bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Pathways: Fatty Acid Synthase
Authors: Jones Suzanne F. , Infante Jeffrey R. 
Published: October 2015

Abstract
Therapies that target tumor metabolism represent a new horizon in anticancer therapies. In particular, cancer cells are dependent on the generation of lipids, which are essential for cell membrane synthesis, modification of proteins, and localization of many oncogenic signal transduction enzymes. Because fatty acids are the building blocks of these important lipids, fatty acid synthase (FASN) emerges as a unique oncologic target. FASN inhibitors are being studied preclinically and beginning to transition to first-in-human trials. Early generation FASN inhibitors have been studied preclinically but were limited by their pharmacologic properties and side-effect profiles. A new generation of molecules, including GSK2194069, JNJ-54302833, IPI-9119, and TVB-2640, are in development, but only TVB-2640 has moved into the clinic. FASN inhibition, either alone or in combination, holds promise as a novel therapeutic approach for patients with cancer. Clin Cancer Res; 21(24); 5434–8. ©2015 AACR.
Molecular Pathways: Targeting IDO1 and Other Tryptophan Dioxygenases for Cancer Immunotherapy
Authors: Zhai Lijie , Spranger Stefani , Binder David C. , Gritsina Galina , Lauing Kristen L. , Giles Francis J. , Wainwright Derek A. 
Published: October 2015

Abstract
Indoleamine 2, 3-dioxygenase 1 (IDO1), IDO2, and tryptophan 2, 3-dioxygenase (TDO) comprise a family of enzymes that catalyze the first- and rate-limiting step associated with the catabolic conversion of tryptophan (Trp) into kynurenine (Kyn). Through subsequent enzymatic and spontaneous reactions, Kyn is further converted into the energetic substrates, NAD+ and ATP, to fuel cellular metabolic functions. Coincidently, the depletion of Trp and accumulation of Kyn has been demonstrated to induce effector T-cell apoptosis/dysfunction and immunosuppressive regulatory T-cell induction, respectively. Similar to other immune checkpoints, IDO1 and TDO are suggested to be important targets for immunotherapeutic intervention. This is represented by the recent growth of efforts to inhibit the Trp-to-Kyn pathway as a means to control immunosuppression. Inhibitors currently in clinical trials, INCB024360, GDC-0919, indoximod, and an IDO1 peptide-based vaccine, are being evaluated for their efficacy against a wide range of cancers including melanoma, glioblastoma, non–small cell lung, pancreatic, and/or breast cancer, as well as metastatic disease. Despite the rapid development of potent clinical grade inhibitors, strategic questions remain. Here, we review the state of the literature with respect to current therapeutic inhibitors of tryptophan catabolism, evaluation of those efforts preclinically and clinically, compensatory changes that occur with therapeutic targeting, as well as newly recognized signaling features that raise critical questions to the field. Given the rapidly evolving interest in determining how IDO1/TDO, and to an unknown extent, IDO2, can be targeted for increasing cancer immunotherapeutic efficacy, we present a brief but comprehensive analysis that addresses critical questions, while highlighting the mechanics that remain to be explored. Clin Cancer Res; 21(24); 5427–33. ©2015 AACR.
Functional Genomics Analysis of Big Data Identifies Novel Peroxisome Proliferator–Activated Receptor γ Target Single Nucleotide Polymorphisms Showing Association With Cardiometabolic Outcomes
Authors: Richardson Kris , Schnitzler Gavin R. , Lai Chao-Qiang , Ordovas Jose M. 
Published: October 2015

Background—
Cardiovascular disease and type 2 diabetes mellitus represent overlapping diseases where a large portion of the variation attributable to genetics remains unexplained. An important player in their pathogenesis is peroxisome proliferator–activated receptor γ (PPARγ) that is involved in lipid and glucose metabolism and maintenance of metabolic homeostasis. We used a functional genomics methodology to interrogate human chromatin immunoprecipitation-sequencing, genome-wide association studies, and expression quantitative trait locus data to inform selection of candidate functional single nucleotide polymorphisms (SNPs) falling in PPARγ motifs.

