bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic evolution and diverse models of systemic metastases in colorectal cancer
Authors: Chen Hai-Ning , Shu Yang , Liao Fei , Liao Xue , Zhang Hongying , Qin Yun , Wang Zhu , Luo Maochao , Liu Qiuluo , Xue Zhinan , Cao Minyuan , Zhang Shouyue , Zhang Wei-Han , Hou Qianqian , Xia Xuyang , Luo Han , Zhang Yan , Yang Lie , Hu Jian-Kun , Fu Xianghui , Liu Bo , Hu Hongbo , Huang Canhua , Peng Yong , Cheng Wei , Dai Lunzhi , Yang Li , Zhang Wei , Dong Biao , Li Yuan , Wei Yuquan , Xu Heng , Zhou Zong-Guang 
Published: February 2021

ObjectiveThe systemic spread of colorectal cancer (CRC) is dominated by the portal system and exhibits diverse patterns of metastasis without systematical genomic investigation. Here, we evaluated the genomic evolution of CRC with multiorgan metastases using multiregion sequencing.DesignWhole-exome sequencing was performed on multiple regions (n=74) of matched primary tumour, adjacent non-cancerous mucosa, liver metastasis and lung metastasis from six patients with CRC. Phylogenetic reconstruction and evolutionary analyses were used to investigate the metastatic seeding pattern and clonal origin. Recurrent driver gene mutations were analysed across patients and validated in two independent cohorts. Metastatic assays were performed to examine the effect of the novel driver gene on the malignant behaviour of CRC cells.ResultsBased on the migration patterns and clonal origins, three models were revealed (sequential, branch-off and diaspora), which not only supported the anatomic assumption that CRC cells spread to lung after clonally expanding in the liver, but also illustrated the direct seeding of extrahepatic metastases from primary tumours independently. Unlike other cancer types, polyphyletic seeding occurs in CRC, which may result in late metastases with intermetastatic driver gene heterogeneity. In cases with rapid dissemination, we found recurrent trunk loss-of-function mutations inZFP36L2, which is enriched in metastatic CRC and associated with poor overall survival. CRISPR/Cas9-mediated knockout ofZFP36L2enhances the metastatic potential of CRC cells.ConclusionOur results provide genomic evidence for metastatic evolution and indicate that biopsy/sequencing of metastases may be considered for patients with CRC with multiorgan or late postoperative metastasis.
Influence of childhood socioeconomic position and ability on mid-life cognitive function: evidence from three British birth cohorts
Authors: McElroy Eoin , Richards Marcus , Fitzsimons Emla , Conti Gabriella , Ploubidis George B , Sullivan Alice , Moulton Vanessa 
Published: February 2021

BackgroundChildhood socioeconomic position (SEP) is robustly associated with cognitive function later in life. However, it is unclear whether this reflects a direct relationship, or an indirect association via modifiable factors such as educational attainment and occupation. We sought to clarify these associations using retrospectively harmonised data from three ongoing British birth cohorts.MethodsWe analysed data from the 1946 National Survey of Health and Development (n=2283), the 1958 National Child Development Study (n=9385) and the 1970 British Cohort Study (n=7631). Retrospective harmonisation was used to derive equivalent indicators of cognition, SEP, education and occupation across the three cohorts. Structural equation modelling was used to examine the association between childhood SEP and mid-life cognitive function, via childhood cognitive ability, educational attainment and mid-life occupation.ResultsAcross all three cohorts, no direct pathways were observed between childhood SEP and mid-life cognitive function. Rather, this association was indirect via the three temporally ordered mediators. In addition, the direct pathway between childhood cognition and adult cognitive function was weaker in the two younger studies.ConclusionsAcross three British birth cohorts, we found that the association between early life SEP and mid-life cognitive function was fully mediated by childhood cognitive ability, educational attainment and occupational status. Furthermore, the association between early cognitive ability and mid-life cognitive function has decreased in younger generations. Therefore, cognitive function in adulthood may be influenced by modifiable factors and societal change.
Incidence of psychological illness after coronavirus outbreak: a meta-analysis study
Authors: Fan Fang Cheng , Zhang Shu Yao , Cheng Yong 
Published: February 2021

