bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density
Authors: Bossuyt Peter , Nakase Hiroshi , Vermeire Séverine , de Hertogh Gert , Eelbode Tom , Ferrante Marc , Hasegawa Tadashi , Willekens Hilde , Ikemoto Yousuke , Makino Takao , Bisschops Raf 
Published: January 2020

BackgroundThe objective evaluation of endoscopic disease activity is key in ulcerative colitis (UC). A composite of endoscopic and histological factors is the goal in UC treatment. We aimed to develop an operator-independent computer-based tool to determine UC activity based on endoscopic images.MethodsFirst, we built a computer algorithm using data from 29 consecutive patients with UC and 6 healthy controls (construction cohort). The algorithm (red density: RD) was based on the red channel of the red-green-blue pixel values and pattern recognition from endoscopic images. The algorithm was refined in sequential steps to optimise correlation with endoscopic and histological disease activity. In a second phase, the operating properties were tested in patients with UC flares requiring treatment escalation. To validate the algorithm, we tested the correlation between RD score and clinical, endoscopic and histological features in a validation cohort.ResultsWe constructed the algorithm based on the integration of pixel colour data from the redness colour map along with vascular pattern detection. These data were linked with Robarts histological index (RHI) in a multiple regression analysis. In the construction cohort, RD correlated with RHI (r=0.74, p<0.0001), Mayo endoscopic subscores (r=0.76, p<0.0001) and UC Endoscopic Index of Severity scores (r=0.74, p<0.0001). The RD sensitivity to change had a standardised effect size of 1.16. In the validation set, RD correlated with RHI (r=0.65, p=0.00002).ConclusionsRD provides an objective computer-based score that accurately assesses disease activity in UC. In a validation study, RD correlated with endoscopic and histological disease activity.
The effect of welfare reform on the health of the unemployed: evidence from a natural experiment in Germany
Authors: Shahidi Faraz V , Muntaner Carles , Shankardass Ketan , Quiñonez Carlos , Siddiqi Arjumand 
Published: January 2020

BackgroundOver the past several decades, governments have enacted far-reaching reforms aimed at reducing the generosity and coverage of welfare benefits. Prior literature suggests that these policy measures may have deleterious effects on the health of populations. In this study, we evaluate the impact of one of the largest welfare reforms in recent history—the 2005 Hartz IV reform in Germany—with a focus on estimating its effect on the health of the unemployed.MethodsWe employed a quasi-experimental difference-in-differences (DID) design using population-based data from the German Socio-Economic Panel Study, covering the period between 1994 and 2016. We applied DID linear probability modelling to examine the association between the Hartz IV reform and poor self-rated health, adjusting for a range of demographic and socioeconomic confounders.ResultsThe Hartz IV reform was associated with a 3.6 (95% CI 0.9 to 6.2) percentage point increase in the prevalence of poor self-rated health among unemployed persons affected by the reform relative to similar but unaffected controls. This negative association appeared immediately following the implementation of the reform and has persisted over time.ConclusionGovernments in numerous European and North American jurisdictions have introduced measures to further diminish the generosity and coverage of welfare benefits. In line with growing concerns over the potential consequences of austerity and associated policy measures, our findings suggest that these reform efforts pose a threat to the health of socioeconomically disadvantaged populations.
Mortality in a cohort of 3.1 million children, adolescents and young adults
Authors: Ray Joel G , Guttmann Astrid , Silveira Jose , Park Alison L 
Published: January 2020

