bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased Mitochondrial Mutagenesis during Transformation of Human Breast Stem Cells into Tumorigenic Cells
Authors: Ahn Eun Hyun , Lee Seung Hyuk , Kim Joon Yup , Chang Chia-Cheng , Loeb Lawrence A. 
Published: May 2016

Abstract
Rare stochastic mutations may accumulate during dormancy of stem-like cells, but technical limitations in DNA sequencing have limited exploring this possibility. In this study, we employed a recently established deep-sequencing method termed Duplex Sequencing to conduct a genome-wide analysis of mitochondrial (mt) DNA mutations in a human breast stem cell model that recapitulates the sequential stages of breast carcinogenesis. Using this method, we found significant differences in mtDNA among normal stem cells, immortal/preneoplastic cells, and tumorigenic cells. Putative cancer stem-like cell (CSC) populations and mtDNA copy numbers increased as normal stem cells become tumorigenic cells. Transformed cells exhibited lower rare mutation frequencies of whole mtDNA than did normal stem cells. The predicted mtDNA rare mutation pathogenicity was significantly lower in tumorigenic cells than normal stem cells. Major rare mutation types in normal stem cells are C&gt;T/G&gt;A and T&gt;C/A&gt;G transitions, while only C&gt;T/G&gt;A are major types in transformed cells. We detected a total of 1,220 rare point mutations, 678 of which were unreported previously. With only one possible exception (m10342T&gt;C), we did not find specific mutations characterizing mtDNA in human breast CSCs; rather, the mitochondrial genome of CSCs displayed an overall decrease in rare mutations. On the basis of our work, we suggest that this decrease (in particular T&gt;C/A&gt;G transitions), rather than the presence of specific mitochondrial mutations, may constitute an early biomarker for breast cancer detection. Our findings support the hypothesis that the mitochondrial genome is altered greatly as a result of the transformation of normal stem cells to CSCs, and that mtDNA mutation signatures may aid in delineating normal stem cells from CSCs. Cancer Res; 76(15); 4569–78. ©2016 AACR.
The Effect of Hepatic Impairment on Outcomes in Phase I Clinical Trials in Cancer Subjects
Authors: Mansfield Aaron S. , Rudek Michelle A. , Vulih Diana , Smith Gary L. , Harris Pamela Jo , Ivy S. Percy 
Published: May 2016

Abstract
Purpose: The NCI Cancer Therapy Evaluation Program sponsors hepatic dysfunction phase I clinical trials (HDCT) and phase 1 clinical trials (P1CT) to determine safe doses and schedules of antineoplastic therapeutics. We sought to compare clinical outcomes between these trial types while stratifying by hepatotoxic agents.
Experimental Design: Individual subject data were extracted from the records of 51 NCI-sponsored HDCT and P1CT. The NCI's Organ Dysfunction Working Group's hepatic impairment categorization and two drug-induced liver injury (DILI) scales (FDA R ratio and Hy's law) were used to classify subjects. The number of cycles administered and treatment discontinuation reason were also evaluated and compared between groups.
Results: There were 513 and 1,328 subjects treated on HDCT (n = 9) and P1CT (n = 42), respectively. There were differing patterns of DILI with significant worsening of total bilirubin in subjects on HDCT, and worsening of alanine aminotransferase (ALT) in subjects on P1CT. Cholestatic peak patterns of liver impairment (predominant increases in alkaline phosphatase rather than transaminases) were more frequent in HDCT. Criteria for Hy's law were met by 11 subjects on P1CT, but not by any subjects on HDCT. Disease progression was the most common reason for treatment discontinuation, followed by adverse events at similar frequencies in both HDCT and P1CT.
Conclusions: The differential effects on hepatotoxicity suggest that underlying hepatic function may affect susceptibility to and patterns of DILI. The incorporation of additional measures of hepatic function may help identify those at highest risk of hepatotoxicity in future trials because baseline liver tests did not. Clin Cancer Res; 22(22); 5472–9. ©2016 AACR.
Poor Outcome of Stroke Patients With Atrial Fibrillation in the Presence of Coexisting Spontaneous Echo Contrast
Authors: Yoo Joonsang , Song Dongbeom , Baek Jang-Hyun , Kim Young Dae , Nam Hyo Suk , Hong Geu-Ru , Kim Jinkwon , Lee Hye Sun , Heo Ji Hoe 
Published: May 2016

Background and Purpose—
Spontaneous echo contrast (SEC) is frequently detected in patients with atrial fibrillation (AF). Coexisting SEC in patients with AF may be associated with heightened thrombogenicity, which affects stroke outcomes.

