bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory measures of coagulation among trauma patients on NOAs: results of the AAST-MIT
Authors: Kobayashi Leslie M , Brito Alexandra , Barmparas Galinos , Bosarge Patrick , Brown Carlos V , Bukur Marko , Carrick Matthew M , Catalano Richard D , Holly-Nicolas Jan , Inaba Kenji , Kaminski Stephen , Klein Amanda L , Kopelman Tammy , Ley Eric J , Martinez Ericca M , Moore Forrest O , Murry Jason , Nirula Raminder , Paul Douglas , Quick Jacob , Rivera Omar , Schreiber Martin , Coimbra Raul 
Published: October 2018

BackgroundWarfarin is associated with poor outcomes after trauma, an effect correlated with elevations in the international normalized ratio (INR). In contrast, the novel oral anticoagulants (NOAs) have no validated laboratory measure to quantify coagulopathy. We sought to determine if use of NOAs was associated with elevated activated partial thromboplastin time (aPTT) or INR levels among trauma patients or increased clotting times on thromboelastography (TEG).MethodsThis was a post-hoc analysis of a prospective observational study across 16 trauma centers. Patients on dabigatran, rivaroxaban, or apixaban were included. Laboratory data were collected at admission and after reversal. Admission labs were compared between medication groups. Traditional measures of coagulopathy were compared with TEG results using Spearman’s rank coefficient for correlation. Labs before and after reversal were also analyzed between medication groups.Results182 patients were enrolled between June 2013 and July 2015: 50 on dabigatran, 123 on rivaroxaban, and 34 apixaban. INR values were mildly elevated among patients on dabigatran (median 1.3, IQR 1.1–1.4) and rivaroxaban (median 1.3, IQR 1.1–1.6) compared with apixaban (median 1.1, IQR 1.0–1.2). Patients on dabigatran had slightly higher than normal aPTT values (median 35, IQR 29.8–46.3), whereas those on rivaroxaban and apixaban did not. Fifty patients had TEG results. The median values for R, alpha, MA and lysis were normal for all groups. Prothrombin time (PT) and aPTT had a high correlation in all groups (dabigatran p=0.0005, rivaroxaban p<0.0001, and apixaban p<0.0001). aPTT correlated with the R value on TEG in patients on dabigatran (p=0.0094) and rivaroxaban (p=0.0028) but not apixaban (p=0.2532). Reversal occurred in 14%, 25%, and 18% of dabigatran, rivaroxaban, and apixaban patients, respectively. Both traditional measures of coagulopathy and TEG remained within normal limits after reversal.DiscussionNeither traditional measures of coagulation nor TEG were able to detect coagulopathy in patients on NOAs.Level of evidenceLevel IV.
Localization of massless Elko spinor fields on de Sitter thick branes
Authors: Sorkhi Masoumeh Moazzen , Ghalenovi Zahra 
Published: October 2018

In this work, we investigate the localization of a five-dimensional (5D) free massless Elko spinor field on de Sitter thick branes that are generated by a canonical or phantom scalar field. It is shown that the zero mode of Elko field cannot be localized on the de Sitter brane. In order to circumvent this problem, we employ a nonminimal coupling term in the 5D Elko spinor field action and find that the Elko field can be localized on the de Sitter brane with this mechanism.
The Impact of Early-Phase Trial Design in the Drug Development Process
Authors: Conaway Mark R. , Petroni Gina R. 
Published: October 2018

Abstract

Purpose:
Many of the therapeutic agents that are being used currently were developed using the 3+3 decision rule for dose finding. Over the past 30 years, several dose-finding designs have been proposed and evaluated, including the “continual reassessment method” (CRM) and the “Bayesian optimal interval design” (BOIN). This research investigates the role of the choice of an early-phase design on the likelihood that drugs entering the drug development pipeline will have 2 successful phase III trials.
Experimental Design: Using simulation, each agent in a population of hypothetical agents was tracked through the drug development process, from initial dose finding to 2 confirmatory phase III trials. Varying the designs of the phase I, II, and III trials allows for an assessment of the effect of the choice of designs on the proportion of agents with successful phase III trials.

Results:
The results indicate that using the CRM or BOIN, rather than the 3+3, substantially enhances the proportion of effective agents that have successful phase III trials, with the CRM having a greater effect than BOIN. A larger phase II trial magnifies the effect of the phase I design.

