bluuebunny/crossref_metadata_2025 huggingface dataset:
How much has urbanisation affected United Kingdom temperatures?
Authors: Goddard Ian L. M. , Tett Simon F. B.
Published: March 2019

This study aims to estimate the affect of urbanisation on daily maximum and minimum temperatures in the United Kingdom. Urban fractions were calculated for 10 km × 10 km areas surrounding meteorological weather stations. Using robust regression a linear relationship between urban fraction and temperature difference between station measurements and ERA‐Interim reanalysis temperatures was estimated. For an urban fraction of 1.0, the daily minimum 2‐m temperature was estimated to increase by 1.90 ± 0.88 K while the daily maximum temperature was not significantly affected by urbanisation. This result was then applied to the whole United Kingdom with a maximum T
min urban heat island intensity (UHII) of about 1.7K in London and with many UK cities having T
min UHIIs above one degree.

This paper finds through the method of observation minus reanalysis that urbanisation has significantly increased the daily minimum 2‐m temperature in the United Kingdom by up to 1.70 K.
Individual identification and correction of mistakes in statements of biochemical significance: An effective learning process for graduate medical students
Authors: Bobby Zachariah , Radhika M. R. , Srilatha K. , Nithin Kumar U. , Kavitha S.
Published: March 2019

Focused self‐directed learning process needs to be promoted at present among graduate medical students in view of the information load and limited time available with them. In this study, comparison of the effect of identifying and correcting the mistakes in a given set of wrong statements with the effect of studying correct statements individually by graduate medical students on their understanding of the topic “Cancer Biology” was carried out. At the end of regular teaching module, students were asked to identify the mistakes in a set of seven incorrect statements and correct them individually without peer consultation. Another set of seven correct statements were also provided to them and were asked to study their significance. The effects on low, medium, and high achievers were evaluated by pre‐ and post‐tests with the same set of Multiple Choice Questions (MCQs). Mean post‐test marks were significantly higher among all the three groups compared to pretest marks for the wrong statements given. For the correct statements, the post‐test marks were significantly higher than the pretest marks only for the low and medium achievers. The gain from identifying the mistakes was higher than studying the correct statements for all the three groups of students. Individual correction of errors in statements is a superior active learning process in comparison to the study of correct statements. © 2019 International Union of Biochemistry and Molecular Biology, 47(4):476–480, 2019.
Counsellors in the National Health Service: A mixed‐method study of efficacy and satisfaction from the counsellor perspective
Authors: Ryan Gemma , Duncan Charlie , Moller Naomi P.
Published: March 2019

Background

It is difficult to know how many counsellors work in the UK's National Health Service (NHS). At a time when the British Government is pledging an expansion of the mental health workforce, it is important to understand both the opportunities and barriers for counsellors to work in the NHS.

Aim

To understand counsellors’ job roles, pay, perceptions of services, workplace stress and reasons for leaving the NHS.

Method

An online survey was advertised to members of the British Association for Counselling and Psychotherapy (BACP); just under 2,000 counsellors responded. The sample was majority female, white and had completed training. Mixed methods were utilised to analyse the data which incorporated use of thematic analysis.

Findings

The data suggest that, as a workforce, counsellors are prone to being “squeezed” out of the NHS workforce; that they are comparatively “underpaid,” are “pressurised” by high level of work demand and are consequently experiencing concerning levels of workplace stress; and that they perceive themselves to be, in multiple ways, “undervalued.” Despite this, members reported high adequacy of therapist qualifications and supervision quality within NHS services.

Conclusions

Counsellors have expressed a desire to undertake more work in the NHS and are a potentially cost‐effective mental health workforce in comparison with other types of professionals. However, this study has evidenced significant structural, cultural and pay and promotion‐related barriers that are pushing counsellors out of the NHS. Of particular concern is what appears to be a broad undervaluing of counsellors as a professional group.
A homozygous genome‐edited Sept2‐EGFP fibroblast cell line
Authors: Banko Monika , Mucha‐Kruczynska Iwona , Weise Christoph , Heyd Florian , Ewers Helge
Published: March 2019

Septins are a conserved, essential family of GTPases that interact with actin, microtubules, and membranes and form scaffolds and diffusion barriers in cells. Several of the 13 known mammalian septins assemble into nonpolar, multimeric complexes that can further polymerize into filamentous structures. While some GFP‐coupled septins have been described, overexpression of GFP‐tagged septins often leads to artifacts in localization and function. To overcome this ubiquitous problem, we have here generated a genome‐edited rat fibroblast cell line expressing Septin 2 (Sept2) coupled to enhanced green fluorescent protein (EGFP) from both chromosomal loci. We characterize these cells by genomic polymerase chain reaction (PCR) for genomic integration, by western blot and reverse transcriptase‐PCR for expression, by immunofluorescence and immunoprecipitation for the colocalization of septins with one another and cellular structures and for complex formation of different septins. By live cell imaging, proliferation and migration assays we investigate proper function of septins in these cells. We find that EGFP is incorporated into both chromosomal loci and only EGFP‐coupled Sept2 is expressed in homozygous cells. We find that endogenous Sept2‐EGFP exhibits expression levels, localization and incorporation into cellular septin complexes similar to the wt in these cells. The expression level of other septins is not perturbed and cell division and cell migration proceed normally. We expect our cell line to be a useful tool for the cell biology of septins, especially for quantitative biology.
Azobenzene‐Based Photoswitches Facilitating Reversible Regulation of Kinesin and Myosin Motor Systems for Nanotechnological Applications
Authors: Amrutha Ammathnadu S. , Sunil Kumar K. R. , Tamaoki Nobuyuki
Published: March 2019

