bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Short BRCA2-Derived Cell-Penetrating Peptide Targets RAD51 Function and Confers Hypersensitivity toward PARP Inhibition
Authors: Trenner Anika , Godau Julia , Sartori Alessandro A. 
Published: April 2018

Abstract
Under conditions of genotoxic stress, cancer cells strongly rely on efficient DNA repair to survive and proliferate. The human BRCA2 tumor suppressor protein is indispensable for the repair of DNA double-strand breaks by homologous recombination (HR) by virtue of its ability to promote RAD51 loading onto single-stranded DNA. Therefore, blocking the interaction between BRCA2 and RAD51 could significantly improve the efficacy of conventional anticancer therapies. However, targeting protein–protein interaction (PPI) interfaces has proven challenging because flat and large PPI surfaces generally do not support binding of small-molecule inhibitors. In contrast, peptides are more potent for targeting PPIs but are otherwise difficult to deliver into cells. Here, we report that a synthetic 16-mer peptide derived from the BRC4 repeat motif of BRCA2 is capable of blocking RAD51 binding to BRCA2. Efficient noncytotoxic cellular uptake of a nona-arginine (R9)-conjugated version of the BRC4 peptide interferes with DNA damage–induced RAD51 foci formation and HR. Moreover, transduction of the BRC4 peptide impairs replication fork–protective function of BRCA2 and triggers MRE11-dependent degradation of nascent DNA in response to DNA replication stress. Finally, the BRC4 cell-penetrating peptide (CPP) confers selective hypersensitivity to PARP inhibition in cancer cells but spares noncancerous cells. Taken together, our data highlight an innovative approach to develop novel peptide-based DNA repair inhibitors and establish BRCA2-derived CPPs as promising anticancer agents. Mol Cancer Ther; 17(7); 1392–404. ©2018 AACR.
The OCT-ORION Study
Authors: Lee Stephen W.L. , Tam Frankie C.C. , Lam Simon C.C. , Kong Shun-Ling , Shea Catherine P. , Chan Kelvin K.W. , Wong Michael K.L. , Chan Michael P.H. , Wong Anthony Y.T. , Yung Arthur S.Y. , Lam Yui-Ming , Zhang Lei-Wei , Wu Karl K.Y. , Mintz Gary S. , Maehara Akiko 
Published: April 2018

Background—
Durable polymers used in drug-eluting stents are considered a potential cause of hypersensitivity inflammatory response adversely affecting stent healing. Using a sequential follow-up with optical coherence tomography, we compared the differences in healing profiles of 2 drug-eluting stents with a biodegradable or durable polymer.

Methods and Results—

Sixty patients with multivessel disease were prospectively enrolled to receive both study stents, which were randomly assigned to 2 individual vessels, a Resolute Integrity zotarolimus-eluting stent with a durable BioLinx polymer and a BioMatrix NeoFlex Biolimus A9–eluting stent with a biodegradable polylactic acid polymer. Optical coherence tomography was performed at baseline, then in 5 randomly assigned monthly groups at 2 to 6 months, and at 9 months in all patients. The primary end point was the difference in optical coherence tomography strut coverage at 9 months. Key secondary end points included angiographic late lumen loss and composite major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 9 months. Resolute Integrity zotarolimus-eluting stent showed significantly better strut coverage than BioMatrix NeoFlex Biolimus A9–eluting stent at 2 to 6 months (
P
<0.001) and less variance of percent coverage at 9 months, 99.7% (interquartile range, 99.1–100) versus 99.6% (interquartile range, 96.8–99.9; difference, 0.10; 95% confidence interval, 0.00–1.05;
P
<0.001). No significant difference was observed in major adverse cardiac events or angiographic end points.

Conclusions—
Despite having a durable polymer, Resolute Integrity zotarolimus-eluting stent exhibited better strut coverage than BioMatrix NeoFlex Biolimus A9–eluting stent having a biodegradable polymer; both showed similar antiproliferative efficacy. This novel, longitudinal, sequential optical coherence tomography protocol using each patient as own control could achieve conclusive results in small sample size.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01742507.
Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation
Authors: Martinez Brandon K. , Sood Nitesh A. , Bunz Thomas J. , Coleman Craig I. 
Published: April 2018

Background
Frailty predicts poorer outcomes and decreased anticoagulation use in patients with nonvalvular atrial fibrillation. We sought to assess the effectiveness and safety of apixaban, dabigatran and rivaroxaban versus warfarin in frail nonvalvular atrial fibrillation patients.