BackgroundThe COVID-19 has had an enormous impact worldwide and is still spreading. Globally confirmed infections have surpassed 41.1 million, of which more than 1 million resulted in deaths. Considering the relationship between public health disasters and emotional disorders, it is essential to examine psychological well-being related to this pandemic.MethodWe performed a systematic search on psychological problems from PubMed to 10 October 2020, and conducted a meta-analysis using Comprehensive Meta-Analysis V.3 software.ResultsThe results showed a 19.4% and 26.8% pooled incidence for depression and post-traumatic stress disorder (PTSD), respectively, during the SARS and Middle East Respiratory Syndrome (MERS)-related coronavirus outbreaks. However, overall prevalence of depression was somewhat higher at 27.0% during the COVID-19 period. The pooled incidence of PTSD during COVID-19 compared with SARS and MERS outbreaks, was lower, at 16.4%.ConclusionThe results suggest that there are shared and distinct psychological responses following SARS, MERS and COVID-19, and show pessimistic estimates of a wide range of potentially upcoming psychological problems.
The sensitivity and specificity of TOF-MRA compared with DSA in the follow-up of treated intracranial aneurysms
Authors: Xiang Sishi , Fan Fu , Hu Peng , Yang Kun , Zhai Xiaodong , Geng Jiewen , Ji Zhe , Lu Jie , Zhang Hongqi 
Published: February 2021

BackgroundTime-of-flight magnetic resonance angiography (TOF-MRA) is widely used in detecting intracranial aneurysms (IA), but it is limited and controversial for use during follow-up to assess the outcome of interventional coiling or clipping surgery.MethodsTo evaluate the specificity and sensitivity of using TOF-MRA as an imaging follow-up for IA with different treatments. A total of 280 patients with 326 treated IA underwent simultaneous TOF-MRA and digital subtraction angiography (DSA) as follow-up imaging on the same day. All images were independently reviewed by two neurosurgeons and two radiologists. The consensus evaluation of intra-arterial DSA as a reference test was used to evaluate the result of aneurysm occlusions. The aneurysmal embolization status was assessed with two ratings involving complete or incomplete occlusions. We calculated the sensitivity, specificity, negative predictive value, and positive predictive value of three-dimensional-TOF-MRA to investigate the diagnostic performance.ResultsOverall sensitivity and specificity of TOF-MRA for diagnosing the remnant were 83.3% and 95.2%, respectively. The sensitivity and specificity of interventional therapy was 90.0% and 94.2%, respectively, while the clipping group showed sensitivity and specificity of 50.0% and 100%, respectively. For additional groups, involving coil only, stent-assisted, and flow diverter, the analysis of interventional therapy showed sensitivities and specificities of 100.0% and 90.1%, 66.7% and 95.1%, and 91.7% and 100%, respectively.ConclusionsTOF-MRA can be used as a first-line noninvasive imaging modality during follow-up, especially for the patients treated with a pipeline embolization device and coils only. But it may not be enough for clipped aneurysms.
Insights into the pathogenesis of cerebral fusiform aneurysms: high-resolution MRI and computational analysis
Authors: Sabotin Ryan Phillip , Varon Alberto , Roa Jorge A , Raghuram Ashrita , Ishii Daizo , Nino Marco , Galloy Adam E , Patel Devanshee , Raghavan Madhavan L , Hasan David , Samaniego Edgar A 
Published: February 2021

BackgroundIntracranial fusiform aneurysms are complex and poorly characterized vascular lesions. High-resolution magnetic resonance imaging (HR-MRI) and computational morphological analysis may be used to characterize cerebral fusiform aneurysms.ObjectiveTo use advanced imaging and computational analysis to understand the unique pathophysiology, and determine possible underlying mechanisms of instability of cerebral fusiform aneurysms.MethodsPatients with unruptured intracranial aneurysms prospectively underwent imaging with 3T HR-MRI at diagnosis. Aneurysmal wall enhancement was objectively quantified using signal intensity after normalization of the contrast ratio (CR) with the pituitary stalk. Enhancement between saccular and fusiform aneurysms was compared, as well as enhancement characteristics of fusiform aneurysms. The presence of microhemorrhages in fusiform aneurysms was determined with quantitative susceptibility mapping (QSM). Three distinct types of fusiform aneurysms were analyzed with computational fluid dynamics (CFD) and finite element analysis (FEA).ResultsA total of 130 patients with 160 aneurysms underwent HR-MRI. 136 aneurysms were saccular and 24 were fusiform. Fusiform aneurysms had a significantly higher CR and diameter than saccular aneurysms. Enhancing fusiform aneurysms exhibited more enhancement of reference vessels than non-enhancing fusiform aneurysms. Ten fusiform aneurysms underwent QSM analysis, and five aneurysms showed microhemorrhages. Microhemorrhage-positive aneurysms had a larger volume, diameter, and greater enhancement than aneurysms without microhemorrhage. Three types of fusiform aneurysms exhibited different CFD and FEA patterns.ConclusionFusiform aneurysms exhibited more contrast enhancement than saccular aneurysms. Enhancing fusiform aneurysms had larger volume and diameter, more enhancement of reference vessels, and more often exhibited microhemorrhage than non-enhancing aneurysms. CFD and FEA suggest that various pathophysiological processes determine the formation and growth of fusiform aneurysms.
Repeatability and sensitivity to change of non-invasive end points in PAH: the RESPIRE study
Authors: Swift Andrew J , Wilson Frederick , Cogliano Marcella , Kendall Lindsay , Alandejani Faisal , Alabed Samer , Hughes Paul , Shahin Yousef , Saunders Laura , Oram Charlotte , Capener David , Rothman Alex , Garg Pankaj , Johns Christopher , Austin Matthew , Macdonald Alistair , Pickworth Jo , Hickey Peter , Condliffe Robin , Cahn Anthony , Lawrie Allan , Wild Jim M , Kiely David G 
Published: February 2021

