bluuebunny/crossref_metadata_2025_split huggingface dataset:
British Army recruits with low serum vitamin D take longer to recover from stress fractures
Authors: Richards Thomas , Wright C 
Published: October 2018

BackgroundRecruits undergoing military training experience a particularly high incidence of stress fractures. The role of combined calcium and vitamin D (25-OHD) deficiency and subsequent supplementation has been well described in the literature, but the role of 25-OHD deficiency alone is less well understood, particularly its influence on recovery once a stress fracture has been incurred.MethodsRetrospective data of recruits who had incurred stress fractures were collected (n=37). Independent-samples t-tests were conducted in Microsoft Excel to investigate the association between serum-25 OHD and the time taken to recover.ResultsSignificant differences (p<0.05) were found in the mean time taken to recover from stress fractures when participants were grouped according to serum 25-OHD level. Sufficient levels of serum 25-OHD (>50 nmol/L) at the time of injury resulted in shorter recovery times than all other groups.ConclusionThe study demonstrated an association between serum 25-OHD level and the time taken to recover from a stress fracture. The sample population of this study was too small to contribute to the discussion about whether a minimum serum 25-OHD status should be met before entering British Army training, but a larger prospective study should be able to provide the data required for a cost benefit analysis to be conducted and a decision made.
Futile inter-hospital transfer for mechanical thrombectomy in a semi-rural context: analysis of a 6-year prospective registry
Authors: Sablot Denis , Dumitrana Adrian , Leibinger Franck , Khlifa Khaled , Fadat Bénédicte , Farouil Geoffroy , Allou Thibaut , Coll Francis , Mas Julie , Smadja Philippe , Ferraro-Allou Adelaïde , Mourand Isabelle , Dutray Anaïs , Tardieu Maxime , Jurici Snejana , Bonnec Jean-Marie , Olivier Nadège , Cardini Sandra , Damon Frédérique , Van Damme Laurène , Aptel Sabine , Gaillard Nicolas , Marquez Ana-Maria , Nguyen Them Ludovic , Ibanez Majo , Arquizan Caroline , Costalat Vincent , Bonafe Alain 
Published: October 2018

Background and purposeInter-hospital transfer for mechanical thrombectomy (MT) might result in the transfer of patients who finally will not undergo MT (ie, futile transfers [FT]). This study evaluated FT frequency in a primary stroke center (PSC) in a semi-rural area and at 156 km from the comprehensive stroke center (CSC).MethodologyRetrospective analysis of data collected in a 6-year prospective registry concerning patients admitted to our PSC within 4.5 hours of acute ischemic stroke (AIS) symptom onset, with MR angiography indicating the presence of large vessel occlusion (LVO) without large cerebral infarction (DWI-ASPECT ≥5), and selected for transfer to the CSC to undergo MT. Futile transfer rate and reasons were determined, and the relevant time measures recorded.ResultsAmong the 529 patients screened for MT, 278 (52.6%) were transferred to the CSC. Futile transfer rate was 45% (n=125/278) and the three main reasons for FT were: clinical improvement and reperfusion on MRI on arrival at the CSC (58.4% of FT); clinical worsening and/or infarct growth (16.8%); and longer than expected inter-hospital transfer time (11.2%). Predictive factors of FT due to clinical improvement/reperfusion on MRI could not be identified. Baseline higher NIHSS (21 vs 17; P=0.01) and lower DWI-ASPECT score (5 vs 7; P=0.001) were associated with FT due to clinical worsening/infarct growth on MRI.ConclusionsIn our setting, 45% of transfers for MT were futile. None of the baseline factors could predict FT, but the initial symptom severity was associated with FT caused byclinical worsening/infarct growth.
Mitral valve and left ventricular features in malignant mitral valve prolapse
Authors: Garbi Madalina , Lancellotti Patrizio , Sheppard Mary N 
Published: October 2018

