bluuebunny/crossref_metadata_2025_split huggingface dataset:
An e-consent framework for tiered informed consent for human genomic research in the global south, implemented as a REDCap template
Authors: Tamuhla Tsaone , Tiffin Nicki , Allie Taryn 
Published: November 2022

AbstractResearch involving human participants requires their consent, and it is common practice to capture consent information on paper and store those hard copies, presenting issues such as long-term storage requirements, inefficient retrieval of consent forms for reference or future use, and the potential for transcription errors when transcribing captured informed consent. There have been calls to move to electronic capture of the consent provided by research participants (e-consent) as a way of addressing these issues. A tiered framework for e-consent was designed using the freely available features in the inbuilt REDCap e-consent module. We implemented ‘branching logic’, ‘wet signature’ and ‘auto-archiver’ features to the main informed consent and withdrawal of consent documents. The branching logic feature streamlines the consent process by making follow-up information available depending on participant response, the ‘wet signature’ feature enables a timestamped electronic signature to be appended to the e-consent documents and the ‘auto-archiver’ allows for PDF copies of the e-consent documents to be stored in the database. When designing the content layout, we provided example participant information text which can be modified as required. Emphasis was placed on the flow of information to optimise participant understanding and this was achieved by merging the consent and participant information into one document where the consent questions were asked immediately after the corresponding participant information. In addition, we have provided example text for a generic human genomic research study, which can be easily edited and modified according to specific requirements. Building informed consent protocols and forms without prior experience can be daunting, so we have provided researchers with a REDCap template that can be directly incorporated into REDCap databases. It prompts researchers about the types of consent they can request for genomics studies and assists them with suggestions for the language they might use for participant information and consent questions. The use of this tiered e-consent module can ensure the accurate and efficient electronic capture and storage of the consents given by participants in a format that can be easily queried and can thus facilitate ethical and effective onward sharing of data and samples whilst upholding individual participant preferences.
Nurse-led consultations reinforced with eHealth technology: a qualitative study of the experiences of patients with gynecological cancer
Authors: Skorstad Mette , Vistad Ingvild , Fegran Liv , Berntsen Sveinung , Johannessen Berit 
Published: November 2022

Abstract
Background
During the last decade, the health care profession has moved toward personalized care and has focused on the diversity of survivorship needs after initial cancer treatment. Health care providers encourage empowering patients to participate actively in their own health management and survivorship. Consequently, we developed and piloted a new follow-up model for patients at a Norwegian hospital, referred to as the Lifestyle and Empowerment Techniques in Survivorship of Gynecologic Oncology (LETSGO) model. Using LETSGO, a dedicated nurse replaces the physician in every second follow-up consultation, providing patients who have undergone cancer treatment with self-management techniques that are reinforced with eHealth technology via a specially designed app. Encouraging behavioral change and evaluating the late effects of treatment and recurrence symptoms are central components of self-management techniques. In addition, the app encourages physical activity and positive lifestyle changes, helps identify recurrence-related symptoms, and provides reminders of activity goals. This study aims to investigate experiences with nurse-led consultations supported by eHealth technology among the patients who piloted the LETSGO intervention.

Methods
Semi-structured qualitative interviews were conducted to analyze the participants’ experiences with the LETSGO intervention after six to seven months.

Results
The participants in the LETSGO pilot felt safe and well cared for. They thought the nurse was less busy than the doctors appear to be, which made it easy for them to share any cancer-related challenges. Many participants reported increased empowerment and confidence in recognizing symptoms of cancer recurrence, and participants who used the app regularly were motivated to increase their physical activity levels. However, the participants also experienced some limitations and technical errors with the app.

Conclusions
Generally, the participants positively received the nurse-led consultations and eHealth technology, but an intervention study is required for further evaluation. In addition, the reported technical app errors should be resolved and tested prior to eHealth application implementation. Regardless, this study may be useful in planning personalized survivorship care studies.

