bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low copy numbers of complement C4 and homozygous deficiency of C4A may predispose to severe disease and earlier disease onset in patients with systemic lupus erythematosus
Authors: Jüptner M , Flachsbart F , Caliebe A , Lieb W , Schreiber S , Zeuner R , Franke A , Schröder J O 
Published: October 2017

Objectives Low copy numbers and deletion of complement C4 genes are potent risk factors for systemic lupus erythematosus (SLE). However, it is not known whether this genetic association affects the clinical outcome. We investigated C4 copy number variation and its relationship to clinical and serological features in a Northern European lupus cohort. Methods We genotyped the C4 gene locus using polymerase chain reaction (PCR)-based TaqMan assays in 169 patients with SLE classified according to the 1997 revised American College of Rheumatology (ACR) criteria and in 520 matched controls. In the patient group the mean C4 serum protein concentrations nephelometrically measured during a 12-month period prior to genetic analysis were compared to C4 gene copy numbers. Severity of disease was classified according to the intensity of the immunosuppressive regimens applied and compared to C4 gene copy numbers, too. In addition, we performed a TaqMan based analysis of three lupus-associated single-nucleotide polymorphisms (SNPs) located inside the major histocompatibility complex (MHC) to investigate the independence of complement C4 in association with SLE. Results Homozygous deficiency of the C4A isotype was identified as the strongest risk factor for SLE (odds ratio (OR) = 5.329; p = 7.7 × 10−3) in the case-control comparison. Moreover, two copies of total C4 were associated with SLE (OR = 3.699; p = 6.8 × 10−3). C4 serum levels were strongly related to C4 gene copy numbers in patients, the mean concentration ranging from 0.110 g/l (two copies) to 0.256 g/l (five to six copies; p = 4.9 × 10−6). Two copies of total C4 and homozygous deletion of C4A were associated with a disease course requiring cyclophosphamide therapy (OR = 4.044; p = 0.040 and OR = 5.798; p = 0.034, respectively). Homozygous deletion of C4A was associated with earlier onset of SLE (median 24 vs. 34 years; p = 0.019) but not significant after correction for multiple testing. SNP analysis revealed a significant association of HLA-DRB1*0301 with SLE (OR = 2.231; p = 1.33 × 10−5). Conclusions Our findings confirm the important role of complement C4 genes in the development of SLE. Beyond the impact on the susceptibility for lupus, C4 copy numbers may be related to earlier onset and a more severe course of the disease. The association of homozygous deletion of C4A and SLE is accompanied by the presence of HLA-DRB1*0301 without a proven pathophysiological mechanism.
Prevalence of Dementia in a Geriatric Palliative Care Unit
Authors: Lo Amanda T. , Karuza Jurgis , Berall Anna , Perri Giulia-Anna 
Published: October 2017

Objectives: To determine the prevalence of dementia in a palliative care unit (PCU) and to determine whether there is a difference between length of stay (LOS) and Palliative Performance Scale (PPS) score in individuals admitted with a primary diagnosis of dementia compared to individuals admitted with other noncancer and cancer diagnoses. Design: Descriptive retrospective chart review. Setting: Geriatric PCU in an academic community geriatric hospital. Participants: All individuals admitted to the Baycrest Health Sciences PCU from January 1, 2014, to September 1, 2016. Measurements: Individuals with an admission diagnosis of cancer, noncancer, and dementia and their corresponding PPS scores were identified. Data were analyzed using descriptive statistics. Results: A total of 780 patients were admitted to the PCU during the study period: 32 (4.1%) individuals had advanced dementia, 121 (15.5%) had a noncancer diagnosis, and 627 (80.4%) had cancer as the primary reason for admission. In the cancer and noncancer groups, 113 patients had a comorbid dementia diagnosis. The mean admission PPS score in patients with cancer was 36%, noncancer was 32.6%, and dementia was 23.8% ( P < .001). Mean LOS in patients with cancer was 32 days, noncancer patients was 34.3 days, and patients with advanced dementia was 33.3 days ( P = .90). Conclusions: Individuals with an admission diagnosis of advanced dementia had a lower mean PPS score than individuals admitted with other noncancer and cancer diagnoses. There was no difference in the mean LOS between the 3 groups. Individuals with an admission diagnosis of advanced dementia should not be refused admission because of fear of outliving their prognosis.
Evaluation of the head and neck cancer patient population and the incidence of hospitalization at an academic medical center
Authors: Hazelden Lindsay A , Newman Matthew J , Shuey Stephanie , Waldfogel Julie M , Brown Victoria T 
Published: October 2017

