bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of dexamethasone in idiopathic, acute pediatric rhabdomyolysis
Authors: Summerlin Maxwell L. , Regier Debra S. , Fraser Jamie L. , Chapman Kimberly A. , Kafashzadeh Dariush , Billington Charles , Kisling Monisha , Grochowsky Angela , Ah Mew Nicholas , Shur Natasha
Published: December 2020

Current rhabdomyolysis treatment guidelines vary based on the etiology and diagnosis, yet many cases evade conclusive diagnosis. In these cases, treatment options remain largely limited to fluids and supportive therapy. We present two cases of acute rhabdomyolysis diagnosed in the emergency department: a 5‐year‐old boy with sudden onset bilateral flank pain, and a 13‐year‐old boy with 2–3 days of worsening pectoral and shoulder pain. Each patient had a prior similar episode requiring hospitalization in the past. The 5‐year‐old had no inciting trauma or trigger, medication use, or illness. The 13‐year‐old previously had an upper respiratory infection during the week prior and had been strenuously exercising at the time of onset. Genetic testing results were unknown for both patients during their hospitalizations, and insurance and other barriers led to delay. Later results for the first patient revealed a heterozygous deletion in intron 19 on the LPIN1 gene interpreted as a variant of unknown significance. During their hospitalizations, both children were started on intravenous (i.v.) fluids, and creatine kinase (CK) initially trended downward, but then began to rise or plateau. After reviewing the cases, prior literature, and anecdotal evidence of benefit from corticosteroid therapy in rhabdomyolysis with our consultant metabolic physicians, dexamethasone was initiated. In both patients, dexamethasone use correlated with relief of patient symptoms, significantly decreased CK value, and our ability to discharge these patients home quickly. Our cases, discussion, and literature review all lead to the consideration of the use of dexamethasone in conjunction with standard therapy for acute rhabdomyolysis.
Delineation of the clinical and radiological features of Stuve–Wiedemann syndrome childhood survivors, four new cases and review of the literature
Authors: Siccha Sofía M. , Cueto Anna María , Parrón‐Pajares Manuel , González‐Morán Gaspar , Pacio‐Miguez Marta , Del Pozo Ángela , Solís Mario , Rodriguez‐Jimenez Carmen , Caino Silvia , Fano Virginia , Heath Karen E. , García‐Miñaúr Sixto , Palomares‐Bralo María , Santos‐Simarro Fernando
Published: December 2020

Stuve–Wiedemann syndrome (SWS; MIM 601559) is a rare autosomal recessive disease caused by mutations in the leukemia inhibitor factor receptor gene (LIFR). Common clinical and radiological findings are often observed, and high neonatal mortality occurs due to respiratory distress and hyperthermic episodes. Despite initially considered as a lethal disorder during the newborn period, in recent years, several SWS childhood survivors have been reported. We report a detailed clinical and radiological characterization of four unrelated childhood SWS molecularly confirmed patients and review 22 previously reported childhood surviving cases. We contribute to the definition of the childhood survival phenotype of SWS, emphasizing the evolving phenotype, characterized by skeletal abnormalities with typical radiological findings, distinctive dysmorphic features, and dysautonomia. Based on the typical features and clinical course, early diagnosis is possible and crucial to plan appropriate management and prevent potential complications. Genetic confirmation is advisable in order to improve genetic counseling to the patients and their families.
Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations
Authors: Hirata Katsuya , Okamoto Nobuhiko , Ichikawa Chihiro , Inoue Shouta , Nozaki Masatoshi , Banno Kimihiko , Takenouchi Toshiki , Suzuki Hisato , Kosaki Kenjiro
Published: December 2020

Infantile liver failure syndrome type 1 (ILFS1) is a recently recognized autosomal recessive disorder caused by deleterious mutations in the leucyl‐tRNA synthetase 1 gene (LARS1). The LARS1 enzyme is responsible for incorporation of the amino acid leucine during protein polypeptide synthesis. Individuals with LARS1 mutations typically show liver failure from infancy to early childhood during periods of illness or other physiological stress. While 25 patients from 15 families with ILFS1 have been reported in the literature, histological reports from autopsy findings are limited. We report here a premature male neonate who presented with severe intrauterine growth retardation, microcytic anemia, and fulminant liver failure, and who was a compound heterozygote for two novel deleterious mutations in LARS1. An autopsy showed fulminant hepatitis‐like hepatocellular injury and fibrogenesis in the liver and a lack of uniformity in skeletal muscle, accompanied by the disruption of striated muscle fibers. Striking dysgenesis in skeletal muscle detected in the present case indicates the effect of LARS1 functional deficiency on the musculature. Whole‐exome sequencing may be useful for neonates with unexplained early liver failure if extensive genetic and metabolic testing is inconclusive.
Violence in the first millenniumBCEEurasian steppe: Cranial trauma in three Turpan Basin populations from Xinjiang, China
Authors: Zhang Wenxin , Zhang Qun , McSweeney Kathleen , Han Tao , Man Xingyu , Yang Shiyu , Wang Long , Zhu Hong , Zhang Quanchao , Wang Qian
Published: December 2020

Objectives

Violence affected daily life in prehistoric societies, especially at conflict zones where different peoples fought over resources and for other reasons. In this study, cranial trauma was analyzed to discuss the pattern of violence experienced by three Bronze to early Iron Age populations (1,000–100 BCE) that belonged to the Subeixi culture. These populations lived in the Turpan Basin, a conflict zone in the middle of the Eurasian Steppe.

