bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients
Authors: Wu Xuemei , Venkataramanan Raman , Rivosecchi Ryan M. , Tang Chenxiao , Marini Rachel V. , Shields Ryan K. , Clancy Cornelius J. , Nguyen M. Hong 
Published: November 2019

Isavuconazole (ISA) is a triazole antifungal with activity against yeasts and molds. We established a population pharmacokinetic (pop PK) model of intravenous (i.v.) ISA to identify covariates that affect pharmacokinetics, using plasma samples from solid-organ transplant (SOT) recipients receiving peritransplant prophylaxis. Samples (
n
= 471) from 79 SOT recipients were utilized for pop PK analysis using nonlinear mixed-effect modeling NONMEM software.
Explosive interaction of impact melt and seawater following the Chicxulub impact event
Authors: Osinski Gordon R. , Grieve Richard A.F. , Hill Patrick J.A. , Simpson Sarah L. , Cockell Charles , Christeson Gail L. , Ebert Matthias , Gulick Sean , Melosh H. Jay , Riller Ulrich , Tikoo Sonia M. , Wittmann Axel 
Published: November 2019

Abstract
The impact of asteroids and comets with planetary surfaces is one of the most catastrophic, yet ubiquitous, geological processes in the solar system. The Chicxulub impact event, which has been linked to the Cretaceous-Paleogene (K-Pg) mass extinction marking the beginning of the Cenozoic Era, is arguably the most significant singular geological event in the past 100 million years of Earth’s history. The Chicxulub impact occurred in a marine setting. How quickly the seawater re-entered the newly formed basin after the impact, and its effects of it on the cratering process, remain debated. Here, we show that the explosive interaction of seawater with impact melt led to molten fuel–coolant interaction (MFCI), analogous to what occurs during phreatomagmatic volcanic eruptions. This process fractured and dispersed the melt, which was subsequently deposited subaqueously to form a series of well-sorted deposits. These deposits bear little resemblance to the products of impacts in a continental setting and are not accounted for in current classification schemes for impactites. The similarities between these Chicxulub deposits and the Onaping Formation at the Sudbury impact structure, Canada, are striking, and suggest that MFCI and the production of volcaniclastic-like deposits is to be expected for large impacts in shallow marine settings.
Effects of supervised exercise training during pregnancy on psychological well-being among overweight and obese women: secondary analyses of the ETIP-trial, a randomised controlled trial
Authors: Garnæs Kirsti Krohn , Helvik A S , Stafne Signe N , Mørkved Siv , Salvesen Kjell , Salvesen Øyvind , Moholdt Trine 
Published: November 2019

ObjectivesWomen with high body mass index (BMI) have increased risk for symptoms of anxiety and depression during pregnancy and postpartum. In this prespecified secondary analysis from the exercise training in pregnancy trial, our aim was to examine effects of supervised exercise during pregnancy on psychological well-being in late pregnancy and postpartum among women with a prepregnancy BMI ≥28 kg/m2.DesignSingle-centre, parallel group, randomised controlled trial.SettingUniversity Hospital, Norway.ParticipantsNinety-one women (age 31.2±4.1 years, BMI 34.5±4.2 kg/m2), 46 in the exercise group, 45 in the control group, were included in the trial.InterventionThe exercise group was offered 3 weekly supervised exercise sessions (35 min of moderate intensity walking/running and 25 min of resistance training), until delivery.Primary and secondary outcomes measuresPrimary analyses were based on intention to treat, with secondary perprotocol analyses. To assess psychological well-being, we used the ‘Psychological General Well-Being Index’ (PGWBI) at inclusion (gestational week 12–18), late pregnancy (gestational week 34–37) and 3 months postpartum. We assessed postpartum depression using the ‘Edinburgh Postnatal Depression Scale’ (EPDS).ResultsNumbers completed data collection: late pregnancy 72 (exercise 38, control 36), postpartum 70 (exercise 36, control 34). In the exercise group, 50% adhered to the exercise protocol. Baseline PGWBI for all women was 76.4±12.6. Late pregnancy PGWBI; exercise 76.6 (95% CI 72.2 to 81.0), control 74.0 (95% CI 69.4 to 78.5) (p=0.42). Postpartum PGWBI; exercise 85.4 (95% CI 81.9 to 88.8), control 84.6 (95% CI 80.8 to 88.4) (with no between-group difference, p=0.77). There was no between-group difference in EPDS; exercise 2.96 (95% CI 1.7 to 4.2), control 3.48 (95% CI 2.3 to 4.7) (p=0.55).ConclusionsWe found no effect of supervised exercise during pregnancy on psychological well-being among women with high BMI. Our findings may be hampered by low adherence to the exercise protocol.Trial registration numberNCT01243554
Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement
Authors: Christersson Christina , James Stefan K , Lindhagen Lars , Ahlsson Anders , Friberg Örjan , Jeppsson Anders , Ståhle Elisabeth 
Published: November 2019