AbstractEnd points that are repeatable and sensitive to change are important in pulmonary arterial hypertension (PAH) for clinical practice and trials of new therapies. In 42 patients with PAH, test–retest repeatability was assessed using the intraclass correlation coefficient and treatment effect size using Cohen’s d statistic. Intraclass correlation coefficients demonstrated excellent repeatability for MRI, 6 min walk test and log to base 10 N-terminal pro-brain natriuretic peptide (log10NT-proBNP). The treatment effect size for MRI-derived right ventricular ejection fraction was large (Cohen’s d 0.81), whereas the effect size for the 6 min walk test (Cohen’s d 0.22) and log10NT-proBNP (Cohen’s d 0.20) were fair. This study supports further evaluation of MRI as a non-invasive end point for clinical assessment and PAH therapy trials.Trial registration number NCT03841344.
Point-of-sale cigarette pricing strategies and young adult smokers’ intention to purchase cigarettes: an online experiment
Authors: Choi Kelvin , Kreuger Kurt , McNeel Timothy S , Osgood Nathaniel 
Published: February 2021

BackgroundPoint-of-sale tobacco marketing has been shown to be related to tobacco use behaviours; however, specific influences of cigarette price discounts, price tiers and pack/carton availability on cigarette purchasing intention are less understood by the tobacco control community.MethodsWe conducted discrete choice experiments among an online sample of US young adult smokers (aged 18–30 years; n=1823). Participants were presented scenarios depicting their presence at a tobacco retail outlet with varying availability of cigarette price discounts, price tiers and pack/carton. At each scenario, participants were asked whether they would purchase cigarettes. Generalised linear regression models were used to examine the associations between of cigarette price discounts, price tiers and pack/carton with intention to purchase cigarettes overall and stratified by educational attainment.ResultsParticipants chose to purchase cigarettes in 70.9% of the scenarios. Offering price discounts were associated with higher odds of choosing to purchase cigarettes. Reducing the number of cigarette price tiers available in the store was associated with lower odds of choosing to purchase cigarettes. Stratified analysis showed that offering discounts on high-tier cigarette packs increased odds of choosing to purchase cigarettes among young adult smokers with at least some college education, while offering discounts on medium-tier cigarette packs increased odds of choosing to purchase cigarettes among those with some college education or less (eg, with a 10% discount, adjusted odds ratio [AOR]some college=1.62, 95% confidence interval [CI] 1.21 to 2.16; AOR≤high school=1.44, 95% CI 1.08 to 1.93).ConclusionsAvailability of cigarette price discounts, price tiers and pack/carton could potentially influence cigarette purchasing behaviours among young adult smokers. Regulating these marketing strategies may, therefore, reduce education-related smoking disparities.
Palaeogeographical homogeneity of trace-fossil assemblages in Lower Jurassic spotted marls and limestones: comparison of the Western Carpathians and the Betic Cordillera
Authors: Šimo Vladimír , Reolid Matías 
Published: February 2021