Conclusions:
The results underscore the importance of the choice of the early-phase designs. Use of the 3+3 results in fewer agents with successful phase III trials compared with the CRM or BOIN. The difference is more pronounced among highly effective agents. In addition, the results show the importance of a sufficiently powered phase II trial.
KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition
Authors: Misale Sandra , Fatherree Jackson P. , Cortez Eliane , Li Chendi , Bilton Samantha , Timonina Daria , Myers David T. , Lee Dana , Gomez-Caraballo Maria , Greenberg Max , Nangia Varuna , Greninger Patricia , Egan Regina K. , McClanaghan Joseph , Stein Giovanna T. , Murchie Ellen , Zarrinkar Patrick P. , Janes Matthew R. , Li Lian-Sheng , Liu Yi , Hata Aaron N. , Benes Cyril H. 
Published: October 2018

Abstract

Purpose:
KRAS-mutant lung cancers have been recalcitrant to treatments including those targeting the MAPK pathway. Covalent inhibitors of KRAS p.G12C allele allow for direct and specific inhibition of mutant KRAS in cancer cells. However, as for other targeted therapies, the therapeutic potential of these inhibitors can be impaired by intrinsic resistance mechanisms. Therefore, combination strategies are likely needed to improve efficacy.
Experimental Design: To identify strategies to maximally leverage direct KRAS inhibition we defined the response of a panel of NSCLC models bearing the KRAS G12C–activating mutation in vitro and in vivo. We used a second-generation KRAS G12C inhibitor, ARS1620 with improved bioavailability over the first generation. We analyzed KRAS downstream effectors signaling to identify mechanisms underlying differential response. To identify candidate combination strategies, we performed a high-throughput drug screening across 112 drugs in combination with ARS1620. We validated the top hits in vitro and in vivo including patient-derived xenograft models.

Results:
Response to direct KRAS G12C inhibition was heterogeneous across models. Adaptive resistance mechanisms involving reactivation of MAPK pathway and failure to induce PI3K–AKT pathway inactivation were identified as likely resistance events. We identified several model-specific effective combinations as well as a broad-sensitizing effect of PI3K-AKT–mTOR pathway inhibitors. The G12Ci+PI3Ki combination was effective in vitro and in vivo on models resistant to single-agent ARS1620 including patient-derived xenografts models.

Conclusions:
Our findings suggest that signaling adaptation can in some instances limit the efficacy of ARS1620 but combination with PI3K inhibitors can overcome this resistance.
Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer
Authors: Vaishampayan Ulka N. , Podgorski Izabela , Heilbrun Lance K. , Lawhorn-Crews Jawana M. , Dobson Kimberlee C. , Boerner Julie , Stark Karri , Smith Daryn W. , Heath Elisabeth I. , Fontana Joseph A. , Shields Anthony F. 
Published: October 2018

Abstract

Purpose:
Cabozantinib is a multitargeted tyrosine kinase inhibitor that demonstrated remarkable responses on bone scan in metastatic prostate cancer. Randomized trials failed to demonstrate statistically significant overall survival (OS). We studied the dynamics of biomarker changes with imaging and biopsies pretherapy and posttherapy to explore factors that are likely to be predictive of efficacy with cabozantinib.
Experimental Design: Eligibility included patients with metastatic castrate-resistant prostate cancer with normal organ function and performance status 0–2. Cabozantinib 60 mg orally was administered daily. Pretherapy and 2 weeks post, 99mTc-labeled bone scans, positron emission tomography with 18F-sodium fluoride (NaF-PET) and 18F-(1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) thymine (FMAU PET) scans were conducted. Pretherapy and posttherapy tumor biopsies were conducted, and serum and urine bone markers were measured.

Results:
Twenty evaluable patients were treated. Eight patients had a PSA decline, of which 2 had a decline of ≥50%. Median progression-free survival (PFS) and OS were 4.1 and 11.2 months, respectively, and 3 patients were on therapy for 8, 10, and 13 months. The NaF-PET demonstrated a median decline in SUVmax of −56% (range, −85 to −5%, n = 11) and −41% (range, −60 to −25%, n = 9) for patients who were clinically stable and remained on therapy for ≥4 or &lt;4 cycles, respectively. The FMAU PET demonstrated a median decline in SUVmax of −44% (−60 to −14%) and −42% (−63% to −23%) for these groups. The changes in bone markers and mesenchymal epithelial transition/MET testing did not correlate with clinical benefit.