Purpose Patients with head and neck cancer are at risk for disease- and treatment-related toxicities that may be severe enough to require hospitalization. The risk factors associated with hospitalization in these patients are not well defined. Methods We conducted a single-center, retrospective observational study of patients with head and neck cancer receiving chemotherapy at an academic medical center infusion clinic in a one-year period. The primary objective was to characterize the head and neck cancer population at an academic medical center. Secondary objectives included describing the clinical and social factors associated with hospitalization. Results There were 109 patients with head and neck cancer included in the analysis. Of these patients, 38 (35%) were hospitalized. The factors that were significantly associated with hospitalization on univariable logistic regression were former alcohol abuse, being on a nonstandard of care chemotherapy regimen, and having a chemotherapy agent discontinued. On multivariable logistic regression, the factor that was significantly associated with hospitalization was having a chemotherapy agent discontinued. The most common reasons for hospitalization included shortness of breath/respiratory failure, fever/neutropenic fever, and infection. The most common new supportive care medications prescribed at discharge were stool softeners or laxatives and opioids. Conclusion This study identified several factors which may be useful to identify patients as high risk for hospitalization and the next steps will be to determine and study the role of the pharmacist in preventing hospitalization of these patients. Further studies are needed to assess the impact of adding a pharmacist to the head and neck cancer multidisciplinary team.
High overall cardiovascular risk and mortality in patients with atrial fibrillation and diabetes: A nationwide report
Authors: Karayiannides Stelios , Lundman Pia , Friberg Leif , Norhammar Anna 
Published: October 2017

Aim: To describe nationwide complication patterns in patients with atrial fibrillation and diabetes mellitus. Methods: All ( n = 326,832) patients in Sweden with non-valvular atrial fibrillation during 2006–2012 were identified, and information on events, comorbidities and pharmacological therapy was extracted using nationwide mandatory registers. Patients were followed until 31 December 2013 and the mean follow-up time was 3.7 years (0.9–8 years). Results: Diabetes was present in 17.7%. The most frequent events in those with and without diabetes were mortality (48.8% vs 36.4%; p < 0.001), heart failure (21.4% vs 13.1%; p < 0.001), ischaemic stroke (8.2% vs 6.8%; p < 0.001), myocardial infarction (7.3% vs 4.3%; p < 0.001) and any bleeding (6.3% vs 5.2%; p < 0.001), respectively. Diabetes predicted mortality (hazard ratio = 1.28; 95% confidence interval = 1.25–1.31), combined event (first of mortality, heart failure, ischaemic stroke or myocardial infarction; hazard ratio = 1.22; 95% confidence interval = 1.20–1.25), single events and bleeding (hazard ratio = 1.12; 95% confidence interval = 1.06–1.19). The standardised mortality ratio for patients with atrial fibrillation and diabetes compared to the general population was 2.06 (95% confidence interval = 2.00–2.12) and for patients with atrial fibrillation without diabetes was 1.33 (95% confidence interval = 1.31–1.35). Conclusion: In this real-world setting, patients with atrial fibrillation and diabetes have a high cardiovascular risk, with mortality and heart failure rates exceeding those for stroke.
Assessing the Training Effectiveness of an Intelligent Tutoring System for Marksmanship Skills
Authors: Zotov Vlad , Jarmasz Jerzy , Ueno Ken , Kramkowski Eric 
Published: October 2017

