bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage dysfunction in the pathogenesis and treatment of asthma
Authors: Fricker Michael , Gibson Peter G. 
Published: September 2017

Asthma is a chronic respiratory condition frequently associated with aberrant airway and systemic inflammation. Various inflammatory phenotypes in asthmatic airways have been described that relate to clinical phenotypes and impact on responses to conventional and novel asthma therapies. Macrophages are abundant immunocytes in the lung, capable of mounting diverse responses required for homeostasis and defence against pathogens.Here, we summarise the clinical evidence regarding macrophage dysfunction in asthma. We also describe evidence supporting the role of macrophages as therapeutic targets in asthma. We conclude that macrophage dysfunction in asthma is highly prevalent and heterogeneous, and hypothesise that macrophages may play roles in promoting the discrete inflammatory phenotypes of asthma.These clinical findings, along with recent ground-breaking insights into the ontogeny, behavioural complexity and longevity of pulmonary macrophages, support continued research into the role of macrophages as disease modifiers, biomarkers and therapeutic targets in asthma.
Treating breathlessnessviathe brain: changes in brain activity over a course of pulmonary rehabilitation
Authors: Herigstad Mari , Faull Olivia K. , Hayen Anja , Evans Eleanor , Hardinge F. Maxine , Wiech Katja , Pattinson Kyle T.S. 
Published: September 2017

Breathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (“over-perception”). Pulmonary rehabilitation profoundly affects breathlessness, without influencing lung function. Learned associations influence brain mechanisms of sensory perception. We hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations.In 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during a breathlessness-related word-cue task (using functional magnetic resonance imaging), and clinical and psychological measures of breathlessness.Changes in ratings of breathlessness word cues positively correlated with changes in activity in the insula and anterior cingulate cortex. Changes in ratings of breathlessness-anxiety negatively correlated with activations in attention regulation and motor networks. Baseline activity in the insula, anterior cingulate cortex and prefrontal cortex correlated with improvements in breathlessness and breathlessness-anxiety.Pulmonary rehabilitation is associated with altered neural responses related to learned breathlessness associations, which can ultimately influence breathlessness perception. These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.
Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma
Authors: Motzer Robert J. , Haas Naomi B. , Donskov Frede , Gross-Goupil Marine , Varlamov Sergei , Kopyltsov Evgeny , Lee Jae Lyun , Melichar Bohuslav , Rini Brian I. , Choueiri Toni K. , Zemanova Milada , Wood Lori A. , Reaume M. Neil , Stenzl Arnulf , Chowdhury Simon , Lim Ho Yeong , McDermott Ray , Michael Agnieszka , Bao Weichao , Carrasco-Alfonso Marlene J. , Aimone Paola , Voi Maurizio , Doehn Christian , Russo Paul , Sternberg Cora N. ,   on behalf of the PROTECT investigators
Published: September 2017

Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-to-treat (ITT) pazopanib 600 mg group (ITT600mg), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT800mg) and safety. Results The primary analysis results of DFS ITT600mg favored pazopanib but did not show a significant improvement over placebo (hazard ratio [HR], 0.86; 95% CI, 0.70 to 1.06; P = .165). The secondary analysis of DFS in ITT800mg (n = 403) yielded an HR of 0.69 (95% CI, 0.51 to 0.94). Follow-up analysis in ITT600mg yielded an HR of 0.94 (95% CI, 0.77 to 1.14). Increased ALT and AST were common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT, 16%; AST, 5%) and 800 mg (ALT, 18%; AST, 7%) groups. Conclusion The results of the primary DFS analysis of pazopanib 600 mg showed no benefit over placebo in the adjuvant setting.
Estrogen Activation by Steroid Sulfatase Increases Colorectal Cancer Proliferation via GPER
Authors: Gilligan Lorna C , Rahman Habibur P , Hewitt Anne-Marie , Sitch Alice J , Gondal Ali , Arvaniti Anastasia , Taylor Angela E , Read Martin L , Morton Dion G , Foster Paul A 
Published: September 2017

Abstract

Context
Estrogens affect the incidence and progression of colorectal cancer (CRC), although the precise molecular mechanisms remain ill-defined.