Methods and Results

Using
US
MarketScan claims data from November 2011 to December 2016, we identified frail oral anticoagulant‐naïve nonvalvular atrial fibrillation patients with ≥12 months of continuous insurance coverage before oral anticoagulant initiation. Frailty status was determined using the Johns Hopkins Claims‐based Frailty Indicator score (≥0.20 indicating frailty). Users of apixaban, dabigatran, or rivaroxaban were separately 1:1 matched to warfarin users via propensity‐scores, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed for up to 2 years or until an event, insurance disenrollment or end of follow‐up. Rates of stroke or systemic embolism and major bleeding were compared using Cox regression and reported as hazard ratios (
HR
s) and 95% confidence intervals (
CI
s). In total, 2700, 2784, and 5270 patients were included in the apixaban, dabigatran, and rivaroxaban 1:1 matched analyses to warfarin. At 2 years, neither apixaban nor dabigatran were associated with differences in the hazard of stroke or systemic embolism (
HR
=0.78; 95%
CI
=0.46–1.35 and
HR
=0.94; 0.60–1.45) or major bleeding (
HR
=0.72; 95%
CI
=0.49–1.06 and
HR
=0.87; 95%
CI
=0.63–1.19) versus warfarin. Rivaroxaban was associated with reduced stroke or systemic embolism at 2 years (
HR
=0.68; 95%
CI
=0.49–0.95) without significantly altering major bleeding risk (
HR
=1.07; 95%
CI
=0.81–1.32).

Conclusions

Our study found rivaroxaban but not apixaban or dabigatran to be associated with reduced
SSE
versus warfarin in frail nonvalvular atrial fibrillation patients. No direct‐acting oral anticoagulants demonstrated a significant difference in major bleeding versus warfarin.
<p class="Default">Evolution of trichome morphology in Mimosa (Leguminosae-Mimosoideae)
Authors: SANTOS-SILVA JULIANA , TOZZI ANA MARIA GOULART DE AZEVEDO , SIMON MARCELO FRAGOMENI , URQUIZA NAZARETH GUEDES , MORALES MATÍAS 
Published: April 2018

With more than 500 species, Mimosa L. is one of the largest genera of the Leguminosae. It exhibits considerable trichome diversity among species. Trichome types have been used as diagnostic characters, but some are not well known and have been poorly described in taxonomic works, causing some difficulties for species identification and description. The morphology of trichomes of 35 species was studied using scanning electron microscopy and light microscopy to define the types of trichomes precisely. An ancestral character state reconstruction using a densely-sampled phylogeny of the genus was performed in order to investigate the evolution of trichome types in Mimosa. Two basic types of trichomes can be distinguished: glandular and non-glandular. The glandular trichomes can be sessile or stalked. The non-glandular trichomes can be unbranched or branched. Unbranched trichomes are unicellular and conical or cylindrical, whereas branched trichomes are multicellular and verruciform, medusiform, plumose, barbellate, stellate, stellate-lepidote, or lepidote. Character optimization analysis suggests that glandular and branched trichomes are derived and evolved independently in different lineages within Mimosa. The ancestral condition in Mimosa was probably non-glandular and unbranched trichomes, which was retained from piptadenioid ancestors. Our study provides a first insight into the evolutionary history of trichome morphology in the genus. Despite high levels of homoplasy, trichome morphology offers a set of characters that can be used for differentiating species and species groups in combination with other characters.
Revision of the cicada genus Dilobopyga (Hemiptera, Cicadidae) from Sulawesi and the Moluccas
Authors: DUFFELS J.P. 
Published: April 2018

