bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hallmark Circulating Tumor-Associated Cell Clusters Signify 230 Times Higher One-Year Cancer Risk
Authors: Ranade Anantbhushan , Bhatt Amit , Page Raymond , Limaye Sewanti , Crook Timothy , Akolkar Dadasaheb , Patil Darshana 
Published: September 2020

AbstractWe have previously shown that circulating ensembles of tumor-associated cells (C-ETACs) are a systemic hallmark of cancer based on analysis of blood samples from 16,134 individuals including 10,625 asymptomatic individuals and 5,509 diagnosed cases of cancer. C-ETACs were ubiquitously (90%) detected across all cancer types and were rare (3.6%) among the asymptomatic population. Consequently, we hypothesized that asymptomatic individuals with detectable C-ETACs would have a definitively elevated risk of developing cancer as compared with individuals without C-ETACs. In the present manuscript we present 1-year follow-up data of the asymptomatic cohort which shows that C-ETAC positive individuals have a 230-fold (P &lt; 0.00001) higher 1-year cancer risk as compared with individuals where C-ETACs were undetectable. Simultaneously, we also expanded the study to include 4,419 symptomatic individuals, suspected of cancer, prior to undergoing an invasive biopsy for diagnosis. C-ETACs were detected in 4,101 (92.8%) of these 4,419 cases where cancer was eventually confirmed. We conclude that detection of C-ETACs can identify patients at risk of cancer and can be reliably used to stratify asymptomatic individuals with an elevated 1-year risk of cancer.Prevention Relevance:The study evaluated a blood test that can determine if healthy (‘asymptomatic’) individuals without a history of cancer have an increased risk of developing cancer within the next one year. This test can significantly minimize radiological or invasive screening in the majority individuals who do not have any increased risk.
Habitual Night Eating Was Positively Associated With Progress of Arterial Stiffness in Chinese Adults
Authors: Zhang Xinyuan , Wu Yuntao , Na Muzi , Lichtenstein Alice H. , Xing Aijun , Chen Shuohua , Wu Shouling , Gao Xiang 
Published: September 2020

Background
Night eating has been associated with an elevated risk of obesity, dyslipidemia, and cardiovascular disease. However, there is no longitudinal study on whether habitual night eating, regardless of diet quality and energy intake, is associated with arterial stiffness, a major etiological factor in the development of cardiovascular disease.

Methods and Results

The study included 7771 adult participants without cardiovascular disease, cancer, or diabetes mellitus prior to dietary assessment by a validated food frequency questionnaire in 2014 through 2015. Participants were categorized into 3 groups based on self‐reported night‐eating habits: never or rarely, some days (1–5 times per week), or most days (6+ times per week). Arterial stiffness was assessed by brachial‐ankle pulse wave velocity at baseline and repeatedly during follow‐ups. Mean differences and 95% CIs in the yearly change rate of brachial‐ankle pulse wave velocity across the 3 groups were calculated, adjusting for age, sex, socioeconomic status, total energy intake, diet quality, sleep quality, and other cardiovascular disease risk factors. At baseline, 6625 (85.2%), 610 (7.8%), and 536 (6.9%) participants reported night eating as never or rarely, some days, or most days, respectively. During a mean 3.19 years, we observed a positive association between night‐eating frequency and progression of arterial stiffness (
P
trend=0.01). The adjusted difference in brachial‐ankle pulse wave velocity change rate between the group that ate at night most days and the group that never or rarely ate at night was 14.1 (95% CI, 0.6–27.5) cm/s per year. This association was only significant in women, but not in men (
P
interaction=0.03).

Conclusions
In an adult population free of major chronic diseases, habitual night eating was positively associated with the progression of arterial stiffness, a hallmark of arteriosclerosis and biological aging.

Registration

URL:
https://www.chictr.org.cn
; Unique identifier: ChiCTR‐TNRC‐11001489.
Prospective Screening of Extracranial Systemic Arteriopathy in Young Adults with Moyamoya Disease
Authors: Jee Tae Keun , Yeon Je Young , Kim Sung Mok , Bang Oh Young , Kim Jong-Soo , Hong Seung‐Chyul 
Published: September 2020

Background

RNF213
is a major susceptibility gene for moyamoya disease (MMD), characterized by chronic progressive steno‐occlusion of the intracranial arteries. However, coincidental extracranial arteriopathy is sporadically described in a few cases and in children with MMD.

