bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher‐Order Assessment in Gross Anatomy: A Comparison of Performance on Higher‐ Versus Lower‐Order Anatomy Questions between Undergraduate and First‐Year Medical Students
Authors: Thompson Andrew R. , Giffin Bruce F.
Published: October 2020

Gross anatomy is considered by many the backbone of medical education. While learning anatomy has a reputation of requiring mainly rote memorization, modern day anatomy education often involves instruction and assessment at cognitive levels that foster higher‐order thinking. In many instances, these higher‐order anatomical concepts are taught to graduate students in healthcare‐related fields, such as medicine. At this level, students are expected to apply and analyze anatomical information since that is what will ultimately be expected of them as professionals. In contrast, undergraduate anatomy education is typically more introductory in nature and often takes place in the setting of a large‐enrollment course that serves as a prerequisite for many health sciences degree programs. In this study, variables related to the assessment of higher‐order concepts in clinical anatomy were compared between first‐year medical students and undergraduate students enrolled in an upper‐level human gross anatomy course. Results demonstrate that undergraduate students perform lower than medical students overall, but the degree of difference in how they perform on higher‐ versus lower‐order questions is comparable. The most notable exception is on practical examinations, where undergraduate students tend to struggle more with applying and analyzing information. Exploration of additional variables provides insight into how the cognitive level being assessed affects the time it takes to answer a question and how different practical examination question types and formats influence student performance. Findings presented in this study have implications for designing anatomy courses and underscore the importance of blueprinting assessments.
Causal pathways linking different flavours of ENSO with the Greater Horn of Africa short rains
Authors: MacLeod David , Graham Richard , O'Reilly Chris , Otieno George , Todd Martin
Published: October 2020

There is a strong association between canonical El Niño and a wet Greater Horn of Africa (GHA) short rains. However, the link with Modoki El Niño events appears to be significantly weaker. In order to understand this, we present an analysis of observational data and idealised climate model experiments. Idealised atmospheric simulations isolate the direct influence of Pacific heating on the GHA and reveal that neither the longitudinal position nor the observed weaker magnitude of Modoki Pacific heating anomalies can explain the difference in teleconnections. The direct effect of canonical or Modoki Pacific heating patterns on the GHA is similar and neither reproduces the structure of the full GHA teleconnection: they both generate a wet‐dry dipole over the GHA instead of large‐scale single‐signed wet anomalies. Our results indicate that the strong canonical ENSO influence on GHA is indirect, mediated through its strong relationship with the Indian Ocean Dipole (IOD). By contrast, Modoki ENSO is uncorrelated with the IOD, resulting in weak teleconnection to GHA. Understanding these differences aids seasonal forecast interpretation, whilst their representation in models is likely a prerequisite for making accurate projections of changes in extremes over the GHA and beyond.
Characterizing the effect of substrate stiffness on the extravasation potential of breast cancer cells using a 3D microfluidic model
Authors: Azadi Shohreh , Tafazzoli Shadpour Mohammad , Warkiani Majid E.
Published: October 2020

Different biochemical and biomechanical cues from tumor microenvironment affect the extravasation of cancer cells to distant organs; among them, the mechanical signals are poorly understood. Although the effect of substrate stiffness on the primary migration of cancer cells has been previously probed, its role in regulating the extravasation ability of cancer cells is still vague. Herein, we used a microfluidic device to mimic the extravasation of tumor cells in a 3D microenvironment containing cancer cells, endothelial cells, and the biological matrix. The microfluidic‐based extravasation model was utilized to probe the effect of substrate stiffness on the invasion ability of breast cancer cells. MCF7 and MDA‐MB‐231 cancer cells were cultured among substrates with different stiffness which followed by monitoring their extravasation capability through the microfluidic device. Our results demonstrated that acidic collagen at a concentration of 2.5 mg/ml promotes migration of cancer cells. Additionally, the substrate softening resulted in up to 46% reduction in the invasion of breast cancer cells. The substrate softening not only affected the number of extravasated cells but also reduced their migration distance up to 53%. We further investigated the secreted level of matrix metalloproteinase 9 (MMP9) and identified that there is a positive correlation between substrate stiffening, MMP9 concentration, and extravasation of cancer cells. These findings suggest that the substrate stiffness mediates the cancer cells extravasation in a microfluidic model. Changes in MMP9 level could be one of the possible underlying mechanisms which need more investigations to be addressed thoroughly.
Utility of the dual antiplatelet therapy score to guide antiplatelet therapy: A systematic review and meta‐analysis
Authors: Mihatov Nino , Secemsky Eric A. , Kereiakes Dean J. , Steg Gabriel , Serruys Patrick W. , Chichareon Ply , Shen Changyu , Yeh Robert W.
Published: October 2020

Background

The dual antiplatelet therapy (DAPT) score, one of the first prediction tools to attempt to uncouple bleeding and ischemic risk following percutaneous coronary intervention, can help guide antiplatelet duration after coronary intervention. Evaluating the generalizability of the score is important to understand its utility in clinical practice.

