bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a first-trimester prognostic model to improve screening for gestational diabetes mellitus
Authors:   On behalf of the RESPECT 2 study group, van Hoorn Fieke , Koster Maria P. H. , Kwee Anneke , Groenendaal Floris , Franx Arie , Bekker Mireille N. 
Published: April 2021

Abstract
Background
Improvement in the accuracy of identifying women who are at risk to develop gestational diabetes mellitus (GDM) is warranted, since timely diagnosis and treatment improves the outcomes of this common pregnancy disorder. Although prognostic models for GDM are externally validated and outperform current risk factor based selective approaches, there is little known about the impact of such models in day-to-day obstetric care.

Methods
A prognostic model was implemented as a directive clinical prediction rule, classifying women as low- or high-risk for GDM, with subsequent distinctive care pathways including selective midpregnancy testing for GDM in high-risk women in a prospective multicenter birth cohort comprising 1073 pregnant women without pre-existing diabetes and 60 obstetric healthcare professionals included in nine independent midwifery practices and three hospitals in the Netherlands (effectiveness-implementation hybrid type 2 study). Model performance (c-statistic) and implementation outcomes (acceptability, adoption, appropriateness, feasibility, fidelity, penetration, sustainability) were evaluated after 6 months by indicators and implementation instruments (NoMAD; MIDI).

Results
The adherence to the prognostic model (c-statistic 0.85 (95%CI 0.81–0.90)) was 95% (n = 1021). Healthcare professionals scored 3.7 (IQR 3.3–4.0) on implementation instruments on a 5-point Likert scale. Important facilitators were knowledge, willingness and confidence to use the model, client cooperation and opportunities for reconfiguration. Identified barriers mostly related to operational and organizational issues. Regardless of risk-status, pregnant women appreciated first-trimester information on GDM risk-status and lifestyle advice to achieve risk reduction, respectively 89% (n = 556) and 90% (n = 564)).

Conclusions
The prognostic model was successfully implemented and well received by healthcare professionals and pregnant women. Prognostic models should be recommended for adoption in guidelines.
Carnitine palmitoyl transferase 1A is a novel diagnostic and predictive biomarker for breast cancer
Authors: Tan Zheqiong , Zou Yaru , Zhu Man , Luo Zhenzhao , Wu Tangwei , Zheng Chao , Xie Aqing , Wang Hui , Fang Shiqiang , Liu Shuiyi , Li Yong , Lu Zhongxin 
Published: April 2021

Abstract
Background
Carnitine palmitoyl transferase 1A (CPT1A), the key regulator of fatty acid oxidation, contributes to tumor metastasis and therapeutic resistance. We aimed to identify its clinical significance as a biomarker for the diagnosis and prediction of breast cancer.

Methods
Western blot, ELISA and in silico analysis were used to confirm CPT1A levels in breast cancer cell lines, cell culture medium and breast cancer tissues. Four hundred thirty breast cancer patients, 200 patients with benign breast disease, and 400 healthy controls were enrolled and randomly divided into a training set and a test set with a 7:3 ratio. Training set was used to build diagnostic models and 10-fold cross validation was used to demonstrate the performance of the models. Then test set was aimed to validate the effectiveness of the diagnostic models. ELISA was conducted to detect individual serum CPT1A levels. Receiver operating characteristic (ROC) curves were generated, and binary logistic regression analyses were performed to evaluate the effectiveness of CPT1A as a biomarker in breast cancer diagnosis. CPT1A levels between post-operative and pre-operative samples were also compared.

Results
CPT1A was overexpressed in breast cancer tissues, cell lines and cell culture medium. Serum CPT1A levels were higher in breast cancer patients than in controls and were significantly associated with metastasis, TNM stage, histological grading and molecular subtype. CPT1A levels were decreased in post-operative samples compared with paired pre-operative samples. Moreover, CPT1A exhibited a higher efficacy in differentiating breast cancer patients from healthy controls (training set: area under the curve, AUC, 0.892, 95% CI, 0.872–0.920; test set, AUC, 0.904, 95% CI, 0.869–0.939) than did CA15–3, CEA, or CA125.