The development of embedded trainers and intelligent tutoring systems (ITS) may allow modern militaries to maintain high proficiency in marksmanship skills despite limitations on training personnel and resources. A system embedding an ITS in a future rifle concept was developed to examine the potential of such technologies. This system was based on two main concepts: 1) instance-based learning and practice that uses a Smart Sight System to present a perceptual cue adjusted for the target’s properties and environmental variables and 2) rule-based learning that relies on artificial intelligence algorithm that delivers training tips and feedback to participants. The experimental task involved engaging moving targets on a virtual shooting range. Three types of training were compared: a control group that received no additional training, a standard Canadian Armed Forces (CAF) training group, and an advanced training group that received ITS training. The results showed that additional training—both CAF and ITS—improved shooting accuracy. The performance in the ITS condition was consistently better than in the Control group or in the CAF training group on selected measures of performance.
Familial Consent for Deceased Organ Donation Among Immigrants and Long-term Residents in Ontario, Canada: A Population-Based Retrospective Cohort Study
Authors: Li Alvin Ho-ting , Al-Jaishi Ahmed A. , Weir Matthew , Lam Ngan N. , Maclean Janet , Dhanani Sonny , Kim S. Joseph , Knoll Greg , Garg Amit X. 
Published: October 2017

Background: Many families choose not to consent to organ donation at the time of their loved one’s death. In Ontario, Canada, whether these decisions vary by ethnicity remains unclear. Objective: To compare the proportion of families of immigrants who consented for deceased organ donation with families of long-term residents. Design: Population-based retrospective cohort study. Setting: Potential donors in Ontario, Canada, between November 2008 and March 2013. Methods: We used linked administrative databases to study the proportion of families who consented for deceased organ donation. Results: Overall, of the 2873 families of potential donors approached, 1912 (67%) provided consent for deceased organ donation. Families of immigrants were less likely to provide consent compared with families of long-term residents (46% [135 of 291] vs 69% [1777 of 2582]; adjusted rate ratio (RR): 0.72; 95% confidence interval [CI]: 0.63-0.81). When examined by the country of birth, families of immigrants from the following regions were less likely to consent to organ donation compared with long-term residents: South Asia (RR: 0.71; 95% CI: 0.55-0.91), East Asia and Pacific (RR: 0.68; 95% CI: 0.53-0.88) and Middle East, North Africa, and sub-Saharan Africa (RR: 0.58; 95% CI: 0.37-0.91). Limitations: We could not determine why consent was not obtained. We had a small sample of immigrants. We only had access to the potential donors’ information and not the family member who was approached for consent. Many characteristics that we examined were nonmodifiable (eg, age, sex). Conclusions: In Ontario, families of immigrants are less likely to consent to deceased organ donation. There is an opportunity to better understand the reasons for lower consent among certain immigrant groups.
Can a Drill Guide Improve the Coracoid Graft Placement During the Latarjet Procedure? A Prospective Comparative Study With the Freehand Technique
Authors: Barth Johannes , Boutsiadis Achilleas , Neyton Lionel , Lafosse Laurent , Walch Gilles 
Published: October 2017

Background: One of the factors that can affect the success of the Latarjet procedure is accurate coracoid graft (CG) placement. Hypothesis: The use of a guide can improve placement of the CG and screw positioning in the sagittal and axial planes as compared with the classic open (“freehand”) technique. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 49 patients who underwent a Latarjet procedure for the treatment of recurrent anterior shoulder instability were prospectively included; the procedure was performed with the freehand technique in 22 patients (group 1) and with use of a parallel drill guide during screw placement in 27 patients (group 2). All patients underwent a postoperative computed tomography scan with the same established protocol. The scans were used to evaluate and compare the position of the CG in the sagittal and axial planes, the direction of the screws (α angle), and overall contact of the graft with the anterior surface of the glenoid after the 2 surgical techniques. Results: The CG was placed >60% below the native glenoid equator in 23 patients (85.2%) in group 2, compared with 14 patients (63.6%) in group 1 ( P = .004). In the axial plane, the position of the CG in group 2 patients was more accurate (85.2% and 88.9% flush) at the inferior and middle quartiles of the glenoid surface ( P = .012 and .009), respectively. Moreover, with the freehand technique (group 1), the graft was in a more lateral position in the inferior and middle quartiles ( P = .012 and .009, respectively). No differences were found between groups 1 and 2 regarding the mean α angle of the superior (9° ± 4.14° vs 11° ± 6.3°, P = .232) and inferior (9.5° ± 6° vs 10° ± 7.5°, P = .629) screws. However, the mean contact angle (angle between the posterior coracoid and the anterior glenoid surface) with the freehand technique (3.8° ± 6.8°) was better than that of the guide (8.55° ± 8°) ( P = .05). Conclusion: Compared with the classic freehand operative technique, the parallel drill guide can ensure more accurate placement of the CG in the axial and sagittal planes, although with inferior bone contact.
What is precision medicine?
Authors: König Inke R. , Fuchs Oliver , Hansen Gesine , von Mutius Erika , Kopp Matthias V. 
Published: October 2017

