bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53 and ΔNp63α Coregulate the Transcriptional and Cellular Response to TGFβ and BMP Signals
Authors: Balboni Amanda L. , Cherukuri Pratima , Ung Matthew , DeCastro Andrew J. , Cheng Chao , DiRenzo James 
Published: February 2015

Abstract
The TGFβ superfamily regulates a broad range of cellular processes, including proliferation, cell-fate specification, differentiation, and migration. Molecular mechanisms underlying this high degree of pleiotropy and cell-type specificity are not well understood. The TGFβ family is composed of two branches: (i) TGFβs, activins, and nodals, which signal through SMAD2/3, and (ii) bone morphogenetic proteins (BMP), which signal through SMAD1/5/8. SMADs have weak DNA-binding affinity and rely on coactivators and corepressors to specify their transcriptional outputs. This report reveals that p53 and ΔNp63α act as transcriptional partners for SMAD proteins and thereby influence cellular responses to TGFβ and BMPs. Suppression of p53 or overexpression of ΔNp63α synergistically enhance BMP-induced transcription. Mechanistically, p53 and ΔNp63α physically interact with SMAD1/5/8 proteins and co-occupy the promoter region of inhibitor of differentiation (ID2), a prosurvival BMP target gene. Demonstrating further convergence of these pathways, TGFβ-induced canonical BMP regulated transcription in a ΔNp63α- and p53-dependent manner. Furthermore, bioinformatic analyses revealed that SMAD2/3 and ΔNp63α coregulate a significant number of transcripts involved in the regulation of epithelial-to-mesenchymal transition. Thus, p53 and ΔNp63α are transcriptional partners for a subset of TGFβ- and BMP-regulated SMAD target genes in the mammary epithelium. Collectively, these results establish an integrated gene network of SMADs, p53, and ΔNp63α that contribute to EMT and metastasis.
Implications: This study identifies aberrant BMP activation as a result of p53 mutation or ΔNp63α expression. Mol Cancer Res; 13(4); 732–42. ©2015 AACR.
PD-1 Restrains Radiotherapy-Induced Abscopal Effect
Authors: Park Sean S. , Dong Haidong , Liu Xin , Harrington Susan M. , Krco Christopher J. , Grams Michael P. , Mansfield Aaron S. , Furutani Keith M. , Olivier Kenneth R. , Kwon Eugene D. 
Published: February 2015

AbstractWe investigated the influence of PD-1 expression on the systemic antitumor response (abscopal effect) induced by stereotactic ablative radiotherapy (SABR) in preclinical melanoma and renal cell carcinoma models. We compared the SABR-induced antitumor response in PD-1–expressing wild-type (WT) and PD-1–deficient knockout (KO) mice and found that PD-1 expression compromises the survival of tumor-bearing mice treated with SABR. None of the PD-1 WT mice survived beyond 25 days, whereas 20% of the PD-1 KO mice survived beyond 40 days. Similarly, PD-1–blocking antibody in WT mice was able to recapitulate SABR-induced antitumor responses observed in PD-1 KO mice and led to increased survival. The combination of SABR plus PD-1 blockade induced near complete regression of the irradiated primary tumor (synergistic effect), as opposed to SABR alone or SABR plus control antibody. The combination of SABR plus PD-1 blockade therapy elicited a 66% reduction in size of nonirradiated, secondary tumors outside the SABR radiation field (abscopal effect). The observed abscopal effect was tumor specific and was not dependent on tumor histology or host genetic background. The CD11ahigh CD8+ T-cell phenotype identifies a tumor-reactive population, which was associated in frequency and function with a SABR-induced antitumor immune response in PD-1 KO mice. We conclude that SABR induces an abscopal tumor-specific immune response in both the irradiated and nonirradiated tumors, which is potentiated by PD-1 blockade. The combination of SABR and PD-1 blockade has the potential to translate into a potent immunotherapy strategy in the management of patients with metastatic cancer. Cancer Immunol Res; 3(6); 610–9. ©2015 AACR.
PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer
Authors: Severson Jill J. , Serracino Hilary S. , Mateescu Valerica , Raeburn Christopher D. , McIntyre Robert C. , Sams Sharon B. , Haugen Bryan R. , French Jena D. 
Published: February 2015

