bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impending radiographic erosive progression over the following year in a cohort of consecutive patients with inflammatory polyarthritis: prediction by serum biomarkers
Authors: Carrier Nathalie , de Brum-Fernandes Artur J , Liang Patrick , Masetto Ariel , Roux Sophie , Biln Norma K , Maksymowych Walter P , Boire Gilles 
Published: May 2020

Background/PurposeTo evaluate biomarkers as predictors of impending erosion progression.MethodsVariables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits. Generalised estimating equations (GEEs) evaluated the effect on REP of positive anticyclic citrullinated peptides (ACPAs) and/or rheumatoid factor (RF), C-reactive protein ˃8.0 mg/L (High-CRP) and 14-3-3η protein ≥0.50 ng/mL (High-14-3-3η), alone and in combinations.ResultsOut of 2155 evaluations in 749 consecutive patients, REP occurred after 186 (8.6%) visits, including 13 (2.2%) in patients recruited since 2010. Only 18/537 (3.4%; 6/411 (1.5%) in non-erosive vs 12/126 (9.5%) in patients already erosive) visits without any positive biomarker were followed by REP; at least one biomarker was positive prior to REP in 168/186 (90.3%) visits. Being positive for all four biomarkers conferred a positive predictive value (PPV) of 30.0% (RR 21.8) in patients non-erosive at the visit versus 35.5% (RR 3.07) in those already erosive. High-14-3-3η increased REP only in visits with High-CRP (eg, RR 2.5 to 3.9 when ACPA also positive) and in patients with non-erosive status (eg, RR from 4.3 to 9.4 when also High-CRP).ConclusionsAdding High-14-3-3η to positive antibodies and CRP improves prediction of impending REP. Although REP is becoming rarer, signatures of biomarkers might help to adapt treatment strategies in at-risk individuals, even those already erosive.
A Qualitative Transcriptional Signature for Predicting Prognosis and Response to Bevacizumab in Metastatic Colorectal Cancer
Authors: Yang Jing , Song Kai , Guo Wenbing , Zheng Hailong , Fu Yelin , You Tianyi , Wang Kai , Qi Lishuang , Zhao Wenyuan , Guo Zheng 
Published: May 2020

Abstract
Bevacizumab is the molecular-targeted agent used for the antiangiogenic therapy of metastatic colorectal cancer. But some patients are resistant to bevacizumab, it needs an effective biomarker to predict the prognosis and responses of metastatic colorectal cancer (mCRC) to bevacizumab therapy. In this work, we developed a qualitative transcriptional signature to individually predict the response of bevacizumab in patients with mCRC. First, using mCRC samples treated with bevacizumab, we detected differentially expressed genes between response and nonresponse groups. Then, the gene pairs, consisting of at least one differentially expressed gene, with stable relative expression orderings in the response samples but reversal stable relative expression orderings in the nonresponse samples were identified, denoted as pairs-bevacizumab. Similarly, we screened the gene pairs significantly associated with primary tumor locations, donated as pairs-LR. Among the overlapped gene pairs between the pairs-bevacizumab and pairs-LR, we adopted a feature selection process to extract gene pairs that reached the highest F-score for predicting bevacizumab response status in mCRC as the final gene pair signature (GPS), denoted as 64-GPS. In two independent datasets, the predicted response group showed significantly better overall survival than the nonresponse group (P = 6.00e−4 in GSE72970; P = 0.04 in TCGA). Genomic analyses showed that the predicted response group was characterized by frequent copy number alternations, whereas the nonresponse group was characterized by hypermutation. In conclusion, 64-GPS was an objective and robust predictive signature for patients with mCRC treated with bevacizumab, which could effectively assist in the decision of clinical therapy.
FGFR Inhibition Enhances Sensitivity to Radiation in Non–Small Cell Lung Cancer
Authors: SenthilKumar Gopika , Fisher Michael M. , Skiba Justin H. , Miller Margot C. , Brennan Sean R. , Kaushik Saakshi , Bradley Samantha T. , Longhurst Colin A. , Buehler Darya , Nickel Kwangok P. , Iyer Gopal , Kimple Randall J. , Baschnagel Andrew M. 
Published: May 2020

