bluuebunny/crossref_metadata_2025_split huggingface dataset:
Setting up a rapid diagnostic clinic for patients with vague symptoms of cancer: a mixed method process evaluation study
Authors: Vasilakis Christos , Forte Paul 
Published: April 2021

Abstract
Background
The study sought to evaluate the impact of a Rapid Diagnostic Clinic (RDC) service designed to improve general practitioner (GP) referral processes for patients who do not meet existing referral criteria yet present with vague - but potentially concerning - symptoms of cancer. We sought to investigate how well the RDC has performed in the views of local GPs and patients, and through analysis of its activity and performance in the first two years of operation.

Methods
The study setting was a single, hospital-based RDC clinic in a University Health Board in South Wales. We used a mixed-method process evaluation study, including routinely collected activity and diagnosis data. All GPs were invited to participate in an online survey (34/165 responded), and a smaller group (n = 8) were interviewed individually. Two focus groups with patients and their carers (n = 7) provided in-depth personal accounts of their experiences.

Results
The focus groups revealed high rates of patient satisfaction with the RDC. GPs were also overwhelmingly positive about the value of the RDC to their practice. There were 574 clinic attendances between July 2017 and March 2019; the mean age of attendees was 68, 57% were female, and approximately 30% had three or more vague symptoms. Of those attending, we estimated between 42 to 71 (7.3 and 12.3%) received preliminary cancer diagnoses. Median time from GP referral to RDC appointment was 12 days; from GP referral to cancer diagnosis was 34 days. Overall, 73% of RDC patients received either a new diagnosis (suspected cancer 23.2%, non-cancer 35.9%) or an onward referral to secondary care for further investigation with no new diagnosis (13.9%), and 27% were referred to primary care with no new diagnosis.

Conclusions
The RDC appears to enable a good patient experience in cancer diagnosis. Patients are seen in timely fashion, and the service is highly regarded by them, their carers, and referring GPs. Although too early to draw conclusions about long-term patient outcomes, there are strong indications to suggest that this model of service provision can set higher standards for a strongly patient-centred service.
MALDI-TOF mass spectrometry and high-resolution melting PCR for the identification of Mycoplasma bovis isolates
Authors: McDaniel Aric J. , Derscheid Rachel J. 
Published: April 2021

Abstract
Background
Mycoplasma bovis is an important pathogen of cattle worldwide. Many different clinical manifestations of infection can occur, including respiratory disease, arthritis, and mastitis, causing heavy losses to beef and dairy industries. Because Mycoplasma species are slow-growing and fastidious, traditional identification methods are not cost- or time-effective, and improved methods are sought to streamline laboratory processes. High-resolution melting PCR (HRM-PCR) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) are 2 relatively recent tools that are rapid and inexpensive to use; we tested 9 isolates of M. bovis using both assays. The HRM-PCR assay used universal mycoplasma primers for the 16S–23S intergenic spacer region (IGSR).

Results
The resulting melting profiles of the field isolates were indistinguishable from the reference strain, indicating accurate identification. For the MALDI-TOF MS, each M. bovis isolate was accurately identified. Mycoplasma arginini and Mycoplasma alkalescens isolates did not identify as M. bovis when tested by either assay.

Conclusions
Our work shows that either assay could be used to identify unknown M. bovis isolates. For future work, the MALDI-TOF MS library should be expanded to include more mycoplasmas, and the HRM-PCR assay should be tested on additional mycoplasmas to ensure that the melting profiles are sufficiently distinctive.
Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management
Authors: Luppi Fabrizio , Kalluri Meena , Faverio Paola , Kreuter Michael , Ferrara Giovanni 
Published: April 2021

AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with an estimated median survival time of 3–5 years after diagnosis. This condition occurs primarily in elderly subjects, and epidemiological studies suggest that the main risk factors, ageing and exposure to cigarette smoke, are associated with both pulmonary and extrapulmonary comorbidities (defined as the occurrence of two or more disorders in a single individual). Ageing and senescence, through interactions with environmental factors, may contribute to the pathogenesis of IPF by various mechanisms, causing lung epithelium damage and increasing the resistance of myofibroblasts to apoptosis, eventually resulting in extracellular matrix accumulation and pulmonary fibrosis. As a paradigm, syndromes featuring short telomeres represent archetypal premature ageing syndromes and are often associated with pulmonary fibrosis. The pathophysiological features induced by ageing and senescence in patients with IPF may translate to pulmonary and extrapulmonary features, including emphysema, pulmonary hypertension, lung cancer, coronary artery disease, gastro-oesophageal reflux, diabetes mellitus and many other chronic diseases, which may lead to substantial negative consequences in terms of various outcome parameters in IPF. Therefore, the careful diagnosis and treatment of comorbidities may represent an outstanding chance to improve quality of life and survival, and it is necessary to contemplate all possible management options for IPF, including early identification and treatment of comorbidities.
MicroRNAs and angiogenesis: a new era for the management of colorectal cancer
Authors: Tang Yufei , Zong Shaoqi , Zeng Hailun , Ruan Xiaofeng , Yao Liting , Han Susu , Hou Fenggang 
Published: April 2021

AbstractMicroRNAs (miRNAs) are a class of small noncoding RNA molecules containing only 20–22 nucleotides. MiRNAs play a role in gene silencing and translation suppression by targeting and binding to mRNA. Proper control of miRNA expression is very important for maintaining a normal physiological environment because miRNAs can affect most cellular pathways, including cell cycle checkpoint, cell proliferation, and apoptosis pathways, and have a wide range of target genes. With these properties, miRNAs can modulate multiple signalling pathways involved in cancer development, such as cell proliferation, apoptosis, and migration pathways. MiRNAs that activate or inhibit the molecular pathway related to tumour angiogenesis are common topics of research. Angiogenesis promotes tumorigenesis and metastasis by providing oxygen and diffusible nutrients and releasing proangiogenic factors and is one of the hallmarks of tumour progression. CRC is one of the most common tumours, and metastasis has always been a difficult issue in its treatment. Although comprehensive treatments, such as surgery, radiotherapy, chemotherapy, and targeted therapy, have prolonged the survival of CRC patients, the overall response is not optimistic. Therefore, there is an urgent need to find new therapeutic targets to improve CRC treatment. In a series of recent reports, miRNAs have been shown to bidirectionally regulate angiogenesis in colorectal cancer. Many miRNAs can directly act on VEGF or inhibit angiogenesis through other pathways (HIF-1a, PI3K/AKT, etc.), while some miRNAs, specifically many exosomal miRNAs, are capable of promoting CRC angiogenesis. Understanding the mechanism of action of miRNAs in angiogenesis is of great significance for finding new targets for the treatment of tumour angiogenesis. Deciphering the exact role of specific miRNAs in angiogenesis is a challenge due to the high complexity of their actions. Here, we describe the latest advances in the understanding of miRNAs and their corresponding targets that play a role in CRC angiogenesis and discuss possible miRNA-based therapeutic strategies.
Climate-proofing a malaria eradication strategy
Authors: Nissan Hannah , Ukawuba Israel , Thomson Madeleine 
Published: April 2021

AbstractTwo recent initiatives, the World Health Organization (WHO) Strategic Advisory Group on Malaria Eradication and the Lancet Commission on Malaria Eradication, have assessed the feasibility of achieving global malaria eradication and proposed strategies to achieve it. Both reports rely on a climate-driven model of malaria transmission to conclude that long-term trends in climate will assist eradication efforts overall and, consequently, neither prioritize strategies to manage the effects of climate variability and change on malaria programming. This review discusses the pathways via which climate affects malaria and reviews the suitability of climate-driven models of malaria transmission to inform long-term strategies such as an eradication programme. Climate can influence malaria directly, through transmission dynamics, or indirectly, through myriad pathways including the many socioeconomic factors that underpin malaria risk. These indirect effects are largely unpredictable and so are not included in climate-driven disease models. Such models have been effective at predicting transmission from weeks to months ahead. However, due to several well-documented limitations, climate projections cannot accurately predict the medium- or long-term effects of climate change on malaria, especially on local scales. Long-term climate trends are shifting disease patterns, but climate shocks (extreme weather and climate events) and variability from sub-seasonal to decadal timeframes have a much greater influence than trends and are also more easily integrated into control programmes. In light of these conclusions, a pragmatic approach is proposed to assessing and managing the effects of climate variability and change on long-term malaria risk and on programmes to control, eliminate and ultimately eradicate the disease. A range of practical measures are proposed to climate-proof a malaria eradication strategy, which can be implemented today and will ensure that climate variability and change do not derail progress towards eradication.
Inequalities in antenatal care coverage and quality: an analysis from 63 low and middle-income countries using the ANCq content-qualified coverage indicator
Authors: Arroyave Luisa , Saad Ghada E. , Victora Cesar G. , Barros Aluisio J. D. 
Published: April 2021

