bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Mammalian Safety Studies of EPHARNA (DOPC Nanoliposomal EphA2-Targeted siRNA)
Authors: Wagner Michael J. , Mitra Rahul , McArthur Mark J. , Baze Wallace , Barnhart Kirstin , Wu Sherry Y. , Rodriguez-Aguayo Cristian , Zhang Xinna , Coleman Robert L. , Lopez-Berestein Gabriel , Sood Anil K. 
Published: March 2017

Abstract
To address the need for efficient and biocompatible delivery systems for systemic siRNA delivery, we developed 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine (DOPC) nanoliposomal EphA2-targeted therapeutic (EPHARNA). Here, we performed safety studies of EPHARNA in murine and primate models. Single dosing of EPHARNA was tested at 5 concentrations in mice (N = 15 per group) and groups were sacrificed on days 1, 14, and 28 for evaluation of clinical pathology and organ toxicity. Multiple dosing of EPHARNA was tested in mice and Rhesus macaques twice weekly at two dose levels in each model. Possible effects on hematologic parameters, serum chemistry, coagulation, and organ toxicity were assessed. Following single-dose EPHARNA administration to mice, no gross pathologic or dose-related microscopic findings were observed in either the acute (24 hours) or recovery (14 and 28 days) phases. The no-observed-adverse-effect level (NOAEL) for EPHARNA is considered &gt;225 μg/kg when administered as a single injection intravenously in CD-1 mice. With twice weekly injection, EPHARNA appeared to stimulate a mild to moderate inflammatory response in a dose-related fashion. There appeared to be a mild hemolytic reaction in the female mice. In Rhesus macaques, minimal to moderate infiltration of mononuclear cells was found in some organs including the gastrointestinal tract, heart, and kidney. No differences attributed to EPHARNA were observed. These results demonstrate that EPHARNA is well tolerated at all doses tested. These data, combined with previously published in vivo validation studies, have led to an ongoing first-in-human phase I clinical trial (NCT01591356). Mol Cancer Ther; 16(6); 1114–23. ©2017 AACR.
Loss of BRCA1 in the Cells of Origin of Ovarian Cancer Induces Glycolysis: A Window of Opportunity for Ovarian Cancer Chemoprevention
Authors: Chiyoda Tatsuyuki , Hart Peter C. , Eckert Mark A. , McGregor Stephanie M. , Lastra Ricardo R. , Hamamoto Ryuji , Nakamura Yusuke , Yamada S. Diane , Olopade Olufunmilayo I. , Lengyel Ernst , Romero Iris L. 
Published: March 2017

Abstract
Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of developing epithelial ovarian cancer. However, beyond the role of BRCA1 in DNA repair, little is known about other mechanisms by which BRCA1 impairment promotes carcinogenesis. Given that altered metabolism is now recognized as important in the initiation and progression of cancer, we asked whether the loss of BRCA1 changes metabolism in the cells of origin of ovarian cancer. The findings show that silencing BRCA1 in ovarian surface epithelial and fallopian tube cells increased glycolysis. Furthermore, when these cells were transfected with plasmids carrying deleterious BRCA1 mutations (5382insC or the P1749R), there was an increase in hexokinase-2 (HK2), a key glycolytic enzyme. This effect was mediated by MYC and the STAT3. To target the metabolic phenotype induced by loss of BRCA1, a drug-repurposing approach was used and aspirin was identified as an agent that counteracted the increase in HK2 and the increase in glycolysis induced by BRCA1 impairment. Evidence from this study indicates that the tumor suppressor functions of BRCA1 extend beyond DNA repair to include metabolic endpoints and identifies aspirin as an ovarian cancer chemopreventive agent capable of reversing the metabolic derangements caused by loss of BRCA1. Cancer Prev Res; 10(4); 255–66. ©2017 AACR.
Incident Coronary Heart Disease After Preeclampsia: Role of Reduced Fetal Growth, Preterm Delivery, and Parity
Authors: Riise Hilde Kristin Refvik , Sulo Gerhard , Tell Grethe S. , Igland Jannicke , Nygård Ottar , Vollset Stein Emil , Iversen Ann‐Charlotte , Austgulen Rigmor , Daltveit Anne Kjersti 
Published: March 2017

Background
Preeclampsia is a severe pregnancy disorder often complicated by reduced fetal growth or preterm delivery and is associated with long‐term maternal morbidity and mortality. We aimed to assess the association between preeclampsia phenotypes and risk of subsequent coronary heart disease and maternal cardiovascular mortality.