This revision of the cicadas of the genus Dilobopyga provides a diagnosis of the genus and descriptions, illustrations and distribution maps for 48 species. The following 33 species described here are new to science: D. angulata, angustata, bifida, curvispina, fasciata, hayashii, hollowayi, johani, knighti, langeraki, laterocurvata, latifascia, luwukensis, macrocerata, maleo, mamasa, mediolobata, nebulosa, operculata, palopoensis, pelengensis, platyacantha, quadrimaculata, rantemario, recurvata, rozendaali, sangihensis, sarasinorum, splendida, tambusisi, toraja, vantoli and watuwila. The key presented is designed for the identification of males of Dilobopyga to the species level. The subdivision of the genus in five species groups viz., opercularis group (17 species), nebulosa group (1 species), chlorogaster group (16 species), minahassae group (6 species) and watuwila group (8 species), is sustained by a phylogenetic analysis of morphological characters of all species described. The cicadas of the genus Dilobopyga are found in Sulawesi, neighbouring islands and southern Moluccas. Of the 48 species of Dilobopyga 43 species are endemic to Sulawesi. Most of these Sulawesi species are restricted to either one peninsula or to a part of Central Sulawesi. The remaining five species are endemic to either the Sangihe Islands, Banggai Islands or the southern Moluccas. A taxon-area cladogram for the species of Dilobopyga provides a basis for a discussion on the historic biogeography of the genus.
Variation in Birth Outcomes by Mother’s Country of Birth Among Hispanic Women in the United States, 2013
Authors: DeSisto Carla L. , McDonald Jill A. 
Published: April 2018

Objectives: Despite knowledge that the Hispanic population is growing in the United States and that birth outcomes may vary by maternal country of birth, data on birth outcomes by maternal country of birth among Hispanic women are scant. We compared the rates of 3 birth outcomes for infants born in the United States—preterm birth, low birth weight, and small for gestational age—between foreign-born Hispanic women and US-born Hispanic women, and then we examined these birth outcomes by mother’s country of birth for foreign-born Hispanic women. Methods: Using the 2013 natality file from the National Vital Statistics System of the National Center for Health Statistics, we examined data on the 3 birth outcomes and maternal characteristics by maternal country of birth. We used log binomial models to calculate unadjusted and adjusted relative risks for preterm birth, low birth weight, and small for gestational age for US-born Hispanic women compared with foreign-born Hispanic women. We also compared the relative risk of each adverse birth outcome for foreign-born Hispanic women by country of birth. Results: US-born Hispanic women had higher rates of the 3 birth outcomes than did foreign-born Hispanic women (preterm birth: 8.0% vs 7.0%; low birth weight: 6.1% vs 5.2%; small for gestational age: 9.2% vs 7.9%). These higher rates persisted after adjusting for maternal characteristics. The rates for these 3 birth outcomes varied significantly by country of birth for foreign-born Hispanic women, with Puerto Rican women consistently having the poorest birth outcomes. Conclusions: Our results demonstrated heterogeneity in rates of adverse birth outcomes by country of birth for foreign-born Hispanic women. Presenting rates for foreign-born mothers as a group masks differences by country. To understand possible changes in data on birth outcomes, states should stratify data by maternal country of birth.
The effectiveness of 12 weeks of Pilates intervention on disability, pain and kinesiophobia in patients with chronic low back pain: a randomized controlled trial
Authors: Cruz-Díaz David , Romeu Marta , Velasco-González Carmen , Martínez-Amat Antonio , Hita-Contreras Fidel 
Published: April 2018

Objective: To assess the effectiveness of 12 weeks of Pilates practice on disability, pain and kinesiophobia in patients with chronic non-specific low back pain. Design: This is a randomized controlled trial. Setting: This study was conducted in the university laboratory. Subjects: A total of 64 participants with chronic non-specific low back pain were included. Interventions: Participants were randomly allocated to intervention group consisted in Pilates intervention during 12 weeks ( n = 32) or control group who received no treatment ( n = 32). Main measures: Disability, pain and kinesiophobia were assessed by Roland Morris Disability Questionnaire, visual analogue scale and Tampa Scale of Kinesiophobia, respectively. Measurements were performed at baseline, at 6 and 12 weeks after study completion. Results: There were significant differences between groups with observed improvement in Pilates intervention group in all variables after treatment ( P < 0.001). Major changes on disability and kinesiophobia were observed at six weeks of intervention with no significant difference after 12 weeks ( P < 0.001). Mean changes of the intervention group compared with the control group were 4.00 (0.45) on the Roland Morris Disability Questionnaire and 5.50 (0.67) in the Tampa Scale of Kinesiophobia. Pain showed better results at six weeks with a slightly but statistically significant improvement at 12 weeks with Visual Analogue Scale scores of 2.40 (0.26) ( P < 0.001). Conclusion: Pilates intervention in patients with chronic non-specific low back pain is effective in the management of disability, pain and kinesiophobia.
Understanding activity participation among individuals with Wolfram syndrome
Authors: Bumpus Emily , Hershey Tamara , Doty Tasha , Ranck Samantha , Gronski Meredith , Urano Fumihko , Foster Erin R 
Published: April 2018