The past decade has witnessed several significant efforts made towards implementing the biomolecular functions of motor proteins for nanotechnological applications. However, employing motor protein systems in artificial environments demands for a precise and flexible spatiotemporal control mechanism. Light being an ideal external stimulus offers major advantages, allowing better spatial and temporal resolution compared to other diffusion‐based approaches. Robust photochromic properties of azobenzene make it a prime candidate that could be incorporated into biologically active molecules to realize two‐way regulation of motor protein function. In this Minireview, we summarize the design strategies of azobenzene‐based photoswitches for reversibly regulating kinesin‐ and myosin‐driven shuttle movements and briefly discuss photoisomerization‐induced modulation in motor protein activity.
Interaction phenomena of ion‐acoustic quasi‐solitons and classical‐solitons in three component plasma
Authors: Alam M S , Talukder M R
Published: March 2019

The space–time evolution of the cnoidal‐soliton solution, characteristics of the quasi‐soliton solution of Korteweg‐de‐Vries (KdV) equation, and the interaction phenomena of ion‐acoustic waves (IAWs) are investigated in a plasma system consisting of positive and negative ions with superthermal electrons. To do this, and (Ar+, F−) plasmas are considered and two‐sided KdV equations (KdVEs) are derived applying the extended Poincaré‐Lighthill‐Kuo (ePLK) method. The effects on wave structures, potential profiles, and propagation characteristics with plasma parameters of the cnoidal‐wave, quasi‐soliton solution, and head‐on collision phenomena of IAWs are presented graphically. It was found that the superthermality parameter and the mass ratio of ions play a significant role in the head‐on collision between soliton and standing cnoidal wave and reveal that the collision is elastic and both waves change their phase shifts due to collision. Moreover, the superthermality parameters are also responsible for the production of compressive and rarefactive phase shifts in overtaking collision processes between right travelling classical soliton (CS) and cnoidal wave (CW) and reduced the amplitudes of IAWs. It was also found that a new wave is created with a high amplitude in the interacting region during collision depending on the plasma parameters.
Effect of magnetic field and friction force on the velocity autocorrelation in two‐dimensional Yukawa liquids
Authors: Dzhumagulova Karlygash N. , Masheyeva Ranna U. , Ramazanov Tlekkabul S.
Published: March 2019

The effect of an external magnetic field and gas‐induced friction on the velocity autocorrelation of the dust particles in strongly coupled two‐dimensional Yukawa liquids was investigated. The Langevin dynamics computer simulation method was used. The presence of the friction originating from the background gas leads to the disappearance of a collective oscillation mode, corresponding to the cyclotron frequency of the dust particles, and a decrease in the dominant mode.
Warming at the population level: Effects on age structure, density, and generation cycles
Authors: Laughton Alice M. , Knell Robert J.
Published: March 2019

The impact of climate change on strongly age‐structured populations is poorly understood, despite the central role of temperature in determining developmental rates in ectotherms. Here we examine the effect of warming and its interactions with resource availability on the population dynamics of the pyralid moth Plodia interpunctella, populations of which normally show generation cycles, a consequence of strong and asymmetric age‐related competition. Warming by 3°C above the standard culture temperature led to substantial changes in population density, age structure, and population dynamics. Adult populations were some 50% larger in warmed populations, probably because the reduced fecundity associated with warming leads to reduced larval competition, allowing more larvae to develop to adulthood. Warming also interacted with resource availability to alter population dynamics, with the generation cycles typical of this species breaking down in the 30° populations when standard laboratory diet was provided but not when a reduced nutrient poor diet was used. Warming by 6° led to either rapid extinction or the persistence of populations at low densities for the duration of the experiment. We conclude that even moderate warming can have considerable effects on population structure and dynamics, potentially leading to complete changes in dynamics in some cases. These results are particularly relevant given the large number of economically important species that exhibit generation cycling, in many cases arising from similar mechanisms to those operating in P. interpunctella.
Hg2NF, Analogue of HgO
Authors: Manjunath Krishnappa , Prasad Suchitra , Servottam Swaraj , Waghmare Umesh V. , Rao C. N. R.
Published: March 2019

Substitution of aliovalent anions in metal oxides imparts significant changes to the electronic structure of the materials. We have been able to fully substitute N3– and F– in place of O2– to obtain Hg2NF. Hg2NF is isostructural with orthorhombic HgO (mineral montroydite). The bond lengths of Hg2NF obtained by Rietveld refinement are dissimilar and the optical band gap of Hg2NF (2.56 eV) is higher than that of HgO (2.2 eV). The elemental composition of Hg, N, and F were obtained by X‐ray photoelectron spectroscopy and found to be 2:1:1. First‐principles calculations show Hg2NF to be a direct band gap semiconductor with the valence band consisting mainly of N (2p) orbitals. The conduction band minimum (CBM) has a mixed contribution from Hg‐6s and N‐2p orbitals. The lowest energy band has a dominant contribution from Hg‐5d states in all the configurations.
Switching the N‐Alkylation of Arylamines with Benzyl Alcohols to Imine Formation Enables the One‐Pot Synthesis of Enantioenriched α‐N‐Alkylaminophosphonates
Authors: Hofmann Natalie , Hultzsch Kai C.
Published: March 2019

