bluuebunny/crossref_metadata_2025_split huggingface dataset:
NRF2 Induction Supporting Breast Cancer Cell Survival Is Enabled by Oxidative Stress–Induced DPP3–KEAP1 Interaction
Authors: Lu Kevin , Alcivar Allen L. , Ma Jianglin , Foo Tzeh Keong , Zywea Susan , Mahdi Amar , Huo Yanying , Kensler Thomas W. , Gatza Michael L. , Xia Bing 
Published: April 2017

Abstract
NRF2 is a transcription factor serving as a master regulator of the expression of many genes involved in cellular responses to oxidative and other stresses. In the absence of stress, NRF2 is constantly synthesized but maintained at low levels as it is targeted by KEAP1 for ubiquitination and proteasome-mediated degradation. NRF2 binds KEAP1 mainly through a conserved “ETGE” motif that has also been found in several other proteins, such as DPP3, which has been shown to bind KEAP1 and enhance NRF2 function upon overexpression. Here we demonstrate the interaction between endogenous DPP3 and endogenous KEAP1. We further show that the DPP3–KEAP1 interaction is strongly induced by hydrogen peroxide and that DPP3 is required for timely NRF2 induction and nuclear accumulation in the estrogen receptor (ER)-positive MCF7 breast cancer cells. Moreover, we present evidence that the binding of DPP3 to KEAP1 stabilizes the latter. Finally, we show that DPP3 is overexpressed in breast cancer and that elevated levels of DPP3 mRNA correlate with increased NRF2 downstream gene expression and poor prognosis, particularly for ER-positive breast cancer. Our studies reveal novel insights into the regulation of NRF2 and identify DPP3 and an NRF2 transcriptional signature as potential biomarkers for breast cancer prognosis and treatment. Cancer Res; 77(11); 2881–92. ©2017 AACR.
Targeting Autocrine CCL5–CCR5 Axis Reprograms Immunosuppressive Myeloid Cells and Reinvigorates Antitumor Immunity
Authors: Ban Yi , Mai Junhua , Li Xin , Mitchell-Flack Marisa , Zhang Tuo , Zhang Lixing , Chouchane Lotfi , Ferrari Mauro , Shen Haifa , Ma Xiaojing 
Published: April 2017

Abstract
The tumor-promoting potential of CCL5 has been proposed but remains poorly understood. We demonstrate here that an autocrine CCL5–CCR5 axis is a major regulator of immunosuppressive myeloid cells (IMC) of both monocytic and granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation of granulocytic myeloid-derived suppressor cells and tumor-associated macrophages. In parallel, enhanced maturation of intratumoral neutrophils and macrophages occurred in spite of tumor-derived CCL5. The refractory nature of ccl5-null myeloid precursors to tumor-derived CCL5 was attributable to their persistent lack of membrane-bound CCR5. The changes in the ccl5-null myeloid compartment subsequently resulted in increased tumor-infiltrating cytotoxic CD8+ T cells and decreased regulatory T cells in tumor-draining lymph nodes. An analysis of human triple-negative breast cancer specimens demonstrated an inverse correlation between "immune CCR5" levels and the maturation status of tumor-infiltrating neutrophils as well as 5-year-survival rates. Targeting the host CCL5 in bone marrow via nanoparticle-delivered expression silencing, in combination with the CCR5 inhibitor Maraviroc, resulted in strong reductions of IMC and robust antitumor immunities. Our study suggests that the myeloid CCL5–CCR5 axis is an excellent target for cancer immunotherapy. Cancer Res; 77(11); 2857–68. ©2017 AACR.
Treatment Deintensification Is Uncommon in Adults With Type 2 Diabetes Mellitus
Authors: McAlister Finlay A. , Youngson Erik , Eurich Dean T. 
Published: April 2017

Background—
Whether treatment deintensification in Americans with diabetes mellitus varies by glycemic control, health status, and calendar year (before/after February 2008 when safety concerns about intensive glucose control were reported in the ACCORD trial [Action to Control Cardiovascular Risk in Diabetes]) is unclear.