BackgroundMany youth deaths occur in the first year of life, from prematurity and anomalies. Detailing mortality after age 1 year may differentially guide preventive strategies in children, adolescents and young adults.MethodsA cohort study in Ontario, Canada comprised 3 139 698 children born from 1990 to 2016. Adjusted HR (aHR) for death between 1 and 24 years were generated, comparing demographic variables and parity.ResultsAfter a median of 13.7 years of follow-up, 6930 deaths occurred between ages 1 and 24 years (incidence rate 17.0 per 100 000 person-years), peaking at age 23 years (43.7 per 100 000). The aHR for death was higher among males than females (1.44, 95% CI 1.37 to 1.51), rural versus urban areas (1.48, 95% CI 1.39 to 1.58), lowest versus highest income areas (1.39, 95% CI 1.29 to 1.51) and at parity 1 (1.16, 95% CI 1.10 to 1.23), parity 2 (1.34, 95% CI 1.23 to 1.45), parity 3+ (1.96, 95% CI 1.74 to 2.21), each relative to a child without an older sibling. Among males, the proportion of deaths due to injury jumped from 30% before age 15 years to 65% thereafter, and in females, from 28% to 51%. Intentional self-harm/assault explained 11% of injury-related deaths among males before age 15 years, and 20% thereafter, with respective figures of 18% and 17% for females. Deaths outside of hospital increased with age, from 35% at age 1 year, to 66% at age 22 years.ConclusionThere is a heightened susceptibility of dying starting at age 15 years, especially among males, from injury, and arising outside of hospital.
Impact of fetal-type posterior cerebral artery on recanalization of posterior communicating artery aneurysms after coil embolization: matched-pair case–control study
Authors: Choi Hyun Ho , Cho Young Dae , Yoo Dong Hyun , Lee Heui Seung , Kim Sung-Hyun , Jang Donghwan , Lee Sung Ho , Cho Won-Sang , Kang Hyun-Seung , Kim Jeong Eun 
Published: January 2020

BackgroundIt is well known that hemodynamic stress may impact the recanalization of coiled aneurysms. One of the most common sites for aneurysms to develop is the posterior communicating artery (PcoA), the variants of which are defined by diameter ratios (PcoA/P1 segment).ObjectiveThis study was undertaken to investigate the impact of a fetal-type posterior cerebral artery (PCA) on recanalization of PcoA aneurysms after coil embolization based on matched-pair (fetal vs non-fetal PCA) analysis.MethodsA total of 480 consecutive PcoA aneurysms (PCA: fetal, n=156; non-fetal, n=324) subjected to coil embolization between January 2007 and June 2017 were selected for study. All lesions were followed for ≥6 months via radiologic imaging, grouped by adjacent PCAs as fetal (PcoA/P1 >1) or non-fetal (PcoA/P1 ≤1) type. Paired subjects were matched (1:1) for several relevant variables.ResultsOf the 480 coiled aneurysms, 159 (33.1%) showed recanalization (minor, 76; major, 83) in the course of follow-up (mean 33.8±21.9 months), developing significantly more often in fetal (37.8%) than in non-fetal (26.9%; p=0.020) PCA types. Once matched, however, 6-month and cumulative recanalization rates did not differ significantly by group (p=0.531 and p=0.568, respectively). Complications (hemorrhage, p=0.97; thromboembolism, p=0.94) during endovascular coil embolization also showed similar rates in these groups.ConclusionsThe chances of recanalization after coil embolization seem to be greater in PcoA aneurysms than in intracranial aneurysms overall, thus calling for careful follow-up monitoring. Surprisingly, PcoA type appeared unrelated in this regard.
Computational Staining of Pathology Images to Study the Tumor Microenvironment in Lung Cancer
Authors: Wang Shidan , Rong Ruichen , Yang Donghan M. , Fujimoto Junya , Yan Shirley , Cai Ling , Yang Lin , Luo Danni , Behrens Carmen , Parra Edwin R. , Yao Bo , Xu Lin , Wang Tao , Zhan Xiaowei , Wistuba Ignacio I. , Minna John , Xie Yang , Xiao Guanghua 
Published: January 2020

Abstract

The spatial organization of different types of cells in tumor tissues reveals important information about the tumor microenvironment (TME). To facilitate the study of cellular spatial organization and interactions, we developed Histology-based Digital-Staining, a deep learning-based computation model, to segment the nuclei of tumor, stroma, lymphocyte, macrophage, karyorrhexis, and red blood cells from standard hematoxylin and eosin–stained pathology images in lung adenocarcinoma. Using this tool, we identified and classified cell nuclei and extracted 48 cell spatial organization-related features that characterize the TME. Using these features, we developed a prognostic model from the National Lung Screening Trial dataset, and independently validated the model in The Cancer Genome Atlas lung adenocarcinoma dataset, in which the predicted high-risk group showed significantly worse survival than the low-risk group (P = 0.001), with a HR of 2.23 (1.37–3.65) after adjusting for clinical variables. Furthermore, the image-derived TME features significantly correlated with the gene expression of biological pathways. For example, transcriptional activation of both the T-cell receptor and programmed cell death protein 1 pathways positively correlated with the density of detected lymphocytes in tumor tissues, while expression of the extracellular matrix organization pathway positively correlated with the density of stromal cells. In summary, we demonstrate that the spatial organization of different cell types is predictive of patient survival and associated with the gene expression of biological pathways.

