bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking Tumor Mutations to Drug Responses via a Quantitative Chemical–Genetic Interaction Map
Authors: Martins Maria M. , Zhou Alicia Y. , Corella Alexandra , Horiuchi Dai , Yau Christina , Rakhshandehroo Taha , Gordan John D. , Levin Rebecca S. , Johnson Jeff , Jascur John , Shales Mike , Sorrentino Antonio , Cheah Jaime , Clemons Paul A. , Shamji Alykhan F. , Schreiber Stuart L. , Krogan Nevan J. , Shokat Kevan M. , McCormick Frank , Goga Andrei , Bandyopadhyay Sourav 
Published: December 2014

Abstract
There is an urgent need in oncology to link molecular aberrations in tumors with therapeutics that can be administered in a personalized fashion. One approach identifies synthetic–lethal genetic interactions or dependencies that cancer cells acquire in the presence of specific mutations. Using engineered isogenic cells, we generated a systematic and quantitative chemical–genetic interaction map that charts the influence of 51 aberrant cancer genes on 90 drug responses. The dataset strongly predicts drug responses found in cancer cell line collections, indicating that isogenic cells can model complex cellular contexts. Applying this dataset to triple-negative breast cancer, we report clinically actionable interactions with the MYC oncogene, including resistance to AKT–PI3K pathway inhibitors and an unexpected sensitivity to dasatinib through LYN inhibition in a synthetic lethal manner, providing new drug and biomarker pairs for clinical investigation. This scalable approach enables the prediction of drug responses from patient data and can accelerate the development of new genotype-directed therapies.
Significance: Determining how the plethora of genomic abnormalities that exist within a given tumor cell affects drug responses remains a major challenge in oncology. Here, we develop a new mapping approach to connect cancer genotypes to drug responses using engineered isogenic cell lines and demonstrate how the resulting dataset can guide clinical interrogation. Cancer Discov; 5(2); 154–67. ©2014 AACR.
This article is highlighted in the In This Issue feature, p. 97
Primary Prevention Implantable Cardioverter-Defibrillators in Older Racial and Ethnic Minority Patients
Authors: Pokorney Sean D. , Hellkamp Anne S. , Yancy Clyde W. , Curtis Lesley H. , Hammill Stephen C. , Peterson Eric D. , Masoudi Frederick A. , Bhatt Deepak L. , Al-Khalidi Hussein R. , Heidenreich Paul A. , Anstrom Kevin J. , Fonarow Gregg C. , Al-Khatib Sana M. 
Published: December 2014

Background—
Racial and ethnic minorities are under-represented in clinical trials of primary prevention implantable cardioverter-defibrillators (ICDs). This analysis investigates the association between primary prevention ICDs and mortality among Medicare, racial/ethnic minority patients.

Methods and Results—

Data from Get With The Guidelines-Heart Failure Registry and National Cardiovascular Data Registry’s ICD Registry were used to perform an adjusted comparative effectiveness analysis of primary prevention ICDs in Medicare, racial/ethnic minority patients (nonwhite race or Hispanic ethnicity). Mortality data were obtained from the Medicare denominator file. The relationship of ICD with survival was compared between minority and white non-Hispanic patients. Our analysis included 852 minority patients, 426 ICD and 426 matched non-ICD patients, and 2070 white non-Hispanic patients (1035 ICD and 1035 matched non-ICD patients). Median follow-up was 3.1 years. Median age was 73 years, and median ejection fraction was 23%. Adjusted 3-year mortality rates for minority ICD and non-ICD patients were 44.9% (95% confidence interval [CI], 44.2%–45.7%) and 54.3% (95% CI, 53.4%–55.1%), respectively (adjusted hazard ratio, 0.79; 95% CI, 0.63–0.98;
P
=0.034). White non-Hispanic patients receiving an ICD had lower adjusted 3-year mortality rates of 47.8% (95% CI, 47.3%–48.3%) compared with 57.3% (95% CI, 56.8%–57.9%) for those with no ICD (adjusted hazard ratio, 0.75; 95% CI, 0.67%–0.83%;
P
<0.0001). There was no significant interaction between race/ethnicity and lower mortality risk with ICD (
P
=0.70).