Conclusion
CPT1A is overexpressed in breast cancer and can be secreted out of breast cancer cell. Serum CPT1A is positively associated with breast cancer progression and could serve as an indicator for disease monitoring. Serum CPT1A displayed a remarkably high diagnostic efficiency for breast cancer and could be a novel biomarker for the diagnosis of breast cancer.
Role of palliative radiotherapy in bleeding control in patients with unresectable advanced gastric cancer
Authors: Yu Jesang , Jung Jinhong , Park Sook Ryun , Ryu Min-Hee , Park Jin-hong , Kim Jong Hoon , Yoon Sang Min 
Published: April 2021

Abstract
Background
This study analyzed the clinical results of palliative radiotherapy for bleeding control in patients with unresectable advanced gastric cancer.

Methods
We retrospectively reviewed the medical records of patients who met the following inclusion criteria between January 2002 and June 2018: histologically proven gastric cancer, gastric tumor bleeding confirmed by upper gastrointestinal endoscopy, and palliative radiotherapy performed for hemostasis. The median radiotherapy dose was 30 Gy, with a daily dose ranging from 1.8 to 3 Gy.

Results
Sixty-one patients were included in this analysis. The study population was predominantly male (72.1%), with a median age of 62 years (range: 32–92). The median baseline hemoglobin level was 7.1 g/dL, and the most common presenting symptom of gastric tumor bleeding was melena (85.2%). Bleeding control was achieved in 54 (88.5%) patients. The median levels of hemoglobin at 1, 2, and 3 months after completion of radiotherapy were 10.1 g/dL, 10.2 g/dL, and 10.4 g/dL, respectively; these values were significantly different from that before radiotherapy (7.1 g/dL; p < 0.001). The median overall survival was 4.8 months. Among the 54 patients who achieved bleeding control after radiotherapy, 19 (35.2%) experienced re-bleeding during the follow-up period. The median time to re-bleeding was 6.0 months. Multivariate analysis demonstrated that a higher radiation dose (p = 0.007) and additional chemotherapy after radiotherapy (p = 0.004) were significant factors for prolonging the time to re-bleeding.

Conclusions
Tumor bleeding was adequately controlled by radiotherapy in patients with unresectable advanced gastric cancer.
The mediation effect of serum metabolites on the relationship between long-term smoking exposure and esophageal squamous cell carcinoma
Authors: Wei Mengke , Zhao Lihong , Lv Jiali , Li Xia , Zhou Guangshuai , Fan Bingbing , Shen Xiaotao , Zhao Deli , Xue Fuzhong , Wang Jialin , Zhang Tao 
Published: April 2021

Abstract
Background
Long-term smoking exposure will increase the risk of esophageal squamous cell carcinoma (ESCC), whereas the mechanism is still unclear. We conducted a cross-sectional study to explore whether serum metabolites mediate the occurrence of ESCC caused by cigarette smoking.

Methods
Serum metabolic profiles and lifestyle information of 464 participants were analyzed. Multiple logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of smoking exposure to ESCC risk. High-dimensional mediation analysis and univariate mediation analysis were performed to screen potential intermediate metabolites of smoking exposure for ESCC.

Results
Ever smoking was associated with a 3.11-fold increase of ESCC risk (OR = 3.11, 95% CI 1.63–6.05), and for each cigarette-years increase in smoking index, ESCC risk increased by 56% (OR = 1.56, 95% CI 1.18–2.13). A total of 5 metabolites were screened as mediators by high-dimensional mediation analysis. In addition, glutamine, histidine, and cholic acid were further proved existing mediation effects according to univariate mediation analysis. And the proportions of mediation of histidine and glutamine were 40.47 and 30.00%, respectively. The mediation effect of cholic acid was 8.98% according to the analysis of smoking index.

Conclusions
Our findings suggest that cigarette smoking contributed to incident ESCC, which may be mediated by glutamine, histidine and cholic acid.
The diagnostic and prognostic value of H2AFY in hepatocellular carcinoma
Authors: Ma Xuyang , Ding Ying , Zeng Li 
Published: April 2021

Abstract
Background
The potential correlation between H2AFY (also known as MacroH2A1) and the clinical characteristics of hepatocellular carcinoma (HCC) patients was analysed through gene expression profiles and clinical data in The Cancer Genome Atlas (TCGA) database, and the diagnostic and prognostic value of H2AFY in HCC was discussed.