ObjectiveMitral valve prolapse is a benign condition, however with occasional reports of sudden cardiac death or out-of-hospital cardiac arrest in the absence of severe mitral regurgitation or coronary artery disease, suggesting the existence of a malignant form. The objective of our study was to contribute to the characterisation of malignant mitral valve prolapse.MethodsWe performed a retrospective analysis of pathology findings in 68 consecutive cases of sudden cardiac death with mitral valve prolapse as lone abnormal finding, reported as cause of death.ResultsAll mitral valve prolapse sudden death cases had mitral valve characteristics of Barlow disease, with extensive bileaflet multisegmental prolapse and dilatation of the annulus. The majority of cases (80.9%) had microscopic left ventricular fibrosis with associated hypertrophy and degenerative features of the myocytes, and some cases (10.9%) had right ventricular fibrosis as well.ConclusionsMalignant mitral valve prolapse is Barlow disease. Sudden cardiac death in mitral valve prolapse is due to Barlow disease, which besides the typical mitral valve degeneration may comprise a distinct Barlow disease cardiomyopathy, as suggested by myocyte degeneration and bi-ventricular involvement.
Effects of nucleotide supplementation on growth performance, nutrient digestibility, and immune blood profiles related to foot-and-mouth disease in vaccinated growing pigs
Authors: Jiao Yang , Kim In Ho 
Published: October 2018

A 6 wk trial was conducted to evaluate the effects of nucleotide supplementation in improving performance, nutrient digestibility, and immune blood profiles so as to reduce foot-and-mouth disease (FMD) vaccine stress in growing pigs. A total of 120 growing pigs [(Yorkshire × Landrace) × Duroc] with an average body weight (BW) of 25.76 ± 1.83 kg were used. Pigs were allocated to one of three treatments (eight pens per treatment; three barrows and two gilts per pen) based on BW and sex. Pigs were injected with FMD vaccine at 84 d of age (2 wk after experiment started). Dietary treatments consisted of (1) CON: corn–soybean-meal-based diet, (2) NUC1: CON + 0.5% nucleotide, and (3) NUC2: CON + 1.0% nucleotide. In the current study, the growth performance of gain:feed ratio (G:F), the apparent total tract digestibility of dry matter and nitrogen was linearly (P < 0.05) increased with the increasing level of nucleotide. After injection, the concentration of cortisol and epinephrine was decreased (P < 0.05) linearly in nucleotide treatments. In conclusion, nucleotide supplementation to FMD vaccinated pigs showed positive effects on improving performance, immune system health, and reducing vaccine stress in growing pigs.
Antibody-based Delivery of TNF to the Tumor Neovasculature Potentiates the Therapeutic Activity of a Peptide Anticancer Vaccine
Authors: Probst Philipp , Stringhini Marco , Ritz Danilo , Fugmann Tim , Neri Dario 
Published: October 2018

Abstract

Purpose:
There is a growing interest in the use of tumor antigens for therapeutic vaccination strategies. Unfortunately, in most cases, the use of peptide vaccines in patients does not mediate shrinkage of solid tumor masses.
Experimental Design: Here, we studied the opportunity to boost peptide vaccination with F8-TNF, an antibody fusion protein that selectively delivers TNF to the tumor extracellular matrix. AH1, a model antigen to investigate CD8+ T-cell immunity in BALB/c mice, was used as vaccine.

Results:
Peptide antigens alone exhibited only a modest tumor growth inhibition. However, anticancer activity could be substantially increased by combination with F8-TNF. Analysis of T cells in tumors and in draining lymph nodes revealed a dramatic expansion of AH1-specific CD8+ T cells, which were strongly positive for PD-1, LAG-3, and TIM-3. The synergistic anticancer activity, observed in the combined use of peptide vaccination and F8-TNF, was largely due to the ability of the fusion protein to induce a rapid hemorrhagic necrosis in the tumor mass, thus leaving few residual tumor cells. While the cell surface phenotype of tumor-infiltrating CD8+ T cells did not substantially change upon treatment, the proportion of AH1-specific T cells was strongly increased in the combination therapy group, reaching more than 50% of the CD8+ T cells within the tumor mass.

Conclusions:
Because both peptide vaccination strategies and tumor-homing TNF fusion proteins are currently being studied in clinical trials, our study provides a rationale for the combination of these 2 regimens for the treatment of patients with cancer.
PTEN Expression, Not Mutation Status in TSC1, TSC2, or mTOR, Correlates with the Outcome on Everolimus in Patients with Renal Cell Carcinoma Treated on the Randomized RECORD-3 Trial
Authors: Voss Martin H. , Chen David , Reising Albert , Marker Mahtab , Shi Jiayuan , Xu Jianning , Ostrovnaya Irina , Seshan Venkatraman E. , Redzematovic Almedina , Chen Ying-Bei , Patel Parul , Han Xia , Hsieh James J. , Hakimi A. Ari , Motzer Robert J. 
Published: October 2018

Abstract

Purpose:
Genomic alterations in key components of PI3K/mTOR pathway have been proposed as candidate predictive markers for rapalog therapy in renal cell carcinoma (RCC). We tested this hypothesis in patients from a randomized phase II trial of everolimus versus sunitinib.

