bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment planning for Flash radiotherapy: General aspects and applications to proton beams
Authors: Schwarz Marco , Traneus Erik , Safai Sairos , Kolano Anna , van de Water Steven 
Published: February 2022

AbstractThe increased radioresistence of healthy tissues when irradiated at very high dose rates (known as the Flash effect) is a radiobiological mechanism that is currently investigated to increase the therapeutic ratio of radiotherapy treatments. To maximize the benefits of the clinical application of Flash, a patient‐specific balance between different properties of the dose distribution should be found, that is, Flash needs to be one of the variables considered in treatment planning. We investigated the Flash potential of three proton therapy planning and beam delivery techniques, each on a different anatomical region. Based on a set of beam delivery parameters, on hypotheses on the dose and dose rate thresholds needed for the Flash effect to occur, and on two definitions of Flash dose rate, we generated exemplary illustrations of the capabilities of current proton therapy equipment to generate Flash dose distributions. All techniques investigated could both produce dose distributions comparable with a conventional proton plan and reach the Flash regime, to an extent that was strongly dependent on the dose per fraction and the Flash dose threshold. The beam current, Flash dose rate threshold, and dose rate definition typically had a more moderate effect on the amount of Flash dose in normal tissue. A systematic estimation of the impact of Flash on different patient anatomies and treatment protocols is possible only if Flash‐specific treatment planning features become readily available. Planning evaluation tools such as a voxel‐based dose delivery time structure, and the inclusion in the optimization cost function of parameters directly associated with Flash (e.g., beam current, spot delivery sequence, and scanning speed), are needed to generate treatment plans that are taking full advantage of the potential benefits of the Flash effect.
Explanatory factors of dynamic balance impairment in myotonic dystrophy type 1
Authors: Bélair Nicolas , Côté Isabelle , Gagnon Cynthia , Mathieu Jean , Duchesne Elise 
Published: February 2022

AbstractIntroduction/AimsMyotonic dystrophy type 1 (DM1) is a neuromuscular disease affecting many systems and for which muscle weakness is one of the cardinal symptoms. People with DM1 also present with balance‐related impairments and high fall risk. The aim of this study was to explore explanatory factors of dynamic balance impairment in the DM1 population.MethodsA secondary analysis of data collected as part of a larger study was performed. The Mini Balance Evaluation System Test (Mini‐BESTest) was used to assess dynamic balance. Age, sex, and CTG repeat length in blood were retrieved from medical records and research files. The maximal isometric muscle strength of five lower limb muscle groups (hip flexors and extensors, knee flexors and extensors, and ankle dorsiflexors) was quantitatively assessed as well as fatigue. Standard multiple regression analysis was used.ResultsFifty‐two individuals (31 men) aged between 24 and 81 years were included. The final model explains 65.9% of the balance score; ankle dorsiflexor muscle strength was the strongest explanatory factor, followed by CTG repeat length, age and fatigue to a lesser extent.DiscussionDynamic balance is impaired in people with DM1. Results of this study suggest that rehabilitation interventions aimed at improving strength of the ankle dorsiflexors and managing fatigue could help to improve dynamic balance in this specific population.
Practice makes perfect? Inter‐analyst variation in the identification of fish remains from archaeological sites
Authors: Hawkins Alicia L. , Buckley Michael , Needs‐Howarth Suzanne , Orchard Trevor J. 
Published: February 2022