Methods and Results—

We defined deintensification as discontinuation or dosage decrease of at least 1 glycemic medication without addition of, or uptitration of, another agent in the 120 days after the index glycosylated hemoglobin (HbA1C) measurement. Of 99 694 individuals (mean age 54 years) in this retrospective cohort study being actively treated for new diabetes mellitus (50% 1 drug, 33% 2 drugs, and 17% ≥3 drugs), 12 921 (13.0%) had HbA1C <6% after 1 year, 19 670 (19.7%) had HbA1C 6.0% to 6.4%, 35 012 (35.1%) had HbA1C 6.5% to 7.5%, and 32 091 (32.2%) had HbA1C >7.5%. Glycemic therapy was deintensified in 18.3% of patients (21.2% of frail patients, 19.4% of those with multiple comorbidities, and 17.7% of otherwise healthy patients) with no gradient across glycemia levels (20.6% of those with HbA1C<6%, 17.3% of those with HbA1C 6.0%–6.4%, 17.7% of those with HbA1C 6.5%–7.5%, and 18.6% of those with HbA1C>7.5%). Similar proportions were seen even after exclusion of 26 985 patients being treated with metformin monotherapy: 23.3%, 20.4%, 20.3%, and 20% across the HbA1C strata. Therapy was deintensified in 22.5% of patients with index HbA1C <6.0% before February 2008 compared with 19.5% after (
P
<0.001).

Conclusions—
Among frail patients or those with multiple comorbidities, over three quarters with low HbA1C did not have their glycemic therapy deintensified, even after safety concerns were raised in the ACCORD trial.
An Analytical Model of Iceberg Drift
Authors: Wagner Till J. W. , Dell Rebecca W. , Eisenman Ian 
Published: April 2017

AbstractThe fate of icebergs in the polar oceans plays an important role in Earth’s climate system, yet a detailed understanding of iceberg dynamics has remained elusive. Here, the central physical processes that determine iceberg motion are investigated. This is done through the development and analysis of an idealized model of iceberg drift. The model is forced with high-resolution surface velocity and temperature data from an observational state estimate. It retains much of the most salient physics, while remaining sufficiently simple to allow insight into the details of how icebergs drift. An analytical solution of the model is derived, which highlights how iceberg drift patterns depend on iceberg size, ocean current velocity, and wind velocity. A long-standing rule of thumb for Arctic icebergs estimates their drift velocity to be 2% of the wind velocity relative to the ocean current. Here, this relationship is derived from first principles, and it is shown that the relationship holds in the limit of small icebergs or strong winds, which applies for typical Arctic icebergs. For the opposite limit of large icebergs (length > 12 km) or weak winds, which applies for typical Antarctic tabular icebergs, it is shown that this relationship is not applicable and icebergs move with the ocean current, unaffected by the wind. The latter regime is confirmed through comparisons with observed iceberg trajectories near the Antarctic Peninsula.
Can Intracapsular Tonsillectomy Be an Alternative to Classical Tonsillectomy? A Meta‐analysis
Authors: Kim Jong Seung , Kwon Sam Hyun , Lee Eun Jung , Yoon Yong Joo 
Published: April 2017

ObjectiveTonsillectomy is the most common operation performed in the otolaryngologic fields. Efforts have been made to reduce postoperative complications, and one of these is intracapsular tonsillectomy and adenoidectomy (ICTA), which leaves the tonsillar tissue with tonsillar capsule. This study aimed to evaluate intracapsular tonsillectomy compared with classical extracapsular tonsillectomy in terms of efficacy of the technique for managing obstructive sleep apnea (OSA) and reducing postoperative complications.Data SourcesWe performed a literature search using PubMed, EMBASE, and the Cochrane Library through December 2016.Review MethodsSummarized risk ratio (RR), risk differences (RDs), and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were estimated by summarizing the risk estimates of each study using random‐effects models that considered both within‐ and between‐study variations.ResultsOur search included 15 randomized controlled studies. The RRs for postoperative bleeding and residual tonsils were, respectively, 0.44 (P =. 01) and 6.02 (P =. 0002). There were significant differences in postoperative pain (P =. 0022), need for analgesics (P <. 0001), days to normal diet (P =. 006), and days to normal activity (P <. 00001) between intracapsular tonsillectomy and extracapsular tonsillectomy.ConclusionsIntracapsular tonsillectomy can effectively reduce postoperative pain and bleeding, which shortens the time required to return to normal life. There was no difference between microdebrider and coblator in intracapsular tonsillectomy regarding postoperative pain and bleeding. It can increase the risk of remnant tonsils; however, it does not increase the risk of recurrent infection.
The Use of Noninvasive Positive Pressure Ventilation following Pediatric Tonsillectomy
Authors: Buzi Adva , Coblens Orly M. , MacGillivray Michael , Elden Lisa 
Published: April 2017