Methods and Results—
We derived 27 328 chromatin immunoprecipitation-sequencing peaks for PPARγ in human adipocytes through meta-analysis of 3 data sets. The PPARγ consensus motif showed greatest enrichment and mapped to 8637 peaks. We identified 146 SNPs in these motifs. This number was significantly less than would be expected by chance, and Inference of Natural Selection from Interspersed Genomically coHerent elemenTs analysis indicated that these motifs are under weak negative selection. A screen of these SNPs against genome-wide association studies for cardiometabolic traits revealed significant enrichment with 16 SNPs. A screen against the MuTHER expression quantitative trait locus data revealed 8 of these were significantly associated with altered gene expression in human adipose, more than would be expected by chance. Several SNPs fall close, or are linked by expression quantitative trait locus to lipid-metabolism loci including CYP26A1.

Conclusions—
We demonstrated the use of functional genomics to identify SNPs of potential function. Specifically, that SNPs within PPARγ motifs that bind PPARγ in adipocytes are significantly associated with cardiometabolic disease and with the regulation of transcription in adipose. This method may be used to uncover functional SNPs that do not reach significance thresholds in the agnostic approach of genome-wide association studies.
Hypertrophic Cardiomyopathy in Children, Adolescents, and Young Adults Associated With Low Cardiovascular Mortality With Contemporary Management Strategies
Authors: Maron Barry J. , Rowin Ethan J. , Casey Susan A. , Lesser John R. , Garberich Ross F. , McGriff Deepa M. , Maron Martin S. 
Published: October 2015

Background—
Youthful age has been considered the time of greatest risk for patients with hypertrophic cardiomyopathy (HCM), largely because of the possibility of sudden death. The last 2 decades have witnessed more reliable identification of at-risk patients and utilization of implantable cardioverter-defibrillators for prevention of sudden death, and other contemporary treatment options. Whether such management advances have significantly altered the considerable mortality rate for young HCM patients remains unresolved.

Methods and Results—

We studied long-term outcome in 474 consecutive HCM patients between 7 and 29 years of age presenting at 2 referral institutions. Over 7.1±5.1 years of follow-up (6.0 [3.0, 10.0]), 452 patients (95%) survived, with 95% experiencing no or mild symptoms. HCM-related death occurred in 18 patients (3%; 0.54%/y): arrhythmic sudden death (n=12), progressive heart failure and heart transplant complications (n=5), or postoperatively (n=1). In contrast, aborted life-threatening events occurred in 63 other high-risk patients (13%) with implantable cardioverter-defibrillator interventions for ventricular tachyarrhythmias (n=31), resuscitated out-of-hospital cardiac arrest (n=20), or heart transplant for advanced heart failure (n=12), 1.8%/y, 3-fold higher than HCM mortality. Five- and 10-year survival (considering only HCM deaths) was high (97% and 94%, respectively), virtually identical to that reported in middle-aged adult HCM patients (98% and 94%,
P
=0.23).

Conclusions—
In a large hospital-based cohort of young HCM patients, representing an age group considered at greatest risk, low mortality rates can be achieved with the application of contemporary cardiovascular treatment strategies, largely because of reliable identification of high-risk patients who benefited from implantable cardioverter-defibrillators for sudden death prevention, thereby creating the opportunity for extended longevity and good quality of life.
Transvenous Implantable Cardioverter‐Defibrillator (ICD) Lead Performance: A Meta‐Analysis of Observational Studies
Authors: Providência Rui , Kramer Daniel B. , Pimenta Dominic , Babu Girish G. , Hatfield Laura A. , Ioannou Adam , Novak Jan , Hauser Robert G. , Lambiase Pier D. 
Published: October 2015

Background

Despite the widespread use of implantable cardioverter‐defibrillators (
ICD
s) in clinical practice, concerns exist regarding
ICD
lead durability. The performance of specific lead designs and factors determining this in large populations need clarification.