AbstractIdentification of faunal specimens based on a morphological comparison with known‐identity reference specimens is the standard methodology used in zooarchaeological analysis. However, the accuracy of identifications is rarely considered. In this paper, we report results of an experiment in which 13 analysts were asked to identify 50 fish skeletal elements from a reference collection and 50 fish skeletal elements from an archaeological collection in southern Ontario. The type and level of experience of the analysts and the amount of time they invested in the identification were controlled. The archaeological specimens were subsequently identified taxonomically using ZooMS. Our findings demonstrate that taxonomic and element identifications are far from perfect, both in the reference collection set and in the archaeological collection set. Probable contributing factors include the richness of taxonomic groups; distinctiveness of skeletal morphology; experience level of the analyst; and size of the individual specimens and whether the analyst had access to comprehensive, well‐labeled reference collections. We recommend emphasis be placed in training on the importance, for most species, of not making a taxonomic identification unless the element identification is certain; conservatism in identification of species in groups with many members; clear knowledge of the range of species possible within a region; and active involvement by the instructor or mentor to ensure that neophyte analysts are corrected.
X‐ray CT reveals 4D root system development and lateral root responses to nitrate in soil
Authors: Griffiths Marcus , Mellor Nathan , Sturrock Craig J. , Atkinson Brian S. , Johnson James , Mairhofer Stefan , York Larry M. , Atkinson Jonathan A. , Soltaninejad Mohammadreza , Foulkes John F. , Pound Michael P. , Mooney Sacha J. , Pridmore Tony P. , Bennett Malcolm J. , Wells Darren M. 
Published: February 2022

AbstractThe spatial arrangement of the root system, termed root system architecture, is important for resource acquisition as it directly affects the soil zone explored. Methods for phenotyping roots are mostly destructive, which prevents analysis of roots over time as they grow. Here, we used X‐ray microcomputed tomography (μCT) to non‐invasively characterize wheat (Triticum aestivum L.) seedling root development across time under high and low nitrate nutrition. Roots were imaged multiple times with the 3D models co‐aligned and timestamped in the architectural plant model OpenSimRoot for subsequent root growth and nitrate uptake simulations. Through 4D imaging, we found that lateral root traits were highly responsive to nitrate limitation in soil with greater lateral root length under low N. The root growth model using all μCT root scans was comparable to a parameterized model using only the final root scan in the series. In a second μCT experiment, root growth and nitrate uptake simulations of candidate wheat genotypes found significant root growth and uptake differences between lines. A high nitrate uptake wheat line selected from field data had a greater lateral root count and length at seedling growth stage compared with a low uptake line.
Redesign identification criteria for major hazard installation in Malaysia
Authors: Syed Muhammad Syed Malek , Harun Razif 
Published: February 2022

AbstractMalaysia adopted the GHS through the CLASS Regulations of 2013. This new approach for chemical classification is inconsistent with the CIMAH Regulations of 1996 and has introduced new hazard categories, which are not included in the current major hazard identification criteria. For identifying MHI in Malaysia, the chemicals need to be reclassified. Therefore, this study aims to propose the indicative criteria for major hazard installation that are aligned with CLASS in order to simplify the process. The newly listed chemical threshold quantity, focusing on the acute toxicity group, was also identified. The steps involved include comparing major hazard legislation in the selected country, matching the criteria of CIMAH and CLASS, and reclassifying chemicals in Schedule Two of CIMAH. For estimation of TQ for nitric acid, dispersion modeling was selected. A guide for selecting suitable parameters was developed, ALOHA software was used to simulate the model, and the estimation result for nitric acid was 15.5 tonnes. This study provides the opportunity to improve CIMAH by applying CLASS hazard categories to identify major hazard installation. The guide to estimate TQ could be used for other acute toxicity chemicals as an option for regulators to negotiate and decide the TQ in CIMAH.
Recent Progress in Daytime Radiative Cooling: Advanced Material Designs and Applications
Authors: Zhang Qian , Wang Shuaihao , Wang Xueyang , Jiang Yi , Li Jinlei , Xu Weilin , Zhu Bin , Zhu Jia 
Published: February 2022

AbstractPassive daytime radiative cooling (PDRC) is emerging as a promising cooling technology. Owing to the high, broadband solar reflectivity and high mid‐infrared emissivity, daytime radiative cooling materials can achieve passive net cooling power under direct sunlight. The zero‐energy‐consumption characteristic enables PDRC to reduce negative environmental issues compared with conventional cooling systems. In this review, the development of advanced daytime radiative cooling designs is summarized, recent progress is highlighted, and potential correlated applications, such as building cooling, photovoltaic cooling, and electricity generation, are introduced. The remaining challenges and opportunities of PDRCs are also indicated. It is expected that this review provides an overall picture of recent PDRC progress and inspires future research regarding the fundamental understanding and practical applications of PDRC.
Platinum Cluster/Carbon Quantum Dots Derived Graphene Heterostructured Carbon Nanofibers for Efficient and Durable Solar‐Driven Electrochemical Hydrogen Evolution
Authors: Wang Xiaohan , Zhang Yuanming , Li Junzhi , Liu Guiju , Gao Mingzhen , Ren Shihuan , Liu Bingxu , Zhang Lixue , Han Guangting , Yu Jianyong , Zhao Haiguang , Rosei Federico 
Published: February 2022

