bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher donor body mass index is associated with increased hemolysis of red blood cells at 42‐days of storage: A retrospective analysis of routine quality control data
Authors: Sparrow Rosemary L. , Payne Katherine A. , Adams Geoffrey G.
Published: November 2020

Background

For reasons unclear, some stored red blood cells (RBCs) have low hemolysis, while others have high hemolysis, which impacts quality consistency. To identify variables that influence hemolysis, routine quality control (QC) data for 42‐days‐stored RBCs with corresponding donor information were analyzed.

Study Design and Methods

RBC QC and donor data were obtained from a national blood supplier. Regression models and analyses were performed on total cohort stratified by donor sex and by high hemolysis (≥90th percentile) vs control (<90th percentile) samples, including matching.

Results

Data included 1734 leukoreduced RBCs (822 female, 912 male), processed by buffy coat–poor or whole blood filtration methods. Male RBCs had larger volume, hemoglobin content, and higher hemolysis than female RBCs (median hemolysis, 0.24% vs 0.21%; all P < .0001). Multivariable regression identified increased body mass index (BMI) and RBC variables were associated with higher hemolysis (P < .0001), along with older female age and buffy coat–poor processing method (P < .002). Logistic regression models comparing the high and control hemolysis subsets, matched for RBC component variables and processing method, identified overweight‐obese BMI (>27 kg/m2) in males remained the single donor‐related variable associated with higher hemolysis (P < .0001); odds ratio, 3 (95% confidence interval [CI], 1.3‐6.7), increasing to 4 (95% CI, 1.8‐8.6) for obese males (BMI > 30 kg/m2). Female donor obesity and older age trended toward higher hemolysis.

Conclusion

Donor BMI, sex, and female age influence the level of hemolysis of 42‐days‐stored RBCs. Other factors, not identified in this study, also influence the level of hemolysis.
Management of canine perianal fistula with fluorescence light energy: preliminary findings
Authors: Marchegiani Andrea , Tambella Adolfo M. , Fruganti Alessandro , Spaterna Andrea , Cerquetella Matteo , Paterson Susan
Published: November 2020

Contexte

Les fistules anales canines (CPF) sont une dermatose sévère, douloureuse et invalidante de la peau périanale. Elle interfère souvent avec la qualité de vie du chien comme de son propriétaire. Les traitements médicaux conventionnels impliquent les immunosuppresseurs ; cependant, la résolution des lésions peut être limitée par la faible compliance du propriétaire, les effets indésirables des traitements et leur coût.

Hypothèses/Objectifs

Cette étude a pour objectif de déterminer les effets bénéfiques potentiels de la lumière fluorescente (FLE) sur des cas de CPF.

Sujets

Quatre chiens avec fistules périanales actives.

Matériels et méthodes

FLE a été appliqué en traitement unique une fois par semaine, deux fois consécutives au cours de la même session pour chaque chien jusqu’à amélioration clinique significative avec évaluation chaque semaine pendant six semaines. Les chiens étaient évalués par la mesure de la taille des lésions au départ et chaque semaine pendant six semaines, à l’aide d’un logiciel de planimétrie. Les propriétaires notaient les vocalises et les efforts de poussée au cours de la défécation de leur animal ainsi que la fréquence de léchage sur une échelle de 0 à 5 pour déterminer la réponse au traitement.

Résultats

Tous les chiens se sont améliorés avec FLE, avec une réduction significative des vocalises, poussées et léchage après deux semaines (P = 0.002). Après cinq semaines de traitement FLE, les zones lésionnelles avaient significativement diminuées (P = 0.04). Seulement un chien a nécessité plus de sept applications. Aucun effet secondaire n’a été décrit.

Conclusion et importance clinique

FLE semble être un traitement alternatif prometteur de CPF.
Weed infestation is affected by chickpea farmer demographics and agronomic practices
Authors: Bagheri Alireza , Sohrabi Naser , Mondani Farzad , Nosratti Iraj
Published: November 2020

To investigate the effects of agronomic practices and farmer demographics on levels of weed infestation in chickpea fields, a survey was conducted during 2015 in Sanjabi district, Kermanshah, Iran. Two sets of data were collected: (a) weed sampling from the selected chickpea fields, and (b) questionnaire recording of farmer demographics and agronomic management. The farmers were asked about their residence status (resident or migrant), occupation (farming only, farming plus a second job), experience and education levels, as well as seedbed preparation, sowing date and method, source of seed supply, crop cultivar, sowing seed rate, weed control operation and crop rotation history. The results showed that weed species composition was similar across the studied fields. The use of a row crop planter, a sowing rate of 45 kg ha‐1, and weed control resulted in 30.2, 23.03 and 34.2% reductions in weed infestation compared with hand sowing, a sowing rate of 30 kg ha‐1 and lack of weed control, respectively. Weed density decreased with increasing farmer experience and decreased by 33.0% and 23.5% in chickpea fields of resident farmers and owners whose sole occupation was agriculture. We found that 89.5% of the most experienced farmers adopted weed control operations and most resident landowners (77.4%) opted for crop planter (77.4%) and weed control (90.3%) compared to migrant farmers (50 and 68.5%, respectively). More landowners who were exclusively farmers performed weed control (90.6%) than owners who had a second job (67.9%).
Impact of donor and prolonged cold ischemia time of neonatal pig pancreas on neonatal pig islet transplant outcome
Authors: Huang Wenlong , Shimizu Hirofumi , Bianchi John , Matovinovic Kaja , Ayares David L. , Gotoh Mitsukazu , Korbutt Gregory S. , Rajotte Ray V. , Rayat Gina R.
Published: November 2020

Background

Genetically modified pigs (GMP) have been developed to alleviate the shortage of donors in human islet transplantation and rejection. In this study, we characterized and compared the islets from GalTKO, GalTKO/hCD46, GalTKO/hCD46/hCD39, and wild‐type (WT) neonatal pigs.

