bluuebunny/crossref_metadata_2025_split huggingface dataset:
A lncRNA TCL6-miR-155 Interaction Regulates the Src-Akt-EMT Network to Mediate Kidney Cancer Progression and Metastasis
Authors: Kulkarni Priyanka , Dasgupta Pritha , Hashimoto Yutaka , Shiina Marisa , Shahryari Varahram , Tabatabai Z. Laura , Yamamura Soichiro , Tanaka Yuichiro , Saini Sharanjot , Dahiya Rajvir , Majid Shahana 
Published: January 2021

AbstractMetastasis is the leading cause of mortality from kidney cancer, and understanding the underlying mechanism of this event will provide better strategies for its management. Here we investigated the biological, functional, and clinical significance of lncTCL6 and its interacting miR-155 in clear cell renal cell carcinoma (ccRCC). We employed a comprehensive approach to investigate the lncTCL6-miR-155-Src/Akt–mediated epithelial-to-mesenchymal transition (EMT) pathway as a novel regulatory mechanism in ccRCC progression. Expression analyses revealed that lncTCL6 is downregulated in ccRCC compared with normal tissues. Overexpression of lncTCL6 in ccRCC cell lines impaired their oncogenic functions, such as cell proliferation and migration/invasion, and induced cell-cycle arrest and apoptosis; conversely, depletion of lncTCL6 rescued these phenotypic effects. Furthermore, lncTCL6 directly interacted with miR-155. Unlike lncTCL6, miR-155 was overexpressed in ccRCC. Stable knockdown of miR-155 phenocopied the effects of lncTCL6 overexpression. Conversely, reconstitution of miR-155 and suppression of lncTCL6 in noncancerous renal cell HK2 induced tumorigenic characteristics. Patients with higher expression of lncTCL6 and lower expression of miR-155 had better survival probability. When overexpressed, lncTCL6 recruited STAU1 and mediated decay of Src mRNA, followed by a marked downregulation of an integrated network of Src target genes involved in migration, invasion, and EMT. However, the interaction between miR-155 and lncTCL6 attenuated the regulatory role of lncTCL6 on Src-mediated EMT. In conclusion, this study is the first report documenting the lncTCL6-miR155-Src/Akt/EMT network as a novel regulatory mechanism in aggressive ccRCC and a promising therapeutic target to inhibit renal cancer.Significance:This study's investigation of noncoding RNA interactions in renal cell carcinoma identify miRNA-155-lncRNA TCL6-mediated regulation of the Src-Akt-EMT network as a novel mechanism of disease progression and metastasis.
Variables Associated with Detection of Methylated BCAT1 or IKZF1 in Blood from Patients Without Colonoscopically Evident Colorectal Cancer
Authors: Saluja Hariti , Young Graeme P. , Kholmurodova Feruza , Symonds Erin L. 
Published: January 2021

Abstract

Background:
DNA methylated in BCAT1 and IKZF1 are promising circulating tumor DNA (ctDNA) biomarkers for colorectal cancer detection. This study tested for variables that might be associated with their detection in patients without colonoscopically evident colorectal cancer so-called false positives.

Methods:
A retrospective review of demographic and clinical variables was conducted on patients who were assayed for these biomarkers prior to a colonoscopy for any indication. Potential relationships between detection of these biomarkers and patient variables in patients without colorectal cancer were identified by logistic regression. An age- and sex-matched case–control study was undertaken to identify additional associations.

Results:
A total of 196 of 1,593 patients undergoing colonoscopy were positive for BCAT1 and/or IKZF1 methylation; 70 (35.7%) had confirmed diagnosis of colorectal cancer. Of the 126 false positives, biomarker levels were significantly lower than in those with colorectal cancer (P &lt; 0.05), with the total cell-free circulating DNA concentration associated with biomarker detection (OR, 1.16; 95% CI, 1.10–1.22), and 83 (65.9%) of the non-colorectal cancer cases positive for methylated BCAT1 only. Age ≥70 years was the only demographic variable associated with biomarker detection (OR, 4.31; 95% CI, 1.50–12.41). No significant associations were seen with medications or comorbidities (P &gt; 0.05). Four cases without colonoscopically evident colorectal cancer but with biomarker levels above the median for patients with colorectal cancer were diagnosed with metastatic adenocarcinoma within 1 year.

