bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerating Pharmaceutical Development via Metal‐Mediated Bond Formation
Authors: Borths Christopher J. , Walker Shawn D.
Published: April 2020

A perspective of our work on the development of practical metal‐mediated carbon‐carbon and carbon‐heteroatom bond forming processes within a modern drug portfolio is presented. The case studies selected from our laboratories highlight the synthetic challenges and opportunities presented by pharmaceutically relevant scaffolds. In many cases, the target structures challenged available synthetic methods and inspired the invention of enabling technology to accelerate drug development. Additionally, considerations for running metal‐mediated processes on large scale are discussed.
Delivery in pregnant women infected with SARS‐CoV‐2: A fast review
Authors: Parazzini Fabio , Bortolus Renata , Mauri Paola Agnese , Favilli Alessandro , Gerli Sandro , Ferrazzi Enrico
Published: April 2020

Background

Few case reports and clinical series exist on pregnant women infected with SARS‐CoV‐2 who delivered.

Objective

To review the available information on mode of delivery, vertical/peripartum transmission, and neonatal outcome in pregnant women infected with SARS‐CoV‐2.

Search strategy

Combination of the following key words: COVID‐19, SARS‐CoV‐2, and pregnancy in Embase and PubMed databases.

Selection criteria

Papers reporting cases of women infected with SARS‐CoV‐2 who delivered.

Data collection and analysis

The following was extracted: author; country; number of women; study design; gestational age at delivery; selected clinical maternal data; mode of delivery; selected neonatal outcomes.

Main results

In the 13 studies included, vaginal delivery was reported in 6 cases (9.4%; 95% CI, 3.5–19.3). Indication for cesarean delivery was worsening of maternal conditions in 31 cases (48.4%; 95% CI, 35.8–61.3). Two newborns testing positive for SARS‐CoV‐2 by real‐time RT‐PCR assay were reported. In three neonates, SARS‐CoV‐2 IgG and IgM levels were elevated but the RT‐PCR test was negative.

Conclusions

The rate of vertical or peripartum transmission of SARS‐CoV‐2 is low, if any, for cesarean delivery; no data are available for vaginal delivery. Low frequency of spontaneous preterm birth and general favorable immediate neonatal outcome are reassuring.
Spatio‐temporal context based recurrent visual attention model for lymph node detection
Authors: Peng Haixin , Peng Yinjun
Published: April 2020

False‐positive reduction is one of the most crucial components in an automated lymph nodes (LNs) detection task in volumetric computed tomography (CT) scans, which is a highly sought goal for cancer diagnosis and early treatment. In this article, treating the three‐dimensional (3D) LN detection task as object detection on sequence problem, we propose a novel spatio‐temporal context‐based recurrent visual attention model (STRAM) for the LNs false positive reduction. We firstly extract the deep spatial features maps for two‐dimensional LN patches from pre‐trained Inception‐V3 model. A new Gaussian kernel‐based spatial attention method is then presented to extract the most discriminating spatial features for the corresponding center slices. Additionally, to combine the temporal information between 3D CT slices, we devise a novel “Siamese” mixture density networks which can learn to adaptively focus on the most relevant parts of the CT slices. Considering the lesion areas always locate around the centroid of the 3D CT scans, a hard constraint is imposed on the predicted attention locations with batch normalization technique and the Siamese architecture. The proposed model is a fully differentiable unit that can be optimized end‐to‐end by using stochastic gradient descent. The effectiveness of our method is verified on LN dataset: 388 mediastinal LNs labeled by radiologists in 90 patient CT scans, and 595 abdominal LNs in 86 patient CT scans. Our method demonstrates sensitivities of about 87%/82% at 3 FP/vol. and 93%/89% at 6 FP/vol. for mediastinum and abdomen, respectively, which compares favorably to previous methods.
Effects of High-Intensity Resistance Training on Osteopenia and Sarcopenia Parameters in Older Men with Osteosarcopenia—One-Year Results of the Randomized Controlled Franconian Osteopenia and Sarcopenia Trial (FrOST)
Authors: Kemmler Wolfgang , Kohl Matthias , Fröhlich Michael , Jakob Franz , Engelke Klaus , von Stengel Simon , Schoene Daniel
Published: April 2020