Methods

Islets were isolated from GMP and WT pig pancreases that have been packaged with ice pack for at least 24 hours. The difference in gene expression and function of islets were evaluated by microarray analysis and transplantation of islets under the kidney capsule of streptozotocin‐induced diabetic immune‐deficient mice, respectively. Blood glucose levels of these mice were monitored weekly post‐transplantation for >100 days, and islet grafts were collected and evaluated for the presence of endocrine cells.

Results

The genes involved in extracellular components, cell adhesion, glucose metabolism, and inflammatory response are differentially expressed between GMP and WT pig islets. Variation in the ability of pig islets in correcting the diabetic state of the mouse recipients appears to be dependent on the pig donor. In addition, prolonged cold ischemia time had a negative effect on the transplant outcome. All normoglycemic mice were able to respond well to glucose challenge despite the initial differences in the ability of islet transplants to reverse their diabetic state. Islet xenografts of normoglycemic mice contained abundant insulin‐ and glucagon‐positive cells.

Conclusion

The effect of GMP and WT neonatal pig islet transplants on hyperglycemia in mice appears to be dependent on the pig donor, and prolonged cold ischemia time negatively affects the neonatal pig islet transplant outcome.
Enhancing nanostructured nickel-rich lithium-ion battery cathodes via surface stabilization
Authors: Lim Jin-Myoung , Luu Norman S. , Park Kyu-Young , Tan Mark T. Z. , Kim Sungkyu , Downing Julia R. , He Kai , Dravid Vinayak P. , Hersam Mark C.
Published: November 2020

Layered, nickel-rich lithium transition metal oxides have emerged as leading candidates for lithium-ion battery (LIB) cathode materials. High-performance applications for nickel-rich cathodes, such as electric vehicles and grid-level energy storage, demand electrodes that deliver high power without compromising cell lifetimes or impedance. Nanoparticle-based nickel-rich cathodes seemingly present a solution to this challenge due to shorter lithium-ion diffusion lengths compared to incumbent micrometer-scale active material particles. However, since smaller particle sizes imply that surface effects become increasingly important, particle surface chemistry must be well characterized and controlled to achieve robust electrochemical properties. Moreover, residual surface impurities can disrupt commonly used carbon coating schemes, which result in compromised cell performance. Using x-ray photoelectron spectroscopy, here we present a detailed characterization of the surface chemistry of LiNi0.8Al0.15Co0.05O2 (NCA) nanoparticles, ultimately identifying surface impurities that limit LIB performance. With this chemical insight, annealing procedures are developed that minimize these surface impurities, thus improving electrochemical properties and enabling conformal graphene coatings that reduce cell impedance, maximize electrode packing density, and enhance cell lifetime fourfold. Overall, this work demonstrates that controlling and stabilizing surface chemistry enables the full potential of nanostructured nickel-rich cathodes to be realized in high-performance LIB technology.
The Hydrostatic Paradox Redux
Authors: Greenslade Thomas B.
Published: November 2020

A good paradox has the viewer confused, but the best paradoxes lead the viewer to try to understand what is happening. One of my favorites is the hydrostatic paradox, in which a short and slender column of water supports a relatively enormous weight. Figure 1 shows this paradox in action. In the picture a student weighing 60 pounds stands on a platform placed atop a flat water-filled rubber hot-water bottle. Connected to the bottle is a slender upright glass tube, also filled with water. A column of water only four or so feet high supports the student.
Tradition Meets Technology: Acoustical Analysis of a Kazakh Dombra with Smartphones
Authors: Kasper Lutz , Vogt Patrik
Published: November 2020

The aim of this paper is to provide physics teachers and physics students with interdisciplinary cultural and scientific related content. The dombra is on the one hand a cultural symbol of Kazakhstan with a long tradition. On the other hand, the dombra as a musical instrument is an object of interest in acoustics. The topic can lead to deeper insights into theory of musical instruments and acoustics and to positive motivational effects as well. The idea of this article originated in a guest lecture in physics at Taraz State Pedagogical University (Kazakhstan), where one of the authors introduced physics teacher students to “New Technologies in Physics Education.” This course was about good practice examples of integration of mobile devices and their built-in sensors in physics classes. An overview of this innovative educational field is given in Ref. 1. There is a wide range of smartphone-enhanced experiments, from simple hands-on experiments to complex digital data collection and modeling tasks in particular in the field of acoustics.
Where Do Women of Color Complete Physics Degrees?
Authors: Johnson Angela , Young Rose , Mulvey Elizabeth
Published: November 2020

