bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer-Related Risk Perceptions and Beliefs in Texas: Findings from a 2018 Population-Level Survey
Authors: Cunningham Sonia A. , Yu Robert , Shih Tina , Giordano Sharon , McNeill Lorna H. , Rechis Ruth , Peterson Susan K. , Cinciripini Paul , Foxhall Lewis , Hawk Ernest , Shete Sanjay 
Published: January 2019

Abstract

Background:
Cancer beliefs and perceptions of cancer risk affect the cancer continuum. Identifying underlying factors associated with these beliefs and perceptions in Texas can help inform and target prevention efforts.

Methods:
We developed a cancer-focused questionnaire and administered it online to a nonprobability sample of the Texas population. Weighted multivariable logistic regression analysis identified key factors associated with perceptions and beliefs about cancer.

Results:
The study population comprised 2,034 respondents (median age, 44.4 years) of diverse ethnicity: 45.5% were non-Hispanic white, 10.6% non-Hispanic black, and 35.7% Hispanic. Self-reported depression was significantly associated with cancer risk perceptions and cancer beliefs. Those indicating frequent and infrequent depression versus no depression were more likely to believe that: (i) compared to other people their age, they were more likely to get cancer in their lifetime [OR, 2.92; 95% confidence interval (CI), 1.95–4.39 and OR, 1.79; 95% CI, 1.17–2.74, respectively]; and (ii) when they think about cancer, they automatically think about death (OR, 2.05; 95% CI, 1.56–2.69 and OR, 1.46; 95% CI, 1.11–1.92, respectively). Frequent depression versus no depression was also associated with agreement that (i) it seems like everything causes cancer (OR, 1.67; 95% CI, 1.26–2.22) and (ii) there is not much one can do to lower one's chance of getting cancer (OR, 1.44; 95% CI, 1.09–1.89). Other predictors for perceived cancer risk and/or cancer beliefs were sex, age, ethnicity/race, being born in the United States, marital status, income, body mass index, and smoking.

Conclusions:
Depression and other predictors are associated with cancer risk perceptions and beliefs in Texas.

Impact:
Increased attention to reducing depression may improve cancer risk perceptions and beliefs.
MicroRNA Dysregulation and Non-Muscle–Invasive Bladder Cancer Prognosis
Authors: Andrew Angeline S. , Karagas Margaret R. , Schroeck Florian R. , Marsit Carmen J. , Schned Alan R. , Pettus Jason R. , Armstrong David A. , Seigne John D. 
Published: January 2019

Abstract

Background:
The high rate of non-muscle–invasive bladder cancer recurrence is a major challenge in patient management. miRNAs functionally regulate tumor cell proliferation and invasion, and have strong potential as biomarkers because they are robust to degradation. The objective of this project was to identify reproducible prognostic miRNAs in resected non-muscle–invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype.

Methods:
We utilized patients diagnosed with primary non-muscle–invasive bladder cancer in three independent cohorts for a biomarker discovery/validation approach. Baseline tumor tissue from patients with the clinically challenging, non-muscle–invasive primary low stage (Ta), high grade, and T1 tumors (tumors extending into the lamina propria) comprised the discovery cohort (n = 38). We isolated the tumor tissue RNA and assessed a panel of approximately 800 miRNAs.

Results:
miR-26b-5p was the top-ranking prognostic tumor tissue miRNA, with a time-to-recurrence HR 0.043 for levels above versus below median, (Padj = 0.0003). miR-26b-5p was related to a dose-response reduction in tumor recurrence, and levels above the median were also associated with reduced time-to-progression (Padj = 0.02). We used two independent longitudinal cohorts that included both low-grade and high-grade Ta and T1 tumors for validation and found a consistent relationship between miR-26b-5p and recurrence and progression.

Conclusions:
Our results suggest that miR-26b-5p levels may be prognostic for non-muscle–invasive bladder cancer recurrence, and can feasibly be assessed in baseline tumor tissue from a wide variety of clinical settings.

