bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemoenzymatic Synthesis of Fluorinated Cellodextrins Identifies a New Allomorph for Cellulose‐Like Materials**
Authors: de Andrade Peterson , Muñoz‐García Juan C. , Pergolizzi Giulia , Gabrielli Valeria , Nepogodiev Sergey A. , Iuga Dinu , Fábián László , Nigmatullin Rinat , Johns Marcus A. , Harniman Robert , Eichhorn Stephen J. , Angulo Jesús , Khimyak Yaroslav Z. , Field Robert A.
Published: September 2020

Understanding the fine details of the self‐assembly of building blocks into complex hierarchical structures represents a major challenge en route to the design and preparation of soft‐matter materials with specific properties. Enzymatically synthesised cellodextrins are known to have limited water solubility beyond DP9, a point at which they self‐assemble into particles resembling the antiparallel cellulose II crystalline packing. We have prepared and characterised a series of site‐selectively fluorinated cellodextrins with different degrees of fluorination and substitution patterns by chemoenzymatic synthesis. Bearing in mind the potential disruption of the hydrogen‐bond network of cellulose II, we have prepared and characterised a multiply 6‐fluorinated cellodextrin. In addition, a series of single site‐selectively fluorinated cellodextrins was synthesised to assess the structural impact upon the addition of one fluorine atom per chain. The structural characterisation of these materials at different length scales, combining advanced NMR spectroscopy and microscopy methods, showed that a 6‐fluorinated donor substrate yielded multiply 6‐fluorinated cellodextrin chains that assembled into particles presenting morphological and crystallinity features, and intermolecular interactions, that are unprecedented for cellulose‐like materials.
BIAN‐NHC Ligands in Transition‐Metal‐Catalysis: A Perfect Union of Sterically Encumbered, Electronically Tunable N‐Heterocyclic Carbenes?
Authors: Chen Changpeng , Liu Feng‐Shou , Szostak Michal
Published: September 2020

The discovery of NHCs (NHC = N‐heterocyclic carbenes) as ancillary ligands in transition‐metal‐catalysis ranks as one of the most important developments in synthesis and catalysis. It is now well‐recognized that the strong σ‐donating properties of NHCs along with the ease of scaffold modification and a steric shielding of the N‐wingtip substituents around the metal center enable dramatic improvements in catalytic processes, including the discovery of reactions that are not possible using other ancillary ligands. In this context, although the classical NHCs based on imidazolylidene and imidazolinylidene ring systems are now well‐established, recently tremendous progress has been made in the development and catalytic applications of BIAN‐NHC (BIAN = bis(imino)acenaphthene) class of ligands. The enhanced reactivity of BIAN‐NHCs is a direct result of the combination of electronic and steric properties that collectively allow for a major expansion of the scope of catalytic processes that can be accomplished using NHCs. BIAN‐NHC ligands take advantage of (1) the stronger σ‐donation, (2) lower lying LUMO orbitals, (3) the presence of an extended π‐system, (4) the rigid backbone that pushes the N‐wingtip substituents closer to the metal center by buttressing effect, thus resulting in a significantly improved control of the catalytic center and enhanced air‐stability of BIAN‐NHC‐metal complexes at low oxidation state. Acenaphthoquinone as a precursor enables facile scaffold modification, including for the first time the high yielding synthesis of unsymmetrical NHCs with unique catalytic properties. Overall, this results in a highly attractive, easily accessible class of ligands that bring major advances and emerge as a leading practical alternative to classical NHCs in various aspects of catalysis, cross‐coupling and C−H activation endeavors.
Bisubstrate Ether‐Linked Uridine‐Peptide Conjugates as O‐GlcNAc Transferase Inhibitors
Authors: Makwana Vivek , Ryan Philip , Malde Alpeshkumar K. , Anoopkumar‐Dukie Shailendra , Rudrawar Santosh
Published: September 2020