The selective N‐alkylation of anilines with benzylic alcohols can be switched in favor of the dehydrogenative condensation process using the nitrile‐ligated Knölker's complex by conducting the reaction either in a closed system under inert conditions, or in an open system in air. The selective formation of imines, containing reactive C=N bonds, provides an opportunity towards further functionalization. Indeed, a one‐pot three‐component condensation of alcohols, amines and phosphites, promoted by an iron‐based Knölker‐type complex in combination with a chiral BINOL‐based phosphoric acid, provides access to enantioenriched α‐N‐alkylaminophosphonates.
Pseudo‐Crown Ethers as Novel Scaffolds for the Development of Al3+‐Selective Fluorescent Probes
Authors: Kozlov Mikhail A. , Uvarov Denis Y. , Gorbatov Sergey A. , Kolotirkina Natalya G. , Averin Alexey D. , Kachala Vadim V. , Lyssenko Konstantin A. , Zavarzin Igor V. , Volkova Yulia A.
Published: March 2019

Herein, we report the systematic evaluation of the BODIPY series functionalized with pseudo‐crown ethers against metal cations and assessment of their potential as novel off‐on fluorescent probes selective for aluminum(III) cations.
Effect of Co‐Based Metal–Organic Framework Prepared by an In Situ Growth Method on the Photoelectrochemical Performance of Electrodeposited Hematite Photoanode
Authors: Li Longzhu , Zhang Honglei , Liu Changhai , Liang Penghua , Mitsuzaki Naotoshi , Chen Zhidong
Published: March 2019

The Co‐based metal–organic framework (Co‐MOF) is successfully prepared on the Ti‐modified hematite nanosheet photoelectrode via a simple in situ hydrothermal method, and the sample is named as Co‐MOF@TiFe. Under the bias potential of 1.23 and 1.43 V (vs reversible hydrogen electrode [RHE]), the photocurrents of the Co‐MOF@TiFe photoanode are 1.24 and 1.78 mA cm−2, respectively. Furthermore, the onset potential of the Co‐MOF@TiFe photoanode is negatively shifted by about 120 mV than that of the Ti‐modified hematite sample. At 1.23 V (vs RHE), the enhanced photoelectrochemical (PEC) performance of the Co‐MOF@TiFe photoanode is attributed to its substantially increased surface charge injection efficiency and its small increased bulk charge separation efficiency. The reasons for the increased surface charge injection efficiency are its decreased surface states 1 (SS1), the appearance of surface states 2 (SS2), and the Co‐MOF acting as a catalyst. The increased bulk charge separation efficiency is attributed to the formation of the hematite/Co‐MOF heterojunction and the rougher surface caused by etching. Herein, the effects of the in situ prepared Co‐MOF coating on the crystalline structure, morphology, and PEC performance of Ti‐modified hematite are systematically investigated by characterization.
Model‐Based Uncertainty Quantification for the Product Properties of Lithium‐Ion Batteries
Authors: Laue Vincent , Schmidt Oke , Dreger Henning , Xie Xiangzhong , Röder Fridolin , Schenkendorf René , Kwade Arno , Krewer Ulrike
Published: March 2019

A model‐based uncertainty quantification (UQ) approach is applied to the manufacturing process of lithium‐ion batteries (LIB). Cell‐to‐cell deviations and the influence of sub‐cell level variations in the material and electrode properties of the cell performance are investigated experimentally and via modeling. The electrochemical battery model of the Doyle–Newman type is extended to cover the effect of sub‐cell deviation of product properties of the LIB. The applied model is parameterized and validated using a stacked pouch cell containing Li(Ni1/3Co1/3Mn1/3)O2 (NMC) and graphite (LixC6). It is integrated into a sampling‐based UQ framework. A nested point estimate method (PEM) is applied to a large number of independent normal distributed parameters. The simulations follow two consecutive nonideal manufacturing process steps: coating and calendering. The nested PEM provides a global sensitivity analysis that shows a change in sensitivity of the investigated parameters depending on the applied C‐rate. Furthermore, the sub‐cell level deviation of parameters in heterogeneous electrodes provokes a nonuniform current distribution in the cell. This alters the variance of the discharge capacity distribution. Therefore, sub‐cell deviation has to be considered to quantify process uncertainties. The applied method is feasible and highly efficient for this purpose.
Dynamic energy efficiency of slack‐based measure in high‐income economies
Authors: Lu Ching‐Cheng , Chen Xiang , Hsieh Chia‐Leng , Chou Kuo‐Wei
Published: March 2019