Abstract

Micritic sediments containing dark, discrete, organic-rich burrows, situated in a light grey background carbonate mud, were deposited over a broad geographical area in deep-shelf, bathyal and basinal environments in the western margin of the Tethys Ocean during the Early and Middle Jurassic. These hemipelagic deposits represent a distinct depositional regime marked by low-energy, soft-bottom and only locally dysoxic environments. Still, it is unclear whether the trace-fossil assemblages occurring in these deposits pertain to a network of several community types – the ichnotaxa differing from basin to basin – or to a single community of environmentally broad-ranging, burrow-producing species. Lower Jurassic trace-fossil assemblages are found in the Western Carpathians and in the Subbetic, Betic Cordillera: that is, in basins separated by more than 2000 km in their original palaeogeographical areas. The stereotypical
Chondrites
and
Zoophycos
trace-fossil assemblages that occur in the analysed deposits share two ichnogenera of distinctive morphology (
Lamellaeichnus
and
Teichichnus
). Agglutinated foraminifera
Bathysiphon
occurs together with the described trace-fossil assemblage and determines the epibenthic palaeoenvironmental conditions. In the Western Carpathians, a
Lamellaeichnus
-dominated assemblage alternates with a
Zoophycos
-dominated assemblage in small, metre-scale cycles in the upper Pliensbachian, and the proportion of the
Zoophycos
assemblage increases stratigraphically upwards, probably owing to reduced basin ventilation during the early Toarcian. Within the southern Iberian palaeomargin, represented by the Betic Cordillera,
Zoophycos
is scarce in the facies.
Experimental and Numerical Studies on Permeability Properties of Thermal Damaged Red Sandstone under Different Confining Pressures
Authors: Zhao Zhenlong , Jing Hongwen , Fu Guangping , Yin Qian , Shi Xinshuai , Gao Yuan 
Published: February 2021

The stability and safety of underground rock mass engineering are closely related to the permeability process of fluids and permeability properties of rocks. To reveal the flow behavior of fluid in thermal damaged rock, first, a rock seepage testing system was applied to study the permeability properties of red sandstone specimens after different high-temperature treatments from 200 to 800°C under different confining pressures of 10 to 30 MPa. Meanwhile, the microstructures of the red sandstone specimens were characterized by the mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). Then, the permeability process of pore water pressure and the flow form of fluid also were investigated by the numerical modeling method. The results show that the permeability properties of red sandstone specimens after high-temperature exposure follow linear Darcy’s law, and the relation between confining pressures and equivalent permeability coefficient (

K

0

) can be described by a power function. Besides, the phenomenon that microscopic structural deterioration is intensified with increasing temperature and the average pore size and porosity of the red sandstone specimens are both power functions is related to the equivalent permeability coefficient. Furthermore, the results of numerical modeling indicated that the flow field within the range affected by confining pressures gradually becomes stable and orderly from disorder, and flow lines of the fluid become smooth and straight, and perpendicular to the isosurface of pore water pressure as time goes by. Moreover, the nonlinear correlation between pore water pressure and seepage path length changes to a linear correlation, which is consistent with linear Darcy’s law.
Cardiovascular Risk Factor Profiles and Disease in Black Compared to Other Africans with Chronic Kidney Disease
Authors: Hsu Hon-Chun , Robinson Chanel , Woodiwiss Angela J. , Norton Gavin R. , Dessein Patrick H. 
Published: February 2021

Background and Objectives. The extent to which chronic kidney disease (CKD) impacts cardiovascular disease (CVD) in black Africans is uncertain. We compared cardiovascular risk factors and CVD between black and other African CKD patients. Methods. Cardiovascular risk factors, aortic and cardiac function, atherosclerosis extent, and cardiovascular event rates were assessed in 115 consecutive predialysis (n = 67) and dialysis patients (n = 48) including 46 black and 69 other (32 Asian, 28 white, and 9 mixed race) participants. Data were analysed in multivariable regression models. Results. Overall, black compared to other African CKD patients had less frequent carotid artery plaque (OR (95% CI) = 0.38 (0.16–0.91)) despite an increased cardiovascular risk factor burden. In receiver operator characteristic curve analysis, the Framingham score performed well in identifying non-black but not black CKD patients with carotid plaque (area under the curve (AUC) (95% CI) = 0.818 (0.714–0.921) and AUC (95% CI) = 0.556 (0.375–0.921), respectively). Black compared to other African predialysis patients experienced larger Framingham scores and more adverse nontraditional cardiovascular risk factors, impaired arterial and diastolic function but similar cardiovascular event rates (OR (95% CI) = 0.93 (0.22 to 3.87)). Among dialysis patients, black compared to other Africans had an overall similar traditional and nontraditional cardiovascular risk factor burden, similar arterial and diastolic function but increased systolic function (partial R = 0.356,