Dynamic resistance exercise (DRT) might be the most promising agent for fighting sarcopenia in older people. However, the positive effect of DRT on osteopenia/osteoporosis in men has still to be confirmed. To evaluate the effect of low-volume/high-intensity (HIT)-DRT on bone mineral density (BMD) and skeletal muscle mass index (SMI) in men with osteosarcopenia, we initiated the Franconian Osteopenia and Sarcopenia Trial (FrOST). Forty-three sedentary community-dwelling older men (aged 73 to 91 years) with osteopenia/osteoporosis and SMI-based sarcopenia were randomly assigned to a HIT-RT exercise group (EG; n = 21) or a control group (CG; n = 22). HIT-RT provided a progressive, periodized single-set DRT on machines with high intensity, effort, and velocity twice a week, while CG maintained their lifestyle. Both groups were adequately supplemented with whey protein, vitamin D, and calcium. Primary study endpoint was integral lumbar spine (LS) BMD as determined by quantitative computed tomography. Core secondary study endpoint was SMI as determined by dual-energy X-ray absorptiometry. Additional study endpoints were BMD at the total hip and maximum isokinetic hip−/leg-extensor strength (leg press). After 12 months of exercise, LS-BMD was maintained in the EG and decreased significantly in the CG, resulting in significant between-group differences (p < 0.001; standardized mean difference [SMD] = 0.90). In parallel, SMI increased significantly in the EG and decreased significantly in the CG (p < 0.001; SMD = 1.95). Total hip BMD changes did not differ significantly between the groups (p = 0.064; SMD = 0.65), whereas changes in maximum hip−/leg-extensor strength were much more prominent (p < 0.001; SMD = 1.92) in the EG. Considering dropout (n = 2), attendance rate (95%), and unintended side effects/injuries (n = 0), we believe our HIT-RT protocol to be feasible, attractive, and safe. In summary, we conclude that our combined low-threshold HIT-RT/protein/vitamin D/calcium intervention was feasible, safe, and effective for tackling sarcopenia and osteopenia/osteoporosis in older men with osteosarcopenia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Diffusion tensor imaging of the anterior cruciate ligament following primary repair with internal bracing: A longitudinal study
Authors: Van Dyck Pieter , Froeling Martijn , Heusdens Christiaan H. W. , Sijbers Jan , Ribbens Annemie , Billiet Thibo
Published: April 2020

Diffusion tensor imaging (DTI) provides information about tissue microstructure and its degree of organization by quantifying water diffusion. We aimed to monitor longitudinal changes in DTI parameters (fractional isotropy, FA; mean diffusivity, MD; axial diffusivity, AD; radial diffusivity, RD) of the anterior cruciate ligament (ACL) following primary repair with internal bracing (IBLA). Fourteen patients undergoing IBLA were enrolled prospectively and scheduled for clinical follow‐up, including instrumented laxity testing, and DTI at 3, 6, 12, and 24 months postoperatively. DTI was also performed in seven healthy subjects. Fiber tractography was used for 3D segmentation of the whole ACL volume, from which median DTI parameters were calculated. The posterior cruciate ligament (PCL) served as a control. Longitudinal DTI changes were assessed using a linear mixed model, and repeated measures correlations were calculated between DTI parameters and clinical laxity tests. At follow‐up, thirteen patients had a stable knee and one patient sustained an ACL rerupture after 12 months postoperatively. The ACL repair showed a significant decrease of FA within the first 12 months after surgery, followed by stable FA values thereafter, while ACL diffusivities decreased over time returning towards normal values at 24 months postoperatively. For PCL there were no significant DTI changes over time. There was a significant correlation between ACL FA and laxity tests (r = −0.42, P = .017). This study has shown the potential of DTI to longitudinally monitor diffusion changes in the ACL following IBLA. The DTI findings suggest that healing of the ACL repair is incomplete at 24 months postoperatively.
Blurring the boundaries between synthesis and evaluation. A customized realist evaluative synthesis into adolescent risk behavior prevention
Authors: Cooper Christina , Lhussier Monique , Carr Susan
Published: April 2020

Realist methodologies have been increasingly advocated for the investigation of complex social issues. Public health programs, such as those designed to prevent adolescent risk behavior, are typically considered complex. In conducting a realist review of the empirical literature relating to such programs, we encountered several challenges, including (a) an overabundance of empirical evidence, (b) a problematic level of heterogeneity within and between methodological approaches, (c) discrepancies between theoretical underpinnings and program operationalization, (d) homogeneity of program outcomes, with very little variation in program effectiveness, and (d) a paucity of description relating to content and process. To overcome these challenges, we developed a customized approach to realist evidence synthesis, drawing on the VICTORE (Volition, Implementation, Contexts, Time, Outcomes, Rivalry, and Emergence) complexity checklist and incorporating stakeholder engagement as primary data to achieve greater depth of understanding relating to contextual and mechanistic factors, and the complex interactions between them. Here we discuss the benefits of this adapted methodology alongside an overview of the research through which the methodology was developed. A key finding from this research was that combining the complexity checklist with primary data from stakeholder engagement enabled us to systematically interrogate the data across data sources, uncovering and evidencing mechanisms which may otherwise have remained hidden, giving greater ontological depth to our research findings. This paper builds on key methodological developments in realist research, demonstrating how realist methodologies can be customized to overcome challenges in developing and refining program theory from the literature, and contributes to the broader literature of innovative approaches to realist research.

Highlights

Published reporting standards for realist review provide a set of guiding principles for conducting realist research. However, these are not recommended to be used in a prescriptive sense, and customization of the methodology to account for potential idiosyncrasies within a specific evidence base is accepted.

A small number of papers within the existing literature have used each of the two key adaptions discussed within this study, though reasons for doing so have not been considered in any great depth. Furthermore, combining both of these adaptions to take an evaluative approach to realist synthesis is novel to this work and lends greater ontological depth to the research findings than may otherwise have been achieved.