Objective
The present study investigated prereceptor estrogen metabolism through steroid sulphatase (STS) and 17β-hydroxysteroid dehydrogenase activity and subsequent nongenomic estrogen signaling in human CRC tissue, in The Cancer Genome Atlas colon adenocarcinoma data set, and in in vitro and in vivo CRC models. We aimed to define and therapeutically target pathways through which estrogens alter CRC proliferation and progression.

Design, Setting, Patients, and Interventions
Human CRC samples with normal tissue-matched controls were collected from postmenopausal female and age-matched male patients. Estrogen metabolism enzymes and nongenomic downstream signaling pathways were determined. CRC cell lines were transfected with STS and cultured for in vitro and in vivo analysis. Estrogen metabolism was determined using an ultra-performance liquid chromatography–tandem mass spectrometry method.

Primary Outcome Measure
The proliferative effects of estrogen metabolism were evaluated using 5-bromo-2′-deoxyuridine assays and CRC mouse xenograft studies.

Results
Human CRC exhibits dysregulated estrogen metabolism, favoring estradiol synthesis. The activity of STS, the fundamental enzyme that activates conjugated estrogens, is significantly (P &lt; 0.001) elevated in human CRC compared with matched controls. STS overexpression accelerates CRC proliferation in in vitro and in vivo models, with STS inhibition an effective treatment. We defined a G-protein–coupled estrogen receptor (GPER) proproliferative pathway potentially through increased expression of connective tissue growth factor in CRC.

Conclusion
Human CRC favors estradiol synthesis to augment proliferation via GPER stimulation. Further research is required regarding whether estrogen replacement therapy should be used with caution in patients at high risk of developing CRC.
Effect of an Intravenous Dexamethasone Added to Caudal Local Anesthetics to Improve Postoperative Pain: A Systematic Review and Meta-analysis With Trial Sequential Analysis
Authors: Kawakami Hiromasa , Mihara Takahiro , Nakamura Nobuhito , Ka Koui , Goto Takahisa 
Published: September 2017

BACKGROUND:
Caudal anesthesia has been used for postoperative pain control in pediatric surgical patients, but the duration of the analgesic effect is occasionally unsatisfactory. Intravenous steroids have been shown to be effective for postsurgical pain management after certain surgeries. The aim of this meta-analysis with trial sequential analysis (TSA) was to evaluate the analgesic effect of steroids in patients administered with caudal anesthesia.

METHODS:
This study was a systematic review and meta-analysis. A search of published literature was conducted in the MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases and in trial registration sites. Randomized controlled trials that compared intravenous steroids with a placebo in pediatric patients who had received caudal anesthesia for surgery were included in the study. The primary outcomes from the present meta-analysis were the analgesic duration and the number of patients who required rescue analgesics. The analgesic duration and incidence of rescue use were summarized using mean difference or risk ratio with a 97.5% confidence interval (CI), respectively. If the 97.5% CI of the mean difference or risk ratio included a value of 0 or 1, respectively, we considered the difference not to be significant. We used the random effects model to combine the results. Heterogeneity was quantified with the I
2 statistic. The quality of the trials was evaluated using the Cochrane methodology. Moreover, a TSA with a risk of type 1 error of 2.5% and power of 90% was performed. We established the minimum clinically meaningful difference of analgesic duration as 3 hours. The target sample size for meta-analysis was also calculated in the TSA. We also assessed adverse events.