Methods—
Consecutive stroke patients with nonvalvular AF who underwent transesophageal echocardiography were included in this study. We compared initial stroke severity and functional outcome at 3 months between the patients with and those without SEC.

Results—

Of 440 patients with nonvalvular AF who underwent transesophageal echocardiography during a 7-year period, 193 (43.9%) patients had SEC. Stroke was more severe in the patients with SEC than in those without SEC (National Institute of Health Stroke Scale score: median [interquartile range], 5 [2–12] versus 3 [1–8];
P
=0.004). The patients with SEC more frequently had poor functional outcomes (modified Rankin scale score of >2) at 3 months than those without SEC (32.3% versus 16.1%;
P
<0.001). On multivariate analysis, the presence of SEC was an independent factor of poor outcome (odds ratio, 2.09; 95% confidence interval, 1.24–3.53).

Conclusions—
In the ischemic stroke patients with nonvalvular AF, coexisting SEC was associated with more severe stroke and was predictive of poor long-term functional outcome.
New Legal Capacity Laws and the United Nations Convention on the Rights of Persons with Disabilities: An Overview of Five Countries in Europe
Authors: Fallon-Kund Marie , Bickenbach Jerome E 
Published: May 2016

AbstractSeveral state parties to the United Nations Convention on the Rights of Persons with Disabilities (CRPD) undertook recent revisions of their national legal capacity laws. These revisions aim to promote the autonomy of persons with disabilities as set forward by the CRPD. At the same time, the CRPD Committee calls for the abolishment of all forms of substitute decision-making through its first General Comment on Article 12 of the Convention. We thus describe the main components of new legal capacity laws of Belgium, the Czech Republic, France, Germany, and Switzerland and assess those in light of the General Comment. We argue that none of these countries completely abolished substitute decision-making regimes and align with the views that a more realistic interpretation should be given to the CRPD. Such interpretation would provide better guidance for countries in the implementation of Article 12.
Impact of Synoptic Atmospheric Forcing on the Mean Ocean Circulation
Authors: Wu Yang , Zhai Xiaoming , Wang Zhaomin 
Published: May 2016

Abstract
The impact of synoptic atmospheric forcing on the mean ocean circulation is investigated by comparing simulations of a global eddy-permitting ocean–sea ice model forced with and without synoptic atmospheric phenomena. Consistent with previous studies, transient atmospheric motions such as weather systems are found to contribute significantly to the time-mean wind stress and surface heat loss at mid- and high latitudes owing to the nonlinear nature of air–sea turbulent fluxes. Including synoptic atmospheric forcing in the model has led to a number of significant changes. For example, wind power input to the ocean increases by about 50%, which subsequently leads to a similar percentage increase in global eddy kinetic energy. The wind-driven subtropical gyre circulations are strengthened by about 10%–15%, whereas even greater increases in gyre strength are found in the subpolar oceans. Deep convection in the northern North Atlantic becomes significantly more vigorous, which in turn leads to an increase in the Atlantic meridional overturning circulation (AMOC) by as much as 55%. As a result of the strengthened horizontal gyre circulations and the AMOC, the maximum global northward heat transport increases by almost 50%. Results from this study show that synoptic atmospheric phenomena such as weather systems play a vital role in driving the global ocean circulation and heat transport, and therefore should be properly accounted for in paleo- and future climate studies.
The Eddy–Mean Flow Interaction and the Intrusion of Western Boundary Current into the South China Sea–Type Basin in an Idealized Model
Authors: Zhong Linhao , Hua Lijuan , Luo Dehai 
Published: May 2016