AbstractLarge scale solar‐driven hydrogen production is a crucial step toward decarbonizing society. However, the solar‐to‐hydrogen (STH) conversion efficiency, long‐term stability, and cost‐effectiveness in hydrogen evolution reaction (HER) still need to be improved. Herein, an efficient approach is demonstrated to produce low‐dimensional Pt/graphene‐carbon nanofibers (CNFs)‐based heterostructures for bias‐free, highly efficient, and durable HER. Carbon dots are used as efficient building blocks for the in situ formation of graphene along the CNFs surface. The presence of graphene enhances the electronic conductivity of CNFs to ≈3013.5 S m−1 and simultaneously supports the uniform Pt clusters growth and efficient electron transport during HER. The electrode with a low Pt loading amount (3.4 µg cm−2) exhibits a remarkable mass activity of HER in both acidic and alkaline media, which is significantly better than that of commercial Pt/C (31 µg cm−2 of Pt loading). In addition, using a luminescent solar concentrator‐coupled solar cell to provide voltage, the bias‐free water splitting system exhibits an STH efficiency of 0.22% upon one‐sun illumination. These results are promising toward using low‐dimensional heterostructured catalysts for future energy storage and conversion applications.
Influence of Large Steric Hinderance Substituent Position on Conformation and Charge Transfer Process for Non‐Fused Ring Acceptors
Authors: Li Jiayao , Li Hao , Ma Lijiao , Xu Ye , Cui Yong , Wang Jingwen , Ren Junzhen , Zhu Jincheng , Zhang Shaoqing , Hou Jianhui 
Published: February 2022

AbstractTo obtain stable and planar molecular geometry in non‐fused electron acceptors, A4T‐25 and A4T‐26 are designed and synthesized by introducing the bulk 2,4,6‐triisopropylphenyl side groups onto different positions of the central two thiophene units. A4T‐25 and A4T‐26 both show a narrow‐bandgap of 1.39 and 1.46 eV, with highest occupied molecular orbital/lowest unoccupied molecular orbital levels of −5.56/−3.81 and −5.65/−3.83 eV, respectively, and the electrostatic potential distributions imply that they have strong electron‐accepting capability. The single crystal structure analysis and the transfer integral calculation demonstrate that the much more compact π‐π stacking in A4T‐26 can promote efficient charge transportation compared to that in A4T‐25. Therefore, the electron mobility of A4T‐26 is obviously higher and more balanced than that of A4T‐25. When blending the two acceptors with the same polymer donor PBDB‐TF, the photovoltaic cell based on PBDB‐TF:A4T‐25 has an inadequate power conversion efficiency (PCE) of 7.83%, while the PBDB‐TF:A4T‐26‐based one yields an enhanced PCE of 12.1%. Overall, this study offers an insight into the relationship between the fine‐tuning of the molecular structure of non‐fused ring acceptors and the corresponding charge transfer process in organic solar cells.
Learning to think spatially through curricula that embed spatial training
Authors: Plummer Julia D. , Udomprasert Patricia , Vaishampayan Abha , Sunbury Susan , Cho Kyungjin , Houghton Harry , Johnson Erin , Wright Erika , Sadler Philip M. , Goodman Alyssa 
Published: February 2022