Between 2006 and 2016, women made up 19% of the U.S. citizens and permanent residents who received bachelor’s degrees in physics. Women of Color (which includes women who indicated Black, Latina, American Indian, Alaska Native, Asian American, Pacific Islander, Native Hawaiian, or mixed as their ethnicity or race) received 4% of all physics degrees; African American, Latina, and Native American (ALANA) women received 2%. ALANA women are more underrepresented in physics than in any of the other major STEM disciplines, including computer science and engineering (see Fig. 1).
Is My Physics Textbook Sexist?
Authors: Rosa Katemari , Silva Maria Ruthe Gomes da
Published: November 2020

This paper is intended to foster conversations about stereotypes, prejudice, and our day-to-day work in the classroom. The focus is on sexism and how it can affect our teaching, particularly looking at physics textbooks. Maybe you are already familiar with debates around feminist movements, gender studies, patriarchy, performance, and all of those issues common to people like me, whose research work considers the intersections of gender, sexuality, and physics teaching. I (first author) am a professor in a physics department; because of my work with pre- and in-service physics teacher education, I frequent several high schools. In my experience, many physics teachers (and other teachers too!) have a hard time seeing how these gender discussions connect to their classroom; part of my work is to help them identify these connections. This paper was motivated by my failure to detect broader gender connections in physics textbooks.
Momentum Vector Diagrams
Authors: Unyapoti Trai , Arayathanitkul Kwan , Emarat Narumon
Published: November 2020

Collisions are real-world situations from everyday life (such as car crashes, playing billiards, etc.) that can be described and understood by the principle of conservation of momentum. One might expect that learning from simple collisions might help students understand more complicated physical phenomena. However, from our teaching experiences we often find that even in a physics problem involving a simple physics collision, students have trouble arriving at the correct answer. Multiple representations are tools to help students think and act like physicists when solving problems. Examples of these representations are motion diagrams, free-body diagrams, energy bar charts, impulse-momentum bar charts, and impulse-momentum diagrams. Impulse-momentum diagrams were designed to help students understand the principle of conservation of momentum. They effectively show the magnitude of the momentum but are limited to only problems in one dimension. In this paper we will show a structured teaching method using momentum vector diagrams (MVD) as a tool. The MVD method is developed to help students understand the principle of conservation of momentum and vector property of momentum, and to be able to use it to solve collision problems especially in two dimensions.
Pseudo-Double-Slit Experiment with Two Glass Plates
Authors: Kang Chang-won , Nam Hyen-Jung , Kim Jung Bog
Published: November 2020

We have demonstrated both interference and diffraction of a pseudo-double slit using two glass plates with a width and a length of about 5 cm and a thickness of about 5 mm. The plates are attached at the upper and lower ends with Scotch tape of about 0.1 to 0.3 mm between the plates. By adjusting the angle between the two plates, we are able to demonstrate a single-slit diffraction pattern or a double-slit interference pattern. Also we can simulate a changing separation between slits by changing the angle between the plates.
Development of an Augmented Reality-Based Game for Projectile Motion
Authors: Chandrakar Milan , Bhagat Kaushal Kumar
Published: November 2020

Recent years have seen an immense development in the field of X Reality (augmented, virtual, and mixed reality), empowering healthcare, education, and entertainment, and the trend predicts an exponential increase in the upcoming years. Augmented reality is a technology in which real-world environments can be enhanced by adding computer-generated graphics, animations, and sound. Many studies investigated the potential of augmented reality (AR) and found the sectors that could take advantage of such technology. The studies showed that AR tools have the capability to enhance teaching and learning as they can provide better visualization of the concepts, e.g., concepts such as Kirchhoff’s law and thermal flux, than conventional methods.
Inertia is how much, not if
Authors: Milliano Joe
Published: November 2020

Inertia is an elusive concept in physics, and it is occasionally used to explain similar-seeming yet different concepts. The goal of this article is to describe two scenarios that are commonly explained using the word inertia, even though that same word is being used to describe two different phenomena. A discussion clearing up this ambiguity follows the examples.
Off-Target
In Vitro
Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent
Authors: Xu Yili , Barauskas Ona , Kim Cynthia , Babusis Darius , Murakami Eisuke , Kornyeyev Dmytro , Lee Gary , Stepan George , Perron Michel , Bannister Roy , Schultz Brian E. , Sakowicz Roman , Porter Danielle , Cihlar Tomas , Feng Joy Y.
Published: November 2020

Remdesivir (RDV, GS-5734), the first FDA-approved antiviral for the treatment of COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. It is intracellularly metabolized into the active triphosphate form, which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases.
Structure and Double-Stranded RNA-Binding Activity of the Birnavirus Drosophila X Virus VP3 Protein
Authors: Ferrero Diego S. , Busnadiego Idoia , Garriga Damià , Guerra Pablo , Martín María Teresa , Kremer Leonor , Usón Isabel , Rodriguez José Francisco , Verdaguer Nuria
Published: November 2020

The birnavirus moonlighting protein VP3 plays crucial roles in interacting with the dsRNA genome segments to form stable ribonucleoprotein complexes and controlling host cell immune responses, presumably by binding to and shielding the dsRNA from recognition by the host silencing machinery. The structural, biophysical, and functional data presented in this work identified the N-terminal domain of VP3 as being responsible for the dsRNA-binding and silencing suppression activities of the protein in drosophila X virus.
Feces Metagenomes and Metagenome-Assembled Genome Sequences from Two Separate Dogs (Canis lupus familiaris) with Multiple Diarrheal Episodes
Authors: Ateba Tshepiso Pleasure , Alayande Kazeem Adekunle , Mwanza Mulunda
Published: November 2020