The O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) transferase (OGT) is a master regulator of installing O‐GlcNAc onto serine or threonine residues on a multitude of target proteins. Numerous nuclear and cytosolic proteins of varying functional classes, including translational factors, transcription factors, signaling proteins, and kinases are OGT substrates. Aberrant O‐GlcNAcylation of proteins is implicated in signaling in metabolic diseases such as diabetes and cancer. Selective and potent OGT inhibitors are valuable tools to study the role of OGT in modulating a wide range of effects on cellular functions. We report linear bisubstrate ether‐linked uridine‐peptide conjugates as OGT inhibitors with micromolar affinity. In vitro evaluation of the compounds revealed the importance of donor substrate, linker and acceptor substrate in the rational design of bisubstrate analogue inhibitors. Molecular dynamics simulations shed light on the binding of this novel class of inhibitors and rationalized the effect of amino acid truncation of acceptor peptide on OGT inhibition.
Pediatric cancer communication in low‐ and middle‐income countries: A scoping review
Authors: Graetz Dylan E. , Garza Marcela , Rodriguez‐Galindo Carlos , Mack Jennifer W.
Published: September 2020

The burden of global childhood cancer lies in low‐ and middle‐income countries (LMICs). Communication is essential to pediatric cancer care, and the National Cancer Institute (NCI) has defined 6 functions of communication between patients, family members, and providers, including 1) fostering healing relationships, 2) responding to emotions, 3) exchanging information, 4) making decisions, 5) managing uncertainty, and 6) enabling self‐management. Nevertheless, communication needs and practices in LMICs remain incompletely understood. For this review, the Web of Science, Scopus, PubMed, and Turning Research Into Practice databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis Extension for Scoping Reviews. Searching identified 2988 articles, with 11 added through snowballing. Forty articles met the inclusion criteria. Two reviewers extracted data on study characteristics, communication functions, enablers, barriers, and additional major themes. This review included work from 17 countries. Most studies (85%) used qualitative methodology; the number of participants ranged from 7 to 304. All 6 of the NCI‐defined communication functions were identified in included studies, with rates ranging from 100% of studies for information exchange to 28% of studies for decision making. Communication barriers included cancer misconceptions, stigma, and hierarchy between parents and providers. Provider training and community education facilitated communication. Additional themes included disclosure to children, family dynamics, and the multidisciplinary health care team. In conclusion, all 6 of the communication functions defined by the NCI were applied by pediatric cancer researchers in LMICs. Additional barriers, enablers, and communication themes noted in LMICs deserve further exploration, and a relative paucity of research in comparison with high‐income countries highlights the need for further work.
Effect of matrix metalloproteinase inhibitors on microtensile bond strength of dental composite restorations to dentin in use of an etch‐and‐rinse adhesive system
Authors: Saffarpour Aida , Valizadeh Sara , Amini Abolghasem , Kharazifard Mohammad‐Javd , Rohaninasab Marzieh
Published: September 2020

Aim

This study assesses the effect of matrix metalloproteinases on microtensile bond strength (μTBS) of an etch‐and‐rinse adhesive system.

Methods

This in vitro study evaluated 88 extracted premolars. The teeth were sectioned to expose dentin and were then randomly divided into four groups (n= 22). In group 1 (control), dentin surface was etched, and Adper Single Bond 2 was applied. In groups 2–4, dentin surface was etched and chlorhexidine (CHX), 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC), and dimethyl sulfoxide (DMSO) were applied on the surfaces, respectively, and blotted dry. Next, Adper Single Bond 2 was applied and all teeth were built up with Z350 composite. In each group, half the samples immediately and the other half after 10,000 thermal cycles underwent μTBS test. Data were analyzed using ANOVA and Tukey's test (α= .05).

Results

In thermocycled samples, maximum μTBS was noted in CHX group followed by DMSO, EDC, and control group (p < .001). The thermocycled μTBS of composite to dentin was significantly higher in CHX group compared with EDC, DMSO, and control groups (p < .001) but was not significantly different in EDC and DMSO groups (p= .498).

