bluuebunny/crossref_metadata_2025_split huggingface dataset:
SMAD4 Suppresses WNT-Driven Dedifferentiation and Oncogenesis in the Differentiated Gut Epithelium
Authors: Perekatt Ansu O. , Shah Pooja P. , Cheung Shannon , Jariwala Nidhi , Wu Alex , Gandhi Vishal , Kumar Namit , Feng Qiang , Patel Neeket , Chen Lei , Joshi Shilpy , Zhou Anbo , Taketo M. Mark , Xing Jinchuan , White Eileen , Gao Nan , Gatza Michael L. , Verzi Michael P. 
Published: July 2018

Abstract
The cell of origin of colon cancer is typically thought to be the resident somatic stem cells, which are immortal and escape the continual cellular turnover characteristic of the intestinal epithelium. However, recent studies have identified certain conditions in which differentiated cells can acquire stem-like properties and give rise to tumors. Defining the origins of tumors will inform cancer prevention efforts as well as cancer therapies, as cancers with distinct origins often respond differently to treatments. We report here a new condition in which tumors arise from the differentiated intestinal epithelium. Inactivation of the differentiation-promoting transcription factor SMAD4 in the intestinal epithelium was surprisingly well tolerated in the short term. However, after several months, adenomas developed with characteristics of activated WNT signaling. Simultaneous loss of SMAD4 and activation of the WNT pathway led to dedifferentiation and rapid adenoma formation in differentiated tissue. Transcriptional profiling revealed acquisition of stem cell characteristics, and colabeling indicated that cells expressing differentiated enterocyte markers entered the cell cycle and reexpressed stem cell genes upon simultaneous loss of SMAD4 and activation of the WNT pathway. These results indicate that SMAD4 functions to maintain differentiated enterocytes in the presence of oncogenic WNT signaling, thus preventing dedifferentiation and tumor formation in the differentiated intestinal epithelium.
Significance: This work identifies a mechanism through which differentiated cells prevent tumor formation by suppressing oncogenic plasticity. Cancer Res; 78(17); 4878–90. ©2018 AACR.
Prognostic Significance of HPV and p16 Status in Men Diagnosed with Penile Cancer: A Systematic Review and Meta-analysis
Authors: Sand Freja Lærke , Rasmussen Christina Louise , Frederiksen Marie Hoffmann , Andersen Klaus Kaae , Kjaer Susanne K. 
Published: July 2018

Abstract
It has been shown that human papillomavirus (HPV) and p16 status has prognostic value in some HPV-associated cancers. However, studies examining survival in men with penile cancer according to HPV or p16 status are often inconclusive, mainly because of small study populations. The aim of this systematic review and meta-analysis was to examine the association between HPV DNA and p16 status and survival in men diagnosed with penile cancer. Multiple electronic databases were searched. Twenty studies were ultimately included and study-specific and pooled HRs of overall survival and disease-specific survival (DSS) were calculated using a fixed effects model. In the analysis of DSS, we included 649 men with penile cancer tested for HPV (27% were HPV-positive) and 404 men tested for p16 expression (47% were p16-positive). The pooled HRHPV of DSS was 0.61 [95% confidence interval (CI), 0.38–0.98], and the pooled HRp16 of DSS was 0.45 (95% CI, 0.30–0.69). In conclusion, men with HPV or p16-positive penile cancer have a significantly more favorable DSS compared with men with HPV or p16-negative penile cancer. These findings point to the possible clinical value of HPV and p16 testing when planning the most optimal management and follow-up strategy. Cancer Epidemiol Biomarkers Prev; 27(10); 1123–32. ©2018 AACR.
Electrophysiological Characteristics of Bundle Branch Reentry Ventricular Tachycardia in Patients Without Structural Heart Disease
Authors: Chen Hongwu , Shi Linsheng , Yang Bing , Ju Weizhu , Zhang Fengxiang , Yang Gang , Gu Kai , Li Mingfang , Cao Kejiang , Ouyang Feifan , Chen Minglong 
Published: July 2018

Background:
The distinct electrophysiological features of bundle branch reentry ventricular tachycardia (VT) in patients without structural heart disease have not been systemically characterized.

