bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Methylation Controls Metastasis-Suppressive 14q32-Encoded miRNAs
Authors: Oshima Go , Poli Elizabeth C. , Bolt Michael J. , Chlenski Alexandre , Forde Martin , Jutzy Jessica M.S. , Biyani Neha , Posner Mitchell C. , Pitroda Sean P. , Weichselbaum Ralph R. , Khodarev Nikolai N. 
Published: December 2018

Abstract

Expression of 14q32-encoded miRNAs is a favorable prognostic factor in patients with metastatic cancer. In this study, we used genomic inhibition of DNA methylation through disruption of DNA methyltransferases DNMT1 and DNMT3B and pharmacologic inhibition with 5-Aza-2′-deoxycytidine (5-Aza-dC, decitabine) to demonstrate that DNA methylation predominantly regulates expression of metastasis-suppressive miRNAs in the 14q32 cluster. DNA demethylation facilitated CCCTC-binding factor (CTCF) recruitment to the maternally expressed gene 3 differentially methylated region (MEG3-DMR), which acts as a cis-regulatory element for 14q32 miRNA expression. 5-Aza-dC activated demethylation of the MEG3-DMR and expression of 14q32 miRNAs, which suppressed adhesion, invasion, and migration (AIM) properties of metastatic tumor cells. Cancer cells with MEG3-DMR hypomethylation exhibited constitutive expression of 14q32 miRNAs and resistance to 5-Aza-dC–induced suppression of AIM. Expression of methylation-dependent 14q32 miRNAs suppressed metastatic colonization in preclinical models of lung and liver metastasis and correlated with improved clinical outcomes in patients with metastatic cancer. These findings implicate epigenetic modification via DNA methylation in the regulation of metastatic propensity through miRNA networks and identify a previously unrecognized action of decitabine on the activation of metastasis-suppressive miRNAs.

Significance:
This study investigates epigenetic regulation of metastasis-suppressive miRNAs and the effect on metastasis.
Coordinately Targeting Cell-Cycle Checkpoint Functions in Integrated Models of Pancreatic Cancer
Authors: Chung Sejin , Vail Paris , Witkiewicz Agnieszka K. , Knudsen Erik S. 
Published: December 2018

Abstract

Purpose:
Cancer cells often have deficiencies in cell-cycle control mechanisms and could be dependent on specific cell-cycle checkpoints to maintain viability. Because of the documented role of KRAS in driving replication stress, we targeted the checkpoint governing DNA replication using CHK1 kinase inhibitors in pancreatic ductal adenocarcinoma (PDAC) models and examined mechanisms of resistance.

Experimental Design:
Single-agent efficacy of CHK1 inhibition was investigated in established and primary PDAC lines. Drug screening was performed to identify cooperative agents. In vitro and in vivo studies were employed to interrogate combination treatment efficacy and mechanisms of resistance.

Results:
Many PDAC models evade single-agent inhibition through mechanisms that allow S-phase progression with CHK1 inhibited. Gene expression analysis revealed FOXM1 as a potential marker of CHK1 sensitivity and defined a form of pancreatic cancer with poor prognosis. Drug screen analysis identified WEE1 as a cooperative agent with CHK1 and was effective in cell culture. In vivo experiments validated the combination efficacy; however, resistance could evolve. Resistance was due to selection of a stable subclone from the original PDX tumor, which harbored high baseline replication stress. In vitro analysis revealed that gemcitabine could eliminate viability in the resistant models. The triplet regimen of gemcitabine, CHK1, and WEE1 inhibition provided strong disease control in all xenograft models interrogated.

Conclusions:
These results demonstrate the therapeutic resiliency of pancreatic cancer and indicate that coordinately targeting cell-cycle checkpoints in concert with chemotherapy could be particularly efficacious.
A new host for Philornis torquans (Diptera, Muscidae) from the Brazilian Cerrado
Authors: Couri Márcia Souto , Barbosa Leandro , Marini Miguel Ângelo , Duca Charles , Pujol-Luz José Roberto 
Published: December 2018