Abstract
FGFRs are commonly altered in non–small cell lung cancer (NSCLC). FGFRs activate multiple pathways including RAS/RAF/MAPK, PI3K/AKT, and STAT, which may play a role in the cellular response to radiation. We investigated the effects of combining the selective FGFR 1-3 tyrosine kinase inhibitor AZD4547 with radiation in cell line and xenograft models of NSCLC. NSCLC cell lines were assessed with proliferation, clonogenic survival, apoptosis, autophagy, cell cycle, and DNA damage signaling and repair assays. In vivo xenografts and IHC were used to confirm in vitro results. NSCLC cell lines demonstrated varying degrees of FGFR protein and mRNA expression. In vitro clonogenic survival assays showed radiosensitization with AZD4547 in two NSCLC cell lines. In these two cell lines, an increase in apoptosis and autophagy was observed with combined radiation and AZD4547. The addition of AZD4547 to radiation did not significantly affect γH2AX foci formation. Enhanced xenograft tumor growth delay was observed with the combination of radiation and AZD4547 compared with radiation or drug alone. IHC results revealed inhibition of pMAPK and pS6 and demonstrated an increase in apoptosis in the radiation plus AZD4547 group. This study demonstrates that FGFR inhibition by AZD4547 enhances the response of radiation in FGFR-expressing NSCLC in vitro and in vivo model systems. These results support further investigation of combining FGFR inhibition with radiation as a clinical therapeutic strategy.
A Novel Combination Approach Targeting an Enhanced Protein Synthesis Pathway in MYC-driven (Group 3) Medulloblastoma
Authors: Chaturvedi Nagendra K. , Kling Matthew J. , Griggs Connor N. , Kesherwani Varun , Shukla Mamta , McIntyre Erin M. , Ray Sutapa , Liu Yutong , McGuire Timothy R. , Sharp J. Graham , Band Hamid , Joshi Shantaram S. , Coulter Don W. 
Published: May 2020

Abstract
The MYC oncogene is frequently amplified in patients with medulloblastoma, particularly in group 3 patients, who have the worst prognosis. mTOR signaling–driven deregulated protein synthesis is very common in various cancers, including medulloblastoma, that can promote MYC stabilization. As a transcription factor, MYC itself is further known to regulate transcription of several components of protein synthesis machinery, leading to an enhanced protein synthesis rate and proliferation. Thus, inhibiting enhanced protein synthesis by targeting the MYC and mTOR pathways together may represent a highly relevant strategy for the treatment of MYC-driven medulloblastoma. Here, using siRNA and small-molecule inhibitor approaches, we evaluated the effects of combined inhibition of MYC transcription and mTOR signaling on medulloblastoma cell growth/survival and associated molecular mechanism(s) in MYC-amplified (group 3) medulloblastoma cell lines and xenografts. Combined inhibition of MYC and mTOR synergistically suppressed medulloblastoma cell growth and induced G1 cell-cycle arrest and apoptosis. Mechanistically, the combined inhibition significantly downregulated the expression levels of key target proteins of MYC and mTOR signaling. Our results with RNA-sequencing revealed that combined inhibition synergistically modulated global gene expression including MYC/mTOR components. In addition, the combination treatment significantly delayed tumor growth and prolonged survival of MYC-amplified medulloblastoma xenografted mice by downregulating expression of MYC and the key downstream components of mTOR signaling, compared with single-agent therapy. Together, our findings demonstrated that dual inhibition of MYC (transcription) and mTOR (translation) of the protein synthesis pathway can be a novel therapeutic approach against MYC-driven medulloblastoma.
A Genome-scale CRISPR Screen Identifies the ERBB and mTOR Signaling Networks as Key Determinants of Response to PI3K Inhibition in Pancreatic Cancer
Authors: Milton Charlotte K. , Self Annette J. , Clarke Paul A. , Banerji Udai , Piccioni Federica , Root David E. , Whittaker Steven R. 
Published: May 2020