ObjectivesTo compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR).MethodsThe study included all patients in Sweden undergoing a bioSAVR during 2008–2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis.ResultsWe identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year.ConclusionIn patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incidence of bleeding events but with similar mortality.
Revolving doors of tendinopathy: definition, pathogenesis and treatment
Authors: Ahmad Zafar , Parkar Asif , Shepherd Jennifer , Rushton Neil 
Published: November 2019

AbstractThe ultimate cure for the tendon pathology continues to elude current science. Despite great steps in technology, the causation and treatment is still not clear. The number of different theories and treatment modalities in the literature may confuse clinicians and patients. In this paper we outline the definitions, evolution of pathogenesis and treatment for tendinopathy. By highlighting these, the aim of this paper is to guide the practitioner in counselling and treating their patients.
Characteristics and burden of disease in patients with radiographic and non-radiographic axial Spondyloarthritis: a comparison by systematic literature review and meta-analysis
Authors: López-Medina Clementina , Ramiro Sofia , van der Heijde Desirée , Sieper Joachim , Dougados Maxime , Molto Anna 
Published: November 2019

ObjectivesTo compare the clinical characteristics, burden of disease (eg, disease activity, function, quality of life), treatment modalities and treatment effect in patients with radiographic and non-radiographic axial Spondyloarthritis (r-axSpA and nr-axSpA).MethodsA systematic literature review (2009–2018) was performed using the participants, intervention, comparator and outcomes methodology. Studies reporting outcomes (clinical presentation, burden of disease, treatment modalities and treatment effect) of both r-axSpA and nr-axSpA were included. A pooled analysis was performed (standardised means difference and relative risk for continuous and binary variables, respectively) and random or fixed effects methods were used depending on the heterogeneity of the studies.Results60 studies out of 787 references were included. Pooled analysis showed that, compared with patients with nr-axSpA, patients with r-axSpA were more frequently men (69.6% vs 53.6%), smokers (37.7% vs 31.1%) and had higher mean disease duration (8.6 vs 5.0 years) and longer time to diagnosis (6.1 vs 4.2 years). Peripheral manifestations were more prevalent in nr-axSpA, while uveitis and structural damage on MRI of the sacroiliac joints were more prevalent in r-axSpA. C-reactive protein and the Bath Ankylosing Spondylitis Mobility Index were higher in r-axSpA, while Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index and Ankylosing Spondylitis Quality of Life were similar in both groups. No significant differences were found with regard to treatment effect.ConclusionsPatients with r-axSpA and nr-axSpA share a similar clinical presentation except for peripheral involvement, which is more prevalent among nr-axSpA. Except for a more impaired mobility in r-axSpA, both groups showed a comparable burden of disease, treatment modalities and treatment effect.
Bondi accretion in the spherically symmetric Johannsen–Psaltis spacetime
Authors: John Anslyn J. , Stevens Chris Z. 
Published: November 2019

AbstractThe Johannsen–Psaltis spacetime explicitly violates the no-hair theorem. It describes rotating black holes with scalar hair in the form of parametric deviations from the Kerr metric. In principle, black hole solutions in any modified theory of gravity could be written in terms of the Johannsen–Psaltis metric. We study the accretion of gas onto a static limit of this spacetime. We utilise a recently proposed pseudo–Newtonian formulation of the dynamics around arbitrary static, spherically symmetric spacetimes. We obtain a potential that generalises the Paczyński–Wiita potential to the static Johannsen–Psaltis metric. We also perform a fully relativistic analysis of the geodesic equations in the static Johannsen–Psaltis spacetime. We find that positive (negative) values of the scalar hair parameter, $$\epsilon _{3}$$ϵ3, lower (raise) the accretion rate. Similarly, positive (negative) values of $$\epsilon _{3}$$ϵ3 reduce (increase) the gravitational acceleration of radially infalling massive particles.
Monitoring the encapsulation of chlorin e6 derivatives into polymer carriers by NMR spectroscopy
Authors: Pfister Sara , Sauser Luca , Gjuroski Ilche , Furrer Julien , Vermathen Martina 
Published: November 2019