Significance:
These findings present a deep learning-based analysis tool to study the TME in pathology images and demonstrate that the cell spatial organization is predictive of patient survival and is associated with gene expression.
See related commentary by Rodriguez-Antolin, p. 1912
Fusobacterium nucleatum in the Colorectum and Its Association with Cancer Risk and Survival: A Systematic Review and Meta-analysis
Authors: Gethings-Behncke Christian , Coleman Helen G. , Jordao Haydee W.T. , Longley Daniel B. , Crawford Nyree , Murray Liam J. , Kunzmann Andrew T. 
Published: January 2020

Abstract

Background:
The gut microbiome, in particular Fusobacterium nucleatum, has been reported to play a role in colorectal cancer development and in patient prognosis. We aimed to perform a systematic review and meta-analysis of published studies to assess the prevalence of F. nucleatum in colorectal tumors and evaluate the association between F. nucleatum and colorectal cancer development and prognosis.

Methods:
MEDLINE, EMBASE, and Web of Science databases were systematically searched for studies published until January 2019. Random effects meta-analyses were used to assess the prevalence of F. nucleatum in patients with colorectal cancer or tissues relative to controls and survival in F. nucleatum–positive versus –negative patients.

Results:
Forty-five relevant articles were identified. Meta-analyses indicated higher odds of F. nucleatum being present in colorectal tissue samples from patients with colorectal cancer [n = 6 studies, pooled OR = 10.06; 95% confidence intervals (CI), 4.48–22.58] and individuals with colorectal polyps (n = 5 studies, pooled OR = 1.83; 95% CI, 1.07–3.16) compared with healthy controls. Similar results were apparent in fecal samples, and when comparing tumor with adjacent normal tissue. Meta-analyses indicated poorer survival in patients with colorectal cancer with high versus low F. nucleatum abundance (n = 5 studies, pooled HR = 1.87; 95% CI, 1.12–3.11).

Conclusions:
A consistent increase in the prevalence and/or abundance of F. nucleatum in colorectal cancer tissue and fecal samples compared with controls was apparent. High abundance of F. nucleatum in colorectal tumors was also associated with poorer overall survival.

Impact:
F. nucleatum could be useful as a diagnostic and prognostic marker for colorectal cancer or as a treatment target.
Association of Diet Quality and Physical Activity on Obesity-Related Cancer Risk and Mortality in Black Women: Results from the Women's Health Initiative
Authors: Chebet Joy J. , Thomson Cynthia A. , Kohler Lindsay N. , Ehiri John E. , Luo Juhua , Cheng Ting-Yuan David , Pan Kathy , Chlebowski Rowan T. , Nassir Rami , Sealy-Jefferson Shawnita , Manson JoAnn E. , Saquib Nazmus , Bell Melanie L. 
Published: January 2020

Abstract

Background:
Obesity-related cancers disproportionately affect the Black community. We assessed the relationship between diet quality, physical activity, and their combined effect on obesity-related cancer risk and mortality in Black women enrolled in the Women's Health Initiative (WHI).

Methods:
Data from postmenopausal (50–79 years of age) Black women enrolled in WHI clinical trials or observational studies were analyzed. Exposure variables included baseline physical activity [metabolic equivalent of tasks (MET)-hours/week of moderate-to-vigorous physical activity (MVPA)] and diet quality [Healthy Eating Index (HEI)-2015]. Outcomes included adjudicated obesity-related cancer incidence and mortality. Cox proportional hazard models were used to evaluate the association between MVPA and HEI-2015 and obesity-related cancer risk and mortality.

Results:
The analytical sample included 9,886 Black women, with a baseline mean body mass index (BMI) of 31.1 kg/m2 (SD = 6.8); mean HEI-2015 score of 63.2 (SD = 11.0, possible range 0 to 100); and mean MVPA of 5.0 (SD = 9.4) MET-hours/week. Over an average of 13 years of follow-up, 950 (9.6%) obesity-related cancer cases were observed, with 313 (32.9%) resulting in death. Physical activity [HR, 1.05; 95% confidence interval (CI), 0.86–1.30], diet quality (HR, 0.99; 95% CI, 0.92–1.08), and their combination (HR, 1.05; 95% CI, 0.85–1.29) were not associated with risk for any or site-specific obesity-related cancers. Similarly, these health behaviors had no association with mortality.