Philornis larvae and pupae were collected in nestlings of Neothraupis fasciata (Lichtenstein), the White-banded Tanager (Passeriformes, Thraupidae), in three breeding seasons, between October and November 2003‑2005 in a reserve in central Brazil. Here, we present biological data, diagnosis to the recognition of the species and a key to the segregation of species occurring in the Cerrado. The larvae were intradermic in the nestlings and the pupae were collected in the nests after the birds have abandoned them. The immatures collected were taken to the laboratory and reared under laboratory conditions, until emergence. The species identified as Philornis torquans (Nielsen), is here firstly recorded from the Brazilian Cerrado, and firstly recorded its association with N. fasciata. With this record, the number of Philornis species occurring in the Cerrado rises to three.
A new species of Novamundoniscus Schultz, 1995 (Isopoda, Oniscidea, Dubioniscidae) from the state of Tocantins, Brazil
Authors: Campos-Filho Ivanklin Soares , Cardoso Giovanna Monticelli , Aguiar José Otávio 
Published: December 2018

The genus Novamundoniscus includes eight species with distribution in Brazil and Venezuela. The new species Novamundoniscus adhara Campos-Filho & Cardoso sp. nov. from the state of Tocantins, northern Brazil, is described, which represents the first record to the family for the state of Tocantins.
National Burden of Heart Failure Events in the United States, 2006 to 2014
Authors: Jackson Sandra L. , Tong Xin , King Raymond J. , Loustalot Fleetwood , Hong Yuling , Ritchey Matthew D. 
Published: December 2018

Background:
Heart failure (HF)—a serious and costly condition—is increasingly prevalent. We estimated the US burden including emergency department (ED) visits, inpatient hospitalizations and associated costs, and mortality.

Methods and Results:

We analyzed 2006 to 2014 data from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample, the Healthcare Cost and Utilization Project National (nationwide) Inpatient Sample, and the National Vital Statistics System.
International Classification of Disease
codes identified HF and comorbidities. Burden was estimated separately for ED visits, hospitalizations, and mortality. In addition, criteria were applied to identify total unique acute events. Rates of primary HF (primary diagnosis or underlying cause of death) and comorbid HF (comorbid diagnosis or contributing cause of death) were calculated, age standardized to the 2010 US population. In 2014, there were an estimated 1 068 412 ED visits, 978 135 hospitalizations, and 83 705 deaths with primary HF. There were 4 071 546 ED visits, 3 370 856 hospitalizations, and 230 963 deaths with comorbid HF. Between 2006 and 2014, the total unique acute event rate for primary HF declined from 536 to 449 per 100 000 (relative percent change of –16%;
P
for trend, <0.001) but increased for comorbid HF from 1467 to 1689 per 100 000 (relative percentage change, 15%;
P
for trend, <0.001). HF-related mortality decreased significantly from 2006 to 2009 but did not change meaningfully after 2009. For hospitalizations with primary HF, the estimated mean cost was $11 552 in 2014, totaling an estimated $11 billion.

Conclusions:
Given substantial healthcare and mortality burden of HF, rising healthcare costs, and the aging US population, continued improvements in HF prevention, management, and surveillance are important.
Clinical Phenotype and Genotype Associations With Improvement in Left Ventricular Function in Dilated Cardiomyopathy
Authors: Verdonschot Job A.J. , Hazebroek Mark R. , Wang Ping , Sanders-van Wijk Sandra , Merken Jort J. , Adriaansen Yvonne A. , van den Wijngaard Arthur , Krapels Ingrid P.C. , Brunner-La Rocca Hans-Peter , Brunner Han G. , Heymans Stephane R.B. 
Published: December 2018

Background:
Improvement of left ventricular function (also called left ventricular reverse remodeling [LVRR]) is an important treatment goal in patients with dilated cardiomyopathy (DCM) and hypokinetic non-DCM (HNDC) and is prognostically favorable. We tested whether genetic DCM mutations impact LVRR independent from clinical parameters.