Methods

The injuries on 129 complete crania unearthed from the Subeixi cemeteries were examined for crude prevalence rate (CPR), trauma type, time of occurrence, possible weapon, and direction of the blow. Thirty‐three injuries identified from poorly preserved crania were also included in the analyses except for the CPR. Data was also compared between the samples and with four other populations that had violence‐related backgrounds.

Results

Overall, 16.3% (21/129) of the individuals showed violence‐induced traumatic lesions. Results also indicated that most of the injuries were perimortem (81.6%), and that women and children were more involved in conflict than the other comparative populations. Wounds from weapons accounted for 42.1% of the identified cranial injuries. Distribution analysis suggested no dominant handedness of the attackers, and that blows came from all directions including the top (17.1%). Wounds caused by arrowheads and a special type of battle‐ax popular in middle and eastern Eurasian Steppe were also recognized.

Discussion

A comprehensive analysis of the skeletal evidence, historical records, and archeological background would suggest that the raiding to be the most possible conflict pattern reflected by the samples. The attackers were likely to have been nomadic invaders from the steppe (such as the Xiongnu from historical records), who attacked the residents in the basin more likely for their resources rather than territory or labor force.
Fabrication and characterization of high flux poly(vinylidene fluoride) electrospun nanofibrous membrane using amphiphilic polyethylene‐block‐poly(ethylene glycol) copolymer
Authors: Gandhimathi Chinnasamy , Sundarrajan Subramanian , Matsuura Takeshi , Srinivasan Dinesh Kumar , Wei He , Xuecheng Dong , Ramakrishna Seeram
Published: December 2020

Electrospun nanofiber membranes (ENM) made of polymers such as polysulfone and poly(vinylidene fluoride) (PVDF) have a much higher contact angle (CA) and also more hydrophobic when compared to the virgin polymers. For water treatment applications, membranes with hydrophilic nature are highly desirable in order to achieve high flux and less fouling potentials. Hence, in the present study, highly hydrophilic electrospun nanofiber membranes (ENMs) were prepared by blending PVDF polymer with amphiphilic polyethylene‐block‐poly (ethylene glycol) (PE‐b‐PEG) copolymer. Resulting amphiphilic ENMs were highly porous (77%–92%) and the breaking elongation of 140% with a young's modulus of 2.55 MPa was observed. When compared with the control PVDF membrane, PE‐b‐PEG blended ENMs revealed higher water permeation flux owing to the enrichment of the hydrophilic PEG segments at the membrane surface, which was confirmed by using X‐ray photoelectric spectroscopy and Energy‐dispersive spectroscopy measurements. When compared to the phase inversion process (CA of 97.3°) blended ENM had CA of 0°, which indicates that besides hydrophilic block copolymer segments, the nature of membrane formation also contributes its role in influencing the hydrophilicity of the membrane. This improved hydrophilicity in combination with larger pore sizes of the PVDF/ PE‐b‐PEG membranes have contributed to enhancement of pure water flux, protein solution permeability and water flux recovery, which can be applied potentially for water treatment applications.
Electromechanical deformation and failure of multilayered films
Authors: Zhang Ci , Zhu Lei , Olah Andrew , Baer Eric
Published: December 2020

Layer thickness was found to have a significant effect on the irreversible electromechanical deformation and the failure mechanism in polycarbonate (PC)/poly (vinylidene fluoride) (PVDF) multilayered films when subjected to an electrical impulse in a DC needle‐plane configuration. Three distinct regions of behavior were observed. Region I comprised thick layer systems that exhibited only irreversible center deformation. The improvement to failure resistance compared to the monolithic films was attributed to the interphase between the two components. Region II films with an intermediate layer thickness showed both an irreversible center deformation and a treeing mechanism which were observed to simultaneously occur. The surface treeing mechanism, similar to the lightning treeing phenomena in nature, occurs only at impact rates. The tree morphology showed large amounts of plowing, indicating that this damage mechanism can dissipate a large amount of energy prior to electromechanical fracture of the film. Region III films comprise ultrathin layers in the nanoscale and showed no treeing. The unique interphase region between these ultrathin layers was estimated to be at least ten percent of the overall layered structure. These films behaved similar to monolithic materials with improved electromechanical failure characteristics. This work complements the enhanced dielectric performance of multilayer films observed in earlier investigations.
Comparison of Lesional Juvenile Myositis and Lupus Skin Reveals Overlapping Yet Unique Disease Pathophysiology
Authors: Turnier Jessica L. , Pachman Lauren M. , Lowe Lori , Tsoi Lam C. , Elhaj Sultan , Menon Rajasree , Amoruso Maria C. , Morgan Gabrielle A. , Gudjonsson Johann E. , Berthier Celine C. , Kahlenberg J. Michelle
Published: December 2020

Objective

Skin inflammation heralds systemic disease in juvenile myositis, yet we lack an understanding of pathogenic mechanisms driving skin inflammation in this disease. We undertook this study to define cutaneous gene expression signatures in juvenile myositis and identify key genes and pathways that differentiate skin disease in juvenile myositis from childhood‐onset systemic lupus erythematosus (SLE).