Methods and Results

Women aged 16 to 49 years who gave birth during 1980–2002 and registered in the Medical Birth Registry of Norway were followed prospectively (1–29 years) for an incident major coronary event and mortality through linkage with the Cardiovascular Disease in Norway 1994–2009 (
CVDNOR
) project and the Norwegian Cause of Death Registry. Preeclampsia was subdivided based on the presence of a child born small for gestational age or preterm delivery. Among 506 350 women with 1 to 5 singleton births, there were 1275 (0.3%) occurrences of major coronary event, 468 (0.1%) cardiovascular deaths, and 5411 (1.1%) deaths overall. Compared with women without preeclampsia, the hazard ratio (95% CI) for major coronary event was 2.1 (1.73–2.65) after preeclampsia alone, 3.3 (2.37–4.57) after preeclampsia in combination with small for gestational age, and 5.4 (3.74–7.74) after preeclampsia in combination with preterm delivery. Analyses distinguishing women with 1 (n=61 352) or >1 (n=281 069) lifetime pregnancy and analyses with cardiovascular mortality as outcome followed the same pattern.

Conclusions
The occurrence of major coronary events was increased among women with preeclampsia and highest for preeclampsia combined with a child born small for gestational age and/or preterm delivery.
Absent Filling of Ipsilateral Superficial Middle Cerebral Vein Is Associated With Poor Outcome After Reperfusion Therapy
Authors: Zhang Sheng , Lai Yangxiao , Ding Xinfa , Parsons Mark , Zhang John H. , Lou Min 
Published: March 2017

Background and Purpose—
Our aim was to study the effect of drainage of cortical veins, including the superficial middle cerebral vein (SMCV), vein of Trolard, and vein of Labbé on neurological outcomes after reperfusion therapy.

Methods—
Consecutive ischemic stroke patients who underwent pretreatment computed tomographic perfusion and 24-hour computed tomographic perfusion or magnetic resonance perfusion after intravenous thrombolysis were included. We defined “absent filling of ipsilateral cortical vein” (eg, SMCV−) as no contrast filling of the vein across the whole venous phase on 4-dimensional computed tomographic angiography in the ischemic hemisphere.

Results—

Of 228 patients, SMCV−, vein of Trolard− and vein of Labbé− were observed in 50 (21.9%), 27 (11.8%), and 32 (14.0%) patients, respectively. Only SMCV− independently predicted poor outcome (3-month modified Rankin Scale score of >2; odds ratio, 2.710;
P
=0.040). No difference was found in reperfusion rate after treatment between patients with and without SMCV− (
P
>0.05). In patients achieving major reperfusion (≥80%), there was no difference in 24-hour infarct volume, or rate of poor outcome between patients with and without SMCV− (
P
>0.05). However, in those without major reperfusion, patients with SMCV− had larger 24-hour infarct volume (
P
=0.011), higher rate of poor outcome (
P
=0.012), and death (
P
=0.032) compared with those with SMCV filling. SMCV− was significantly associated with brain edema at 24 hours (
P
=0.037), which, in turn, was associated with poor 3-month outcome (
P
=0.002).

Conclusions—
Lack of SMCV filling contributed to poor outcome after thrombolysis, especially when reperfusion was not achieved. The main deleterious effect of poor venous filling appears related to the development of brain edema.
RECAST (Remote Ischemic Conditioning After Stroke Trial)
Authors: England Timothy J. , Hedstrom Amanda , O’Sullivan Saoirse , Donnelly Richard , Barrett David A. , Sarmad Sarir , Sprigg Nikola , Bath Philip M. 
Published: March 2017

Background and Purpose—
Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke.

Methods—
We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures.