Conclusions:
False-positive results were most commonly associated with detection of methylated BCAT1 only, as well as age ≥70 years.

Impact:
In the absence of colonoscopically evident colorectal cancer, a high level of circulating methylated DNA warrants investigations for cancers at other sites.
Functional Hierarchy and Cooperation of EMT Master Transcription Factors in Breast Cancer Metastasis
Authors: Addison Joseph B. , Voronkova Maria A. , Fugett James H. , Lin Chen-Chung , Linville Nathaniel C. , Trinh Brandon , Livengood Ryan H. , Smolkin Matthew B. , Schaller Michael D. , Ruppert J. Michael , Pugacheva Elena N. , Creighton Chad J. , Ivanov Alexey V. 
Published: January 2021

Abstract

Several master transcription factors (TF) can activate the epithelial-to-mesenchymal transition (EMT). However, their individual and combinatorial contributions to EMT in breast cancer are not defined. We show that overexpression of EMT-TFs individually in epithelial cells upregulated endogenous SNAI2, ZEB1/2, TCF4, and TWIST1/2 as a result of positive feedback mediated in part by suppression of their negative regulator miRNAs miR200s/203/205. We identified TCF4 as a potential new target of miR200s. Expression of ZEB1/2 strongly correlated with the mesenchymal phenotype in breast cancer cells, with the CD24−/CD44+ stemness profile, and with lower expression of core epithelial genes in human breast tumors. Knockdown of EMT-TFs identified the key role of ZEB1 and its functional cooperation with other EMT-TFs in the maintenance of the mesenchymal state. Inducible ZEB1+2 knockdown in xenograft models inhibited pulmonary metastasis, emphasizing their critical role in dissemination from primary site and in extravasation. However, ZEB1+2 depletion one-week after intravenous injection did not inhibit lung colonization, suggesting that ZEB1/2 and EMT are not essential for macrometastatic outgrowth. These results provide strong evidence that EMT is orchestrated by coordinated expression of several EMT-TFs and establish ZEB1 as a key master regulator of EMT and metastasis in breast cancer.

Implications:
The EMT program is orchestrated by coordinated expression of multiple EMT transcription factors, whereas ZEB1 integrates the EMT master regulatory network and plays the major role in promoting EMT and metastasis.
Old Dog, New Trick: Type I IFN–Based Treatment for Acute Myeloid Leukemia
Authors: Alsufyani Abdullah , Alanazi Rehab , Woolley John F. , Dahal Lekh N. 
Published: January 2021

Abstract
Despite strong biological rationale for the use of type-I IFNs for the treatment of acute myeloid leukemia (AML), their usage is limited to few hematologic malignancies. Here, we propose that innate immune sensing machinery, particularly the stimulator of IFN genes pathway, may be exploited to deliver antileukemic effects in AML.
Trajectories of Left Ventricular Ejection Fraction After Acute Decompensation for Systolic Heart Failure: Concomitant Echocardiographic and Systemic Changes, Predictors, and Impact on Clinical Outcomes
Authors: Albert Judith , Lezius Susanne , Störk Stefan , Morbach Caroline , Güder Gülmisal , Frantz Stefan , Wegscheider Karl , Ertl Georg , Angermann Christiane E. 
Published: January 2021

Background
Prospective longitudinal follow‐up of left ventricular ejection fraction (LVEF) trajectories after acute cardiac decompensation of heart failure is lacking. We investigated changes in LVEF and covariates at 6‐months' follow‐up in patients with a predischarge LVEF ≤40%, and determined predictors and prognostic implications of LVEF changes through 18‐months' follow‐up.

