bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of confirming the underlying diagnosis in patients with myocardial infarction and non-obstructive coronary arteries (MINOCA): a single-centre retrospective cohort study
Authors: Pustjens T. F. S. , Meerman A. , Vranken N. P. A. , Ruiters A. W. , Gho B. , Stein M. , Ilhan M. , Veenstra L. , Winkler P. , Lux Á. , Rasoul S. , van ‘t Hof A. W. J. 
Published: July 2021

AbstractBackgroundMany patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) are discharged without a known aetiology for their clinical presentation. This study sought to assess the effect of this ‘indeterminate MINOCA’ diagnosis on the prevalence of recurrent cardiovascular events and presentations to the Cardiac Emergency Department (CED).MethodsWe retrospectively analysed all patients meeting the diagnostic MINOCA criteria presenting at a large secondary hospital between January 2017 and April 2019.ParticipantsPatients were divided into the (1) ‘indeterminate MINOCA’, or (2) ‘MINOCA with diagnosis’ group. The primary outcome was the occurrence of major adverse cardiac events (MACE) defined as the composite of all-cause mortality, non-fatal myocardial infarction, stroke and any revascularisation procedure. Secondary outcomes were all recurrent visits at the CED, and MACE including unplanned cardiac hospitalisation.ResultsIn 62/198 (31.3%) MINOCA patients, a conclusive diagnosis was found (myocardial infarction, (peri)myocarditis, cardiomyopathy, or miscellaneous). MINOCA patients with a confirmed diagnosis were younger compared to those with an indeterminate diagnosis (56.7 vs. 62.3 years,p = 0.007), had higher maximum troponin-T [238 ng/L vs. 69 ng/L,p < 0.001] and creatine kinase (CK) levels [212U/L vs. 152U/L,p = 0.007], and presented more frequently with electrocardiographic signs of ischaemia (71.0% vs. 47.1%,p = 0.002). Indeterminate MINOCA patients more often showed recurrent CED presentations (36.8% vs. 22.6%,p = 0.048), however the occurrence of cardiovascular events was equal (8.8 vs. 8.1%,p = 0.86). Multivariable analysis showed that elevated levels of troponin-T and CK, ST-segment deviation on electrocardiography, reduced left ventricular ejection fraction, regional wall motion abnormalities, and performance of additional examination methods were independent predictors for finding the underlying MINOCA cause.ConclusionsOnly in one-third of MINOCA patients a conclusive diagnosis for the acute presentation was identified. Recurrent CED visits were more often observed in the indeterminate MINOCA group, while the occurrence of cardiovascular events was similar across groups.Trial registrationRetrospectively registered
Proteomic analysis identifies deregulated metabolic and oxidative-associated proteins in Italian intrahepatic cholangiocarcinoma patients
Authors: Cavalloni Giuliana , Peraldo-Neia Caterina , Massa Annamaria , Bergamini Carlo , Trentini Alessandro , De Rosa Giovanni , Daniele Lorenzo , Ciccosanti Fabiola , Cervellati Carlo , Leone Francesco , Aglietta Massimo 
Published: July 2021

Abstract
Background
Cholangiocarcinoma (CCA) is an aggressive disease with poor prognosis. A molecular classification based on mutational, methylation and transcriptomic features could allow identifying tailored therapies to improve CCA patient outcome. Proteomic remains partially unexplored; here, we analyzed the proteomic profile of five intrahepatic cholangiocarcinoma (ICC) derived from Italian patients undergone surgery and one normal bile duct cell line.

Methods
Proteome profile was investigated by using 2D electrophoresis followed by Mass Spectrometry (MS). To validate proteomic data, the expression of four overexpressed proteins (CAT, SOD, PRDX6, DBI/ACBP) was evaluated by immunohistochemistry in an independent cohort of formalin fixed, paraffin-embedded (FFPE) ICC tissues. We also compared proteomic data with those obtained by transcriptomic profile evaluated by microarray analysis of the same tissues.

Results
We identified 19 differentially expressed protein spots, which were further characterized by MS; 13 of them were up- and 6 were down-regulated in ICC. These proteins are mainly involved in redox processes (CAT, SODM, PRDX2, PRDX6), in metabolism (ACBP, ACY1, UCRI, FTCD, HCMS2), and cell structure and organization (TUB2, ACTB). CAT is overexpressed in 86% of patients, PRDX6 in 73%, SODM in 100%, and DBI/ACBP in 81% compared to normal adjacent tissues. A concordance of 50% between proteomic and transcriptomic data was observed.