The encapsulation of five derivatives of chlorin e6 with different hydrophobicity and aggregation properties into a series of five poloxamer-type triblock copolymer micelles (BCMs) with varying numbers of polyethylene and polypropylene glycol (PEG, PPG) units was monitored using 1H NMR spectroscopy. NMR chemical shift and line shape analysis, as well as dynamic methods including diffusion ordered spectroscopy (DOSY) and T1 and T2 relaxation time measurements of the chlorin and the polymer resonances, proved useful to assess the chlorin–BCM compatibility. The poloxamers had high capability to break up aggregates formed by chlorins up to intermediate hydrophobicity. Physically entrapped chlorins were always localized in the BCM core region. The loading capacity correlated with chlorin polarity for all poloxamers among which those with the lowest number of PPG units were most efficient. DOSY data revealed that relatively weakly aggregating chlorins partition between the aqueous bulk and micellar environment whereas more hydrophobic chlorins are well retained in the BCM core region, rendering these systems more stable. T1 and T2 relaxation time measurements indicated that motional freedom in the BCM core region contributes to encapsulation efficiency. The BCM corona dynamics were rather insensitive towards chlorin entrapment except for the poloxamers with short PEG chains. The presented data demonstrate that 1H NMR spectroscopy is a powerful complementary tool for probing the compatibility of porphyrinic compounds with polymeric carriers such as poloxamer BCMs, which is a prerequisite in the development of stable and highly efficient drug delivery systems suitable for medical applications like photodynamic therapy of tumors.
Postablation Modulation after Single High-Dose Radiation Therapy Improves Tumor Control via Enhanced Immunomodulation
Authors: Savage Talicia , Pandey Sanjay , Guha Chandan 
Published: November 2019

Abstract

Purpose:
Radiotherapy (RT) is frequently used for local control of solid tumors using equal dose per fraction. Recently, single high-dose radiation has been used for ablation of solid tumors. In this report, we provide a novel immunological basis for radiation dose fractionation consisting of a single high-dose radiotherapy, followed by postablation modulation (PAM) with four daily low-dose fractions (22 Gy + 0.5 Gy × 4) to reprogram the tumor microenvironment by diminishing immune suppression, enabling infiltration of effector cells and increasing efficacy of tumor control.

Experimental Design:
Palpable 3LL and 4T1 tumors in C57Bl/6 and Balb/c mice were irradiated with the Small-Animal Radiation Research Platform irradiator, and tumor growth and survival were monitored. Immunomodulation of tumor and immune cells in vitro and in vivo characterization of tumor-infiltrating immune effector cells were performed by FACS. For systemic application of PAM-RT, whole-lung irradiation was administered in 4T1-bearing Balb/c mice.

Results:
We report significant tumor growth delays and increased survival in 3LL tumor–bearing mice with PAM. Primary tumor PAM-RT increased infiltration of immune effector cells and decreased Treg in irradiated tumors and secondary lymphoid organs. In a model of murine metastatic breast cancer (4T1), we demonstrated that systemic PAM-RT to the whole lung, 12 days after primary tumor ablative radiotherapy, increased survival with suppression of pulmonary metastases.

Conclusions:
We provide a novel immunologic basis for radiation dose fractionation consisting of a single high dose of radiotherapy followed by daily low-dose PAM-RT fractionation to improve the immunogenic potential of ablative radiotherapy.
Rapid Generation of Sustainable HER2-specific T-cell Immunity in Patients with HER2 Breast Cancer using a Degenerate HLA Class II Epitope Vaccine
Authors: Knutson Keith L. , Block Matthew S. , Norton Nadine , Erskine Courtney L. , Hobday Timothy J. , Dietz Allan B. , Padley Douglas , Gustafson Michael P. , Puglisi-Knutson Danell , Mangskau Toni Kay , Chumsri Saranya , Dueck Amylou C. , Karyampudi Lavakumar , Wilson Glynn , Degnim Amy C. 
Published: November 2019