Methods

We conducted a systematic review and meta‐analysis of studies that validated the DAPT score. A random effect meta‐analysis was performed of ischemic and bleeding risk based on DAPT score. A secondary analysis assessed the risk of longer versus shorter P2Y12 inhibitor duration on ischemic and bleeding risk in randomized controlled trials of DAPT duration.

Results

We identified 10 patient cohorts involving 88,563 patients. Compared with a low DAPT score, a high DAPT score was associated with increased ischemic risk (RR: 1.62, 95% CI: 1.41–1.87) and reduced bleeding risk (RR: 0.80, 95% CI: 0.70–0.92). In three randomized trials of DAPT duration that contained information on the DAPT score, the relative risk of net adverse clinical events (combined ischemic and bleeding events) with longer duration of DAPT was 1.56 (95% CI: 0.77–3.19) for low DAPT score patients, and 0.86 (95% CI: 0.61–1.21) for high DAPT score patients (pinteraction = .14).

Conclusions

In this large meta‐analysis, the DAPT score consistently stratified bleeding and ischemic risk in opposing directions across several different study populations. More evaluation is needed to understand if the effect of longer DAPT duration on NACE is modified by the DAPT score in current practice.
Right atrial thrombus mimicking cardiac tumor in a neonate
Authors: Samanidis George , Kanakis Meletios , Bobos Dimitrios , Kousi Theofili , Dimitropoulou Maria , Karafotia Afroditi , Sofianidou Ioanne , Giannopoulos Nicholas
Published: October 2020

Does the cardiac mass should be operated in neonates? When diagnosis of cardiac tumor or mass has been made, the surgical excision should not be delayed for prevention of life‐treating complications
Impact of Particle Size Distribution on Performance of Lithium‐Ion Batteries
Authors: Bläubaum Lars , Röder Fridolin , Nowak Christine , Chan Hoon Seng , Kwade Arno , Krewer Ulrike
Published: October 2020

This work reveals the impact of particle size distribution of spherical graphite active material on negative electrodes in lithium‐ion batteries. Basically all important performance parameters, i. e. charge/discharge characteristics, capacity, coulombic and energy efficiencies, cycling stability and C‐rate capability are shown to be affected by distribution shapes. A narrow distribution with smaller particles results in better cell performance than broader and coarser distributions. However, particle size reduction has a limitation as extremely small particles show negative effect in performance. More critically, independent of the particle size distribution, the existence of coarse particles are found to promote lithium plating, which lowers cell performance and threatens the safety of battery operation. Furthermore, impedance analysis and cycling stability show huge differences for different electrodes. Our study shows that a better understanding of the influence of particle size distribution is an important base to engineer electrodes with higher C‐rate capability, higher performance, and lower safety risk due to lithium plating.
Low‐Flammable Parahydrogen‐Polarized MRI Contrast Agents
Authors: Joalland Baptiste , Ariyasingha Nuwandi M. , Younes Hassan R. , Nantogma Shiraz , Salnikov Oleg G. , Chukanov Nikita V. , Kovtunov Kirill V. , Koptyug Igor V. , Gelovani Juri G. , Chekmenev Eduard Y.
Published: October 2020

Many MRI contrast agents formed with the parahydrogen‐induced polarization (PHIP) technique exhibit biocompatible profiles. In the context of respiratory imaging with inhalable molecular contrast agents, the development of nonflammable contrast agents would nonetheless be highly beneficial for the biomedical translation of this sensitive, high‐throughput and affordable hyperpolarization technique. To this end, we assess the hydrogenation kinetics, the polarization levels and the lifetimes of PHIP hyperpolarized products (acids, ethers and esters) at various degrees of fluorine substitution. The results highlight important trends as a function of molecular structure that are instrumental for the design of new, safe contrast agents for in vivo imaging applications of the PHIP technique, with an emphasis on the highly volatile group of ethers used as inhalable anesthetics.
Pain in long‐term survivors of childhood cancer: A systematic review of the current state of knowledge and a call to action from the Children's Oncology Group
Authors: Schulte Fiona S. M. , Patton Michaela , Alberts Nicole M. , Kunin‐Batson Alicia , Olson‐Bullis Barbara A. , Forbes Caitlin , Russell K. Brooke , Neville Alexandra , Heathcote Lauren C. , Karlson Cynthia W. , Racine Nicole M. , Charnock Courtney , Hocking Matthew C. , Banerjee Pia , Tutelman Perri R. , Noel Melanie , Krull Kevin R.
Published: October 2020