Conclusions
This study pointed out that the impairment of the metabolic and antioxidant systems, with a subsequent accumulation of free radicals, might be a key step in CCA development and progression.
Prediction of lymphovascular space invasion using a combination of tenascin-C, cox-2, and PET/CT radiomics in patients with early-stage cervical squamous cell carcinoma
Authors: Li Xiaoran , Xu Chen , Yu Yang , Guo Yan , Sun Hongzan 
Published: July 2021

Abstract
Background
Lymphovascular space invasion is an independent prognostic factor in early-stage cervical cancer. However, there is a lack of non-invasive methods to detect lymphovascular space invasion. Some researchers found that Tenascin-C and Cyclooxygenase-2 was correlated with lymphovascular space invasion. Radiomics has been studied as an emerging tool for distinguishing tumor pathology stage, evaluating treatment response, and predicting prognosis. This study aimed to establish a machine learning model that combines radiomics based on PET imaging with tenascin-C (TNC) and cyclooxygenase-2 (COX-2) for predicting lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer.

Methods
One hundred and twelve patients with early-stage cervical squamous cell carcinoma who underwent PET/CT examination were retrospectively analyzed. Four hundred one radiomics features based on PET/CT images were extracted and integrated into radiomics score (Rad-score). Immunohistochemical analysis was performed to evaluate TNC and COX-2 expression. Mann-Whitney U test was used to distinguish differences in the Rad-score, TNC, and COX-2 between LVSI and non-LVSI groups. The correlations of characteristics were tested by Spearman analysis. Machine learning models including radiomics model, protein model and combined model were established by logistic regression algorithm and evaluated by ROC curve. Pairwise comparisons of ROC curves were tested by DeLong test.

Results
The Rad-score of patients with LVSI was significantly higher than those without. A significant correlation was shown between LVSI and Rad-score (r = 0.631, p < 0.001). TNC was correlated to both the Rad-score (r = 0.244, p = 0.024) and COX-2 (r = 0.227, p = 0.036). The radiomics model had the best predictive performance among all models in training and external dataset (AUCs: 0.914, 0.806, respectively, p < 0.001). However, in testing dataset, the combined model had better efficiency for predicting LVSI than other models (AUCs: 0.801 vs. 0.756 and 0.801 vs. 0.631, respectively).

Conclusion
The machine learning model of the combination of PET radiomics with COX-2 and TNC provides a new tool for detecting LVSI in patients with early-stage cervical cancer. In the future, multicentric studies on larger sample of patients will be used to test the model.

Trial registration
This is a retrospective study and there is no experimental intervention on human participants. The Ethics Committee has confirmed that retrospectively registered is not required.
Mental health and its association with coping strategies and intolerance of uncertainty during the COVID-19 pandemic among the general population in Saudi Arabia: cross-sectional study
Authors: AlHadi Ahmad N. , Alarabi Mohammed A. , AlMansoor Khulood M. 
Published: July 2021

Abstract
Background
The COVID-19 pandemic has had a major impact on people’s lives globally. The outbreak in Saudi Arabia worsened when the number of cases and deaths rose in March and April of 2020, leading to a national lockdown. This study aimed to assess the factors associated with mental health symptoms in a sample of people residing in Saudi Arabia during the COVID-19 pandemic.

Methods
We conducted an observational cross-sectional study using an online survey distributed via social media, completed by 3032 respondents from all Saudi regions. We collected demographic data, illness history, and scores of validated self-report scales to assess mental health symptoms, intolerance of uncertainty, and coping strategies.

Results
In total, respondents indicated moderate to very severe symptoms during the pandemic as follows: 20.9% for depression, 17.5% for anxiety, and 12.6% for stress. Younger age, female gender, and history of mental illness were associated with higher levels of depression, anxiety, stress, and insomnia. Intolerance of uncertainty and certain coping strategies (such as denial or self-blame) were associated with more severe symptoms.