Impact:
Early identification of those non-muscle–invasive bladder tumor patients with refractory phenotypes would enable individualized treatment and surveillance.
Allergies and the Subsequent Risk of Cancer among Elderly Adults in the United States
Authors: D'Arcy Monica , Rivera Donna R. , Grothen Andrew , Engels Eric A. 
Published: January 2019

AbstractBackground:Allergic conditions may prevent some cancers by promoting immune surveillance. We examined associations of allergic rhinitis, asthma, and eczema with cancer risk among elderly Americans.Methods:We used Surveillance Epidemiology and End Results (SEER)-Medicare linked data to perform a case–control study. Cases were individuals with first cancer diagnosed in SEER registries (1992–2013, ages 66–99; N = 1,744,575). Cancer-free controls (N = 100,000) were randomly selected from Medicare and matched on sex, age, and selection year. Allergic conditions were identified using Medicare claims, and logistic regression was used to estimate adjusted ORs (aOR) with significance gauged with a Bonferroni P cutoff (P &lt; 0.00034).Results:Allergic rhinitis, asthma, and eczema were present in 8.40%, 3.45%, and 0.78% of controls, respectively. For allergic rhinitis, strong inverse associations (aORs, 0.66–0.79) were observed for cancers of the hypopharynx, esophagus (squamous cell), cervix, tonsil/oropharynx, and vagina/vulva. More modest but significant inverse associations were noted for cancers of the esophagus (adenocarcinoma), stomach, colon, rectosigmoid/rectum, liver, gallbladder, lung, uterus, bladder, and miscellaneous sites. Associations were stronger in analyses requiring a dispensed medication to confirm the presence of allergic rhinitis. Asthma was associated with reduced risk of liver cancer [aOR 0.82; 95% confidence interval (CI), 0.75–0.91], whereas eczema was associated with elevated risk of T-cell lymphoma (aOR, 4.12; 95% CI, 3.43–4.95).Conclusions:Inverse associations with allergic rhinitis are present for multiple cancers and require etiologic investigation.Impact:Understanding of mechanisms by which allergic conditions reduce cancer risk may advance cancer prevention and treatment.
Hypoxia-Associated Factor (HAF) Mediates Neurofibromin Ubiquitination and Degradation Leading to Ras–ERK Pathway Activation in Hypoxia
Authors: Green Yangsook Song , Sargis Timothy , Reichert Ethan Conrad , Rudasi Eleanor , Fuja Daniel , Jonasch Eric , Koh Mei Yee 
Published: January 2019

AbstractLow oxygen or hypoxia is a feature of all solid tumors and has been associated with aggressive disease. Here, we describe a novel mechanism for the hypoxia-dependent degradation of the Ras-GTPase–activating protein neurofibromin, by hypoxia-associated factor (HAF). We have previously characterized HAF as an oxygen-independent ubiquitin ligase for HIF-1α. Here, we show that HAF promotes neurofibromin ubiquitination and degradation independently of oxygen and pVHL, resulting in Ras–ERK pathway activation. Hypoxia enhanced HAF:neurofibromin binding independently of HAF-SUMOylation, whereas HAF knockdown increased neurofibromin levels primarily in hypoxia, supporting the role of HAF as a hypoxia-specific neurofibromin regulator. HAF overexpression increased p-ERK levels and promoted resistance of clear cell kidney cancer (ccRCC) cells to sorafenib and sunitinib in both normoxia and hypoxia. However, a greater-fold increase in sorafenib/sunitinib resistance was observed during hypoxia, particularly in pVHL-deficient cells. Intriguingly, HAF-mediated resistance was HIF-2α–dependent in normoxia, but HIF-2α–independent in hypoxia indicating two potential mechanisms of HAF-mediated resistance: a HIF-2α–dependent pathway dominant in normoxia, and the direct activation of the Ras–ERK pathway through neurofibromin degradation dominant in hypoxia. Patients with ccRCC with high HAF transcript or protein levels showed significantly decreased overall survival compared with those with low HAF. Thus, we establish a novel, nonmutational pathway of neurofibromin inactivation through hypoxia-induced HAF-mediated degradation, leading to Ras–ERK activation and poor prognosis in ccRCC.Implications:We describe a novel mechanism of neurofibromin degradation induced by hypoxia that leads to activation of the prooncogenic Ras–ERK pathway and resistance to therapy.
Alpha-Blockers As Colorectal Cancer Chemopreventive: Findings from a Case–Control Study, Human Cell Cultures, and In Vivo Preclinical Testing
Authors: Suzuki Nobumi , Niikura Ryota , Ihara Sozaburo , Hikiba Yohko , Kinoshita Hiroto , Higashishima Naoko , Hayakawa Yoku , Yamada Atsuo , Hirata Yoshihiro , Nakata Ryo , Okamoto Makoto , Sano Munetaka , Kushiyama Akifumi , Ichinose Mari , Woods Susan L. , Worthley Daniel , Iwamoto Yasuhiko , Koike Kazuhiko 
Published: January 2019

