bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of the role of Cuproptosis genes and their related long non-coding RNA in clear cell renal cell carcinoma: a comprehensive bioinformatics study
Authors: Xia Dian , Liu Qi , Jiao Wen , Peng Longfei , Wang Qi , Tuo ZhouTing , Bi Liangkuan 
Published: November 2022

AbstractClear cell renal cell carcinoma is a common malignant tumor of the urinary system. The mechanism of its occurrence and development is unknown, and there is currently few effective comprehensive predictive markers for prognosis and treatment response. With the discovery of a new cell death process – cuproptosis drew the attention of researchers. We constructed a model for the prediction of clinical prognosis and immunotherapy response through integrative analysis of gene expression datasets from KIRC samples in The Cancer Genome Atlas (TCGA) database. During the course of the study, we found that cuproptosis genes are significantly differentially expressed between clear cell renal cell carcinoma samples and normal samples. Based on this, we put forward the prognostic model for cuproptosis gene related-long non-coding RNA. And through various statistic and external independent cohorts, we proved that the model is accurate and stable, worthy of clinical application and further exploration and validation.
Oral cancer patients experience mechanical and chemical sensitivity at the site of the cancer
Authors: Sawicki Caroline M. , Janal Malvin N. , Nicholson Samuel J. , Wu Angie K. , Schmidt Brian L. , Albertson Donna G. 
Published: November 2022

Abstract
Introduction
Oral cancer patients suffer severe chronic and mechanically-induced pain at the site of the cancer. Our clinical experience is that oral cancer patients report new sensitivity to spicy foods. We hypothesized that in cancer patients, mechanical and chemical sensitivity would be greater when measured at the cancer site compared to a contralateral matched normal site.

Methods
We determined mechanical pain thresholds (MPT) on the right and left sides of the tongue of 11 healthy subjects, and at the cancer and contralateral matched normal site in 11 oral cancer patients in response to von Frey filaments in the range of 0.008 to 300 g (normally not reported as painful). We evaluated chemical sensitivity in 13 healthy subjects and seven cancer patients, who rated spiciness/pain on a visual analog scale in response to exposure to six paper strips impregnated with capsaicin (0–10 mM).

Results
Mechanical detection thresholds (MDT) were recorded for healthy subjects, but not MPTs. By contrast, MPTs were measured at the site of the cancer in oral cancer patients (7/11 patients). No MPTs were measured at the cancer patients’ contralateral matched normal sites. Measured MPTs were correlated with patients’ responses to the University of California Oral Cancer Pain Questionnaire. Capsaicin sensitivity at the site of the cancer was evident in cancer patients by a leftward shift of the cancer site capsaicin dose-response curve compared to that of the patient’s contralateral matched normal site. We detected no difference in capsaicin sensitivity on the right and left sides of tongues of healthy subjects.

Conclusions
Mechanical and chemical sensitivity testing was well tolerated by the majority of oral cancer patients. Sensitivity is greater at the site of the cancer than at a contralateral matched normal site.
Prevalence and determinants of hypertension among urban slum dwellers in Bangladesh
Authors: Mistry Sabuj Kanti , Hossain Md. Belal , Parvez Mahmood , Gupta Rajat Das , Arora Amit 
Published: November 2022

Abstract
Background
In low- and middle- income countries such as Bangladesh, urban slum dwellers are particualry vulnerable to hypertension due to inadequate facilities for screening and management, as well as inadequate health literacy among them. However, there is scarcity of evidence on hypertension among the urban slum dwellers in Bangladesh. The present study aimed to determine the prevalence and factors associated with hypertension among urban slum dwellers in Bangladesh.

Methods
Data were collected as part of a large-scale cross-sectional survey conducted by Building Resources Across Communities (BRAC) between October 2015 and January 2016. The present analysis was performed among 1155 urban slum dwellers aged 35 years or above. A structured questionnaire was adminstered to collect data electronically and blood pressure measurements were taken using standardised procedures. Binary logistic regression with generalized estimating equation modelling was performed to estimate the factors associated with hypertension.