Abstract
Regional metastatic differentiated thyroid cancer (mDTC) provides a unique model in which to study the tumor–immune interface. These lymph node metastases persist for years, generally without progression to distant metastases. Although the immune system likely impedes disease progression, it is unsuccessful in eliminating disease. Our previous studies revealed that programmed death-1 (PD-1)+ T cells were enriched in tumor-involved lymph nodes (TILN). Tumor-associated leukocytes and tumor cells were collected from grossly involved lymph nodes from 12 patients to further characterize the phenotype and functional potential of mDTC-associated PD-1+ T cells. PD-1+CD4+ and PD-1+CD8+ T cells were enriched in 8 of 12 TILN samples. PD-1+ T cells coexpressed Tim-3 and CD69 and failed to downregulate CD27. CD8+ T cells, but not CD4+ T cells, from these samples were variably deficient in their ability to produce effector cytokines when compared with control TILNs that lacked resident PD-1+ T cells. PD-1+CD8+ T cells were capable of exocytosis but lacked intracellular perforin. Surprisingly, T-cell proliferative capacity was largely maintained in all samples. Thus, although PD-1 expression by mDTC-associated CD8+ T cells was associated with dysfunction, exhaustion was not complete. Notably, molecular markers of exhaustion did not translate to dysfunction in all samples or in CD4+ T cells. Regulatory T cells (Treg), PD-L1, and galectin-9 were commonly found in mDTC and likely contributed to the initiation of T-cell exhaustion and disease progression. Therapies that release the effects of PD-1 and Tim-3 and reduce the suppressive effects of Tregs may encourage tumor elimination in patients with mDTC. Cancer Immunol Res; 3(6); 620–30. ©2015 AACR.
Left Ventricular Reverse Remodeling With Biventricular Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Heart Failure in the BLOCK HF Trial
Authors: St. John Sutton Martin , Plappert Ted , Adamson Philip B. , Li Pei , Christman Shelly A. , Chung Eugene S. , Curtis Anne B. 
Published: February 2015

Background—
Biventricular pacing in heart failure (HF) improves survival, relieves symptoms, and attenuates left ventricular (LV) remodeling. However, little is known about biventricular pacing in HF patients with atrioventricular block because they are typically excluded from biventricular trials.

Methods and Results—

The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial randomized patients with atrioventricular block, New York Heart Association symptom classes I to III HF, and LV ejection fraction ≤50% to biventricular or right ventricular pacing. Doppler echocardiograms were obtained at randomization (after 30 to 60 days of right ventricular pacing postimplant) and every 6 months through 24 months. Data analysis comparing changes in 10 prespecified echo parameters over time was conducted using a Bayesian design. LV end systolic volume index was also evaluated as a predictor of mortality/morbidity. Of 691 randomized subjects, 624 had paired Doppler echocardiogram data for ≥1 analyses at 6, 12, 18, or 24 months. Biventricular pacing significantly reduced LV volume indices and intraventricular mechanical delay, and improved LV ejection fraction, consistent with LV reverse remodeling. These parameters showed little change with right ventricular pacing alone, indicating no systematic reverse remodeling with right ventricular pacing. LV end systolic volume index was predictive of mortality/morbidity; the estimated risk increased up to 1% for every 1 mL/m
2
increase in LV end systolic volume index.

Conclusions—
LV end systolic volume index is a significant predictor of mortality/morbidity in this population. Cardiac structure and function are improved with biventricular pacing for patients with atrioventricular block and LV systolic dysfunction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00267098.
Prospective, Multicenter, Randomized, Controlled Pilot Trial of Peritoneal Hypothermia in Patients With ST-Segment— Elevation Myocardial Infarction
Authors: Nichol Graham , Strickland Warren , Shavelle David , Maehara Akiko , Ben-Yehuda Ori , Genereux Philippe , Dressler Ovidiu , Parvataneni Rupa , Nichols Melissa , McPherson John , Barbeau Gérald , Laddu Abhay , Elrod Jo Ann , Tully Griffeth W. , Ivanhoe Russell , Stone Gregg W. 
Published: February 2015

Background—
Systemic hypothermia may reduce infarct size if established before reperfusion. The large surface area of the bowel may facilitate rapid hypothermia. We therefore examined the feasibility, safety, and efficacy of hypothermia induced by an automated peritoneal lavage system in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Methods and Results—