The term “precision medicine” has become very popular over recent years, fuelled by scientific as well as political perspectives. Despite its popularity, its exact meaning, and how it is different from other popular terms such as “stratified medicine”, “targeted therapy” or “deep phenotyping” remains unclear. Commonly applied definitions focus on the stratification of patients, sometimes referred to as a novel taxonomy, and this is derived using large-scale data including clinical, lifestyle, genetic and further biomarker information, thus going beyond the classical “signs-and-symptoms” approach.While these aspects are relevant, this description leaves open a number of questions. For example, when does precision medicine begin? In which way does the stratification of patients translate into better healthcare? And can precision medicine be viewed as the end-point of a novel stratification of patients, as implied, or is it rather a greater whole?To clarify this, the aim of this paper is to provide a more comprehensive definition that focuses on precision medicine as a process. It will be shown that this proposed framework incorporates the derivation of novel taxonomies and their role in healthcare as part of the cycle, but also covers related terms.
Effect of morphine on breathlessness and exercise endurance in advanced COPD: a randomised crossover trial
Authors: Abdallah Sara J. , Wilkinson-Maitland Courtney , Saad Nathalie , Li Pei Zhi , Smith Benjamin M. , Bourbeau Jean , Jensen Dennis 
Published: October 2017

The objective of the present study was to evaluate the effect of morphine on exertional breathlessness and exercise endurance in advanced chronic obstructive pulmonary disease (COPD).In a randomised crossover trial, we compared the acute effect of immediate-release oral morphineversusplacebo on physiological and perceptual responses during constant-load cardiopulmonary cycle exercise testing (CPET) in 20 adults with advanced COPD and chronic breathlessness syndrome.Compared with placebo, morphine reduced exertional breathlessness at isotime by 1.2±0.4 Borg units and increased exercise endurance time by 2.5±0.9 min (both p≤0.014). During exercise at isotime, morphine decreased ventilation by 1.3±0.5 L·min−1and breathing frequency by 2.0±0.9 breaths·min−1(both p≤0.041). Compared with placebo, morphine decreased exertional breathlessness at isotime by ≥1 Borg unit in 11 participants (responders) and by <1 Borg unit in nine participants (non-responders). Baseline participant characteristics, including pulmonary function and cardiorespiratory fitness, were similar between responders and non-responders. A higher percentage of respondersversusnon-responders stopped incremental CPET due to intolerable breathlessness: 82versus33% (p=0.028).Immediate-release oral morphine improved exertional breathlessness and exercise endurance in some, but not all, adults with advanced COPD. The locus of symptom-limitation on laboratory-based CPET may help to identify patients most likely to benefit from morphine.
Constitutive activity of the Ghrelin receptor reduces surface expression of voltage-gated Ca2+ channels in a CaVβ-dependent manner
Authors: Mustafá Emilio R. , López Soto Eduardo J. , Martínez Damonte Valentina , Rodríguez Silvia S. , Lipscombe Diane , Raingo Jesica 
Published: October 2017