Results
The prevalence of hypertension was 28.3% among urban slum dwellers aged 35 years and above. In adjusted analysis, urban slum dwellers aged 45–54 years (AOR: 1.64, 95% CI: 1.17–2.28), 55–64 years (AOR: 2.47, 95% CI: 1.73–3.53) and ≥ 65 years (AOR: 2.34, 95% CI: 1.47–3.72), from wealthier households (AOR: 1.94, 95% CI: 1.18–3.20), sleeping < 7 h per day (AOR: 1.87, 95% CI: 1.39–2.51), who were overweight (AOR: 1.53, 95% CI: 1.09–2.14) or obese (AOR: 2.34, 95% CI: 1.71–3.20), and having self-reported diabetes (AOR: 3.08, 95% CI: 1.88–5.04) had an increased risk of hypertension. Moreover, 51.0% of the participants were taking anti-hypertensive medications and 26.4% of them had their hypertension in control.

Conclusions
The findings highlight a high burden of hypertension and poor management of it among the slum dwellers in Bangladesh requiring a novel approach to improve care. It is integral to effectively implement the available national non-communicable disease (NCD) control guidelines and redesign the current urban primary health care system to have better coordination.
Final year undergraduate nursing and midwifery students’ perspectives on simulation-based education: a cross-sectional study
Authors: Moloney Mairead , Murphy Louise , Kingston Liz , Markey Kathleen , Hennessy Therese , Meskell Pauline , Atkinson Sandra , Doody Owen 
Published: November 2022

Abstract
Background
Simulation-based education is a teaching and learning approach that can enhance learning experiences for students on healthcare programmes. Within undergraduate nursing and midwifery education, simulation can support students in developing graduate attributes necessary to become practice-ready professionals. This paper reports on the evaluation of a simulation-based education initiative, which was introduced to support final year undergraduate nursing and midwifery students in preparation for their upcoming clinical internship in practice.

Methods
This study aimed to evaluate a simulation-based education initiative from the perspectives of final year undergraduate nursing and midwifery students (N = 95). An online survey, using the validated Simulation Effectiveness Tool – Modified (SET-M), was distributed to final year nursing and midwifery students at one university in Ireland. This study was conducted and reported in line with the Consensus-Based Checklist for Reporting of Survey Studies (CROSS).

Results
The results of the study highlight final year nursing and midwifery students’ perceptions, experiences, and satisfaction with learning in a simulated environment. Students reported their simulation-based learning experiences as worthwhile, motivating, and as important opportunities to build on previous learning, increase confidence and gain experience in preparation for real-life practice. Students reported feeling more confident in their assessment skills, in providing care and interventions in responding to changes in a person’s health status. All students reported that the simulation-based learning experiences enabled them to think more critically about the clinical case scenarios and critically question their actions and decision-making processes. Pre-briefing and debriefing sessions were highlighted as important aspects of the simulation which helped to increase student confidence and cultivate meaningful learning.

Conclusion
Simulation-based education is a valuable teaching and learning modality, particularly for final year students who are transitioning to real-life clinical practice. Student-centred simulation-based learning experiences can cultivate professional development and support learners in their transition from university student to healthcare professional.
Willingness to pay for HPV vaccine among female health care workers in a Chinese nationwide survey
Authors: Lu Xinyue , Ji Mengdi , Wagner Abram L. , Huang Weifeng , Shao Xiaoping , Zhou Weiyu , Lu Yihan 
Published: November 2022

Abstract
Background
Payment methods for human papillomavirus (HPV) vaccine could substantially influence vaccination behavior. In China, HPV vaccination uptake remains currently low. This study aims to determine willingness to pay (WTP) for HPV vaccines among Chinese female health care workers under different payment scenarios.

Methods
This is a nationwide online survey recruiting female health care workers aged 18–45 years from 31 provinces throughout China. We collected the respondents’ vaccination status of HPV vaccines and their sociodemographics. Two WTPs were defined and estimated in the study. A general WTP for HPV vaccination was determined using the contingent valuation method with double dichotomous choice bidding. A WTP out-of-pocket was estimated for each HPV vaccine under two scenarios, including partial coverage by governmental subsidy or partial incorporation in basic medical insurance. Accordingly, a multivariable linear regression model was employed to determine the association between sociodemographis and general WTP. Then the maximum WTP out-of-pocket was compared among the respondents’ attitude shift towards HPV vaccination, payment scenarios, and levels of vaccine attributes, using non-parametric Kruskal-Wallis test.