Trial registration
ClinicalTrials.gov,NCT03453788. Registration March 5, 2018.
Medicine in older age—perception and assessment of ageing processes by older people and medical and nursing professionals: study protocol for a qualitative focus group design (FOR TiMed_Life)
Authors: Kleinert Evelyn , Mohacsi Laura , Heim Susanne , Hummers Eva 
Published: November 2022

Abstract
Background
This study is conducted by a subproject of the DFG research group "Medicine, Time and the Good Life" FOR 5022 (FOR TiMed_Life) and investigates the care preferences of individuals of advanced age and the care priorities of medical and nursing professionals in times of increasing medical options and more complex decision-making processes, especially for elderly patients. We assume that the preference for or rejection of medical treatment is shaped by individual and social age patterns and by the awareness of the finiteness of life. Just like older people themselves, professionals are also influenced by societal images of age(ing) and associated notions of age-appropriate health. These concepts are subject to constant change, which means that what was considered to be a 'normal' symptom of older age 100 years ago is now treated medically as a disease. The aim of the study is to identify the underlying perceptions of ageing and their influence on medical decisions.

Methods
By means of semi-structured focus group discussions and supplementary individual interviews with older people and medical and nursing professionals, the subproject investigates the perception of ageing processes and the resulting care preferences and priorities of these three groups. The evaluation of the interview material is carried out in two stages: First, the recorded group discussions are pre-structured using knowledge mapping. Based on the mapping results, the interview passages are selected, transcribed, and analysed in detail based on qualitative content analysis.

Discussion
Because the nature of the research question is exploratory, qualitative methods provide a suitable approach. The mapping technique provides early initial results that are used by the other subprojects. Within the research group, the results of the interviews provide an empirical basis for ethical discourses on the influence of medicine on ideas of a good life, and in particular, on successful ageing.

Trial registration
German Clinical Trials Register: DRKS00027076, 05/11/2021.
Development and initial testing of a multi-stakeholder intervention for Lynch syndrome cascade screening: an intervention mapping approach
Authors: Passero Lauren , Srinivasan Swetha , Grewe Mary E. , Leeman Jennifer , Berg Jonathan , Reuland Daniel , Roberts Megan C. 
Published: November 2022

Abstract
Background
Lynch syndrome is an underdiagnosed hereditary condition carrying an increased lifetime risk for colorectal and endometrial cancer and affecting nearly 1 million people in the United States. Cascade screening, systematic screening through family members of affected patients, could improve identification of Lynch syndrome, but this strategy is underused due to multi-level barriers including low knowledge about Lynch syndrome, low access to genetics services, and challenging family dynamics.

Methods
We used intervention mapping, a 6-step methodology to create stakeholder-driven interventions that meet the needs of a target population, to develop an intervention to improve cascade screening for Lynch syndrome. The intervention development process was guided by input from key stakeholders in Lynch syndrome care and patients. We conducted usability testing on the intervention with Lynch syndrome patients using qualitative semi-structured interviewing and rapid qualitative analysis.

Results
We developed a workbook intervention named Let’s Talk that addresses gaps in knowledge, skills, self-efficacy, outcome expectancy and other perceived barriers to cascade screening for Lynch syndrome. Let’s Talk contained educational content, goal setting activities, communication planning prompts and supplemental resources for patients to plan family communication. Evidence-based methods used in the workbook included information chunking, guided practice, goal setting and gain-framing. We conducted usability testing focused on the complexity and relative advantage of the intervention through 45-min virtual interviews with 10 adult patients with Lynch syndrome recruited from a national advocacy organization in the United States. Usability testing results suggested the intervention was acceptable in terms of complexity and relative advantage to other available resources, but additional information for communication with young or distant family members and a web-based platform could enhance the intervention’s usability.

Conclusions
Intervention mapping provided a framework for intervention development that addressed the unique needs of Lynch syndrome patients in overcoming barriers to cascade screening. Future work is needed to transform Let’s Talk into a web-based tool and evaluate the effectiveness of the intervention in clinical practice with patients and genetic counselors. Intervention mapping can be useful to researchers as an evidence-based technique to develop stakeholder-centered interventions for addressing the needs of other unique populations.
Effective hospital readmission prediction models using machine-learned features
Authors: Davis Sacha , Zhang Jin , Lee Ilbin , Rezaei Mostafa , Greiner Russell , McAlister Finlay A. , Padwal Raj 
Published: November 2022

Abstract
Background:
Hospital readmissions are one of the costliest challenges facing healthcare systems, but conventional models fail to predict readmissions well. Many existing models use exclusively manually-engineered features, which are labor intensive and dataset-specific. Our objective was to develop and evaluate models to predict hospital readmissions using derived features that are automatically generated from longitudinal data using machine learning techniques.