Methods and Results

Interdisciplinary Network Heart Failure program participants (n=633) were categorized into subgroups based on LVEF at 6‐months' follow‐up: normalized LVEF (>50%; heart failure with normalized ejection fraction, n=147); midrange LVEF (41%–50%; heart failure with midrange ejection fraction, n=195), or persistently reduced LVEF (≤40%; heart failure with persistently reduced LVEF , n=291). All received guideline‐directed medical therapies. At 6‐months' follow‐up, compared with patients with heart failure with persistently reduced LVEF, heart failure with normalized LVEF or heart failure with midrange LVEF subgroups showed greater reductions in LV end‐diastolic/end‐systolic diameters (both
P
<0.001), and left atrial systolic diameter (
P
=0.002), more increased septal/posterior end‐diastolic wall‐thickness (both
P
<0.001), and significantly greater improvement in diastolic function, biomarkers, symptoms, and health status. Heart failure duration <1 year, female sex, higher predischarge blood pressure, and baseline LVEF were independent predictors of LVEF improvement. Mortality and event‐free survival rates were lower in patients with heart failure with normalized LVEF (
P
=0.002). Overall, LVEF increased further at 18‐months' follow‐up (
P
<0.001), while LV end‐diastolic diameter decreased (
P
=0.048). However, LVEF worsened (
P
=0.002) and LV end‐diastolic diameter increased (
P
=0.047) in patients with heart failure with normalized LVEF hospitalized between 6‐months' follow‐up and 18‐months' follow‐up.

Conclusions
Six‐month survivors of acute cardiac decompensation for systolic heart failure showed variable LVEF trajectories, with >50% showing improvements by ≥1 LVEF category. LVEF changes correlated with various parameters, suggesting multilevel reverse remodeling, were predictable from several baseline characteristics, and were associated with clinical outcomes at 18‐months' follow‐up. Repeat hospitalizations were associated with attenuation of reverse remodeling.

Registration

URL:
https://www.controlled‐trials.com
; Unique identifier: ISRCTN23325295.
Independent and Synergistic Effects of High Blood Pressure and Obesity on Retinal Vasculature in Young Children: The Hong Kong Children Eye Study
Authors: Ho Agnes , Cheung Carol Y. , Wong Jason S. , Zhang Yuzhou , Tang Fang Yao , Kam Ka Wai , Young Alvin L. , Chen Li Jia , Ip Patrick , Wong Tien Y. , Pang Chi Pui , Tham Clement C. , Yam Jason C. 
Published: January 2021

Background
High blood pressure (BP) and obesity are becoming increasingly prevalent among children globally. Although prior studies have shown their adverse impacts on macrovascular health, less is known about their effects on microvascular heath. This study aims to evaluate the independent and synergistic effects of hypertensive BP and obesity on retinal vasculature in young children.

Method and Results

1006 children aged 6 to 8 years were recruited from the Hong Kong Children Eye Study. Quantitative retinal vascular parameters, including central retinal arteriolar and venular equivalents and retinal arteriolar and venular fractal dimensions, were measured from retinal photographs following a standardized protocol. BP and body mass index were categorized according to reference values from American Academy of Pediatrics and International Obesity Task Force guidelines respectively. Children with hypertensive systolic BP had the narrowest central retinal arteriolar equivalents compared with children with either elevated or normotensive systolic BP (162.4, 164.6, and 167.1 µm;
P
‐trend <0.001). Increased standardized systolic BP was associated with narrower central retinal arteriolar equivalents (β=−2.276 µm,
P
<0.001), wider central retinal venular equivalents (1.177,
P
=0.007), and decreased arteriolar fractal dimensions (β=−0.004,
P
=0.034). Children with obesity had the smallest arteriolar fractal dimensions compared with children with overweightness and normal weight (1.211, 1.234, and 1.240;
P
‐trend=0.004). Children with both hypertensive BP and either overweightness or obesity had the narrowest central retinal arteriolar equivalents and smallest arteriolar

D
f

(
P
‐trend<0.001 and
P
‐trend=0.007).

Conclusions
Our findings demonstrate the potential synergistic or additive effects for both hypertensive BP and obesity on retinal vasculature in children.
New record of Agrisius Walker (Lepidoptera, Erebidae, Arctiinae) from Cambodia, with description of a new species
Authors: BAYARSAIKHAN ULZIIJARGAL , LEE TAK-GI , VOLYNKIN ANTON V. , YUNUSBAEV URAL , KWON HYUNG WOOK , BAE YANG-SEOP 
Published: January 2021