This study builds on key methodological developments in realist research, demonstrating how realist methodologies can be customized to overcome challenges in developing and refining program theory from the literature, and contributes to the broader literature of innovative approaches to realist research.
Investigating Support for Management of the Pet Trade Invasion Risk
Authors: Episcopio‐Sturgeon Diane J. , Pienaar Elizabeth F.
Published: April 2020

The non‐native pet trade contributes directly to species invasions, thereby threatening wildlife. Biological invasions influence environmental change, resulting in species extinctions and biodiversity loss. To mitigate the pet trade invasion risk, interventions are required to prevent trade in non‐native animals with high invasion potential, impulse or ill‐informed purchases of non‐native pets by individuals who may release these animals, and the deliberate release of non‐native animals by pet owners. Interventions are also required to prevent the establishment of non‐native animals that have been released by pet owners (e.g., euthanasia). The successful implementation of these interventions depends on the support of pet owners and the public in the form of political support for, and compliance with, interventions. In 2017–2018, using both mail and online surveys, we measured the support of 1,171 members of the public and 550 owners of non‐native pets in Florida, USA, for 7 different interventions to mitigate the pet trade invasion risk, and we investigated determinants of this support. We found that individuals' support for interventions depended on their concern related to the invasion risks associated with the pet trade, trust in government to manage the pet trade, perceptions of how effective interventions would be in mitigating the pet trade invasion risk, and demographic characteristics. Support for interventions differed across pet owners and the public. Educating pet owners about the traits and cost of care for non‐native animals and providing them with options to relinquish unwanted pets may reduce the pet trade invasion risk. Engaging the pet trade in the design of interventions to mitigate invasion risks is likely important to attain voluntary compliance with these interventions. The effectiveness of interventions also depends on enforcement by agencies. Implementing interventions that effectively reduce the pet trade invasion risk is important to protect native and endangered wildlife. © 2020 The Wildlife Society.
Lifestyle‐Intervention‐Induced Reduction of Abdominal Fat Is Reflected by a Decreased Circulating Glycerol Level and an Increased HDL Diameter
Authors: Beekman Marian , Schutte Bianca A.M. , Akker Erik B. van den , Noordam Raymond , Dibbets‐Schneider Petra , de Geus‐Oei Lioe‐Fee , Deelen Joris , Rest Ondine van de , Heemst Diana van , Feskens Edith J.M. , Slagboom P. Eline
Published: April 2020

Scope

Abdominal obesity is one of the main modifiable risk factors of age‐related cardiometabolic disease. Cardiometabolic disease risk and its associated high abdominal fat mass, cholesterol, and glucose concentrations can be reduced by a healthier lifestyle. Hence, the aim is to understand the relation between lifestyle‐induced changes in body composition, and specifically abdominal fat, and accompanying changes in circulating metabolic biomarkers.

Methods and results

Data from the Growing Old Together (GOTO) study was used, which is a single arm lifestyle intervention in which 164 older adults (mean age 63 years, BMI 23–35 kg/m2) changed their lifestyle during 13 weeks by 12.5% caloric restriction plus 12.5% increase in energy expenditure. It is shown here that levels of circulating metabolic biomarkers, even after adjustment for body mass index, specifically associate with abdominal fat mass. The applied lifestyle intervention mainly reduces abdominal fat mass (−2.6%, SD = 3.0) and this reduction, when adjusted for general weight loss, is highly associated with decreased circulating glycerol concentrations and increased HDL diameter.

Conclusion

The lifestyle‐induced reduction of abdominal fat mass is particularly associated, independent of body mass index or general weight loss, with decreased circulating glycerol concentrations and increased HDL diameter.
Blood flow imaging by optimal matching of computational fluid dynamics to 4D‐flow data
Authors: Töger Johannes , Zahr Matthew J. , Aristokleous Nicolas , Markenroth Bloch Karin , Carlsson Marcus , Persson Per‐Olof
Published: April 2020

Purpose

Three‐dimensional, time‐resolved blood flow measurement (4D‐flow) is a powerful research and clinical tool, but improved resolution and scan times are needed. Therefore, this study aims to (1) present a postprocessing framework for optimization‐driven simulation‐based flow imaging, called 4D‐flow High‐resolution Imaging with a priori Knowledge Incorporating the Navier‐Stokes equations and the discontinuous Galerkin method (4D‐flow HIKING), (2) investigate the framework in synthetic tests, (3) perform phantom validation using laser particle imaging velocimetry, and (4) demonstrate the use of the framework in vivo.

Methods

An optimizing computational fluid dynamics solver including adjoint‐based optimization was developed to fit computational fluid dynamics solutions to 4D‐flow data. Synthetic tests were performed in 2D, and phantom validation was performed with pulsatile flow. Reference velocity data were acquired using particle imaging velocimetry, and 4D‐flow data were acquired at 1.5 T. In vivo testing was performed on intracranial arteries in a healthy volunteer at 7 T, with 2D flow as the reference.

Results

Synthetic tests showed low error (0.4%‐0.7%). Phantom validation showed improved agreement with laser particle imaging velocimetry compared with input 4D‐flow in the horizontal (mean −0.05 vs −1.11 cm/s, P < .001; SD 1.86 vs 4.26 cm/s, P < .001) and vertical directions (mean 0.05 vs −0.04 cm/s, P = .29; SD 1.36 vs 3.95 cm/s, P < .001). In vivo data show a reduction in flow rate error from 14% to 3.5%.

Conclusions

Phantom and in vivo results from 4D‐flow HIKING show promise for future applications with higher resolution, shorter scan times, and accurate quantification of physiological parameters.
Cross‐sectional area in median and ulnar nerve ultrasound correlates with hand volume
Authors: Tahmaz Melis , Yoon Min‐Suk , Schellinger Peter D. , Philipps Jörg
Published: April 2020

Background

The influence of demographic and anthropometric factors on nerve cross‐sectional area (CSA) reference values in high‐resolution ultrasound was evaluated in a prospective observational study.