Conclusions—
Primary prevention ICDs are associated with lower mortality in nonwhite and Hispanic patients, similar to that seen in white, non-Hispanic patients. These data support a similar approach to ICD patient selection, regardless of race or ethnicity.
Predicting Risk of Endovascular Device Infection in Patients With
Staphylococcus aureus
Bacteremia (PREDICT-SAB)
Authors: Sohail M. Rizwan , Palraj Bharath Raj , Khalid Sana , Uslan Daniel Z. , Al-Saffar Farah , Friedman Paul A. , Hayes David L. , Lohse Christine M. , Wilson Walter R. , Steckelberg James M. , Baddour Larry M. 
Published: December 2014

Background—

Prompt recognition of underlying cardiovascular implantable electronic device (CIED) infection in patients presenting with
Staphylococcus aureus
bacteremia (SAB) is critical for optimal management of these cases. The goal of this study was to identify clinical predictors of CIED infection in patients presenting with SAB and no signs of pocket infection.

Methods and Results—

All cases of SAB in CIED recipients at Mayo Clinic from 2001 to 2011 were retrospectively reviewed. We identified 131 patients with CIED who presented with SAB and had no clinical signs of device pocket infection. Forty-five (34%) of these patients had underlying CIED infection based on clinical or echocardiographic criteria. The presence of a permanent pacemaker rather than an implantable cardioverter-defibrillator (odds ratio, 3.90; 95% confidence interval, 1.65–9.23;
P
=0.002), >1 device-related procedure (odds ratio, 3.30; 95% confidence interval, 1.23–8.86;
P
=0.018), and duration of SAB ≥4 days (odds ratio, 5.54; 95% confidence interval, 3.32–13.23;
P
<0.001) were independently associated with an increased risk of CIED infection in a multivariable model. The area under the receiver operating characteristics curve for the multivariable model was 0.79, indicating a good discriminatory capacity to distinguish SAB patients with and without CIED infection.

Conclusions—
Among patients presenting with SAB and no signs of pocket infection, the risk of underlying CIED infection can be calculated based on the type of device, number of device-related procedures, and duration of SAB. We propose that patients without any of these high-risk features have a low risk of underlying CIED infection and may be monitored closely without immediate device extraction. Prospective studies are needed to validate this risk prediction model.
Use and Outcomes Associated With Bridging During Anticoagulation Interruptions in Patients With Atrial Fibrillation
Authors: Steinberg Benjamin A. , Peterson Eric D. , Kim Sunghee , Thomas Laine , Gersh Bernard J. , Fonarow Gregg C. , Kowey Peter R. , Mahaffey Kenneth W. , Sherwood Matthew W. , Chang Paul , Piccini Jonathan P. , Ansell Jack 
Published: December 2014

Background—
Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown.

Methods and Results—

The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%;
P
=0.0003) and mechanical valve replacements (9.6% versus 2.4%;
P
<0.0001); however, there was no difference in CHA
2
DS
2
-VASc scores (scores ≥2 in 94% versus 95%;
P
=0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84;
P
<0.0001). The incidence of myocardial infarction, stroke or systemic embolism, major bleeding, hospitalization, or death within 30 days was also significantly higher in patients receiving bridging (13% versus 6.3%; adjusted odds ratio, 1.94;
P
=0.0001).