Methods and Results
The Medline, Embase, and Cochrane Collaboration databases were searched for studies including ≥2 of the most commonly implanted leads. The Mantel‐Haenszel random‐effects model was used. Seventeen studies were selected, including a total of 49 871 patients—5538 implanted with Durata (St. Jude Medical Inc), 10 605 with Endotak Reliance (Boston Scientific), 16 119 with Sprint Quattro (Medtronic Corp), 11 709 with Sprint Fidelis (Medtronic Corp), and 5900 with Riata (St. Jude Medical Inc)—with follow‐up of 136 509 lead‐years. Although the Durata lead presented a numerically higher rate, no statistically significant differences in the mean incidence of lead failure (0.29%–0.45% per year) were observed in comparison of the 3 nonrecalled leads. A higher event rate was documented with the Riata (1.0% per‐year increase) and Sprint Fidelis (>2.0% per‐year increase) leads compared with nonrecalled leads. An indication of increased incidence of Durata lead failure versus Sprint Quattro and Endotak Reliance leads was observed in 1 of 3 included studies, allowing for comparison of purely electrical lead failure, but this requires further evaluation.

Conclusions
Endotak Reliance (8F), Sprint Quattro (8F), and Durata (7F) leads displayed low annual incidence of failure; however, long‐term follow‐up data are still scarce. More data are needed to clarify the performance and safety of the Durata lead.
The Effect of Incorrect Reliability Information on Expectations, Perceptions, and Use of Automation
Authors: Barg-Walkow Laura H. , Rogers Wendy A. 
Published: October 2015

Objective: We examined how providing artificially high or low statements about automation reliability affected expectations, perceptions, and use of automation over time. Background: One common method of introducing automation is providing explicit statements about the automation’s capabilities. Research is needed to understand how expectations from such introductions affect perceptions and use of automation. Method: Explicit-statement introductions were manipulated to set higher-than (90%), same-as (75%), or lower-than (60%) levels of expectations in a dual-task scenario with 75% reliable automation. Two experiments were conducted to assess expectations, perceptions, compliance, reliance, and task performance over (a) 2 days and (b) 4 days. Results: The baseline assessments showed initial expectations of automation reliability matched introduced levels of expectation. For the duration of each experiment, the lower-than groups’ perceptions were lower than the actual automation reliability. However, the higher-than groups’ perceptions were no different from actual automation reliability after Day 1 in either study. There were few differences between groups for automation use, which generally stayed the same or increased with experience using the system. Conclusion: Introductory statements describing artificially low automation reliability have a long-lasting impact on perceptions about automation performance. Statements including incorrect automation reliability do not appear to affect use of automation. Application: Introductions should be designed according to desired outcomes for expectations, perceptions, and use of the automation. Low expectations have long-lasting effects.
Optimizing water supply pump replacement in buildings of Hong Kong
Authors: Wong LT , Zhou Y , Mui KW , Lau CP 
Published: October 2015

This paper investigates the pump efficiency of existing water supply systems in high-rise buildings in Hong Kong and provides economic justification for pump replacement by comparing the long-term energy cost savings to the initial installation costs. Energy consumptions of water supply pumps were measured with the pump efficiencies determined from the water consumptions of 20 water supply systems in buildings. The study results indicate that for typical pump motor ratings that range from 1 to 40 kW in a high-rise water system, with new pump efficiencies and annual pump efficiency drops that range from 0.68 to 0.74 and 0.012 to 0.028 respectively, a shorter replacement period can be justified on energy cost grounds for larger pumps with greater annual efficiency drops. Practical application: This paper exhibits numerical solutions of replacement period justified on energy cost grounds for typical pump motor ratings that range from 1 to 40 kW in a high-rise water system, with new pump efficiencies and annual pump efficiency drops that range from 0.68 to 0.74 and 0.012 to 0.028, respectively.
Tracheostomy Complications as a Trigger for an Airway Rapid Response
Authors: Rassekh Christopher H. , Zhao Jing , Martin Niels D. , Chalian Ara A. , Atkins Joshua H. 
Published: October 2015