Abstract
A retrospective case–controlled analysis was performed to identify drug candidates in the current use that may prevent colorectal cancer, outside of aspirin. A total of 37,510 patients aged ≥20 years were assessed to identify subjects who had been diagnosed with colorectal cancer by colonoscopy without a previous diagnosis of colorectal cancer, inflammatory bowel disease (IBD), or gastrointestinal symptoms; 1,560 patients were identified who were diagnosed with colorectal cancer by colonoscopy. The patients with colorectal cancer were matched with 1,560 age, gender, family history of colorectal cancer and comorbidity-matched control patients who were not diagnosed with colorectal cancer at colonoscopy. The medication histories were compared between the two groups. Next, candidate drugs that were more frequently used by the control patients were selected and their effects on human colorectal cancer cell lines in vitro and an inflammation-induced mouse model of colorectal cancer were tested. Putative colorectal cancer preventative agents were identified, including aspirin, vitamin D, vitamin B, vitamin C, vitamin E, xanthine oxidase inhibitor, alpha-blockers, angiotensin receptor blocker, nateglinide, probiotics, thienopyridine, folic acid, nitrovasodilators, bisphosphonates, calcium channel blockers, steroids, and statins (P &lt; 0.05). Alpha-blockers and xanthine oxidase inhibitors were selected for further study because these agents have not been analyzed previously as factors that may affect colorectal cancer outcomes. In vitro doxazosin (alpha-blocker), but not febuxostat (xanthine oxidase inhibitor), suppressed the proliferation of human colorectal cancer cells. Doxazosin also decreased tumorigenesis in an AOM/DSS mouse colorectal cancer model. Alpha-blockers may prevent colorectal cancer.
An Abstract Provides “seAFOod” for Thought
Authors: DeCensi Andrea , Gescher Andreas 
Published: January 2019

Abstract
A recent article published in The Lancet reports on the seAFOod trial, in which patients with colorectal adenomas received aspirin and/or eicosapentaenoic acid (EPA, an omega-3 polyunsaturated fatty acid) post-resection. The article's abstract indicates that the primary trial endpoint, adenoma detection rate, is negative, but it does not give any indication of the remarkable secondary endpoint (adenoma number) results, which strongly suggest chemopreventive efficacy of both agents. Given the difficulty researchers and physician-scientists experience in staying abreast of the latest literature in the field, inclusion of secondary findings in abstracts should be strongly considered.
Molecular and Genetic Characterization of MHC Deficiency Identifies EZH2 as Therapeutic Target for Enhancing Immune Recognition
Authors: Ennishi Daisuke , Takata Katsuyoshi , Béguelin Wendy , Duns Gerben , Mottok Anja , Farinha Pedro , Bashashati Ali , Saberi Saeed , Boyle Merrill , Meissner Barbara , Ben-Neriah Susana , Woolcock Bruce W. , Telenius Adèle , Lai Daniel , Teater Matt , Kridel Robert , Savage Kerry J. , Sehn Laurie H. , Morin Ryan D. , Marra Marco A. , Shah Sohrab P. , Connors Joseph M. , Gascoyne Randy D. , Scott David W. , Melnick Ari M. , Steidl Christian 
Published: January 2019

Abstract

We performed a genomic, transcriptomic, and immunophenotypic study of 347 patients with diffuse large B-cell lymphoma (DLBCL) to uncover the molecular basis underlying acquired deficiency of MHC expression. Low MHC-II expression defines tumors originating from the centroblast-rich dark zone of the germinal center (GC) that was associated with inferior prognosis. MHC-II–deficient tumors were characterized by somatically acquired gene mutations reducing MHC-II expression and a lower amount of tumor-infiltrating lymphocytes. In particular, we demonstrated a strong enrichment of EZH2 mutations in both MHC-I– and MHC-II–negative primary lymphomas, and observed reduced MHC expression and T-cell infiltrates in murine lymphoma models expressing mutant Ezh2Y641. Of clinical relevance, EZH2 inhibitors significantly restored MHC expression in EZH2-mutated human DLBCL cell lines. Hence, our findings suggest a tumor progression model of acquired immune escape in GC-derived lymphomas and pave the way for development of complementary therapeutic approaches combining immunotherapy with epigenetic reprogramming.