Mankind is constantly pursuing economic growth and social development, and while these bring convenience to people, they involve large amounts of greenhouse gas emissions under the heavy use of energy, which produces quite serious air pollution, which not only affects people's health but also leads to ecological environmental damage. Nowadays, the impact of the environment and the negative impacts of the world's economies while promoting economic growth are the most important issues for economies to achieve balanced development. This study uses the dynamic slack‐based data envelopment analysis (DEA) model to assess the environmental energy efficiency of high‐income economies (including China) and explore the negative impacts on the environment, to obtain a basis for energy‐saving emission reduction methods or configurations by using 48 high‐income economies (including China) from 2010 to 2014. The interperiod (carryover) variable is gross domestic product (GDP). The empirical results show that economies with high energy efficiency have a large consumption of energy and are unable to reduce carbon dioxide emissions. We also find that there exists a difference in the results depending on whether GDP is considered as the carryover variable. European economies are more efficient in energy consumption than others, and Asian economies are the most inefficient. In order to pursue GDP growth, economies need to consider reducing their energy consumption and CO2 emissions and improve their energy usage efficiency, further implementing sustainability.
Brain MRI shows white matter sparing in Kennedy's disease and slow‐progressing lower motor neuron disease
Authors: Spinelli Edoardo G. , Agosta Federica , Ferraro Pilar M. , Querin Giorgia , Riva Nilo , Bertolin Cinzia , Martinelli Ilaria , Lunetta Christian , Fontana Andrea , Sorarù Gianni , Filippi Massimo
Published: March 2019

The extent of central nervous system involvement in Kennedy's disease (KD) relative to other motor neuron disease (MND) phenotypes still needs to be clarified. In this study, we investigated cortical and white matter (WM) MRI alterations in 25 patients with KD, compared with 24 healthy subjects, 25 patients with sporadic amyotrophic lateral sclerosis (ALS), and 35 cases with lower motor neuron‐predominant disease (LMND). LMND patients were clinically differentiated into 24 fast and 11 slow progressors. Whole‐brain cortical thickness, WM tract‐based spatial statistics and corticospinal tract (CST) tractography analyses were performed. No significant difference in terms of cortical thickness was found between groups. ALS patients showed widespread decreased fractional anisotropy and increased mean (MD) and radial diffusivity (radD) in the CST, corpus callosum and fronto‐temporal extra‐motor tracts, compared with healthy controls and other patient groups. CST tractography showed significant alterations of DT MRI metrics in ALS and LMND‐fast patients whereas KD and LMND‐slow patients were comparable with healthy controls. Our study demonstrated the absence of WM abnormalities in patients with KD and LMND‐slow, in contrast with diffuse WM damage in ALS and focal CST degeneration in LMND‐fast, supporting the use of DT MRI measures as powerful tools to differentiate fast‐ and slow‐progressing MND syndromes, including KD.
Abdominal Surgery in Patients With Idiopathic Noncirrhotic Portal Hypertension: A Multicenter Retrospective Study
Authors: Elkrief Laure , Ferrusquia‐Acosta José , Payancé Audrey , Moga Lucile , Tellez Luis , Praktiknjo Michael , Procopet Bogdan , Farcau Oana , De Lédinghen Victor , Yuldashev Rustam , Tabchouri Nicolas , Barbier Louise , Dumortier Jérôme , Menahem Benjamin , Magaz Marta , Hernández‐Gea Virginia , Albillos Agustin , Trebicka Jonel , Spahr Laurent , De Gottardi Andrea , Plessier Aurélie , Valla Dominique , Rubbia‐Brandt Laura , Toso Christian , Bureau Christophe , Garcia‐Pagan Juan‐Carlos , Rautou Pierre‐Emmanuel ,   for VALDIG, an EASL consortium
Published: March 2019

In patients with idiopathic noncirrhotic portal hypertension (INCPH), data on morbidity and mortality of abdominal surgery are scarce. We retrospectively analyzed the charts of patients with INCPH undergoing abdominal surgery within the Vascular Liver Disease Interest Group network. Forty‐four patients with biopsy‐proven INCPH were included. Twenty‐five (57%) patients had one or more extrahepatic conditions related to INCPH, and 16 (36%) had a history of ascites. Forty‐five procedures were performed, including 30 that were minor and 15 major. Nine (20%) patients had one or more Dindo‐Clavien grade ≥ 3 complication within 1 month after surgery. Sixteen (33%) patients had one or more portal hypertension–related complication within 3 months after surgery. Extrahepatic conditions related to INCPH (P = 0.03) and history of ascites (P = 0.02) were associated with portal hypertension–related complications within 3 months after surgery. Splenectomy was associated with development of portal vein thrombosis after surgery (P = 0.01). Four (9%) patients died within 6 months after surgery. Six‐month cumulative risk of death was higher in patients with serum creatinine ≥ 100 μmol/L at surgery (33% versus 0%, P < 0.001). An unfavorable outcome (i.e., either liver or surgical complication or death) occurred in 22 (50%) patients and was associated with the presence of extrahepatic conditions related to INCPH, history of ascites, and serum creatinine ≥ 100 μmol/L: 5% of the patients with none of these features had an unfavorable outcome versus 32% and 64% when one or two or more features were present, respectively. Portal decompression procedures prior to surgery (n = 10) were not associated with postoperative outcome. Conclusion: Patients with INCPH are at high risk of major surgical and portal hypertension–related complications when they harbor extrahepatic conditions related to INCPH, history of ascites, or increased serum creatinine.
A Pilot Clinical Trial of Nitazoxanide in the Treatment of Chronic Hepatitis B
Authors: Rossignol Jean‐François , Bréchot Christian
Published: March 2019