RESULTS:
Six trials with 424 patients were included; 211 patients received intravenous steroids. All trials compared dexamethasone of at least 0.5 mg/kg dose with a placebo. Dexamethasone prolonged the duration of caudal analgesia (mean difference, 244 minutes; 97.5% CI, 188–300). Heterogeneity was considerable with an I
2 value of 94.8%. Quality of evidence was very low. The TSA suggested that only 17.0% of the target sample size had been reached, but the cumulative Z score crossed the trial sequential monitoring boundary to indicate a benefit. Rescue use was reported in 4 studies with 260 patients. Rescue use was not significantly reduced in the dexamethasone group (risk ratio, 0.53; 97.5% CI, 0.09–3.30; I
2, 98.7%). No increase in adverse events was reported.

CONCLUSIONS:
Intravenous dexamethasone prolongs the analgesic duration of caudal anesthesia. Trials to investigate the effectiveness of a lower dose of the dexamethasone in prolonging analgesic effects would be of interest. Further trials with a low risk of bias are necessary.
Common Ice Hockey Injuries and Treatment: A Current Concepts Review
Authors: Mosenthal William , Kim Michael , Holzshu Robert , Hanypsiak Bryan , Athiviraham Aravind 
Published: September 2017

Abstract
Injuries are common in ice hockey, a contact sport where players skate at high speeds on a sheet of ice and shoot a vulcanized rubber puck in excess of one hundred miles per hour. This article reviews the diagnoses and treatment of concussions, injuries to the cervical spine, and lower and upper extremities as they pertain to hockey players. Soft tissue injury of the shoulder, acromioclavicular joint separation, glenohumeral joint dislocation, clavicle fractures, metacarpal fractures, and olecranon bursitis are discussed in the upper-extremity section of the article. Lower-extremity injuries reviewed in this article include adductor strain, athletic pubalgia, femoroacetabular impingement, sports hernia, medial collateral and anterior cruciate ligament tears, skate bite, and ankle sprains. This review is intended to aid the sports medicine physician in providing optimal sports-specific care to allow their athlete to return to their preinjury level of performance.
Sacroiliac Joint Dysfunction in the Athlete: Diagnosis and Management
Authors: Peebles Rebecca , Jonas Christopher E. 
Published: September 2017

Abstract
Sacroiliac joint (SIJ) dysfunction is a common cause of low back pain in the athlete, especially in sports with repetitive, asymmetric loading. Complex anatomy and broad pain referral pattern make diagnosis difficult. Identifying three or more positive physical examination maneuvers for the SIJ improves examination sensitivity and specificity. Imaging is rarely helpful in establishing the diagnosis but is often used to rule out other pathology. Conservative management with activity modification, medication, physical therapy, manipulation and bracing is first line treatment. After at least 6 weeks of conservative efforts or if pain limits the athlete’s tolerance of these measures, diagnostic and therapeutic intra-articular or periarticular injections or nerve blocks can be used. Radiofrequency ablation is recommended as the next approach for treatment. When all other options have been exhausted, surgical management can be considered. For athletes, once the underlying dysfunction is adequately addressed, gradual progression to full participation is encouraged.
A Randomized Controlled Trial of a CPR Decision Support Video for Patients Admitted to the General Medicine Service
Authors: Merino Aimee M. , Greiner Ryan , Hartwig Kristopher 
Published: September 2017