Patients and Methods:
Archival specimens collected at baseline were analyzed with targeted next-generation sequencing (NGS). Focus of interest were alterations in key PI3K pathway components. PTEN expression was assessed by IHC. Association between molecular findings and treatment outcomes was investigated; same associations were tested for 2 everolimus-treated trial cohorts in gastric and hepatocellular carcinoma (HCC).

Results:
Among 184 everolimus-treated patients with RCC with NGS data, mutation rates in genes of interest were 6% (TSC1), 4.4% (TSC2), and 8.2% (mTOR); 44% harbored alterations in ≥1 PI3K pathway component. For subjects with presence versus absence of mutations in TSC1, TSC2, or mTOR progression-free survival (PFS) neither differed on univariate analysis (HR, 1.0; P = 0.895) nor on multivariate testing stratified by MSKCC risk group and other established prognostic factors (HR, 1.1; P = 0.806). Everolimus-treated patients with retained (n = 50) versus lost (n = 50) PTEN IHC expression had median PFS of 5.3 months versus 10.5 months (HR, 2.5; P &lt; 0.001). Such differences were not seen with sunitinib (10.9 months vs. 10.3 months; HR, 0.8; P = 0.475). Molecular findings did not correlate with outcomes in gastric and HCC cohorts.

Conclusions:
Association between mutation status for TSC1/TSC2/mTOR and therapeutic outcome on everolimus was not confirmed. Clinically meaningful differences in PFS were seen based on PTEN expression by IHC, lost in &gt;50% of patients.
A Phase I Dose-Escalation Study of Veliparib Combined with Carboplatin and Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer and Other Solid Tumors
Authors: Atrafi Florence , Groen Harry J.M. , Byers Lauren A. , Garralda Elena , Lolkema Martijn P. , Sangha Randeep S. , Viteri Santiago , Chae Young Kwang , Camidge D. Ross , Gabrail Nashat Y. , Hu Beibei , Tian Tian , Nuthalapati Silpa , Hoening Elizabeth , He Lei , Komarnitsky Philip , Calles Antonio 
Published: October 2018

Abstract

Purpose:
This study examined safety, pharmacokinetics, and efficacy of veliparib, a PARP inhibitor, combined with carboplatin and etoposide in patients with extensive-stage (ED) small cell lung cancer (SCLC) and other solid tumors.

Patients and Methods:
The 3 + 3 design was used for dose escalation of oral veliparib in combination with carboplatin (AUC 5 on day 1) and etoposide (100 mg/m2 on days 1–3) in 21-day cycles. Veliparib dose was explored from 80 to 240 mg b.i.d. on 7-day, 14-day, or continuous schedules. Patients without disease progression continued on maintenance monotherapy (veliparib 400 mg b.i.d.) until disease progression or unacceptable toxicity.

Results:
Thirty-nine patients were enrolled to determine the recommended phase II dose of 240 mg veliparib for 14 days combined with carboplatin and etoposide based on long-term tolerability. Dose-limiting toxicity occurred in 1 patient (grade 2 toxic motor polyneuropathy) at veliparib 240 mg b.i.d. for 7 days. Most common adverse events related to veliparib were nausea (39%), fatigue (39%), and hematologic toxicities. Continuous dosing of veliparib 240 mg b.i.d. with carboplatin and etoposide resulted in excessive chemotherapy dose delays due to hematologic toxicity (grade 3/4 neutropenia/thrombocytopenia). Etoposide pharmacokinetics was not affected by veliparib. Confirmed responses occurred in 17 of 39 (44%) and 16 of 25 (64%) of all enrolled and ED SCLC patients, respectively. At the RP2D, confirmed responses occurred in 6 of 13 (46%) and 5 of 6 (83%) of all enrolled and ED SCLC patients, respectively.