Patients with ST-segment–elevation myocardial infarction within 6 hours of symptom onset were randomized to peritoneal hypothermia before and for 3 hours after percutaneous coronary intervention versus control. The primary safety end point was the 30-day composite rate of death, reinfarction, ischemia-driven target vessel revascularization, major bleeding, sepsis, pneumonia, peritonitis, severe arrhythmia, or renal failure. The primary efficacy end point was infarct size assessed by cardiac MRI on day 3 to 5. Fifty-four patients were randomized at 7 centers to hypothermia (n=28) versus control (n=26). Hypothermia was successfully initiated in 96.3% of patients, and median [interquartile range] temperature at first balloon inflation was 34.7 [34.0–34.9]°C. Median door-to-balloon times in the hypothermia and control groups were 62 [51–81] and 47 [37–55] minutes, respectively (
P
=0.007). The primary safety end point occurred in 6 (21.4%) and 0 (0%) patients in the hypothermia and control groups, respectively (
P
=0.01), including 3 versus 0 stent thrombosis events. Infarct size was 17.2% [15.1–20.6] and 16.1% [10.0–22.2] in the hypothermia and control groups, respectively (
P
=0.54).

Conclusions—
Peritoneal hypothermia is feasible and achieves rapid cooling with only a modest increase in treatment times in the setting of ST-segment–elevation myocardial infarction. However, in the present randomized trial, peritoneal hypothermia was associated with an increased rate of adverse events without reducing infarct size.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01655433.
Low Cardiac Index Is Associated With Incident Dementia and Alzheimer Disease
Authors: Jefferson Angela L. , Beiser Alexa S. , Himali Jayandra J. , Seshadri Sudha , O’Donnell Christopher J. , Manning Warren J. , Wolf Philip A. , Au Rhoda , Benjamin Emelia J. 
Published: February 2015

Background—
Cross-sectional epidemiological and clinical research suggests that lower cardiac index is associated with abnormal brain aging, including smaller brain volumes, increased white matter hyperintensities, and worse cognitive performances. Lower systemic blood flow may have implications for dementia among older adults.

Methods and Results—

A total of 1039 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, and dementia formed our sample (age, 69±6 years; 53% women). Multivariable-adjusted proportional hazard models adjusting for Framingham Stroke Risk Profile score (age, sex, systolic blood pressure, antihypertensive medication, diabetes mellitus, cigarette smoking, cardiovascular disease history, atrial fibrillation), education, and apolipoprotein E4 status related cardiac magnetic resonance imaging–assessed cardiac index (cardiac output divided by body surface area) to incident all-cause dementia and Alzheimer disease (AD). Over the median 7.7-year follow-up period, 32 participants developed dementia, including 26 cases of AD. Each 1-SD unit decrease in cardiac index increased the relative risk of both dementia (hazard ratio [HR]=1.66; 95% confidence interval [CI], 1.11–2.47;
P
=0.013) and AD (HR=1.65; 95% CI, 1.07–2.54;
P
=0.022). Compared with individuals with normal cardiac index, individuals with clinically low cardiac index had a higher relative risk of dementia (HR=2.07; 95% CI, 1.02–4.19;
P
=0.044). If participants with clinically prevalent cardiovascular disease and atrial fibrillation were excluded (n=184), individuals with clinically low cardiac index had a higher relative risk of both dementia (HR=2.92; 95% CI, 1.34–6.36;
P
=0.007) and AD (HR=2.87; 95% CI, 1.21–6.80;
P
=0.016) compared with individuals with normal cardiac index.

Conclusion—
Lower cardiac index is associated with an increased risk for the development of dementia and AD.
Prehypertension and the Risk of Coronary Heart Disease in Asian and Western Populations: A Meta‐analysis
Authors: Huang Yuli , Cai Xiaoyan , Liu Changhua , Zhu Dingji , Hua Jinghai , Hu Yunzhao , Peng Jian , Xu Dingli 
Published: February 2015

Background

The results of studies on the association between prehypertension (blood pressure 120 to 139/80 to 89 mm Hg) and coronary heart disease (
CHD
) remain controversial. Furthermore, it is unclear whether prehypertension affects the risk of
CHD
in Asian and Western populations differently. This meta‐analysis evaluated the risk of
CHD
associated with prehypertension and its different subgroups.