Abstract
KRAS mutation is a key driver of pancreatic cancer and PI3K pathway activity is an additional requirement for Kras-induced tumorigenesis. Clinical trials of PI3K pathway inhibitors in pancreatic cancer have shown limited responses. Understanding the molecular basis for this lack of efficacy may direct future treatment strategies with emerging PI3K inhibitors. We sought new therapeutic approaches that synergize with PI3K inhibitors through pooled CRISPR modifier genetic screening and a drug combination screen. ERBB family receptor tyrosine kinase signaling and mTOR signaling were key modifiers of sensitivity to alpelisib and pictilisib. Inhibition of the ERBB family or mTOR was synergistic with PI3K inhibition in spheroid, stromal cocultures. Near-complete loss of ribosomal S6 phosphorylation was associated with synergy. Genetic alterations in the ERBB–PI3K signaling axis were associated with decreased survival of patients with pancreatic cancer. Suppression of the PI3K/mTOR axis is potentiated by dual PI3K and ERBB family or mTOR inhibition. Surprisingly, despite the presence of oncogenic KRAS, thought to bestow independence from receptor tyrosine kinase signaling, inhibition of the ERBB family blocks downstream pathway activation and synergizes with PI3K inhibitors. Further exploration of these therapeutic combinations is warranted for the treatment of pancreatic cancer.
Inactivation of Fbxw7 Impairs dsRNA Sensing and Confers Resistance to PD-1 Blockade
Authors: Gstalder Cécile , Liu David , Miao Diana , Lutterbach Bart , DeVine Alexander L. , Lin Chenyu , Shettigar Megha , Pancholi Priya , Buchbinder Elizabeth I. , Carter Scott L. , Manos Michael P. , Rojas-Rudilla Vanesa , Brennick Ryan , Gjini Evisa , Chen Pei-Hsuan , Lako Ana , Rodig Scott , Yoon Charles H. , Freeman Gordon J. , Barbie David A. , Hodi F. Stephen , Miles Wayne , Van Allen Eliezer M. , Haq Rizwan 
Published: May 2020

Abstract

The molecular mechanisms leading to resistance to PD-1 blockade are largely unknown. Here, we characterize tumor biopsies from a patient with melanoma who displayed heterogeneous responses to anti–PD-1 therapy. We observe that a resistant tumor exhibited a loss-of-function mutation in the tumor suppressor gene FBXW7, whereas a sensitive tumor from the same patient did not. Consistent with a functional role in immunotherapy response, inactivation of Fbxw7 in murine tumor cell lines caused resistance to anti–PD-1 in immunocompetent animals. Loss of Fbxw7 was associated with altered immune microenvironment, decreased tumor-intrinsic expression of the double-stranded RNA (dsRNA) sensors MDA5 and RIG-I, and diminished induction of type I IFN and MHC-I expression. In contrast, restoration of dsRNA sensing in Fbxw7-deficient cells was sufficient to sensitize them to anti–PD-1. Our results thus establish a new role for the commonly inactivated tumor suppressor FBXW7 in viral sensing and sensitivity to immunotherapy.

Significance:
Our findings establish a role of the commonly inactivated tumor suppressor FBXW7 as a genomic driver of response to anti–PD-1 therapy. Fbxw7 loss promotes resistance to anti–PD-1 through the downregulation of viral sensing pathways, suggesting that therapeutic reactivation of these pathways could improve clinical responses to checkpoint inhibitors in genomically defined cancer patient populations.
This article is highlighted in the In This Issue feature, p. 1241
Life‐Course Reproductive History and Cardiovascular Risk Profile in Late Mid‐Life: The CARDIA Study
Authors: Lane‐Cordova Abbi D. , Gunderson Erica P. , Greenland Philip , Catov Janet M. , Lewis Cora E. , Pettee Gabriel Kelley , Wellons Melissa F. , Carnethon Mercedes R. 
Published: May 2020

Background

Reproductive events, that is, a preterm birth (
PTB
), small‐for‐gestational‐age infant (
SGA
), and vasomotor symptoms of menopause, are associated with subclinical atherosclerotic cardiovascular disease (
ASCVD
). We evaluated whether women with a past
PTB
and/or
SGA
(henceforth
PTB
/
SGA
) were more likely to have severe vasomotor symptoms of menopause and whether the estimated 10‐year
ASCVD
risk was higher in women with
PTB
/
SGA
and vasomotor exposures.

Methods and Results

We assigned 1866 women (mean age=55±1 years) in the
CARDIA
(Coronary Artery Risk Development in Young Adults) study to the following categories of reproductive exposures: none,
PTB
/
SGA
only, vasomotor symptoms only, or both
PTB
/
SGA
and vasomotor symptoms. We used Kruskal‐Wallis tests to evaluate the differences in pooled cohort equation
ASCVD
risk scores by category and linear regression to evaluate the associations of categories with
ASCVD
risk scores adjusted for study center,
body mass index
, education, current hormone replacement therapy use, parity, and hysterectomy. Women with
PTB
/
SGA
were more likely to have severe vasomotor symptoms, 36% versus 30%,
P
<0.02.
ASCVD
risk score was higher in women with both
PTB
/
SGA
and vasomotor symptoms (4.6%; 95% CI, 4.1%–5.1%) versus women with no exposures (3.3%; 95%
CI
, 2.9%–3.7%) or vasomotor symptoms only (3.8%; 95%
CI
, 3.5%–4.0%).
ASCVD
risk score was higher in women
PTB
/
SGA
(4.8%; 95%
CI
, 3.6%–5.9%) versus no exposures.
PTB
/
SGA
and vasomotor symptoms was associated with
ASCVD
risk score in white women versus no exposures (β=0.40; 95% CI, 0.02–0.78).