Methods

We used formalin‐fixed paraffin‐embedded skin biopsy samples from 15 patients with juvenile myositis (9 lesional, 6 nonlesional), 5 patients with childhood‐onset SLE, and 8 controls to perform transcriptomic analysis and identify significantly differentially expressed genes (DEGs; q ≤ 5%) between patient groups. We used Ingenuity Pathway Analysis (IPA) to highlight enriched biologic pathways and validated DEGs by immunohistochemistry and quantitative real‐time polymerase chain reaction.

Results

Comparison of lesional juvenile myositis to control samples revealed 221 DEGs, with the majority of up‐regulated genes representing interferon (IFN)–stimulated genes. CXCL10, CXCL9, and IFI44L represented the top 3 DEGs (fold change 23.2, 13.3, and 13.0, respectively; q < 0.0001). IPA revealed IFN signaling as the top canonical pathway. When compared to childhood‐onset SLE, lesional juvenile myositis skin shared a similar gene expression pattern, with only 28 unique DEGs, including FBLN2, CHKA, and SLURP1. Notably, patients with juvenile myositis who were positive for nuclear matrix protein 2 (NXP‐2) autoantibodies exhibited the strongest IFN signature and also demonstrated the most extensive Mx‐1 immunostaining, both in keratinocytes and perivascular regions.

Conclusion

Lesional juvenile myositis skin demonstrates a striking IFN signature similar to that previously reported in juvenile myositis muscle and peripheral blood. Further investigation into the association of a higher IFN score with NXP‐2 autoantibodies may provide insight into disease endotypes and pathogenesis.
Cationic Nonporous Macrocyclic Organic Compounds for Multimedia Iodine Capture
Authors: Xu Xiao‐Qian , Cao Li‐Hui , Yang Yan , Bai Xiang‐Tian , Zhao Fang , He Zhen‐Hong , Yin Zheng , Ma Yang‐Min
Published: December 2020

Over the past two decades, progress in chemistry has generated various types of porous materials for removing iodine (129I or 131I) that can be formed during nuclear energy generation or nuclear waste storage. However, most studies for iodine capture are based on the weak host‐guest interactions of the porous materials. Here, we present two cationic nonporous macrocyclic organic compounds, namely, MOC‐1 and MOC‐2, in which 6I‐ and 8I− were as counter anions, for highly efficient iodine capture. MOC‐1 and MOC‐2 were formed by reacting 1,1′‐diamino‐4,4′‐bipyridylium di‐iodide with 1,2‐diformylbenzene or 1,3‐diformylbenzene, respectively. The presence of a large number of I− anions results in high I2 affinity with uptake capacities up to 2.15 g ⋅ g−1 for MOC‐1 and 2.25 g ⋅ g−1 for MOC‐2.
Baroque Science, Experimental Art? Jusepe de Ribera and other Neapolitan Sceptics
Authors: Sapir Itay
Published: December 2020

Current attempts by historians of science to revise the narrative of the Scientific Revolution by using the concept of the Baroque have important implications for art history. Correspondences between baroque art and baroque science gain new complexity when the rational, epistemologically optimistic image of the New Science is put in doubt. Rather than a method of objective observation, early seventeenth‐century science and art share an acceptance of the constructed nature of reality, of human epistemological limitations and of the role of passions in the observation of the world. While Caravaggio has revolutionised art precisely through his interest in questions of knowledge and sensorial perception and by his subversive transformation of Renaissance epistemological values and ideals, this article concentrates on the work of Jusepe de Ribera, who made the senses and their shortcomings a major theme of his pictorial research. Ribera's epistemology is examined in the context of contemporary Neapolitan philosophy and science. Through the confrontation of some of the Spagnoletto's paintings with the work of figures such as Giovanni Battista della Porta, Federico Cesi and particularly Colantonio Stigliola, it becomes clear that early modern Neapolitan faith in rational knowledge was more ambiguous than is sometimes assumed.
Proposal of a laboratory course dedicated to the generation of protein molecular weight standards for sodium dodecyl sulfate‐polyacrylamide gel electrophoresis
Authors: Bubis José
Published: December 2020

Protein molecular weight standards are routinely employed in sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) to estimate the apparent sizes of unknown proteins within a sample. For training students, a laboratory course based on the production of marker proteins is proposed. Following fractionation by column chromatography, a series of purified proteins and mixtures of proteins were combined to generate various sets of unstained, prestained and fluorescently labeled molecular weight ladders for SDS‐PAGE. The produced material can be used in successive laboratory practices as an alternative to commercial protein markers.
Economic assessment of continuous processing for manufacturing of biotherapeutics
Authors: Gupta Paridhi , Kateja Nikhil , Mishra Somesh , Kaur Harmeet , Rathore Anurag S.
Published: December 2020