Methods and Results

The PubMed and Embase databases were searched for prospective cohort studies with data on prehypertension and the risk of
CHD
. Studies were included if they reported multivariate‐adjusted relative risks (
RR
s) with 95%
CI
s of
CHD
from prehypertension. A total of 591 664 participants from 17 prospective cohort studies were included. Prehypertension increased the risk of
CHD
(
RR
1.43, 95%
CI
1.26 to 1.63,
P
<0.001) compared with optimal blood pressure (<120/80 mm Hg). The risk of
CHD
was higher in Western than in Asian participants (Western:
RR
1.70, 95%
CI
1.49 to 1.94; Asian:
RR
1.25, 95%
CI
1.12 to 1.38; ratio of
RR
s 1.36, 95%
CI
1.15 to 1.61). The population‐attributable risk indicated that 8.4% of
CHD
in Asian participants was attributed to prehypertension, whereas this proportion was 24.1% in Western participants.

Conclusions

Prehypertension, even at the low range, is associated with an increased risk of
CHD
. This risk is more pronounced in Western than in Asian populations. These results supported the heterogeneity of target‐organ damage caused by prehypertension and hypertension among different ethnicities and underscore the importance of prevention of
CHD
in Western patients with prehypertension.
Impacts of Indo-Pacific Sea Surface Temperature Anomalies on the Summer Monsoon Circulation and Heavy Precipitation over Northwest India–Pakistan Region during 2010
Authors: Priya P. , Mujumdar Milind , Sabin T. P. , Terray Pascal , Krishnan R. 
Published: February 2015

Abstract
Quite a few studies have documented the evolution of monsoon synoptic systems and midlatitude atmospheric blocking associated with the recent heavy precipitation and floods over northwest Pakistan during 2010. This period also witnessed a very unusual Indo-Pacific sea surface temperature (SST) evolution with a strong La Niña event in the Pacific, substantial Indian Ocean warming, and a negative Indian Ocean dipole event, together with significant enhancement of precipitation over both the equatorial western Pacific Ocean and the eastern Indian Ocean.
Here, the authors perform a suite of high-resolution atmospheric general circulation model experiments to investigate the influence of Indo-Pacific SST anomalies on the South Asian monsoon circulation and heavy precipitation over Pakistan and adjoining northwest India during 2010. The realistic simulation of these rainfall anomalies using observed SSTs motivated the authors to explore the specific influence of Indian Ocean and Pacific SST anomalies through additional simulation experiments. The authors find that, in addition to strengthening of the Pacific Walker circulation, the anomalous intensification of east–west circulation over the Indian Ocean in 2010 was a key element in contributing to precipitation enhancement over the northwest India–Pakistan region. It is found that the subsiding branch of the east–west circulation over the Indian Ocean induced anomalous subsidence over the western tropical Indian Ocean and played a key role in inducing northward transport of moisture and promoting generation of strong upward motion and heavy precipitation events over the northwest India–Pakistan region.
The prevalence and correlates of chronic pain and suicidality in a nationally representative sample
Authors: Campbell Gabrielle , Darke Shane , Bruno Raimondo , Degenhardt Louisa 
Published: February 2015

Background: Research suggests that people suffering from chronic pain have elevated rates of suicidality. With an ageing population, more research is essential to gain a better understanding of this association. Aims: To document the prevalence and correlates of chronic pain and suicide, and estimate the contribution of chronic pain to suicidality. Method: Data from the 2007 Australian National Survey of Mental Health and Wellbeing, a nationally representative household survey on 8841 people, aged 16–85 years, was analysed. Results: The odds of lifetime and past 12-month suicidality were two to three times greater in people with chronic pain. Sixty-five percent of people who attempted suicide in the past 12 months had a history of chronic pain. Chronic pain was independently associated with lifetime suicidality after controlling for demographic, mental health and substance use disorders. Conclusions: Health care professionals need to be aware of the risk of suicidality in patients with chronic pain, even in the absence of mental health problems.
Suicide-related Internet use: A review
Authors: Mok Katherine , Jorm Anthony F , Pirkis Jane 
Published: February 2015