Results—

Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75–9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group (
P
=0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5–5) versus 3 (interquartile range, 2–9.5;
P
=0.04); RIC augmented plasma HSP27 (heat shock protein 27;
P
<0.05, repeated 2-way ANOVA) and phosphorylated HSP27 (
P
<0.001) but not plasma S100-β, matrix metalloproteinase-9, endocannabinoids, or arterial compliance.

Conclusions—
RIC after acute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted.

Clinical Trial Registration—

URL:
http://www.isrctn.com
. Unique identifier: ISRCTN86672015.
Impacts of Boreal Winter Monsoon Cold Surges and the Interaction with MJO on Southeast Asia Rainfall
Authors: Lim See Yee , Marzin Charline , Xavier Prince , Chang Chih-Pei , Timbal Bertrand 
Published: March 2017

Abstract
TRMM rainfall data from 1998–2012 are used to study the impacts and interactions of cold surges (CSs) and the Madden–Julian oscillation (MJO) on rainfall over Southeast Asia during the boreal winter season from November to February. CSs are identified using a new large-scale index. The frequencies of occurrences of these two large-scale events are comparable (about 20% of the days each), but the spatial pattern of impacts show differences resulting from the interactions of the general flow with the complex orography of the region. The largest impact of CSs occurs in and around the southern South China Sea as a result of increased low-level convergence on the windward side of the terrain and increased shear vorticity off Borneo that enhances the Borneo vortex. The largest impact of the MJO is in the eastern equatorial Indian Ocean, sheltered from CSs by Sumatra. In general CSs are significantly more likely to trigger extreme rainfall. When both systems are present, the rainfall pattern is mainly controlled by the CSs. However, the MJO makes the environment more favorable for convection by moistening the atmosphere and facilitating conditional instability, resulting in a significant increased rainfall response compared to CSs alone. In addition to the interactions of the two systems in convection, this study confirms a previously identified mechanism in which the MJO may reduce CS frequency through opposing dynamic structures.
Morbidity and Survival in Elderly Patients Undergoing Free Flap Reconstruction: A Retrospective Cohort Study
Authors: Mitchell Candace A. , Goldman Richard A. , Curry Joseph M. , Cognetti David M. , Krein Howard , Heffelfinger Ryan , Luginbuhl Adam 
Published: March 2017

ObjectiveTo review a single institution’s outcomes of free flap reconstruction of the head and neck in patients aged ≥80 years as compared with those <80 years.Study DesignRetrospective cohort study.SettingTertiary academic hospital.Subjects and MethodsPatients aged ≥ 80 years who underwent free flap reconstruction of the head and neck between 2007 and 2013 were identified and matched by type of reconstruction with a cohort of younger patients. Outcome measures included flap success, length of stay, discharge disposition, complications, and 2‐year mortality. Associations between complications and comorbidities were also evaluated.ResultsSixty‐six patients aged ≥80 years were identified, and a paired sample <80 years old was selected. There were 3 flap failures per group and 1 perioperative mortality in the elderly group. There was no significant difference in length of stay or major complications between groups. Significantly more elderly patients were discharged to a nursing facility. There was no significant difference in mortality rates at 2 years postoperatively. No associations were seen between level of comorbidity and complications among the elderly group.ConclusionFree flap reconstruction of the head and neck remains a viable option in patients of advanced age. Similar outcomes in terms of flap success, complications, and length of hospitalization can be achieved as compared with younger patients undergoing similar reconstructions. The role of comorbid disease as a predictor of complications remains unclear. There is no significant difference in 2‐year mortality for elderly free flap patients versus younger controls.
Coping strategies and adjustment to multiple sclerosis among recently diagnosed patients: the mediating role of sense of coherence
Authors: Calandri Emanuela , Graziano Federica , Borghi Martina , Bonino Silvia 
Published: March 2017