Continuous processing offers a promising approach to revolutionize biotherapeutics manufacturing as reflected in recent years. The current study offers a comparative economic assessment of batch and continuous processing for the production of biotherapeutic products. Granulocyte‐colony stimulating factor (GCSF), a protein expressed in E. coli, and an IgG1 monoclonal antibody, were chosen as representatives of microbial and mammalian derived products for this assessment. Economic indicators—cost of goods (COGs), net present value (NPV), and payback time have been estimated for the assessment. For the case of GCSF, conversion from batch to integrated continuous manufacturing induced a $COGs/g reduction of 83% and 73% at clinical and commercial scales, respectively. For the case of mAb therapeutic, a 68% and 35% reduction in $COGs/g on translation from batch to continuous process was projected for clinical and commercial scales, respectively. Upstream mAb titer was also found to have a significant impact on the process economics. With increasing mAb titer, the $COG/g decreases in both operating modes. With titer increasing from 2 to 8 g/L, the $COG/g of batch process was reduced by 53%, and that of the continuous process was reduced by 63%. Cost savings in both the cases were attributed to increased productivity, efficient equipment and facility utilization, smaller facility footprint, and reduction in utilization of consumables like resin media and buffers actualized by the continuous processing platform. The current study quantifies the economic benefits associated with continuous processing and highlights its potential in reducing the manufacturing cost of biotherapeutics.
Prediction of adolescent pelvis development using femoral head and acetabulum growth in a longitudinal radiographic study
Authors: Keller Nicole B. , Liu Raymond W.
Published: December 2020

Introduction

Adolescent total hip arthroplasty (THA) is guarded partially due unclarity as to when pediatric hip joints reach full development. This study sought to identify when maximum acetabular and femoral head diameters are achieved with relation to chronological and skeletal age.

Materials and Methods

Consecutive femoral head and acetabular diameters were measured in a random sample of 54 female and 78 male subjects, which were queried from a historical collection of annual radiographs of children. Femoral head and triradiate physeal plates were scored according to Oxford bone parameters.

Results

At 14 years females had femoral diameters of 4.16 +/− 0.23 cm and acetabular diameters of 5.15 +/− 0.30 cm. At 16 years males had femoral diameters of 4.85 +/− 0.30 cm and acetabular diameters of 5.90 +/− 0.35 cm. In the year following maximal femoral Oxford scores, no significant change was seen in femur and acetabulum diameters in females and in femur diameters in males. In the year following maximal acetabular Oxford scores, there was a significant increase in both femur and acetabulum diameters in both females and males.

Conclusions

Females on average reach maximum pelvis maturity at 14 years and males reach maximum pelvis maturity at 16 years. A closed femoral head was found to be a good marker of full hip growth, while a closed triradiate was not. This study provides anatomical data for surgeons to consider in assessing risk factors of THA failure in adolescents.
Percutaneous axillary access: A call to arms
Authors: Seto Arnold H. , Baran David A.
Published: December 2020

Key Points

The axillary artery is a useful alternative access site for large‐bore interventions as it is rarely atherosclerotic.

This systematic review of percutaneous large‐bore axillary artery access suggests that it is as safe and effective as open surgical access.

The Society of Cardiovascular Angiography and Interventions (SCAI) Expert Consensus Statement will soon be convened to provide best practice recommendations on transaxillary access including technique, training, and safety.
Prenatal characterization of a novel inverted SMAD2 duplication by mate pair sequencing in a fetus with dextrocardia
Authors: Zepeda‐Mendoza Cinthya J. , Essendrup Anna , Smoley Stephanie A. , Johnson Sarah H. , Hoppman Nicole L , Vasmatzis George , Jackson Daniel L. , Kearney Hutton M. , Baughn Linda B.
Published: December 2020

This case report underlines the importance of molecular characterization of genomic duplications and other structural variants in the prenatal setting to guide clinical interpretation, genetic counseling, and perinatal medical care.
A power optimization model for the long‐term planning scenarios: Case study of Mexico's power system decarbonization
Authors: Martínez‐Quintana Marco Antonio , Martín‐del‐Campo Cecilia , Cruz‐Mendoza Guadalupe
Published: December 2020

Mexico is committed to reducing its CO2 emissions according to the Paris Agreement. A relevant effort must be made for the analysis of Mexico's electric energy system towards a progressive decarbonization with a larger participation of intermittent renewable energies. The analysis of power planning scenarios, with different assumptions on costs, emissions, and intermittent performance of the power generating technologies, is needed to make sustainable decisions in the transition toward a cleaner power sector. Tools for energy modelling are required to develop and analyze scenarios with minimum costs subject to environmental constraints. The purpose of the article is to explain the modelling approach of a novel and flexible power planning tool, which is based on a well‐known linear programming optimization method combined with a computing strategy to optimize time consumed for reading, processing calculations, and writing the huge number of economic and technical parameters required for the hourly power dispatch in complex interconnected electric systems. The time consumed has been optimized by means of a binary matrix that activates the input and use of only the data needed for the solution of the problem. The paper describes the MC model and demonstrates some of its analytical capabilities through a Mexican case study with a least cost scenario and two decarbonization scenarios of the power interconnected system for the period from 2020‐2050.
History of nitroxide mediated polymerization in Canada
Authors: Marić Milan
Published: December 2020

