bluuebunny/crossref_metadata_2025_split huggingface dataset:
The new cultural norm: reasons why UK foundation doctors are choosing not to go straight into speciality training
Authors: Hollis Alexander Conor , Streeter Jack , Van Hamel Clare , Milburn Louise , Alberti Hugh 
Published: August 2020

Abstract
Background
The number of UK foundation doctors choosing to go straight into speciality training has fallen drastically over the last 10 years: We sought to explore and understand the reasons for this change.

Methods
We undertook semi-structured interviews with 16 foundation year two doctors, who had not applied to speciality training, from two regional foundation schools. Transcripts were thematically analysed.

Results
The reasons that foundation doctors are choosing not to go straight into speciality training centre around the themes of feeling undervalued, career uncertainty and a new cultural norm. They report major feelings of uncertainty regarding career choice at such an early stage of their profession and this challenge was magnified by a perceived lack of flexibility of training and the growing normality of taking time out from training. Trainees feel a lack of support in planning and undertaking an “FY3” year and being helped back into the workforce.
Trainees overwhelmingly reported that they feel undervalued by their employers. Importantly, however, not going into training directly was not always a reflection of dissatisfaction with training. Many trainees spoke very positively about their planned activities and often saw a break in training as an excellent way to recharge, develop skills and prepare for the rest of their careers in medicine.

Conclusions
Taking a year or more out of training after foundation years has become the new cultural norm for UK junior doctors and reasons for this include feeling undervalued, career uncertainty and the perception that this is now “normal”. Exploring these factors with participants has generated a number of recommendations related to improving the workplace environment, allowing more flexibility in training and supporting those who chose to take an FY3.
From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses
Authors: Zhu Zhixing , Lian Xihua , Su Xiaoshan , Wu Weijing , Marraro Giuseppe A. , Zeng Yiming 
Published: August 2020

AbstractWithin two decades, there have emerged three highly pathogenic and deadly human coronaviruses, namely SARS-CoV, MERS-CoV and SARS-CoV-2. The economic burden and health threats caused by these coronaviruses are extremely dreadful and getting more serious as the increasing number of global infections and attributed deaths of SARS-CoV-2 and MERS-CoV. Unfortunately, specific medical countermeasures for these hCoVs remain absent. Moreover, the fast spread of misinformation about the ongoing SARS-CoV-2 pandemic uniquely places the virus alongside an annoying infodemic and causes unnecessary worldwide panic. SARS-CoV-2 shares many similarities with SARS-CoV and MERS-CoV, certainly, obvious differences exist as well. Lessons learnt from SARS-CoV and MERS-CoV, timely updated information of SARS-CoV-2 and MERS-CoV, and summarized specific knowledge of these hCoVs are extremely invaluable for effectively and efficiently contain the outbreak of SARS-CoV-2 and MERS-CoV. By gaining a deeper understanding of hCoVs and the illnesses caused by them, we can bridge knowledge gaps, provide cultural weapons for fighting and controling the spread of MERS-CoV and SARS-CoV-2, and prepare effective and robust defense lines against hCoVs that may emerge or reemerge in the future. To this end, the state-of-the-art knowledge and comparing the biological features of these lethal hCoVs and the clinical characteristics of illnesses caused by them are systematically summarized in the review.
Long noncoding RNA MIR99AHG promotes gastric cancer progression by inducing EMT and inhibiting apoptosis via miR577/FOXP1 axis
Authors: Meng Qingyang , Wang Xiangjun , Xue Tongqing , Zhao Qiangfang , Wang Wei , Zhao Kun 
Published: August 2020

Abstract
Background
Long non-coding RNAs (lncRNAs) play a vital role in the genesis and development of human cancer. LncRNA MIR99AHG has been reported to be upregulated in acute myeloid leukemia (AML); however, its function in gastric cancer (GC) is still not clear. Here we were aiming to screen the prognostic lncRNA candidates and to explore the function of MIR99AHG in GC.