Objective: To examine the relationship between coping strategies (problem solving, emotional release, and avoidance) and adjustment (health-related quality of life, depression, and affective well-being) in a group of recently diagnosed multiple sclerosis patients (up to three years since diagnosis), and to explore the mediating role of sense of coherence between coping strategies and adjustment. Design: Cross-sectional. Setting: Multiple Sclerosis Clinic Centre. Subjects: A total of 102 patients (61.8% women; age (years): M = 35.8, SD = 11.9; 95% with a relapsing–remitting form of multiple sclerosis; Expanded Disability Status Scale score, between 1 and 4). Interventions: Not applicable. Main measures: Coping with multiple sclerosis (problem solving, emotional release, and avoidance), sense of coherence, health-related quality of life (SF-12), depression (CES-D), and affective well-being (PANAS). Results: Problem solving was linked to higher mental health ( β = 0.28) and higher affective well-being ( β = 0.36), emotional release was related to lower depression ( β = −0.22); avoidance was associated to higher mental health ( β = 0.25), higher affective well-being ( β = 0.24), and lower depression ( β = −0.29 ) (all betas were significant at p < 0.05). Sense of coherence mediated the relationship between emotional release and depression (Sobel z-value = −2.00; p < 0.05) and the relationship between avoidance and all the indicators of adjustment (mental health: Sobel z-value = 1.97; depression: Sobel z-value = −2.02; affective well-being: Sobel z-value= 2.05; p < 0.05). Conclusions: Emotional and avoidant coping strategies seem to be adaptive among recently diagnosed multiple sclerosis patients. A mediating role between coping strategies and adjustment is played by sense of coherence.
Effects of scalp block with bupivacaine versus levobupivacaine on haemodynamic response to head pinning and comparative efficacies in postoperative analgesia: A randomized controlled trial
Authors: Can Banu O. , Bilgin Hülya 
Published: March 2017

Objective This study was performed to determine the effects of scalp blocks with bupivacaine versus levobupivacaine on the haemodynamic response during craniotomy and the efficacies and analgesic requirements of these drugs postoperatively. Methods This randomized, prospective, placebo-controlled, double-blind study included 90 patients (age, 18–85 years; American Society of Anesthesiologists physical status, I or II). The patients were randomly divided into three groups: those who received 20 mL of 0.5% bupivacaine (Group B, n = 30), 20 mL of 0.5% levobupivacaine (Group L, n = 30), or saline as a placebo (Group C, n = 30). Scalp blocks were performed 5 min before head pinning. The primary outcome was the mean arterial pressure (MAP), and the secondary outcomes were the heart rate (HR), visual analogue scale (VAS) scores, and additional intraoperative and postoperative drug use. Postoperative pain was evaluated using a 10-cm VAS. Results During head pinning and incision, the MAP and HR were significantly higher in Group C. The additional drug requirement for intraoperative hypertension and tachycardia was significantly higher in Group C. There were no significant differences in MAP, HR, or VAS scores between Groups B and L. Conclusion Both bupivacaine and levobupivacaine can be effectively and safely used for scalp blocks to control haemodynamic responses and postoperative pain.
Barriers to Engagement in a Workplace Weight Management Program: A Qualitative Study
Authors: Clancy Shayna M. , Stroo Marissa , Schoenfisch Ashley , Dabrera Thushani , Østbye Truls 
Published: March 2017

Purpose: To investigate (1) why some participants in a workplace weight management program were more engaged in the program, (2) specific barriers and facilitators for engagement and weight loss, and (3) suggest how workplaces may better engage employees in these programs to improve their effectiveness. Design: Qualitative study (8 focus groups). Setting: A large academic university and medical system. Participants: Twenty-six (5%) of the 550 employees who participated in a weight management program as part of the Steps to Health study. Measures: A trained moderator guided the audio-recorded focus groups. Analysis: Transcripts were analyzed using the directed content analysis approach. Results: Participants faced numerous barriers to engagement in workplace weight management programs, both within and outside the workplace. Participants viewed the coaches positively and reported that the coaches had a strong influence on their engagement in the program. Participants suggested increased frequency and variety of contact by coaches, on-site group exercise classes, and tailored educational materials. Conclusion: Workplace weight management programs may be improved by being more flexible around participants’ schedules and changing needs, by increasing access to affordable, convenient exercise facilities, and by implementing institutional changes that encourage healthy eating and physical activity during the workday. Employers should measure program engagement and solicit participant feedback to ensure that the programs are appropriate and delivered in an optimal manner.
Methamphetamine and psychiatry: A story of the colourless substance of abuse
Authors: Suetani Shuichi , Reddan Jill , Anderson Carrick 
Published: March 2017

