bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacist Outpatient Prescription Review in the Emergency Department
Authors: Shah Dhara , Manzi Shannon 
Published: October 2016

Objectives
This study aimed to assess the frequency, type, and potential severity of errors intercepted by pharmacists on review of discharge prescriptions in a pediatric emergency department (ED).

Methods
This was a retrospective, observational study conducted in the ED of a pediatric teaching hospital. A daily report of prescriptions from the previous day was reviewed by a pharmacist for safety and efficacy. If an intervention was deemed necessary, the prescriber was contacted for clarification. In situations where patient harm could occur, the physician performing follow-ups was contacted by phone. The interventions were categorized based on type and potential severity. Physician response rates and intervention acceptance rates were assessed.

Results
Approximately 23,600 prescriptions were reviewed during a 1-year period with 60 interventions (0.25% intervention rate). Of the 60 interventions, 3% were estimated to have no severity, 80% were estimated to have minor, 12% moderate, and 5% major potential severity. The most common types of interventions were optimization of therapy, drug overdose, or dose omission at 33%, 32%, and 14%, respectively. Eighty-five percent of physicians responded; 73% accepted the intervention whereas 27% provided a rationale for their decision. More importantly, valuable information was gained, allowing for implementation of system fixes to prevent future errors. On an average, pharmacists spent 45 minutes reviewing and clarifying prescriptions each day.

Conclusions
Pharmacists in the ED can provide a valuable service by reviewing discharge prescriptions. A small amount of time dedicated to this service can lead to detection of clinically significant preventable medication errors and optimization of prescription therapy.
Effect of a Computerized Reminder on Splinting of Pediatric Upper Limb Fractures in the Emergency Department
Authors: Mills Erin , Craig Simon , Oakley Ed 
Published: October 2016

Objective
The primary objective was to assess if a computerized pop-up reminder increased splint application before X-ray in pediatric emergency department patients with deformed upper limb fractures. The secondary objective was to evaluate whether this same reminder improved pharmaceutical analgesia provision in this population.

Methodology
This was a prospective study of 518 pediatric emergency department patients with upper limb fractures after the implementation of a computerized pop-up reminder to give analgesia and apply a splint. The records of those with fractures requiring manipulation were identified and reviewed for data on demographics, clinical characteristics, splint application, and analgesic use. These data were compared with that in a previous retrospective study of 1407 patients in the same population before implementation of the computerized reminder.

Results
There were 86 patients with upper limb fractures requiring manipulation identified during the study period. After the computerized intervention, splint application rates improved from 22% to 49% (P = <0.001). There was no significant change to analgesia provision in the first hour after presentation.

Conclusions
A computerized reminder at the point of X-ray ordering significantly improved splint application rates for children with deformed upper limb fractures, though it did not affect pharmaceutical analgesia provision. The computerized pop-up is cheap to implement, easy to use, and potentially transferrable to other institutions and for other uses.
Role of monkeys in the sylvatic cycle of chikungunya virus in Senegal
Authors: Althouse Benjamin M. , Guerbois Mathilde , Cummings Derek A. T. , Diop Ousmane M. , Faye Ousmane , Faye Abdourahmane , Diallo Diawo , Sadio Bakary Djilocalisse , Sow Abdourahmane , Faye Oumar , Sall Amadou A. , Diallo Mawlouth , Benefit Brenda , Simons Evan , Watts Douglas M. , Weaver Scott C. , Hanley Kathryn A. 
Published: October 2016

AbstractAthropod-borne viruses (arboviruses) pose the greatest risk of spillover into humans of any class of pathogens. Such spillover may occur as a one-step jump from areservoirhost species into humans or as a two-step jump from the reservoir to a differentamplificationhost species and thence to humans. Despite the widespread havoc wreaked by emerging arboviruses, little is known about their transmission dynamics in reservoir and amplification hosts. Here we used serosurveillance and mathematical modeling to elucidate the role of monkeys in the sylvatic, enzootic cycle of chikungunya virus (CHIKV). Over three years, 219 African green monkeys, 78 patas monkeys, and 440 Guinea baboons were captured in the region surrounding Kedougou, Senegal. The age of each animal was determined by anthropometry and dentition, and exposure to CHIKV was determined by detection of neutralizing antibodies. We estimate age-specific CHIKV seroprevalence, force of infection (FoI), and basic reproductive number (R0) in each species. Among the different species, CHIKV Fol ranged from 0.13 to 1.12 (95% CI, 0.81–2.28) andR0ranged from 1.5 (95% CI, 1.3–1.9) to 6.6 (95% CI, 5.1–10.4). CHIKV infection of infant monkeys was detected even when the virus was not detected in a concurrent survey of primatophilic mosquitoes and when population seropositivity, and therefore immunity, was too high for monkeys themselves to support continuous CHIKV transmission. We therefore conclude that monkeys in this region serve primarily as amplification rather than reservoir hosts of CHIKV. Additional efforts are needed to identify other vertebrate hosts capable of supporting continuous circulation.
Rate of rise in diastolic blood pressure influences vascular sympathetic response to mental stress
Authors: El Sayed Khadigeh , Macefield Vaughan G. , Hissen Sarah L. , Joyner Michael J. , Taylor Chloe E. 
Published: October 2016