Conclusions—
Bridging anticoagulation is used in one quarter of anticoagulation interruptions and is associated with higher risk for bleeding and adverse events. These data do not support the use of routine bridging, and additional data are needed to identify best practices concerning anticoagulation interruptions.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01165710.
A Conceptual Tool for Climate Change Risk Assessment
Authors: Higgins Paul A. T. , Steinbuck Jonah V. 
Published: December 2014

Abstract
This study develops a new conceptual tool to explore the potential societal consequences of climate change. The conceptual tool delineates three quasi-independent factors that contribute to the societal consequences of climate change: how climate changes; the sensitivity of physical systems, biological resources, and social institutions to climate change; and the degree of human dependence on those systems, resources, and institutions. This conceptual tool, as currently developed, is not predictive, but it enables the exploration of the dependence of climate change risks on key contributing factors. In exploring a range of plausible behaviors for these factors and methods for their synthesis, the authors show that plausible assumptions lead to a wide range in potential societal consequences of climate change. This illustrates that the societal consequences of climate change are currently difficult to constrain and that high-consequence climate change outcomes are not necessarily low probability, as suggested by leading economic analyses. With careful implementation, this new conceptual tool has potential to increase public understanding of climate change risks, to support risk management decision making, or to facilitate communication of climate risks across disciplinary boundaries.
The role and impact of student leadership on participants in a healthy eating and physical activity programme
Authors: Gutuskey Lila , McCaughtry Nate , Shen Bo , Centeio Erin , Garn Alex 
Published: December 2014

Objective: In the USA there are rising rates of obesity among children, at least in part due to unhealthy eating and physical inactivity. Implementing school-based health interventions with elementary school children focused on youth empowerment could lead to improved health environments and behaviours. The purpose of the present study was to examine elementary students’ perceptions of participating in a student-led school health improvement team. Empowerment theory guided the research, specifically the concept of including participants in programming to identify possible individual-level outcomes. Design: Qualitative research. Setting: One US elementary school formed a student-led school health improvement team, focusing on healthy eating and physical activity, comprising nine students and two adult co-advisers. Methods: Data collection included 19 individual interviews with students and advisers and four non-participant observations of team meetings and reform initiatives. To ensure the perceptions of the research participants’ guided data analysis, analytic induction was undertaken using grounded theory. Results: Students and advisers shared similar perceptions that the student-led health reform process had a significant impact on several areas of students’ life skills and health behaviours. Specifically, they identified improved leadership skills (assuming responsibility, self-confidence in public speaking and pride in becoming healthy role models) and health behaviours (dietary intake and physical activity) as outcomes of their emerging identities as health reform leaders. Conclusion: This study documented previously identified psychological empowerment outcomes, such as perceived control and proactive health behaviours, and additional positive outcomes, such as peer modelling. The findings suggest that team membership may positively impact on young people, which could support the inclusion of students as leaders in future interventions.
Effect of n‐Butyl‐2‐cyanoacrylate on the Tensile Strength and Pressure Resistance of Tracheal Anastomoses Ex Vivo
Authors: Bicer Yusuf Ozgur , Koybasi Serap , Kazaz Hasan , Seyhan Sinan 
Published: December 2014

ObjectivesTo investigate the effects of n‐butyl‐2‐cyanoacrylate on tracheal anastomoses in terms of increased tension and intraluminal pressure ex vivo.Study DesignEx vivo experimental study.SettingTertiary referral center (Department of Otolaryngology).Subjects and MethodsThirty sheep tracheas were used. Four cartilage rings were resected from the tracheas that were 20 cm in length. End‐to‐end anastomoses were performed by using Vicryl only (group 1), Vicryl and n‐butyl‐2‐cyanoacrylate (group 2), and n‐butyl‐2‐cyanoacrylate only (group 3). The amount of force to break off the anastomosis and the amount of intraluminal pressure to arouse air leakage through the anastomosis were measured.ResultsThe mean force required to break off was 171.9 ± 29.7 N in group 1, 164.8 ± 26 N in group 2, and 13.52 ± 2 N in group 3. The mean force required to break off in group 3 was significantly lower than those in groups 1 and 2 (P =. 008 and P =. 008, respectively). The mean pressure required to cause air leakage was 49.6 ± 9.1 mm Hg in group 1, 113 ± 14.4 mm Hg in group 2, and 15 ± 4.2 mm Hg in group 3. Group 2 was found to be more resistant to intraluminal pressure than groups 1 and 3 (P =. 008 and P =. 008, respectively).Conclusionn‐Butyl‐2‐cyanoacrylate had no significant effect on tensile strength. However, its application on the suture line provided extra pressure resistance ex vivo. We believe that further studies need to be conducted to investigate its long‐term effects and histological impact on tracheal anastomoses in vivo.
Correlating Regional Aeroallergen Effects on Internet Search Activity
Authors: Willson Thomas J. , Lospinoso Joshua , Weitzel Erik , McMains Kevin 
Published: December 2014