Conclusion

The thermocycled μTBS obtained by the application of CHX, EDC, and DMSO was significantly higher compared with the value to the control group.
Differences among eighteen winter pea genotypes for forage and cover crop use in the southeastern United States
Authors: Vann Rachel A. , Reberg‐Horton S. Chris , Castillo Miguel S. , Murphy J. Paul , Martins Lais B. , Mirsky Steven B. , Saha Uttam , McGee Rebecca J.
Published: September 2020

Winter pea (Pisum sativumL.) can be used as a forage and cover crop in the southeast and mid‐Atlantic United states; however, minimal effort has been devoted to optimize winter pea genetics for forage and cover crop production in these regions. Studies were conducted from 2015–2017 in Maryland and North Carolina screening 18 winter pea genotypes for forage and cover crop use. Winter pea genotypes were compared with widely grown crimson clover (Trifolium incarnatumL.) and hairy vetch (Vicia villosaRoth]. All legume genotypes were harvested across four timings. Legume winter hardiness, disease incidence, biomass production, quality, and N release were estimated. Winter hardiness was severe with many winter pea genotypes at the Maryland environments, which restricted winter pea biomass production. There was considerable variation for disease incidence among the winter pea genotypes depending on biotic stressors at each environment. At the North Carolina environments, several winter pea genotypes produced similar biomass to crimson clover and hairy vetch across harvest timings. At the Maryland environments, crimson clover and hairy vetch biomass exceeded winter pea biomass. The winter pea genotypes varied considerably for quality traits including protein, lignin, and cellulose. Relative forage value declined as biomass harvest was delayed and was generally higher with all winter pea genotypes than crimson clover or hairy vetch. These results show wide genetic variation in the winter pea genotypes screened for biomass and quality; this variation could be utilized in breeding efforts to enhance winter pea production in the region.
Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice
Authors: Wei Shasha , Bi Jianbin , Yang Lifei , Zhang Jia , Wan Yafeng , Chen Xue , Wang Yawen , Wu Zheng , Lv Yi , Wu Rongqian
Published: September 2020

Background

Sepsis remains a major health issue without an effective therapy. Ferroptosis, an iron‐dependent programmed cell death, has been proposed to be related to the pathogenesis of sepsis. Irisin, a myokine released during exercise, improves mitochondrial function under various conditions. Ferroptosis is closely related to mitochondrial function. However, the role of irisin in sepsis‐induced ferroptosis and mitochondrial dysfunction in the liver remained unknown. Thus, we hypothesize that irisin treatment suppresses ferroptosis and improves mitochondrial function in sepsis.

Methods

To study this, we first explored the role of serum irisin levels in patients with sepsis, and then determined the effect of irisin administration on ferroptosis and mitochondrial function in the liver of septic mice.

Results

Serum irisin levels were decreased and negatively correlated with the APACHE II scores in patients with sepsis. In mice subjected to cecal ligation and puncture (CLP), exogenous irisin administration suppressed ferroptosis, inhibited inflammatory response, decreased reactive oxygen species (ROS) production, restored abnormal mitochondrial morphology, and increased mtDNA copy number and adenosine triphosphate (ATP) content. The effect of irisin on ferroptosis was confirmed in LPS‐treated hepatocytes and CLP‐induced septic mice. Inhibition of glutathione peroxidase 4 (GPX4), a central regulator of ferroptosis, reduced irisin's protective effects in LPS‐treated hepatocytes and CLP‐induced septic mice, while blocking the irisin receptor with RGD peptide or Echistain decreased irisin‐induced GPX4 expression.

Conclusions

Serum irisin levels are decreased and negatively correlated with disease severity in patients with sepsis, and irisin treatment suppresses ferroptosis and restores mitochondrial function in experimental sepsis. Irisin may offer therapeutic potential in the management of sepsis.
Extrapair paternity in two populations of the socially monogamous Thorn‐tailed RayaditoAphrastura spinicauda(Passeriformes: Furnariidae)
Authors: Botero‐Delgadillo Esteban , Quirici Verónica , Poblete Yanina , Ippi Silvina , Kempenaers Bart , Vásquez Rodrigo A.
Published: September 2020