Chronic infection by the hepatitis B virus (HBV) has remained a major public health problem. To achieve an HBV cure, we will likely need to combine antivirals with different viral targets as well as immunotherapy. Here, we report data from a pilot proof‐of‐concept clinical trial of nitazoxanide in treating chronic hepatitis B. Conclusion: Nitazoxanide offers novel mechanisms of antiviral activity, and it would be interesting to evaluate the potential of combining nitazoxanide with oral nucleos(t)ide analogues.
Development of Quantified Model for Application of Control Systems in Irrigation Networks by System Dynamic Approach
Authors: Hosseinzadeh Ghazichaki Zeinab , Monem Mohammad Javad
Published: March 2019

Because of water scarcity, improvement of water management has been gaining in importance. Agriculture is the largest water consumer, so improvement of irrigation networks is the priority. An automatic control system is one measure for achieving this goal. With the exception of automatic hydraulic structures, other automatic systems are new to Iranian irrigation networks, which make their selection a complicated task. In this paper, a dynamic system approach was used to investigate the interactions among automatic system components and the long‐term behaviour of irrigation networks. The conceptual model was developed and presented in a separate article. In this research, the quantified model is developed and verified for the Qazvin irrigation network (QIN). A data series of conveyance and distribution efficiency, and groundwater withdrawal, are used for verification using statistical indicators and extreme condition tests. The results show that the model simulates the system behaviour correctly. Sensitivity analysis shows that distribution and delivery management is the most effective parameter in irrigation network utility. Some improvement scenarios are tested. The results show that improving managerial structure has the greatest impact on network utility; in fact, other measures are not so useful, unless managerial structure is improved. © 2019 John Wiley & Sons, Ltd.
Studies on mechanism of free Nε‐(carboxymethyl)lysine‐induced toxic injury in mice
Authors: Wang Yi‐Xin , Xu Hao , Liu Xin , Liu Liang , Wu Yong‐Ning , Gong Zhi‐Yong
Published: March 2019

Nε‐(carboxymethyl)lysine (CML), which is a compound produced when food is processed, has aroused concern in recent years because of its potentially dangerous effects. This study aimed to investigate the mechanism of free CML‐induced toxic injury in mice. The inflammatory cytokine tumor necrosis factor‐α, transforming growth factor‐β, vascular cell adhesion molecule‐1 mRNA expression levels of CML‐infected mice liver and kidney tissues significantly increased. While CML receptor—receptor for advanced glycation end products (RAGE) protein expression in male mice liver tissue had a more significant change than the control group, there was no significant difference in other dose groups compared with the control group. In conclusion, the foodborne free CML can be induced by oxidative stress and immune response to liver and kidney tissue injury in mice. Additionally, the free CML may also bind to RAGE, which activates the downstream inflammatory pathway.
Alkannin attenuates lipopolysaccharide‐induced lung injury in mice via Rho/ROCK/NF‐κB pathway
Authors: Li Bin , Lin Qingling , Hou Qiliang , Yin Chao , Zhang Lei , Li Yumin
Published: March 2019

We investigated the effects and associated mechanism of alkannin (AL) on lipopolysaccharide (LPS)‐induced acute lung injury in a mouse model. Pretreatment with AL in vivo significantly reduced the lung wet/dry weight ratio and inhibited lung myeloperoxidase activity and malondialdehyde content, while increasing superoxide dismutase activity. Hematoxylin and eosin staining demonstrated that AL attenuated lung histopathological changes. In addition, AL‐inhibited overproduction of proinflammatory cytokines in bronchoalveolar lavage fluid and lung tissues in LPS‐injured mice and LPS‐exposed A549 cells. Further analysis showed that AL‐inhibited induction of the Rho/ROCK/NF‐κB pathway via LPS‐induced inflammation in mice and A549 cells. Fasudil, a selective ROCK inhibitor, showed similar effects. Overall, the findings indicate that AL suppresses the expression of messenger RNAs and proteins associated with Rho/ROCK/NF‐κB signaling to effectively ameliorate lung injury.
Castration‐induced prostate epithelial cell apoptosis results from targeted oxidative stress attack of M1142‐macrophages
Authors: Barbosa Guilherme O. , Silva Juliete A. F. , Siqueira‐Berti Aline , Nishan Umar , Rosa‐Ribeiro Rafaela , Oliveira Silvia B. P. , Baratti Mariana O. , Ferrucci Danilo , Santana Julio C. O. , Damas‐Souza Danilo M. , Bruni‐Cardoso Alexandre , Augusto Taize M. , Corrêa‐da‐Silva Felipe , Moraes‐Vieira Pedro M. , Stach‐Machado Dagmar R. , Felisbino Sergio L. , Menezes Gustavo B. , Cesar Carlos L. , Carvalho Hernandes F.
Published: March 2019

Prostate development and function are regulated by androgens. Epithelial cell apoptosis in response to androgen deprivation is caspase‐9‐dependent and peaks at Day 3 after castration. However, isolated epithelial cells survive in the absence of androgens. Znf142 showed an on‐off expression pattern in intraepithelial CD68‐positive macrophages, with the on‐phase at Day 3 after castration. Rats treated with gadolinium chloride to deplete macrophages showed a significant drop in apoptosis, suggesting a causal relationship between macrophages and epithelial cell apoptosis. Intraepithelial M1‐polarization was also limited to Day 3, and the inducible nitric oxide synthase (iNOS) knockout mice showed significantly less apoptosis than wild‐type controls. The epithelial cells showed focal DNA double‐strand breaks (DSB), 8‐oxoguanine, and protein tyrosine‐nitrosylation, fingerprints of exposure to peroxinitrite. Cultured epithelial cells induced M1‐polarization and showed focal DSB and underwent apoptosis. The same phenomena were reproduced in LNCaP cells cocultured with Raw 264.7 macrophages. In conclusion, the M1
142‐macrophage (named after Znf142) attack causes activation of the intrinsic apoptosis pathway in epithelial cells after castration.
Weakly supervised 3D deep learning for breast cancer classification and localization of the lesions in MR images
Authors: Zhou Juan , Luo Lu‐Yang , Dou Qi , Chen Hao , Chen Cheng , Li Gong‐Jie , Jiang Ze‐Fei , Heng Pheng‐Ann
Published: March 2019