ObjectiveTo analyze the subset of airway rapid response (ARR) calls related to tracheostomy identified over a 46‐month period from August 2011 to May 2015 to determine proximate cause, intervention, and outcome and to develop process improvement initiatives.DesignSingle‐institution multidisciplinary retrospective cohort study.SettingTertiary care academic medical center in a large urban setting.SubjectsHospital inpatients with an in situ tracheostomy or laryngectomy who experienced an ARR.MethodsDetailed review of operator, hospital, and patient records related to ARR system activations over a 46‐month period.ResultsARR was activated for 28 patients with existing tracheostomy. The cohort included open tracheostomy (n = 14), percutaneous tracheostomy (n = 8), laryngectomy stoma (n = 3), and indeterminate technique (n = 3). The most frequent triggers for emergency airway intervention were decannulation (n = 16), followed by mucus plugging (n = 4). The mean body mass index of ARR patients was higher than that of a comparator tracheostomy cohort (32.9 vs 26.3, P <. 001). BMI was >40 in 9 ARR patients. There was 1 mortality in the series.ConclusionsTracheostomy is a major trigger for ARR with potential fatal outcome. Factors that may contribute to tracheostomy emergencies include high body mass index, surgical technique for open tracheostomy or percutaneous tracheostomy, tracheostomy tube size, and bedside tracheostomy management. Results have triggered a hospital‐wide practice improvement plan focused on tracheostomy awareness and documentation, discrete process changes, and implementation of guidelines for emergency management.
Paranasal Sinus Balloon Catheter Dilation for Treatment of Chronic Rhinosinusitis
Authors: Levy Joshua M. , Marino Michael J. , McCoul Edward D. 
Published: October 2015

ObjectiveParanasal sinus balloon catheter dilation (BCD) represents a commonly used tool in the management of chronic rhinosinusitis (CRS) for which the indications, utilization, and outcomes have not been well established. A systematic review and meta‐analysis were undertaken to evaluate change in quality of life and sinus opacification following paranasal sinus BCD in the treatment of CRS.Data SourcesMEDLINE and EMBASE databases.Review MethodsPreferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines were utilized to identify English‐language studies reporting patient outcomes following BCD for CRS. Primary outcomes included the impact of BCD on validated measures of quality of life and sinonasal opacification.ResultsSystematic review identified 17 studies for qualitative analysis. Studies generally included cases with limited disease based on radiographic opacification. Five studies contained extractable data for change in 20‐Item Sinonasal Outcome Test (SNOT‐20) 1 year following BCD, with significant improvement in self‐reported quality of life (P =. 04). Five studies reported a significant change in paranasal sinus opacification following BCD (P <. 001). Two studies directly compared change in SNOT‐20 between BCD and endoscopic sinus surgery, without demonstration of significant difference in outcome (P =. 07). Subgroup analysis found that change in SNOT‐20 score was greater after BCD in the operating room than in the office (P =. 004).ConclusionCurrent evidence supporting the role of BCD in CRS remains incomplete. Long‐term within‐group improvements in quality‐of‐life and sinus opacification scores are demonstrated among a restricted adult population with CRS. Additional study is needed to further evaluate the role for BCD in specific settings and patient subgroups.
Smoking Cessation and Electronic Cigarette Use among Head and Neck Cancer Patients
Authors: McQueen Nicholas , Partington Erin J. , Harrington Kathleen F. , Rosenthal Eben L. , Carroll William R. , Schmalbach Cecelia E. 
Published: October 2015

Objectives(1) Investigate electronic cigarette (e‐cig) use among head and neck (HN) cancer patients; (2) define quit methods, success, motivations, and barriers to smoking cessation; and (3) determine the impact of e‐cig use in smoking cessation.Study DesignCross‐sectional study.SettingTertiary care center.MethodsAn in‐office survey was administered to HN cancer patients ≥19 years of age with past/present tobacco use. Patient demographics were collected. Quit methods, success, and motivations/barriers were surveyed. The Alcohol Use Disorders Identification Test was used to correlate alcohol use and cessation. Independent variables associated with cessation were studied with Fisher’s exact test and Student’s t test. Subgroup analysis was performed for e‐cig users.ResultsOf 110 eligible patients, 106 (96%) enrolled (83% male, 82% Caucasian), of whom 69 (65%) successfully quit. Age of first tobacco use did not differ between the smoking and cessation groups (P =. 14), nor did hazardous drinking (30% smoking vs 14% cessation; P =. 072). “Cold turkey” (ie, stopping abruptly without smoking cessation aids) was the most common method attempted (n = 88, 83%) and most successful (n = 65, 94%). There was no statistical difference in age, sex, race, drinking, or socioeconomic status between e‐cig users and nonusers. Nonusers achieved higher quit rates as compared with e‐cig users (72% vs 39%; P =. 0057). E‐cig use did not decrease the number of cigarettes smoked (463 cigarettes/month) versus that of nonusers (341 cigarettes/month; P =. 2). Seventy percent of e‐cig users wore a nicotine patch.ConclusionsHN cancer patients desire smoking cessation. E‐cig did not decrease tobacco use, and patients who utilize e‐cigs are less likely to achieve smoking cessation.
Adherence to and efficacy of different compression methods for treating chronic venous insufficiency in the elderly
Authors: Suehiro Kotaro , Morikage Noriyasu , Yamashita Osamu , Harada Takasuke , Ueda Koshiro , Samura Makoto , Tanaka Yuya , Takeuchi Yuriko , Hamano Kimikazu 
Published: October 2015