Survivors of childhood cancer may be at risk of experiencing pain, and a systematic review would advance our understanding of pain in this population. The objective of this study was to describe: 1) the prevalence of pain in survivors of childhood cancer, 2) methods of pain measurement, 3) associations between pain and biopsychosocial factors, and 4) recommendations for future research. Data sources for the study were articles published from January 1990 to August 2019 identified in the PubMed, PsycINFO, EMBASE, and Web of Science data bases. Eligible studies included: 1) original research, 2) quantitative assessments of pain, 3) articles published in English, 4) cancers diagnosed between birth and age 21 years, 5) survivors at 5 years from diagnosis and/or at 2 years after therapy completion, and 6) a sample size >20. Seventy‐three articles were included in the final review. Risk of bias was considered using the Cochrane risk of bias tool. The quality of evidence was evaluated according to Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria. Common measures of pain were items created by the authors for the purpose of the study (45.2%) or health‐related quality‐of‐life/health status questionnaires (42.5%). Pain was present in from 4.3% to 75% of survivors across studies. Three studies investigated chronic pain according the definition in the International Classification of Diseases. The findings indicated that survivors of childhood cancer are at higher risk of experiencing pain compared with controls. Fatigue was consistently associated with pain, females reported more pain than males, and other factors related to pain will require stronger evidence. Theoretically grounded, multidimensional measurements of pain are absent from the literature.
Bergenin inhibits bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway
Authors: Liu Junjiang , Zhang Yunxia , Yu Chunhong , Zhang Panying , Gu Shouyi , Wang Gang , Xiao Helong , Li Shoubin
Published: October 2020

Bladder cancer is one of the most common malignant tumors in the urinary system with high mortality and morbidity. Evidence revealed that bergenin could affect the development of cancer. Here, we aimed to investigate the effect of bergenin on bladder cancer progression and its mechanism. The effect of bergenin on cell function was first detected, followed by assessing the changes of the epithelial‐mesenchymal transition (EMT) in bergenin‐treated cells. The effect of bergenin on peroxisome proliferator‐activated receptor γ (PPARγ)/phosphatase and tensin homolog (PTEN)/Akt signal pathway was measured by Western blotting, followed by the rescue experiments. The results showed that bergenin treatment significantly decreased cell viability and increased G1 phase arrest, accompanied by reduced expression of Ki67, cycling D1, and cycling B1 in bladder cancer cells. Apoptosis was induced by bergenin in bladder cancer cells, as evidenced by increased Bax and cleaved caspase 3 protein levels and decreased Bcl‐2 level in bergenin‐treated cells. Meanwhile, the inhibition of the invasion, migration, and EMT was also observed in bergenin‐treated cells. Mechanism studies showed that bergenin treatment could activate PPARγ/PTEN/Akt signal pathway, as evidence by the increased nucleus PPARγ and phosphatase and tensin homolog (PTEN) expression and decreased Akt expression. Moreover, PPARγ inhibitor administration inverted the effects of bergenin on bladder cancer cell function, including the proliferation, apoptosis, invasion, and migration in bladder cancer cells. Our findings revealed that bergenin could inhibit bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway, indicating that bergenin may be a potential therapeutic medicine for bladder cancer treatment.
NAFLD: Reporting Histologic Findings in Clinical Practice
Authors: Brunt Elizabeth M. , Kleiner David E. , Carpenter Danielle H. , Rinella Mary , Harrison Stephen A. , Loomba Rohit , Younossi Zobair , Neuschwander‐Tetri Brent A. , Sanyal Arun J. ,   for the American Association for the Study of Liver Diseases NASH Task Force
Published: October 2020

The role of liver biopsy in NASH has evolved along with the increased recognition of the significance of this disease, and the unmet medical need it presents. Drug development and clinical trials are rapidly growing, as are noninvasive tests for markers of steatosis, inflammation, injury, and fibrosis. Liver biopsy evaluation remains necessary for both drug development and clinical trials as the most specific means of diagnosis and patient identification for appropriate intervention. This White Paper, sponsored by the American Association for the Study of Liver Disease NASH Task Force, is a focused review of liver biopsy evaluation in fatty liver disease in subjects with presumed NAFLD for practicing clinical hepatologists and pathologists. The goal is to provide succinct and specific means for reporting the histopathologic elements of NASH, distinguishing NASH from nonalcoholic fatty liver without steatohepatitis, and from alcohol‐associated steatohepatitis when possible. The discussion includes the special situations of NASH in advanced fibrosis or cirrhosis, and in the pediatric population. Finally, there is discussion of semiquantitative methods of evaluation of lesions of “disease activity” and fibrosis. Tables are presented for scoring and a suggested model for final reporting. Figures are presented to highlight the histopathologic elements of NASH.
On the validity of data produced by isolated and synthesized contingencies during the functional analysis of problem behavior
Authors: Tiger Jeffrey H. , Effertz Hannah M.
Published: October 2020

Functional analyses are intended to identify the reinforcers maintaining problem behavior in order to inform clinicians' selection of interventions. Traditionally, these analyses have exposed problem behavior to multiple, isolated reinforcement contingencies and in doing so, have ruled in and ruled out potential sources of reinforcement. Recently, some functional analysis models have forgone testing individual reinforcement contingencies and instead exposed problem behavior to 2 or more reinforcers simultaneously in a single, synthesized reinforcement contingency. The current review applies assessment analytics to these approaches to consider their relative sensitivity, specificity, discriminant validity, and predictive validity to yield practice recommendations and to nominate areas of future research.
A review on nanotoxicity and nanogenotoxicity of different shapes of nanomaterials
Authors: Demir Eşref
Published: October 2020