Methods

We measured CSA of median, ulnar, radial, and sural nerves in 80 healthy adults from 18 to 98 years of age. Pearson's correlation and multiple linear regression with age, gender, body mass index, and hand volume were calculated.

Results

Ulnar and median nerve CSA showed a significant positive correlation with ipsilateral hand volume. Median nerve CSA in the left forearm (mean, 6.2 mm2; SD, 1.2) increased by 0.006 mm2 (SE = 0.002; P < .001) per cm3 of hand volume, resulting in a difference of 1.9 mm2 predictable by hand volume (mean, 326 cm3; SD, 81; range, 180–500).

Conclusions

The observed correlation of CSA and hand volume may influence the interpretation of CSA values in patients with very large or small hands.
Guidelines on clinical presentation and management of nondystrophic myotonias
Authors: Stunnenberg Bas C. , LoRusso Samantha , Arnold W. David , Barohn Richard J. , Cannon Stephen C. , Fontaine Bertrand , Griggs Robert C. , Hanna Michael G. , Matthews Emma , Meola Giovanni , Sansone Valeria A. , Trivedi Jaya R. , van Engelen Baziel G.M. , Vicart Savine , Statland Jeffrey M.
Published: April 2020

The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain‐of‐function mutations in the SCN4A gene or loss‐of‐function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation. In the absence of genetic confirmation, the diagnosis is supported by detailed electrophysiological testing, exclusion of other related disorders, and analysis of a variant of uncertain significance if present. Symptomatic treatment with a sodium channel blocker, such as mexiletine, is usually the first step in management, as well as educating patients about potential anesthetic complications.
A novel method to quantify cutaneous vascular innervation
Authors: Sohn Eunhee , Suh Bum Chun , Wang Ningshan , Freeman Roy , Gibbons Christopher H.
Published: April 2020

Introduction

To develop a new method to quantify the density of nerves, vessels, and the neurovascular contacts, we studied skin biopsies in diabetes and control subjects.

Methods

Skin biopsies with dual immunofluorescent staining were used to visualize nerves and blood vessels. The density of nerves, vessels, and their neurovascular contacts were quantified with unbiased stereology. Results were compared with examination findings, validated questionnaires, and autonomic function.

Results

In tissue from 19 controls and 20 patients with diabetes, inter‐rater and intra‐rater intraclass correlation coefficients were high (>0.85; P < .001) for all quantitative methods. In diabetes, the nerve densities (P < .05), vessel densities (P < .01), and the neurovascular densities (P < .01) were lower compared with 20 controls. Results correlated with autonomic function, examination and symptom scores.

Discussion

We report an unbiased, stereological method to quantify the cutaneous nerve, vessel and neurovascular density and offer new avenues of investigation into cutaneous neurovascular innervation in health and disease.
Optical and Depolarization Spectroscopy of Doubly Doped Alkaline‐Earth Fluorides
Authors: Radzhabov Evgeny
Published: April 2020

The process of recharging heterogeneous lanthanides in SrF2 and BaF2 crystals is studied by parallel measurements of optical absorption spectra and thermodepolarization curves. Electron transfer between lanthanides Yb2+–Nd3+, Eu2+–Yb3+ in SrF2, and between Yb2+–Nd3+, Eu2+–Yb3+, and Yb2+–Dy3+ in BaF2 is studied. Electron phototransfer between lanthanides, registered by a change in the absorption bands of divalent lanthanides, is accompanied by a backward migration of charge‐compensating interstitial fluorine, which is detected by a change in the corresponding thermodepolarization peaks of .
Fertilizer source and placement influence ammonia volatilization losses from water‐seeded rice systems
Authors: Chuong Thort , Plant Richard , Linquist Bruce A.
Published: April 2020

Ammonia volatilization, a primary N loss pathway from rice (Oryza sativaL.) production systems, leads to a reduction in N use efficiency and environmental problems. Ammonia volatilization has not been studied in water‐seeded rice systems or where aqueous NH3is the primary fertilizer N source. Our objective was to quantify NH3volatilization from preplant aqueous NH3and compare it with drilled or broadcast urea. In addition, NH3volatilization from a topdress N application applied midseason was quantified. This was accomplished with 10 field experiments representing a range of soil types. Preplant N treatments were a zero‐N control, injected aqueous NH3, broadcast urea, and drilled urea all applied at the farmer application rate to a dry soil. For the topdress experiment, the treatments were a zero‐N control and urea or (NH4)2SO4applied at 34 kg N ha−1. Ammonia volatilization was measured up to 3 and 1 wk after the preplant and topdress N was applied, respectively, using a semi‐open static chamber. Losses due to NH3volatilization from preplant broadcast urea were significantly higher than from the other other treatments but accounted for <2% of applied N. Losses from aqueous NH3and banded urea were lower but were significantly greater than from the control. The losses occurred in the first week after flooding. When N was topdressed, 1.5 and 2.6% of applied N were lost via volatilization from urea and (NH4)2SO4, respectively.
Diet, Lifestyle, Smoking
Authors: Tokgozoglu Lale , Hekimsoy Vedat , Costabile Giuseppina , Calabrese Ilaria , Riccardi Gabriele
Published: April 2020

Cardiovascular disease is the leading cause of death globally The past few decades have shown that especially low- and middle-income countries have undergone rapid industrialization, urbanization, economic development and market globalization. Although these developments led to many positive changes in health outcomes and increased life expectancies, they all also caused inappropriate dietary patterns, physical inactivity and obesity. Evidence shows that a large proportion of the cardiovascular disease burden can be explained by behavioural factors such as low physical activity, unhealthy diet and smoking. Controlling these risk factors from early ages is important for maintaining cardiovascular health. Even in patients with genetic susceptibility to cardiovascular disease, risk factor modification is beneficial.