Abstract
Background
Antenatal care (ANC) is an essential intervention associated with a reduction of maternal and new-born morbidity and mortality. However, evidence suggested substantial inequalities in maternal and child health, mainly in low- and middle-income countries (LMICs). We aimed to conduct a global analysis of socioeconomic inequalities in ANC using national surveys from LMICs.

Methods
ANC was measured using the ANCq, a novel content-qualified ANC coverage indicator, created and validated using national surveys, based upon contact with the health services and content of care received. We performed stratified analysis to explore the socioeconomic inequalities in ANCq. We also estimated the slope index of inequality, which measures the difference in coverage along the wealth spectrum.

Results
We analyzed 63 national surveys carried out from 2010 to 2017. There were large inequalities between and within countries. Higher ANCq scores were observed among women living in urban areas, with secondary or more level of education, belonging to wealthier families and with higher empowerment in nearly all countries. Countries with higher ANCq mean presented lower inequalities; while countries with average ANCq scores presented wide range of inequality, with some managing to achieve very low inequality.

Conclusions
Despite all efforts in ANC programs, important inequalities in coverage and quality of ANC services persist. If maternal and child mortality Sustainable Development Goals are to be achieved, those gaps we documented must be bridged.
Air pollution, methane super-emitters, and oil and gas wells in Northern California: the relationship with migraine headache prevalence and exacerbation
Authors: Elser Holly , Morello-Frosch Rachel , Jacobson Alice , Pressman Alice , Kioumourtzoglou Marianthi-Anna , Reimer Richard , Casey Joan A. 
Published: April 2021

Abstract
Background
Migraine–an episodic disorder characterized by severe headache that can lead to disability–affects over 1 billion people worldwide. Prior studies have found that short-term exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone increases risk of migraine-related emergency department (ED) visits. Our objective was to characterize the association between long-term exposure to sources of harmful emissions and common air pollutants with both migraine headache and, among patients with migraine, headache severity.

Methods
From the Sutter Health electronic health record database, we identified 89,575 prevalent migraine cases between 2014 and 2018 using a migraine probability algorithm (MPA) score and 270,564 frequency-matched controls. Sutter Health delivers care to 3.5 million patients annually in Northern California. Exposures included 2015 annual average block group-level PM2.5 and NO2 concentrations, inverse-distance weighted (IDW) methane emissions from 60 super-emitters located within 10 km of participant residence between 2016 and 2018, and IDW active oil and gas wells in 2015 within 10 km of each participant. We used logistic and negative binomial mixed models to evaluate the association between environmental exposures and (1) migraine case status; and (2) migraine severity (i.e., MPA score > 100, triptan prescriptions, neurology visits, urgent care migraine visits, and ED migraine visits per person-year). Models controlled for age, sex, race/ethnicity, Medicaid use, primary care visits, and block group-level population density and poverty.

Results
In adjusted analyses, for each 5 ppb increase in NO2, we observed 2% increased odds of migraine case status (95% CI: 1.00, 1.05) and for each 100,000 kg/hour increase in IDW methane emissions, the odds of case status also increased (OR = 1.04, 95% CI: 1.00, 1.08). We found no association between PM2.5 or oil and gas wells and migraine case status. PM2.5 was linearly associated with neurology visits, migraine-specific urgent care visits, and MPA score > 100, but not triptans or ED visits. NO2 was associated with migraine-specific urgent care and ED visits, but not other severity measures. We observed limited or null associations between continuous measures of methane emissions and proximity to oil and gas wells and migraine severity.