Conclusions:
Early changes in imaging and tissue or serum/urine biomarkers did not demonstrate utility in predicting clinical benefit with cabozantinib therapy.
Genome-Wide Meta-analysis of Gene–Environmental Interaction for Insulin Resistance Phenotypes and Breast Cancer Risk in Postmenopausal Women
Authors: Jung Su Yon , Mancuso Nick , Yu Herbert , Papp Jeanette , Sobel Eric , Zhang Zuo-Feng 
Published: October 2018

Abstract
Insulin resistance (IR)–related genetic variants are possibly associated with breast cancer, and the gene–phenotype–cancer association could be modified by lifestyle factors including obesity, physical inactivity, and high-fat diet. Using data from postmenopausal women, a population highly susceptible to obesity, IR, and increased risk of breast cancer, we implemented a genome-wide association study (GWAS) in two steps: (1) GWAS meta-analysis of gene–environmental (i.e., behavioral) interaction (G*E) for IR phenotypes (hyperglycemia, hyperinsulinemia, and homeostatic model assessment–insulin resistance) and (2) after the G*E GWAS meta-analysis, the identified SNPs were tested for their associations with breast cancer risk in overall or subgroup population, where the SNPs were identified at genome-wide significance. We found 58 loci (55 novel SNPs; 5 index SNPs and 6 SNPs, independent of each other) that are associated with IR phenotypes in women overall or women stratified by obesity, physical activity, and high-fat diet; among those 58 loci, 29 (26 new loci; 2 index SNPs and 2 SNPs, independently) were associated with postmenopausal breast cancer. Our study suggests that a number of newly identified SNPs may have their effects on glucose intolerance by interplaying with obesity and other lifestyle factors, and a substantial proportion of these SNPs’ susceptibility can also interact with the lifestyle factors to ultimately influence breast cancer risk. These findings may contribute to improved prediction accuracy for cancer and suggest potential intervention strategies for those women carrying genetic risk that will reduce their breast cancer risk.
On Brazilian Helobata Bergroth, 1888 (Coleoptera: Hydrophilidae) II: new distribution data
Authors: Clarkson Bruno , Almeida Lucia M. 
Published: October 2018

As an add-on to the work of Clarkson et al. (2016), new distributional data on species of Helobata Bergroth, 1888 (Hydrophilidae: Acidocerinae) from Brazil is provided. Helobata amazonensis Clarkson, Santos & Ferreira‑Jr., 2016, is recorded for the first time for Roraima State and its female is recorded for the first time. Helobata quatipuru Fernández & Bachmann, 1987 and H. larvalis (Horn, 1873) are recorded for the first time for Minas Gerais, Cerrado Biome area. The genus is recorded for the first time for Goiás State. Additions and modifications in the previously published key to Brazilian species are provided.
Six new species and new records of the genus Desmopachria Babington (Coleoptera: Dytiscidae: Hyphidrini) from Brazil and redescription of D. varians Wehncke, 1877
Authors: Braga Rafael Benzi , Ferreira-Jr. Nelson 
Published: October 2018

Six new species of the genus Desmopachria Babington, 1841 are described and illustrated from Brazil: D. anauine sp. nov., D. carranca sp. nov., D. francischettii sp. nov., D. nigrasphera sp. nov., D. nigricoxa sp. nov. and D. yanomami sp. nov. Desmopachria varians is redescribed and illustrated from syntypes photos and material identified by Dr. Frank Young. New records for eight other species from Brazilian states are presented here: D. amyae Miller, 2001 has a new record from Minas Gerais State, D. grammosticta Braga & Ferreira‑Jr., 2015 have new records from Minas Gerais and São Paulo States, D. granoides Young, 1986 has a new record from Espirito Santo State, D. laevis Sharp, 1882 have new records from Espírito Santo and Parana States, D. leptophallica Braga & Ferreira‑Jr., 2014 has a new record from Paraná State, D. sioli Young, 1980 has a new record from Minas Gerais State, D. striola Sharp, 1887 have new records from Rio de Janeiro and São Paulo States and D. volatidisca Miller, 2001 has a new record from Paraíba States and an unpublished record of D. challeti Miller, 2001 from Brazil.
Medical Therapy for Systemic Right Ventricles: A Systematic Review (Part 1) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
Authors: Zaragoza-Macias Elisa , Zaidi Ali N. , Dendukuri Nandini , Marelli Ariane 
Published: October 2018