Despite the tremendous advances in the medical treatment of cardiovascular risk factors to reduce overall cardiovascular risk, the modern lifestyle which has led to greater sedentary time, lower participation in active transport and time spent in leisure or purposeful physical activity, unhealthy diets and increased exposure to stress, noise and pollution have diminished the beneficial effects of contemporary medical cardiovascular prevention strategies. Therefore attenuating or eliminating these health risk behaviours and risk factors is imperative in the prevention of cardiovascular diseases.
Gender norms about romantic relationships and sexual experiences among very young male adolescents in Korogocho slum in Kenya
Authors: Maina Beatrice W. , Orindi Benedict O. , Sikweyiya Yandisa , Kabiru Caroline W.
Published: April 2020

Objectives

To investigate the association between gender norms about romantic relationships and sexual experiences of very young male adolescents (VYMA) living in Korogocho slum in Nairobi, Kenya.

Methods

We used cross-sectional data from a sample of 426 VYMA living in Korogocho slum. We conducted an exploratory factor analysis and confirmatory factor analysis to, respectively, explore and validate the factor structure underlying gender norms scale items. We used structural equation modelling to assess the association between gender norms and sexual experiences of VYMA.

Results

We found high endorsement of heteronormative beliefs about romantic relationships and low endorsement of sexual double standards. Sexual experience was associated with low endorsement of heteronormative beliefs, being pre-pubertal, school absenteeism and being below recommended grade for age. Sharing a sleeping room with more than two people, been born outside Nairobi, and living in households headed by older persons lowered the likelihood of sexual experience.

Conclusions

Our findings underscore the need for further research to understand how gender norms evolve as young boys transition through adolescence to adulthood and how these changes impact on sexual behaviors
Synthesis and cytotoxic evaluation of malachite green derived oleanolic and ursolic acid piperazineamides
Authors: Friedrich Sander , Serbian Immo , Hoenke Sophie , Wolfram Ratna Kancana , Csuk René
Published: April 2020

The coupling of acetylated piperazinylamide spacered triterpenoic oleanolic acid and ursolic acid withmetaorparasubstituted carboxylated malachite green analogs gave conjugates10,11,15, and16that were cytotoxic for several human tumor cell lines. Especially, an oleanolic acid-derived compound10was cytotoxic for MCF-7 human breast carcinoma cells (EC50 = 0.7 μM). These derivatives represent first examples of triterpenoic acid derivatives holding a cationic scaffold derived from malachite green.
Sorafenib administered using a high-dose, pulsatile regimen in patients with advanced solid malignancies: a phase I exposure escalation study
Authors: Mammatas L. H. , Zandvliet A. S. , Rovithi M. , Honeywell R. J. , Swart E. L. , Peters G. J. , Menke-van der Houven van Oordt C. W. , Verheul H. M. W.
Published: April 2020

Background

(Pre)clinical evidence is accumulating that intermittent exposure to increased doses of protein kinase inhibitors may improve their treatment benefit. In this phase I trial, the safety of high-dose, pulsatile sorafenib was studied.

Patients and methods

High-dose sorafenib was administered once weekly in exposure escalation cohorts according to a 3 + 3 design. Drug monitoring was performed in weeks 1–3 and doses were adjusted to achieve a predefined target plasma area under the curve (AUC)(0–12 h). The effect of low gastric pH on improving sorafenib exposure was investigated by intake of the acidic beverage cola.

Results

Seventeen patients with advanced malignancies without standard treatment options were included. Once weekly, high-dose sorafenib exposure was escalated up to a target AUC(0–12 h) of 125–150 mg/L/h, achieving a twofold higher Cmax compared to standard continuous dosing. Dose-limiting toxicity was observed in three patients: grade 3 duodenal perforation (2800 mg sorafenib), grade 5 multiorgan failure (2800 mg sorafenib) and grade 5 biliary tract perforation (3600 mg sorafenib). The mean difference between observed and target AUC(0–12 h) was 45% (SD ± 56%) in week 1 using a fixed starting dose of sorafenib compared to 2% (SD ± 32%) in week 3 as a result of drug monitoring (P = 0.06). Dissolving sorafenib in cola, instead of water, did not improve sorafenib exposure. Clinical benefit with stable disease as the best response was observed in two patients.

Conclusion

Treatment with high-dose, once weekly sorafenib administration resulted in dose-limiting toxicity precluding dose escalation above the exposure cohort of 125–150 mg/L/h. Drug monitoring was a successful strategy to pursue a target exposure.
GM-CSF does not rescue poor-quality embryos: secondary analysis of a randomized controlled trial
Authors: Rodriguez-Wallberg Kenny A. , Munding Bibi , Ziebe Søren , Robertson Sarah A.
Published: April 2020

Purpose

To evaluate implantation potential of cleavage-stage embryos cultured in medium containing 2 ng/ml granulocyte–macrophage colony-stimulating factor (GM-CSF) versus control medium, according to embryo morphological quality and then transferred on day 3.