Methods
The gene expression data of HCC and the corresponding clinical characteristics of HCC patients were downloaded from the TCGA database. The differences in H2AFY in normal liver tissues and HCC were analysed. The relationship between H2AFY and clinical characteristics was analysed by Wilcoxon signed-rank test, logistic regression and Kruskal-Wallis test. The Kaplan-Meier method and the Cox regression method were used to analyse the relationship between overall survival and clinical characteristics of the patients. An ROC curve was used to predict the diagnostic value of H2AFY in HCC. Gene set enrichment analysis (GSEA) was used to analyse the pathway enrichment of H2AFY.

Result
Compared with normal liver tissues, H2AFY was significantly highly expressed in HCC. H2AFY was positively correlated with the age, clinical stage, G stage (grade) and T stage (tumor stage) of liver cancer patients. Higher H2AFY expression predicted a poor prognosis in HCC patients. Cox regression analysis suggested that H2AFY was an independent risk factor for the prognosis of HCC patients. The ROC curve suggested that H2AFY had certain diagnostic value in HCC. GSEA suggested that H2AFY was correlated with lipid metabolism and a variety of tumour pathways.

Conclusion
Our study showed that H2AFY was significantly overexpressed in HCC. H2AFY may be a potential diagnostic and prognostic marker for HCC, and high expression of H2AFY predicts a poor prognosis in patients with HCC.
Novel mutations in the PHKB gene in an iranian girl with severe liver involvement and glycogen storage disease type IX: a case report and review of literature
Authors: Beyzaei Zahra , Ezgu Fatih , Geramizadeh Bita , Alborzi Alireza , Shojazadeh Alireza 
Published: April 2021

Abstract
Background
Glycogen storage disease (GSD) type IXb is one of the rare variants of GSDs. It is a genetically heterogeneous metabolic disorder due to deficient hepatic phosphorylase kinase activity. Diagnosis of GSD can be difficult because of overlapping manifestations. Mutation analysis of the genes related to each type of GSD is supposed to be problem-solving, however, the presence of novel mutations can be confusing. In this case report, we will describe our experience with a young girl with the diagnosis of GSD and two novel mutations related to GSD type IXb.

Case presentation
A 3-year- old girl presented with short stature, hepatomegaly, and liver cirrhosis. No specific diagnosis was made based on laboratory data, so liver biopsy and targeted-gene sequencing (TGS) were performed to find out the specific molecular basis of her disease. It was confirmed that the patient carries two novel variants in the PHKB gene. The variant in the PHKB gene was classified as pathogenic.

Conclusions
This is the first reported case of a dual molecular mutation of glycogen storage disease type IXb in the same patient. Two novel variants in PHKB were identified and one of them was a pathogenic split-site mutation. In conclusion, for the first time, identification of the novel variants in this patient expands the molecular and the phenotype basis of dual variants in GSD-IXb.
Caffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report
Authors: Yartsev Alex , Peisah Carmelle 
Published: April 2021

Abstract
Background
Caffeine is a known inhibitor of Clozapine metabolism mediated by inhibition of CYP1A2. Hitherto, the effects of caffeine on Clozapine levels have always been modest, as have the clinical manifestations of toxicity resulting from their interaction. We present a case of severe toxicity associated with the co-consumption of caffeine and Clozapine culminating in life-threatening complications requiring management in Intensive Care.

Case presentation
A 34 year old male with a history of chronic schizophrenia, who had been managed stably on 400 mg Clozapine for the previous 5 years, changed his dietary behaviour and began consuming caffeine-containing energy drinks over the course of 3 weeks. The total daily dose of caffeine was estimated as 600 mg/day (four cans of Red Bull). He subsequently presented to the Emergency Department with life-threatening Clozapine toxicity, resulting in a decreased level of consciousness, severe metabolic acidosis, acute respiratory failure, raised inflammatory markers and acute renal failure attributed to interstitial nephritis. Maximum recorded Clozapine level was 1796 ng/ml.