Results
A total of 15,969 respondents were included in the study. The median general WTP was 2000 CNY (interquartile range, 1000–3200 CNY), positively associated with younger age, unmarried status, higher monthly income, fewer children, more positive vaccination behavior, working in tertiary hospital, higher local GDP and HDI (each P < 0.05). Moreover, the median WTP out-of-pocket was 1250 CNY (540–2000 CNY). It was significantly higher for vaccines partly covered by governmental subsidy (median, 1250 CNY; interquartile range, 560–2000 CNY), imported vaccines (1260 CNY; 630–1960 CNY), and 9-valent vaccines (1400 CNY; 750–2240 CNY) (each P < 0.001). Additionally, majority of respondents did not change their attitude towards HPV vaccination between two payment scenarios; those remaining with more expensive HPV vaccines (51.1%) had higher WTP out-of-pocket (1400 CNY; 560–2250 CNY) than those with cheaper vaccines (39.0%) (1120 CNY; 490–1960 CNY) (P < 0.001).

Conclusion
Chinese female health care workers have high WTP for HPV vaccines. A direct public funding for HPV vaccination is more preferable. Our findings may facilitate the adjustment of HPV vaccination strategy and payment mechanism in China.
PTEN regulates invasiveness in pancreatic neuroendocrine tumors through DUSP19-mediated VEGFR3 dephosphorylation
Authors: Chang Tsung-Ming , Chu Pei-Yi , Lin Hui-You , Huang Kuo-Wei , Hung Wen-Chun , Shan Yan-Shen , Chen Li-Tzong , Tsai Hui-Jen 
Published: November 2022

Abstract
Background
Phosphatase and tensin homolog (PTEN) is a tumor suppressor. Low PTEN expression has been observed in pancreatic neuroendocrine tumors (pNETs) and is associated with increased liver metastasis and poor survival. Vascular endothelial growth factor receptor 3 (VEGFR3) is a receptor tyrosine kinase and is usually activated by binding with vascular endothelial growth factor C (VEGFC). VEGFR3 has been demonstrated with lymphangiogenesis and cancer invasiveness. PTEN is also a phosphatase to dephosphorylate both lipid and protein substrates and VEGFR3 is hypothesized to be a substrate of PTEN. Dual-specificity phosphatase 19 (DUSP19) is an atypical DUSP and can interact with VEGFR3. In this study, we investigated the function of PTEN on regulation of pNET invasiveness and its association with VEGFR3 and DUSP19.

Methods
PTEN was knocked down or overexpressed in pNET cells to evaluate its effect on invasiveness and its association with VEGFR3 phosphorylation. In vitro phosphatase assay was performed to identify the regulatory molecule on the regulation of VEGFR3 phosphorylation. In addition, immunoprecipitation, and immunofluorescence staining were performed to evaluate the molecule with direct interaction on VEGFR3 phosphorylation. The animal study was performed to validate the results of the in vitro study.

Results
The invasion and migration capabilities of pNETs were enhanced by PTEN knockdown accompanied with increased VEGFR3 phosphorylation, ERK phosphorylation, and increased expression of epithelial–mesenchymal transition molecules in the cells. The enhanced invasion and migration abilities of pNET cells with PTEN knockdown were suppressed by addition of the VEGFR3 inhibitor MAZ51, but not by the VEGFR3-Fc chimeric protein to neutralize VEGFC. VEGFR3 phosphorylation is responsible for pNET cell invasiveness and is VEGFC-independent. However, an in vitro phosphatase assay failed to show VEGFR3 as a substrate of PTEN. In contrast, DUSP19 was transcriptionally upregulated by PTEN and was shown to dephosphorylate VEGFR3 via direct interaction with VEGFR3 by an in vitro phosphatase assay, immunoprecipitation, and immunofluorescence staining. Increased tumor invasion into peripheral tissues was validated in xenograft mouse model. Tumor invasion was suppressed by treatment with VEGFR3 or MEK inhibitors.