Key points
Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress.
In this study, we examined the early blood pressure responses (including the peak, time of peak and rate of rise in blood pressure) to mental stress in positive and negative responders.
Negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex‐mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA‐driven.
This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task.
AbstractResearch indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. The aim was to examine the early blood pressure response to stress in positive and negative responders and thus its influence on the direction of change in MSNA. Blood pressure and MSNA were recorded continuously in 21 healthy young males during 2 min mental stressors (mental arithmetic, Stroop test) and physical stressors (cold pressor, handgrip exercise, post‐exercise ischaemia). Participants were classified as negative or positive responders according to the direction of the mean change in MSNA during the stressor tasks. The peak changes, time of peak and rate of changes in blood pressure were compared between groups. During mental arithmetic negative responders experienced a significantly greater rate of rise in diastolic blood pressure in the first minute of the task (1.3 ± 0.5 mmHg s−1) compared with positive responders (0.4 ± 0.1 mmHg s−1; P = 0.03). Similar results were found for the Stroop test. Physical tasks elicited robust parallel increases in blood pressure and MSNA across participants. It is concluded that negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex‐mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA‐driven. This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task.
The relationship between pay day and violent death in Guatemala: a time series analysis
Authors: Ramírez Dorian E , Branas Charles C , Richmond Therese S , Bream Kent , Xie Dawei , Velásquez-Tohom Magda , Wiebe Douglas J 
Published: October 2016

ObjectiveTo assess if violent deaths were associated with pay days in Guatemala.DesignInterrupted time series analysis.SettingGuatemalan national autopsy databases.ParticipantsDaily violence-related autopsy data for 22 418 decedents from 2009 to 2012. Data were provided by the Guatemalan National Institute of Forensic Sciences. Multiple pay-day lags and other important days such as holidays were tested.Outcome measuresAbsolute and relative estimates of excess violent deaths on pay days and holidays.ResultsThe occurrence of violent deaths was not associated with pay days. However, a significant association was observed for national holidays, and this association was more pronounced when national holidays and pay days occurred simultaneously. This effect was observed mainly in males, who constituted the vast majority of violent deaths in Guatemala. An estimated 112 (coefficient=3.12; 95% CI 2.15 to 4.08; p<0.01) more male violent deaths occurred on holidays than were expected. An estimated 121 (coefficient=4.64; 95% CI 3.41 to 5.88; p<0.01) more male violent deaths than expected occurred on holidays that coincided with the first 2 days following a pay day.ConclusionsMen in Guatemala experience violent deaths at an elevated rate when pay days coincide with national holidays. Efforts to be better prepared for violence during national holidays and to prevent violent deaths by rescheduling pay days when these days co-occur with national holidays should be considered.
EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance
Authors: Zheng Xiaohu , Fan Xiaolei , Fu Binqing , Zheng Meijuan , Zhang Aimei , Zhong Kai , Yan Jialai , Sun Rui , Tian Zhigang , Wei Haiming 
Published: October 2016

Abstract
The lack of effective tumor-associated antigens restricts the development of targeted therapies against myeloid leukemia. In this study, we compared gene expression patterns of acute myeloid leukemia (AML) and normal bone marrow samples and found that epithelial cell adhesion molecule (EpCAM) is frequently overexpressed in patients with AML, with EpCAM+ leukemic cells exhibiting enhanced chemoresistance and oncogenesis. The chemotherapeutic resistance of EpCAM-positive leukemic cells is a consequence of increased WNT5B signaling. Furthermore, we generated EpCAM antibodies that enabled phagocytosis or cytotoxicity of AML cells by macrophage or natural killer cells, respectively. Finally, EpCAM antibody treatment depleted AML in subcutaneous, disseminated, and intramedullary engrafted mice. In summary, EpCAM exhibits promise as a novel target for the treatment of leukemia. Cancer Res; 77(2); 482–93. ©2016 AACR.
TNFα-Induced Mucin 4 Expression Elicits Trastuzumab Resistance in HER2-Positive Breast Cancer
Authors: Mercogliano María F. , De Martino Mara , Venturutti Leandro , Rivas Martín A. , Proietti Cecilia J. , Inurrigarro Gloria , Frahm Isabel , Allemand Daniel H. , Deza Ernesto Gil , Ares Sandra , Gercovich Felipe G. , Guzmán Pablo , Roa Juan C. , Elizalde Patricia V. , Schillaci Roxana 
Published: October 2016