Nanomaterials (NMs) generally display fascinating physical and chemical properties that are not always present in bulk materials; therefore, any modification to their size, shape, or coating tends to cause significant changes in their chemical/physical and biological characteristics. The dramatic increase in efforts to use NMs renders the risk assessment of their toxicity highly crucial due to the possible health perils of this relatively uncharted territory. The different sizes and shapes of the nanoparticles are known to have an impact on organisms and an important place in clinical applications. The shape of nanoparticles, namely, whether they are rods, wires, or spheres, is a particularly critical parameter to affect cell uptake and site‐specific drug delivery, representing a significant factor in determining the potency and magnitude of the effect. This review, therefore, intends to offer a picture of research into the toxicity of different shapes (nanorods, nanowires, and nanospheres) of NMs to in vitro and in vivo models, presenting an in‐depth analysis of health risks associated with exposure to such nanostructures and benefits achieved by using certain model organisms in genotoxicity testing. Nanotoxicity experiments use various models and tests, such as cell cultures, cores, shells, and coating materials. This review article also attempts to raise awareness about practical applications of NMs in different shapes in biology, to evaluate their potential genotoxicity, and to suggest approaches to explain underlying mechanisms of their toxicity and genotoxicity depending on nanoparticle shape.
Drain site enterocutaneous fistula after hyperthermic intraperitoneal chemotherapy
Authors: Kumar Navin , Lata Kanak , Ray Mukur Dipi
Published: October 2020

Spontaneous sigmoid colon perforation after cytoreduction surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is a rare complication. It is more commonly seen with mitomycin‐based HIPEC. This case study's patient presented with pus discharge at the drain site after 4 weeks of surgery. The symptoms persisted after conservative treatment. High suspicion after the feculent smell of the discharge fluidled to the prompt diagnosis of enterocutaneous fistula. There was limitedperforation with abscess formation, followed by fistula formation. The patient was treated successfully with surgery.
New pathogen, same disparities: why COVID‐19 and HIV remain prevalent in U.S. communities of colour and implications for ending the HIV epidemic
Authors: Millett Gregorio A
Published: October 2020

Introduction

The U.S. Ending the HIV Epidemic (EHE) Initiative was launched nationally in February 2019. With a target of ending the HIV epidemic by 2030, EHE initially scales up effective HIV prevention and care in 57 localities that comprise the greatest proportion of annual HIV diagnoses in the United States (US). However, the EHE effort has been eclipsed by another infectious disease 11 months into the Initiative’s implementation. SARS‐COV‐2, a novel coronavirus, has infected more than eight million Americans and at least 223 000 (as of 23 October 2020) have succumbed to the disease. This commentary explores the social conditions that place communities of colour at greater risk for COVID‐19 and HIV, and assesses challenges to EHE in a post‐COVID‐19 universe.

Discussion

One of the many common threads between HIV and COVID‐19 is the disproportionate impact of each disease among communities of colour. A recent report by the National Academy of Sciences surmised that as much as 70% of health outcomes are due to health access, socio‐economic factors and environmental conditions. Social determinants of health associated with greater HIV burden in Black and Brown communities have re‐emerged in epidemiological studies of disproportionate COVID‐19 cases, hospitalizations and deaths in communities of colour. Using data from the scientific literature, this commentary makes direct comparisons between HIV and COVID‐19 racial disparities across the social determinants of health. Furthermore, I examine three sets of challenges facing EHE: (1) Challenges that hamper both the EHE and COVID‐19 response (i.e. insufficiently addressing the social determinants of health; amplification of disparities as new health technologies are introduced) (2) Challenges posed by COVID‐19 (i.e. diverting HIV resources to address COVID‐19 and tapering of EHE funding generally); and (3) Challenges unrelated to COVID‐19 (i.e. emergence of new and related health disparities; repeal of the Affordable Care Act and long‐term viability of EHE).

Conclusions

Racism and discrimination place communities of colour at greater risk for COVID‐19 as well as HIV. Achieving and sustaining an end to the U.S. HIV epidemic will require structural change to eliminate conditions that give rise to and maintain disparities.
Eliminating irreproducibility in SERS substrates
Authors: Grys David‐Benjamin , Chikkaraddy Rohit , Kamp Marlous , Scherman Oren A. , Baumberg Jeremy J. , de Nijs Bart
Published: October 2020

Irreproducibility in surface‐enhanced Raman spectroscopy (SERS) due to variability among substrates is a source of recurrent debate within the field. It is regarded as a major hurdle towards the widespread adoption of SERS as a sensing platform. Most of the literature focused on developing substrates for various applications considers reproducibility of lower importance. Here, we address and analyse the sources of this irreproducibility in order to show how these can be minimised. We apply our findings to a simple substrate demonstrating reproducible SERS measurements with relative standard deviations well below 1% between different batches and days. Identifying the sources of irreproducibility and understanding how to reduce these can aid in the transition of SERS from the lab to real‐world applications.
Experimental tests of surface‐enhanced Raman scattering: Moving beyond the electromagnetic enhancement theory
Authors: Heeg Sebastian , Mueller Niclas S. , Wasserroth Sören , Kusch Patryk , Reich Stephanie
Published: October 2020