Methods and Results

This study prospectively enrolled 63 young adults (aged 20–49 years) without a known history of systemic vascular diseases who were confirmed to have definite (bilateral, n=54) or probable (unilateral, n=9) MMD, as per typical angiographic findings. Coronary and aorta computed tomography angiography was performed to characterize extracranial arteriopathy and investigate its correlation with clinical characteristics and MMD status, including the
RNF213
p.Arg4810Lys variation (c.14429G>A, rs112735431). Altogether, 11 of 63 patients (17%) had significant (>50%) stenosis in the coronary (n=6), superior mesenteric (n=2), celiac (n=2), renal (n=1), and/or internal iliac artery (n=1). One patient showed both mesenteric and iliac artery stenosis. Patients with extracranial arteriopathy were more likely to have diabetes mellitus and posterior cerebral artery involvement. Moreover, a higher prevalence of extracranial arteriopathy was observed in the presence of the
RNF213
p.Arg4810Lys variant (67% in homozygotes). After controlling for diabetes mellitus and posterior cerebral artery involvement, the p.Arg4810Lys variant was independently associated with extracranial arteriopathy (additive model;
P
=0.035; adjusted odds ratio, 4.57; 95% CI, 1.11–27.20).

Conclusions

Young adults with MMD may have concomitant extracranial arteriopathy in various locations. Patients with
RNF213
variants, especially the p.Arg4810Lys homozygous variant, should be screened for systemic arteriopathy.
Rivaroxaban for Prevention of Covert Brain Infarcts and Cognitive Decline
Authors: Sharma Mukul , Hart Robert G. , Smith Eric E. , Bosch Jacqueline , Eikelboom John W. , Connolly Stuart J. , Dyal Leanne , Reeh Kevin W , Casanova Amparo , Diaz Rafael , Lopez-Jaramillo Patricio , Ertl Georg , Störk Stefan , Dagenais Gilles R. , Lonn Eva M. , Ryden Lars , Tonkin Andrew M. , Varigos John D. , Bhatt Deepak L. , Branch Kelley R.H. , Probstfield Jeffrey L. , Kim Jae-Hyung , O’Donnell Martin , Vinereanu Dragos , A.A. Fox Keith , Liang Yan , Liu Lisheng , Zhu Jun , Pogosova Nana , Maggioni Aldo P. , Avezum Alvaro , Piegas Leopoldo S. , Keltai Katalin , Keltai Matyas , Berkowitz Scott D. , Yusuf Salim 
Published: September 2020

Background and Purpose:
Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities.

Methods:
Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities.

Results:
At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38–0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37–1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27–1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests.

Conclusions:
Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01776424.
Morbidity After Symptomatic Hemorrhage of Cerebral Cavernous Malformation
Authors: Ma Li , Zhang Shuo , Li Zongze , Wu Chun-Xue , Wang Zhaozhao , Zhan Lei , Hao Qiang , Wang Hao , Ye Xun , Chen Xiaolin , Liu Ya-Ou , Wang Shuo , Zhao Yuan-Li 
Published: September 2020

Background and Purpose:
Symptomatic hemorrhage contributes to an increased risk of repeated bleeding and morbidity in cerebral cavernous malformation (CCM). A better understanding of morbidity after CCM hemorrhage would be helpful to identify patients of higher risk for unfavorable outcome and tailor individualized management.

Methods:
We identified 282 consecutive patients who referred to our institute from 2014 to 2018 for CCM with symptomatic hemorrhage and had an untreated follow-up period over 6 months after the first hemorrhage. The morbidity after hemorrhage was described in CCM of different features. Nomogram to predict morbidity was formulated based on the multivariable model of risk factors. The predictive accuracy and discriminative ability of nomogram were determined with concordance index (C-index) and calibration curve, and further validated in an independent CCM cohort of a prospective multicenter study from 2019 to 2020.