Nitroxide mediated polymerization (NMP), sometimes known as stable free radical polymerization (SFRP), is considered one of the main types of reversible deactivation radical polymerization (RDRP) that have emerged as a major advance in polymer synthesis in the past 30 years. This review examines NMP's development from a uniquely Canadian perspective. Inspired by reports of a reversible equilibrium between the TEMPO persistent radical and a growing polymeric radical chain, researchers at the Xerox Research Centre of Canada (XRCC) reported radical polymerizations of styrene with hallmarks typically associated with living polymerizations: linear degree of polymerization of with conversion, narrow molecular weight distributions, and ability to re‐initiate the chain end with additional monomer. This effort expanded to polymerizations in dispersed aqueous media (eg, miniemulsion) and to polymerizations directed for various architectures (block, graft, star), but NMP was ultimately generally limited to styrenic monomers. Consequently, NMP trailed other RDRP methods, such as atom transfer radical polymerization (ATRP) and reversible addition fragmentation transfer polymerization (RAFT), due to its limited monomer choice. With the advent of second‐generation alkoxyamine initiators, however, the range of monomers polymerizable in a controlled manner greatly expanded to include acrylates, acrylamides, and eventually methacrylates (under certain conditions), providing renewed impetus towards using NMP. Consequently, Canadian researchers applied these new alkoxyamines for more versatile polymers, resulting in products such as stimuli‐responsive polymers, CO2‐switchable latexes, bio‐hybrid composites, organic photovoltaic materials, and photolithographic materials. The chronological progression of the developments in NMP from various Canadian laboratories highlights these achievements in new polymeric materials.
CO2 reforming of methane over the growth of hierarchical Ni nanosheets/Al2O3‐MgO synthesized via the ammonia vapour diffusion impregnation
Authors: Dharmasaroja Nichthima , Ratana Tanakorn , Tungkamani Sabaithip , Sornchamni Thana , Simakov David S. A. , Phongaksorn Monrudee
Published: December 2020

A novel ammonia vapour diffusion‐assisted impregnation technique was developed to synthesize the Al2O3‐MgO‐supported hierarchical Ni nanosheets. The resulting catalysts with different times for ammonia vapour treatments (at 12, 18, and 20 hours) were prepared to investigate the growth of Ni nanosheets on the catalyst surface. All catalysts were tested for CO2 reforming of methane and a comprehensive characterization study was conducted by XRD, N2 adsorption‐desorption, H2‐TPD, H2‐TPR, CO2‐TPD, and TGA. The Ni nanosheets were obtained using the ammonia vapour treatment for 20 hours, improving the selectivity toward H2 generation without a lower CH4 conversion. When compared to the reference catalyst prepared by a conventional impregnation method, the H2/CO ratio for CO2 reforming of the methane process was enhanced by 0.35. Additionally, the carbon deposition was reduced by half using hierarchical Ni nanosheets for the CO2 reforming of methane at 620°C for 20 hours. The mechanism of this improvement was achieved by the increase in medium basicity associated with a strong metal‐support interaction that promotes the CO2 activation‐dissociation pathways, preventing carbon formation and inhibiting the reverse water gas shift.
Acyl Derivatives of Eudesmanolides To Boost their Bioactivity: An Explanation of Behavior in the Cell Membrane Using a Molecular Dynamics Approach
Authors: Mejías Francisco J. R. , Durán Alexandra G. , Zorrilla Jesús G. , Varela Rosa M. , Molinillo José M. G. , Valdivia Manuel M. , Macías Francisco A.
Published: December 2020

Semisynthetic analogs of natural products provide an important approach to obtain safer and more active drugs and they can also have enhanced physicochemical properties such as persistence, cross‐membrane processes and bioactivity. Acyl derivatives of different natural product families, from sesquiterpene lactones to benzoxazinoids, have been synthesized and tested in our laboratories. These compounds were evaluated against tumoral and nontumoral cell lines to identify selective derivatives with a reduced negative impact upon application. The mode of action of these compounds was analyzed by anti‐caspase‐3 assays and molecular dynamics simulations with cell membrane re‐creation were also carried out. Aryl derivatives of eudesmanolide stand out from the other compounds and are better than current anticancer drugs such as etoposide in terms of selectivity and activity. Computational studies provide evidence that lipophilicity plays a key role and the 4‐fluorobenzoyl derivative can pass easily through the cell membrane.
Tautomycetin Synthetic Analogues: Selective Inhibitors of Protein Phosphatase I
Authors: Woydziak Zachary R. , Yucel A. John , Chamberlin A. Richard
Published: December 2020

Ser/Thr protein phosphatases (PPs) regulate a substantial range of cellular processes with protein phosphatases 1 (PP1) and 2 A (PP2A) accounting for over 90 % of the activity within cells. Nevertheless, tools to study PPs are limited as PPs inhibitors, particularly those selective for PP1 inhibition, are relatively scarce. Two examples of PP1‐selective inhibitors, which share structural similarities, are tautomycin (TTM) and tautomycetin (TTN). This work describes the development of PP1/PP2A inhibitors that incorporate key structural features of TTM and TTN and are designed to conserve regions known to bind the active site of PP1/PP2A but vary regions that differentially contact the hydrophobic groove of PP1/PP2A. In all 28 TTN analogues were synthetically generated that inhibit PP1/PP2A activity at <250 mM; seven possessed inhibition activity at 100 nM. The IC50 values were determined for the seven most active analogues, which ranged from 34 to 1500 nM (PP1) and 70 to 6800 nM (PP2A). Four of the seven analogues possessed PP1 selectivity, and one demonstrated eightfold selectivity in the nanomolar range (PP1 IC50=34 nM, PP2A IC50=270 nM). A rationale is given for the observed differences in selectivity.
Characterizing clinics with differential changes in the screening rate in the Colorectal Cancer Control Program of the Centers for Disease Control and Prevention
Authors: Sharma Krishna P. , Leadbetter Steven , DeGroff Amy
Published: December 2020

Background

The Centers for Disease Control and Prevention (CDC) funds the Colorectal Cancer Control Program (CRCCP) to increase colorectal cancer (CRC) screening rates in primary care clinics by implementing evidence‐based interventions (EBIs). This study examined differences in clinic characteristics and implementation efforts among clinics with differential changes in screening rates over time.