Conclusions
PTEN regulates pNET invasiveness via DUSP19-mediated VEGFR3 dephosphorylation. VEGFR3 and DUSP19 are potential therapeutic targets for pNET treatment.
A CRISPR-based chromosomal-separation technique for Escherichia coli
Authors: Su Junchang , Wang Pengju , Li Ju , Zhao Dongdong , Li Siwei , Fan Feiyu , Dai Zhubo , Liao Xiaoping , Mao Zhitao , Zhang Chunzhi , Bi Changhao , Zhang Xueli 
Published: November 2022

Abstract
Background
Natural life systems can be significantly modified at the genomic scale by human intervention, demonstrating the great innovation capacity of genome engineering. Large epi-chromosomal DNA structures were established in Escherichia coli cells, but some of these methods were inconvenient, using heterologous systems, or relied on engineered E. coli strains.

Results
The wild-type model bacterium E. coli has a single circular chromosome. In this work, a novel method was developed to split the original chromosome of wild-type E. coli. With this method, novel E. coli strains containing two chromosomes of 0.10 Mb and 4.54 Mb, and 2.28 Mb and 2.36 Mb were created respectively, designated as E. coli0.10/4.54 and E. coli2.28/2.36. The new chromosomal arrangement was proved by PCR amplification of joint regions as well as a combination of Nanopore and Illumina sequencing analysis. While E. coli0.10/4.54 was quite stable, the two chromosomes of E. coli2.28/2.36 population recombined into a new chromosome (Chr.4.64MMut), via recombination. Both engineered strains grew slightly slower than the wild-type, and their cell shapes were obviously elongated.

Conclusion
Finally, we successfully developed a simple CRISPR-based genome engineering technique for the construction of multi-chromosomal E. coli strains with no heterologous genetic parts. This technique might be applied to other prokaryotes for synthetic biology studies and applications in the future.
Novel application of one-step pooled molecular testing and maximum likelihood approaches to estimate the prevalence of malaria parasitaemia among rapid diagnostic test negative samples in western Kenya
Authors: Shah Monica P. , Chebore Winnie , Lyles Robert H. , Otieno Kephas , Zhou Zhiyong , Plucinski Mateusz , Waller Lance A. , Odongo Wycliffe , Lindblade Kim A. , Kariuki Simon , Samuels Aaron M. , Desai Meghna , Mitchell Rebecca M. , Shi Ya Ping 
Published: November 2022

Abstract
Background
Detection of malaria parasitaemia in samples that are negative by rapid diagnostic tests (RDTs) requires resource-intensive molecular tools. While pooled testing using a two-step strategy provides a cost-saving alternative to the gold standard of individual sample testing, statistical adjustments are needed to improve accuracy of prevalence estimates for a single step pooled testing strategy.

Methods
A random sample of 4670 malaria RDT negative dried blood spot samples were selected from a mass testing and treatment trial in Asembo, Gem, and Karemo, western Kenya. Samples were tested for malaria individually and in pools of five, 934 pools, by one-step quantitative polymerase chain reaction (qPCR). Maximum likelihood approaches were used to estimate subpatent parasitaemia (RDT-negative, qPCR-positive) prevalence by pooling, assuming poolwise sensitivity and specificity was either 100% (strategy A) or imperfect (strategy B). To improve and illustrate the practicality of this estimation approach, a validation study was constructed from pools allocated at random into main (734 pools) and validation (200 pools) subsets. Prevalence was estimated using strategies A and B and an inverse-variance weighted estimator and estimates were weighted to account for differential sampling rates by area.

Results
The prevalence of subpatent parasitaemia was 14.5% (95% CI 13.6–15.3%) by individual qPCR, 9.5% (95% CI (8.5–10.5%) by strategy A, and 13.9% (95% CI 12.6–15.2%) by strategy B. In the validation study, the prevalence by individual qPCR was 13.5% (95% CI 12.4–14.7%) in the main subset, 8.9% (95% CI 7.9–9.9%) by strategy A, 11.4% (95% CI 9.9–12.9%) by strategy B, and 12.8% (95% CI 11.2–14.3%) using inverse-variance weighted estimator from poolwise validation. Pooling, including a 20% validation subset, reduced costs by 52% compared to individual testing.