Results:
The overall morbidity of CCM was 26.2% after a mean follow-up of 1.9 years (range 0.5–3.5 years) since the first hemorrhage. The morbidity during untreated follow-up was associated with hemorrhage ictus (adjusted odds ratio per ictus increase, 4.17 [95% CI, 1.86–9.33]), modified Rankin Scale score at initial hemorrhage (adjusted odds ratio per point increase, 2.57 [95% CI, 1.82–3.63]), brainstem location (adjusted odds ratio, 2.93 [95% CI, 1.28–6.68]), and associated developmental venous anomaly (adjusted odds ratio, 2.21 [95% CI, 1.01–4.83]). Subgroup analysis revealed similar findings in brainstem and non-brainstem CCM. Nomogram was contracted based on these features. The calibration curve showed good agreement between nomogram prediction and actual observation. The C-index of nomogram predicting morbidity was 0.83 (95% CI, 0.77–0.88). In validation cohort, the nomogram maintained the discriminative ability (C-index, 0.87 [95% CI, 0.78–0.96]).

Conclusions:
Multiple symptomatic hemorrhages, initial neurological function after hemorrhage, brainstem location, and associated developmental venous anomaly were associated with morbidity of CCM hemorrhage. The nomogram represented a practical approach to provide individualized risk assessment for CCM patients.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT04076449.
A 1D Var Retrieval of Relative Humidity Using the ERA5 Dataset for the Assimilation of Raman Lidar Measurements
Authors: Gamage S. Mahagammulla , Sica R. J. , Martucci G. , Haefele A. 
Published: September 2020

AbstractWe present a one-dimensional variational (1D Var) retrieval of fifth-generation European Centre for Medium-Range Weather Forecast reanalysis (ERA5) temperature and relative humidity profiles above Payerne, Switzerland, assimilating raw backscatter measurements from the MeteoSwiss Raman Lidar for Meteorological Observations (RALMO). Our reanalysis is called ERA5-reRH. We use an optimal estimation method to perform the 1D Var data retrieval. The forward model combines the Raman lidar equation with the Hyland and Wexler expression for water vapor saturation pressure. The error covariance matrix of ERA5 was derived from the differences between ERA5 and a set of 50 special radiosoundings that have not been assimilated into ERA5. We validate ERA5-reRH, ERA5, and RALMO temperature and relative humidity profiles against the same set of special radiosoundings and found the best agreement was with our reanalysis, with a bias of less than 2% relative humidity with respect to water (%RHw) and a spread of less than 8%RHw below 8 km in terms of relative humidity. Improvements for temperature in our reanalysis are only found in the boundary layer, as ERA5 assimilates a large number of upper-air temperature observations. Our retrieval also provides a full uncertainty budget of the reanalyzed temperature and relative humidity including both random and systematic uncertainties.
Personalized drug testing in a patient with non-small-cell lung cancer using cultured cancer cells from pleural effusion
Authors: Wu Ming , Hong Guodai , Chen Yu , Ye Lina , Zhang Kang , Cai Kaihong , Yang Huadong , Long Xiang , Gao Wenbin , Li Hui 
Published: September 2020

Objective Patients with non-small-cell lung cancer (NSCLC) and primary or acquired resistance do not respond to targeted drugs. We explored whether cancer cells can be cultured from liquid biopsies from patients with primary resistance to tyrosine kinase inhibitors (TKIs). We aimed to predict patients’ responses to drugs according to in vitro drug testing results. Methods Cancer cell cultures were established from the pleural effusion of a patient with TKI-resistant NSCLC using a conditional reprogramming technique. Phenotypic drug sensitivity tests were performed using the Cell Counting Kit-8 assay. We tested individual drugs and compared the synergistic and inhibitory effects of drug combinations. Results The results of our in vitro sensitivity test using the combination of cisplatin and pemetrexed were correlated with the patient’s response. Conclusion This represents the first successful report of predictive testing for combination therapy in patients with epidermal growth factor receptor-mutant NSCLC and primary TKI resistance. This strategy should be applicable to both chemotherapies and targeted therapies, and it will significantly improve the clinical treatment and management of patients with NSCLC and primary or acquired resistance to targeted therapies, as well as patients lacking targetable mutations.
Correlation between serum free triiodothyronine levels and risk stratification in Chinese patients with acute coronary syndrome receiving percutaneous coronary intervention
Authors: Li Huiying , Li Chunlin , Bai Yongyi , Wang Zhao , Li Man , Cai Yulun , Zhou Wenli , Zhang Baohua , Liu Hongbin 
Published: September 2020