Background

The usefulness of 3D deep learning‐based classification of breast cancer and malignancy localization from MRI has been reported. This work can potentially be very useful in the clinical domain and aid radiologists in breast cancer diagnosis.

Purpose

To evaluate the efficacy of 3D deep convolutional neural network (CNN) for diagnosing breast cancer and localizing the lesions at dynamic contrast enhanced (DCE) MRI data in a weakly supervised manner.

Study Type

Retrospective study.

Subjects

A total of 1537 female study cases (mean age 47.5 years ±11.8) were collected from March 2013 to December 2016. All the cases had labels of the pathology results as well as BI‐RADS categories assessed by radiologists.

Field Strength/Sequence

1.5 T dynamic contrast‐enhanced MRI.

Assessment

Deep 3D densely connected networks were trained under image‐level supervision to automatically classify the images and localize the lesions. The dataset was randomly divided into training (1073), validation (157), and testing (307) subsets.

Statistical Tests

Accuracy, sensitivity, specificity, area under receiver operating characteristic curve (ROC), and the McNemar test for breast cancer classification. Dice similarity for breast cancer localization.

Results

The final algorithm performance for breast cancer diagnosis showed 83.7% (257 out of 307) accuracy (95% confidence interval [CI]: 79.1%, 87.4%), 90.8% (187 out of 206) sensitivity (95% CI: 80.6%, 94.1%), 69.3% (70 out of 101) specificity (95% CI: 59.7%, 77.5%), with the area under the curve ROC of 0.859. The weakly supervised cancer detection showed an overall Dice distance of 0.501 ± 0.274.

Data Conclusion

3D CNNs demonstrated high accuracy for diagnosing breast cancer. The weakly supervised learning method showed promise for localizing lesions in volumetric radiology images with only image‐level labels.

Level of Evidence: 4

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2019;50:1144–1151.
Lasers and energy‐based devices marketed for vaginal rejuvenation: A cross‐sectional analysis of the MAUDE database
Authors: Ahluwalia Jusleen , Avram Mathew M. , Ortiz Arisa E.
Published: March 2019

Introduction

The FDA issued a statement on July 30, 2018, expressing concern over the marketing of lasers and energy‐based devices to promote “vaginal rejuvenation.” The FDA stated that there is insufficient data to recommend this modality for optimization of sexual function and alleviation of genitourinary syndrome of menopause (GSM)‐related symptoms in postmenopausal or postpartum women. This analysis aims to characterize the mandatory and voluntary reports concerning laser and energy‐based procedures marketed for vaginal rejuvenation.

Methods

Cross‐sectional analysis of the FDA database, Manufacturer and User Facility Device Experience (MAUDE), for events related to laser and energy‐based devices for vaginal rejuvenation.

Results

Between October 2015 and January 2019, 45 distinct events describing 46 patients were recorded and reviewed. The most commonly reported adverse event related to the procedure was pain (vulvar, bladder, urethral, or unspecified) (n = 19). The majority of patients sought medical care for their injuries, which included evaluation by urgent care, urology, gynecology, neurology, gastroenterology, pelvic floor therapy, primary care providers, and the device operator. Thirty‐three patients indicated chronicity of their injury, which included long‐term pain, numbness, burning, bladder disturbances, infections, scarring, dyspareunia, worsening symptoms, aggravation of lichen sclerosis, and disfigurement.

Conclusions

A variety of adverse events associated with the use of laser and energy‐based devices for “vaginal rejuvenation“ was reported to the MAUDE database. Although the circumstances surrounding these events were unclear, these reports signify the importance of clinical trials that investigate the efficacy and safety profile of laser and energy‐based devices for optimization of sexual function and treatment of GSM‐related symptoms. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Influence of temperature and chloride ion concentration on the corrosion behaviour of Mg–4Al–3Ca–0.5RE alloy
Authors: Xiong Xinhong , Chen Lianbo , Hu Kaixiong , Wang Zhiping , Zhang Qiaoxin , Lei Yongjie
Published: March 2019

The influence of temperature and chloride ion concentration on the corrosion behaviour of Mg−4Al−3Ca−0.5RE alloys were studied in this paper. Corrosion rates of the alloys were measured by weight loss test and electrochemical measurement. The results revealed that a shorter incubation period to the onset of corrosion, a more negative corrosion potential, and a higher corrosion rate was correlated with a higher temperature in 3% NaCl solution and a higher chloride ion concentration at 30°C. The corrosion behaviour of the alloys was affected by surface film and the corrosion mainly occurred at the breaks or defects in surface films.
Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate
Authors: Mohamad Shah Nurul Syazana , Sulong Sarina , Wan Sulaiman Wan Azman , Halim Ahmad Sukari
Published: March 2019

Background

Nonsyndromic cleft lip and/or palate is one of the most common human birth defects worldwide that affects the lip and/or palate. The incidence of clefts varies among populations through ethnic, race, or geographical differences. The focus on Malay nonsyndromic cleft lip and/or palate (NSCL/P) is because of a scarce report on genetic study in relation to this deformity in Malaysia. We are interested to discuss about the genes that are susceptible to cause orofacial cleft formation in the family.