Methods

Explorative secondary data analysis of a multicenter, randomized, placebo-controlled, double-blinded prospective study of 1149 couples with embryo transfer after IVF/ICSI. This analysis includes a subgroup of 422 subjects with either single-embryo transfer (SET, N = 286) or double-embryo transfer of two embryos with equivalent morphological quality (DET, N = 136). Implantation rate and live birth rate were assessed according to category of morphological embryo quality on day 3.

Results

Culture with GM-CSF did not increase the implantation rate for embryos classified as poor quality. A trend towards greater benefit of GM-CSF on implantation and survival until live birth for top-quality embryos (TQEs) compared with poor-quality embryos was observed, although not statistically significant. For TQEs, the percentage of transferred embryos resulting in a live born baby was: 40.9 ± 5.3% (GM-CSF) versus 30.5 ± 4.6% (control) (P = 0.24; odds ratio [OR] 1.43, 95% confidence interval [CI] 0.79–2.59), and for embryos with less than 6 cells at day 3 this same rate was: 7.4 ± 3.3% (GM-CSF) versus 12.0 ± 4.0% (control) (P = 0.26; OR 0.53, 95% CI 0.17–1.61).

Conclusion

This exploratory analysis is consistent with GM-CSF protecting morphologically normal embryos from culture-induced stress and does not support an effect of GM-CSF in rescuing poor-quality embryos.

ClinicalTrials.gov identifier: NCT00565747.
Varieties of Power
Authors: Mulder Jesse M.
Published: April 2020

Power enthusiasts are engaged in two projects: (1) developing a decent metaphysical account of powers, and (2) applying that account in order to make progress on various other philosophical issues, ranging from narrowly related topics such as causality to further removed ones such as free will, reasoning, or perception. I argue that an intermediate step may be taken, one that explores ‘varieties of power’ while still staying within the realm of (1), of ‘pure’ powers metaphysics. Taking this intermediate step provides a much more interesting basis for those involved in project (2), ‘applied’ powers metaphysics. I articulate four such varieties of power by exploring various dimensions in which the explanatory profile of a power can be extended. I then briefly survey how these relate to various further metaphysical issues.
Environmental justice and the SDGs: from synergies to gaps and contradictions
Authors: Menton Mary , Larrea Carlos , Latorre Sara , Martinez-Alier Joan , Peck Mika , Temper Leah , Walter Mariana
Published: April 2020

Through their synergies, trade-offs, and contradictions, the sustainable development goals (SDGs) have the potential to lead to environmental justices and injustices. Yet, environmental justice (EJ), and social justice more broadly, are not currently embedded within the language and spirit of the SDGs. We part from the premise that “many ‘environmental’ problems are, by their very nature, problems of justice” (Lele, Wiley Interdiscip Rev Water 4:e1224, 2017). We review progress in EJ frameworks in recent years, arguing for the need to move beyond a focus on the four principles of mainstream EJ (distribution, procedure, recognition, and capabilities) towards a more intersectional decolonial approach to environmental justice that recognises the indispensability of both humans and non-humans. EJ frameworks, and the SDGs should recognise power dynamics, complex interactions among injustices, and listens to the different ‘senses of justice’ and desires of theorists, activists, and other stakeholder from the Global South. We analyze how EJ frameworks are, or fail to be, incorporated in the SDGs with a focus on the food–water–health nexus (SDG2, 3, 6); climate-energy (SDG7, 13), conservation (SDG14, 15); and poverty and inequality (SDG1, 10). We call attention to the ‘elephant in the room’—the failure to go beyond GDP but instead include economic growth as a goal (SDG8). We argue that sustainable degrowth and intersectional decolonial environmental justices would create better conditions for the transformative changes needed to reach the broader aim of the SDGs: to leave no one behind.
The influence of stirring time and frequency of impeller rotation on evaluation of drops dimensions and rheological properties of the multiple emulsion
Authors: Major-Godlewska Marta
Published: April 2020

The analysis of drops and rheological measurements of the emulsion produced were presented in the article. The influence of stirring time and rotation frequency on the drops size of the emulsion produced in the propeller of diameter D = 0.1 m and liquid height H = 0.5D equipped with four standard flat dividers was defined. The Smith turbine stirrer was used to stir the emulsion produced. The drop size was defined for three different propeller rotation frequencies, 500 rpm, 1000 rpm and 1500 rpm. The stirring time, after which the samples were collected, was accordingly 15 min and 45 min. To produce the emulsion, sunflower oil was used in the oil phase and distilled water in the water phase. There were 6 measurement series all together, and they were presented as the diameter size distribution. The mean arithmetic diameter da, median dm and the mean Sauter diameter d32 were determined. The rheological measurements of the produced emulsions were presented in graphics as a function τ = f(γ) and were described as Herschel–Bulkley and Bingham models presented in Table 3.
Chronic activation of GPR40 does not negatively impact upon BRIN-BD11 pancreatic β-cell physiology and function
Authors: Vilas-Boas Eloisa Aparecida , Karabacz Noémie , Marsiglio-Librais Gabriela Nunes , Valle Maíra Melo Rezende , Nalbach Lisa , Ampofo Emmanuel , Morgan Bruce , Carpinelli Angelo Rafael , Roma Leticia Prates
Published: April 2020