ObjectiveTo investigate the correlation between the change in regional aeroallergen levels and Internet search activity related to allergies.Study DesignA retrospective time series analysis using a graphical analytical approach and statistical modeling was used.SettingTertiary academic hospital setting.Subjects and MethodsThere were no specific enrolled subjects. Data from Google Trends were obtained (google.com/trends) for the following search terms: “allergy,” “allergies,” “pollen,” “runny nose,” “congestion,” and “post nasal drainage.” Daily pollen and mold spore count data were obtained for the same period from throughout Texas. Graphical analysis, correlation, and autoregressive integrated moving average (ARIMA) were employed to assess the relationship between aeroallergens on Google search activity.ResultsA strong positive correlation was observed between observed pollen counts and search activity for the terms “allergies” (r
pollen = 0.798), “allergy” (r
pollen = 0.781), and “pollen” (r
pollen = 0.849). Symptom term searches were weakly correlated with pollen and mold counts. Also, ARIMA modeling supported the relationships indicated by the correlations.ConclusionSearch activities for surrogate terms such as “allergy,” “allergies,” and “pollen” correlate strongly with observed pollen counts but not mold counts. These data demonstrate the usefulness of Google Trends search data in assessing regional disease burdens and offer insight into how the public seeks information about their own illness.
Increased Expression of Toll‐Like Receptors 2 and 4 and Related Cytokines in Persistent Allergic Rhinitis
Authors: Cui Xin‐Yan , Chen Xi , Yu Chen‐Jie , Yang Jun , Lin Zi‐Ping , Yin Min , Cheng Lei 
Published: December 2014

ObjectivesToll‐like receptors (TLRs) are the crucial components of host defenses and supposed to play a role in nasal inflammation such as chronic rhinosinusitis and seasonal allergic rhinitis. This study was performed to investigate the expression patterns of TLRs and related cytokines in persistent allergic rhinitis (PER).Study DesignExperimental study of human nasal tissue.SettingAcademic medical center.Subjects and MethodsNasal biopsy specimens were obtained from 21 patients with PER and 21 controls from December 2012 to September 2013. Messenger RNA (mRNA) expression of TLR1‐9, interleukin (IL)–1, IL‐6, IL‐8, IL‐12, interferon (IFN)–α, and tumor necrosis factor (TNF)–α was determined by quantitative reverse transcription polymerase chain reaction. The cellular localizations as well as protein expression of TLR2 and TLR4 were further detected by immunohistochemistry and Western blotting, respectively.ResultsTLR1‐9 mRNA could be determined in nasal mucosa. Compared with the controls, mRNA expression of only TLR2 and TLR4 was significant higher in patients with PER (P <. 05). In addition, mRNA expression of IL‐6 and IL‐8, but not IL‐1, IL‐12, IFN‐α, and TNF‐α, was upregulated in patients with PER vs control subjects (P <. 05). However, these increased cytokines were not correlated with either TLR2 or TLR4 in patients with PER. Protein expression of TLR2 and TLR4 was consistent with mRNA levels (P <. 05). The cellular distributions of TLR2 and TLR4 were localized in nasal epithelium, subepithelial glands and capillary endothelial cells, and immune cells.ConclusionTLR2 and TLR4 are increased in patients with PER and may be one of the major contributors to the persistence and aggravation of allergic inflammation in PER.
The impact of a toolkit on use of standardised measurement tools in stroke rehabilitation
Authors: Tyson SF , Burton L , McGovern A 
Published: December 2014