Conclusions
Our findings illustrate the potential role of long-term exposure to multiple ambient air pollutants for prevalent migraine and migraine severity.
Glycol chitosan-based tacrolimus-loaded nanomicelle therapy ameliorates lupus nephritis
Authors: Kim Chang Seong , Mathew Ansuja Pulickal , Vasukutty Arathy , Uthaman Saji , Joo Soo Yeon , Bae Eun Hui , Ma Seong Kwon , Park In-Kyu , Kim Soo Wan 
Published: April 2021

Abstract
Background
Recently, we developed hydrophobically modified glycol chitosan (HGC) nanomicelles loaded with tacrolimus (TAC) (HGC-TAC) for the targeted renal delivery of TAC. Herein, we determined whether the administration of the HGC-TAC nanomicelles decreases kidney injury in a model of lupus nephritis. Lupus-prone female MRL/lpr mice were randomly assigned into three groups that received intravenous administration of either vehicle control, an equivalent dose of TAC, or HGC-TAC (0.5 mg/kg TAC) weekly for 8 weeks. Age-matched MRL/MpJ mice without Faslpr mutation were also treated with HGC vehicle and used as healthy controls.

Results
Weekly intravenous treatment with HGC-TAC significantly reduced genetically attributable lupus activity in lupus nephritis-positive mice. In addition, HGC-TAC treatment mitigated renal dysfunction, proteinuria, and histological injury, including glomerular proliferative lesions and tubulointerstitial infiltration. Furthermore, HGC-TAC treatment reduced renal inflammation and inflammatory gene expression and ameliorated increased apoptosis and glomerular fibrosis. Moreover, HGC-TAC administration regulated renal injury via the TGF-β1/MAPK/NF-κB signaling pathway. These renoprotective effects of HGC-TAC treatment were more potent in lupus mice compared to those of TAC treatment alone.

Conclusion
Our study indicates that weekly treatment with the HGC-TAC nanomicelles reduces kidney injury resulting from lupus nephritis by preventing inflammation, fibrosis, and apoptosis. This advantage of a new therapeutic modality using kidney-targeted HGC-TAC nanocarriers may improve drug adherence and provide treatment efficacy in lupus nephritis mice.
Validity and responsiveness of EQ-5D-5L and SF-6D in patients with health complaints attributed to their amalgam fillings: a prospective cohort study of patients undergoing amalgam removal
Authors: Lamu Admassu N. , Björkman Lars , Hamre Harald J. , Alræk Terje , Musial Frauke , Robberstad Bjarne 
Published: April 2021

Abstract
Background
Evidence of health utility changes in patients who suffer from longstanding health complaints attributed to dental amalgam fillings are limited. The change in health utility outcomes enables calculating quality-adjusted life-year (QALY) and facilitates the comparison with other health conditions. The purpose of this study was to estimate the validity and responsiveness of the EQ-5D-5L and SF-6D utilities following removal of dental amalgam fillings in patients with health complaints attributed to their amalgam fillings, and examine the ability of these instruments to detect minimally important changes over time.

Methods
Patients with medically unexplained physical symptoms, which they attributed to dental amalgam restorations, were recruited to a prospective cohort study in Norway. Two health state utility instruments, EQ-5D-5L and SF-6D, as well as self-reported general health complaints (GHC-index) and visual analogue scale (EQ-VAS) were administered to all patients (n = 32) at baseline and at follow-up. The last two were used as criteria measures. Concurrent and predictive validities were examined using correlation coefficients. Responsiveness was assessed by the effect size (ES), standardized response mean (SRM), and relative efficiency. Minimally important change (MIC) was examined by distribution and anchor-based approaches.

Results
Concurrent validity of the EQ-5D-5L was similar to that of SF-6D utility. EQ-5D-5L was more responsive than SF-6D: the ES were 0.73 and 0.58 for EQ-5D-5L and SF-6D, respectively; SRM were 0.76 and 0.67, respectively. EQ-5D-5L was more efficient than SF-6D in detecting changes, but both were less efficient compared to criteria-based measures. The estimated MIC of EQ-5D-5L value set was 0.108 and 0.118 based on distribution and anchor-based approaches, respectively. The corresponding values for SF-6D were 0.048 and 0.064, respectively.