The electromagnetic enhancement theory describes surface‐enhanced Raman scattering (SERS) as a Raman effect that takes place in the near‐field of a plasmonic nanostructure. The theory has been very successful in explaining the fundamental properties of SERS, modelling the performance of different metals as enhancing materials and optimizing SERS hotspots for strongest possible enhancement. Over the last decade, a number of carefully designed experimental studies have examined predictions of the electromagnetic theory like the size and shape of SERS hotspots, the absolute magnitude of the enhancement and the width of the SERS resonance. Although the overall picture was quite satisfactory, the theory failed to predict key aspects of SERS, for example, the absolute magnitude of the plasmonic enhancement. We scrutinize these experiments and review them focusing on the results that require going beyond the electromagnetic enhancement theory. We argue that the results of these experiments create the need to develop the theory of SERS further, especially the exact role of plasmonic enhancement in inelastic light scattering.
Customer knowledge management in SMEs: Review and research agenda
Authors: Chaithanapat Pornthip , Rakthin Sirisuhk
Published: October 2020

Customer knowledge is one of the most noteworthy assets for firms to manage in order to improve their products and gain competitive advantage while meeting the customer needs. Customer knowledge management (CKM) arises when firms see the significance of customers as a source of firm's knowledge. More importantly, customers alter from passive product receiver into active knowledge partners and generate co‐created knowledge with firms. However, despite the popularity of promoting entrepreneurship and small and medium enterprises (SMEs) for economic development, research studies, examining CKM in the context of SMEs, are relatively small and diverse. In this paper, the authors discuss the concept of CKM from a comprehensive literature review as well as other related concepts that are anticipated to have relationships with CKM in SMEs, namely knowledge‐oriented leadership (KOL), trust in management, and firm performance. A thorough analysis of past research confirms that the existing literature in this area is highly fragmented. By integrating the main findings of relevant research streams, a detailed overview of the literature on CKM in the context of SMEs is established, and a research agenda is set up.
Weak mineralization despite strong processing of dissolved organic matter in Eastern Arctic tundra ponds
Authors: Laurion Isabelle , Massicotte Philippe , Mazoyer Flora , Negandhi Karita , Mladenov Natalie
Published: October 2020

Permafrost thawing mobilizes large quantities of organic carbon that was sequestered in Arctic regions over the last glacial cycle. Processes involved in the oxidation of this carbon need to be further assessed to estimate the fraction to be released into the atmosphere. Shallow tundra ponds are sites of active carbon turnover on the landscape and significant sources of greenhouse gases. Dissolved organic matter (DOM) leached from thawing peat into these ponds is exposed to sunlight, with the potential to accelerate its mineralization directly into CO2 or through the production of more labile molecules. We tested the catalytic effect of sunlight on DOM mineralization in tundra ponds formed on organic‐rich polygonal landscapes originating from syngenetic permafrost, including a pond exposed to active permafrost erosion. Microbial decay rates, measured as the loss of chromophoric DOM, were similar to photodecay rates (1%–3% d−1). Groups of fluorescing molecules were formed through microbial transformation or lost through photolysis at differing rates among studied ponds, with the erosive trough pond presenting a unique response suggesting the involvement of soil microbes. Despite the stimulation of microbial growth under sunlight and the dynamic response of DOM optical properties, the loss of dissolved organic carbon was not significant under any treatment. This suggests that microbial and photochemical mineralization of DOM was slow and potentially substrate‐limited during the dry period when ponds were sampled. The static nature of tundra ponds, with their long water retention time, may thus constrain hot moments when water moves and transports carbon on the landscape.
Requirements of LEFTY and Nodal overexpression for tumor cell survival under hypoxia in glioblastoma
Authors: Matsumoto Toshihide , Chino Hiromi , Akiya Masashi , Hashimura Miki , Yokoi Ako , Tochimoto Masataka , Nakagawa Mayu , Jiang Zesong , Saegusa Makoto
Published: October 2020

Glioblastomas (GBM) contain numerous hypoxic foci associated with a rare fraction of glioma stem cells (GSCs). Left‐right determination factor (LEFTY) and Nodal, members of the transforming growth factor β (TGF‐β) superfamily, have glycogen synthase kinase 3β (GSK‐3β) phosphorylation motifs and are linked with stemness in human malignancies. Herein, we investigated the roles of LEFTY and Nodal in GBM hypoxic foci. In clinical samples, significantly higher expression of LEFTY, Nodal, phospho (p) GSK‐3β, pSmad2, and Nestin, as well as higher apoptotic and lower proliferation rates, were observed in nonpseudopalisading (non‐Ps) perinecrotic lesions as compared to Ps and non‐necrotic tumor lesions, with a positive correlation between LEFTY, Nodal, pGSK‐3β, or pSmad2 scores. In KS‐1, a GBM cell line that lacks endogenous Nodal expression, treatment with the hypoxic mimetic CoCl2 increased LEFTY, pGSK‐3β, and pSmad2 levels, but decreased pAkt levels. Moreover, the promoter for LEFTY, but not Nodal, was activated by Smad2 or TGF‐β1, suggesting that overexpression of LEFTY and Nodal may be due to Akt‐independent GSK‐3β inactivation, with or without cooperation of the TGF‐β1/Smad2 axis. LEFTY and Nodal overexpression increased proliferation rates and reduced susceptibility to CoCl2‐induced apoptosis, and increased the expression of epithelial‐mesenchymal transition (EMT)/GSC‐related markers. An increased ALDH1high population and more efficient spheroid formation was also observed in LEFTY‐overexpressing cells. These findings suggest that LEFTY and Nodal may contribute to cell survival in non‐Ps GBM perinecrotic lesions, leading to alterations in apoptosis, proliferation, or EMT/GCS features.
Spatial orthogonal attention generative adversarial network for MRI reconstruction
Authors: Zhou Wenzhong , Du Huiqian , Mei Wenbo , Fang Liping
Published: October 2020

