the attended and ignored conditions compared to passive hearing. Neuronal ensemble activity in response to stimuli under attended, ignored and passive conditions are readily distinguishable. Furthermore, ensemble activity under attended and ignored conditions are in closer states compared to passive condition, and they share a component of attentional modulation which drives them to the same direction in the population activity space. Our findings suggest that the ignored condition is very different from the passive condition, and the auditory cortical sensory processing under ignored, attended and passive conditions are modulated differently.
circRNA circAF4 functions as an oncogene to regulate MLL-AF4 fusion protein expression and inhibit MLL leukemia progression
Authors: Huang Wei , Fang Ke , Chen Tian-Qi , Zeng Zhan-Cheng , Sun Yu-Meng , Han Cai , Sun Lin-Yu , Chen Zhen-Hua , Yang Qian-Qian , Pan Qi , Luo Xue-Qun , Wang Wen-Tao , Chen Yue-Qin 
Published: October 2019

Abstract

Background
Circular RNAs (circRNAs) represent a type of endogenous noncoding RNAs that are generated by back-splicing events and favor repetitive sequences. Recent studies have reported that cancer-associated chromosomal translocations could juxtapose distant complementary repetitive intronic sequences, resulting in the aberrant formation of circRNAs. However, among the reported fusion genes, only a small number of circRNAs were found to originate from fusion regions during gene translocation. We question if circRNAs could also originate from fusion partners during gene translocation.

Methods
Firstly, we designed divergent primers for qRT-PCR to identify a circRNA circAF4 in AF4 gene and investigated the expression pattern in different types of leukemia samples. Secondly, we designed two small interfering RNAs specially targeting the back-spliced junction point of circAF4 for functional studies. CCK8 cell proliferation and cell cycle assay were performed, and a NOD-SCID mouse model was used to investigate the contribution of circAF4 in leukemogenesis. Finally, luciferase reporter assay, AGO2 RNA immunoprecipitation (RIP), and RNA Fluorescent in Situ Hybridization (FISH) were performed to confirm the relationship of miR-128-3p, circAF4, and MLL-AF4 expression.

Results
We discovered a circRNA, named circAF4, originating from the AF4 gene, a partner of the MLL fusion gene in MLL-AF4 leukemia. We showed that circAF4 plays an oncogenic role in MLL-AF4 leukemia and promotes leukemogenesis in vitro and in vivo. More importantly, knockdown of circAF4 increases the leukemic cell apoptosis rate in MLL-AF4 leukemia cells, while no effect was observed in leukemia cells that do not carry the MLL-AF4 translocation. Mechanically, circAF4 can act as a miR-128-3p sponge, thereby releasing its inhibition on MLL-AF4 expression. We finally analyzed most of the MLL fusion genes loci and found that a number of circRNAs could originate from these partners, suggesting the potential roles of fusion gene partner-originating circRNAs (named as FP-circRNAs) in leukemia with chromosomal translocations.

Conclusion
Our findings demonstrate that the abnormal elevated expression of circAF4 regulates the cell growth via the circAF4/miR-128-3p/MLL-AF4 axis, which could contribute to leukemogenesis, suggesting that circAF4 may be a novel therapeutic target of MLL-AF4 leukemia.
LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway
Authors: Qiao Kun , Ning Shipeng , Wan Lin , Wu Hao , Wang Qin , Zhang Xingda , Xu Shouping , Pang Da 
Published: October 2019

Abstract

Background
An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play essential roles in tumor initiation and progression. LncRNAs act as tumor promoters or suppressors by targeting specific genes via epigenetic modifications and competing endogenous RNA (ceRNA) mechanisms. In this study, we explored the function and detailed mechanisms of long intergenic nonprotein coding RNA 673 (LINC00673) in breast cancer progression.

Methods
Quantitative real-time PCR (qRT-PCR) was used to examine the expression of LINC00673 in breast cancer tissues and in adjacent normal tissues. Gain-of-function and loss-of function experiments were conducted to investigate the biological functions of LINC00673 in vitro and in vivo. We also explored the potential role of LINC00673 as a therapeutic target using antisense oligonucleotide (ASO) in vivo. RNA sequencing (RNA-seq), dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) assay, and rescue experiments were performed to uncover the detailed mechanism of LINC00673 in promoting breast cancer progression.

Results
In the present study, LINC00673 displayed a trend of remarkably increased expression in breast cancer tissues and was associated with poor prognosis in breast cancer patients. Importantly, LINC00673 depletion inhibited breast cancer cell proliferation by inhibiting the cell cycle and increasing apoptosis. Furthermore, ASO therapy targeting LINC00673 substantially suppressed breast cancer cell proliferation in vivo. Mechanistically, LINC00673 was found to act as a ceRNA by sponging miR-515-5p to regulate MARK4 expression, thus inhibiting the Hippo signaling pathway. Finally, ChIP assay showed that the transcription factor Yin Yang 1 (YY1) could bind to the LINC00673 promoter and increase its transcription in cis.