Conclusions
Compared to individual testing, a one-step pooled testing strategy with an internal validation subset can provide accurate prevalence estimates of PCR-positivity among RDT-negatives at a lower cost.
Mobile phone handover data for measuring and analysing human population mobility in Western Ethiopia: implication for malaria disease epidemiology and elimination efforts
Authors: Haileselassie Werissaw , Getnet Ashagrie , Solomon Hiwot , Deressa Wakgari , Yan Guiyun , Parker Daniel M. 
Published: November 2022

Abstract
Background
Human mobility behaviour modelling plays an essential role in the understanding and control of the spread of contagious diseases by limiting the contact among individuals, predicting the spatio-temporal evolution of an epidemic and inferring migration patterns. It informs programmatic and policy decisions for effective and efficient intervention. The objective of this research is to assess the human mobility pattern and analyse its implication for malaria disease epidemiology.

Methods
In this study, human mobility patterns in Benishangul-Gumuz and Gambella regions in Western Ethiopia were explored based on a cellular network mobility parameter (e.g., handover rate) via real world data. Anonymized data were retrieved for mobile active users with mobility related information. The data came from anonymous traffic records collected from all the study areas. For each cell, the necessary mobility parameter data per hour, week and month were collected. A scale factor was computed to change the mobility parameter value to the human mobility pattern. Finally, the relative human mobility probability for each scenario was estimated. MapInfo and Matlab softwares were used for visualization and analysis purposes. Hourly travel patterns in the study settings were compared with hourly malaria mosquito vector feeding behaviour.

Results
Heterogeneous human movement patterns were observed in the two regions with some areas showing typically high human mobility. Furthermore, the number of people entering into the two study regions was high during the highest malaria transmission season. Two peaks of hourly human movement, 8:00 to 9:00 and 16:00 to 18:00, emerged in Benishangul-Gumuz region while 8:00 to 10:00 and 16:00 to 18:00 were the peak hourly human mobility time periods in Gambella region. The high human movement in the night especially before midnight in the two regions may increase the risk of getting mosquito bite particularly by early biters depending on malaria linked human behaviour of the population.

Conclusions
High human mobility was observed both within and outside the two regions. The population influx and efflux in these two regions is considerably high. This may specifically challenge the transition from malaria control to elimination. The daily mobility pattern is worth considering in the context of malaria transmission. In line with this malaria related behavioural patterns of humans need to be properly addressed.
Association of physical activity and air pollution exposure with the risk of type 2 diabetes: a large population-based prospective cohort study
Authors: Li Zhi-Hao , Zhong Wen-Fang , Zhang Xi-Ru , Chung Vincent CH , Song Wei-Qi , Chen Qing , Wang Xiao-Meng , Huang Qing-Mei , Shen Dong , Zhang Pei-Dong , Liu Dan , Zhang Yu-Jie , Chen Pei-Liang , Cheng Xin , Yang Hai-Lian , Cai Miao-Chun , Gao Xiang , Kraus Virginia Byers , Mao Chen 
Published: November 2022

Abstract
Background
The interplay between physical activity (PA) and air pollution in relation to type 2 diabetes (T2D) remains largely unknown. Based on a large population-based cohort study, this study aimed to examine whether the benefits of PA with respect to the risk of T2D are moderated by exposure to air pollution.

Methods
UK Biobank participants (n = 359,153) without diabetes at baseline were included. Information on PA was obtained using the International Physical Activity Questionnaire short form. Exposure to air pollution, including PM2.5, PMcoarse (PM2.5−10), PM10, and NO2, was estimated from land use regression models. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results
During a median of 8.9 years of follow-up, 13,706 T2D events were recorded. Compared with a low PA level, the HRs for the risk of T2D among individuals with moderate and high PA were 0.82 (95% CI, 0.79–0.86) and 0.73 (95% CI, 0.70–0.77), respectively. Compared with low levels of air pollution, the HRs for risk of T2D for high levels of air pollution (PM2.5, PMcoarse, PM10, and NO2) were 1.19 (1.14–1.24), 1.06 (1.02–1.11), 1.13 (1.08–1.18), and 1.19 (1.14–1.24), respectively. There was no effect modification of the associations between PA and T2D by air pollution (all P-interactions > 0.05). The inverse associations between PA and T2D in each air pollution stratum were generally consistent (all P for trend < 0.05).

Conclusion
A higher PA and lower air pollution level were independently associated with a lower risk of T2D. The beneficial effects of PA on T2D generally remained stable among participants exposed to different levels of air pollution. Further studies are needed to replicate our findings in moderately and severely polluted areas.