AbstractStrong spatial skills are foundational in predicting students' performance in science, technology, engineering, and mathematics education. Decades of research have considered the relationship between thinking spatially and how scientists reason and solve problems. However, few studies have examined the factors that influence improvement in students' spatial thinking during their school science curricula. The present study investigates theThinkSpacecurricula—two middle school astronomy units designed to support students' ability to apply the spatial skill of perspective‐taking (PT) while learning to explain lunar phases (3 days) and the seasons (8 days). U.S. students in 6th and 8th grades (N = 877) across four districts participated in the study, completing assessments before and after theThinkSpacecurricula, along with an additional group of students in 6th and 7th grades (N = 172) who participated as a spatial control group. Data collection included multiple‐choice content assessments, PT skill assessments, and interviews (from a sub‐sample of 96 students), before and after instruction. After participating inThinkSpacecurricula, students demonstrated improved spatial thinking within the domain of astronomy, as measured by improved written content assessments, increased application of PT during conceptual interviews, and a general measurement of PT skill. Higher initial PT skill and higher gain in PT skill predicted greater improvement in students' astronomy understanding, even when accounting for their initial content knowledge. AlthoughThinkSpacestudents in all demographic groups improved PT skill post‐instruction, 8th graders (who were in districts with lower SES), and females were predicted to have smaller gains in their PT skill than the 6th graders (who were in districts with higher SES) and male students. These findings suggest that middle school students' spatial thinking in science can be improved during their middle school science curricula, but questions remain concerning how to reduce spatial‐learning gaps that are associated with gender and possibly SES.
Successful management of feline pemphigus foliaceus with pentoxifylline and topical hydrocortisone aceponate
Authors: Hobi Stefan , Beatty Julia A. , Sandy Jeanine R. , Barrs Vanessa R. 
Published: February 2022

AbstractThe treatment regimen for feline pemphigus foliaceus (PF), an autoimmune disease caused by auto‐antibodies against proteins of the desmosome junction, usually includes high doses of oral or parenteral immunosuppressive drugs, typically glucocorticoids. This case adds to a growing body of evidence that topical hydrocortisone aceponate is effective for the treatment of feline PF, and demonstrates the practical use of a non‐invasive diagnostic method for histopathology when owners refuse a biopsy to support a clinical diagnosis of PF. Finally, this case highlights an international trend of owner‐initiated treatment of feline infectious peritonitis (FIP) using unlicensed, unregistered drugs.
Modeling Splicing Variants Amenable to Antisense Therapy by Use of CRISPR-Cas9-Based Gene Editing in HepG2 Cells
Authors: López-Márquez Arístides , Martínez-Pizarro Ainhoa , Pérez Belén , Richard Eva , Desviat Lourdes R. 
Published: February 2022

AbstractThe field of splice modulating RNA therapy has gained new momentum with FDA approved antisense-based drugs for several rare diseases. In vitro splicing assays with minigenes or patient-derived cells are commonly employed for initial preclinical testing of antisense oligonucleotides aiming to modulate splicing. However, minigenes do not include the full genomic context of the exons under study and patients’ samples are not always available, especially if the gene is expressed solely in certain tissues (e.g. liver or brain). This is the case for specific inherited metabolic diseases such as phenylketonuria (PKU) caused by mutations in the liver-expressed PAH gene.Herein we describe the generation of mutation-specific hepatic cellular models of PKU using CRISPR/Cas9 system, which is a versatile and easy-to-use gene editing tool. We describe in detail the selection of the appropriate cell line, guidelines for design of RNA guides and donor templates, transfection procedures and growth and selection of single-cell colonies with the desired variant, which should result in the accurate recapitulation of the splicing defect.
Establishment of In Vitro Brain Models for AON Delivery
Authors: Daoutsali Elena , Buijsen Ronald A. M. 
Published: February 2022

AbstractProgress in stem cell biology has made it possible to generate human-induced pluripotent stem cells (hiPSC) that can be differentiated into complex, three-dimensional structures, where the cells are spatially organized. To study brain development, Lancaster and colleagues developed an hiPSC-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. Here we describe in detail the generation of cerebral organoids using a modified version of the culture protocol.
Considerations for Generating Humanized Mouse Models to Test Efficacy of Antisense Oligonucleotides
Authors: Vázquez-Domínguez Irene , Garanto Alejandro 
Published: February 2022