Conclusions
YY1-activated LINC00673 may exert an oncogenic function by acting as a sponge for miR-515-5p to upregulate the MARK4 and then inhibit Hippo signaling pathway, and may serve as a potential therapeutic target.
Predicting acute coronary syndrome in males and females with chest pain who call an emergency medical communication centre
Authors: Reuter Paul-Georges , Pradeau Catherine , Huo Yung Kai Samantha , Lhermusier Thibault , Bourdé Arnaud , Tentillier Eric , Combes Xavier , Bongard Vanina , Ducassé Jean-Louis , Charpentier Sandrine 
Published: October 2019

Abstract

Background
Chest pain is a frequent reason for calls in emergency medical communication centre (EMCC). Detecting a coronary origin by phone is a challenge. This is especially so as the presentations differ according to gender. We aimed to establish and validate a sex-based model to predict a coronary origin of chest pain in patients calling an EMCC.

Methods
This prospective cohort study enrolled patients at 18 years of age or older who called the EMCC because of non-traumatic chest pain. The main outcome was the diagnosis of acute coronary syndrome (ACS) determined by expert evaluation of patient files.

Results
During 18 months, 3727 patients were enrolled: 2097 (56%) men and 1630 (44%) women. ACS was diagnosed in 508 (24%) men and 139 (9%) women. For men, independent factors associated with an ACS diagnosis were age, tobacco use, severe and permanent pain; retrosternal, breathing non-related and radiating pain; and additional symptoms. The area under the receiver operating characteristic curve (AUC) was 0.76 (95% confidence interval [CI] 0.73–0.79) for predicting ACS. The accuracy of the male model to predict ACS was validated in a validation dataset (Hosmer-Lemeshow test: p = 0.554); the AUC was 0.77 (95%CI 0.73–0.80). For women, independent factors associated with an ACS diagnosis were age ≥ 60 years, personal history of coronary artery disease, and breathing non-related and radiating pain. The AUC was 0.79 (95%CI 0.75–0.83). The accuracy of the female model to predict ACS was not validated in the validation dataset (Hosmer-Lemeshow test: p = 0.035); the AUC was 0.67 (95%CI 0.60–0.74).

Conclusions
Predictors of an ACS diagnosis in patients calling an EMCC for chest pain differ between men and women. We developed an accurate predictive model for men, but for women, the accuracy was poor.

Trial registration
This study is registered with ClinicalTrials.gov (NCT02042209).
A Delphi consensus study for teaching “Basic Trauma Management” to third-year medical students
Authors: Berger-Estilita Joana , Nabecker Sabine , Greif Robert 
Published: October 2019

AbstractBackgroundThe Basic-Trauma Management (BTM) course has been taught to third-year medical students in small groups for many years without substantial changes. With the introduction of a new curriculum for Swiss medical students, it was necessary to revise the BTM content and re-align it. Our aim was to identify core competencies for the revised BTM course.MethodsWe applied a three-round step-wise Delphi consensus. First, we asked open-ended questions on what were the most important competencies to be taught for BTM; the second round used Likert scales to ensure agreement on the competencies; and the final round reached out for consensus on these BTM competencies. Stakeholders were selected based on their long-standing experience in teaching BTM and in managing trauma patients.ResultsConsensus was found on 29 competencies out of an initial 130 proposals. “Human Factors”, which had not been taught previously, scored relatively high, at 22%. The sole specific trauma skill agreed upon was the use of tourniquets.ConclusionsThis is an example of curricular revision of a clinical skills course after the introduction of a regulatory framework for undergraduate medical education. The revised course curriculum tailors the concepts and skills in trauma that fulfill stakeholder needs, and are in agreement with the new Swiss learning outcomes.
Quantitative nuclear histomorphometric features are predictive of Oncotype DX risk categories in ductal carcinoma in situ: preliminary findings
Authors: Li Haojia , Whitney Jon , Bera Kaustav , Gilmore Hannah , Thorat Mangesh A. , Badve Sunil , Madabhushi Anant 
Published: October 2019

Abstract

Background
Oncotype DX (ODx) is a 12-gene assay assessing the recurrence risk (high, intermediate, and low) of ductal carcinoma in situ (pre-invasive breast cancer), which guides clinicians regarding prescription of radiotherapy. However, ODx is expensive, time-consuming, and tissue-destructive. In addition, the actual prognostic meaning for the intermediate ODx risk category remains unclear.

Methods
In this work, we evaluated the ability of quantitative nuclear histomorphometric features extracted from hematoxylin and eosin-stained slide images of 62 ductal carcinoma in situ (DCIS) patients to distinguish between the corresponding ODx risk categories. The prognostic value of the identified image signature was further evaluated on an independent validation set of 30 DCIS patients in its ability to distinguish those DCIS patients who progressed to invasive carcinoma versus those who did not. Following nuclear segmentation and feature extraction, feature ranking strategies were employed to identify the most discriminating features between individual ODx risk categories. The selected features were then combined with machine learning classifiers to establish models to predict ODx risk categories. The model performance was evaluated using the average area under the receiver operating characteristic curve (AUC) using cross validation. In addition, an unsupervised clustering approach was also implemented to evaluate the ability of nuclear histomorphometric features to discriminate between the ODx risk categories.