Introduction Wolfram syndrome is a rare genetic disease associated with a variety of progressive metabolic and neurologic impairments. Previous research has focused on Wolfram syndrome-related impairments and biomarkers for disease progression; however, information about how Wolfram syndrome impacts participation in daily activities is lacking. Method Wolfram syndrome ( n = 45; 20 children, 25 adults) participants completed an online questionnaire about activity participation. Thirty-six non-Wolfram syndrome comparison participants (11 children; 25 adults) completed a portion of the questionnaire. Symptom data from a subset of Wolfram syndrome participants ( n = 20) were also examined in relation to participation data. Results Wolfram syndrome children and adults had lower participation than non-Wolfram syndrome children and adults in almost all activity domains, and social and exercise-related activities were the most problematic. In the subset of Wolfram syndrome adults with symptom data, poorer vision, balance, gait, hearing, and overall symptom severity were related to lower participation. Conclusion Wolfram syndrome appears to negatively impact participation in a variety of activities, and this effect may increase as people age and/or Wolfram syndrome progresses. The most functionally pertinent Wolfram syndrome symptoms are those associated with neurodegeneration, especially vision loss and walking and balance problems. This study revealed symptoms and activity domains that are most relevant for people with Wolfram syndrome and, thus, can inform current practice and treatment development research.
Spinal dural arteriovenous fistula presenting as low back pain
Authors: Chan Kwok-Chun , Cheng Fu-Jen , Hsu Chih-Wei , Tsai I-Ting , Chua Choon-Bing , Chang Chao-Sheng 
Published: April 2018

Introduction: Low back pain or numbness of the lower extremities is quite common in the present population. Numerous conditions may cause these symptoms, including spinal vascular anomaly. Identifying and diagnosing the cause of these symptoms are crucial for treatment. Accurate diagnosis based on particular radiological findings in magnetic resonance imaging is crucial for administering adequate therapy to patients, especially in spinal dural arteriovenous fistula. Case presentation: We report a case presenting with low back pain and rapid deterioration in paraplegia. Magnetic resonance imaging provided the typical image presentations such as spinal cord edema with tortuous dilated perimedullary venous plexus. The patient was subsequently successfully treated with endovascular embolization. Discussion: Spinal dural arteriovenous fistula should be suspected in any patient who presents with myelopathy. Angiography remains the gold standard for confirmation of diagnosis. Conclusion: Prompt treatment with endovascular embolization or surgery could improve patients’ outcomes.
Assessment of exposure risk of irinotecan and its active metabolite, SN-38, through perspiration during chemotherapy
Authors: Irie Kei , Okada Akira , Masuda Yoshio , Fukushima Keizo , Sugioka Nobuyuki , Okuda Chiyuki , Hata Akito , Kaji Reiko , Okada Yutaka , Katakami Nobuyuki , Fukushima Shoji 
Published: April 2018