Objective: To evaluate the impact of a toolkit of psychometrically robust measurement tools, the Greater Manchester Assessment for Stroke Rehabilitation (G-MASTER) toolkit, on the use of measurement tools during stroke rehabilitation Design: Mixed methods cohort design using non-participant observation of multi-disciplinary team meetings and semi-structured interviews with members of the team over three months before and three months after implementation of the assessment toolkit. Development and implementation of the toolkit are also described. Setting: Ten in-patient stroke services in a large UK city. Subjects: Members of the participating multi-disciplinary stroke teams. Results: Before implementation standardised measures were seldom used in team meetings. After implementation, use of all measurement tools significantly increased (36% to 81% of occasions, P<0.000). Staff were generally positive about the toolkit and felt it enabled more accurate problem identification, effective progress monitoring, timely decision-making, communication and promoted inter-team relationships. Conclusions: A toolkit of standardised measurement tools can be feasibly and acceptably implemented into stroke rehabilitation. It increases the use of measurement tools by the multi-disciplinary team and improves the processes and quality of care.
A mixed-methods qualitative research study to develop a complex intervention for weight loss and anorexia in advanced cancer: The Family Approach to Weight and Eating
Authors: Hopkinson Jane B , Richardson Alison 
Published: December 2014

Background: Worldwide, most people with incurable cancer experience weight loss and anorexia. These symptoms can distress patients and their family caregivers. Interventions that take account of the relationship between patient and family caregiver may improve outcomes for both members of this dyad. Aim: To report an example of process for the development of a complex intervention, the Family Approach to Weight and Eating. Design: A mixed-methods process informed by the Medical Research Council’s guidelines for developing a complex intervention was used to develop a psychosocial intervention for patients with incurable cancer and weight loss or poor appetite and their family caregivers and then to test for its feasibility, acceptability and perceived benefit. Setting: South of England in 2010/2011. Participants: A purposive sample of patient–family caregiver dyads under the care of a specialist community palliative care team. Patient participants had incurable cancer and were cachectic or at risk of cachexia. Results: The patient–family caregiver dyads comprised seven female and nine male patients (age range 41–84 years) and their carers. The emergent form of the Family Approach to Weight and Eating was found to aid family talk about food, feelings and reciprocity, without adverse consequences. Of the dyads, 15 reported benefits of the Family Approach to Weight and Eating. Three patient participants spoke of the approach evoking sadness and three carers of guilt. Conclusion: The Family Approach to Weight and Eating should now be tested in a pilot trial and the effect on emotional health outcomes in patients and their family caregivers evaluated.
Non-medical prescribing in palliative care: A regional survey
Authors: Ziegler Lucy , Bennett Mike , Blenkinsopp Alison , Coppock Sally 
Published: December 2014

Background: The United Kingdom is considered to be the world leader in nurse prescribing, no other country having the same extended non-medical prescribing rights. Arguably, this growth has outpaced research to evaluate the benefits, particularly in areas of clinical practice where patients have complex co-morbid conditions such as palliative care. This is the first study of non-medical prescribing in palliative care in almost a decade. Aim: To explore the current position of nurse prescribing in palliative care and establish the impact on practice of the 2012 legislative changes. Design: An online survey circulated during May and June 2013. Participants: Nurse members ( n = 37) of a regional cancer network palliative care group (61% response rate). Results: While this survey found non-medical prescribers have embraced the 2012 legislative changes and prescribe a wide range of drugs for cancer pain, we also identified scope to improve the transition from qualified to active non-medical prescriber by reducing the time interval between the two. Conclusion: To maximise the economic and clinical benefit of non-medical prescribing, the delay between qualifying as a prescriber and becoming an active prescriber needs to be reduced. Nurses who may be considering training to be a non-medical prescriber may be encouraged by the provision of adequate study leave and support to cover clinical work. Further research should explore the patients’ perspective of non-medical prescribing.