Background

Free fatty acids (FFAs) are known for their dual effects on insulin secretion and pancreatic β-cell survival. Short-term exposure to FFAs, such as palmitate, increases insulin secretion. On the contrary, long-term exposure to saturated FFAs results in decreased insulin secretion, as well as triggering oxidative stress and endoplasmic reticulum (ER) stress, culminating in cell death. The effects of FFAs can be mediated either via their intracellular oxidation and consequent effects on cellular metabolism or via activation of the membrane receptor GPR40. Both pathways are likely to be activated upon both short- and long-term exposure to FFAs. However, the precise role of GPR40 in β-cell physiology, especially upon chronic exposure to FFAs, remains unclear.

Methods

We used the GPR40 agonist (GW9508) and antagonist (GW1100) to investigate the impact of chronically modulating GPR40 activity on BRIN-BD11 pancreatic β-cells physiology and function.

Results

We observed that chronic activation of GPR40 did not lead to increased apoptosis, and both proliferation and glucose-induced calcium entry were unchanged compared to control conditions. We also observed no increase in H2O2 or superoxide levels and no increase in the ER stress markers p-eIF2α, CHOP and BIP. As expected, palmitate led to increased H2O2 levels, decreased cell viability and proliferation, as well as decreased metabolism and calcium entry. These changes were not counteracted by the co-treatment of palmitate-exposed cells with the GPR40 antagonist GW1100.

Conclusions

Chronic activation of GPR40 using GW9508 does not negatively impact upon BRIN-BD11 pancreatic β-cells physiology and function. The GPR40 antagonist GW1100 does not protect against the deleterious effects of chronic palmitate exposure. We conclude that GPR40 is probably not involved in mediating the toxicity associated with chronic palmitate exposure.
Just the Facts: Recommendations on point-of-care ultrasound use and machine infection control during the coronavirus disease 2019 pandemic
Authors: Kim Daniel J. , Jelic Tomislav , Woo Michael Y. , Heslop Claire , Olszynski Paul
Published: April 2020

The World Health Organization declared the novel coronavirus disease 2019 (COVID-19) to be a pandemic on March 11, 2020, and, currently, there are over 10,000 confirmed cases in Canada, with this number expected to grow exponentially. There has been widespread interest in the use of point-of-care ultrasound (POCUS) in the management of patients with suspected COVID-19. The CAEP Emergency Ultrasound Committee has developed recommendations on the use of POCUS in these patients, with an emphasis on machine infection control measures.
Visibility through invisibility: Spatialized political subjectivities of Alevi youth
Authors: Özata Tolga
Published: April 2020

This article investigates Alevi youth subjectivities in a neighborhood of İstanbul, Okmeydanı, in which mainly Alevi people live, through the youth’s self-positionings in revolutionary groups, which has deeply marked the highly politicized history of the district. The grievances of Okmeydanlı Alevi youth have grown increasingly complex, stemming from experiences of violence, family legacies of victimhood, and, in recent years, new forms of exclusion. Coupled with generational ruptures between youth and their families in experiencing Alevi identity, Alevi youth have created a political identity and collectivity in the sphere of revolutionary politics. In this politicization, Okmeydanı becomes a spatialization of resistance which gives the youth a sense of power to achieve solidarity and find intimacy to defend themselves and their rights. Moreover, for the youth, engaging in a revolutionary political identity enables them to define themselves and redefine Alevi identity in contrast with, and sometimes against, the perceptions of their families. I argue that it is through this performativity that Okmeydanlı Alevi youth achieve self-empowerment and identity construction; and through this performativity in street politics that the youth render their agencies and self-representations visible on public space.
Publisher Correction: Ambipolar device simulation based on the drift-diffusion model in ion-gated transition metal dichalcogenide transistors
Authors: Ueda Akiko , Zhang Yijin , Sano Nobuyuki , Imamura Hiroshi , Iwasa Yoshihiro
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Spontaneous emergence of Josephson junctions in homogeneous rings of single-crystal Sr2RuO4
Authors: Yasui Yuuki , Lahabi Kaveh , Becerra Victor Fernández , Fermin Remko , Anwar Muhammad Shahbaz , Yonezawa Shingo , Terashima Takahito , Milošević Milorad V. , Aarts Jan , Maeno Yoshiteru
Published: April 2020

The chiral p-wave order parameter in Sr2RuO4 would make it a special case amongst the unconventional superconductors. A consequence of this symmetry is the possible existence of superconducting domains of opposite chirality. At the boundary of such domains, the locally suppressed condensate can produce an intrinsic Josephson junction. Here, we provide evidence of such junctions using mesoscopic rings, structured from Sr2RuO4 single crystals. Our order parameter simulations predict such rings to host stable domain walls across their arms. This is verified with transport experiments on loops, with a sharp transition at 1.5 K, which show distinct critical current oscillations with periodicity corresponding to the flux quantum. In contrast, loops with broadened transitions at around 3 K are void of such junctions and show standard Little–Parks oscillations. Our analysis demonstrates the junctions are of intrinsic origin and makes a compelling case for the existence of superconducting domains.
Low birth weight influences the postnatal abundance and characteristics of satellite cell subpopulations in pigs
Authors: Stange K. , Miersch C. , Sponder G. , Röntgen M.
Published: April 2020