AbstractPurpose: Although trastuzumab administration improved the outcome of HER2-positive breast cancer patients, resistance events hamper its clinical benefits. We demonstrated that TNFα stimulation in vitro induces trastuzumab resistance in HER2-positive breast cancer cell lines. Here, we explored the mechanism of TNFα-induced trastuzumab resistance and the therapeutic strategies to overcome it.Experimental Design: Trastuzumab-sensitive breast cancer cells, genetically engineered to stably overexpress TNFα, and de novo trastuzumab-resistant tumors, were used to evaluate trastuzumab response and TNFα-blocking antibodies effectiveness respectively. Immunohistochemistry and antibody-dependent cell cytotoxicity (ADCC), together with siRNA strategy, were used to explore TNFα influence on the expression and function of its downstream target, mucin 4 (MUC4). The clinical relevance of MUC4 expression was studied in a cohort of 78 HER2-positive breast cancer patients treated with adjuvant trastuzumab.Results: TNFα overexpression turned trastuzumab-sensitive cells and tumors into resistant ones. Histopathologic findings revealed mucin foci in TNFα-producing tumors. TNFα induced upregulation of MUC4 that reduced trastuzumab binding to its epitope and impaired ADCC. Silencing MUC4 enhanced trastuzumab binding, increased ADCC, and overcame trastuzumab and trastuzumab-emtansine antiproliferative effects in TNFα-overexpressing cells. Accordingly, administration of TNFα-blocking antibodies downregulated MUC4 and sensitized de novo trastuzumab-resistant breast cancer cells and tumors to trastuzumab. In HER2-positive breast cancer samples, MUC4 expression was found to be an independent predictor of poor disease-free survival (P = 0.008).Conclusions: We identified TNFα-induced MUC4 expression as a novel trastuzumab resistance mechanism. We propose MUC4 expression as a predictive biomarker of trastuzumab efficacy and a guide to combination therapy of TNFα-blocking antibodies with trastuzumab. Clin Cancer Res; 23(3); 636–48. ©2016 AACR.
Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer
Authors: Liang Qiaoyi , Chiu Jonathan , Chen Yingxuan , Huang Yanqin , Higashimori Akira , Fang Jingyuan , Brim Hassan , Ashktorab Hassan , Ng Siew Chien , Ng Simon Siu Man , Zheng Shu , Chan Francis Ka Leung , Sung Joseph Jao Yiu , Yu Jun 
Published: October 2016

Abstract
Purpose: Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.
Experimental Design: Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.
Results: Candidates identified by metagenome sequencing, including Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), and one undefined species (labeled as m7), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (r = 0.801–0.934, all P &lt; 0.0001). Fn was significantly more abundant in colorectal cancer than controls (P &lt; 0.0001), with AUROC of 0.868 (P &lt; 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity, Fn discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (Fn + Ch + m7-Bc) showed an improved diagnostic ability compared with Fn alone (AUROC = 0.886, P &lt; 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of Fn alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.
Conclusions: Stool-based colorectal cancer–associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer. Clin Cancer Res; 23(8); 2061–70. ©2016 AACR.
Plerixafor Improves Primary Tumor Response and Reduces Metastases in Cervical Cancer Treated with Radio-Chemotherapy
Authors: Chaudary Naz , Pintilie Melania , Jelveh Salomeh , Lindsay Patricia , Hill Richard P. , Milosevic Michael 
Published: October 2016

Abstract
Purpose: There is an important need to improve the effectiveness of radio-chemotherapy (RTCT) for cervical cancer. The CXCL12/CXCR4 pathway can influence RT response by recruiting normal myeloid cells to the tumor microenvironment that in turn can exert radioprotective effects, and may promote metastases. The objective of this study was to explore the efficacy and toxicity of combining RTCT with CXCL12/CXCR4 inhibition in cervical cancer.
Experimental Design: CXCR4 expression was measured in 115 patients with cervical cancer. Two primary orthotopic cervical cancer xenografts (OCICx) with different levels of CXCR4 expression were treated with RT (30 Gy: 15 daily fractions) and weekly cisplatin (4 mg/kg), with or without the CXCR4 inhibitor Plerixafor (5 mg/kg/day). The endpoints were tumor growth delay and lymph node metastases. Acute intestinal toxicity was assessed using a crypt cell assay.
Results: There was a fivefold variation in CXCR4 mRNA expression in the patient samples, and good correlation between the expression in patients and in the xenografts. The combination of RTCT and Plerixafor produced substantial tumor growth delay and reduced lymph node metastases compared with RTCT alone in both of the xenograft models. There was a trend toward reduced acute intestinal toxicity with the addition of Plerixafor to RTCT. There were no changes in normal organ morphology to suggest increased late toxicity.
Conclusions: This study demonstrates that the addition of Plerixafor to standard RTCT improves primary tumor response and reduces metastases in cervical cancer with no increase in toxicity. This combination warrants further investigation in phase I/II clinical trials. Clin Cancer Res; 23(5); 1242–9. ©2016 AACR.
Introducing Elitist Black-Box Models: When Does Elitist Behavior Weaken the Performance of Evolutionary Algorithms?
Authors: Doerr Carola , Lengler Johannes 
Published: October 2016