This study reports two feces metagenomes (D84 and D85) and six metagenome-assembled genomes (MAGs). The assembled MAGs include
Pseudomonas
sp. strain NID84 and
Acinetobacter
sp. strain N2D84 from D84 and
Enterococcus
sp. strain N4D85,
Enterococcus
sp. strain N5D85,
Lactobacillus
sp. strain N6D85, and
Leuconostoc
sp. strain N7D85 from D85.
Acinetobacter
sp. strain N2D84 was identified as a human pathogen with a probability of 92%.
Homologous Recombination in
Clostridioides difficile
Mediates Diversification of Cell Surface Features and Transport Systems
Authors: Steinberg Hannah D. , Snitkin Evan S.
Published: November 2020

Infections with
C. difficile
result in up to half a million illnesses and tens of thousands of deaths annually in the United States. The severity of
C. difficile
illness is dependent on both host and bacterial factors.
Rice
SST
Variation Shapes the Rhizosphere Bacterial Community, Conferring Tolerance to Salt Stress through Regulating Soil Metabolites
Authors: Lian Tengxiang , Huang Yingyong , Xie Xianan , Huo Xing , Shahid Muhammad Qasim , Tian Lei , Lan Tao , Jin Jing
Published: November 2020

Soil salinization is one of the major environmental stresses limiting crop productivity. Crops in agricultural ecosystems have developed various strategies to adapt to salt stress. We used rice mutant and CRISPR-edited lines to investigate the relationships among the
S
quamosa promoter
B
inding
P
rotein box (SBP box) family gene (
SST
/
OsSPL10
), soil metabolites, and the rhizosphere bacterial community. We found that during salt stress, there are significant differences in the rhizosphere bacterial community and soil metabolites between the plants with the
SST
gene and those without it. Our findings provide a useful paradigm for revealing the roles of key genes of plants in shaping rhizosphere microbiomes and their relationships with soil metabolites and offer new insights into strategies to enhance rice tolerance to high salt levels from microbial and ecological perspectives.
Impact of a demand-side integrated WASH and nutrition community-based care group intervention on behavioural change: a randomised controlled trial in western Kenya
Authors: Freeman Matthew C , Ellis Anna S , Ogutu Emily Awino , Caruso Bethany A , Linabarger Molly , Micek Katie , Muga Richard , Girard Amy Webb , Wodnik Breanna K , Jacob Arriola Kimberly
Published: November 2020

Introduction

Growth shortfalls and diarrhoeal diseases remain a major cause of morbidity and mortality in low-income settings. Due to the multifaceted causes of undernutrition and the identified limitations of siloed nutrition programmes, improving the delivery of integrated water, sanitation, hygiene (WASH) and nutrition programming could improve child health.

Methods

We conducted a cluster randomised trial in western Kenya to assess the impact on household behaviours of a novel, theory-informed and integrated WASH and nutrition intervention delivered through care groups as compared with the standard care group approach. We developed an intervention targeting practices relating to food hygiene, mealtime and feeding, and compound cleanliness, each using various behavioural change techniques to influence the uptake of targeted behaviours. Prespecified behavioural outcomes were verified through direct observation, 24 hours recall, and self-reported picture-based methods.

Results

Compared with control households, a greater proportion of intervention households had a hygienic food preparation area (Risk double difference (RDD) 0.81, 95% CI 0.68 to 0.96), had stored food hygienically (RDD 0.76, 95% CI 0.58 to 1.00), had a functional handwashing station (RDD 0.64, 95% CI 0.56 to 0.74), provided a safe space for their child to play (RDD 0.73, 95% CI 0.56 to 0.96), and who fed their children thickened porridge (RDD 0.56, 95% CI 0.51 to 0.63) at endline. The proportion of children 6–24 months in intervention households consuming a sufficient diversity of foods (RDD 0.81, 95% CI 0.64 to 1.04) was higher than in control households; however, there was a non-significant increase in the percentage of pregnant and lactating women receiving an adequate diversity of foods in their diets (RDD 0.86, 95% CI 0.70 to 1.05) among intervention compared with control households at endline.

Conclusion

Our integrated WASH and nutrition intervention resulted in important changes in behaviours. This theory-informed intervention could be added to existing care group programmes to considerable advantage.
WICID framework version 1.0: criteria and considerations to guide evidence-informed decision-making on non-pharmacological interventions targeting COVID-19
Authors: Stratil Jan M , Voss Maike , Arnold Laura
Published: November 2020

Introduction

Public health decision-making requires the balancing of numerous, often conflicting factors. However, participatory, evidence-informed decision-making processes to identify and weigh these factors are often not possible- especially, in the context of the SARS-CoV-2 pandemic. While evidence-to-decision frameworks are not able or intended to replace stakeholder participation, they can serve as a tool to approach relevancy and comprehensiveness of the criteria considered.

Objective

To develop a decision-making framework adapted to the challenges of decision-making on non-pharmacological interventions to contain the global SARS-CoV-2 pandemic.