Conclusions

Women with prior
PTB
/
SGA
were more likely to have severe vasomotor symptoms of menopause. Reproductive exposures were associated with an estimated 10‐year
ASCVD
risk in white women.
Developing and Testing the Transformative Travel Experience Scale (TTES)
Authors: Soulard Joelle , McGehee Nancy , Knollenberg Whitney 
Published: May 2020

Transformative travel encourages tourists to self-reflect, question their assumptions, and develop a more tolerant worldview. While this form of travel is gaining attention, there is unmet demand for a scale that measures the complex transformative travel experience and potential outcomes. This study focuses on developing the Transformative Travel Experience Scale (TTES). The study applies a well-tested approach based on DeVellis and Podsakoff et al. to reveal that a four-dimensional scale, composed of the dimensions of local residents and culture, self-assurance, disorienting dilemma, and joy, can be successfully used to measure the process and outcomes of transformative travel. From a theoretical perspective, the findings suggest that the disorienting dilemma might occur at different points in time. The Transformative Travel Experience Scale is helpful to organizations that want to capture the positive changes resulting from participation in transformative travel when applying for certifications, awards, and grants.
Pneumatized Crista Galli: A Histopathologic Study
Authors: Marjanovic Kavanagh Marcel , Tokic Tomislav , Jakovcevic Antonia , Smiljanic Ranko , Bumber Boris , Prstacic Ratko 
Published: May 2020

ObjectiveThis is the first histopathologic study that investigates the incidence of the pneumatized crista galli.Study DesignA prospective histopathologic study.SettingTertiary academic medical center.Subjects and MethodsA total of 109 specimens of crista galli were obtained postmortem during 2018 from randomly chosen patients who died at the University Hospital Centre Zagreb and had an autopsy at our Department of Pathology and Cytology. Specimens were surgically resected during the autopsy and then fixed, decalcinated, dehydrated, and embedded in paraffin. All slides were cut into 5‐µm‐thin sections and stained with a standard method (hematoxylin and eosin) for light microscope analysis. Specimens were histopathologically analyzed for the existence of pneumatization inside crista galli. The criterion to declare a specimen pneumatized was the presence of mucosa inside the cavity.ResultsPneumatized crista galli was found in 5 of 109 specimens (4.59%). In 5 of 5 cases (100%) of pneumatized crista galli, there was evidence of chronic inflammation.ConclusionWe found that the incidence of pneumatized crista galli is significantly lower in our histopathologic study in comparison with the majority of previous radiologic studies. Our study also found that all 5 specimens with pneumatized crista galli had chronic inflammation in the mucosa, which is a considerably higher incidence than in the previous studies (7.7%‐44%). Due to the emerging evidence of pneumatized crista galli being of clinical importance, we suggest that a larger study be conducted before the results are generalized to the general population.
The Prevalence of Olfactory and Gustatory Dysfunction in COVID‐19 Patients: A Systematic Review and Meta‐analysis
Authors: Tong Jane Y. , Wong Amanda , Zhu Daniel , Fastenberg Judd H. , Tham Tristan 
Published: May 2020