Methods

Genome‐wide linkage analysis was carried out on eight large extended families of NSCL/P with the total of 91 individuals among Malay population using microarray platform. Based on linkage analyses findings, copy number variation (CNV) of LPHN2, SATB2, PVRL3, COL21A1, and TOX3 were identified in four large extended families that showed linkage evidence using quantitative polymerase chain reaction (qPCR) as for a validation purpose. Copy number calculated (CNC) for each genes were determined with Applied Biosystems CopyCallerTM Software v2.0. Normal CNC of the target sequence expected was set at two.

Results

Genome‐wide linkage analysis had discovered several genes including TOX3 and COL21A1 in four different loci 4p15.2‐p16.1, 6p11.2‐p12.3, 14q13‐q21, and 16q12.1. There was significant decreased, p < 0.05 of SATB2, COL21A1, and TOX3 copy number in extended families compared to the normal controls.

Conclusion

Novel linkage evidence and significant low copy number of COL21A1 and TOX3 in NSCLP family was confirmed. These genes increased the risks toward NSCLP formation in that family traits.
Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva
Authors: Li Changxing , Liang Jingyao , Chen Pingjiao , Zeng Kang , Xue Rujun , Tian Xin , Liang Liuping , Wang Qi , Shi Minglan , Zhang Xibao
Published: March 2019

Background

Erythrokeratodermia variabilis et progressiva (EKVP, OMIM 133200) is a rare hereditary disorder characterized by varies from transient, fast moving erythema to persistent brown hyperkeratotic plaques. Recently, mutations in the genes gap junction alpha 1 gene (GJA1), GJB3, and GJB4 have been reported to cause EKVP. Here, we report the identification of two de novo missense mutations in the GJA1 gene in two unrelated individuals with EKVP.

Methods

The patients and his family members were subjected to mutation detection in the candidate gene GJA1, GJB3, and GJB4 by Sanger sequencing. The expression of connexin (Cx) 43 was detected by immunohistochemistry and immunofluorescence (IF) studies in the lesions.

Results

A 12‐year‐old boy presented with multiple hyperkeratotic plaques on the face, neck, elbows, wrists, limbs, knees, inguinal region, hands, and feet. A 7‐year‐old girl presented with symmetrical erythematous, plaques on the hands, feet, wrists, and ankles. A novel heterozygous missense mutation c.848C > T (p.P283L) in exon 2 of the GJA1 gene was identified in both patients. A novel heterozygous missense mutation c.869C > A (p.T290N) in exon 2 of the GJA1 gene was also identified in the boy. These mutations were not found in the unaffected family members and 100 normal controls. In the patients’ lesions, Cx43 protein was located to the cytomembrane and cytoplasm in the stratum corneum, and granular layer. Compound heterozygous mutations in the boy showed a more severe clinical phenotype and cytoplasmic mislocalization.

Conclusions

The novel mutations c.848C > T (p.P283L) and c.869C > A(p.T290N) arose de novo and were considered as the cause of two Chinese EKVP. GJA1 P283L and T290N mutations lead to Cx43 protein cytoplasmic mislocalization. Our finding expands the mutant spectrum of GJA1 gene and adds new understanding of the genotype‐phenotype correlation.
On positive solutions of fractional differential equations with change of sign
Authors: Wang Fanglei , Zhang Li , Ru Yuanfang , Liu Ronghua
Published: March 2019

We study the existence and uniqueness of positive solutions of fractional differential equations with change of sign

urn:x-wiley:mma:media:mma5619:mma5619-math-0002
where 1 < α ≤ 2,
is continuous and does not vanish identically on any subinterval of [0,1].
Dosimetry and characterization of a 25‐MeV proton beam line for preclinical radiobiology research
Authors: Constanzo Julie , Vanstalle Marie , Finck Christian , Brasse David , Rousseau Marc
Published: March 2019

Purpose

With the increase in proton therapy centers, there is a growing need to make progress in preclinical proton radiation biology to give accessible data to medical physicists and practicing radiation oncologists.

Methods

A cyclotron usually producing radioisotopes with a proton beam at an energy of about 25 MeV after acceleration, was used for radiobiology studies. Depleted silicon surface barrier detectors were used for the beam energy measurement. A complementary metal oxide semiconductor (CMOS) sensor and a plastic scintillator detector were used for fluence measurement, and compared to Geant4 and an in‐house analytical dose modeling developed for this purpose. Also, from the energy measurement of each attenuated beam, the dose‐averaged linear energy transfer (LETd) was calculated with Geant4.

Results

The measured proton beam energy was 24.85 ± 0.14 MeV with an energy straggling of 127 ± 22 keV before scattering and extraction in air. The measured flatness was within ± 2.1% over 9 mm in diameter. A wide range of LETd is achievable: constant between the entrance and the exit of the cancer cell sample ranging from 2.2 to 8 keV/μm, beyond 20 keV/μm, and an average of 2–5 keV/μm in a scattering spread‐out Bragg peak calculated for an example of a 6‐mm‐thick xenograft tumor.