Methods

We employed the ‘best fit’ framework synthesis technique and used the WHO-INTEGRATE framework as a starting point. First, we adapted the framework through brainstorming exercises and application to case studies. Next, we conducted a content analysis of comprehensive strategy documents intended to guide policymakers on the phasing out of applied lockdown measures in Germany. Based on factors and criteria identified in this process, we developed the WICID (WHO-INTEGRATECOVID-19) framework version 1.0.

Results

Twelve comprehensive strategy documents were analysed. The revised framework consists of 11+1 criteria, supported by 48 aspects, and embraces a complex systems perspective. The criteria cover implications for the health of individuals and populations due to and beyond COVID-19, infringement on liberties and fundamental human rights, acceptability and equity considerations, societal, environmental and economic implications, as well as implementation, resource and feasibility considerations.

Discussion

The proposed framework will be expanded through a comprehensive document analysis focusing on key stakeholder groups across the society. The WICID framework can be a tool to support comprehensive evidence-informed decision-making processes.
Disproportionate secondary mitral regurgitation: myths, misconceptions and clinical implications
Authors: Grayburn Paul A , Packer Milton , Sannino Anna , Stone Gregg W
Published: November 2020

Secondary (functional) mitral regurgitation (SMR) most commonly arises secondary to left ventricular (LV) dilation/dysfunction. The concept of disproportionately severe SMR was proposed to help explain the different results of two randomised trials of transcatheter edge-to-edge mitral valve repair (TEER) versus medical therapy. This concept is based on the fact that effective regurgitant orifice area (EROA) depends on LV end-diastolic volume (LVEDV), ejection fraction, regurgitant fraction and the velocity-time integral of SMR. This review focuses on the haemodynamic framework underlying the concept and the myths and misconceptions arising from it. Each component of EROA/LVEDV is prone to measurement error which can result in misclassification of individual patients. Moreover, EROA is typically measured at peak systole rather than its mean value over the duration of MR. This can result in physiologically impossible values of EROA or regurgitant volume. Although the EROA/LVEDV ratio (1) emphasises that grading MR severity needs to consider LV size and function and (2) helps explain the different outcomes between COAPT and MITRAFR, there are important factors that are not included. Among these are left atrial compliance, LV pressure and ejection fraction, pulmonary hypertension, right ventricular function and tricuspid regurgitation. Because medical therapy can reduce LV volumes and improve both LV function and SMR severity, the key to patient selection is forced titration of neurohormonal antagonists to the target doses that have been proven in clinical trials (along with cardiac resynchronisation when appropriate). Patients who continue to have symptomatic severe SMR after doing so should be considered for TEER.
Ran GTPase is an independent prognostic marker in malignant melanoma which promotes tumour cell migration and invasion
Authors: Elsheikh Somaia , Kouzoukakis Ilias , Fielden Catherine , Li Wei , Lashin Shaimaa Elsaid , Khair Nadia , Raposo Teresa Pereira , Fadhil Wakkas , Rudland Philip , Aleskandarany Mohammed , Patel Poulam , El-Tanani Mohamed , Ilyas Mohammad
Published: November 2020

Aims

Ran GTPase is involved in nucleocytoplasmic shuttling of proteins and is overexpressed in several cancers. The expression of Ran in malignant melanoma (MM) and its functional activity have not been described and were investigated in this study.

Methods

The prognostic value of Ran expression was tested in a series of 185 primary cutaneous MM cases using immunohistochemistry. The functional activity of Ran was investigated in the two melanoma cell lines. Ran expression was knocked down using two siRNAs and the effect on the expression of the c-Met oncogene, a potential downstream target of Ran, was tested. Functional effects of Ran knockdown on cell motility and cell proliferation were also assessed.

Results

Positive Ran expression was seen in 12.4% of MM and was associated with advanced clinical stage and greater Breslow thickness. Positive expression was an independent marker of shorter overall survival (p=0.023). Knockdown of Ran results in decreased expression of c-Met and the downstream c-met signalling targets ERK1/2. There was a significant reduction in cell migration (p<0.001) and cell invasion (p<0.001). c-Met knockdown decreased the expression of Ran through MAPK and PI3K-AKT in A375 cell line, inhibited the cell viability and migration of both A375 and G361 melanoma cell lines while invasion was enhanced.

Conclusion

Ran is a poor prognostic marker in cutaneous MM. It upregulates expression of the oncogene c-Met and, possibly through this, it promotes cell motility which may in turn promote metastasis.
Automated digital enumeration of plasma cells in bone marrow trephine biopsies of multiple myeloma
Authors: Malherbe Jacques A J , Fuller Kathryn A , Mirzai Bob , Augustson Bradley M , Erber Wendy N
Published: November 2020

Aims

Determination of the number of plasma cells in bone marrow biopsies is required for the diagnosis and ongoing evaluation of plasma cell neoplasms. We developed an automated digital enumeration platform to assess plasma cells identified by antigen expression in whole bone marrow sections in multiple myeloma, and compared it with manual assessments.