AbstractPurpose:Patients with HER2+ breast cancer benefit from trastuzumab-containing regimens with improved survival. Adaptive immunity, including cytotoxic T-cell and antibody immunity, is critical to clinical efficacy of trastuzumab. Because Th cells are central to the activation of these antitumor effectors, we reason that HER2 patients treated with trastuzumab may benefit by administering vaccines that are designed to stimulate Th-cell immunity.Patients and Methods:We developed a degenerate HER2 epitope–based vaccine consisting of four HLA class II–restricted epitopes mixed with GM-CSF that should immunize most (≥84%) patients. The vaccine was tested in a phase I trial. Eligible women had resectable HER2+ breast cancer and had completed standard treatment prior to enrollment and were disease free. Patients were vaccinated monthly for six doses and monitored for safety and immunogenicity.Results:Twenty-two subjects were enrolled and 20 completed all six vaccines. The vaccine was well tolerated. All patients were alive at analysis with a median follow-up of 2.3 years and only two experienced disease recurrence. The percent of patients that responded with augmented T-cell immunity was high for each peptide ranging from 68% to 88%, which led to 90% of the patients generating T cells that recognized naturally processed HER2 antigen. The vaccine also augmented HER2-specific antibody. Immunity was sustained in patients with little sign of diminishing at 2 years following the vaccination.Conclusions:Degenerate HLA-DR–based HER2 vaccines induce sustainable HER2-specific T cells and antibodies. Future studies, could evaluate whether vaccination during adjuvant treatment with trastuzumab-containing regimens improves patient outcomes.
Capturing Hyperprogressive Disease with Immune-Checkpoint Inhibitors Using RECIST 1.1 Criteria
Authors: Matos Ignacio , Martin-Liberal Juan , García-Ruiz Alonso , Hierro Cinta , Ochoa de Olza Maria , Viaplana Cristina , Azaro Analia , Vieito Maria , Braña Irene , Mur Gemma , Ros Javier , Mateos Jose , Villacampa Guillermo , Berché Roger , Oliveira Mafalda , Alsina Maria , Elez Elena , Oaknin Ana , Muñoz-Couselo Eva , Carles Joan , Felip Enriqueta , Rodón Jordi , Tabernero Josep , Dienstmann Rodrigo , Perez-Lopez Raquel , Garralda Elena 
Published: November 2019

Abstract

Purpose:
Most hyperprogression disease (HPD) definitions are based on tumor growth rate (TGR). However, there is still no consensus on how to evaluate this phenomenon.

Patients and Methods:
We investigated two independent cohorts of patients with advanced solid tumors treated in phase I trials with (i) programmed cell death 1 (PD-1)/PD-L1 antibodies in monotherapy or combination and (ii) targeted agents (TA) in unapproved indications. A Response Evaluation Criteria in Solid Tumors (RECIST) 1.1–based definition of hyperprogression was developed. The primary endpoint was the assessment of the rate of HPD in patients treated with ICIs or TAs using both criteria (RECIST and TGR) and the impact on overall survival (OS) in patients who achieved PD as best response.

Results:
Among 270 evaluable patients treated with PD-1/PD-L1 inhibitors, 29 PD-1/PD-L1–treated patients (10.7%) had HPD by RECIST definition. This group had a significantly lower OS (median of 5.23 months; 95% CI, 3.97–6.45) when compared with the non-HPD progressor group (median, 7.33 months; 95% CI, 4.53–10.12; HR = 1.73, 95% CI, 1.05–2.85; P = 0.04). In a subset of 221 evaluable patients, 14 (6.3%) were categorized as HPD using TGR criteria, differences in median OS (mOS) between this group (mOS 4.2 months; 95% IC, 2.07–6.33) and non-HPD progressors (n = 44) by TGR criteria (mOS 6.27 months; 95% CI, 3.88–8.67) were not statistically significant (HR 1.4, 95% IC, 0.70–2.77; P = 0.346). Among 239 evaluable patients treated with TAs, 26 (10.9%) were classified as having HPD by RECIST and 14 using TGR criteria in a subset of patients. No differences in OS were observed between HPD and non-HPD progressors treated with TAs.