Methods:

Nine patients (mean age, 29.6 years) with normal left ventricular function were enrolled. Bundle branch reentry VT with right and left bundle branch block (BBB) patterns was induced in 1 and 9 patients, respectively. The right bundle was attempted to record by a 6F decapolar or quadripolar catheter. Electroanatomic mapping of the left ventricle was performed in 6 patients. In all left BBB pattern VT, the mean VT cycle length was 329.3±89.1 ms, and the median HV interval during tachycardia was longer than that of baseline (78 [73–100] versus 71 [64.5–88] ms;
P
=0.11).

Results:

The H-RB interval during VT was slightly shorter (
P
=0.14); however, the median RB-V interval was markedly longer than that during sinus rhythm (50 [29.5–83] versus 30 [8–51] ms;
P
=0.043]. In 6 patients with 3-dimensional mapping of the left ventricle, a slow anterograde or retrograde conduction over left HIS-Purkinje system with normal myocardial voltage was identified. In addition, Purkinje-related VTs (1.0±1.3 types) were also induced in 5 patients. Ablation was applied in distal left BB in patients with baseline left BBB and in one narrow QRS patient with sustained Purkinje-related VT, whereas right BB was targeted in other patients. During a mean follow-up of 31.4 months, frequent premature ventricular contractions occurred in one patient, and new VT developed in the other patient.

Conclusions:
Bundle branch reentry VT can occur in young patients with extensive conduction disturbances within HIS-Purkinje system. Ablation targeting at the distal left BB which bifurcates into left posterior and anterior fascicle can preserve the residual atrioventricular conduction, but intensive follow-up is needed.
Mechanisms Responsible for Serotonin Vascular Reactivity Sex Differences in the Internal Mammary Artery
Authors: Lamin Victor , Jaghoori Amenah , Jakobczak Rachel , Stafford Irene , Heresztyn Tamila , Worthington Michael , Edwards James , Viana Fabiano , Stuklis Robert , Wilson David P. , Beltrame John F. 
Published: July 2018

Background

The increased adverse cardiac events in women undergoing coronary artery bypass grafting are multifactorial and may include clinical, psychosocial, and biological factors. Potential contributing biological factors could include vascular hyperreactivity of the internal mammary artery (
IMA
) to endogenous vasoconstrictors in women, resulting in a predilection to myocardial ischemia. This study evaluated sex differences in serotonin and thromboxane A
2
dependent vasoconstriction in human isolated
IMA
, with the mechanistic role of (1) the endothelium, (2) nitric oxide (NO), (3) prostaglandins, and (4) receptor activity investigated for any observed sex difference.

Methods and Results

Viable isolated human
IMA
segments were obtained from 116 patients (44 women [mean age, 66.8±12.2 years] and 72 men [mean age, 66.6±10.4 years]) undergoing coronary artery bypass grafting. Cumulative concentration‐response curves for serotonin and thromboxane A
2
mimetic, U46619, were determined and revealed an increased sensitivity to serotonin but not U46619 in women. This sex difference to serotonin was further assessed by the following: (1) endothelial denudation, (2) endothelial NO synthase inhibition and
NO
quantification using electron paramagnetic resonance, (3) cyclooxygenase inhibition and prostaglandin metabolite quantification using mass spectrometry, and (4) quantification of receptor activity status. The female hyperreactivity to serotonin was (1) abolished by endothelial denudation; (2) unaffected by NO synthase inhibition, with no difference in electron paramagnetic resonance–assessed
NO
levels; (3) abolished by cyclooxygenase inhibition (quantification of prostaglandins in
IMA
revealed a trend towards reduced 6‐keto prostaglandin F1α in female
IMA
;
P
=0.08); and (4) unrelated to receptor activity.

Conclusions

These data indicate that female
IMAs
are hyperreactive to serotonin but not U46619, with the former attributable to an endothelium‐dependent cyclooxygenase pathway.
Characteristics and Treatment Outcomes of Acute Type A Aortic Dissection With Elevated D‐Dimer Concentration
Authors: Itagaki Ryo , Kimura Naoyuki , Mieno Makiko , Hori Daijiro , Itoh Satoshi , Akiyoshi Kei , Yuri Koichi , Tanno Keisuke , Kawahito Koji , Yamaguchi Atsushi 
Published: July 2018

Background
Clinical characteristics and treatment outcomes of acute type A aortic dissection with D‐dimer elevation have not been clarified.