Methods

Bone marrow trephine biopsy specimens from 91 patients with multiple myeloma at diagnosis, remission and relapse were stained for CD138 and multiple myeloma oncogene 1 (MUM1). Manual assessment and digital quantification were performed for plasma cells in the entire trephine section. Concordance rates between manual and digital methods were evaluated for each antigen by intraclass correlation analyses (ICC) with associated Spearman’s correlations.

Results

The digital platform counted 16 484–1 118 868 cells and the per cent CD138 and MUM1-positive plasma cells ranged from 0.05% to 93.5%. Overall concordance between digital and manual methods was 0.63 for CD138 and 0.89 for MUM1. Concordance was highest with diffuse plasma cell infiltrates (MUM1: ICC=0.90) and lowest when in microaggregates (CD138: ICC=0.13). Manual counts exceeded digital quantifications for both antigens (CD138: mean=26.4%; MUM1: mean=9.7%). Diagnostic or relapse threshold counts, as determined by CD138 manual assessments, were not reached with digital counting for 16 cases (18%).

Conclusions

Automated digital enumeration of the entire, immunohistochemically stained bone marrow biopsy section can accurately determine plasma cell burden, irrespective of pattern and extent of disease (as low as 0.05%). This increases precision over manual visual assessments which tend to overestimate plasma burden, especially for CD138, and when plasma cells are in clusters.
Tissue methylation and demethylation influence translesion synthesis DNA polymerases (TLS) contributing to the genesis of chromosomal abnormalities in myelodysplastic syndrome
Authors: Cavalcante Gabrielle Melo , Borges Daniela Paula , de Oliveira Roberta Taiane Germano , Furtado Cristiana Libardi Miranda , Alves Ana Paula Negreiros Nunes , Sousa Alceu Machado , de Paula Dayrine Silveira , Filho Francisco Dário Rocha , Magalhães Silvia Maria Meira , Ribeiro-Jr Howard Lopes , Pinheiro Ronald Feitosa
Published: November 2020

Aims

DNA methylation has its distribution influenced by DNA demethylation processes with the catalytic conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Myelodysplastic syndrome (MDS) has been associated with epigenetic dysregulation of genes related to DNA repair system, chronic immune response and cell cycle.

Methods

We evaluated the tissue DNA methylation/hydroxymethylation in bone marrow trephine biopsies of 73 patients with MDS, trying to correlate with the mRNA expression of 21 genes (POLH, POLL, REV3L, POLN, POLQ, POLI, POLK, IRF-1, IRF-2, IRF-3, IRF-4, IRF-5, IRF6, IRF-7, IRF-8,IRF-9, MAD2,CDC20,AURKA,AURKBandTPX2).

Results

TheM-score (5mC) was significantly higher in patients with chromosomal abnormalities than patients with normal karyotype (95% CI –27.127779 to –2.368020; p=0.022). We observed a higher 5mC/5hmC ratio in patients classified as high-risk subtypes compared with low-risk subtypes (95% CI –72.922115 to –1.855662; p=0.040) as well as patients with hypercellular bone marrow compared with patients with normocellular/hypocellular bone marrow (95% CI –69.189259 to –0.511828; p=0.047) and with the presence of dyserythropoiesis (95% CI 17.077703 to 51.331388; p=0.001). DNA pols with translesion activity are significantly influenced by methylation.As5mC immunoexpression increases, the expressions ofPOLH(r=−0.816; r2=0.665; p=0.000), POLQ(r=−0.790; r2=0.624; p=0.001), PCNA(r=−0.635; r2=0.403; p=0.020), POLK(r=−0.633; r2=0.400; p=0.036 andREV1(r=−0.578; r2=0.334; p=0.049) decrease.

Conclusions

Our results confirm that there is an imbalance in the DNA methylation in MDS, influencing the development of chromosomal abnormalities which may be associated with the low expression of DNA polymerases with translesion synthesis polymerases activity.
Regorafenib combined with PD1 blockade increases CD8 T-cell infiltration by inducing CXCL10 expression in hepatocellular carcinoma
Authors: Shigeta Kohei , Matsui Aya , Kikuchi Hiroto , Klein Sebastian , Mamessier Emilie , Chen Ivy X , Aoki Shuichi , Kitahara Shuji , Inoue Koetsu , Shigeta Ayako , Hato Tai , Ramjiawan Rakesh R , Staiculescu Daniel , Zopf Dieter , Fiebig Lukas , Hobbs Gabriela S , Quaas Alexander , Dima Simona , Popescu Irinel , Huang Peigen , Munn Lance L , Cobbold Mark , Goyal Lipika , Zhu Andrew X , Jain Rakesh K , Duda Dan G
Published: November 2020

Background and purpose

Combining inhibitors of vascular endothelial growth factor and the programmed cell death protein 1 (PD1) pathway has shown efficacy in multiple cancers, but the disease-specific and agent-specific mechanisms of benefit remain unclear. We examined the efficacy and defined the mechanisms of benefit when combining regorafenib (a multikinase antivascular endothelial growth factor receptor inhibitor) with PD1 blockade in murine hepatocellular carcinoma (HCC) models.

Basic procedures

We used orthotopic models of HCC in mice with liver damage to test the effects of regorafenib—dosed orally at 5, 10 or 20 mg/kg daily—combined with anti-PD1 antibodies (10 mg/kg intraperitoneally thrice weekly). We evaluated the effects of therapy on tumor vasculature and immune microenvironment using immunofluorescence, flow cytometry, RNA-sequencing, ELISA and pharmacokinetic/pharmacodynamic studies in mice and in tissue and blood samples from patients with cancer.