ObjectiveTo determine the risks of bleeding and other complications in pediatric patients who require noninvasive positive pressure ventilation (PPV) in the immediate posttonsillectomy period.Study DesignCase series with chart review.SettingSingle tertiary pediatric hospital.Subjects and MethodsSixty‐nine patients who had undergone tonsillectomy from July 2007 through December 2013 and required postoperative PPV were reviewed. Data collected included age, sex, medical history, preoperative polysomnogram parameters, length of use and type of noninvasive ventilatory support, and postoperative complications. Bleeding rate was calculated.ResultsSixty‐nine children met inclusion criteria for the study. Most had comorbid conditions. The mean age of these patients was 6.4 years. The postoperative bleeding rate of children who required operative intervention for control was 5.97%. Patients did not experience other complications.ConclusionThis is the largest study in the literature investigating bleeding in pediatric patients undergoing tonsillectomy who required postoperative noninvasive PPV. Some hesitation may exist in using this form of ventilation when open pharyngeal wounds are exposed to pressure, but this study suggests that it can be used as a suitable alternative to invasive ventilation.
USMLE and Otolaryngology: Predicting Board Performance
Authors: Puscas Liana , Chang C. W. David , Lee Hui‐Jie , Diaz Rodney , Miller Robert 
Published: April 2017

ObjectiveTo ascertain what relationship exists between the United States Medical Licensing Examination (USMLE) and the American Board of Otolaryngology Written Qualifying Examination (WQE).Study DesignRetrospective, longitudinal study.SettingDe‐identified database.SubjectsResidents entering otolaryngology–head and neck surgery (OHNS) residency between 2007 and 2009 and taking the WQE for the first time between 2012 and 2014.MethodsRegression models were used to determine if the USMLE score predicts passage of the WQE on the first attempt, which step score was a better predictor, and whether an increase in the Step 2 score increased the chances of WQE passage.ResultsThere were 611 Step 1 and 402 Step 2 scores. Mean (SD) Step 1 score was 238 (14.4), and the mean (SD) Step 2 score was 243 (16.8). The overall WQE first‐time passage rate was 95.3%. Step 1 score was a better predictor than Step 2 for successful passage of the WQE on the first attempt (P =. 0026). An increase in the Step 2 score compared with the Step 1 score did not predict an improved first‐time passage rate on the WQE.ConclusionsThere is an association between USMLE scores and successful first‐time passage of the WQE, with Step 1 being a stronger predictor than Step 2. Residents with USMLE scores lower than the average successful OHNS applicant still have a high chance of passing the WQE. USMLE scores alone are of limited usefulness in identifying those applicants at risk of failing the WQE on the first attempt.
Clinician views of patient decisional conflict when deciding between dialysis and conservative management: Qualitative findings from the PAlliative Care in chronic Kidney diSease (PACKS) study
Authors: Noble Helen , Brazil Kevin , Burns Aine , Hallahan Sarah , Normand Charles , Roderick Paul , Thompson Colin , Maxwell Peter , Yaqoob Magdi 
Published: April 2017

Background: Only a paucity of studies have addressed clinician perspectives on patient decisional conflict, in making complex decisions between dialysis and conservative management (renal supportive and palliative care). Aim: To explore clinician views on decisional conflict in patients with end-stage kidney disease. Design: Interpretive, qualitative study. Setting and participants: As part of the wider National Institute for Health Research, PAlliative Care in chronic Kidney diSease study, semi-structured interviews were conducted with clinicians (nephrologists n = 12; 7 female and clinical nurse specialists n = 15; 15 female) across 10 renal centres in the United Kingdom. Interviews took place between April 2015 and October 2016 and a thematic analysis of the interview data was undertaken. Results: Three major themes with associated subthemes were identified. The first, ‘Frequent changing of mind regarding treatment options’, revealed how patients frequently altered their treatment decisions, some refusing to make a decision until deterioration occurred. The second theme, ‘Obligatory beneficence’, included clinicians helping patients to make informed decisions where outcomes were uncertain. In weighing up risks and benefits, and the impact on patients, clinicians sometimes withheld information they thought might cause concern. Finally, ‘Intricacy of the decision’ uncovered clinicians’ views on the momentous and brave decision to be made. They also acknowledged the risks associated with this complex decision in giving prognostic information which might be inaccurate. Limitations: Relies on interpretative description which uncovers constructed truths and does not include interviews with patients. Conclusion: Findings identify decisional conflict in patient decision-making and a tension between the prerequisite for shared decision-making and current clinical practice. Clinicians also face conflict when discussing treatment options due to uncertainty in equipoise between treatments and how much information should be shared. The findings are likely to resonate across countries outside the United Kingdom.
Laparoscopic management of cholecystoenteric fistula: A single-center experience
Authors: Li Xiang-yang , Zhao Xin , Zheng Peng , Kao Xiao-Ming , Xiang Xiao-Song , Ji Wu 
Published: April 2017