Background Irinotecan (CPT-11) is the key drug used in chemotherapy for many malignant tumors. CPT-11 has cholinergic activity and induces perspiration during intravenous administration. In this study, concentrations of CPT-11 and its active metabolite, SN-38, released during perspiration were measured and risk of exposure of these drugs was assessed. Method Beads of sweat were collected using a dropper from four patients undergoing a chemotherapy regimen involving intravenous administration of CPT-11. The concentrations of CPT-11 and SN-38 in sweat were measured using liquid chromatography tandem mass spectrometry. Result Chemotherapy regimens were capecitabine and irinotecan plus bevacizumab (n = 1), CPT-11 monotherapy (n = 1), and oxaliplatin–irinotecan–leucovorin–5-fluorouracil (n = 2). Uridine diphosphate-glucuronosyltransferase 1A1 phenotypes were *6 homo-type (n = 1), *6 hetero-type (n = 1), and wild type (n = 2). CPT-11 dose was 292.3 ± 75.5 mg/body weight (mean ± standard deviation). CPT-11 was detected in sweat secreted by all the four patients, and its mean (±standard deviation) concentration was 252.6 (±111.9) ng/ml. SN-38 was detected in only one of the patients who received oxaliplatin–irinotecan–leucovorin–5-fluorouracil treatment and who had the wild-type uridine diphosphate-glucuronosyltransferase 1A1 phenotype at a concentration of 74.37 ng/ml. Conclusion CPT-11 and SN-38 are detected in sweat released during intravenous CPT-11 administration. Beads of sweat or linen clothes that absorb the sweat might be the source of CPT-11 and SN-38 exposure.
Ambulance use, distance and outcomes in patients with suspected cardiovascular disease: a registry-based geographic information system study
Authors: Sepehrvand Nariman , Alemayehu Wendimagegn , Kaul Padma , Pelletier Rick , Bello Aminu K , Welsh Robert C , Armstrong Paul W , Ezekowitz Justin A 
Published: April 2018

Background:Despite guideline recommendations, the majority of patients with symptoms suggestive of acute coronary syndrome do not use emergency medical services to reach the emergency department (ED). The aim of this study was to investigate the factors associated with EMS utilisation and subsequent patient outcomes.Methods:Using administrative data, all patients who presented to an ED in the metropolitan areas of Edmonton and Calgary in the years of 2007–2013 with main ED diagnosis of acute coronary syndrome, stable angina or chest pain were included. The travel distance was estimated using the geographic information system method to approximate the distance between the ED and patient home. The clinical endpoints were the 7-day and 30-day all-cause events (death, re-hospitalisation and repeat ED visit).Results:Of 50,881 patients, 30.5% presented by emergency medical services. Patients with older age, female sex, ED diagnosis of acute coronary syndrome, more comorbidities and lower household income were more likely to use emergency medical services to reach the hospital. Longer travel distance was associated with higher emergency medical services use (odds ratio 1.09, 95% confidence interval 1.09–1.10), but it was not a predictor of clinical events. After adjustment for covariates and inverse propensity score weighting, emergency medical services use was associated with a higher risk of 7-day and 30-day clinical events.Conclusion:Several demographic and clinical features were associated with higher emergency medical services use including geographical variation. Although longer travel distance was shown to be linked to higher emergency medical services use, it was not an independent predictor of patient outcome. This has implications for the design of emergency medical services systems, triage and early diagnosis and treatment options.
Validity of wrist-worn consumer products to measure heart rate and energy expenditure
Authors: Thiebaud Robert S. , Funk Merrill D. , Patton Jacelyn C. , Massey Brook L. , Shay Terri E. , Schmidt Martin G. , Giovannitti Nicolas 
Published: April 2018

Introduction The ability to monitor physical activity throughout the day and during various activities continues to improve with the development of wrist-worn monitors. However, the accuracy of wrist-worn monitors to measure both heart rate and energy expenditure during physical activity is still unclear. The purpose of this study was to determine the accuracy of several popular wrist-worn monitors at measuring heart rate and energy expenditure. Methods Participants wore the TomTom Cardio, Microsoft Band and Fitbit Surge on randomly assigned locations on each wrist. The maximum number of monitors per wrist was two. The criteria used for heart rate and energy expenditure were a three-lead electrocardiogram and indirect calorimetry using a metabolic cart. Participants exercised on a treadmill at 3.2, 4.8, 6.4, 8 and 9.7 km/h for 3 minutes at each speed, with no rest between speeds. Heart rate and energy expenditure were manually recorded every minute throughout the protocol. Results Mean absolute percentage error for heart rate varied from 2.17 to 8.06% for the Fitbit Surge, from 1.01 to 7.49% for the TomTom Cardio and from 1.31 to 7.37% for the Microsoft Band. The mean absolute percentage error for energy expenditure varied from 25.4 to 61.8% for the Fitbit Surge, from 0.4 to 26.6% for the TomTom Cardio and from 1.8 to 9.4% for the Microsoft Band. Conclusion Data from these devices may be useful in obtaining an estimate of heart rate for everyday activities and general exercise, but energy expenditure from these devices may be significantly over- or underestimated.