Conclusions:
Veliparib (240 mg b.i.d. 14 days) plus carboplatin/etoposide can be safely combined. Phase II of this study is ongoing in first-line patients with ED SCLC.
The Effectiveness of Checkpoint Inhibitor Combinations and Administration Timing Can Be Measured by Granzyme B PET Imaging
Authors: Larimer Benjamin M. , Bloch Emily , Nesti Sarah , Austin Emily E. , Wehrenberg-Klee Eric , Boland Genevieve , Mahmood Umar 
Published: October 2018

Abstract

Purpose:
The lack of a timely and reliable measure of response to cancer immunotherapy has confounded understanding of mechanisms of resistance and subsequent therapeutic advancement. We hypothesized that PET imaging of granzyme B using a targeted peptide, GZP, could be utilized for early response assessment across many checkpoint inhibitor combinations, and that GZP uptake could be compared between therapeutic regimens and dosing schedules as an early biomarker of relative efficacy.

Experimental Design:
Two models, MC38 and CT26, were treated with a series of checkpoint inhibitors. GZP PET imaging was performed to assess tumoral GZP uptake, and tumor volume changes were subsequently monitored to determine response. The average GZP PET uptake and response of each treatment group were correlated to evaluate the utility of GZP PET for comparing therapeutic efficacy.

Results:
In both tumor models, GZP PET imaging was highly accurate for predicting response, with 93% sensitivity and 94% negative predictive value. Mean tumoral GZP signal intensity of treatment groups linearly correlated with percent response across all therapies and schedules. Moreover, GZP PET correctly predicted that sequential dose scheduling of PD-1 and CTLA-4 targeted therapies demonstrates comparative efficacy to concurrent administration.

Conclusions:
Granzyme B quantification is a highly sensitive and specific early measure of therapeutic efficacy for checkpoint inhibitor regimens. This work provides evidence that GZP PET imaging may be useful for rapid assessment of therapeutic efficacy in the context of clinical trials for both novel drugs as well as dosing regimens.
Molecular Atlas of Postnatal Mouse Heart Development
Authors: Talman Virpi , Teppo Jaakko , Pöhö Päivi , Movahedi Parisa , Vaikkinen Anu , Karhu S. Tuuli , Trošt Kajetan , Suvitaival Tommi , Heikkonen Jukka , Pahikkala Tapio , Kotiaho Tapio , Kostiainen Risto , Varjosalo Markku , Ruskoaho Heikki 
Published: October 2018

Background

The molecular mechanisms mediating postnatal loss of cardiac regeneration in mammals are not fully understood. We aimed to provide an integrated resource of
mRNA
, protein, and metabolite changes in the neonatal heart for identification of metabolism‐related mechanisms associated with cardiac regeneration.

Methods and Results

Mouse ventricular tissue samples taken on postnatal day 1 (P01), P04, P09, and P23 were analyzed with
RNA
sequencing and global proteomics and metabolomics. Gene ontology analysis,
KEGG
pathway analysis, and fuzzy c‐means clustering were used to identify up‐ or downregulated biological processes and metabolic pathways on all 3 levels, and Ingenuity pathway analysis (Qiagen) was used to identify upstream regulators. Differential expression was observed for 8547
mRNA
s and for 1199 of 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Differentially regulated metabolic pathways include branched chain amino acid degradation (upregulated at P23), fatty acid metabolism (upregulated at P04 and P09; downregulated at P23) as well as the HMGCS (
HMG
‐CoA [hydroxymethylglutaryl‐coenzyme A] synthase)–mediated mevalonate pathway and ketogenesis (transiently activated). Pharmacological inhibition of
HMGCS
in primary neonatal cardiomyocytes reduced the percentage of BrdU‐positive cardiomyocytes, providing evidence that the mevalonate and ketogenesis routes may participate in regulating the cardiomyocyte cell cycle.

Conclusions
This study is the first systems‐level resource combining data from genomewide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses in the mouse heart throughout the early postnatal period. These integrated data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies.
A Prohibited History of Pentecostal Social Engagement
Authors: Florez Joseph 
Published: October 2018

Abstract
This article explores the dynamic intersection of community, conflict, and personal faith among a small group of Pentecostals during Chile’s military dictatorship (1973–1990). It argues that Pentecostal religious experience did not occur only within the framework of prescribed religious traditions and dogma. It seeped deep into the shadows of a powerful military state bent on a radical reordering of the economy and society; one that was willing to reach unthinkable levels of violence to do so. It concludes that we must examine less emblematic manifestations of pentecostal religiosity to fully understand the forms religion and religious practice took as they were folded into the limitations and complications of quotidian life, recognizing, moreover, that devotional and practical improvisations were not always understood as impious or immoral lapses. They were often necessary religious innovations used by believers to find meaning in the difficult circumstances of life under military rule.
How I Learned to Love Normal-Mode Rossby–Haurwitz Waves
Authors: Madden Roland A. 
Published: October 2018