p

= 0.01 and partial R = 0.315,

p

= 0.03 for ejection fraction and stroke volume, respectively) and reduced cardiovascular event rates (OR (95% CI) = 0.22 (0.05 to 0.88)). Conclusion. Black compared to other African CKD patients have less frequent very high risk atherosclerosis and experience weaker cardiovascular risk factor-atherosclerotic CVD relationships. These disparities may be due to differences in epidemiological health transition stages. Among dialysis patients, black compared to other Africans have less cardiovascular events, which may represent a selection bias as previously documented in black Americans.
Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules
Authors: Singh Kamini , Lin Jianan , Lecomte Nicolas , Mohan Prathibha , Gokce Askan , Sanghvi Viraj R. , Jiang Man , Grbovic-Huezo Olivera , Burčul Antonija , Stark Stefan G. , Romesser Paul B. , Chang Qing , Melchor Jerry P. , Beyer Rachel K. , Duggan Mark , Fukase Yoshiyuki , Yang Guangli , Ouerfelli Ouathek , Viale Agnes , de Stanchina Elisa , Stamford Andrew W. , Meinke Peter T. , Rätsch Gunnar , Leach Steven D. , Ouyang Zhengqing , Wendel Hans-Guido 
Published: February 2021

AbstractPancreatic adenocarcinoma (PDAC) epitomizes a deadly cancer driven by abnormal KRAS signaling. Here, we show that the eIF4A RNA helicase is required for translation of key KRAS signaling molecules and that pharmacological inhibition of eIF4A has single-agent activity against murine and human PDAC models at safe dose levels. EIF4A was uniquely required for the translation of mRNAs with long and highly structured 5′ untranslated regions, including those with multiple G-quadruplex elements. Computational analyses identified these features in mRNAs encoding KRAS and key downstream molecules. Transcriptome-scale ribosome footprinting accurately identified eIF4A-dependent mRNAs in PDAC, including critical KRAS signaling molecules such as PI3K, RALA, RAC2, MET, MYC, and YAP1. These findings contrast with a recent study that relied on an older method, polysome fractionation, and implicated redox-related genes as eIF4A clients. Together, our findings highlight the power of ribosome footprinting in conjunction with deep RNA sequencing in accurately decoding translational control mechanisms and define the therapeutic mechanism of eIF4A inhibitors in PDAC.Significance:These findings document the coordinate, eIF4A-dependent translation of RAS-related oncogenic signaling molecules and demonstrate therapeutic efficacy of eIF4A blockade in pancreatic adenocarcinoma.
PGE2 Released by Pancreatic Cancer Cells Undergoing ER Stress Transfers the Stress to DCs Impairing Their Immune Function
Authors: Gilardini Montani Maria Saveria , Benedetti Rossella , Piconese Silvia , Pulcinelli Fabio Maria , Timperio Anna Maria , Romeo Maria Anele , Masuelli Laura , Mattei Maurizio , Bei Roberto , D'Orazi Gabriella , Cirone Mara 
Published: February 2021

AbstractThis study shows that pancreatic cancer cells undergoing cell death by valproic acid (VPA) treatment activated dendritic cells (DCs) more efficiently than those treated with trichostatin A (TSA), as demonstrated by CD86 and CD80 surface expression. Surprisingly though, DCs cultured in the presence of supernatant derived from VPA-treated cancer cells showed a reduced allostimulatory capacity and an increased release of IL10 and IL8 cytokines in comparison with those exposed to TSA-treated cell culture supernatant. Searching for molecular mechanisms leading to such differences, we found that VPA treatment dysregulated choline metabolism and triggered a stronger endoplasmic reticulum (ER) stress in pancreatic cancer cells than TSA, upregulating CCAAT/enhancer-binding protein homologous protein, and activated cyclooxygenase-2, thus promoting the release of prostaglandin (PG) E2. Interestingly, dysfunctional DCs cultured in the presence of VPA-treated cells culture supernatant showed a higher level of intracellular reactive oxygen species, 4-hydroxy-trans-2-nonenal protein adducts, and ER stress, as evidenced by the upregulation of spliced X-box binding protein 1 (XBP1s), effects that were reduced when DCs were exposed to supernatant of cancer cells treated with Celecoxib before VPA. Celecoxib prevented PGE2 release, restoring the function of DCs exposed to VPA-treated cells culture supernatant, and a similar effect was obtained by silencing XBP1s in DCs treated with VPA-treated cells culture supernatant. These results suggest that PGE2 could be one of the yet unidentified factors able to transfer the stress from cancer cells to DCs, resulting in an impairment of their function.