Methods
We have preliminarily screened some candidate lncRNA biomarkers in GC tissues through analyzing microarray datasets. The expression level of MIR99AHG in GC cell lines and tissues was monitored via qPCR. Survival analysis was performed with the patients of our hospital and TCGA database cases. CCK-8 assay, trans-well assay and flow cytometry were performed to determine cell proliferation, invasion, migration and apoptosis. Meanwhile, a target of MIR99AHG was predicted and identified by luciferase reporter gene detection experiments.

Results
MIR99AHG was strongly up-regulated in human GC and contributed to cancer progression. Kaplan–Meier analysis revealed that up-regulating MIR99AHG expression was positively correlated with unfavorable overall survival (P < 0.01) of patients from our hospital and TCGA database. Knockdown of MIR99AHG expression inhibited cell proliferation, invasion, migration and promoted cell apoptosis. Moreover, MIR99AHG worked as an oncogenic gene though competing for endogenous RNA (ceRNA) of miR-577.

Conclusions
Our findings suggested that MIR99AHG contributes to malignant phenotypes of GC and may become a promising therapeutic target.
Comparative evaluation of two commercial real-time PCR kits (QuantiFast™ and abTES™) for the detection of Plasmodium knowlesi and other Plasmodium species in Sabah, Malaysia
Authors: Nuin Nor Afizah , Tan Angelica F. , Lew Yao Long , Piera Kim A. , William Timothy , Rajahram Giri S. , Jelip Jenarun , Dony Jiloris F. , Mohammad Rashidah , Cooper Daniel J. , Barber Bridget E. , Anstey Nicholas M. , Chua Tock H. , Grigg Matthew J. 
Published: August 2020

Abstract
Background
The monkey parasite Plasmodium knowlesi is an emerging public health issue in Southeast Asia. In Sabah, Malaysia, P. knowlesi is now the dominant cause of human malaria. Molecular detection methods for P. knowlesi are essential for accurate diagnosis and in monitoring progress towards malaria elimination of other Plasmodium species. However, recent commercially available PCR malaria kits have unpublished P. knowlesi gene targets or have not been evaluated against clinical samples.

Methods
Two real-time PCR methods currently used in Sabah for confirmatory malaria diagnosis and surveillance reporting were evaluated: the QuantiFast™ Multiplex PCR kit (Qiagen, Germany) targeting the P. knowlesi 18S SSU rRNA; and the abTES™ Malaria 5 qPCR II kit (AITbiotech, Singapore), with an undisclosed P. knowlesi gene target. Diagnostic accuracy was evaluated using 52 P. knowlesi, 25 Plasmodium vivax, 21 Plasmodium falciparum, and 10 Plasmodium malariae clinical isolates, and 26 malaria negative controls, and compared against a validated reference nested PCR assay. The limit of detection (LOD) for each PCR method and Plasmodium species was also evaluated.

Results
The sensitivity of the QuantiFast™ and abTES™ assays for detecting P. knowlesi was comparable at 98.1% (95% CI 89.7–100) and 100% (95% CI 93.2–100), respectively. Specificity of the QuantiFast™ and abTES™ for P. knowlesi was high at 98.8% (95% CI 93.4–100) for both assays. The QuantiFast™ assay demonstrated falsely-positive mixed Plasmodium species at low parasitaemias in both the primary and LOD analysis. Diagnostic accuracy of both PCR kits for detecting P. vivax, P. falciparum, and P. malariae was comparable to P. knowlesi. The abTES™ assay demonstrated a lower LOD for P. knowlesi of ≤ 0.125 parasites/µL compared to QuantiFast™ with a LOD of 20 parasites/µL. Hospital microscopy demonstrated a sensitivity of 78.8% (95% CI 65.3–88.9) and specificity of 80.4% (95% CI 67.6–89.8) compared to reference PCR for detecting P. knowlesi.