Conclusions:
HPD measured by TGR or by RECIST was observed in both cohorts of patients; however, in our series, there was an impact on survival only in the immune-checkpoint inhibitor cohort when evaluated by RECIST. We propose a new way to capture HPD using RECIST criteria that is intuitive and easy to use in daily clinical practice.
Doxorubicin-Induced Cardiac Abnormalities in Rats: Attenuation via Sandalwood Oil
Authors: Younis Nancy S. 
Published: November 2019

<b><i>Introduction:</i></b> The clinical use of doxorubicin (DOX) is challenged by its incremental dose-related cardiotoxicity. <b><i>Objective:</i></b> The aim of the hereby study was to investigate sandalwood essential oil (SEO) against DOX-induced cardiac toxicity. <b><i>Methods:</i></b> Male Sprague-Dawley rats were allocated into 4 groups. Groups 1 signified the control, whereas group 2 administered 100 mg/kg/day SEO, both act as control. In group 3, DOX was given intraperitoneal in a dose of 3 mg/kg/ every other day for 2 weeks to induced cardiotoxicity. While group 4 received a combination of SEO and DOX for 2 weeks. DOX prompted variations were assessed by measuring cardiac injury biomarkers, including creatine phosphokinase, cardiac troponin T, and lactate dehydrogenase (LDH), electrocardiogram (ECG) fluctuations, heart rate (HR), and blood pressure (BP) indices. The effect of both DOX and SEO on various antioxidants such as glutathione, superoxide dismutase, and catalase and inflammatory mediators including interleukin-1β, tumor necrosis factor-alpha, and NF-κB was quantified. <b><i>Results:</i></b> DOX augmented cardiac injury biomarkers, altered ECG, deceased HR and antioxidants, and finally increased BP indices. Treatment with SEO significantly (<i>p</i> &#x3c; 0.05) decreased cardiac biomarkers and reversing ECG changes and BP. Moreover, treatment with SEO enhanced HR anomalies and antioxidant activity reduction and precluded the intensive inflammatory response induced by DOX. <b><i>Conclusion:</i></b> SEO may have the potential of mitigating cardiac rhythm and BP indices changes induced with DOX. SEO modifications may be due to antioxidant capacity improvement and inflammatory response prohibition of the heart muscle.
Female Mice Exposed to Postnatal Neglect Display Angiotensin II–Dependent Obesity‐Induced Hypertension
Authors: Dalmasso Carolina , Leachman Jacqueline R. , Ensor Charles M. , Yiannikouris Frederique B. , Giani Jorge F. , Cassis Lisa A. , Loria Analia S. 
Published: November 2019

Background
We have previously reported that female mice exposed to maternal separation and early weaning (MSEW), a model of early life stress, show exacerbated diet‐induced obesity associated with hypertension. The goal of this study was to test whether MSEW promotes angiotensin II–dependent hypertension via activation of the renin‐angiotensin system in adipose tissue.

Methods and Results

MSEW was achieved by daily separations from the dam and weaning at postnatal day 17, while normally reared controls were weaned at postnatal day 21. Female controls and MSEW weanlings were placed on a low‐fat diet (LF, 10% kcal from fat) or high‐fat diet (HF, 60% kcal from fat) for 20 weeks. MSEW did not change mean arterial pressure in LF–fed mice but increased it in HF–fed mice compared with controls (
P
<0.05). In MSEW mice fed a HF, angiotensin II concentration in plasma and adipose tissue was elevated compared with controls (
P
<0.05). In addition, angiotensinogen concentration was increased solely in adipose tissue from MSEW mice (
P
<0.05), while angiotensin‐converting enzyme protein expression and activity were similar between groups. Chronic enalapril treatment (2.5 mg/kg per day, drinking water, 7 days) reduced mean arterial pressure in both groups of mice fed a HF (
P
<0.05) and abolished the differences due to MSEW. Acute angiotensin II–induced increases in mean arterial pressure (10 μg/kg SC) were attenuated in untreated MSEW HF–fed mice compared to controls (
P
<0.05); however, this response was similar between groups in enalapril‐treated mice.

Conclusions
The upregulation of angiotensinogen and angiotensin II in adipose tissue could be an important mechanism by which female MSEW mice fed a HF develop hypertension.