Significance:
We demonstrate how MHC-deficient lymphoid tumors evolve in a cell-of-origin–specific context. Specifically, EZH2 mutations were identified as a genetic mechanism underlying acquired MHC deficiency. The paradigmatic restoration of MHC expression by EZH2 inhibitors provides the rationale for synergistic therapies combining immunotherapies with epigenetic reprogramming to enhance tumor recognition and elimination.
See related commentary by Velcheti et al., p. 472.
This article is highlighted in the In This Issue feature, p. 453
АНАЛІЗ РЕСУРСІВ СИСТЕМИ НАДАННЯ ПЕРВИННОЇ МЕДИЧНОЇ ДОПОМОГИ НАСЕЛЕННЮ УКРАЇНИ ПРИ ХРОНІЧНОМУ ОБСТРУКТИВНОМУ ЗАХВОРЮВАННІ ЛЕГЕНЬ
Authors: Vasylyev A. H. 
Published: January 2019

Мета: вивчення ресурсів системи надання первинної медичної допомоги населенню України при хронічному обструктивному захворюванні легень.
Матеріали і методи. Наказом МОЗ України від 27.06.2013 р. № 555 передбачено відповідний обсяг надання медичної допомоги пацієнтам із хронічним обструктивним захворюванням легень лікарем загальної практики – сімейним лікарем.
Результати. Провівши аналіз ресурсів системи надання первинної медичної допомоги при хронічному обструктивному захворюванні легень, встановлено, що наразі відсутній чіткий механізм діяльності закладів охорони здоров’я, які надають медичну допомогу пацієнтам із хронічним обструктивним захворюванні легень, немає фактичного розмежування їх за рівнями, наявний кадровий дефіцит лікарів, відзначається низький рівень матеріально-технічного та фінансового забезпечення галузі.
Висновки. Впровадження нових організаційних засад щодо надання первинної медичної допомоги, які передбачатимуть вирішення питань діяльності закладів охорони здоров’я різних рівнів, кадрового дефіциту лікарів, підвищення матеріально-технічного та фінансового забезпечення первинної медико-санітарної допомоги, дасть змогу пацієнтам із хронічним обструктивним захворюванням легень отримувати якісну медичну допомогу, зберегти здоров’я та забезпечити перспективу подальшого життя на достатньому фізичному та соціальному рівнях.
Функціональний стан м’язів зубощелепного апарату до та після лікування дітей з аномаліями прикусу та мовленнєвими порушеннями
Authors: Flis P. S. , Raschenko N. V. , Filonenko V. V. , Melnyk A. O. , Etnis L. O. 
Published: January 2019

Під час обстеження ортодонтичних пацієнтів були діти з мовленнєвими порушеннями. Міодинамічна рівновага м’язів-антагоністів та синергістів – це відносна стійкість жувальних та мімічних м’язів, що протягом тривалого часу зберігається без помітних коливань, сприяє відносно стабільного стану зубощелепного апарату.
Мета дослідження – визначити функціональний стан м’язів зубощелепного апарату до та після лікування дітей з аномаліями прикусу та мовленнєвими порушеннями.
Матеріали і методи. Для досягнення поставленої мети було прийнято на лікування 44 пацієнти з вираженою ортодонтичною патологією та мовленнєвими порушеннями із нормальним слухом та інтелектом. Для визначення та аналізу показників біоелектричної активності м’язів використано метод сумарної (поверхневої) електроміографії.
Результати досліджень та їх обговорення. Після проведеного лікування спостерігали нормалізацію показників біоелектричної активності, зменшення парафункціональних проявів у м’язах та частоти спалахів спонтанної активності м’язів у стані спокою, нормалізація середньої амплітуди біопотенціалів у стані активності, відсутність фрагментацій, покращення синхронності та координації скорочень обстежених м’язів при усіх патологіях прикусу.
Висновки. Проведене ортодонтичне лікування забезпечило відновлення нейром’язового балансу зубощелепного апарату пацієнтів із різними патологіями прикусу, що має сприятливий вплив на корекцію мовленнєвих порушень.
Ambient Air Pollution Is Associated With HDL (High-Density Lipoprotein) Dysfunction in Healthy Adults
Authors: Li Jianping , Zhou Changping , Xu Hongbing , Brook Robert D. , Liu Shengcong , Yi Tieci , Wang Yang , Feng Baihuan , Zhao Mingming , Wang Xu , Zhao Qian , Chen Jie , Song Xiaoming , Wang Tong , Liu Shuo , Zhang Yi , Wu Rongshan , Gao Jianing , Pan Bing , Pennathur Subramaniam , Rajagopalan Sanjay , Huo Yong , Zheng Lemin , Huang Wei 
Published: January 2019

Objective—
We aimed to assess whether exposure to higher levels of ambient air pollution impairs HDL (high-density lipoprotein) function and to elucidate the underlying biological mechanisms potentially involved.