Conclusions
Mental health is a key concern during the COVID-19 pandemic, especially for the identified vulnerable groups. Agencies concerned with mental health during crises may use the studied associated factors of mental health symptoms to generate targeted policies or interventions.
Opioid use disorder treatment disruptions during the early COVID-19 pandemic and other emergent disasters: a scoping review addressing dual public health emergencies
Authors: Henderson Rita , McInnes Ashley , Mackey Leslee , Bruised Head Myles , Crowshoe Lindsay , Hann Jessica , Hayward Jake , Holroyd Brian R. , Lang Eddy , Larson Bonnie , Leonard Ashley Jane , Persaud Steven , Raghavji Khalil , Sarin Chris , Virani Hakique , Wadsworth Iskotoahka William , Whitman Stacey , McLane Patrick 
Published: July 2021

Abstract
Background
During public health emergencies, people with opioid use disorder (PWOUD) may be particularly impacted. Emergent disasters such as the COVID-19 pandemic disrupt already-strained harm reduction efforts and treatment availability. This study aims to answer three research questions. How do public health emergencies impact PWOUD? How can health systems respond to novel public health emergencies to serve PWOUD? How can the results of this scoping review be contextualized to the province of Alberta to inform local stakeholder responses to the pandemic?

Methods
We conducted a scoping review using the 6-stage Arksey and O’Malley framework to analyse early-pandemic and pre-pandemic disaster literature. The results of the scoping review were contextualized to the local pandemic response, through a Nominal Group Technique (NGT) process with frontline providers and stakeholders in Alberta, Canada.

Results
Sixty one scientific journal articles and 72 grey literature resources were included after full-text screening. Forty sources pertained to early COVID-19 responses, and 21 focused on OUD treatment during other disasters. PWOUD may be more impacted than the general population by common COVID-19 stressors including loss of income, isolation, lack of rewarding activities, housing instability, as well as fear and anxiety. They may also face unique challenges including threats to drug supplies, stigma, difficulty accessing clean substance use supplies, and closure of substance use treatment centres. All of these impacts put PWOUD at risk of negative outcomes including fatal overdose. Two NGT groups were held. One group (n = 7) represented voices from urban services, and the other (n = 4) Indigenous contexts. Stakeholders suggested that simultaneous attention to multiple crises, with adequate resources to allow attention to both social and health systems issues, can prepare a system to serve PWOUD during disasters.

Conclusion
This scoping review and NGT study uncovers how disasters impact PWOUD and offers suggestions for better serving PWOUD.
Sexual behaviour, human papillomavirus and its vaccine: a qualitative study of adolescents and parents in Andalusia
Authors: González-Cano María , Garrido-Peña Francisco , Gil-Garcia Eugenia , Lima-Serrano Marta , Cano-Caballero María Dolores 
Published: July 2021

AbstractBackgroundHuman papillomavirus (HPV) is one of the most common sexually transmitted infections and can be prevented by vaccination. The purpose of this study is to gain a better understanding, by analysing interview responses of adolescents and parents, of how adolescent sexual behaviour is approached in families, how widespread knowledge about HPV is in Andalusia, the autonomous region with the lowest vaccination rate in Spain, as well as to learn more about the interviewees’ position regarding vaccination.MethodsA qualitative study by means of 15 focus groups of adolescents (N = 137, aged 14–17 years) and five focus groups of parents with children of those ages (N = 37) was conducted in the provinces of Granada, Seville and Jaén (Andalusia, Spain). The audio data were transcribed verbatim, coded and analysed thematically using NVIVO-10 software.ResultsThere were three major results: (1) There is a lack of communication between adolescents and parents regarding sexual behaviour; (2) In both groups, scarce knowledge about HPV and vaccination was found; (3) Parents mistrust vaccination due to a lack of qualified and verified information about its benefits.ConclusionsHealthy adolescent sexual behaviour is aided by communication within the family. Families need more information based on the evidence about HPV and vaccination. Health professionals are a key element in this process.
Chronic respiratory disease disparity between American Indian/Alaska Native and white populations, 2011–2018
Authors: Laffey Kimberly G. , Nelson Alfreda D. , Laffey Matthew J. , Nguyen Quynh , Sheets Lincoln R. , Schrum Adam G. 
Published: July 2021

Abstract
Background
American Indian/Alaska Native (AI/AN) populations have been disproportionately affected by chronic respiratory diseases for reasons incompletely understood. Past research into disease disparity using population-based surveys mostly focused on state-specific factors. The present study investigates the independent contributions of AI/AN racial status and other socioeconomic/demographic variables to chronic respiratory disease disparity in an 11-state region with historically high AI/AN representation. Using data from the Behavioral Risk Factor Surveillance System (BRFSS) spanning years 2011–2018, this work provides an updated assessment of disease disparity and potential determinants of respiratory health in AI/AN populations.