Objectives To investigate the adherence to and efficacy of different compression methods in elderly patients. Methods A retrospective review of compression therapy in 120 elderly patients (≥65 years) with chronic venous insufficiency was performed to study the initially preferred compression method, adherence to each method, and its efficacy. Results Initially, an oversize strong stocking (24%), an appropriate size moderate stocking (19%), and bandages (37%) were equally preferred. Adherence at 1 month was 69%, 96%, and 91%, respectively, and they reduced ankle circumferences in C3 patients by 1.8 ± 1.9 cm, 0.3 ± 1.7 cm, and 2.9 ± 1.7 cm, respectively. The improvement rates of C4 symptoms were 79%, 60%, and 91%, respectively. Only three patients (2%) preferred an appropriate size strong stocking. Conclusions In elderly patients, an appropriate size strong stocking was not preferred. The best adherence was achieved by using a moderate stocking, while the best efficacy was achieved by using bandages.
Problems and needs in helping older people with dementia with daily activities: Perspectives of Thai caregivers
Authors: Griffiths Jiranan , Bunrayong Wannipa 
Published: October 2015

Introduction Caring for people with dementia can be stressful and demanding. The purpose of this qualitative descriptive study was to investigate the problems and needs of caregivers who help older people with dementia to do activities of daily living. Method Thirty caregivers who took older people with dementia to get treatment at a memory clinic in a hospital in the north of Thailand were interviewed using a semistructured interview. Transcribed data were analysed using inductive analysis. Findings The analysis generated five themes related to problems experienced by caregivers: toileting is the hardest job, lifting causes back pain, loss of memory problems, economic hardships and psychological distress. These issues aggregated into support needs from three sources: information and rehabilitation services from health professionals, assistance with everyday tasks from family members and financial support from society. Conclusion The findings reveal that the kind of support Thai caregivers seek from various groups differs according to their perceived expertise and availability. Further studies are needed to explore how that assistance might be delivered and whether it is in fact helpful.
Student Pharmacist Perceptions of a Behind-The-Counter Class of Medications
Authors: Slazak Erin M. , Fodero Kristen E. , Albanese Nicole P. 
Published: October 2015

Objectives: To report perceptions of PharmD candidates regarding a behind-the-counter (BTC) class of medications and to identify perceived barriers to its successful implementation. Methods: PharmD candidates in their second, third, and fourth professional years were invited to complete an online survey. Responses were used to assess perceptions of competency and willingness to participate in a BTC program and perceived preparedness of the current community pharmacy practice environment for a BTC class of medications with regard to 8 specific classes of medications. Results: The survey response rate was 28%. In all, 78% of respondents agreed or strongly agreed that a BTC class of medications is a change that they would be willing to embrace, and 54% agreed or strongly agreed that their PharmD curriculum provided them with adequate training in laboratory and diagnostic test interpretation. Less than half of the respondents agreed or strongly agreed that community pharmacies are currently equipped with the resources necessary to clinically assess a patient and dispense BTC medications. Conclusion: PharmD candidates are prepared and willing to participate in a BTC program but believe that the current community practice environment lacks access to resources necessary to do so.