Main findings

Regorafenib/anti-PD1 combination therapy increased survival compared with regofarenib or anti-PD1 alone in a regorafenib dose-dependent manner. Combination therapy increased regorafenib uptake into the tumor tissues by normalizing the HCC vasculature and increasing CD8 T-cell infiltration and activation at an intermediate regorafenib dose. The efficacy of regorafenib/anti-PD1 therapy was compromised in mice lacking functional T cells (Rag1-deficient mice). Regorafenib treatment increased the transcription and protein expression of CXCL10—a ligand for CXCR3 expressed on tumor-infiltrating lymphocytes—in murine HCC and in blood of patients with HCC. UsingCxcr3-deficient mice, we demonstrate that CXCR3 mediated the increased intratumoral CD8 T-cell infiltration and the added survival benefit when regorafenib was combined with anti-PD1 therapy.

Principal conclusions

Judicious regorafenib/anti-PD1 combination therapy can inhibit tumor growth and increase survival by normalizing tumor vasculature and increasing intratumoral CXCR3+CD8 T-cell infiltration through elevated CXCL10 expression in HCC cells.
Neurodegenerative diseases among miners in Ontario, Canada, using a linked cohort
Authors: Zeng Xiaoke , DeBono Nathan L , Harris Anne M , Arrandale Victoria H , Demers Paul A
Published: November 2020

Objectives

We examined employment in mining occupations and industries and its association with neurological disease incidence in a linkage cohort from Ontario, Canada. Outcomes included Alzheimer’s disease (alone and with other dementias), Parkinson’s disease, parkinsonism, motor neuron disease and amyotrophic lateral sclerosis (ALS).

Methods

The Occupational Disease Surveillance System cohort was created by linking workers’ compensation data and healthcare usage records. This analysis included over 1.1 million male workers, followed between 1999 and 2016. Neurological diseases were ascertained using physician billing and hospital discharge records. Adjusted Poisson regression models were used to estimate incidence rate ratios (RR) comparing mining to non-mining workers overall and by ore (industry) and occupation group.

Results

Suggested elevations in incidence rates were observed for ALS among workers of metal mines (RR 2.21, 95% CI 1.04 to 4.69) and for motor neuron disease among those employed in mining occupations within metal mining industries (RR 1.96, 95% CI 1.01 to 3.79), though these were based on relatively few cases. In miscellaneous metal mines, workers who held mining occupations had an elevated rate of Alzheimer’s disease (RR 1.27, 95% CI 0.92 to 1.77). Parkinson’s disease rate was elevated among workers with rock and soil drilling occupations (RR 1.60, 95% CI 1.04 to 2.45).

Conclusions

Mining hazards may be associated with elevated rates of neurodegenerative diseases among workers in mining occupations and industries. More work is needed to better understand mining exposures and their associations with neurodegenerative diseases.
Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study
Authors: Nwaru Bright I , Tibble Holly , Shah Syed A , Pillinger Rebecca , McLean Susannah , Ryan Dermot P , Critchley Hilary , Price David B , Hawrylowicz Catherine M , Simpson Colin R , Soyiri Ireneous N , Appiagyei Francis , Sheikh Aziz
Published: November 2020

Background

Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma.

Methods

We used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000–31 December 2016) retrospective cohort of reproductive-age (16–45 years, n=83 084) women with asthma. Using Read codes, we defined use, subtypes and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendations of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition.

Results

The 17-year follow-up resulted in 456 803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen) and 9% progestogen-only contraceptives. Previous (incidence rate ratio (IRR) 0.94, 95% CI 0.92 to 0.97) and current (IRR 0.96, 95% CI 0.94 to 0.98) use of any, previous (IRR 0.92, 95% CI 0.87 to 0.97) and current use of combined (IRR 0.93, 95% CI 0.91 to 0.96) and longer duration of use (3–4 years: IRR 0.94, 95% CI 0.92 to 0.97; 5+ years: IRR 0.91, 95% CI 0.89 to 0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared with non-use.

Conclusions

Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for the influence of hormonal contraceptives on clinical outcomes of asthma in women are required.

Protocol registration number

European Union electronic Register of Post-Authorisation Studies (EUPAS22967).
Growing medium soluble carbon and nitrogen influence xylem sap and soluble solid contents in greenhouse cucumber fruits
Authors: Dion Pierre-Paul , Jämtgård Sandra , Bertrand Annick , Thériault Mireille , Pepin Steeve , Dorais Martine
Published: November 2020