AbstractSeveral important developments in the 1960s showed the way to using spectral analysis to identify and describe atmospheric waves predicted by theory. Among these waves were normal-mode Rossby–Haurwitz waves (NMRHWs). What follows is, first, a brief outline of how the influence of these developments on analyses of data collected during the Line Islands Experiment led to work on NMRHWs. Next, theoretical expectations of free NMRHWs as described by Kasahara and Kasahara and Puri in the early 1980s are discussed. Finally, spectral analyses of observed vorticity fields are presented for easy comparison with those expectations. The similarity between these relatively simple model predictions and observations is unique in meteorology, where complexity is the general rule. Readily available routines coded in NCAR Command Language (NCL) were used to isolate NMRHWs. It should be noted that, while these routines provide approximations to the theoretical predictions, open-access software for exact solutions has become available.
Annual and Interannual Variability in the California Current System: Comparison of an Ocean State Estimate with a Network of Underwater Gliders
Authors: Zaba Katherine D. , Rudnick Daniel L. , Cornuelle Bruce D. , Gopalakrishnan Ganesh , Mazloff Matthew R. 
Published: October 2018

AbstractA data-constrained state estimate of the southern California Current System (CCS) is presented and compared with withheld California Cooperative Oceanic Fisheries Investigations (CalCOFI) data and assimilated glider data over 2007–17. The objective of this comparison is to assess the ability of the California State Estimate (CASE) to reproduce the key physical features of the CCS mean state, annual cycles, and interannual variability along the three sections of the California Underwater Glider Network (CUGN). The assessment focuses on several oceanic metrics deemed most important for characterizing physical variability in the CCS: 50-m potential temperature, 80-m salinity, and 26 kg m−3 isopycnal depth and salinity. In the time mean, the CASE reproduces large-scale thermohaline and circulation structures, including observed temperature gradients, shoaling isopycnals, and the locations and magnitudes of the equatorward California Current and poleward California Undercurrent. With respect to the annual cycle, the CASE captures the phase and, to a lesser extent, the magnitude of upper-ocean warming and stratification from late summer to early fall and of isopycnal heave during springtime upwelling. The CASE also realistically captures near-surface diapycnal mixing during upwelling season and the semiannual cycle of the California Undercurrent. In terms of interannual variability, the most pronounced signals are the persistent warming and downwelling anomalies of 2014–16 and a positive isopycnal salinity anomaly that peaked with the 2015–16 El Niño.
High-Resolution Rapid Refresh Model Data Analytics Derived on the Open Science Grid to Assist Wildland Fire Weather Assessment
Authors: Blaylock Brian K. , Horel John D. , Galli Chris 
Published: October 2018

AbstractTerabytes of weather data are generated every day by gridded model simulations and in situ and remotely sensed observations. With this accelerating accumulation of weather data, efficient computational solutions are needed to process, archive, and analyze the massive datasets. The Open Science Grid (OSG) is a consortium of computer resources around the United States that makes idle computer resources available for use by researchers in diverse scientific disciplines. The OSG is appropriate for high-throughput computing, that is, many parallel computational tasks. This work demonstrates how the OSG has been used to compute a large set of empirical cumulative distributions from hourly gridded analyses of the High-Resolution Rapid Refresh (HRRR) model run operationally by the Environmental Modeling Center of the National Centers for Environmental Prediction. These cumulative distributions derived from a 3-yr HRRR archive are computed for seven variables, over 1.9 million grid points, and each hour of the calendar year. The HRRR cumulative distributions are used to evaluate near-surface wind, temperature, and humidity conditions during two wildland fire episodes—the North Bay fires, a wildfire complex in Northern California during October 2017 that was the deadliest and costliest in California history, and the western Oklahoma wildfires during April 2018. The approach used here illustrates ways to discriminate between typical and atypical atmospheric conditions forecasted by the HRRR model. Such information may be useful for model developers and operational forecasters assigned to provide weather support for fire management personnel.