AbstractIn this paper, an ideal model of the role of mesoscale eddies in the Kuroshio intruding into the South China Sea (SCS) is developed, which represents the northwestern Pacific and the SCS as two rectangular basins connected by a gap. In the case of considering only intrinsic ocean variability, a time-dependent western boundary current (WBC) driven by steady wind is modeled under both eddy-resolving and noneddy-resolving resolutions. Almost all simulated WBCs intrude into the adjacent sea in the form of the Loop Current with multiple-state transitions and eddy-shedding processes, which have aperiodic variations on intraseasonal or interannual scales, determined by the eddy-induced WBC variation. For the parameters considered in this paper, the WBC intrusion exhibits a 30–90-day cycle in the presence of the subgrid-scale eddy forcing (SSEF) but a 300–500-day cycle in the absence of SSEF. Moreover, the roles of the grid-scale and subgrid-scale eddies in the WBC intrusion are studied by using the dynamically consistent decomposition developed by Berloff. Based on the large-sample composite analysis of the intrusion events, it is found that the Loop Current intensity is mainly determined by baroclinic processes through grid-scale, eddy–eddy interaction and subgrid-scale, eddy–flow interaction. The intrusion position and period are mainly regulated by the SSEF to the west of gap, where the balance between relative vorticity and isopycnal thickness SSEFs determines eddy detachment. Generally, the relative vorticity SSEF therein tends to induce WBC intrusion. However, the isopycnal thickness SSEF tends to induce eddy shedding, and WBC retreat thus determines the intrusion cycle through counteracting relative vorticity SSEF.
Improving Access to Head and Neck Cancer Surgical Services through the Incorporation of Associate Providers
Authors: Paydarfar Joseph A. , Gosselin Benoit J. , Tietz Annette M. 
Published: May 2016

ObjectiveThe urgent nature of head and neck cancer referrals often results in overbooked schedules, access delays, and patient, physician, and staff dissatisfaction. The goal of this study is to examine how incorporation of associate providers (APs) into a head and neck tumor clinic (HNTC) can improve access.MethodsScheduling data for the Dartmouth‐Hitchcock HNTC 2 years prior (January 2011 to December 2012) and 2 years subsequent (January 2013 to December 2014) to program initiation were abstracted, including number of new patients seen per month, third available for new and established patients, overbooked hours, surgeon productivity, and patient satisfaction scores.ResultsNew patients seen per month increased from 44 ± 4 to 60 ± 5 (P <. 001). Third available for new patients decreased from 56 ± 4 to 27 ± 2 days and from 43 ± 3 to 35 ± 2 days for follow‐ups (P <. 001). Overbooked hours decreased from 14.7 ± 3.1 to 8.6 ± 1.7 hours (P <. 001). Surgeon productivity remained stable (109% ± 11% vs 113% ± 6%, P =. 56). Patient satisfaction in seeing APs versus surgeons was comparable (94 ± 2 vs 94 ± 3, P =. 79).DiscussionIncorporation of APs into the HNTC increases the number of new patients seen by the surgeon, decreases wait times for all appointments, and decreases overbooking while maintaining patient satisfaction and surgeon productivity.Implications for PracticeAP incorporation significantly improves access to head and neck surgical services. With improved access, new cancer patients could start treatment sooner, potentially affecting outcome.
Adverse Event Reporting for Proton Pump Inhibitor Therapy
Authors: Abramowitz Jason , Thakkar Punam , Isa Arton , Truong Alan , Park Connie , Rosenfeld Richard M. 
Published: May 2016

ObjectiveTo assist clinicians in counseling patients regarding the risk of adverse events from proton pump inhibitors (PPIs), by synthesizing evidence from published systematic reviews of antireflux therapy.Data SourcesCochrane Library, CINAHL, PubMed, Web of Knowledge.Review MethodsOverview based on PRISMA reporting standards (preferred reporting items for systematic reviews and meta‐analyses) of English‐language meta‐analyses and systematic reviews of PPI therapy for reflux disease through December 2014. Two independent investigators assessed study eligibility, rated the review quality with AMSTAR criteria (assessing the methodological quality of systematic reviews), and abstracted data for adverse events.ResultsThirty‐three systematic reviews met inclusion criteria. The most commonly reported adverse events were community‐acquired pneumonia (odds ratios, 1.04‐1.92), with a greater association noted with shorter duration of therapy and higher doses. Hip fractures were also associated with PPI use (odds ratios, 1.16‐1.50), especially with long‐term therapy. Last, enteric infection with Clostridium difficile was more common with PPI therapy (odds ratios, 1.69‐1.33). Other less commonly reported adverse events included electrolyte and vitamin deficiency. Risk factors for adverse events are reported in the text.ConclusionOur overview shows that PPI therapy is associated with significant and potentially serious adverse events that should be discussed with patients. The effect sizes and risk factors provided should facilitate this discussion and promote shared decision making.
Incidence, Degree, and Clinical Effect of Subchondral Bone Overgrowth After Microfracture in the Knee
Authors: Mithoefer Kai , Venugopal Vivek , Manaqibwala Moiz 
Published: May 2016