Black-box complexity theory provides lower bounds for the runtime of black-box optimizers like evolutionary algorithms and other search heuristics and serves as an inspiration for the design of new genetic algorithms. Several black-box models covering different classes of algorithms exist, each highlighting a different aspect of the algorithms under considerations. In this work we add to the existing black-box notions a new elitist black-box model, in which algorithms are required to base all decisions solely on (the relative performance of) a fixed number of the best search points sampled so far. Our elitist model thus combines features of the ranking-based and the memory-restricted black-box models with an enforced usage of truncation selection. We provide several examples for which the elitist black-box complexity is exponentially larger than that of the respective complexities in all previous black-box models, thus showing that the elitist black-box complexity can be much closer to the runtime of typical evolutionary algorithms. We also introduce the concept of p-Monte Carlo black-box complexity, which measures the time it takes to optimize a problem with failure probability at most p. Even for small p, the p-Monte Carlo black-box complexity of a function class [Formula: see text] can be smaller by an exponential factor than its typically regarded Las Vegas complexity (which measures the expected time it takes to optimize [Formula: see text]).
Meniscal Tearing after ACL Reconstruction
Authors: Ichinohe S , Yoshida M , Murakami H , Takayama H , Izumiyama S , Shimamura T 
Published: October 2016

The knees of 72 patients with unilateral anterior-cruciate-ligament (ACL) injury were analyzed before ACL reconstruction as well as by follow-up arthroscopy on the day of staple removal. At ACL reconstruction 31 lateral menisci and 40 medial menisci were found to be normal. 28 lateral menisci and 24 medial menisci were treated surgically, while 13 lateral menisci and 8 medial menisci with small or incomplete meniscal tearing were not treated. At follow-up arthroscopy there were 3 new cases of lateral meniscal tearing and 3 new cases of medial meniscal tearing in the groups diagnosed as normal prior to surgery. Two of the 13 cases with small or incomplete lateral meniscal tearing required resection, 8 healed and the other 3 demonstrated no progressive change. Four of the 8 cases with small or incomplete medial meniscal tears healed, 3 exhibited no progressive change and one required surgical treatment. There was no correlation between meniscal tearing and knee instability as indicated by a positive Lachman test or a positive pivot shift sign. The results of the present study indicate that ACL reconstruction prevents progressive changes in meniscal tears and will prevent secondary osteoarthritis, and that some small tears of the lateral meniscus require no surgical treatment.
Prevention of Heterotopic Bone Formation in High Risk Patients Post-Total Hip Arthroplasty
Authors: Ashton L Andrew , Bruce Warwick , Goldberg Jerome , Walsh Willliam 
Published: October 2016

A retrospective study was carried out to evaluate prophylaxis for heterotopic ossification (HO) about the hip joint post total hip arthroplasty (THA). Between 1990 and 1996, 20 patients with known risk for developing HO were treated prophylactically to prevent this complication. Patients at risk were divided into 3 groups based on risk factors for HO formation (previous ipsilateral hip HO formation, previous contralateral hip HO formation and bilateral hypertrophic osteoarthritis) Single fraction radiotherapy of 600, 700 or 800 cGy was administered postoperatively to all patients. The aim was to irradiate all patients within 72 hours of THA. 12 (60%) patients received in addition a short course of postoperative indomethacin for less than 13 days. Patients in this study were investigated for the following treatment variables: relative risk for forming HO, radiotherapy doses administered, time delays between surgery and irradiation, combined radiotherapy and indomethacin treatment versus radiotherapy alone, and surgical approach used for THA. Heterotopic ossification in patients was measured radiographically by use of the Brooker grading sytem, and was assessed clinically by use of the Harris Hip Score (HHS). A significant difference was found between relative risk groups (p = 0.02). Patients with previous HO formation in the ipsilateral hip joint were at greater risk of developing HO than those with previous contralateral HO formation. Moreover both of these groups were at greater risk than those with advanced bilateral hypertrophic osteoarthritis. Other variables studied showed differences that were not significant due to small sample numbers. This study, though limited by sample number, addresses questions regarding effective radiotherapy dosage, time delays acceptable before irradiation postoperatively, usefulness of short course postoperative indomethacin, and preferred operative approaches to minimise HO.