Objective: The current paper aims to provide an overview of methamphetamine in its historical context, integrated with a current understanding derived from animal studies and clinical experience. Conclusion: Despite over a century of clinical experience, methamphetamine remains a troublesome substance. There remains an urgent need at multiple levels from various sectors to combat this ongoing problem, and psychiatry has an essential role in this endeavour.
Comparison of real-time PCR with fungal culture for the diagnosis of Microsporum canis dermatophytosis in shelter cats: a field study
Authors: Jacobson Linda S , McIntyre Lauren , Mykusz Jenny 
Published: March 2017

Objectives Fungal culture requires at least 14 days for a final result, compared with 1–3 days for PCR. The study compared a commercial real-time dermatophyte PCR panel with fungal culture in cats in a shelter setting for: (1) diagnosis of Microsporum canis infection; and (2) determination of mycological cure. Methods This was a cross-sectional, observational study of cats with suspicious skin lesions or suspected exposure to dermatophytosis. Hair samples were collected for fungal culture and PCR prior to treatment and at weekly intervals until two negative culture results were obtained. Results One hundred and thirty-two cats were included, of which 28 (21.2%) were culture positive and 104 (78.8%) culture-negative for M canis. PCR correctly identified all culture-positive cats and 92/104 culture negative cats; there were 12 false-positive PCR results. The sensitivity and specificity of PCR were 100% (95% confidence interval [CI] 87.7–100) and 88.5% (95% CI 80.7–93.9), respectively. Data from 17 cats were available for assessment of mycological cure. At the time of the first and second negative fungal cultures, 14/17 (82.4%) and 11/17 (64.7%) tested PCR positive, respectively. Conclusions and relevance PCR showed high sensitivity and specificity for diagnosis of M canis dermatophytosis compared with fungal culture, but was unreliable for identifying mycological cure. False-positive results were relatively common. There were no false-negative PCR results and a negative PCR test was a reliable finding in this study. The ability to rapidly diagnose or rule out dermatophytosis could be a valuable tool to increase life-saving capacity in animal shelters.
Research to Advance Undergraduate HRD Education: “Please Sir, I Want Some More”
Authors: Nimon Kim , Roberts Paul B. 
Published: March 2017

The Problem There is a dearth of research focusing on undergraduate human resource development (HRD) education. As a result, programs offering undergraduate degrees in HRD or degrees related to HRD may be making program decisions without the benefit of empirical research. Alternatively, programs may be conducting their own action research projects where the results may not be generalizable to other institutions. The Solution The present issue takes one small step forward related to filling the gap in undergraduate HRD education. The empirical articles in this issue are reviewed and synthesized to identify five opportunities for research that can inform education and practice. The Stakeholders The primary audience includes HRD scholars and scholar-practitioners, including master and doctorate students, interested in conducting research relevant to undergraduate HRD education. The secondary audience includes leaders of the field, including board members of the Academy of Human Resource Development (AHRD), the AHRD Foundation, the University Council for Workforce and Human Resource Education (UCWHRE), program administrators, department chairs, associate deans, and deans.
Ssb1 and Ssb2 cooperate to regulate mouse hematopoietic stem and progenitor cells by resolving replicative stress
Authors: Shi Wei , Vu Therese , Boucher Didier , Biernacka Anna , Nde Jules , Pandita Raj K. , Straube Jasmin , Boyle Glen M. , Al-Ejeh Fares , Nag Purba , Jeffery Jessie , Harris Janelle L. , Bain Amanda L. , Grzelak Marta , Skrzypczak Magdalena , Mitra Abhishek , Dojer Norbert , Crosetto Nicola , Cloonan Nicole , Becherel Olivier J. , Finnie John , Skaar Jeffrey R. , Walkley Carl R. , Pandita Tej K. , Rowicka Maga , Ginalski Krzysztof , Lane Steven W. , Khanna Kum Kum 
Published: March 2017

Key Points
Combined loss of Ssb1/Ssb2 induces rapid lethality due to replication stress–associated loss of hematopoietic stem and progenitor cells. Functionally, loss of Ssb1/Ssb2 activates p53 and IFN pathways, causing enforced cell cycling in quiescent HSPCs and apoptotic cell loss.