BACKGROUNDPatient preferences regarding cardiopulmonary resuscitation (CPR) are important, especially during hospitalization when a patient's health is changing. Yet many patients are not adequately informed or involved in the decision‐making process.OBJECTIVESWe examined the effect of an informational video about CPR on hospitalized patients' code status choices.DESIGNThis was a prospective, randomized trial conducted at the Minneapolis Veterans Affairs Health Care System in Minnesota.PARTICIPANTSWe enrolled 119 patients, hospitalized on the general medicine service, and at least 65 years old. The majority were men (97%) with a mean age of 75.INTERVENTIONA video described code status choices: full code (CPR and intubation if required), do not resuscitate (DNR), and do not resuscitate/do not intubate (DNR/DNI). Participants were randomized to watch the video (n = 59) or usual care (n = 60).MEASUREMENTSThe primary outcome was participants' code status preferences. Secondary outcomes included a questionnaire designed to evaluate participants' trust in their healthcare team and knowledge and perceptions about CPR.RESULTSParticipants who viewed the video were less likely to choose full code (37%) compared to participants in the usual care group (71%) and more likely to choose DNR/DNI (56% in the video group vs. 17% in the control group) (P < 0.00001). We did not see a difference in trust in their healthcare team or knowledge and perceptions about CPR as assessed by our questionnaire.CONCLUSIONSHospitalized patients who watched a video about CPR and code status choices were less likely to choose full code and more likely to choose DNR/DNI.
Influenza Season Hospitalization Trends in Israel: A Multi‐Year Comparative Analysis 2005/2006 Through 2012/2013
Authors: Glatman‐Freedman Aharona , Kaufman Zalman , Stein Yaniv , Sefty Hanna , Zadka Hila , Gordon Barak , Meron Jill , Gordon Ethel‐Sherry , Dichtiar Rita , Haklai Ziona , Afek Arnon , Shohat Tamy 
Published: September 2017

BACKGROUNDInfluenza‐related morbidity impacts healthcare systems, including hospitals.OBJECTIVETo obtain a quantitative assessment of hospitalization burden in pediatric and internal medicine departments during influenza seasons compared with the summer months in Israel.METHODSData on pediatric and internal medicine hospitalized patients in general hospitals in Israel during the influenza seasons between 2005 and 2013 were analyzed for rate of hospitalizations, rate of hospitalization days, hospital length of stay (LOS), and bed occupancy and compared with the summer months. Data were analyzed for hospitalizations for all diagnoses, diagnoses of respiratory or cardiovascular disease (ICD9 390‐519), and influenza or pneumonia (ICD9 480‐487), with data stratified by age. The 2009‐2010 pandemic influenza season was excluded.RESULTSRates of monthly hospitalizations and hospitalization days for all diagnoses were 4.8% and 8% higher, respectively, during influenza seasons as compared with the summers. The mean LOS per hospitalization for all diagnoses demonstrated a small increase during influenza seasons as compared with summer seasons. The excess hospitalizations and hospitalization days were especially noticed for the age groups under 1 year, 1‐4 years, and 85 years and older. The differences were severalfold higher for patients with a diagnosis of respiratory or cardiovascular disease and influenza or pneumonia. Bed occupancy was higher during influenza seasons compared with the summer, particularly in pediatric departments.CONCLUSIONSHospital burden in pediatric and internal medicine departments during influenza seasons in Israel was associated with age and diagnosis. These results are important for optimal preparedness for influenza seasons.
Does Offline TV Advertising Affect Online Chatter? Quasi-Experimental Analysis Using Synthetic Control
Authors: Tirunillai Seshadri , Tellis Gerard J. 
Published: September 2017

This study analyzes the impact of offline television advertising on multiple metrics of online chatter or user-generated content. The context is a quasi experiment in which a focal brand undertakes a massive advertising campaign for a short period of time. The authors estimate multiple dimensions of chatter (popularity, negativity, visibility, and virality) from numerous raw metrics using the content and the hyperlink structure of consumer reviews and blogs. The authors use the method of synthetic control to construct a counterfactual (synthetic) brand as a convex combination of the rivals during the preadvertising period. The gap in the dimensions of chatter between the focal brand and the synthetic brand in the test versus advertising periods assesses the influence of advertising. Offline television advertising causes a short but significant positive effect on online chatter. This effect is stronger on information-spread dimensions (visibility and virality) than on content-based dimensions (popularity and negativity). Importantly, advertising has a small short-term effect in decreasing negativity in online chatter. Data and the online appendix are available at https://doi.org/10.1287/mksc.2017.1040
Can Trustworthiness in a Supply Chain Be Signaled?
Authors: Beer Ruth , Ahn Hyun-Soo , Leider Stephen 
Published: September 2017