Aim To report our experience regarding management of cholecystoenteric fistula (CEF) and identify the most effective diagnostic methods and surgical treatment. Methods In total, 10,588 patients underwent laparoscopic cholecystectomy for cholecystolithiasis from January 2000 to December 2014 at the Research Institute of General Surgery, Jinling Hospital (Nanjing, China). Twenty-nine patients were diagnosed with CEF preoperatively or intraoperatively. Data were retrospectively collected on demographics, preoperative diagnostics, intraoperative findings, laparoscopic procedures, complications, and follow-up. Results Twenty-nine patients (female/male ratio, 2.2; mean age, 68.7 years) with CEF were evaluated. Twenty-three (79.3%) patients had a cholecystoduodenal fistula (CDF), four (13.8%) had a cholecystocolonic fistula (CCF), one (3.4%) had a cholecystogastric fistula, and one (3.4%) had a CDF combined with a CCF. Only nine (31.0%) patients obtained a preoperative diagnosis. All patients initially underwent laparoscopic treatment, but five (17.2%) underwent conversion to open surgery; three of these five developed postoperative morbidity or mortality, and the other two had an uneventful postoperative course. Among patients managed successfully by laparoscopy, the hospital stay ranged from 3 to 6 days (mean, 4 days). All patients were asymptomatic at a mean follow-up of 13 months (range, 3–21 months). Conclusion Ultrasound and computed tomography can provide valuable diagnostic clues for CEF. Laparoscopic management of CEF in experienced hands is safe, feasible, and associated with rapid postoperative recovery.
Global scientific production in the field of knee arthroplasty: A cross-sectional survey of research activities
Authors: Wang Lu , Li Lingxia , Cheng Cai , Tian Hua , Li Yang , Zhao Minwei 
Published: April 2017

Objective To determine the quantity and quality of articles in the field of knee arthroplasty worldwide and elucidate the characteristics of global scientific production. Methods Web of Science was used to identify articles in the field of knee arthroplasty from 2011 to 2015. The total number of papers, number of papers per capita, total number of citations, and mean number of citations were collected. Results In total, 11,590 papers were identified. The number of publications significantly increased from 2011 to 2015. Most originated from North America, East Asia, and West Europe. Most (88.51%) were from high-income countries, 11.48% were from middle-income countries, and only 0.01% were from lower-income countries. The United States had the most articles and total citations. Sweden had the highest mean citations, followed by Denmark and Canada. However, when adjusted by population size, Denmark had the most articles per million population, followed by Switzerland and the Netherlands. Conclusions The number of knee arthroplasty publications has rapidly increased in recent years. The United States is the most prolific, but some European countries are more productive relative to their population.
Objectively Measured Physical Activity in Patients After Anterior Cruciate Ligament Reconstruction
Authors: Bell David R. , Pfeiffer Karin A. , Cadmus-Bertram Lisa A. , Trigsted Stephanie M. , Kelly Adam , Post Eric G. , Hart Joseph M. , Cook Dane B. , Dunn Warren R. , Kuenze Christopher 
Published: April 2017