Methods
This cross-sectional study used data from the BRFSS survey, 2011–2018. The study population included AI/AN and non-Hispanic white individuals resident in 11 states with increased proportion of AI/AN individuals. The yearly number of respondents averaged 75,029 (62878–87,350) which included approximately 5% AI/AN respondents (4.5–6.3%). We compared the yearly adjusted prevalence for chronic respiratory disease, where disease status was defined by self-reported history of having asthma and/or chronic obstructive pulmonary disease (COPD). Multivariable logistic regression was performed to determine if being AI/AN was independently associated with chronic respiratory disease. Covariates included demographic (age, sex), socioeconomic (marital status, education level, annual household income), and behavioral (smoking, weight morbidity) variables.

Results
The AI/AN population consistently displayed higher adjusted prevalence of chronic respiratory disease compared to the non-Hispanic white population. However, the AI/AN race/ethnicity characteristic was not independently associated with chronic respiratory disease (OR, 0.93; 95% CI, 0.79–1.10 in 2017). In contrast, indicators of low socioeconomic status such as annual household income of <$10,000 (OR, 2.02; 95% CI, 1.64–2.49 in 2017) and having less than high school education (OR, 1.37; 95% CI, 1.16–1.63 in 2017) were positively associated with disease. These trends persisted for all years analyzed.

Conclusions
This study highlighted that AI/AN socioeconomic burdens are key determinants of chronic respiratory disease, in addition to well-established risk factors such as smoking and weight morbidity. Disease disparity experienced by the AI/AN population is therefore likely a symptom of disproportionate socioeconomic challenges they face. Further promotion of public health and social service efforts may be able to improve AI/AN health and decrease this disease disparity.
Association of pelvic inflammatory disease (PID) with ovarian cancer: a nationwide population-based retrospective cohort study from Taiwan
Authors: Chang Cherry Yin-Yi , Lin Kent Yu-Hsien , Huang Chien-Chu , Lin Wu-Chou 
Published: July 2021

Abstract
Background
Pelvic inflammatory disease (PID) is an important health issue for women. Infection and inflammation play an important role in carcinogenesis and PID has been reported to be associated with ovarian cancer in some small scale studies.

Aim
We sought to determine whether PID is associated with an elevated risk of ovarian cancer in Asian women.

Methods
Using data from Taiwan’s National Health Insurance Research Database (NHIRD), our retrospective cohort study included women diagnosed with PID (cases) between the years of 2000 till 2012. Each case was matched with two women without PID (controls) by age and the year of first entry into the database. Both study cohorts were followed-up until the first event of ovarian cancer, withdrawal from the NHI program, death, or the end of the study period (December 31, 2012). Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios (HRs and aHRs) with their corresponding 95% confidence intervals (95% CIs) for the association of PID and ovarian cancer risk, with and without adjusting for potential confounders.

Results
During an approximate 10 years of follow-up, cases were significantly more likely than controls to develop ovarian cancer (incidence rates of 0.27 and 0.16 per 1,000 person-years, respectively; P < 0.001). Women with a history of PID had a 1.49-fold elevated risk for ovarian cancer (aHR, 1.49; 95% CI, 1.21–1.84; P < 0.001).

Conclusion
Our study evidence supports the contention that PID increases the risk of developing ovarian cancer among Taiwanese women. Gynecologists should undertake careful assessments and closely follow patients with PID, who are at long-term risk of developing ovarian cancer. Our findings need further verification in other international cohorts.
Outcomes of blended learning for capacity strengthening of health professionals in Guinea
Authors: Millimouno Tamba Mina , Delamou Alexandre , Kourouma Karifa , Kolié Jean Michel , Béavogui Abdoul Habib , Roegiers Sara , Garcia Marlon , Tsunami Carlos Kiyan , Van Bastelaere Stefaan , Van Damme Wim , Delvaux Thérèse 
Published: July 2021

Abstract
Background
Quality human resources constitute an essential pillar of an effective health system. This paper analyzes the outcomes of blended learning for post-Ebola capacity strengthening of health professionals in Guinea.