Conclusion

The dosimetry and the characterization of a 25‐MeV proton beam line for preclinical radiobiology research was performed by measurements and modeling, demonstrating the feasibility of delivering a proton beam for preclinical in vivo and in vitro studies with LETd of clinical interest.
Impact of SBRT fractionation in hypoxia dose painting — Accounting for heterogeneous and dynamic tumor oxygenation
Authors: Kjellsson Lindblom Emely , Ureba Ana , Dasu Alexandru , Wersäll Peter , Even Aniek J. G. , van Elmpt Wouter , Lambin Philippe , Toma‐Dasu Iuliana
Published: March 2019

Purpose

Tumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on 18F‐HX4 positron emission tomography (PET) imaging of NSCLC.

Methods

Positron emission tomography imaging data based on the hypoxia tracer 18F‐HX4 of 19 NSCLC patients were included in the study. Normalized tracer uptake was converted to oxygen partial pressure (pO2) and hypoxic target volumes (HTVs) were segmented using a threshold of 10 mmHg. Uniform doses required to overcome the hypoxic resistance in the target volumes were calculated based on a previously proposed method taking into account the effect of interfraction reoxygenation, for fractionation schedules ranging from extremely hypofractionated stereotactic body radiotherapy (SBRT) to conventionally fractionated radiotherapy.

Results

Gross target volumes ranged between 6.2 and 859.6 cm3, and the hypoxic fraction < 10 mmHg between 1.2% and 72.4%. The calculated doses for overcoming the resistance of cells in the HTVs were comparable to those currently prescribed in clinical practice as well as those previously tested in feasibility studies on dose escalation in NSCLC. Depending on the size of the HTV and the distribution of pO2, HTV doses were calculated as 43.6–48.4 Gy for a three‐fraction schedule, 51.7–57.6 Gy for five fractions, and 59.5–66.4 Gy for eight fractions. For patients in whom the HTV pO2 distribution was more favorable, a lower dose was required despite a bigger volume. Tumor control probability was lower for single‐fraction schedules, while higher levels of tumor control probability were found for schedules employing several fractions.

Conclusions

The method to account for heterogeneous and dynamic hypoxia in target volume segmentation and dose prescription based on 18F‐HX4‐PET imaging appears feasible in NSCLC patients. The distribution of oxygen partial pressure within HTV could impact the required prescribed dose more than the size of the volume.
Reproducibility of human cardiac phosphorus MRS (31P‐MRS) at 7 T
Authors: Ellis Jane , Valkovič Ladislav , Purvis Lucian A.B. , Clarke William T. , Rodgers Christopher T.
Published: March 2019

Purpose

We test the reproducibility of human cardiac phosphorus MRS (31P‐MRS) at ultra‐high field strength (7 T) for the first time. The primary motivation of this work was to assess the reproducibility of a ‘rapid’ 6½ min 31P three‐dimensional chemical shift imaging (3D‐CSI) sequence, which if sufficiently reproducible would allow the study of stress‐response processes. We compare this with an established 28 min protocol, designed to record high‐quality spectra in a clinically feasible scan time. Finally, we use this opportunity to compare the effect of per‐subject B0 shimming on data quality and reproducibility in the 6½ min protocol.

Methods

10 healthy subjects were scanned on two occasions: one to test the 28 min 3D‐CSI protocol, and one to test the 6½ min protocol. Spectra were fitted using the OXSA MATLAB toolbox. The phosphocreatine to adenosine triphosphate concentration ratio (PCr/ATP) from each scan was analysed for intra‐ and intersubject variability. The impact of different strategies for voxel selection was assessed.

Results

There were no significant differences between repeated measurements in the same subject. For the 28 min protocol, PCr/ATP in the midseptal voxel across all scans was 1.91 ± 0.36 (mean ± intersubject SD). For the 6½ min protocol, PCr/ATP in the midseptal voxel was 1.76 ± 0.40. The coefficients of reproducibility (CRs) were 0.49 (28 min) and 0.67 (6½ min). Per‐subject B0 shimming improved the fitted PCr/ATP precision (for 6½ min scans), but had negligible effect on the CR (0.67 versus 0.66).

Conclusions

Both 7 T protocols show improved reproducibility compared with a previous 3 T study by Tyler et al. Our results will enable informed power calculations and protocol selection for future clinical research studies.
An interview study of the care manager function—Opening the door to continuity of care for patients with depression in primary care
Authors: Udo Camilla , Svenningsson Irene , Björkelund Cecilia , Hange Dominique , Jerlock Margareta , Petersson Eva‐Lisa
Published: March 2019

Aim

To explore experiences among patients with depression of contact with a care manager at a primary care centre.

Design

A qualitative explorative study.

Methods

During spring and summer 2016, 20 individual face‐to‐face interviews were conducted with patients with experience of care manager contact. The material was analysed using systematic text condensation.

Results

The participants described that having contact with a care manager was a support in their recovery process. Care became more available, and the structured continuous contact and the care manager's availability contributed to a trusting relationship. Having someone to share their burden with was a relief. However, it was described as negative when the care manager was perceived as inflexible and not open to issues that the participants felt a need to discuss. For the care manager contact to be successful, there is a need for flexibility and individually tailored contact.