Conclusions:
Diet quality, physical activity and their combined effect, as measured, were not associated with obesity-related cancer risk and mortality in Black women enrolled in WHI.

Impact:
Other social, behavioral, and biological factors may contribute to racial disparities observed in obesity-related cancer rates.
Opiate and Tobacco Use and Exposure to Carcinogens and Toxicants in the Golestan Cohort Study
Authors: Etemadi Arash , Poustchi Hossein , Calafat Antonia M. , Blount Benjamin C. , De Jesús Victor R. , Wang Lanqing , Pourshams Akram , Shakeri Ramin , Inoue-Choi Maki , Shiels Meredith S. , Roshandel Gholamreza , Murphy Gwen , Sosnoff Connie S. , Bhandari Deepak , Feng Jun , Xia Baoyun , Wang Yuesong , Meng Lei , Kamangar Farin , Brennan Paul , Boffetta Paolo , Dawsey Sanford M. , Abnet Christian C. , Malekzadeh Reza , Freedman Neal D. 
Published: January 2020

AbstractBackground:There is little information on human exposure to carcinogens and other toxicants related to opiate use, alone or in combination with tobacco.Methods:Among male participants of the Golestan Cohort Study in Northeast Iran, we studied 28 never users of either opiates or tobacco, 33 exclusive cigarette smokers, 23 exclusive users of smoked opiates, and 30 opiate users who also smoked cigarettes (dual users; 21 smoked opiates and 9 ingested them). We quantified urinary concentrations of 39 exposure biomarkers, including tobacco alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC), and used decomposition to parse out the share of the biomarker concentrations explained by opiate use and nicotine dose.Results:Dual users had the highest concentrations of all biomarkers, but exclusive cigarette smokers and exclusive opiate users had substantially higher concentrations of PAH and VOC biomarkers than never users of either product. Decomposition analysis showed that opiate use contributed a larger part of the PAH concentrations than nicotine dose, and the sum of 2- and 3-hydroxyphenanthrene (∑2,3-phe) resulted almost completely from opiate use. Concentrations of most VOC biomarkers were explained by both nicotine dose and opiate use. Two acrylamide metabolites, a 1,3-butadiene metabolite and a dimethylformamide metabolite, were more strongly explained by opiate use. Acrylamide metabolites and ∑2,3-phe were significantly higher in opiate smokers than opiate eaters; other biomarkers did not vary by the route of opiate intake.Conclusions:Both cigarette smokers and opiate users (by smoking or ingestion) were exposed to many toxicants and carcinogens.Impact:This high exposure, particularly among dual opiate and cigarette users, can have a substantial global public health impact.
Racial Difference in Prostate Cancer Cell Telomere Lengths in Men with Higher Grade Prostate Cancer: A Clue to the Racial Disparity in Prostate Cancer Outcomes
Authors: Heaphy Christopher M. , Joshu Corinne E. , Barber John R. , Davis Christine , Zarinshenas Reza , De Marzo Angelo M. , Lotan Tamara L. , Sfanos Karen S. , Meeker Alan K. , Platz Elizabeth A. 
Published: January 2020

Abstract

Background:
Black men have worse prostate cancer outcomes following treatment than White men even when accounting for prognostic factors. However, biological explanations for this racial disparity have not been fully identified. We previously showed that more variable telomere lengths among cancer cells and shorter telomere lengths in cancer-associated stromal (CAS) cells individually and together (“telomere biomarker”) are associated with prostate cancer–related death in surgically treated men independent of currently used prognostic indicators. Here, we hypothesize that Black–White differences in the telomere biomarker and/or in its components may help explain the racial disparity in prostate cancer outcomes.

Methods:
Black [higher grade (Gleason ≥4+3) = 34 and lower grade = 93] and White (higher grade = 34 and lower grade = 89) surgically treated men were frequency matched on age, pathologic stage, and grade. We measured telomere lengths in cancer and CAS cells using a robust telomere-specific FISH assay. Tissue microarray and grade-specific distributional cutoff points without regard to race were evaluated.

Results:
Among men with higher grade disease, the proportion of Black men (47.1%) with more variable cancer cell telomere lengths was 2.3-times higher (P = 0.02) than that in White men (20.6%). In contrast, among men with lower grade disease, cancer cell telomere length variability did not differ by race. The proportion of men with shorter CAS cell telomeres did not differ by race for either higher or lower grade disease.