Objective: To systematically review research on how people use the Internet for suicide-related reasons and its influence on users. This review summarises the main findings and conclusions of existing work, the nature of studies that have been conducted, their strengths and limitations, and directions for future research. Method: An online search was conducted through PsycINFO, PubMed, Ovid MEDLINE and CINAHL databases for papers published between 1991 and 2014. Papers were included if they examined how the Internet was used for suicide-related reasons, the influence of suicide-related Internet use, and if they presented primary data, including case studies of Internet-related suicide attempts and completions. Results: Findings of significant relationships between suicide-related search trends and rates of suicide suggest that search trends may be useful in monitoring suicide risk in a population. Studies that examine online communications between people who are suicidal can further our understanding of individuals’ suicidal experiences. While engaging in suicide-related Internet use was associated with higher levels of suicidal ideation, evidence of its influence on suicidal ideation over time was mixed. There is a lack of studies directly recruiting suicidal Internet users. Only case studies examined the influence of suicide-related Internet use on suicidal behaviours, while no studies assessed the influence of pro-suicide or suicide prevention websites. Online professional services can be useful to suicide prevention and intervention efforts, but require more work in order to demonstrate their efficacy. Conclusions: Research has shown that individuals use the Internet to search for suicide-related information and to discuss suicide-related problems with one another. However, the causal link between suicide-related Internet use and suicidal thoughts and behaviours is still unclear. More research is needed, particularly involving direct contact with Internet users, in order to understand the impact of both informal and professionally moderated suicide-related Internet use.
Chronic disease health risk behaviours amongst people with a mental illness
Authors: Bartlem Kate M , Bowman Jennifer A , Bailey Jacqueline M , Freund Megan , Wye Paula M , Lecathelinais Christophe , McElwaine Kathleen M , Campbell Elizabeth M , Gillham Karen E , Wiggers John H 
Published: February 2015

Objective: Amongst people with a mental illness, modifiable health risk behaviours contribute substantially to increased chronic disease morbidity and mortality. This study examined the prevalence of and interest in changing such behaviours amongst community mental health service clients in Australia. Method: A telephone interview was undertaken with Australian community mental health service clients. Participants reported engagement in four health risk behaviours: tobacco smoking, fruit and vegetable consumption, alcohol consumption, and physical activity. Participants were classified as at risk based upon Australian national guidelines. At-risk participants were asked whether they were considering improving their health risk behaviour within the next month. The association between psychiatric diagnosis and risk, and interest in improving health risk behaviours was examined. Results: Risk prevalence was highest for inadequate vegetable consumption (78.3%), followed by inadequate fruit consumption (60%), smoking (50.7%), physical inactivity (46.8%), short-term alcohol risk (40.3%) and chronic alcohol risk (35.3%). A majority of at-risk participants were considering improving their health risk behaviour for smoking, physical inactivity and inadequate fruit and vegetable consumption (65.1%, 71.1%, and 53.3%, respectively). After adjusting for demographic factors, no diagnostic categories were associated with risk for any behaviour. Those with a diagnosis of depression were more likely to be interested in quitting smoking and increasing physical activity. Conclusions: Regardless of diagnosis, a high prevalence of chronic disease health risk behaviours was identified, with many participants expressing an interest in improving these behaviours. Such findings reinforce recommendations that preventive care addressing the chronic disease risks of clients be provided routinely by mental health clinicians. Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000693729. URL: www.anzctr.org.au/
Screening for sensory impairment in older adults: Training and practice of occupational therapists in Quebec
Authors: Wittich Walter , Barstow Elizabeth A. , Jarry Jonathan , Thomas Aliki 
Published: February 2015

Background. The goal of occupational therapy education is to train generalists who can refine their knowledge after graduation according to the requirements of the professional environment. However, it is currently unclear to what extent sensory screening should be included in the educational curricula. Purpose. The purpose of this study was to examine the sensory screening education for and practice by occupational therapists working with older adults. Method. A cross-sectional survey was used to collect data from members of the Quebec Order of Occupational Therapists. Descriptive statistics were used in the analysis. Findings. Data from 102 respondents indicated that training on sensory impairment–related topics was minimal and in stark contrast to the proportion who reported serving clients with a visual (92%), hearing (84%), or combined impairment (53%). Implications. Occupational therapy considers numerous aspects of physical, cognitive, and emotional well-being. The question remains as to what extent vision and hearing health should take their place among these priorities.