The relationship between a buyer and its suppliers often relies on factors beyond the terms of a contractual agreement. Buyers can therefore benefit from identifying trustworthy suppliers. We argue that precontractual actions by a supplier, for example making costly buyer-specific investments without a long-term contract, can signal a supplier’s trustworthiness. We develop a theoretical model to reflect supplier trustworthiness, and determine when a buyer can benefit from identifying trustworthy suppliers. We show that costly relationship-specific investments can serve as a signal of trustworthiness, and that supply chain profits increase when trustworthy suppliers are able to identify themselves in this fashion. We demonstrate the importance of the signaling mechanism using laboratory experiments. The experimental results show that relationship-specific investments lead to more collaborative transactions, with buyers offering higher prices and suppliers returning higher-quality products. This results in increased profits for both buyers and suppliers. Additionally, we design a treatment which shuts down the signaling mechanism and show that the benefits of the buyer-specific investment are no longer present in this case. Finally, we show that the benefits of buyer-specific investments for both suppliers and buyers are strengthened when firms interact repeatedly. Data and the online appendix are available at https://doi.org/10.1287/mnsc.2017.2817 . This paper was accepted by Yossi Aviv, operations management.
Improving calf-side diagnosis of respiratory disease on UK dairy farms
Authors: Glover Ian D 
Published: September 2017

Bovine respiratory disease complex (BRD) is a common and costly disease on UK dairy farms. Sensitivity and specificity of BRD diagnosis on some UK dairy farms is suboptimal, leading to lack of treatment of affected calves and sometimes inappropriate treatment of healthy calves.Various options are available for calf-side diagnosis of BRD. Unstructured observation of clinical signs is subjective and suffers from poor sensitivity and specificity. Clinical scoring systems such as the Wisconsin Calf Health Score and the California Calf Health Score offer an improvement in terms of diagnostic accuracy and repeatability. Thoracic ultrasonography is available through use of linear ultrasound units commonly carried by farm practitioners, and constitutes a simple, rapid, accurate and repeatable diagnostic test for BRD. Various systems for remote monitoring of body temperature are available, and allow early detection of BRD when used in combination with other diagnostic tests.
A simple method of measuring the wear of explanted acetabular component inserts
Authors: Krakow L. , Klockow A. , Roehner E. , Brodt S. , Eijer H. , Bossert J. , Matziolis G. 
Published: September 2017

Objectives The determination of the volumetric polyethylene wear on explanted material requires complicated equipment, which is not available in many research institutions. Our aim in this study was to present and validate a method that only requires a set of polyetheretherketone balls and a laboratory balance to determine wear. Methods The insert to be measured was placed on a balance, and a ball of the appropriate diameter was inserted. The cavity remaining between the ball and insert caused by wear was filled with contrast medium and the weight of the contrast medium was recorded. The volume was calculated from the known density of the liquid. The precision, inter- and intraobserver reliability, were determined by four investigators on four days using nine inserts with specified wear (0.094 ml to 1.626 ml), and the intra-class correlation coefficient was calculated. The feasibility of using this method in routine clinical practice and the time required for measurement were tested on 84 explanted inserts by one investigator. Results In order to get the mean for all investigators and determinations, the deviation between the measured and specified wear was -0.08 ml (sd 0.12; -0.21 to 0.11). The interobserver reliability was 0.989 ml (95% confidence interval (CI) 0.964 to 0.997) and the intraobserver reliability was 0.941 for observer 1 (95% CI 0.846 to 0.985), 0.983 for observer 2 (95% CI 0.956 to 0.995), 0.939 for observer 3 (95% CI 0.855 to 0.984), and 0.934 for observer 4 (95% CI 0.790 to 0.984). The mean time required to examine the samples was two minutes (sd 2; 1 to 5). Conclusion The method presented here was shown to be sufficiently precise for many settings and is a cost-effective and quick method of determining the volumetric wear of explanted acetabular components. However, the measurement of wear for scientific purposes will probably continue to involve more accurate and dedicated laboratory equipment. Cite this article: Bone Joint Res 2017;6:530–534.