Methods:
We studied patients discharged from acute care facilities in 2015 and 2016 in Alberta, Canada, excluding those who were hospitalized to give birth or for a psychiatric condition. We used population-level linked administrative hospital data from 2011 to 2017 to train prediction models using both manually derived features and features generated automatically from observational data. The target value of interest was 30-day all-cause hospital readmissions, with the success of prediction measured using the area under the curve (AUC) statistic.

Results:
Data from 428,669 patients (62% female, 38% male, 27% 65 years or older) were used for training and evaluating models: 24,974 (5.83%) were readmitted within 30 days of discharge for any reason. Patients were more likely to be readmitted if they utilized hospital care more, had more physician office visits, had more prescriptions, had a chronic condition, or were 65 years old or older. The LACE readmission prediction model had an AUC of 0.66 ± 0.0064 while the machine learning model’s test set AUC was 0.83 ± 0.0045, based on learning a gradient boosting machine on a combination of machine-learned and manually-derived features.

Conclusion:
Applying a machine learning model to the computer-generated and manual features improved prediction accuracy over the LACE model and a model that used only manually-derived features. Our model can be used to identify high-risk patients, for whom targeted interventions may potentially prevent readmissions.
Noninvasive detection of pancreatic ductal adenocarcinoma using the methylation signature of circulating tumour DNA
Authors: Wu Huanwen , Guo Shiwei , Liu Xiaoding , Li Yatong , Su Zhixi , He Qiye , Liu Xiaoqian , Zhang Zhiwen , Yu Lianyuan , Shi Xiaohan , Gao Suizhi , Wang Huan , Pan Yaqi , Ma Chengcheng , Liu Rui , Dai Menghua , Jin Gang , Liang Zhiyong 
Published: November 2022

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) has the lowest overall survival rate primarily due to the late onset of symptoms and rapid progression. Reliable and accurate tests for early detection are lacking. We aimed to develop a noninvasive test for early PDAC detection by capturing the circulating tumour DNA (ctDNA) methylation signature in blood.

Methods
Genome-wide methylation profiles were generated from PDAC and nonmalignant tissues and plasma. Methylation haplotype blocks (MHBs) were examined to discover de novo PDAC markers. They were combined with multiple cancer markers and screened for PDAC classification accuracy. The most accurate markers were used to develop PDACatch, a targeted methylation sequencing assay. PDACatch was applied to additional PDAC and healthy plasma cohorts to train, validate and independently test a PDAC-discriminating classifier. Finally, the classifier was compared and integrated with carbohydrate antigen 19-9 (CA19-9) to evaluate and maximize its accuracy and utility.

Results
In total, 90 tissues and 546 plasma samples were collected from 232 PDAC patients, 25 chronic pancreatitis (CP) patients and 323 healthy controls. Among 223 PDAC cases with known stage information, 43/119/38/23 cases were of Stage I/II/III/IV. A total of 171 de novo PDAC-specific markers and 595 multicancer markers were screened for PDAC classification accuracy. The top 185 markers were included in PDACatch, from which a 56-marker classifier for PDAC plasma was trained, validated and independently tested. It achieved an area under the curve (AUC) of 0.91 in both the validation (31 PDAC, 26 healthy; sensitivity = 84%, specificity = 89%) and independent tests (74 PDAC, 65 healthy; sensitivity = 82%, specificity = 88%). Importantly, the PDACatch classifier detected CA19-9-negative PDAC plasma at sensitivities of 75 and 100% during the validation and independent tests, respectively. It was more sensitive than CA19-9 in detecting Stage I (sensitivity = 80 and 68%, respectively) and early-stage (Stage I-IIa) PDAC (sensitivity = 76 and 70%, respectively). A combinatorial classifier integrating PDACatch and CA19-9 outperformed (AUC=0.94) either PDACatch (0.91) or CA19-9 (0.89) alone (p < 0.001).