Purpose

Recent studies have witnessed that self‐attention modules can better solve the vision understanding problems by capturing long‐range dependencies. However, there are very few works designing a lightweight self‐attention module to improve the quality of MRI reconstruction. Furthermore, it can be observed that several important self‐attention modules (e.g., the non‐local block) cause high computational complexity and need a huge number of GPU memory when the size of the input feature is large. The purpose of this study is to design a lightweight yet effective spatial orthogonal attention module (SOAM) to capture long‐range dependencies, and develop a novel spatial orthogonal attention generative adversarial network, termed as SOGAN, to achieve more accurate MRI reconstruction.

Methods

We first develop a lightweight SOAM, which can generate two small attention maps to effectively aggregate the long‐range contextual information in vertical and horizontal directions, respectively. Then, we embed the proposed SOAMs into the concatenated convolutional autoencoders to form the generator of the proposed SOGAN.

Results

The experimental results demonstrate that the proposed SOAMs improve the quality of the reconstructed MR images effectively by capturing long‐range dependencies. Besides, compared with state‐of‐the‐art deep learning‐based CS‐MRI methods, the proposed SOGAN reconstructs MR images more accurately, but with fewer model parameters.

Conclusions

The proposed SOAM is a lightweight yet effective self‐attention module to capture long‐range dependencies, thus, can improve the quality of MRI reconstruction to a large extent. Besides, with the help of SOAMs, the proposed SOGAN outperforms the state‐of‐the‐art deep learning‐based CS‐MRI methods.
A variational formulation for motion design of adaptive compliant structures
Authors: Sachse Renate , Bischoff Manfred
Published: October 2020

Adaptive structures are characterized by their ability to adjust their geometrical and other properties to changing loads or requirements during service. This contribution deals with a method for the design of quasi‐static motions of structures between two prescribed geometrical configurations that are optimal with regard to a specified quality function while taking large deformations into account. It is based on a variational formulation and the solution by two finite element discretizations, the spatial discretization (the standard finite element mesh) and an additional discretization of the deformation path or trajectory. For the investigations, an exemplary objective function, the minimization of the internal energy, integrated along the deformation path, is used. The method for motion design presented herein uses the Newton‐Raphson method as a second‐order optimization algorithm and allows for analytical sensitivity analysis. The proposed method is verified and its properties are investigated by benchmark examples including rigid body motions, instability phenomena, and determination of inextensible deformations of shells.
N‐Terminomics for the Identification of In Vitro Substrates and Cleavage Site Specificity of the SARS‐CoV‐2 Main Protease
Authors: Koudelka Tomas , Boger Juliane , Henkel Alessandra , Schönherr Robert , Krantz Stefanie , Fuchs Sabine , Rodríguez Estefanía , Redecke Lars , Tholey Andreas
Published: October 2020

The genome of coronaviruses, including SARS‐CoV‐2, encodes for two proteases, a papain like (PLpro) protease and the so‐called main protease (Mpro), a chymotrypsin‐like cysteine protease, also named 3CLpro or non‐structural protein 5 (nsp5). Mpro is activated by autoproteolysis and is the main protease responsible for cutting the viral polyprotein into functional units. Aside from this, it is described that Mpro proteases are also capable of processing host proteins, including those involved in the host innate immune response. To identify substrates of the three main proteases from SARS‐CoV, SARS‐CoV‐2, and hCoV‐NL63 coronviruses, an LC‐MS based N‐terminomics in vitro analysis is performed using recombinantly expressed proteases and lung epithelial and endothelial cell lysates as substrate pools. For SARS‐CoV‐2 Mpro, 445 cleavage events from more than 300 proteins are identified, while 151 and 331 Mpro derived cleavage events are identified for SARS‐CoV and hCoV‐NL63, respectively. These data enable to better understand the cleavage site specificity of the viral proteases and will help to identify novel substrates in vivo. All data are available via ProteomeXchange with identifier PXD021406.
Thermal unimolecular reactivity pathways in dehydro‐diazines radicals
Authors: Saraswat Mayank , Venkataramani Sugumar
Published: October 2020