Background: Subchondral bone overgrowth has been described with variable frequency after microfracture, but little systematic information is available about the clinical incidence, risk factors, or clinical relevance of this phenomenon. Hypothesis: Subchondral overgrowth (1) occurs with high incidence and various degrees after microfracture, (2) is associated with risk factors, and (3) affects clinical outcome score and failure rate. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 84 patients undergoing microfracture in the knee were prospectively followed up to 6 years postoperatively through use of cartilage-sensitive magnetic resonance imaging to detect the incidence of subchondral bone overgrowth. The quantity of the overgrowth was graded systematically and was then correlated to patient and lesion characteristics, surgical technique, validated functional outcome scores, and failure rate. Results: Subchondral bone overgrowth was observed in 62% of patients at a mean of 22 months after surgery. Most bone overgrowth (64%) was low grade and developed during the first 12 months after microfracture. Risk factors for bone overgrowth included high body mass index, defects on the lateral femoral condyle, and aggressive debridement of the calcified cartilage layer. Knee injury and Osteoarthritis Outcome Score results were not significantly different between patients with or without subchondral bone overgrowth. However, 93% of patients who failed microfracture demonstrated osseous overgrowth, and patients with osseous overgrowth showed a significantly higher failure rate (25%) than patients without overgrowth (3.1%; P < .01). Conclusion: Subchondral bone overgrowth is frequently observed after microfracture surgery but is mostly of low grade. Several risk factors were identified that can affect the incidence of this phenomenon. Importantly, subchondral overgrowth is associated with an increased rate of postoperative failure after microfracture.
Which Way India?
Authors: Sharma Shalendra D. 
Published: May 2016

Jagdish Bhagwati and Arvind Panagariya, Why Growth Matters: How Economic Growth in India Reduced Poverty and the Lessons for Other Developing Countries. New York: Public Affairs, 2014, pp. 280, US$28.99. Jean Dreze and Amartya Sen, An Uncertain Glory: India and its Contradictions. Princeton: Princeton University Press, 2013, pp. 448, Paperback US$19.95, Hardcover US$29.95.
The Productivity Commission and industrial relations reform
Authors: Peetz David 
Published: May 2016

AbstractThis article considers the political economy of the Productivity Commission in industrial relations reform; in particular, its review of the industrial relations framework foreshadowed in 2013 and conducted in 2015. Following a history of the establishment of the Productivity Commission and its predecessor agencies, it argues that the concepts of third-party independence and third-party endorsement are important for understanding the role of the Productivity Commission. A review of the politics of industrial relations reform leads into the central analysis of the political economy of the Productivity Commission’s 2015 inquiry into the Australian workplace relations framework. The concepts of third-party independence and endorsement are applied in analysing some of the inquiry’s key recommendations. The conclusion discusses several difficulties in the political economy of the Productivity Commission and its relationships to government and, indeed, to evidence, when the latter contradicted its mainly liberal market stance.
The Pharmacist as a Member of the CPR Team: Evaluation by other Health Professionals
Authors: Ludwig Dennis J. , Abramowitz Paul W. 
Published: May 2016

Physician and nurse evaluation of the pharmacist's participation on the cardiopulmonary resuscitation (CPR) team was studied, in an attempt to justify the pharmacist's role. A pharmacist-evaluation questionnaire was prepared, based on the Likert Method. This questionnaire contained ten statements related to organizational and mechanical contributions, drug information contributions, and overall contribution and desire, by other health professionals, for continuance of this service. Pharmacists attended all CPRs during a six-month period and distributed a questionnaire to one physician and one nurse in attendance. Verification was obtained that these individuals had attended previous arrests where pharmacists were not in attendance. Only those evaluations that were completed and returned by the physician or the nurse, to the Department of Pharmaceutical Services, were evaluated. Results indicated that physicians and nurses are in agreement with the pharmacist's organizational and mechanical contribution. Both physicians and nurses tended toward agreement with the pharmacist's drug information contribution. Finally, physicians and nurses are in agreement with the pharmacist's overall contribution to the CPR team and desire continuance of this service.
Pharmacy-Enforced Outpatient Drug Treatment Protocols: A Case Study of Medi-Cal Restrictions for Cefaclor
Authors: Mccombs Jeffrey S. , Nichol Michael B. 
Published: May 2016