ABSTRACT
Voltage-gated Ca2+ (CaV) channels couple membrane depolarization to Ca2+ influx, triggering a range of Ca2+-dependent cellular processes. CaV channels are, therefore, crucial in shaping neuronal activity and function, depending on their individual temporal and spatial properties. Furthermore, many neurotransmitters and drugs that act through G protein coupled receptors (GPCRs), modulate neuronal activity by altering the expression, trafficking, or function of CaV channels. GPCR-dependent mechanisms that downregulate CaV channel expression levels are observed in many neurons but are, by comparison, less studied. Here we show that the growth hormone secretagogue receptor type 1a (GHSR), a GPCR, can inhibit the forwarding trafficking of several CaV subtypes, even in the absence of agonist. This constitutive form of GPCR inhibition of CaV channels depends on the presence of a CaVβ subunit. CaVβ subunits displace CaVα1 subunits from the endoplasmic reticulum. The actions of GHSR on CaV channels trafficking suggest a role for this signaling pathway in brain areas that control food intake, reward, and learning and memory.
The evidence on effectiveness of weekly vs triweekly cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC): a systematic review and meta-analysis
Authors: Jacinto JC Kennetth , Co Jayson , Mejia Michael Benedict , Regala Eugenio Emmanuel 
Published: October 2017

Objective:
This study aims to synthesize the current available evidences on the effectiveness of weekly vs triweekly cisplatin concurrent with radiotherapy in the primary and adjuvant treatment of locally advanced head and neck squamous cell carcinoma (HNSCC).

Methods:
A systematic review and meta-analysis of literature were undertaken to assess the effectiveness of weekly vs triweekly schedule in primary and adjuvant treatment for HNSCC with adverse risk features. Search of relevant articles from electronic database from 2000 to March 2016 and appraisal of studies were done.

Results:
Only one randomized controlled trial (RCT) and six retrospective studies were included in this review. The RCT showed less severe mucositis (75 vs 38.5%, p = 0.012) and more patients receiving at least 200 mg/m2 (62.5% vs 88.5%, p = 0.047) of cisplatin in triweekly arm. There was no difference in 1-year progression-free survival (60% vs 71.1%, p = 0.806) and 1-year overall survival (OS) (71.6 vs 79.3%, p = 0.978) between the weekly and triweekly arm. Pooling of data from six studies showed no difference in 5-year progression-free survival (RR 0.84, 95%, CI 0.67–1.07), 5-year OS (RR 0.88, 95% CI 0.73–1.07), severe renal events (RR 0.66, 95% CI 0.42–1.04), severe mucositis (RR 0.92, 95% CI 0.71–1.21), severe dermatitis (RR 0.61, 95% CI 0.37–1.03), treatment interruptions (RR 1.06, 95% CI 0.74–1.52) and number of patients receiving at least 200 mg/m2 (RR 0.83, 95% CI 0.67–1.03).

Conclusion:
The current evidence showed that weekly schedule is not superior to triweekly in improving oncological outcomes and decreasing early effects of treatment. In the absence of compelling data, triweekly schedule should remain the standard of care while more RCTs are warranted.

Advances in knowledge:
While some have proposed that low-dose weekly cisplatin is safer and less toxic, this study emphasized that there is no difference in acute toxicity of the two schedules and it is safe to utilize high-dose cisplatin every 3 weeks to reach the threshold dose of 200 mg/m2 faster. Uniquely, this study excluded nasopharyngeal cancer patients as the biology and treatment response are different with other HNSCC.
Learning Effects of Domain, Technology, and Customer Knowledge in Information Systems Development: An Empirical Study
Authors: Kang Keumseok , Hahn Jungpil , De Prabuddha 
Published: October 2017

This study examines learning effects (i.e., the effects of prior experience) in information systems development (ISD). ISD is characterized by disparate tasks, teams, and levels of project complexity across projects. These features challenge our understanding of how learning effects occur in the ISD context. Drawing on the theory of transfer of learning, this study examines how ISD project teams learn and under what conditions the learning effects are stronger or weaker. We find that ISD project teams’ experience in prior projects translates into performance gains for the current ISD project when the prior and current projects share the same domain, technology, or customer knowledge elements—domain, technology, and customer being the most essential knowledge types for ISD. Moreover, we find that the learning effects of domain, technology, and customer knowledge are substitutive for one another and that these learning effects become stronger or weaker depending on the extent of ISD projects’ team and task complexities. The study makes significant contributions to the ISD literature on learning effects and the roles of domain, technology, customer knowledge, and project complexity, as well as to the general organizational learning literature. It also provides important managerial insights into practical concerns such as project staffing and knowledge acquisition for ISD organizations. The online appendix is available at https://doi.org/10.1287/isre.2017.0713 .