Conclusions
The PDACatch assay demonstrated high sensitivity for early PDAC plasma, providing potential utility for noninvasive detection of early PDAC and indicating the effectiveness of methylation haplotype analyses in discovering robust cancer markers.

Graphic Abstract
Does intraoperative cyst rupture of malignant cystic renal masses really have no negative impact on oncologic outcomes?
Authors: Xu Peirong , Zhang Sihong , Cao Bohong , Huang Jiaqi , Li Yaohui , Cheng Jiangting , Lin Wenyao , Cheng Jie , Chen Weijie , Zhu Yanjun , Jiang Shuai , Hu Xiaoyi , Guo Jianming , Wang Hang 
Published: November 2022

Abstract
Background
To assess the impact of malignant cystic renal masses (CRM) rupture on oncologic outcomes.

Methods
The study included 406 cases with partial nephrectomy (PN) and 17 cases with cyst decortication confirmed as malignant CRM by pathology. Recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank test. Cox regression was used to identify risk factors associated with RFS, MFS, CSS, and OS. Logistic regression was performed to explore predictors of rupture.

Results
Tumor rupture occurred in 32 of 406 cases (7.9%). With median follow-up of 43 months, 4 (12.5%) and 5 (1.3%) cases experienced recurrence in rupture and non-rupture group, respectively (P = 0.003). Estimated RFS, MFS, and CSS were shorter in cyst ruptured (CR) group than non-ruptured (nonCR) cases (P < 0.001; P = 0.001; P < 0.001). Cox regression analysis indicated that CR was an independent prognostic factor for RFS (HR = 7.354; 95% CI = 1.839–29.413; P = 0.005), MFS (HR = 8.069; 95% CI = 1.804–36.095; P = 0.006), and CSS (HR = 9.643; 95% CI = 2.183–42.599; P = 0.003). Multivariable logistic regression showed that Bosniak IV was a protective factor for CR (OR = 0.065; 95% CI = 0.018–0.239; P < 0.001). However, compared to Bosniak III and I-IIF, Bosniak IV CRMs showed higher rate of clear cell renal cell carcinoma (ccRCC) (76.8% vs 36.5% vs 81.4%) (P < 0.001) and lower rate of Fuhrman I staging (11.2% vs 66.7% vs 7.4%) (P < 0.001). Therefore, in ruptured cases, the recurrence rate was higher in CRM with Bosniak IV (50%, 2/4) than Bosniak I-III (4.4%, 2/45) (P = 0.029).

Conclusions
Intraoperative malignant CRM rupture had negative impacts on oncologic outcomes. Bosniak IV was more aggressive than Bosniak I-III and had a higher risk of recurrence after rupture. However, Bosniak IV had a lower risk of rupture, which could weaken even cover-up of the true effect of tumor rupture on oncologic outcomes.
Assessment of antibody responses against SARS-CoV-2 in unvaccinated individuals and vaccinees from Omicron-BA.2 infection in Zhaoqing, Guangdong Province, China
Authors: Zhang Huan , Jiang Yushan , Tan Hanqing , Zou Lirong , Zheng Zhonghua , Huang Yushi , Lin Shujian , Su Lebin , Yu Jianxiang , Deng Xiaoling , He Jianfeng , Liu Chang , Shen Chenguang , Li Baisheng 
Published: November 2022