Results
Features relating to spatial distribution, orientation disorder, and texture of nuclei were identified as most discriminating between the high ODx and the intermediate, low ODx risk categories. Additionally, the AUC of the most discriminating set of features for the different classification tasks was as follows: (1) high vs low ODx (0.68), (2) high vs. intermediate ODx (0.67), (3) intermediate vs. low ODx (0.57), (4) high and intermediate vs. low ODx (0.63), (5) high vs. low and intermediate ODx (0.66). Additionally, the unsupervised clustering resulted in intermediate ODx risk category patients being co-clustered with low ODx patients compared to high ODx.

Conclusion
Our results appear to suggest that nuclear histomorphometric features can distinguish high from low and intermediate ODx risk category patients. Additionally, our findings suggest that histomorphometric features for intermediate ODx were more similar to low ODx compared to high ODx risk category.
Sensitivity of screening mammography by density and texture: a cohort study from a population-based screening program in Denmark
Authors: von Euler-Chelpin My , Lillholm Martin , Vejborg Ilse , Nielsen Mads , Lynge Elsebeth 
Published: October 2019

Abstract

Background
Screening mammography works better in fatty than in dense breast tissue. Computerized assessment of parenchymal texture is a non-subjective method to obtain a refined description of breast tissue, potentially valuable in addition to breast density scoring for the identification of women in need of supplementary imaging. We studied the sensitivity of screening mammography by a combination of radiologist-assessed Breast Imaging Reporting and Data System (BI-RADS) density score and computer-assessed parenchymal texture marker, mammography texture resemblance (MTR), in a population-based screening program.

Methods
Breast density was coded according to the fourth edition of the BI-RADS density code, and MTR marker was divided into quartiles from 1 to 4. Screening data were followed up for the identification of screen-detected and interval cancers. We calculated sensitivity and specificity with 95% confidence intervals (CI) by BI-RADS density score, MTR marker, and combination hereof.

Results
Density and texture were strongly correlated, but the combination led to the identification of subgroups with different sensitivity. Sensitivity was high, about 80%, in women with BI-RADS density score 1 and MTR markers 1 or 2. Sensitivity was low, 67%, in women with BI-RADS density score 2 and MTR marker 4. For women with BI-RADS density scores 3 and 4, the already low sensitivity was further decreased for women with MTR marker 4. Specificity was 97–99% in all subgroups.

Conclusion
Our study showed that women with low density constituted a heterogenous group. Classifying women for extra imaging based on density only might be a too crude approach. Screening sensitivity was systematically high in women with fatty and homogenous breast tissue.
How can we get more people with long-term health conditions involved in parkrun? A qualitative study evaluating parkrun’s PROVE project
Authors: Quirk Helen , Haake Steve 
Published: October 2019

Abstract

Background
People with long-term health conditions face barriers to physical activity and community health interventions despite potential life-changing benefits for self-management of their condition and wellbeing. A weekly mass participation running, walking and volunteering event called parkrun launched a project called PROVE in 2016 to engage people living with long-term health conditions in England. Over the 3 year project, parkrun appointed volunteer Outreach Ambassadors with a specialist interest in the health condition they represented whose role was to ensure parkrun was welcoming, supportive and inclusive. This qualitative study aimed to understand the experience of the PROVE project for people with long-term health conditions.

Methods
Semi-structured interviews were conducted with 15 PROVE Outreach Ambassadors representing 13 different long-term health conditions in England. Interviews were recorded, transcribed verbatim and analysed using thematic analysis. Rigour and transparency were sought in addition to utilising independent researchers to offer alternative interpretations of the data.

Results
Data analysis resulted in 4 overarching themes and 13 subthemes. Outreach Ambassadors believed that parkrun was already supportive of people with long-term health conditions, but that the PROVE project enabled the support to be delivered in a more structured way across health conditions and locations. Outreach Ambassadors believed that the PROVE project had the potential to create a welcoming, safe space for people with long-term health conditions to participate as walkers, runners or volunteers. Success of the PROVE project was believed to be dependent on being realistic about the potential to bring about change, challenging people’s perceptions of parkrun and engaging with key stakeholders and advocacy groups. Challenges for parkrun were believed to be around communication, demonstrating impact and the project’s dependence on volunteers for delivery.

Conclusions
This is the first study of its kind to explore the public health potential of parkrun for people with long-term health conditions. parkrun’s PROVE project was regarded to be important for ensuring that people with long-term health conditions can engage in physical activity and volunteering in a safe and supportive environment. The findings have important implications for parkrun, policy makers and physical activity providers looking to deliver inclusive community physical activity opportunities.