In this work, we investigated the detailed reactivity of dehydro‐diazine radicals through unimolecular dissociation pathways. Aromatic six‐membered rings with two nitrogens as heteroatoms are classified as diazines, which include pyrimidine 1, pyridazine 2, and pyrazine 3. The C–H bond scission in pyrimidine, pyridazine, and pyrazine leads to three (1a–1c), two (2a and 2b), and one (3a) radical isomers, respectively. Through quantum chemical calculations, reactivity aspects of all the six radical isomers have been investigated by considering different modes of unimolecular reactions. On the basis of the computations at (U)B3LYP/cc‐pVTZ, (U)M06‐2X/cc‐pVTZ, and (U)CCSD(T)/cc‐pVTZ//(U)B3LYP/cc‐pVTZ levels of theory and analysis, we found out that ring‐opening pathways were kinetically more favorable compared with isomerization (1,2‐H shift) pathways or C–H bond dissociation leading to biradicals. In all the cases, ring‐opening via C–N bond cleavage has a lower energy barrier compared with C–C bond cleavage owing to the stabilizing interaction between radical electron and the nitrogen lone pair. Moreover, the unimolecular decomposition channels can lead to several fragmentation products, which are interesting in the astrochemical context. On the basis of these investigations and also the impact of three centered–five electrons (3c–5e) interactions on the reactivity aspects, we determined the kinetic stability order among the six isomeric dehydrodiazine radicals.
What we need to know to prevent a mass extinction of plant species
Authors: Pimm Stuart L.
Published: October 2020

Social Impact Statement

Human actions are driving plant species to extinction at rates a hundred to a thousand times faster than normal. To prevent extinctions, it would be helpful to have a more comprehensive taxonomic catalogue and much greater knowledge of where plant species live. Addressing these questions must be a scientific priority. However, what we know at present is enough to effect practical conservation actions, such as protecting more land in biodiverse places, reconnecting fragmented habitats, and eliminating species introduced outside their native ranges. For the benefit of people and the planet, we can, and must act on what we know already, to prevent catastrophic plant extinctions.

Continuing destruction of habitats—and especially tropical forests—the introduction of plant and herbivorous animal species outside their native ranges, and global climate disruption all contribute to the extinction of plant species. What can we do to prevent this? Do we have enough basic information to make effective conservation decisions? First, how many plant species are there? This question has an easy element—how many species we know now—and a much more difficult one—how many do we not know. Second, where are the concentrations of plant species? Third, where are the species we do not yet know? Fourth, what plant species have gone extinct, and where did they live? A related question is which species are threatened with extinction and where do they live? Fifth, how well can we map threats to species? For habitat loss, remote sensing provides satellite images globally and very frequently. It does so at a resolution that often displays individual trees and bushes. Sixth, supposing we had detailed answers to the previous questions, what are we doing to protect species? How well does the existing network of protected areas encompass species, especially those with the smallest ranges? Does that network allow for species moving upslope as the climate heats up? How well are managers doing in removing introduced species? Although answering these questions must be a scientific priority, we cannot wait until we have all the answers. We can, and indeed must, act on what we know already.
The importance of measuring biomarkers in asthma
Authors: Greener Mark
Published: October 2020

Recent studies confirm that one size of asthma management does not fit all and that patients differ in their patterns of inflammation and responses to therapy. This article discusses how measuring biomarkers can allow clinicians to tailor treatment effectively, and how research on the relationship between parasites and the immune system is providing insights into potential new therapies.
Deprescribing antihypertensives in patients with multimorbidity
Authors: Sheppard James P , Payne Rupert A
Published: October 2020

Deprescribing preventative medications such as antihypertensives may reduce adverse events in some older adults, leading to improved quality of life. The Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE) trial examined the safety and efficacy of antihypertensive deprescribing in older patients taking more than one treatment for hypertension. This article discusses the findings of the study and their implications for clinical practice.
Opportunities to optimise direct‐acting oral anticoagulants
Authors: Thompson Angus
Published: October 2020

The newer direct‐acting oral anticoagulants (DOACs) – apixaban, dabigatran, edoxaban, rivaroxaban – offer many advantages over older anticoagulants such as warfarin. However, in order to optimise their benefits, it is important that patients taking them do not become too blasé, advises Angus Thompson.
Enhancement of air stability and photovoltaic performance in organic solar cells by structural modulation of bis‐amide‐based donor‐acceptor copolymers: A computational insight
Authors: Bhattacharya Labanya , Sharma Sagar , Sahu Sridhar
Published: October 2020

The effect of structural modulation on a series of donor‐acceptor (D‐A) copolymers (1‐7), comprising of thieno[3,2‐b]thiophene (TT) donor and thiazole‐flanked different bis‐amide‐functionalized acceptor units, has been explored. Structural functionalization has been performed by incorporating aromatic rings in the bis‐amide‐functionalized bipyrrolylidene‐2,2′(1H,1′H)‐dione (BPD) (1) acceptor unit, and six D‐A copolymers containing isoindigo (2), azaisoindigo (3), benzoisoindigo (4), benzoazaisoindigo (5), 1,5‐naphthyridine‐BPD (6), and 1,8‐naphthyridine‐BPD (7) as acceptor units are designed. Density functional theory has been employed to understand the impact of structural modulation on geometrical, optoelectronic, charge transport, and photovoltaic properties of the copolymers. The higher proportion of N‐heteroatom in copolymers 3, 6, and 7 leads to low‐lying highest occupied molecular orbital (lowest unoccupied molecular orbital) levels and thus improves their air stability and open‐circuit voltage. The computed optical absorption in the visible range (602‐754 nm) ensures that the studied compounds can efficiently harvest photon energy. The ratio of charge transfer rate (KCT) and charge recombination rate (KCR) at donor/PC61BM interfaces of structurally tuned copolymers are found to be ∼107 to 1022 times higher than 1/PC61BM. The maximum predicted power conversion efficiency by Scharber diagram could reach up to ∼8% for 3, 6, and 7. The calculated results shed light on the fact that the structural modulation of bis‐amide‐functionalized D‐A copolymers can efficaciously lead to enhanced air stability and photovoltaic performance.
Sensory nerves in the spotlight of the stem cell niche
Authors: Picoli Caroline C. , Costa Alinne C. , Rocha Beatriz G.S. , Silva Walison N. , Santos Gabryella S.P. , Prazeres Pedro H.D.M. , Costa Pedro A.C. , Oropeza Anderson , Silva Rodrigo A. , Azevedo Vasco A.C. , Resende Rodrigo R. , Cunha Thiago M. , Mintz Akiva , Birbrair Alexander
Published: October 2020