Methods and Results:

Patients with DCM and hypokinetic non-DCM (n=346; mean left ventricular ejection fraction, 30%) underwent genotyping for 47 DCM-associated genes in addition to extensive phenotyping. LVRR was defined as improvement of left ventricular ejection fraction >50% or ≥10% absolute increase, with cardiac dimensions (left ventricular end diastolic diameter) ≤33 mm/m
2
or ≥10% relative decrease. LVRR occurred in 180 (52%) patients after a median follow-up of 12-month optimal medical treatment. Low baseline left ventricular ejection fraction, a hypokinetic non-DCM phenotype, high systolic blood pressure, absence of a family history of DCM, female sex, absence of atrioventricular block, and treatment with β-blockers were all independent positive clinical predictors of LVRR. With the exception of
TTN
, genetic mutations were strongly associated with a lower rate of LVRR (odds ratio, 0.19 [0.09–0.42];
P
<0.0001).
TTN
and
LMNA
were independently associated with LVRR (odds ratio, 2.49 [1.09–6.20];
P
=0.038 and 0.11 [0.01–0.99];
P
=0.049, respectively). Adding mutation status significantly improved discrimination (C statistics) and reclassification (integrated discrimination improvement/net reclassification index) of the clinical model predicting LVRR. Furthermore, the risk for heart failure hospitalization and cardiovascular death is lower in the LVRR patients on the long term (hazard ratio, 0.47 [0.24–0.91];
P
=0.009 and 0.18 [0.04–0.82];
P
=0.007, respectively), and LVRR is an independent predictor for event-free survival.

Conclusions:
The genetic substrate is associated with the clinical course and long-term prognosis of patients with DCM/hypokinetic non-DCM.
Physical Function, Frailty, Cognition, Depression, and Quality of Life in Hospitalized Adults ≥60 Years With Acute Decompensated Heart Failure With Preserved Versus Reduced Ejection Fraction
Authors: Warraich Haider J. , Kitzman Dalane W. , Whellan David J. , Duncan Pamela W. , Mentz Robert J. , Pastva Amy M. , Nelson M. Benjamin , Upadhya Bharathi , Reeves Gordon R. 
Published: December 2018

Background:
Older hospitalized acute decompensated heart failure (HF) patients have persistently poor outcomes and delayed recovery regardless of ejection fraction (EF). We hypothesized that impairments in physical function, frailty, cognition, mood, and quality of life (QoL) potentially contributing to poor clinical outcomes would be similarly severe in acute decompensated HF patients ≥60 years of age with preserved versus reduced EF (HFpEF and HFrEF).

Methods and Results:

In 202 consecutive older (≥60 years) hospitalized acute decompensated HF patients in a multicenter trial, we prospectively performed at baseline: short physical performance battery, 6-minute walk distance, frailty assessment, Geriatric Depression Scale, Montreal Cognitive Assessment, and QoL assessments. Older acute decompensated HFpEF (EF ≥45%, n=96) and HFrEF (EF <45%, n=106) patients had similar impairments in all physical function measures (short physical performance battery [5.9±0.3 versus 6.2±0.2]; 6-minute walk distance [184±10 versus 186±9 m]; and gait speed [0.60±0.02 versus 0.61±0.02 m/s]) and rates of frailty (55% versus 52%;
P
=0.70) and cognitive impairment (77% versus 81%;
P
=0.56) when adjusted for differences in sex, body mass index, and comorbidities. However, depression and QoL were consistently worse in HFpEF versus HFrEF. Depression was usually unrecognized clinically with 38% having Geriatric Depression Scale ≥5 and no documented history of depression.

Conclusions:
Patients ≥60 years hospitalized with acute decompensated HF patients have broad, marked impairments in physical function and high rates of frailty and impaired cognition: these impairments are similar in HFpEF versus HFrEF. Further, depression was common and QoL was reduced, and both were worse in HFpEF than HFrEF. Depression was usually unrecognized clinically. These findings suggest opportunities for novel interventions to improve these important patient-centered outcomes.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02196038.
Evaluating Systolic and Diastolic Cardiac Function in Rodents Using Microscopic Computed Tomography
Authors: Kojonazarov Baktybek , Belenkov Alexander , Shinomiya Shohei , Wilchelm Jochen , Kampschulte Marian , Mizuno Shiro , Ghofrani Hossein Ardeschir , Grimminger Friedrich , Weissmann Norbert , Seeger Werner , Schermuly Ralph Theo 
Published: December 2018

Background:
The use of microscopic computed tomography to assess the key functional parameters of systolic emptying or diastolic filling in small animals has not been previously reported. The aim of the study was to test whether microscopic computed tomography can assess the dynamics of both left ventricle and right ventricle (RV) diastolic filling and systolic emptying in an experimental model of pulmonary arterial hypertension

Methods and Results:

The Wistar-Kyoto rats were injected subcutaneously with the VEGF (vascular endothelial growth factor)-receptor inhibitor SU5416 (20 mg/kg body weight) and were then exposed to chronic hypoxia (10% oxygen) for 21 days (SU5416-hypoxia) followed by normoxia for an additional 2 weeks. Thereafter, multiphase cine cardiac images were acquired using a microscopic computed tomography scanner in conjunction with a blood-pool iodinated contrast agent. Examination of the 3-dimensional images of SU5416-hypoxia rats confirmed the presence of severe pulmonary arterial hypertension. Functional parameters that describe the dynamics of ventricular systolic ejection and diastolic filling were calculated. RV peak ejection rate was significantly decreased (
P
<0.03) in SU5416-hypoxia rats compared with controls. RV peak filling rate had a significant decrease compared with controls (
P
<0.03), particularly in the early phase of diastole (
P
<0.03). This was accompanied by increased time to peak filling rate (
P
<0.03) and total filling time (
P
<0.06). Spearman analysis between microscopic computed tomography RV diastolic indices and invasively derived RV end-diastolic pressure indicated excellent correlation.

Conclusions:
We developed a method that allows rapid and accurate assessment of cardiac functional indices and that paves the way for more extensive preclinical cardiovascular research.
Increased Physical Activity Post–Myocardial Infarction Is Related to Reduced Mortality: Results From the SWEDEHEART Registry
Authors: Ekblom Orjan , Ek Amanda , Cider Åsa , Hambraeus Kristina , Börjesson Mats 
Published: December 2018

Background

With increasing survival rates among patients with myocardial infarction (
MI
), more demands are placed on secondary prevention. While physical activity (
PA
) efforts to obtain a sufficient
PA
level are part of secondary preventive recommendations, it is still underutilized. Importantly, the effect of changes in
PA
after
MI
is largely unknown. Therefore, we sought to investigate the effect on survival from changes in
PA
level, post‐
MI
.

Methods and Results

Data from Swedish national registries were combined, totaling 22 227 patients with
MI
.
PA
level was self‐reported at 6 to 10 weeks post‐
MI
and 10 to 12 months post‐
MI
. Patients were classified as constantly inactive, increased activity, reduced activity, and constantly active. Proportional hazard ratios were calculated. During 100 502 person‐years of follow‐up (mean follow‐up time 4.2 years), a total of 1087 deaths were recorded. Controlling for important confounders (including left ventricular function, type of
MI
, medication, smoking, participation in cardiac rehabilitation program, quality of life, and estimated kidney function), we found lower mortality rates among constantly active (hazard ratio: 0.29, 95% confidence interval: 0.21–0.41), those with increased activity (0.41, 95% confidence interval: 0.31–0.55), and those with reduced activity (hazard ratio: 0.56, 95% confidence interval: 0.45–0.69) during the first year post‐
MI
, compared with those being constantly inactive. Stratified analyses indicated strong effect of
PA
level among both sexes, across age,
MI
type, kidney function, medication, and smoking status.

Conclusions

The present article shows that increasing the
PA
level, compared with staying inactive the first year post‐
MI
, was related to reduced mortality.
An Automated Velocity Dealiasing Scheme for Radar Data Observed from Typhoons and Hurricanes
Authors: He Guangxin , Sun Juanzhen , Ying Zhuming 
Published: December 2018

AbstractAccurate and automated dealiasing of radar data is important for data interpretation and downstream applications such as numerical weather prediction (NWP) models. In this paper an improved radial velocity dealiasing scheme is presented and evaluated using observations from several S-band radars under the severe weather conditions of typhoons and hurricanes. This scheme, named Automated Dealiasing for Typhoon and Hurricane (ADTH), is a further development of the China New Generation Doppler Weather Radar (CINRAD) improved dealiasing algorithm (CIDA). The upgraded algorithm ADTH includes three modules designed to select the first radial from which the dealiasing process starts, to conduct a two-way multipass dealiasing, and to perform an error check for a final local dealiasing. The dealiasing algorithm is applied to two typhoon hurricane cases and four typhoon cases observed with radars from CINRAD, NEXRAD of the United States, and the Taiwan radar network for a continuous period of 12 h for each of the selected cases. The results show that ADTH outperforms CIDA for all of the test cases.
The Food Doctors: A pilot study to connect urban children and medical students using nutrition education
Authors: Johnston Bryan , El-Arabi Ahmad , Tuomela Krista , Nelson David 
Published: December 2018