AbstractOver the last decades, animal models have become increasingly important in therapeutic drug development and assessment. The use of these models, mainly mice and rats, allow evaluating drugs in the real-organism environment and context. However, several molecular therapeutic approaches are sequence-dependent, and therefore, the humanization of such models is required to assess the efficacy. The generation of genetically modified humanized mouse models is often an expensive and laborious process that may not always recapitulate the human molecular and/or physiological phenotype. In this chapter, we summarize basic aspects to consider before designing and generating humanized models, especially when they are aimed to test antisense-based therapies.
Generation of Humanized Zebrafish Models for the In Vivo Assessment of Antisense Oligonucleotide-Based Splice Modulation Therapies
Authors: Schellens Renske , de Vrieze Erik , Slijkerman Ralph , Kremer Hannie , van Wijk Erwin 
Published: February 2022

AbstractAntisense oligonucleotide (AON)-based splice modulation is the most widely used therapeutic approach to redirect precursor messenger RNA (pre-mRNA) splicing. To study the functional effect of humanmutations affecting pre-mRNAsplicing for which AON-based splice redirection would be a potential therapeutic option, humanized knock-in animal models are pivotal. A major limitation of using humanized animal models for this purpose is the reported poor recognition of human splice sites by the splicing machineries of other species. To overcome this problem, we provide a detailed guideline for the generation of functional humanized knock-in zebrafish models to assess the effect of mutation-induced aberrant splicing and subsequent AON-based splice modulation therapy.
Use of Small Animal Models for Duchenne and Parameters to Assess Efficiency upon Antisense Treatment
Authors: Lu-Nguyen Ngoc , Malerba Alberto , Popplewell Linda 
Published: February 2022

AbstractDuchenne muscular dystrophy (DMD) is a rare genetic disease affecting 1 in 5000 newborn boys. It is caused by mutations in the DMD gene with a consequent lack of dystrophin protein that leads to deterioration of myofibers and their replacement with fibro-adipogenic tissue. Using antisense oligonucleotides (AONs) to modify out-of-frame mutations in the DMD gene, named exon skipping, is currently considered among the most promising treatments for DMD patients. The development of this strategy is rapidly moving forward, and AONs designed to skip exons 51 and 53 have received accelerated approval in the USA. In preclinical setting, the mdx mouse model, carrying a point mutation in exon 23 of the murine Dmd gene that prevents production of dystrophin protein, has emerged as a valuable tool, and it is widely used to study in vivo therapeutic approaches for DMD. Here we describe the methodology for intravenous delivery of AONs targeting dystrophin through tail vein of mdx mice. Furthermore, the most relevant functional analyses to be performed in living mice, and the most informative histopathological and molecular assays to evaluate the effect of this treatment are detailed.
Delivery of Antisense Oligonucleotides to the Mouse Brain by Intracerebroventricular Injections
Authors: Metz Tom , Kuijper Elsa C. , van Roon-Mom Willeke M. C. 
Published: February 2022

AbstractThe use of antisense oligonucleotides (AONs) is a promising therapeutic strategy for central nervous system disorders. However, the delivery of AONs to the central nervous system is challenging because their size does not allow them to diffuse over the blood–brain barrier (BBB) when injected systemically. The BBB can be bypassed by administering directly into the brain. Here we describe a method to perform single and repeated intracerebroventricular injections into the lateral ventricle of the mouse brain.
Intrathecal Delivery of Therapeutic Oligonucleotides for Potent Modulation of Gene Expression in the Central Nervous System
Authors: Kennedy Zachary , Gilbert James W. , Godinho Bruno M. D. C. 
Published: February 2022

AbstractTherapeutic oligonucleotides hold tremendous potential for treating central nervous system (CNS) disorders. The route of administration of oligonucleotides significantly impacts both distribution and silencing efficiency. Here, we describe a technically simple, clinically relevant method to administer oligonucleotide compounds into the CNS via direct intrathecal injections. This method achieves distribution throughout the CNS rapidly and permits high-throughput testing of oligonucleotide efficacy and potency in mammals.