Conclusions
This case describes the interaction between a common caffeine-containing beverage and a commonly prescribed antipsychotic medication, associated with severe adverse effects. We call for clinical and scientific attention to the possible interaction between these substances and draw attention to the implications for prescribing practices and patient counselling.
Developing and testing of an interactive internet-based intervention to reduce sexual harm of sexualised drug use (‘chemsex’) among men who have sex with men in Hong Kong: a study protocol for a randomised controlled trial
Authors: Choi Edmond P. H. , Chau Pui Hing , Wong William C. W. , Kowk Jojo Y. Y. , Choi Kitty W. Y. , Chow Eric P. F. 
Published: April 2021

Abstract
Background
Sexualised drug use, known as ‘chemsex’ or ‘chemfun,’ is the practice of intentionally using illicit drugs before or during sexual activates to enhance sexual arousal and pleasure. International and local data have both suggested that chemsex is common among men who have sex with men (MSM). Chemsex is generally seen with the engagement of risky sexual activities and therefore poses a threat regarding the potentially increased spread of human immunodeficiency virus and other sexually transmitted infections. However, little work has been done on the primary prevention of chemsex among MSM. Therefore, the aim of this study is to develop and evaluate an interactive internet-based intervention in reducing the sexual harms of chemsex among MSM in Hong Kong,

Methods
A two-armed, randomised, parallel-group trial with a three-month follow-up period will be conducted. 250 MSM aged 18 years or the above will be recruited through local non-governmental organisations, social media and by snowballing in Hong Kong. Participants will be randomly allocated into either the intervention (n = 125) or control group (n = 125). The interactive internet-based intervention will be developed based on the theory of planned behaviours. Participants in the control group will receive a web-based intervention without any sexual health information and without any interactive components. The primary outcomes will be self-efficacy in refusing risky sexual behaviours and chemsex, as measured by the Drug Avoidance Self-Efficacy Scale, the Self-Efficacy for Sexual Safety and the Condom Self-Efficacy Scale. Subjects in both groups will be evaluated at baseline and 3 months after baseline.

Discussion
To the best of our knowledge, this will be the first interactive internet-based intervention to specifically target chemsex among MSM. This project can help in the development and testing of culturally relevant health promotion programmes that reduce chemsex among MSM. Using an online delivery mode, the intervention is capable of reaching a large population of targets at a relatively low cost and thus has the potential to reduce the public health burden of chemsex and other risky sexual behaviours among MSM in a cost-effective manner.

Trial registration
International standard randomized controlled trial number (ISRCTN) registry: ISRCTN20134522 registered on 17 March 2021.
Revisiting the continuum of resistance model in the digital age: a comparison of early and delayed respondents to the Norwegian counties public health survey
Authors: Clarsen Benjamin , Skogen Jens Christoffer , Nilsen Thomas Sevenius , Aarø Leif Edvard 
Published: April 2021

Abstract
Background
The continuum of resistance model’s premise is that delayed respondents to a survey are more similar to non-respondents than early respondents are. For decades, survey researchers have applied this model in attempts to evaluate and adjust for non-response bias. Despite a recent resurgence in the model’s popularity, its value has only been assessed in one large online population health survey.

Methods
Respondents to the Norwegian Counties Public Health Survey in Hordaland, Norway, were divided into three groups: those who responded within 7 days of the initial email/SMS invitation (wave 1, n = 6950); those who responded after 8 to 14 days and 1 reminder (wave 2, n = 4950); and those who responded after 15 or more days and 2 reminders (wave 3, n = 4045). Logistic regression analyses were used to compare respondents’ age, sex and educational level between waves, as well as the prevalence of poor general health, life dissatisfaction, mental distress, chronic health problems, weekly alcohol consumption, monthly binge drinking, daily smoking, physical activity, low social support and receipt of a disability pension.

Results
The overall response to the survey was 41.5%. Respondents in wave 1 were more likely to be older, female and more highly educated than those in waves 2 and 3. However, there were no substantial differences between waves for any health outcomes, with a maximal prevalence difference of 2.6% for weekly alcohol consumption (wave 1: 21.3%, wave 3: 18.7%).