Background: Children in the USA face increasing nutrition-related health risks, including obesity rates of 16.9% – a figure that has more than tripled over the past four decades. Nutrition education is beneficial to improve children’s health through obesity prevention and the promotion of healthy habits, and the elementary school years are a key time to implement health education interventions. Objective: To develop a medical student created and operated nutrition education intervention for urban underserved elementary school students. Design: The Food Doctors (TFD) programme is a hands-on, interactive, in-class nutrition education pilot initiative for elementary school students and adheres to the established tenets of effective in-class nutrition education whenever possible: (1) interactive hands-on curriculum, (2) use of culturally relevant topics and (3) the inclusion of effective evaluation techniques. Setting: Urban elementary school classrooms in Milwaukee, Wisconsin, USA. Method: A literature review and feedback from partner schools’ needs informed curriculum development. Institutional review board approval was sought and study materials prepared. The pilot programme was carried out at partner schools during class time. Results: A total of 83 students participated in the pilot study: 46 third-grade students and 37 fourth graders. Evaluation focused on assessing student baseline knowledge and exploring post-programme nutrition knowledge gains. Conclusion: TFD pilot programme demonstrated gaps in baseline nutrition knowledge among elementary school students and showed improved post-programme ability to correctly answer basic nutrition knowledge questions.
Embedding Training Within Warnings Improves Skills of Identifying Phishing Webpages
Authors: Xiong Aiping , Proctor Robert W. , Yang Weining , Li Ninghui 
Published: December 2018

Objective: Evaluate the effectiveness of training embedded within security warnings to identify phishing webpages. Background: More than 20 million malware and phishing warnings are shown to users of Google Safe Browsing every week. Substantial click-through rate is still evident, and a common issue reported is that users lack understanding of the warnings. Nevertheless, each warning provides an opportunity to train users about phishing and how to avoid phishing attacks. Method: To test use of phishing-warning instances as opportunities to train users’ phishing webpage detection skills, we conducted an online experiment contrasting the effectiveness of the current Chrome phishing warning with two training-embedded warning interfaces. The experiment consisted of three phases. In Phase 1, participants made login decisions on 10 webpages with the aid of warning. After a distracting task, participants made legitimacy judgments for 10 different login webpages without warnings in Phase 2. To test the long-term effect of the training, participants were invited back a week later to participate in Phase 3, which was conducted similarly as Phase 2. Results: Participants differentiated legitimate and fraudulent webpages better than chance. Performance was similar for all interfaces in Phase 1 for which the warning aid was present. However, training-embedded interfaces provided better protection than the Chrome phishing warning on both subsequent phases. Conclusion: Embedded training is a complementary strategy to compensate for lack of phishing webpage detection skill when phishing warning is absent. Application: Potential applications include development of training-embedded warnings to enable security training at scale.
Bronchoscopic sclerosis of post-resectional bronchial fistulas
Authors: Rivo Eduardo , Quiroga Jorge , García-Prim José-María , Obeso Andrés , Soro Jose , Oseira Anaí , Golpe Antonio 
Published: December 2018

Background Pulmonary resection is, by far, the primary cause of bronchial fistula. This is a severe complication because of its morbidity and mortality and the related consumption of resources. Definitive closure continues to be a challenge with several therapeutic options, but none are optimal. We describe our experience in bronchoscopic application of ethanolamine and lauromacrogol 400 for the treatment of post-resection bronchial fistulas. Methods Clinical records of 8 patients treated using this technique were collected prospectively. The diagnosis of a fistula was confirmed by flexible bronchoscopy. Sclerosis was indicated in the context of multimodal treatment. Sclerosant injection was performed under general anesthesia with a Wang 22G needle through a flexible bronchoscope. The procedure was repeated at 2-week intervals until definitive closure of the fistula was confirmed. Results Fistula closure was achieved in 7 (87.5%) of the 8 patients, with persistence of the fistula in one patient who could not complete the treatment because of recurrence of his neoplastic pathology. No recurrence or complications related to the technique were registered. Conclusions Bronchoscopic sclerosis by means of submucosal injection of lauromacrogol 400 or ethanolamine should be part of the multimodal treatment of bronchopleural fistula after lung resection, pending further studies that contribute to the accurate establishment of optimal indications for this procedure.