Methods and Results

D‐dimer was measured preoperatively within 24 hours of symptom onset in 262 patients with
acute type A aortic dissection
. The median (and interquartile range) admission D‐dimer concentration in our total patient group was 26.7 (8.3–85.9) μg/
mL
. Median (interquartile range) D‐dimer concentrations were 5.0 (2.6–18.0) μg/
mL
for complete false lumen thrombosis (n=33), 60.9 (19.4–160.4) μg/
mL
for partial thrombosis (n=81), 26.5 (10.0–70.6) μg/
mL
for a patent
false lumen
(n=131), and 8.7 (3.2–26.9) μg/
mL
for ulcerlike projection (n=17) (
P<
0.01). With a D‐dimer concentration of ≤8.3 μg/
mL
representing the lower quartile, we then investigated predictors of a low D‐dimer level. Multivariate analysis showed dissection limited to the ascending aorta (
P<
0.01; odds ratio, 9.81) or descending aorta (
P<
0.01; odds ratio, 7.68), a completely thrombosed false lumen (
P<
0.01; odds ratio, 4.02), and absence of brain ischemia (
P=
0.013; odds ratio, 4.74) to be predictors of the lower D‐dimer concentration. Compared with patients with a low D‐dimer concentration (≤8.3 μg/
mL
, n=66), patients with a D‐dimer concentration >8.3 μg/
mL
(n=196) had a reduced preoperative platelet count and increased operation time and transfusion volume. In‐hospital mortality was elevated in this group (1.5% versus 11.2%;
P=
0.031), although 7‐year survival did not differ for hospital survivors (lower versus higher, 93.1% versus 79.1%;
P
=0.21).

Conclusions
D‐dimer concentrations are strongly influenced by the extent of dissection and false lumen status. Operative risks are increased in patients with a relatively high D‐dimer concentration.
Rates and Quality of Preinterventional Reperfusion in Patients With Direct Access to Endovascular Treatment
Authors: Kaesmacher Johannes , Giarrusso Mattia , Zibold Felix , Mosimann Pascal J. , Dobrocky Tomas , Piechowiak Eike , Bellwald Sebastian , Arnold Marcel , Jung Simon , El-Koussy Marwan , Mordasini Pasquale , Gralla Jan , Fischer Urs 
Published: July 2018

Background and Purpose—
Preinterventional reperfusion before endovascular treatment (ET) is a benefit of bridging with intravenous tPA (tissue-type plasminogen activator). However, detailed data on reperfusion quality and rates of obviating ET in a cohort of patients with immediate access to ET is lacking. Purpose of this analysis was to evaluate prevalence and quality of preinterventional reperfusion in mothership patients.

Methods—
All mothership patients (n=627) from a prospective registry subjected to angiography with an intention to perform ET were reviewed. Preinterventional change of occlusion site (COS) was categorized into COS with Thrombolysis in Cerebral Infarction (TICI) 0/1, COS with TICI ≥2a, COS with TICI ≥2b, and COS with perfusion worsening. Predictors and clinical relevance were evaluated using multivariable logistic regression and results are displayed as adjusted odds ratios (aOR) and corresponding 95% confidence intervals (95% CI).

Results—
Prevalence of COS in all patients was 10.7% (95% CI, 8.3%–13.1%), subdividing into 2.7% COS with TICI 0/1, 6.2% COS with ≥TICI 2a (including 2.9% with TICI ≥2b), and 1.8% COS with perfusion worsening. Factors related to COS with ≥TICI 2a were intravenous tPA (aOR, 11.98; 95% CI, 4.5–31.6), cardiogenic thrombus origin (aOR, 2.3; 95% CI, 1.1–4.6), and thrombus length (aOR per 1 mm increase 0.926; 95% CI, 0.87–0.99). Additional ET was performed despite COS with ≥TICI 2a in 51.3%. COS with ≥TICI 2a showed a tendency for favorable outcomes (modified Rankin Scale, ≤2; aOR, 2.65; 95% CI, 0.98–7.17). Rates of COS with ≥TICI 2a were particularly low in internal carotid artery and proximal M1 occlusions (2.2%; 95% CI, 0.9%–5%), where intravenous tPA was associated with perfusion worsening (aOR, 4.33; 95% CI, 1.12–16.80).