Patients with systemic morphological right ventricles (RVs), including congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries with a Mustard or Senning atrial baffle repair, have a high likelihood of developing systemic ventricular dysfunction. Unfortunately, there are a limited number of clinical studies on the efficacy of medical therapy for systemic RV dysfunction.
We performed a systematic review and meta-analysis to assess the effect of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), beta blockers, and aldosterone antagonists in adults with systemic RVs. The inclusion criteria included age ≥18 years, systemic RVs, and at least 3 months of treatment with ACE inhibitor, ARB, beta blocker, or aldosterone antagonist. The outcomes included RV end-diastolic and end-systolic dimensions, RV ejection fraction, functional class, and exercise capacity. EMBASE, PubMed, and Cochrane databases were searched. The selected data were pooled and analyzed with the DerSimonian-Laird random-effects meta-analysis model. Between-study heterogeneity was assessed with Cochran’s Q test. A Bayesian meta-analysis model was also used in the event that heterogeneity was low. Bias assessment was performed with the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar’s test and Egger’s test.
Six studies met the inclusion criteria, contributing a total of 187 patients; treatment with beta blocker was the intervention that could not be analyzed because of the small number of patients and diversity of outcomes reported. After at least 3 months of treatment with ACE inhibitors, ARBs, or aldosterone antagonists, there was no statistically significant change in mean ejection fraction, ventricular dimensions, or peak ventilatory equivalent of oxygen. The methodological quality of the majority of included studies was low, mainly because of a lack of a randomized and controlled design, small sample size, and incomplete follow-up.
In conclusion, pooled results across the limited available studies did not provide conclusive evidence with regard to a beneficial effect of medical therapy in adults with systemic RV dysfunction. Randomized controlled trials or comparative-effectiveness studies that are sufficiently powered to demonstrate effect are needed to elucidate the efficacy of ACE inhibitors, ARBs, beta blockers, and aldosterone antagonists in patients with systemic RVs.
Home-Time as a Surrogate Marker for Functional Outcome After Aneurysmal Subarachnoid Hemorrhage
Authors: Stienen Martin Nikolaus , Smoll Nicolas Roydon , Fung Christian , Goldberg Johannes , Bervini David , Maduri Rodolfo , Chiappini Alessio , Robert Thomas , May Adrien , Bijlenga Philippe , Zumofen Daniel , Roethlisberger Michel , Seule Martin Alexander , Marbacher Serge , Fandino Javier , Schatlo Bawarjan , Schaller Karl , Keller Emanuela , Bozinov Oliver , Regli Luca ,   on behalf of the Swiss SOS Study Group*, Burkhardt Jan-Karl , Neidert Marian C. , Maldaner Nicolai , Finkenstädt Sina , Schöni Daniel , Raabe Andreas , Beck Jürgen , Mariani Luigi , Guzman Raphael , D’Alonzo Donato , Daniel Roy Thomas , Reinert Michael , Ferrari Andrea , Hildebrandt Gerhard , Weyerbrock Astrid , Corniola Marco 
Published: October 2018

Background and Purpose—
Commonly used tools to determine functional outcome after aneurysmal subarachnoid hemorrhage (aSAH) have limitations. Time spent at the patient’s home has previously been proposed as a robust outcome measure after ischemic stroke. Here, we set out to validate home-time as an outcome measure after aSAH.

Methods—
We examined prospectively collected data from a nationwide multicenter registry of aSAH patients admitted to a tertiary neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]; 2009–2015). We calculated mean home-time (defined as days spent at home for the first 90 days after aSAH) and 95% CIs for each category of modified Rankin Scale at discharge and 1-year follow-up, using linear regression models to analyze home-time differences per modified Rankin Scale category.