The genus Agrisius Walker (1855) is reported for the first time in Cambodia, for the new species Agrisius nigripunctata sp. n. Additionally, Agrisius fuliginosus is reported for the first time in Laos, Myanmar, China, Thailand and Vietnam. Illustrations of the adult and genitalia of Agrisius nigripunctata sp. n. and A. fuliginosus Moore are presented.
Drivers of Local Ocean Heat Content Variability in ECCOv4
Authors: Tesdal Jan-Erik , Abernathey Ryan P. 
Published: January 2021

AbstractVariation in upper-ocean heat content is a critical factor in understanding global climate variability. Using temperature anomaly budgets in a two-decade-long physically consistent ocean state estimate (ECCOv4r3; 1992–2015), we describe the balance between atmospheric forcing and ocean transport mechanisms for different depth horizons and at varying temporal and spatial resolutions. Advection dominates in the tropics, while forcing is most relevant at higher latitudes and in parts of the subtropics, but the balance of dominant processes changes when integrating over greater depths and considering longer time scales. While forcing is shown to increase with coarser resolution, overall the heat budget balance between it and advection is remarkably insensitive to spatial scale. A novel perspective on global ocean heat content variability was made possible by combining unsupervised classification with a measure of temporal variability in heat budget terms to identify coherent dynamical regimes with similar underlying mechanisms, which are consistent with prior research. The vast majority of the ocean includes significant contributions by both forcing and advection. However advection-driven regions were identified that coincide with strong currents, such as western boundary currents, the Antarctic Circumpolar Current, and the tropics, while forcing-driven regions were defined by shallower wintertime mixed layers and weak velocity fields. This identification of comprehensive dynamical regimes and the sensitivity of the ocean heat budget analysis to exact resolution (for different depth horizons and at varying temporal and spatial resolutions) should provide a useful orientation for future studies of ocean heat content variability in specific ocean regions.
Gender Differences in Concerns About Participating in Cancer Research During the COVID-19 Pandemic
Authors: Fox Louis , Wylie Harriet , Cahill Fee , Haire Anna , Green Saran , Kibaru Joyce , Hartley Catherine , Sullivan Richard , Van Hemelrijck Mieke 
Published: January 2021

Introduction: The ongoing SARS-CoV-2 pandemic is having major effects on cancer research, including major reductions in participant accrual to cancer clinical trials. Existing research has indicated that these steep drops in accrual rates to cancer clinical trials may be disproportionately affecting women. We sought to determine if there were gender differences in a dataset collected to examine participants’ concerns about taking part in cancer research during the pandemic. Methods: Between 5-19 June 2020, we distributed a fully anonymized survey via social media. We contacted 85 UK cancer patient organizations/charities and asked them to share our questionnaire on their platforms, of which 26 obliged. Patients aged 18 with a cancer diagnosis were eligible to participate and asked about their clinical and demographic characteristics, concerns about research participation given the COVID-19 pandemic, anxiety levels measured using the Generalized Anxiety Disorder-7 (GAD-7) scale, amongst other questions. Anxiety levels and concerns about participating were compared between men and women using univariate and multivariate analyses. Results: 93 individuals, comprising n = 37 women and n = 56 men of various cancer types, provided survey responses. Independent t-tests showed that women reported higher anxiety scores, and concerns about participating in cancer research during COVID-19, than men. Linear regression analyses showed that anxiety scores predicted concerns about research participation in women but not men (pinteraction = 0.002). Conclusions: Cancer patients have concerns about participating in research during the COVID-19 pandemic that range from mild to serious. Furthermore, the relationship between general anxiety and concerns about research participation may be both more relevant and more pronounced in women than in men. Future work should examine the reasons why women are less likely to enrol in cancer trials during the COVID-19 pandemic.
Competitive Risk Analysis of Prognosis in Patients With Cecum Cancer: A Population-Based Study
Authors: Wu Wentao , Yang Jin , Li Daning , Huang Qiao , Zhao Fanfan , Feng Xiaojie , Yan Hong , Lyu Jun 
Published: January 2021