AbstractCurrently, the majority of the global population has been vaccinated with the COVID-19 vaccine, and characterization studies of antibodies in vivo from Omicron breakthrough infection and naive infection populations are urgently needed to provide pivotal clues about accurate diagnosis, treatment, and next-generation vaccine design against SARS-CoV-2 infection. We showed that after infection with Omicron-BA.2, the antibody levels of specific IgM against the Wuhan strain and specific IgG against Omicron were not significantly elevated within 27 days of onset. Interestingly, in this study, the levels of humoral immunity against Omicron-specific IgM were significantly increased after breakthrough infection, suggesting that the detection of Omicron-specific IgM antibodies can be used as a test criterion of Omicron breakthrough infection. In addition, we observed that serums from unvaccinated individuals and the majority of vaccinated infections possessed only low or no neutralizing activity against Omicron at the onset of Omicron breakthrough infections, and at the later stage of Omicron-BA.2 breakthrough infection, levels of neutralization antibody against the Wuhan and Omicron strains were elevated in infected individuals. The findings of this study provide important clues for the diagnosis of Omicron breakthrough infections, antibody characterization studies and vaccine design against COVID-19.
Transcriptomic analysis of a 3D blood–brain barrier model exposed to disturbed fluid flow
Authors: Bouhrira Nesrine , DeOre Brandon J. , Tran Kiet A. , Galie Peter A. 
Published: November 2022

AbstractCerebral aneurysms are more likely to form at bifurcations in the vasculature, where disturbed fluid is prevalent due to flow separation at sufficiently high Reynolds numbers. While previous studies have demonstrated that altered shear stress exerted by disturbed flow disrupts endothelial tight junctions, less is known about how these flow regimes alter gene expression in endothelial cells lining the blood–brain barrier. Specifically, the effect of disturbed flow on expression of genes associated with cell–cell and cell–matrix interaction, which likely mediate aneurysm formation, remains unclear. RNA sequencing of immortalized cerebral endothelial cells isolated from the lumen of a 3D blood–brain barrier model reveals distinct transcriptional changes in vessels exposed to fully developed and disturbed flow profiles applied by both steady and physiological waveforms. Differential gene expression, validated by qRT-PCR and western blotting, reveals that lumican, a small leucine-rich proteoglycan, is the most significantly downregulated gene in endothelial cells exposed to steady, disturbed flow. Knocking down lumican expression reduces barrier function in the presence of steady, fully developed flow. Moreover, adding purified lumican into the hydrogel of the 3D blood–brain barrier model recovers barrier function in the region exposed to fully developed flow. Overall, these findings emphasize the importance of flow regimes exhibiting spatial and temporal heterogeneous shear stress profiles on cell–matrix interaction in endothelial cells lining the blood–brain barrier, while also identifying lumican as a contributor to the formation and maintenance of an intact barrier.
Prevalence and impact of peer victimisation among youth seeking treatment at a tertiary psychiatric institution in Singapore: a cross-sectional study
Authors: Subramaniam Mythily , Shahwan Shazana , Abdin Edimansyah , Verma Swapna , Gupta Bhanu , Chua Boon Yiang , Zhang Yunjue , Sambasivam Rajeswari , Chong Siow Ann 
Published: November 2022

Abstract
Background
Peer victimization is common among adolescents and leads to negative consequences. However, few studies have examined the extent of peer-victimization and its correlates among adolescent patients in a psychiatric setting. The current study aimed to examine the prevalence and correlates of peer victimisation among youth with mental illness and to examine its association with depressive symptoms and health-related quality of life (HRQOL).

Methods
A sample of 239 youths aged 15–24 years were recruited from the outpatient clinics of a tertiary psychiatric hospital in Singapore using convenience sampling. All participants were administered the Multidimensional Peer Victimisation Scale (MPVS), Short Form 12 (SF-12) questionnaire and the Patient Health Questionnaire-8 (PHQ-8). The effect of MPVS total and subscores on depression scores, quality of life subscores and quality of life total scores were examined using multiple linear regression analyses.

Results
The majority of the patients reported that they had experienced at least one form of peer victimisation (95.8%, n = 229) during their school years. Higher levels of ‘verbal victimisation’, ‘attacks on property’ and higher total MPVS scores were significantly associated with lower social functioning; additionally, higher levels of ‘verbal victimisation’ were significantly associated with lower mental component summary scores in the quality of life assessment. Higher scores on all four subscales as well as higher total scores on the MPVS were significantly associated with more severe depressive symptoms.

Conclusions
Given the high prevalence of peer victimisation in our sample and its associations with more severe depressive symptoms and lower quality of life, it is vital to implement interventions that prevent peer victimisation in educational and other social settings and to provide youth with strategies to more effectively manage instances of peer victimisation.