ObjectiveTo determine the pooled global prevalence of olfactory and gustatory dysfunction in patients with the 2019 novel coronavirus (COVID‐19).Data SourcesLiterature searches of PubMed, Embase, and Scopus were conducted on April 19, 2020, to include articles written in English that reported the prevalence of olfactory or gustatory dysfunction in COVID‐19 patients.Review MethodsSearch strategies developed for each database contained keywords such as anosmia, dysgeusia, and COVID‐19. Resulting articles were imported into a systematic review software and underwent screening. Data from articles that met inclusion criteria were extracted and analyzed. Meta‐analysis using pooled prevalence estimates in a random‐effects model were calculated.ResultsTen studies were analyzed for olfactory dysfunction (n = 1627), demonstrating 52.73% (95% CI, 29.64%‐75.23%) prevalence among patients with COVID‐19. Nine studies were analyzed for gustatory dysfunction (n = 1390), demonstrating 43.93% (95% CI, 20.46%‐68.95%) prevalence. Subgroup analyses were conducted for studies evaluating olfactory dysfunction using nonvalidated and validated instruments and demonstrated 36.64% (95% CI, 18.31%‐57.24%) and 86.60% (95% CI, 72.95%‐95.95%) prevalence, respectively.ConclusionsOlfactory and gustatory dysfunction are common symptoms in patients with COVID‐19 and may represent early symptoms in the clinical course of infection. Increased awareness of this fact may encourage earlier diagnosis and treatment, as well as heighten vigilance for viral transmission. To our knowledge, this is the first meta‐analysis to report on the prevalence of these symptoms in COVID‐19 patients.
Is the standard deviation of the apparent diffusion coefficient a potential tool for the preoperative prediction of tumor grade in endometrial cancer?
Authors: Yan Bin , Liang Xiufen , Zhao Tingting , Ding Caixia , Zhang Ming 
Published: May 2020

Background The tumor histological grade is closely related to the prognosis of endometrial cancer (EC). The use of the apparent diffusion coefficient (ADC), tumor volume, and MRI-based texture analysis has allowed exciting advances in predicting EC grade before surgery. However, whether this constitutes a simple, convenient, and powerful diagnostic method remains unknown. Purpose To explore the utility of standard deviation (SD) of the ADC (ADCSD) for predicting the tumor grade in patients with EC. Material and Methods We retrospectively evaluated 138 patients with EC. All patients underwent unenhanced MRI and diffusion-weighted imaging (DWI). The mean ADC value (ADCmean) and SD were obtained using a freehand region of interest traced on the ADC map. Spearman’s linear correlation coefficients were calculated to analyze the correlations between the indexes (including ADCSD and the ADCmean) and the Ki-67 index. The Kruskal–Wallis and Mann–Whitney U tests were used to compare differences in the index results among tumor grades. Results A significant difference in ADCSD was observed among the tumor grades ( P=0.000), and the ADCSD value was significantly higher for high-grade EC than for low-grade tumors (289.7 vs. 216.3×10−6mm2 /s, P=0.000). A statistically significant positive correlation was observed between ADCSD and the Ki-67 index (r=0.364, P=0.000). According to the receiver operating characteristic curve, ADCSD ≥240.2×10−6mm2 /s predicted high-grade EC with a sensitivity, specificity, and accuracy of 73.1%, 80.2%, and 77.5%, respectively. Conclusion Based on the intratumor heterogeneity of EC, ADCSD represents a potential method for the preoperative prediction of high-grade EC, although further studies are needed.
Personal values among undergraduate nursing students: A cross-sectional study
Authors: Luciani Michela , Rampoldi Giulia , Ardenghi Stefano , Bani Marco , Merati Sandra , Ausili Davide , Grazia Strepparava Maria , Di Mauro Stefania 
Published: May 2020

Background: Personal values influence nursing students’ development of professional values, which affect professional outcomes, and how nursing students react to different situations. Personal values can be shaped by different factors, including culture, gender, and age. Aims: To explore personal values held by nursing students, and to verify if and how gender and year of study affect nursing students’ personal values. Research design: A multicenter, cross-sectional study was used. Participants and research context: The whole population of nursing undergraduate students available at the time was recruited from eight centers of two Universities, composing a sample of 947 students. Demographic data were collected and it was administered the Portrait Values Questionnaire. Ethical considerations: Ethical approval was obtained from the Institutional Review Boards of the University of the participating centers. Findings: The study sample was mainly composed of young (92.6%, n = 877), female (77.3%, n = 732), Italian (95.8%, n = 907), and unmarried (98.6%, n = 934) nursing students. The most important value for nursing students, consistently through the years of nursing school, was Self-transcendence, which has the motivational emphasis on helping others and selflessness. Then, we found that male students had higher levels of Power (p < 0.001) and Achievement (p = 0.031), while female students outscored male students in Benevolence (p = 0.005) and Security (p = 0.006). Year of study showed no statistically significant difference. Discussion: Nursing students express high levels in hetero-directed values. Male nursing students, although they choose a stereotypically feminine profession, outscored females in stereotypical masculine values such as dominance and success. This is the first study that describes the personal value profile of undergraduate nursing students, according to the Theory of Basic Human Values, and it is a starting point for future research. Conclusion: Nursing educators might want to consider the findings from this study while guiding students in developing awareness for their personal values.