Conclusions
In patients with health complaints attributed to dental amalgam undergoing amalgam removal, both EQ-5D-5L and SF-6D showed reasonable concurrent and predictive validity and acceptable responsiveness. The EQ-5D-5L utility appears to be more responsive compared to SF-6D.
Trial registration The research was registered at ClinicalTrials.gov., NCT01682278. Registered 10 September 2012, https://clinicaltrials.gov/ct2/show/NCT01682278.
LncRNA ZEB1-AS1 regulates hepatocellular carcinoma progression by targeting miR-23c
Authors: Xue Shuai , Lu Fengqin , Sun Chunhui , Zhao Jingjing , Zhen Honghua , Li Xin 
Published: April 2021

Abstract
Background
It has been reported that long-chain non-coding RNA (lncRNA) zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is an oncogene in various cancers, including hepatocellular carcinoma (HCC). We investigated the role and mechanism of ZEB1-AS1 as a competitive endogenous RNA (ceRNA) combined with miR-23c in HCC cell proliferation and invasion.

Methods
QRT-PCR was used to detect ZEB1-AS1 and miR-23c expressions in HCC tissues and cells. The dual luciferase reporter assay detected the targeted regulation of miR-23c and ZEB1-AS1. We also performed the correlation analysis of their expression in HCC tissues by the Spearman’s correlation analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the proliferation of hepatoma cells. Cell invasion was assessed by the Transwell assay.

Results
QRT-PCR results indicated ZEB1-AS1 was upregulated and miR-23c was downregulated in HCC tissues and cell lines. ZEB1-AS1 knockdown hampered the proliferation and invasion of HCC cells. Dual luciferase reporter assay showed that miR-23c is a target of ZEB1-AS1, and ZEB1-AS1 was significantly negatively correlated with the miR-23c expression in HCC tissues. The results of MTT and Transwell assay showed that miR-23c inhibition restored the inhibitory effect of ZEB1-AS1 knockdown on HCC cells proliferation and invasion.

Conclusions
As a ceRNA, lncRNA ZEB1-AS1 may play a vital role in inhibiting HCC progression through miR-23c, which will provide new clues and theoretical basis for the HCC diagnosis and treatment.
Exposures to 2,4-Dichlorophenoxyacetic acid with or without endotoxin upregulate small cell lung cancer pathway
Authors: Kaur Geetika , Kumar B. V. Sunil , Singh Baljit , Sethi R. S. 
Published: April 2021

Abstract
Background
Pesticide residues in food and environment along with airborne contaminants such as endotoxins pose health risk. Although herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) has been associated with increased risk of lung cancers such as small cell lung cancer (SCLC) among agricultural workers, there are no data on the SCLC signaling pathway upon 2,4-D exposure without LPS or in combination with endotoxin.

Methods
We exposed Swiss albino mice (N = 48) orally to high (37mg kg-1) and low (18.5 mg kg-1) dosages of 2,4-D dissolved in corn oil for 90 days followed by E. coli lipopolysaccharide (LPS) or normal saline solution (80 μl/animal). Lung samples and broncho-alveolar fluid (BALF) were subjected to Total histological score (THS) and total leucocyte count (TLC) and differential leucocytes count (DLC) analyses, respectively. We used microarray and bioinformatics tools for transcriptomic analyses and differentially expressed genes were analyzed to predict the top canonical pathways followed by validation of selected genes by qRT-PCR and immunohistochemistry.

Results
Total histological score (THS) along with BALF analyses showed lung inflammation following long term dietary exposure to high or low doses of 2,4-D individually or in combination with LPS. Microarray analysis revealed exposure to high dose of 2,4-D without or with LPS upregulated 2178 and 2142 and downregulated 1965 and 1719 genes, respectively (p < 0.05; minimum cut off 1.5 log fold change). The low dose without or with LPS upregulated 2133 and 2054 and downregulated 1838 and 1625 genes, respectively. Bioinformatics analysis showed SCLC as topmost dysregulated pathway along with differential expression of Itgb1, NF-κB1, p53, Cdk6 and Apaf1. Immunohistological and quantitative real time PCR (qRT-PCR) analyses also supported the transcriptomic data.

Conclusions
Taken together, the data show exposures to high and low dose of 2,4-D with/without LPS induced lung inflammation and altered pulmonary transcriptome profile with the involvement of the SCLC pathway. The data from the study provide the insights of the potential damage on lungs caused by 2,4-D and help to better understand the mechanism of this complex relation.