Background: The presence of competing risks means that the results obtained using the classic Cox proportional-hazards model for the factors affecting the prognosis of patients diagnosed with cecum cancer (CC) may be biased. Objective: The purpose of this study was to establish a competitive risk model for patients diagnosed with CC to evaluate the relevant factors affecting the prognosis of patients, and to compare the results with the classical COX proportional risk model. Methods: We extracted data on patients diagnosed with CC registered between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The univariate analysis utilized the cumulative incidence function and Gray’s test, while a multivariate analysis was performed using the Fine-Gray, cause-specific (CS), and Cox proportional-hazards models. Results: The 54463 eligible patients diagnosed with CC included 24387 who died: 12087 from CC and 12300 from other causes. The multivariate Fine-Gray analysis indicated that significant factors affecting the prognosis of patients diagnosed with CC include: age, race, AJCC stage, differentiation grade, tumor size, surgery, radiotherapy, chemotherapy and regional lymph nodes metastasis. Due to the presence of competitive risk events, COX model results could not provide accurate estimates of effects and false-negative results occurred. In addition, COX model misestimated the direction of association between regional lymph node metastasis and cumulative risk of death in patients diagnosed with CC. Competitive risk models tend to be more advantageous when analyzing clinical survival data with multiple endpoints. Conclusions: The present study can help clinicians to make better clinical decisions and provide patients diagnosed with CC with better support.
A systematic review of quality of life in sickle cell disease and thalassemia after stem cell transplant or gene therapy
Authors: Badawy Sherif M. , Beg Usman , Liem Robert I. , Chaudhury Sonali , Thompson Alexis A. 
Published: January 2021

Abstract
Patients with sickle cell disease (SCD) and thalassemia experience several complications across their lifespan that lead to impairment in different health-related quality of life (HRQOL) domains. There is increasing interest in curative therapies for patients with SCD and thalassemia, including hematopoietic stem cell transplant (HSCT) and gene therapy; however, the effect of these therapies on various HRQOL domains remains unclear. Our objective was to systematically evaluate the most recent evidence for the effect of HSCT and gene therapy on HRQOL in patients with SCD and thalassemia. A systematic search of medical literature databases was conducted. A total of 16 studies (thalassemia, n = 9; SCD, n = 6; both, n = 1) involving 517 participants met inclusion criteria (thalassemia, n = 416; SCD, n = 101). HSCT was associated with a small to large positive effects in most HRQOL domains (Cohen’s d; mean = 0.47; median = 0.37; range, 0.27-2.05). In thalassemia, HSCT was frequently associated with large positive effects in physical and emotional HRQOL domains (median d = 0.79 and d = 0.57, respectively). In SCD, HSCT was associated with large positive effects in all HRQOL domains. Emerging data suggest improvement in HRQOL outcomes across different domains following gene therapy in thalassemia and SCD. The quality of evidence was moderate in 13 studies (81%). HSCT has a positive impact on several HRQOL domains in patients with SCD and thalassemia; however, more longitudinal studies are warranted to assess the sustainability of these effects. Reporting HRQOL outcomes from ongoing gene therapy or gene-editing trials in SCD and thalassemia is key to better understand the benefits of such therapies.
Impact of SARS-CoV-2 on the mobility behaviour in Germany
Authors: Anke Juliane , Francke Angela , Schaefer Lisa-Marie , Petzoldt Tibor 
Published: January 2021

AbstractBackgroundThe COVID-19 pandemic and the measures taken to combat it led to severe constraints for various areas of life, including mobility. To study the effects of this disruptive situation on the mobility behaviour of entire subgroups, and how they shape their mobility in reaction to the special circumstances, can help to better understand, how people react to external changes.MethodologyAim of the study presented in this article was to investigate to what extent, how and in what areas mobility behaviour has changed during the outbreak of SARS-CoV-2 in Germany. In addition, a focus was put on the comparison of federal states with and without lockdown in order to investigate a possible contribution of this measure to changes in mobility. We asked respondents via an online survey about their trip purposes and trip frequency, their choice of transport mode and the reasons for choosing it in the context of the COVID-19 crisis. For the analyses presented in this paper, we used the data of 4157survey participants (2512 without lockdown, 1645 with lockdown).ResultsThe data confirmed a profound impact on the mobility behaviour with a shift away from public transport and increases in car usage, walking and cycling. Comparisons of federal states with and without lockdown revealed only isolated differences. It seems that, even if the lockdown had some minor effects, its role in the observed behavioural changes was minimal.