Methods

CRCCP clinic data collected by the CDC were used. The outcome was the clinic status (highest quartile [Q4] vs lowest quartile [Q1]), which was based on the absolute screening rate change between the first and second program years. Five clinic characteristic variables and 12 clinic‐level CRCCP variables (eg, EBIs) were assessed in bivariable analyses, and logistic regression was used to determine significant predictors of the outcome.

Results

Each group included 78 clinics (N = 156). Clinics with a Q4 status saw a 14.9 percentage point increase in the screening rate, whereas clinics with a Q1 status experienced a 9.1 percentage point decline. Q4s were more likely than Q1s to have a CRC champion, implement 4 EBIs versus fewer EBIs, implement at least 1 new EBI, and increase the number of implemented EBIs. The adjusted odds of Q4 status were 5.3 times greater (95% confidence interval [CI], 1.9‐14.9) if a clinic implemented an additional EBI. The adjusted odds of Q4 status increased to 7.1 (95% CI, 2.2‐23.1) if a clinic implemented 2 to 4 additional EBIs.

Conclusions

Implementing new EBIs or enhancing existing ones improves CRC screening rates. Additionally, clinics with lower screening rates had greater rate increases and may have benefited more from the CRCCP.
Sensitivity analysis of non‐local damage in soft biological tissues
Authors: Zuo Di , Avril Stéphane , Ran Chunjiang , Yang Haitian , Mousavi S. Jamaleddin , Hackl Klaus , He Yiqian
Published: December 2020

Computational modeling can provide insight into understanding the damage mechanisms of soft biological tissues. Our gradient‐enhanced damage model presented in a previous publication has shown advantages in considering the internal length scales and in satisfying mesh independence for simulating damage, growth and remodeling processes. Performing sensitivity analyses for this model is an essential step towards applications involving uncertain patient‐specific data. In this paper, a numerical analysis approach is developed. For that we integrate two existing methods, that is, the gradient‐enhanced damage model and the surrogate model‐based probability analysis. To increase the computational efficiency of the Monte Carlo method in uncertainty propagation for the nonlinear hyperelastic damage analysis, the surrogate model based on Legendre polynomial series is employed to replace the direct FEM solutions, and the sparse grid collocation method (SGCM) is adopted for setting the collocation points to further reduce the computational cost in training the surrogate model. The effectiveness of the proposed approach is illustrated by two numerical examples, including an application of artery dilatation mimicking to the clinical problem of balloon angioplasty.
GHub: Building a glaciology gateway to unify a community
Authors: Sperhac Jeanette M. , Poinar Kristin , Jones‐Ivey Renette , Briner Jason , Csatho Beata , Nowicki Sophie , Simon Erika , Larour Eric , Quinn Justin , Patra Abani
Published: December 2020

There is no consensus on how quickly the earth's ice sheets are melting due to global warming, nor on the ramifications to sea level rise. Due to its potential effects on coastal populations and global economies, sea level rise is a grave concern, making ice melt rates an important area of study. The ice‐sheet science community consists of two groups that perform related but distinct kinds of research: a data community, and a model building community. The data community characterizes past and current states of the ice sheets by assembling data from field and satellite observations. The modeling community forecasts the rate of ice‐sheet decline with computational models validated against observations. Although observational data and models depend on one another, these two groups are not well integrated. Better coordination between data collection efforts and modeling efforts is imperative if we are to improve our understanding of ice sheet loss rates. We present a new science gateway, GHub, a collaboration space for ice sheet scientists. This web‐accessible gateway will host datasets and modeling workflows, and provide access to codes that enable tool building by the ice sheet science community. Using GHub, we will collect and centralize existing datasets, creating data products that more completely catalog the ice sheets of Greenland and Antarctica. We will build workflows for model validation and uncertainty quantification, extending existing ice sheet models. Finally, we will host existing community codes, enabling scientists to build new tools utilizing them. With this new cyberinfrastructure, ice sheet scientists will gain integrated tools to quantify the rate and extent of sea level rise, benefitting human societies around the globe.
Coprecipitation Temperature Effects of Morphology‐Controlled Nickel Hexacyanoferrate on the Electrochemical Performance in Aqueous Sodium‐Ion Batteries
Authors: Park Sungjun , Kim Jihwan , Yi Seong‐Hoon , Chun Sang‐Eun
Published: December 2020

Coprecipitation effortlessly fabricated nickel hexacyanoferrate (NiHCF) with outstanding rate capability and stability for aqueous batteries. Citrate‐aided coprecipitation decelerated the crystallization, assembling cubic‐shaped powder based on separation between nucleation and growth. This study revealed that coprecipitation temperature determined the electrochemical performance. With lower temperatures, smaller particles with more water were formed by predominant nucleation, resulting in low crystallinity and capacity of 58 mAh g−1. Expanded surface area reduced electrode/electrolyte interface charge‐transfer resistance and showed excellent rate capability (79 % of initial capacity at 100 C‐rate). However, poor cyclability was obtained. At elevated temperatures, nuclei growth and dehydration occurred, and thus highly crystalline large particles were formed. In turn, NiHCF delivered excellent capacity of 76 mAh g−1 at 1 C‐rate but exhibited inferior rate performance because of longer diffusional path. Meanwhile, normal coprecipitation at 70 °C induced irregular‐shaped tiny particles, presenting 93 % retention of initial capacity at 100 C‐rate.
Practical application of microsphere samples for benchmarking a quantitative phase imaging system
Authors: Kwee Edward , Peterson Alexander , Halter Michael , Elliott John
Published: December 2020