Background: Returning to a healthy level of physical activity is among the most commonly discussed clinical goals for patients recovering from anterior cruciate ligament reconstruction (ACLR). However, physical activity has not been objectively measured in this population. Purpose: To investigate differences in the mean time (min/d) spent in moderate-to-vigorous physical activity (MVPA) as well as the daily step count (steps/d) between patients who underwent ACLR and matched controls. A second purpose was to investigate relationships between MVPA and objective assessments of the daily step count and Tegner and Marx activity scales. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Physical activity was assessed using ActiGraph accelerometers in 33 participants with a history of primary unilateral or bilateral ACLR (mean time from surgery, 27.8 ± 17.5 months; range, 6-67 months) as well as in 33 healthy controls (matched on age, sex, and activity level). Participants wore the accelerometer for 7 days and completed the International Knee Documentation Committee subjective form and the Tegner and Marx activity scales. Independent t tests were used to determine differences in each dependent variable per group. Results: Patients who underwent ACLR spent less time in MVPA (ACLR: 79.37 ± 23.95 min/d; control: 93.12 ± 23.94 min/d; P = .02) and had a lower daily step count (ACLR: 8158 ± 2780 steps/d; control: 9769 ± 2785 steps/d; P = .02) compared with healthy matched controls. However, the Marx (ACLR median: 11.0 [interquartile range (IQR), 7-14]; control median: 12.0 [IQR, 8-13]; P = .85) and Tegner (ACLR median: 6.0 [IQR, 5-8]; control median: 7.0 [IQR, 6-8]; P = .12) scores did not differ between the groups, and no relationships were observed between objectively measured physical activity and scale measures ( P > .05), except for a moderate relationship between the Tegner score and daily step count in the ACLR group ( r = 0.36, P = .04). Only 24% of patients who underwent ACLR met the guideline of 10,000 steps per day compared with 42% of controls. Conclusion: Patients who underwent ACLR spent less time in MVPA and had a lower daily step count compared with highly matched controls (age, sex, and activity level) with no history of knee injuries. This was true despite being similar in activity levels, which brings into question the utility of the Tegner and Marx activity scales.
High Rate of Osteoarthritis After Osteochondritis Dissecans Fragment Excision Compared With Surgical Restoration at a Mean 16-Year Follow-up
Authors: Sanders Thomas L. , Pareek Ayoosh , Obey Mitchel R. , Johnson Nicholas R. , Carey James L. , Stuart Michael J. , Krych Aaron J. 
Published: April 2017

Background: Osteochondritis dissecans (OCD) is a disorder of subchondral bone that causes adverse effects on the overlying cartilage and commonly affects the knee. The incidence of OCD and its long-term effect on the knee joint are controversial. Hypothesis/Purpose: The purpose of this study was to (1) evaluate the rate of osteoarthritis and knee arthroplasty in a population-based cohort of patients with OCD lesions treated operatively and (2) evaluate factors that may predispose patients to knee osteoarthritis and arthroplasty. The investigators hypothesized that OCD lesions diagnosed after skeletal maturity and treatment with fragment excision would be predictive of a diagnosis of osteoarthritis. Study Design: Cohort study; Level of evidence, 3. Methods: The investigators identified 221 patients (mean ± SD age, 26.1 ± 13.6 years) with OCD lesions treated operatively between 1976 and 2010 and followed for 16.3 ± 11.4 years (mean ± SD) from diagnosis. Information related to the diagnosis, laterality of lesion, details of treatment, and progression to osteoarthritis was obtained from the medical record. Surgical treatment was classified as fragment excision, fragment preservation (lesion drilling and/or fragment fixation), or chondral defect grafting (osteochondral allograft or autograft). Factors predictive of osteoarthritis and arthroplasty were examined. Results: There were 134 patients in the fragment excision group, 78 patients in the fragment preservation group, and 9 patients in the chondral defect grafting group. In the fragment excision group, the cumulative incidence of osteoarthritis was 12.0% at 5 years, 17.0% at 10 years, 26.0% at 15 years, 39.0% at 20 years, and 70% at 30 years. The cumulative incidence of arthroplasty was 2.0% at 5 years, 4.0% at 10 years, 4.0% at 15 years, 10.0% at 20 years, and 32.0% at 30 years. In the fragment preservation group, the cumulative incidence of osteoarthritis was 3.0% at 5 years, 7.0% at 10 years, 16.0% at 15 years, 25.0% at 20 years, and 51% at 30 years. The cumulative incidence of arthroplasty was 0.0% at 5 years, 0.0% at 10 years, 3.0% at 15 years, 6.0% at 20 years, and 11.0% at 30 years. No patients in the chondral defect grafting group developed osteoarthritis or underwent arthroplasty. Body mass index (BMI) greater than 25 kg/m2 (hazard ratio [HR] 3.3; 95% CI, 1.6-7.0), older age at diagnosis (HR 4.9; 95% CI, 1.8-17.3), and fragment excision (HR 2.3; 95% CI, 1.2-4.6) were predictive of osteoarthritis. Conclusion: OCD patients treated with fragment excision have a high rate of osteoarthritis and knee arthroplasty at long-term follow-up. In contrast, patients treated with fragment preservation or chondral defect grafting have lower rates of osteoarthritis and arthroplasty. BMI greater than 25 kg/m2, older age at diagnosis, and fragment excision were predictive of osteoarthritis.