Results—

We had home-time data from 1076 of 1866 patients (57.7%), and multiple imputation was used to fill-in missing data from the remaining 790 patients. Increasing home-time was associated with improved modified Rankin Scale scores at time of hospital discharge (
P
<0.0001) and at 1-year follow-up (
P
<0.0001). Within each of the 8 participating hospitals, the relationship between home-time and modified Rankin Scale was maintained.

Conclusions—
Home-time for the first 90 days after aSAH offers a robust and easily ascertainable outcome measure, discriminating particularly well across better recovery levels at time of hospital discharge and at 1-year follow-up. This measure complies with the modern trend of patient-centered healthcare and research, representing an outcome that is particularly relevant to the patient.

Clinical Trial Registration—

URL:
https://clinicaltrials.gov
. Unique identifier: NCT03245866.
A Newfound Friend or a Good Old Companion?
Authors: Lin Judith C.P. 
Published: October 2018

Abstract
Recent studies suggest that a significant number of Taiwanese Protestant churches have been heavily influenced by the charismatic movement since the 1980s. A strong case can be made, however, that the “charismatic” character has been inherent in Taiwanese Protestantism since long before 1980, not least because the charismatic character has much in common with the spiritual instincts of people in Taiwan. By studying the works of two prominent preachers (Kou Shih-yuan and Wu Yung) and certain issues of the Taiwan Church News (Presbyterian Church in Taiwan), I will show that a sizeable number of Protestants in Taiwan before 1980 embraced the realm of spiritual and demonic beings, although they showed different degrees of friendliness towards charisms. I will conclude that, rather than speaking of the “charismaticization” of churches in Taiwan, perhaps we ought to speak of the rediscovery of the charismatic character that is inherent in churches in Taiwan.
“Piercing the Veil” and African Dreams and Visions
Authors: Droll Anna Marie 
Published: October 2018

Abstract
Pentecostal scholarship is conscientiously examining gaps in Western theology in regard to pneumatology. This article describes the phenomena of pentecostal dreams and visions (D/V s) in the African context as significant to that dialogue, pointing to their spiritual value in many African churches. I suggest that they can be seen as existential samples of the pneumatological imagination as put forth by Amos Yong and also as described by Nimi Wariboko. I use Yong’s theology to argue that the pneumatological imagination in African contexts readdresses the experience of D/V s, which are normative phenomena in indigenous religions, through the hermeneutical interplay of Spirit-Word-community. I also suggest that the experience of D/V s satisfies Wariboko’s definition of grace, that they are subject to his politics of spiritual warfare, and that their interpretation and application exemplify the transformation of “ontological and epistemological coordinates of existence” by “piercing the veil” of phenomenality for the experience of the noumenal.
The mental representation of the human gait in hip osteoarthrosis and total hip arthroplasty patients: A clinical cross-sectional study
Authors: Jacksteit Robert , Mau-Moeller Anett , Völker Antje , Bader Rainer , Mittelmeier Wolfram , Skripitz Ralf , Stöckel Tino 
Published: October 2018

Objective: To explore differences in gait-specific long-term memory structures and actual gait performance between patients with hip osteoarthrosis, patients seen six months after total hip arthroplasty and healthy controls to gain insights into the role of the gait-specific mental representation for rehabilitation. Design: Cross-sectional study Subjects: Twenty hip osteoarthrosis patients, 20 patients seen six months after total hip arthroplasty and 20 healthy controls Methods: Spatio-temporal (gait speed, step length) and temporophasic (stance time, swing time, single support time, total double support time) gait parameters, and gait variability were measured with an electronic walkway (OptoGait). The gait-specific mental representation was assessed using the structural dimensional analysis of mental representations (SDA-M). Results: Hip osteoarthrosis patients showed significantly longer stance and total double support times, shorter swing and single support times, and a decreased gait speed as compared with healthy controls (all P < 0.01). The differences in double support times were still evident in patients seen six months after total hip arthroplasty ( P < 0.01). The gait-specific mental representation differed between hip osteoarthrosis patients and healthy controls with regard to mid-stance and mid-swing phases; the mid-stance phase was still affected six months after total hip arthroplasty (both P < 0.05). Conclusion: Our data indicated that actual gait performance and gait-specific long-term memory structures differ between hip osteoarthrosis patients and healthy controls. Important, some of these disease-related changes were still evident in patients seen six months after total hip arthroplasty.