Conclusions—
Prevalence of preinterventional reperfusion is non-negligible in patients with direct access to ET and is clearly favored by intravenous tPA treatment. However, it is often incomplete and often requires additional ET. Preinterventional reperfusion of internal carotid artery and proximal M1 occlusions is rare and usually of low quality, where intravenous tPA may also promote perfusion worsening.
Endovascular Treatment in the DEFUSE 3 Study
Authors: Marks Michael P. , Heit Jeremy J. , Lansberg Maarten G. , Kemp Stephanie , Christensen Soren , Derdeyn Colin P. , Rasmussen Peter A. , Zaidat Osama O. , Broderick Joseph P. , Yeatts Sharon D. , Hamilton Scott , Mlynash Michael , Albers Gregory W. ,   on behalf of the DEFUSE 3 Investigators
Published: July 2018

Background and Purpose—
Endovascular therapy in an extended time window has been shown to be beneficial in selected patients. This study correlated angiographic outcomes of patients randomized to endovascular therapy with clinical and imaging outcomes in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3).

Methods—
Angiograms were assessed for the primary arterial occlusive lesion and the modified Thrombolysis in Cerebral Infarction (TICI) score at baseline and the final modified TICI score. Clinical outcomes were assessed using an ordinal analysis of 90-day modified Rankin Scale and a dichotomous analysis for functional independence (modified Rankin Scale score of 0–2). TICI scores were correlated with outcome, types of device used for thrombectomy, and 24-hour follow-up imaging.

Results—

TICI 2B-3 reperfusion was achieved in 70 of 92 patients (76%). TICI 2B-3 reperfusion showed a more favorable distribution of Rankin scores compared with TICI 0-2A; odds ratio, 2.77; 95% confidence interval, 1.17–6.56;
P
=0.019. Good functional outcome (90-day modified Rankin Scale score of 0–2) increased with better TICI scores (
P
=0.0028). There was less disability comparing TICI 3 patients to TICI 2B patients (
P
=0.037). Successful reperfusion (TICI 2B-3) was independent of the device used, the site of occlusion (internal carotid artery or M1) or adjunctive use of carotid angioplasty and stenting. Significantly less infarct growth at 24 hours was seen in TICI 3 patients compared with TICI 0-2A (
P
=0.0015) and TICI 2B (
P
=0.0002) patients.

Conclusions—
Thrombectomy in an extended time window demonstrates similar rates of TICI 2B-3 reperfusion to earlier time window studies. Successful reperfusion was independent of the device used, the site of occlusion or adjunctive use of carotid angioplasty and stenting. TICI 3 reperfusion was more likely to result in low rates of infarct growth at 24 hours and good functional outcome at 90 days.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02586415.
Reaction in Politics
Authors: Alexander James 
Published: July 2018

Abstract
Reaction is a subject usually avoided by political theorists, since it raises awkward historical, philosophical and political questions. Perhaps philosophers of history might make better sense of it. In this article I claim that reaction has to be understood in relation to the concepts of revolution, tradition, progress and conservatism. I argue that the specific meaning of reaction is a response to the specific action that establishes the principle that order should be established only on enlightened principles. The few theorists who have dealt with reaction have disagreed about whether it is the same as conservatism or not. I show that reaction is not an element in what I call a status quo conservatism, though it is an element in any conservatism conceived more broadly. I characterise reaction in full as the attempt to reverse the establishment of the principle that only enlightened principles shall be the basis of political order, the attempt to resist the further establishment of those enlightened principles, and also the attempt to criticise contemporary enlightened politics in terms of the unenlightened standards which existed before the revolution.
Correlation-Cutoff Method for Covariance Localization in Strongly Coupled Data Assimilation
Authors: Yoshida Takuma , Kalnay Eugenia 
Published: July 2018

AbstractStrongly coupled data assimilation (SCDA), where observations of one component of a coupled model are allowed to directly impact the analysis of other components, sometimes fails to improve the analysis accuracy with an ensemble Kalman filter (EnKF) as compared with weakly coupled data assimilation (WCDA). It is well known that an observation’s area of influence should be localized in EnKFs since the assimilation of distant observations often degrades the analysis because of spurious correlations. This study derives a method to estimate the reduction of the analysis error variance by using estimates of the cross covariances between the background errors of the state variables in an idealized situation. It is shown that the reduction of analysis error variance is proportional to the squared background error correlation between the analyzed and observed variables. From this, the authors propose an offline method to systematically select which observations should be assimilated into which model state variable by cutting off the assimilation of observations when the squared background error correlation between the observed and analyzed variables is small. The proposed method is tested with the local ensemble transform Kalman filter (LETKF) and a nine-variable coupled model, in which three Lorenz models with different time scales are coupled with each other. The covariance localization with the correlation-cutoff method achieves an analysis more accurate than either the full SCDA or the WCDA methods, especially with smaller ensemble sizes.
Hacking the Human: The Prevalence Paradox in Cybersecurity
Authors: Sawyer Ben D. , Hancock Peter A. 
Published: July 2018