Methods
Two courses lasting 3 months each (7–8 modules) were developed and implemented: one in Primary Health Care (eSSP) and the other in Sexual and Reproductive Health Services Management (eSSR). Both eSSP and eSSR courses were offered online on the Moodle platform, followed by a face-to-face capacity-building workshop. A cross-sectional study using a mixed-methods approach was conducted in 2018–19. As outcomes, we described learners’ sociodemographic characteristics, course completion and success, and perceptions of the courses and support from the instructors, analyzed the factors associated with learners’ successful completion and reported on learners’ feedback on their blended learning experience. Quantitative data were analyzed using the STATA 15 software, and qualitative data were analyzed through content analysis.

Results
Overall, 282 health professionals were enrolled for both eSSP and eSSR courses. The completion rate was 69.5% (196/282). The success rate for learners who completed the courses was 80% (156/196), and the overall success rate for enrollees was 55% (156/282). The dropout and abstention rates were 22 and 9%, respectively. On both eSSP and eSSR courses, the success rate of women enrolled was higher than or equal to men’s. The success rate of medical doctors enrolled (53% for eSSP and 67% for eSSR) was higher than for other health professionals, in particular nurses (9% for eSSP) and midwives (40% for eSSR). Course type was associated with success (AOR = 1.93; 95% CI = 1.15–3.24). Most learners strongly agreed that the courses are relevant for targeted health professionals (81 to 150/150), pdf course materials are well-structured and useful (105/150), the content of the modules is relevant, comprehensible, and clear (90/150), self-assessment quizzes are helpful (105/150), summative assessment assignments are relevant (90/150), the course administrators and IT manager were responsive to learners’ concerns (90/150), they will recommend the courses to colleagues and friends (120/150).

Conclusion
Two blended courses for capacity strengthening of health professionals were successfully developed and implemented in Guinea.
Characterization of DNA lesions associated with cell-free DNA by targeted deep sequencing
Authors: Shin Seung-Ho , Park Woong-Yang , Park Donghyun 
Published: July 2021

Abstract
Background
Recently, a next-generation sequencing (NGS)-based method has been used for the successful detection of circulating tumor DNA (ctDNA) in various cancer types. Thus, the use of NGS on liquid biopsies will improve cancer diagnosis and prognosis. However, the low-allelic fraction of ctDNA poses a challenge for the sensitive and specific detection of tumor variants in cell-free DNA (cfDNA). To distinguish true variants from false positives, the characteristics of errors that occur during sample preparation and sequencing need to be elucidated.

Methods
We generated capture-based targeted deep sequencing data from plasma cfDNA and peripheral blood leucocyte (PBL) gDNA to profile background errors. To reveal cfDNA-associated DNA lesions, background error profiles from two sample types were compared in each nucleotide substitution class.

Results
In this study, we determined the prevalence of single nucleotide substitutions in cfDNA sequencing data to identify DNA damage preferentially associated with cfDNA. On comparing sequencing errors between cfDNA and cellular genomic DNA (gDNA), we observed that the total substitution error rates in cfDNA were significantly higher than those in gDNA. When the substitution errors were divided into 12 substitution error classes, C:G>T:A substitution errors constituted the largest difference between cfDNA and gDNA samples. When the substitution error rates were estimated based on the location of DNA-fragment substitutions, the differences in error rates of most substitution classes between cfDNA and gDNA samples were observed only at the ends of the DNA fragments. In contrast, C:G>T:A substitution errors in the cfDNA samples were not particularly associated with DNA-fragment ends. All observations were verified in an independent dataset.

Conclusions
Our data suggested that cytosine deamination increased in cfDNA compared to that in cellular gDNA. Such an observation might be due to the attenuation of DNA damage repair before the release of cfDNA and/or the accumulation of cytosine deamination after it. These findings can contribute to a better understanding of cfDNA-associated DNA damage, which will enable the accurate analysis of somatic variants present in cfDNA at an extremely low frequency.