Conclusions
There appeared to be a mild continuum of resistance for demographic variables. However, this was not reflected in health and related outcomes, which were uniformly similar across waves. The continuum of resistance model is unlikely to be useful to adjust for nonresponse bias in large online surveys of population health.
The epidemiological trends in the burden of lung cancer attributable to PM2.5 exposure in China
Authors: Wu Xiaomei , Zhu Bo , Zhou Jin , Bi Yifei , Xu Shuang , Zhou Baosen 
Published: April 2021

Abstract
Objective
PM2.5, which is a major contributor to air pollution, has large effects on lung cancer mortality. We want to analyse the long-term trends in lung cancer burden attributable to PM2.5 exposure and provide evidence that can be used for preventive measures and health resource planning.

Methods
Mortality data related to lung cancer were obtained from the Global Burden of Disease (GBD) 2019 project. A joinpoint regression analysis was used to assess the magnitude and direction of the trends in mortality from 1990 to 2019, and the age-period-cohort method was used to analyse the temporal trends in the mortality rate of lung cancer attributable to PM2.5 exposure by age, period, and cohort.

Results
From 1990 to 2019, the age-standardized mortality rate (ASMR) attributable to PM2.5 exposure trended slowly upwards, and the ASMR due to ambient PM2.5 exposure (APE) increased significantly, that due to household PM2.5 exposure (HPE) decreased. The longitudinal age curves show that the mortality rates due to PM2.5 exposure among younger individuals were low, and they significantly increased from their levels among those in the 45–49 age group to their levels among those in the over-85 age group. From 1990 to 2019, the period RRs due to APE increased, but those due to HPE decreased. Similar trends were observed in the cohort RRs. The overall net drift per year attributable to PM2.5 exposure was below 0. The local drift values increased with age and were above 0 for the over-80 age groups. The overall net drifts per year were above zero for APE and below zero for HPE. The corresponding results among males were higher than those among females.

Conclusions
In China, the type of air pollution responsible for lung cancer has changed from household air pollution to ambient air pollution. PM2.5 exposure is more harmful among males and older people. Ambient air pollution should be emphasized, and China should strengthen its implementation of effective public policies and other interventions.
The understanding, acceptability, and relevance of personalised multidimensional physical activity feedback among urban adults: evidence from a qualitative feasibility study in Sri Lanka
Authors: Arambepola Carukshi , Perera Madhawa , Gillison Fiona , Peacock Oliver , Thompson Dylan 
Published: April 2021

Abstract
Background
Wearable technologies are being used to provide personalised feedback across multiple physical activity dimensions in countries such as the UK, but their feasibility has not been tested in South Asia, where physical inactivity is increasing. This study assessed the understanding, acceptability, and relevance of personalised multidimensional physical activity feedback in urban dwellers in Colombo, Sri Lanka.

Methods
A qualitative feasibility study was conducted among 35 adults to assess a community-based approach to provide multidimensional physical activity feedback. Healthy adults, adults at risk of non-communicable diseases and community-based primary healthcare professionals wore a physical activity monitor for 7 days and were then guided through their personalised multidimensional physical activity feedback. One-to-one interviews were conducted, transcribed verbatim and analysed using framework analysis.

Results
Four themes were generated: understanding of personalised physical activity feedback, perceived novelty of the feedback, motivation, and consideration of the multidimensional nature of physical activity. A majority of participants required guidance initially to understand the feedback, following which most were quickly able to interpret the data shown, and were willing to use the feedback as a basis for identifying goals to improve physical activity. Participants perceived the feedback and its delivery as novel because it provided new knowledge about physical activity guidelines and awareness on their own behaviour through graphics. Comparisons of personal performance against recommended physical activity levels and information on sedentary time were the most commonly motivating aspects of the feedback, prompting talk about behaviour change. All three groups showed poor planning on goal achievement, with some noticeable differences between those with and without health risk of non-communicable diseases. Following the feedback, most participants understood that physical activity is composed of several dimensions, while around half could recognise more suitable options to change behaviour. Of the physical activity dimensions, calorie burn received more attention than others.

Conclusions
Multidimensional physical activity feedback was considered understandable and acceptable and has the potential to support behaviour change among urban Sri Lankans with or without identified health risk. These findings highlight the feasibility of this technology-enabled approach as a personalised intervention to improve knowledge and motivation for physical activity behaviour.