Niches are specialized tissue microenvironments that control stem cells functioning. The bone marrow mesenchymal stem cell niche defines a location within the marrow in which mesenchymal stem cells are retained and produce new cells throughout life. Deciphering the signaling mechanisms by which the niche regulates stem cell fate will facilitate the use of these cells for therapy. Recent studies, by using state-of-the-art methodologies, including sophisticated in vivo inducible genetic techniques, such as lineage-tracing Cre/loxP mediated systems, in combination with pharmacological inhibition, provide evidence that sensory neuron is an important component of the bone marrow mesenchymal stem cell niche. Strikingly, knockout of a specific receptor in sensory neurons blocked stem cell function in the bone marrow. The knowledge arising from these discoveries will be crucial for stem cell manipulation in the future. Here, we review recent progress in our understanding of sensory nerves biology in the stem cell niche.
A cloud‐based integration platform for enterprise application integration: A Model‐Driven Engineering approach
Authors: Frantz Rafael Z. , Corchuelo Rafael , Basto‐Fernandes Vitor , Rosa‐Sequeira Fernando , Roos‐Frantz Fabricia , L. Arjona José
Published: October 2020

This article addresses major information systems integration problems, approaches, technologies, and tools within the context of Model‐Driven Software Engineering. The Guaraná integration platform is introduced as an innovative platform amongst state‐of‐the‐art technologies available for enterprises to design and implement integration solutions. In this article, we present its domain‐specific modeling language and its industrial cloud‐based web development platform, which supports the design and implementation of integration solutions. A real‐world case study is described and analyzed; then, we delve into its design and implementation, to finally disclose ten measures that empirically help estimating the amount of effort involved in the development of integration solutions.
Structural health monitoring methods, dispersion of fibers, micro and macro structural properties, sensing, and mechanical properties of self‐sensing concrete—A review
Authors: Reddy Panga Narasimha , Kavyateja Bode Venkata , Jindal Bharat Bhushan
Published: October 2020

Self‐sensing composites are now becoming extremely attractive for the applications in civil engineering structures in order to enhance the safety and service life. In the new generation carbon nanofibers (CNFs) and nanotubes (CNTs) have shown good electrical, mechanical, and thermal parameters which inspired in the development of innovative nanocomposites with great and multifunctional properties. Among the numerous advances in civil engineering, the introduction of such carbon fibers to cement based materials produces cementitious materials as a smart or self‐sensing. Such smart composites reveal a noticeable change in their electrical conductivity with applied stress/strain and this special characteristic makes them helpful for monitoring of structures. However, there are still issues with CNFs and CNTs dispersion in case of cementitious composites, which impede the effective transfer of nanomaterials properties into the composites. Present paper presents a critical review on the dispersion of CNFs and CNTs within cementitious matrices, mechanical and electrical properties for the health monitoring of civil engineering structures.
Violation Witnesses and Result Validation for Multi-Threaded Programs
Authors: Beyer Dirk , Friedberger Karlheinz
Published: October 2020

Invariants and error traces are important results of a program analysis, and therefore, a standardized exchange format for verification witnesses is used by many program analyzers to store and share those results. This way, information about program traces and variable assignments can be shared across tools, e.g., to validate verification results, or provided to users, e.g., to visualize and explore the results in order to fix bugs or understand the reason for a program’s correctness. The standard format for correctness and violation witnesses that was used by SV-COMP for several years was only applicable to sequential (single-threaded) programs. To enable the validation of results for multi-threaded programs, we extend the existing standard exchange format by adding information about thread management and thread interleaving. We contribute a reference implementation of a validator for violation witnesses in the new format, which we implemented as component of the software-verification framework
"Image missing"
. We experimentally evaluate the format and validator on a large set of violation witnesses. The outcome is promising: several verification tools already produce violation witnesses that help validating the verification results, and our witness validator can re-verify most of the produced witnesses.
Erratum to: Symanzik improvement with dynamical charm: a 3+1 scheme for Wilson quarks
Authors: Fritzsch Patrick , Sommer Rainer , Stollenwerk Felix , Wolff Ulli
Published: October 2020

We correct for typos and add a few missing details that can help to reproduce our calculations. The results of our original paper remain unchanged.