Conclusion
The QuantiFast™ and abTES™ commercial PCR kits performed well for the accurate detection of P. knowlesi infections. Although the QuantiFast™ kit is cheaper, the abTES™ kit demonstrated a lower LOD, supporting its use as a second-line referral-laboratory diagnostic tool in Sabah, Malaysia.
Greenness, civil environment, and pregnancy outcomes: perspectives with a systematic review and meta-analysis
Authors: Lee Kyung Ju , Moon Hyemi , Yun Hyo Ri , Park Eun Lyeong , Park Ae Ran , Choi Hijeong , Hong Kwan , Lee Juneyoung 
Published: August 2020

Abstract
Background
Various maternal conditions, especially in utero conditions and prenatal exposure to environments with air pollution and greenness, have been reviewed to address the enhancement and prevention of susceptibility to health risks, including low birthweight, preterm delivery, and preeclampsia. This study aimed to qualitatively and quantitatively investigate the associations between pregnancy outcomes and the characteristics of surrounding living environment, including greenness, air pollution, and civilization.

Methods
A secondary search of the MEDLINE, EMBASE, Cochrane Library, K-eArticles, and CINAHL databases was conducted without language restrictions to identify the relevant publications from the time of inception of the databases to April 2019.

Results
A total of 89 studies were identified, and 10 were included in the quantitative synthesis. The greenness of the environment within 100-, 250- and 500-m buffers, after adjusting for the air quality and civilization factors, was weakly but positively associated with birthweight. The pooled regression slope was 0.00134 (95% confidence interval [CI], 0.000, 0.0020). The greenness of the environment was also associated with a significant decrease in the incidence of poor pregnancy outcomes, namely, low birthweight, small for gestational age (odds ratio [OR] 0.94; 95% CI, 0.92, 0.97), and preterm delivery (OR 0.98; 95% CI, 0.97, 0.99).

Conclusions
The greenness of the environment had a positive effect on the pregnancy outcomes, despite poor air quality and civilization. Following urbanization, planning for greenness management, environmental medicine, and public health is important and thus should be proposed as preventive methods as way of increasing birthweight and life expectancy.
The involvement of exosomes in the diagnosis and treatment of pancreatic cancer
Authors: Ariston Gabriel Abakundana Nsenga , Wang Fang , Jiao Qinlian , Yvette Umwali , Yang Xuemei , Al-Ameri Samed Ahmed , Du Lutao , Wang Yun-shan , Wang Chuanxin 
Published: August 2020

AbstractAt the moment, pancreatic cancer is among the deadliest gastrointestinal diseases, and pancreatic cancer growth is a complex biological process that is based on different kinds of genes. Exosomes are extracellular vesicles containing microRNAs (miRNAs), messenger RNA (mRNA), and proteins, they act as the most prominent mediator of intercellular communication, and they regulate, instruct, and re-educate their surrounding microenvironment and target specific organs. Due to accumulative evidence proved that exosomes are involved in metastasis, cell proliferation, EMT, angiogenesis, and TME of pancreatic cancer, exosomes are crucial potential candidates to detect pancreatic cancer early. This review aims to convey the current understanding of the main functions employed by exosomes in early diagnosis and treatment of pancreatic cancer.
Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy
Authors: Zheng Juyan , Mo Junluan , Zhu Tao , Zhuo Wei , Yi Yueneng , Hu Shuo , Yin Jiye , Zhang Wei , Zhou Honghao , Liu Zhaoqian 
Published: August 2020