Compelling evidence recently demonstrated that plants can take up nitrogen (N) as organic molecules. Yet, very little research addressed this issue in the context of organic horticulture, where N is provided as organic residues. Organic N and carbon (C) transported from roots to shoots could contribute significantly to the plant C and N accumulation. We posited that the type (organic or mineral) and amount of N fertilization affect the soluble organic N and C content of the growing medium, in turn influencing xylem sap N and C and fruit soluble solids content (SSC). To test this hypothesis, we collected growing medium, xylem sap, and fruit samples in a greenhouse cucumber crop grown in a peat-based growing medium and fertilized with organic (blood and feather meals) or mineral (ammonium nitrate) N fertilizers. The organic N source reduced growing medium concentrations of soluble mineral and organic N relative to the mineral source through microbial immobilization. Xylem sap C and N were positively linked to the soluble C and N contents of the growing medium, contributing to higher fruit SSC. A causal model is proposed, in which 62.6% of the variance observed in fruit SSC is explained by variation in mineral soluble N and soluble organic C in the growing medium and dissolved organic C and amino acids in xylem sap. Our results provide in situ indications that organic molecules in the growing medium are taken up by cucumber plants and contribute to fruit soluble solids in a context relevant to greenhouse horticulture.
Hierarchically nanostructured thermoelectric materials: challenges and opportunities for improved power factors
Authors: Neophytou Neophytos , Vargiamidis Vassilios , Foster Samuel , Graziosi Patrizio , de Sousa Oliveira Laura , Chakraborty Dhritiman , Li Zhen , Thesberg Mischa , Kosina Hans , Bennett Nick , Pennelli Giovanni , Narducci Dario
Published: November 2020

The field of thermoelectric materials has undergone a revolutionary transformation over the last couple of decades as a result of the ability to nanostructure and synthesize myriads of materials and their alloys. TheZTfigure of merit, which quantifies the performance of a thermoelectric material has more than doubled after decades of inactivity, reaching values larger than two, consistently across materials and temperatures. Central to thisZTimprovement is the drastic reduction in the material thermal conductivity due to the scattering of phonons on the numerous interfaces, boundaries, dislocations, point defects, phases, etc., which are purposely included. In these new generation of nanostructured materials, phonon scattering centers of different sizes and geometrical configurations (atomic, nano- and macro-scale) are formed, which are able to scatter phonons of mean-free-paths across the spectrum. Beyond thermal conductivity reductions, ideas are beginning to emerge on how to use similar hierarchical nanostructuring to achieve power factor improvements. Ways that relax the adverse interdependence of the electrical conductivity and Seebeck coefficient are targeted, which allows power factor improvements. For this, elegant designs are required, that utilize for instance non-uniformities in the underlying nanostructured geometry, non-uniformities in the dopant distribution, or potential barriers that form at boundaries between materials. A few recent reports, both theoretical and experimental, indicate that extremely high power factor values can be achieved, even for the same geometries that also provide ultra-low thermal conductivities. Despite the experimental complications that can arise in having the required control in nanostructure realization, in this colloquium, we aim to demonstrate, mostly theoretically, that it is a very promising path worth exploring. We review the most promising recent developments for nanostructures that target power factor improvements and present a series of design ‘ingredients’ necessary to reach high power factors. Finally, we emphasize the importance of theory and transport simulations for materialoptimization, and elaborate on the insight one can obtain from computational tools routinely used in the electronic device communities.

Graphical abstract
Further results on the arcwise connectedness of solution sets of discontinuous quantum stochastic differential inclusions
Authors: Dikko D. A.
Published: November 2020

In the framework of the Hudson–Parthasarathy quantum stochastic calculus, we employ a recent generalization of the Michael selection results in the present noncommutative settings to prove that the function space of the matrix elements of solutions to discontinuous quantum stochastic differential inclusion (DQSDI) is arcwise connected.
Simultaneous Online Damage Detection and Vibration Control of Structures Using Synchronization and Semi-Active Control
Authors: Moradmand Mahdi , Amini Fereidoun , Ghaderi Pedram
Published: November 2020

In this paper, a smart structure is developed by integrating a semi-active control strategy with an online synchronization-based damage detection method. In this algorithm, the structural damages are identified in real-time with the synchronization-based method using displacement and velocity measurements of the structure. Then, a fuzzy logic controller is applied for determination of the control forces according to the occurrence of damages. A five-story linear shear building equipped with magneto-rheological (MR) dampers is studied numerically to verify the performance and efficiency of the proposed integrated method for both damage detection and vibration suppression. One damage scenario and four earthquake records are used for such purpose. Results demonstrate that the proposed algorithm has the capability of identifying structural damages satisfactorily while exerting suitable control forces to compensate for the damages occurrence and mitigating the dynamic responses of the structure. Furthermore, it is shown that in comparison with the long-established method of only vibration control, the total energy consumption is significantly reduced, an issue of concern in optimal control of structures.
Solitary wave solutions of mKdV–Calogero–Bogoyavlenskii–Schiff equation by using Lie symmetry analysis
Authors: Kumar Mukesh , Manju Kumari
Published: November 2020

In this paper, we introduced and established some group invariant results of [Formula: see text]-dimensional mKdV–Calogero–Bogoyavlenskii–Schiff equation. Using the one-parameter Lie-group of transformations, we explored various closed-form solutions. The procedure minimizes the number of independent variables by one in every proceeding stage leading to form a system of the ordinary differential equations. The nature of solutions is investigated both analytically and physically through their evolutionary profiles by considering adequate choices of arbitrary functions and constants. The obtained results have been plotted with the aid of numerical simulation to obtain a significant appearance of the traced results. Simulation is carried out by taking an adequate option of arbitrary constants and functions, applying MATLAB code through progressing profiles. Wave solutions derived here are positons, multiple solitons, negaton and kink types which are shown through graph analysis.