Low birth weight (LBW) can cause lifelong impairments in muscle development and growth. Satellite cells (SC) and their progeny are crucial contributors to myogenic processes. This study provides new data on LBW in piglets combining insights on energy metabolism, muscle capillarization and differences in SC presence and function. To this aim, muscle tissues as well as isolated myogenic cells of 4-day-old German Landrace piglets were analyzed. For the first time two heterogeneous SC subpopulations, which contribute differently to muscle development, were isolated from LBW pigs by Percoll density gradient centrifugation. The muscles of LBW piglets showed a reduced DNA, RNA, and protein content as well as lower activity of the muscle specific enzymes CK, ICDH, and LDH compared to their normal birth weight siblings. We assume that deficits in energy metabolism and capillarization are associated with reduced bioavailability of SC, possibly leading to early exhaustion of the SC reserve cell pool and the cells’ premature differentiation.
A Randomised Control Trial and Comparative Analysis of Multi-Dimensional Learning Tools in Anatomy
Authors: Wang Chris , Daniel Ben Kei , Asil Mustafa , Khwaounjoo Prashanna , Cakmak Yusuf Ozgur
Published: April 2020

This article presents the results of a study that examined students’ ability to retain what they have learned in an anatomy course after thirty days via using various learning tools for twenty minutes. Fifty-two second-year medical students were randomly assigned to three learning tools: text-only, three-dimension visualisation in a two-dimensional screen (3DM), or mixed reality (MR). An anatomy test lasting for twenty minutes measuring spatial and nominal knowledge was taken immediately after the learning intervention and another thirty days later. Psychometric tests were also used to measure participants’ memory, reasoning and concentration abilities. Additionally, electroencephalogram data was captured to measure the participants’ awakeness during the learning session. Results of this study showed that the MR group performed poorly in the nominal questions compared to the other groups; however, the MR group demonstrated higher retention in both the nominal and spatial type information for at least a month compared to the other groups. Furthermore, participants in the 3DM and MR groups reported increased engagement. The results of this study suggest that three-dimensional visualiser tools are likely to enhance learning in anatomy education. However, the study itself has several limitations; some include limited sample size and various threats to internal validity.
Evaluation of the role of mitochondria in the non-targeted effects of ionizing radiation using cybrid cellular models
Authors: Miranda Silvana , Correia Marcelo , Dias Anabela G. , Pestana Ana , Soares Paula , Nunes Joana , Lima Jorge , Máximo Valdemar , Boaventura Paula
Published: April 2020

Radiobiology is moving towards a better understanding of the intercellular signaling that occurs upon radiation and how its effects relate to the dose applied. The mitochondrial role in orchestrating this biological response needs to be further explored. Cybrids (cytoplasmic hybrids) are useful cell models for studying the involvement of mitochondria in cellular processes. In the present study we used cybrid cell lines to investigate the role of mitochondria in the response to radiation exposure. Cybrid cell lines, derived from the osteosarcoma human cell line 143B, harboring, either wild-type mitochondrial DNA (Cy143Bwt), cells with mitochondria with mutated DNA that causes mitochondrial dysfunction (Cy143Bmut), as well as cells without mitochondrial DNA (mtDNA) (143B-Rho0), were irradiated with 0.2 Gy and 2.0 Gy. Evaluation of the non-targeted (or bystander) effects in non-irradiated cells were assessed by using conditioned media from the irradiated cells. DNA double stranded breaks were assessed with the γH2AX assay. Both directly irradiated cells and cells treated with the conditioned media, showed increased DNA damage. The effect of the irradiated cells media was different according to the cell line it derived from: from Cy143Bwt cells irradiated with 0.2 Gy (low dose) and from Cy143Bmut irradiated with 2.0 Gy (high dose) induced highest DNA damage. Notably, media obtained from cells without mtDNA, the143B-Rho0 cell line, produced no effect in DNA damage. These results point to a possible role of mitochondria in the radiation-induced non-targeted effects. Furthermore, it indicates that cybrid models are valuable tools for radiobiological studies.
Spontaneously Conversion from Film to High Crystalline Quality Stripe during Molecular Beam Epitaxy for High Sn Content GeSn
Authors: Wang Nan , Xue Chunlai , Wan Fengshuo , Zhao Yue , Xu Guoyin , Liu Zhi , Zheng Jun , Zuo Yuhua , Cheng Buwen , Wang Qiming
Published: April 2020

Two series of Ge0.8Sn0.2 samples were grown on Ge buffered Si substrate by molecular beam epitaxy (MBE) to investigate the influence of growth temperature and film thickness towards the evolution of surface morphology. A novel phenomena was observed that the Ge0.8Sn0.2 film was segregated and relaxed by the formation of GeSn stripes on the film. Under specific growth condition, the stripes can cover nearly the whole surface. XRD, TEM, AFM, PL and TEM results indicated that the stripes are high quality single crystalline GeSn with Sn content around 5%. The formation of GeSn stripes proposes an effective strategy to fabricate high crystalline quality GeSn stripe on Si, where the Ge0.8Sn0.2 film serves as precursor and the segregated Sn works as catalyst droplets. This technique has great potential for future optoelectronic and microelectronic applications.