Objective Low serum free triiodothyronine (FT3) levels are associated with the occurrence of coronary heart disease and with the prognosis of cardiovascular diseases. This study aimed to investigate the relationship between FT3 levels and risk stratification in Chinese Han patients with acute coronary syndrome (ACS) receiving percutaneous coronary intervention (PCI) treatment. Methods Plasma FT3 levels and other parameters were measured in 191 patients with ACS who received PCI. The risk of adverse cardiovascular events was assessed using the Age, Creatinine, and Ejection Fraction (ACEF) score. Results FT3 levels were significantly lower in the high-risk group than in the medium- and low-risk groups. Serum FT3 levels were negatively linearly correlated with the ACEF score (r = −0.590). Stepwise regression analysis showed a negative correlation between FT3 levels and the risk of adverse cardiovascular events as measured by the ACEF score (standardized β = −0.261). Conclusion Serum FT3 levels are negatively related to risk stratification in patients with ACS. Serum FT3 levels may be used as a potential predictor for adverse outcomes of patients with ACS undergoing PCI.
Predicting the response to a triptan in migraine using deep attack phenotyping: A feasibility study
Authors: Viana Michele , Sances Grazia , Terrazzino Salvatore , Zecca Chiara , Goadsby Peter J , Tassorelli Cristina 
Published: September 2020

Background Triptans, specific symptomatic medications for migraine, are not effective in a proportion of patients, or in all attacks, hence the importance of identifying predictors of response. Our aim was to investigate the association between the efficacy of oral frovatriptan 2.5 mg and clinical characteristics of migraine attacks. Methods We enrolled 29 consecutive patients affected by migraine without aura at the Headache Center of “Mondino” Institute of Pavia. Each patient was given a diary and asked to record prospectively the features of three consecutive migraine attacks while using frovatriptan. A generalized estimating equations approach was used to determine phenotypic features associated with the pain free response at 2 hours. Results Participants provided complete data for 85 attacks. Thirty of these (34%) patients reported being pain free 2 hours after taking frovatriptan 2.5 mg intake. Unilateral pain, presence of phonophobia, presence of one or more cranial autonomic symptoms and presence of one or more premonitory symptom were each associated with being pain free at 2 hours. Conclusions The response to frovatriptan was associated with particular features of the migraine attack, either before or during the pain phase of attacks. The data support larger studies to explore detailed attack phenotyping, with particular attention to early signs, to enable individualized treatment in migraine.
Providing Evidence-Based Care, Day and Night: A Quality Improvement Initiative to Improve Intensive Care Unit Patient Sleep Quality
Authors: Douglas Stuart L. , Hobbs Hailey A. , Sibley Stephanie R. , Digby Geneviève C. 
Published: September 2020

Objective: Evidence-based guidelines recommend promoting sleep in the Intensive Care Unit (ICU), yet many patients experience poor sleep quality. We sought to engage allied health staff and patient families to determine barriers to sleep promotion, to measure sleep quality for ICU patients, and to evaluate the improvement in sleep quality after implementation of nursing morning report protocol and a doorway poster. Design: The study followed an interrupted time-series framework of quality improvement. Qualitative diagnostics included focus groups and interviews with patients, families, and allied health care workers, analyzed by qualitative descriptive analysis. Quantitative diagnostics included direct observation of nurses and patients overnight. Analysis of primary outcome data used statistical process control methodology. Patients: Patients included were >18 years old, admitted overnight to a Canadian tertiary academic ICU, with a Richards Agitation Sedation Scale (RASS) ≥−2. Interventions: Sleep quality was measured using the Richards Campbell Sleep Questionnaire (RCSQ). Two interventions were developed: sleep quality in morning nursing report, and a doorway poster. Main results: A total of 2332 patient nights across 7 consecutive months were included for analysis. Baseline sleep in the ICU was poor (mean RCSQ 53.7/100). Root cause-analysis identified the most prominent sleep barriers as nurse stigma associated with less active management of patients and lack of physician engagement. No significant improvement occurred over the sleep quality improvement initiative (mean RCSQ 59.5/100). Sleep quality was better among non-delirious patients compared with delirious patients (mean RCSQ 62.7 vs 53.3). Conclusion: The intervention of a nursing morning report protocol and sleep posters did not improve the quality of ICU patient sleep in this study. Structured interviews revealed potential sleep barriers to be addressed such as nursing stigma and inappropriate awakenings. Nursing stigma has not been previously linked to sleep quality.
Morbidity and mortality following major large bowel resection for colorectal cancer detected by a population-based screening program
Authors: Paszat Lawrence F , Sutradhar Rinku , Corn Elyse , Luo Jin , Baxter Nancy N , Tinmouth Jill , Rabeneck Linda 
Published: September 2020