Objective To evaluate whether a pharmacy-enforced treatment protocol successfully limited the use of a high-cost medication to high-risk patients. Design A case study cost-effectiveness analysis was conducted to evaluate a treatment protocol for cefaclor. Episodes of care were defined, healthcare expenditures for all services were aggregated, and demographic data were retrieved from a five percent random sample of California Medicaid (Medi-Cal) recipients. Data were available for episodes occurring before cefaclor was made available under Medi-Cal. Setting Medi-Cal added cefaclor to its formulary, limiting its use to patients over 50 years of age with lower respiratory tract infections (LRTIs). The unit of analysis was an episode of outpatient antibiotic treatment. Patients Confirmed LRTI episodes and unconfirmed LRTI cefaclor episodes were analyzed, including multiple episodes of treatment for individual patients. A total of 7855 non-cefaclor LRTI episodes and 2556 cefaclor episodes were analyzed. Main outcome Measures The primary outcome measures were healthcare expenditures three months after the initiation of antibiotic therapy, differentiated by type of service. Results Physicians directed cefaclor toward higher-risk patients over age 50 years, even in unconfirmed LRTI episodes. Cefaclor use was estimated to reduce posttreatment costs by $388 per patient (p<0.001), primarily because of reduced hospital expenditures of $366 (p<0.001). Conclusions Pharmacy-enforced outpatient drug treatment protocols may be a viable alternative to restrictive formularies and prior authorization. In the case of cefaclor, the Medi-Cal treatment protocol appeared to allow high-risk patients better access to a high-cost medication while reducing total posttreatment costs.
Hepatotoxicity Associated with Angiotensin-Converting Enzyme Inhibitors
Authors: Hagley Michael T. , Hulisz Darrell T. , Burns Colleen M. , Hartshorn Edward A. 
Published: May 2016

Objective To review published reports of hepatotoxicity associated with angiotensin-converting enzyme (ACE) inhibitors and to explore possible mechanisms of injury. Data Sources Published reports of hepatotoxicity associated with use of ACE inhibitors and investigations that suggest potential mechanisms of injury. Data Synthesis Nineteen cases of ACE-inhibitor–associated hepatotoxicity are presented. Early theories regarding mechanisms are reviewed. Laboratory investigations of hepatic effects of eicosanoids on hepatic function are reviewed and a novel mechanism by which ACE inhibitors may cause hepatic injury is postulated. Conclusions Hepatotoxicity, usually cholestatic in nature, has been reported with captopril, enalapril, and lisinopril use. Apparent cross-reactivity has been reported twice. Potential mechanisms of injury include idiopathic hypersensitivity and modulation of eicosanoid metabolism by inhibition of kininase II and subsequent increased hepatic bradykinin activity. Mediation via altered eicosanoid metabolism provides a plausible explanation for cross-reactivity among ACE inhibitors. Hepatotoxicity resolves if ACE inhibitors are stopped but may progress to liver failure if treatment is continued.
Radiographic Evaluation of Ankle Joint Stability After Calcaneofibular Ligament Elevation During Open Reduction and Internal Fixation of Calcaneus Fracture
Authors: Wang Chien-Shun , Tzeng Yun-Hsuan , Lin Chun-Cheng , Huang Ching-Kuei , Chang Ming-Chau , Chiang Chao-Ching 
Published: May 2016

Background: The aim of this prospective study was to evaluate the influence of sectioning the calcaneofibular ligament (CFL) during an extensile lateral approach during open reduction and internal fixation (ORIF) of calcaneal fractures on ankle joint stability. Methods: Forty-two patients with calcaneal fractures that received ORIF were included. Talar tilt stress and anterior drawer radiographs were performed on the operative and contralateral ankles 6 months postoperatively. Results: The average degree of talar tilt on stress radiographs was 3.4 degrees (range, 0-12 degrees) on the operative side and 3.2 degrees (range, 0-14 degrees) on the contralateral side. The mean anterior drawer on stress radiographs of the CFL incised ankle was 6.1 mm (range, 2.4-11.8 mm) and on the contralateral ankle was 5.7 mm (range, 2.6-8.6 mm). There was no statistically significant difference of talar tilt and anterior drawer between the CFL incised side and the contralateral side ( P = .658 and .302, respectively). Conclusion: The results suggest that sectioning of the CFL without any repair during ORIF of a calcaneal fracture does not have a negative effect on stability of the ankle. Repair of the CFL is, thus, probably not necessary following extended lateral approach for ORIF of calcaneal fractures. Level of Evidence: Level II, comparative study.