Quantitative phase imaging (QPI) provides an approach for monitoring the dry mass of individual cells by measuring the optical pathlength of visible light as it passes through cells. A distinct advantage of QPI is that the measurements result in optical path length quantities that are, in principle, instrument independent. Reference materials that induce a well‐defined optical pathlength shift and are compatible with QPI imaging systems will be valuable in assuring the accuracy of such measurements on different instruments. In this study, we evaluate seven combinations of microspheres embedded in index refraction matching media as candidate reference materials for benchmarking the performance of a QPI system and as calibration standards for the optical pathlength measurement. Poly(methyl metharylate) microspheres and mineral oil were used to evaluate the range of illumination apertures, signal‐to‐noise ratios, and focus positions that allow an accurate quantitative optical pathlength measurement. The microsphere‐based reference material can be used to verify settings on an instrument that are suitable for obtaining an accurate pathlength measurement from biological cells. The microsphere/media reference material is applied to QPI‐based dry mass measurements of a population of HEK293 cells to benchmark and provide evidence that the QPI image data are accurate.
Adaptation and validation of the Eating Disorder Examination‐Questionnaire in English among urban Indian adolescents
Authors: Lewis‐Smith Helena , Garbett Kirsty M. , Chaudhry Anshula , Uglik‐Marucha Nora , Vitoratou Silia , Dhillon Megha , Shroff Hemal , Diedrichs Phillippa C.
Published: December 2020

Objective

Eating pathology is a salient issue in India, with clinical features reported among adults and adolescents. However, there are currently no validated measures of disordered eating in the Indian context. The present study therefore aimed to validate a culturally appropriate English language version of the Eating Disorder Examination Questionnaire (EDE‐Q), a widely used measure, among adolescents in India.

Method

We adapted and examined the factor structure, reliability, and construct validity of the EDE‐Q among an urban sample of 1,413 Indian adolescents (mean age = 13 years; 45% girls).

Results

In contrast to the original four‐factor model, exploratory factor analysis identified a two‐factor solution for girls and boys, which was verified by confirmatory factor analysis; a “Preoccupation and Control” subscale and a “Weight and Shape Concerns” subscale. The total scale comprised 15 items for girls and 18 items for boys. Test–retest reliability and internal consistency were satisfactory for the girls' and boys' scales (Cronbach's α = .91 for both) and their comprising subscales (αs ≥ .80). Concurrent validity was established through medium‐high significant correlations with measures of body image and internalization of appearance ideals. Combining items common to both versions of the scale led to a psychometrically acceptable model which was largely invariant across both genders, thus facilitating gendered comparison.

Discussion

Findings indicate the reliability and validity of the EDE‐Q among English‐speaking urban Indian adolescents. This will facilitate further research examining the prevalence and nature of eating pathology among adolescents in India.
Accuracy improvement of terminal voltage self‐coupled laser distance sensor
Authors: Ohba Tatsuya , Mizushima Daisuke , Goshima Keishiro , Tsuda Norio , Yamada Jun
Published: December 2020

Measurements performed using the self‐coupling effect of a semiconductor laser utilize an external resonator by exploiting the reflected light from the surface of an object. The improvement of the measurement accuracy due to the use of self‐coupled signals acquired from terminal voltages has not been thoroughly investigated. The current that flows through a semiconductor laser is adjusted so that its wavelength changes at a specific rate when it is modulated using an arbitrary waveform. As such, the spread of the self‐coupled signal is suppressed, and precision is improved. In addition, the accuracy is improved by considering the influence of lenses on the optical path.
Neurosteroid involvement in threatened preterm labour
Authors: Turkmen Sahruh , Bäckström Torbjörn , Kangas Flodin Yvonne , Bixo Marie
Published: December 2020

Introduction

The neurosteroid allopregnanolone modulates oxytocin expression in the brain, and its effects arise from its action on the GABAA receptor. Whether neurosteroid levels and the function of the GABAA receptor are involved in the risk of preterm labour in pregnant women is unknown.

Methods

Pregnant women with (n = 16) or without (n = 20) threatened preterm labour (TPL) in gestational week 33 + 6 days to 37 + 0 days were studied prospectively with procedures including foetal heart rate monitoring, vaginal examination, ultrasound examination and blood tests to determine allopregnanolone, progesterone and oxytocin levels. The GABAA receptor function in both groups was measured with a saccadic eye velocity test (SEVT).

Results

Plasma oxytocin levels were higher in the TPL group than in the control group (41.5 vs. 37.0 pmol/L, respectively, p = .021). Although the allopregnanolone and progesterone levels in both groups did not differ, there was a negative association between blood oxytocin and allopregnanolone (as predictor) levels in the TPL group (B: −3.2, 95% confidence interval (CI): −5.5 to −0.9, p = .012). As a predictor of TPL, progesterone was associated with cervix maturity (odds ratio: 1.02, 95% CI: 1.00–1.04, p = .038). SEVT showed that the women in both groups had similar GABAA receptor functions. In both groups, body mass index correlated with peak saccadic eye velocity (r = .34, p = .044) and negatively with allopregnanolone (r = −.41, p = .013).