Background and aims In 2008, Ontario initiated a population-based colorectal screening program using guaiac fecal occult blood testing. This work was undertaken to fill a major gap in knowledge by estimating serious post-operative complications and mortality following major large bowel resection of colorectal cancer detected by a population-based screening program. Methods We identified persons with a first positive fecal occult blood result between 2008 and 2016, at the age of 50–74 years, who underwent a colonoscopy within 6 months, and proceeded to major large bowel resection for colon cancer within 6 months or rectosigmoid/rectal cancer within 12 months, and identified an unscreened cohort of resected cases diagnosed during the same years at the age of 50–74 years. We identified serious postoperative complications and readmissions ≤30 days following resection, and postoperative mortality ≤30 days, and between 31 and 90 days among the screen-detected and the unscreened cohorts. Results Serious post-operative complications or readmissions within 30 days were observed among 1476/4999 (29.5%) cases in the screen-detected cohort, and among 3060/8848 (34.6%) unscreened cases. Mortality within 30 days was 43/4999 (0.9%) among the screen-detected cohort, and 208/8848 (2.4%) among the unscreened cohort. Among 30 day survivors, mortality between 31 and 90 days was 28/4956 (0.6%) and 111/8640 (1.3%), respectively. Conclusion Serious post-operative complications, readmissions, and mortality may be more common following major large bowel resection for colorectal cancer between the ages of 50 and 74 among unscreened compared to screen-detected cases.
Evaluation of real-time video from the digital indirect ophthalmoscope for telemedicine consultations in retinopathy of prematurity
Authors: Ho Tiffany , Lee Thomas C , Choe Ja-Yoon , Nallasamy Sudha 
Published: September 2020

Introduction This study aimed to evaluate the validity of using real-time video indirect ophthalmoscopy for telemedicine consultations for paediatric retinal findings, using retinopathy of prematurity (ROP) as a model disease. Methods An ophthalmologist simultaneously performed and recorded routine ROP screenings on enrolled premature infants (aged ≤30 weeks and weighing <1500 g) using the Keeler digital indirect ophthalmoscope. Examinations were graded as no ROP, mild, type 1 or type 2. Masked to clinical findings, another ophthalmologist reviewed and graded streamed video feed transmitted at 4096 kbps. We compared the sensitivity and specificity of diagnosing ROP via streamed and stored-and-forwarded video clips to the gold-standard in-person examination. Results A total of 150 examinations of individual eyes from 34 babies were included. The median postmenstrual age (PMA) at delivery was 24 weeks (range 23–34 weeks), the median birth weight was 630 g (range 455–1530 g) and the median PMA at examination was 37 weeks (range 31–54 weeks). Of those infants with any ROP, the sensitivity and specificity of streamed examinations were 100% and 70.6%, respectively. For type 2 or worse ROP, the sensitivity and specificity were 92.5% and 86.1%, respectively. For type 1 ROP, the sensitivity and specificity were 100% and 99.3%, respectively. Sensitivities (unless already 100%) and specificities were slightly higher for store-and-forward evaluations. Discussion Streamed video feed from the digital indirect ophthalmoscope can be utilised to diagnose clinically significant ROP accurately, though store-and-forward video review yielded slightly better results.