Approach and Results—

In the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults), 73 healthy adults (23.3±5.4 years) were followed-up with 4 repeated study visits in 2014 to 2016. During each visit, ambient air pollution concentrations, HDL function metrics, and parameters of inflammation and oxidative stress were measured. Average daily concentrations of ambient particulate matter in diameter <2.5 μm were 62.9 µg/m
3
(8.1–331.0 µg/m
3
). We observed significant decreases in HDL cholesterol efflux capacity of 2.3% (95% CI, −4.3 to −0.3) to 5.0% (95% CI, −7.6 to −2.4) associated with interquartile range increases in moving average concentrations of particulate matter in diameter <2.5 μm and traffic-related air pollutants (black carbon, nitrogen dioxide, and carbon monoxide) during the 1 to 7 days before each participant’s clinic visit. Higher ambient air pollutant levels were also associated with significant reductions in circulating HDL cholesterol and apoA-I (apolipoprotein A-I), as well as elevations in HDL oxidation index, oxidized LDL (low-density lipoprotein), malondialdehyde, and high-sensitivity C-reactive protein.

Conclusions—
Higher ambient air pollution concentrations were associated with impairments in HDL functionality, potentially because of systemic inflammation and oxidative stress. These novel findings further our understanding of the mechanisms whereby air pollutants promote cardiometabolic disorders.
Adherence to Guideline-Directed Stroke Prevention Therapy for Atrial Fibrillation Is Achievable
Authors: Piccini Jonathan P. , Xu Haolin , Cox Margueritte , Matsouaka Roland A. , Fonarow Gregg C. , Butler Javed , Curtis Anne B. , Desai Nihar , Fang Margaret , McCabe Pamela J. , Page II Robert L. , Turakhia Mintu , Russo Andrea M. , Knight Bradley P. , Sidhu Mandeep , Hurwitz Jodie L. , Ellenbogen Kenneth A. , Lewis William R. ,   For the Get With The Guidelines-AFIB Clinical Working Group and Hospitals
Published: January 2019

Background:
Efforts to improve prescription of oral anticoagulation (OAC) drugs in patients with atrial fibrillation have had limited success in improving guideline adherence.

Methods:

We evaluated adherence to the American College of Cardiology/American Heart Association performance measures for OAC in eligible patients with a CHA
2
DS
2
-VASc score ≥2 and trends in prescription over time in the American Heart Association’s Get With The Guidelines–AFIB (atrial fibrillation) registry. Adjusted associations with in-hospital outcomes were also determined. The cohort included 33 235 patients with a CHA
2
DS
2
-VASc score ≥2 who were admitted for atrial fibrillation and were enrolled at 115 sites between January 1, 2013, and September 31, 2017.

Results:

The median (25th, 75th percentile) age was 73 years (65, 81 years); 51% were female; and the median (25th, 75th percentile) CHA
2
DS
2
-VASc score was 4 (3, 5). At admission, 16 206 (59.5%) of 27 221 patients with a previous diagnosis of atrial fibrillation were taking OAC agents, and OAC drug use at admission was associated with a lower adjusted odds of in-hospital ischemic stroke (odds ratio, 0.38; 95% CI, 0.24–0.59;
P
<0.0001). At discharge, prescription of OAC in eligible patients (no contraindications) was 93.5% (n=25 499 of 27 270). In a sensitivity analysis, when excluding only strict contraindications (4.6%, n=1497 of 32 806), OAC prescription at discharge was 80.3%. OAC prescription at discharge was higher in those aged ≤75 years, men, those with heart failure, those with previous atrial fibrillation ablation, and those with rhythm control (
P
<0.0001 for all). OAC use was lowest in Hispanic patients (90.2%,
P
<0.0001). Prescription of OAC at discharge in eligible patients improved over time from 79.9% to 96.6% (
P
<0.0001).

Conclusions:
Among hospitals participating in the GWTG-AFIB quality improvement program, OAC prescription at discharge in eligible guideline-indicated patients increased significantly and improved consistently over time. These data confirm that high-level adherence to guideline-recommended stroke prevention is achievable.