AbstractCellular recognition of microbial DNA is an evolutionarily conserved mechanism by which the innate immune system detects pathogens. Cyclic GMP-AMP synthase (cGAS) and its downstream effector, stimulator of interferon genes (STING), are involved in mediating fundamental innate antimicrobial immunity by promoting the release of type I interferons (IFNs) and other inflammatory cytokines. Accumulating evidence suggests that the activation of the cGAS-STING axis is critical for antitumor immunity. The downstream cytokines regulated by cGAS-STING, especially type I IFNs, serve as bridges connecting innate immunity with adaptive immunity. Accordingly, a growing number of studies have focused on the synthesis and screening of STING pathway agonists. However, chronic STING activation may lead to a protumor phenotype in certain malignancies. Hence, the cGAS-STING signaling pathway must be orchestrated properly when STING agonists are used alone or in combination. In this review, we discuss the dichotomous roles of the cGAS-STING pathway in tumor development and the latest advances in the use of STING agonists.
A nomogram based on a patient-reported outcomes measure: predicting the risk of readmission for patients with chronic heart failure
Authors: Han Qiang , Ren Jia , Tian Jing , Yang Hong , Zhang Qing , Wang Ruoya , Zhao Jinghua , Han Linai , Li Chenhao , Yan Jingjing , Wang Ke , Zheng Chu , Han Qinghua , Zhang Yanbo 
Published: August 2020

Abstract
Background
Health-related quality of life, as evaluated by a patient-reported outcomes measure (PROM), is an important prognostic marker in patients with chronic heart failure. This study aimed to use PROM to establish an effective readmission nomogram for chronic heart failure.

Methods
Using a PROM as a measurement tool, we conducted a readmission nomogram for chronic heart failure on a prospective observational study comprising of 454 patients with chronic heart failure hospitalized between May 2017 to January 2020. A Concordance index and calibration curve were used to evaluate the discriminative ability and predictive accuracy of the nomogram. A bootstrap resampling method was used for internal validation of results.

Results
The median follow-up period in the study was 372 days. After a final COX regression analysis, the gender, income, health care, appetite-sleep, anxiety, depression, paranoia, support, and independence were identified and included in the nomogram. The nomogram showed moderate discrimination, with a concordance index of 0.737 (95% CI 0.673–0.800). The calibration curves for the probability of readmission for patients with chronic heart failure showed high consistency between the probability, as predicted, and the actual probability.

Conclusions
This model offers a platform to assess the risk of readmission for different populations with CHF and can assist clinicians with personalized treatment recommendations.
Cardiac metastases from primary myxoid liposarcoma of the thigh: a case report
Authors: Ikuta Kunihiro , Sakai Tomohisa , Koike Hiroshi , Okada Tohru , Imagama Shiro , Nishida Yoshihiro 
Published: August 2020

Abstract
Background
Myxoid liposarcoma is well known to have an unusual proclivity for extrapulmonary metastasis. However, cardiac metastasis of myxoid liposarcoma is very rare, even in patients with advanced disease.

Case presentation
A 40-year-old man was diagnosed with myxoid liposarcoma of the right thigh and treated with wide resection. Two years after the surgery, a low-density area in the left ventricle was found on follow-up chest computed tomography, and was suspected of being metastatic disease. He underwent surgical treatment, and the lesion was pathologically confirmed as metastasis of myxoid liposarcoma. Fifteen months later, he complained of slight dyspnea and developed metastatic disease in the right atrium. He was treated with surgical excision, followed by radiotherapy. Although there was no recurrence in the heart since the second cardiac metastasectomy, multiple metastases occurred in the abdominal cavity, lungs, and muscles. He finally died of the disease 2 years after the second cardiac metastasectomy.

Conclusion
We experienced a case of primary myxoid liposarcoma in the thigh, accompanied by ectopic and metachronous cardiac metastases. Although this condition is rare, we should follow-up patients with myxoid liposarcoma, considering the possibility of cardiac metastasis.
Global research priorities for social, behavioural and community engagement interventions for maternal, newborn and child health
Authors: Chan Geoffrey , Storey J. Douglas , Das Manoja Kumar , Sacks Emma , Johri Mira , Kabakian-Khasholian Tamar , Paudel Deepak , Yoshida Sachiyo , Portela Anayda 
Published: August 2020

Abstract
Background
Social, behavioural and community engagement (SBCE) interventions are essential for global maternal, newborn and child health (MNCH) strategies. Past efforts to synthesise research on SBCE interventions identified a need for clear priorities to guide future research. WHO led an exercise to identify global research priorities for SBCE interventions to improve MNCH.