Objective: This work assesses the efficacy of the “prevalence effect” as a form of cyberattack in human-automation teaming, using an email task. Background: Under the prevalence effect, rare signals are more difficult to detect, even when taking into account their proportionally low occurrence. This decline represents diminished human capability to both detect and respond. As signal probability (SP) approaches zero, accuracy exhibits logarithmic decay. Cybersecurity, a context in which the environment is entirely artificial, provides an opportunity to manufacture conditions enhancing or degrading human performance, such as prevalence effects. Email cybersecurity prevalence effects have not previously been demonstrated, nor intentionally manipulated. Method: The Email Testbed (ET) provides a simulation of a clerical email work involving messages containing sensitive personal information. Using the ET, participants were presented with 300 email interactions and received cyberattacks at rates of either 1%, 5%, or 20%. Results: Results demonstrated the existence and power of prevalence effects in email cybersecurity. Attacks delivered at a rate of 1% were significantly more likely to succeed, and the overall pattern of accuracy across declining SP exhibited logarithmic decay. Application: These findings suggest a “prevalence paradox” within human-machine teams. As automation reduces attack SP, the human operator becomes increasingly likely to fail in detecting and reporting attacks that remain. In the cyber realm, the potential to artificially inflict this state on adversaries, hacking the human operator rather than algorithmic defense, is considered. Specific and general information security design countermeasures are offered.
Massive heterotopic ossification after distal femur fracture
Authors: Ozkocak Gokhan , Cakir Kandemirli Guzin , Ozcakir Suheda 
Published: July 2018

Introduction Heterotopic ossification is the formation of lamellar bone in periarticular soft tissue that can be seen in paralysed patients or following trauma. It can cause significant burden to already debilitated patients. Case presentation A 12-year-old boy with paraplegia due to neuromyelitis optica presented with progressive right knee pain and swelling. There was no history of trauma to the knee. Anteroposterior radiograph of femur at the initial presentation showed a supracondylar femur fracture for which casting was performed. Six weeks later, when casting was removed, swelling along with increased rubor in distal thigh region was noted. Radiography of the right femur revealed an unhealed distal femur fracture along with massive ossification extending from lesser trochanter to fracture line along the soft tissue around the femoral shaft. Conclusion This case presented the clinical and imaging findings of a giant heterotopic ossification in the thigh region following an extra-articular fracture.
Physical activity and disability measures in chronic non-specific low back pain: a study of responsiveness
Authors: Morelhão Priscila K , Franco Márcia R , Oliveira Crystian B , Hisamatsu Thalysi M , Ferreira Paulo H , Costa Leonardo OP , Maher Chris G , Pinto Rafael Zambelli 
Published: July 2018

Objectives: To compare the responsiveness of disability measures with physical activity measures in patients with chronic low back pain (CLBP) undergoing a course of physical therapy treatment. Design: This is a prospective cohort study with two-month follow-up. Subjects: A total of 106 patients presenting with non-specific CLBP of more than three months duration were recruited. Main measures: Disability measures investigated were Quebec Back Pain Disability Scale and Roland Morris Disability Questionnaire. Physical activity measures analyzed include the Baecke Habitual Physical Activity Questionnaire and objective measures derived from an accelerometer (i.e. total time spent in moderate-to-vigorous and light physical activity, number of steps and counts per minute). Disability and physical activity measures were collected at the baseline and after eight weeks of treatment. For the responsiveness analyses, effect size (ES) and standardized response mean (SRM) were calculated. Correlations between the change in disability and physical activity measures were calculated. Results: Responsiveness for disability measures was considered to be large with ESs ranging from −1.03 to −1.45 and SRMs ranging from −0.99 to −1.34, whereas all physical activity measures showed values lower than 0.20. Changes in disability measures did not correlate with changes in physical activity measures (correlation coefficients ranged from −0.10 to 0.09). Conclusion: Disability measures were responsive after a course of physical therapy treatment in patients with CLBP. The lack of responsiveness in the physical activity measures might be due to the inability of these measures to detect change over time or the use of an intervention not designed to increase physical activity levels.