Conclusions:
A greater proportion of Black men with higher grade disease have an adverse prostate cancer cell telomere phenotype than White men with higher grade disease.

Impact:
Our findings suggest a possible explanation for the racial disparity in prostate cancer outcomes.
Combination Lenalidomide/Bortezomib Treatment Synergistically Induces Calpain-Dependent Ikaros Cleavage and Apoptosis in Myeloma Cells
Authors: Ganesan Saravanan , Palani Hamenth Kumar , Balasundaram Nithya , David Sachin , Devasia Anup J. , George Biju , Mathews Vikram 
Published: January 2020

Abstract

Multiple myeloma had been successfully treated by combining lenalidomide and bortezomib with reports suggesting benefits of such a combination even in relapsed/refractory cases. Recently, it was demonstrated that Ikaros degradation by lenalidomide happens via proteasome-dependent pathway and this process is critical for the eradication of myeloma cells. On the basis of this, an antagonistic effect should be observed if a combination of both these agents were used, which however is not the observation seen in the clinical setting. Our study demonstrates that when these agents are combined they exhibit a synergistic activity against myeloma cells and degradation of Ikaros happens by a proteasome-independent calcium-induced calpain pathway. Our study identifies the crucial role of calcium-induced calpain pathway in inducing apoptosis of myeloma cells when this combination or lenalidomide and bortezomib is used. We also report that this combination enhanced the expression of CD38 compared with lenalidomide alone. Thus, data from our study would establish the rationale for the addition of daratumumab along with this combination to further enhance therapeutic activity against multiple myeloma.

Implications:
Lenalidomide and bortezomib combination degrades IKZF1 in multiple myeloma through a calcium-dependent calpain and caspase pathway.

Visual Overview:
http://mcr.aacrjournals.org/content/molcanres/18/4/529/F1.large.jpg.
OUTSMART HF
Authors: Paterson D. Ian , Wells George , Erthal Fernanda , Mielniczuk Lisa , O’Meara Eileen , White James , Connelly Kim A. , Knuuti Juhani , Radja Miroslaw , Laine Mika , Chow Benjamin J.W. , Kandolin Riina , Chen Li , Dick Alexander , Dennie Carole , Garrard Linda , Ezekowitz Justin , Beanlands Rob , Chan Kwan-Leung , Brown Peter , Kartikainen Juha , Hedman Marja , Larose Eric , Pibarot Philippe , Tardif Jean-Claude , Leipsic Jonathan , Kiess Marla , Howarth Andrew , Hanninen Helena , Duchesne Lloyd , Freeman Michael , Leong-Poi Howard , Wright Graham , Ukkonen Heikki 
Published: January 2020

Background:
Cardiac magnetic resonance (CMR) is a recommended imaging test for patients with heart failure (HF); however, there is a lack of evidence showing incremental benefit over transthoracic echocardiography. Our primary hypothesis was that routine use of CMR will yield more specific diagnoses in nonischemic HF. Our secondary hypothesis was that routine use of CMR will improve patient outcomes.

Methods:
Patients with nonischemic HF were randomized to routine versus selective CMR. Patients in the routine strategy underwent echocardiography and CMR, whereas those assigned to selective use underwent echocardiography with or without CMR according to the clinical presentation. HF causes was classified from the imaging data as well as by the treating physician at 3 months (primary outcome). Clinical events were collected for 12 months.

Results:

A total of 500 patients (344 male) with mean age 59±13 years were randomized. The routine and selective CMR strategies had similar rates of specific HF causes at 3 months clinical follow-up (44% versus 50%, respectively;
P
=0.22). At image interpretation, rates of specific HF causes were also not different between routine and selective CMR (34% versus 30%, respectively;
P
=0.34). However, 24% of patients in the selective group underwent a nonprotocol CMR. Patients with specific HF causes had more clinical events than those with nonspecific caused on the basis of imaging classification (19% versus 12%, respectively;
P
=0.02), but not on clinical assessment (15% versus 14%, respectively;
P
=0.49).

Conclusions:
In patients with nonischemic HF, routine CMR does not yield more specific HF causes on clinical assessment. Patients with specific HF causes from imaging had worse outcomes, whereas HF causes defined clinically did not.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01281384.