Methods
We adapted the Child Health and Nutrition Research Initiative method and combined quantitative and qualitative methods to determine MNCH SBCE intervention research priorities applicable across different contexts. Using online surveys and meetings, researchers and programme experts proposed up to three research priorities and scored the compiled priorities against four criteria – health and social impact, equity, feasibility, and overall importance. Priorities were then ranked by score. A group of 29 experts finalised the top 10 research priorities for each of maternal, newborn or child health and a cross-cutting area.

Results
A total of 310 experts proposed 867 research priorities, which were consolidated into 444 priorities and scored by 280 experts. Top maternal and newborn health priorities focused on research to improve the delivery of SBCE interventions that strengthen self-care/family care practices and care-seeking behaviour. Child health priorities focused on the delivery of SBCE interventions, emphasising determinants of service utilisation and breastfeeding and nutrition practices. Cross-cutting MNCH priorities highlighted the need for better integration of SBCE into facility-based and community-based health services.

Conclusions
Achieving global targets for MNCH requires increased investment in SBCE interventions that build capacities of individuals, families and communities as agents of their own health. Findings from this exercise provide guidance to prioritise investments and ensure that they are best directed to achieve global objectives. Stakeholders are encouraged to use these priorities to guide future research investments and to adapt them for country programmes by engaging with national level stakeholders.
Some reflections on the use of inappropriate comparators in CEA
Authors: Sacristán José Antonio , Abellán-Perpiñán José-María , Dilla Tatiana , Soto Javier , Oliva Juan 
Published: August 2020

AbstractAlthough the choice of the comparator is one of the aspects with a highest effect on the results of cost-effectiveness analyses, it is one of the less debated issues in international methodological guidelines. The inclusion of an inappropriate comparator may introduce biases on the outcomes and the recommendations of an economic analysis. Although the rules for cost-effectiveness analyses of sets of mutually exclusive alternatives have been widely described in the literature, in practice, they are hardly ever applied. In addition, there are many cases where the efficiency of the standard of care has never been assessed; or where the standard of care has demonstrated to be cost-effective with respect to a non-efficient option. In all these cases the comparator may lie outside the efficiency frontier, so the result of the CEA may be biased. Through some hypothetical examples, the paper shows how the complementary use of an independent reference may help to identify potential inappropriate comparators and inefficient use of resources.
Characterization of accessory genes in coronavirus genomes
Authors: Michel Christian Jean , Mayer Claudine , Poch Olivier , Thompson Julie Dawn 
Published: August 2020

Abstract
Background
The Covid19 infection is caused by the SARS-CoV-2 virus, a novel member of the coronavirus (CoV) family. CoV genomes code for a ORF1a / ORF1ab polyprotein and four structural proteins widely studied as major drug targets. The genomes also contain a variable number of open reading frames (ORFs) coding for accessory proteins that are not essential for virus replication, but appear to have a role in pathogenesis. The accessory proteins have been less well characterized and are difficult to predict by classical bioinformatics methods.

Methods
We propose a computational tool GOFIX to characterize potential ORFs in virus genomes. In particular, ORF coding potential is estimated by searching for enrichment in motifs of the X circular code, that is known to be over-represented in the reading frames of viral genes.

Results
We applied GOFIX to study the SARS-CoV-2 and related genomes including SARS-CoV and SARS-like viruses from bat, civet and pangolin hosts, focusing on the accessory proteins. Our analysis provides evidence supporting the presence of overlapping ORFs 7b, 9b and 9c in all the genomes and thus helps to resolve some differences in current genome annotations. In contrast, we predict that ORF3b is not functional in all genomes. Novel putative ORFs were also predicted, including a truncated form of the ORF10 previously identified in SARS-CoV-2 and a little known ORF overlapping the Spike protein in Civet-CoV and SARS-CoV.

Conclusions
Our findings contribute to characterizing sequence properties of accessory genes of SARS coronaviruses, and especially the newly acquired genes making use of overlapping reading frames.