Conclusions

Neurosteroid levels were unchanged in the peripheral blood of women with TPL, despite the increase in available oxytocin. Although the function of the GABAA receptor was unchanged in women with TPL, to ensure reliable results, saccadic eye velocity should be investigated during a challenge test with a GABAA receptor agonist.
Fabrication and evaluation of suspended Micro‐heater using TiN
Authors: Ito Hiroshi , Kawamata Yoshio , Nikkuni Hiroyuki
Published: December 2020

In this study, suspended micro‐heater using TiN for decreasing power dissipation was fabricated and evaluated. The self‐supporting film of the suspended filament was developed by the low compressive stress SiO2 film deposited by the dc reactive sputtering method with rf substrate bias and the post annealing at 900°C. In the suspended structure process, single photolithography process and two wet etching process of HF and KOH solution were used. The power dissipation of the suspended heaters was obtained about 70 mW and it is indicated that the power dissipation is able to reduce than the other structure in previous research. Then, it is expected that the TiN micro‐heater using suspended structure is applicable to several MEMS sensors.
Rationale and methods of a randomized trial evaluating the effect of neprilysin inhibition on left ventricular remodelling
Authors: Docherty Kieran F. , Campbell Ross T. , Brooksbank Katriona J.M. , Godeseth Rosemary L. , Forsyth Paul , McConnachie Alex , Roditi Giles , Stanley Bethany , Welsh Paul , Jhund Pardeep S. , Petrie Mark C. , McMurray John J.V.
Published: December 2020

Aims

In patients at high risk of heart failure following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse left ventricular (LV) remodelling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti‐hypertrophic, anti‐fibrotic, and sympatholytic effects.

Methods

We designed a randomized, double‐blinded, active‐comparator trial to examine the effect of sacubitril/valsartan to the current standard of care in reducing adverse LV remodelling in patients with asymptomatic LVSD following MI. Eligible patients were ≥3 months following MI, had an LV ejection fraction ≤40% as measured by echocardiography, were New York Heart Association functional classification I, tolerant of an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker at equivalent dose of ramipril 2.5 mg twice daily or greater, and taking a beta‐blocker unless contraindicated or intolerant. Patients were randomized to sacubitril/valsartan (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily). The primary endpoint will be change in LV end‐systolic volume indexed for body surface area measured using cardiac magnetic resonance imaging over 52 weeks from randomization. Secondary endpoints include other magnetic resonance imaging‐based metrics of LV remodelling, biomarkers associated with LV remodelling and neurohumoral activation, and change in patient well‐being assessed using a patient global assessment questionnaire.

Conclusions

This trial will investigate the effect of neprilysin inhibition on LV remodelling and the neurohumoral actions of sacubitril/valsartan in patients with asymptomatic LVSD following MI.
Impact of catheter ablation for atrial fibrillation on cardiac disorders in patients with coexisting heart failure
Authors: Kawaji Tetsuma , Shizuta Satoshi , Aizawa Takanori , Yamagami Shintaro , Kato Masashi , Yokomatsu Takafumi , Miki Shinji , Ono Koh , Kimura Takeshi
Published: December 2020

Aims

We sought to investigate the time course of cardiac disorders after catheter ablation for atrial fibrillation (AF) in patients with coexisting heart failure (HF) during long‐term follow‐up.

Methods and results

We analysed consecutive 280 patients undergoing first‐time catheter ablation for AF who had coexisting HF, which was defined as prior HF hospitalization, estimated right ventricular systolic pressure ≥45 mmHg, or B‐type natriuretic peptide (BNP) ≥200 pg/dL before the procedure. The primary endpoints were improvements in left ventricular ejection fraction (LVEF), E/e′, BNP, left atrial dimension (LAD), and mitral regurgitation (MR) at 1 year. The secondary endpoints were serial changes of LVEF, E/e′, BNP, LAD, and MR at 6 months, 1 year, and 5 years and cumulative incidence of HF hospitalization. During the mean follow‐up of 5.1 ± 3.0 years, 70.7% of patients were free from recurrent AF. Among patients with LVEF < 50%, E/e′ ≥ 15, BNP ≥ 200 pg/dL, LAD ≥ 40 mm, and moderate‐to‐severe MR, changes in those parameters from baseline to 1 year were 34.5 ± 9.9% to 43.2 ± 14.4% (P < 0.001), 19.7 ± 3.9 to 12.5 ± 6.6 (P < 0.001), 290 to 85 pg/dL (P < 0.001), and 100% to 37.8% (P < 0.001), respectively. The improvements in the cardiac disorders were maintained up to 5 years except for E/e′. In patients with LVEF < 40%, significant delayed improvement of LVEF beyond 1 year was observed (ΔLVEF = 10.5 ± 18.5, P = 0.001), but not in patients with LVEF of 40–49%. The cumulative incidence of HF hospitalization was 12.6% at 5 years. Baseline diastolic dysfunction was the only independent predictor for subsequent HF hospitalization.

Conclusions

In patients undergoing AF ablation with coexisting HF, all cardiac disorders significantly improved after the procedure, which was mostly maintained during 5 year follow‐up.