Studies on extrapair paternity (EPP) are key to understanding the ecological and evolutionary drivers of variation in avian mating strategies, but information is currently lacking for most tropical and subtropical taxa. We describe the occurrence of EPP in two populations of a South American socially monogamous bird, the Thorn‐tailed Rayadito, based on data from 266 broods and 895 offspring that were sampled during six breeding seasons in north‐central and southern Chile. In the northern population, 21% of the broods contained at least one extrapair young and 14% of all offspring were sired by an extrapair male, while in the southern population, we detected extrapair offspring (EPO) in 14% of the broods, and 6% of all offspring were EPO. Variation in the frequency of EPP could stem from population differences in the duration of the breeding season or the density of breeding individuals. Other factors such as differences in breeding synchrony and variation in food availability need to be evaluated. More reports on EPP rates are necessary to determine the patterns of taxonomic and geographic variation in mating strategies in Neotropical birds, and to better understand the differences in ecological dynamics between northern and southern hemisphere populations.
Evaluation of exercise intensity by real‐time skin lactate monitoring system
Authors: Konno Sakae , Suzuki Yusuke , Suzuki Masanobu , Kudo Hiroyuki
Published: September 2020

A sweat lactic acid (LA) monitoring system embedded on an armband for evaluation of exercise intensity was fabricated and real‐time LA monitoring of a free‐moving subject was conducted for the first time. The LA monitoring system utilizes an electrochemical biosensor, which uses redox reaction of lactate oxidase immobilized on a screen‐printed carbon graphite electrode. The volunteer wearing the system on the upper arm performed bouldering activity (climbing and 2 minutes rest alternately) in two different difficulty levels (100 degrees and 150 degrees). Different secretion of LA was confirmed (11 µg/cm2/min for the 150 degrees course and 2 µg/cm2/min for the 110 degrees course). This indicates that the LA levels obtained with our system successfully reflected the metabolic status of the subject.
Chemical exposure and flammability risks of upholstered furniture
Authors: Harris Debra , Davis Aika , Ryan Peter Barry , Cohen Jordan , Gandhi Pravinray , Dubiel David , Black Marilyn
Published: September 2020

Upholstered furniture remains a consumer fire hazard. Flame retardant technologies are necessary but may present a health risk from chemical exposure. This study developed methodologies for measuring exposure to flame retardants and flammability performance, comparing the effectiveness of differing flammability reduction strategies on upholstered chairs with and without added flame retardants and the use of a barrier material. The chemical analysis focused on volatile organic compounds (VOCs) and flame retardants. Open flame tests were conducted on chair assemblies, and smolder resistance tests were conducted on chair materials. Results showed that VOC inhalation exposure during consumer use was low for all chair types. However, VOCs were significantly elevated during the chair burns. The organophosphorus flame retardant used in this study was found in air, settled dust and dermal transfer samples. The chairs with a barrier material demonstrated significantly lower flammability hazards when compared to the other chair types. All assembled chairs did not meet the criteria for smolder testing, suggesting a lack of correlation with open‐flame performance. This study demonstrated that combined human health and flammability advantages may be achieved for upholstered chairs constructed with an effective fire barrier material without any added flame retardants.
Open Educational Resource Exercises for Fisheries Classes
Authors: Grossman Gary D , Bozeman Bryan B , Sliger Ridge W , Simon Troy N , Matsumoto George I
Published: September 2020

Open Educational Resources (OERs) represent any form of educational resource that is available free of charge. Few OERs exist for courses in fisheries or other life science courses, and the onset of the COVID-19 epidemic only exacerbates the need for such resources. To rectify this shortcoming, we build on earlier work (Grossman and Chernoff 2018) and present four OERs designed for fisheries classes. The OERs may be used as described or may be modified for different class levels by varying their complexity and outcomes. The OERs examine behavioral repertoires and time budgets of Arctic Grayling Thymallus arcticus, factors affecting winners and losers of intraspecific interactions in interior Dolly Varden Charr Salvelinus malma, the effects of velocity on foraging success of Brook Trout S. fontinalis, and an exploration of animal abundance and spatial distributions in a soft-bottom habitat at 875m depth in Monterey Bay, California. We also provide a grading rubric for the first exercise that is easily modified for the other exercises. These exercises should aid fisheries instructors in a time when remote pedagogy may be a necessity.
Some Thoughts on Barry M. Trost and Natural Products
Authors: Massiot Georges
Published: September 2020

Barry and I share a common interest in natural products. In his career, Barry covered all the subfields: isolation, structural determination, synthesis and biological characterization, me too but at a more modest level. I am approaching retirement and I have dedicated all my scientific life to all aspects of natural products chemistry. Based on my own experience and on examples extracted from Barry's immense production, I wish to show some of the fascinating facets of the field, examples of problems that remain to be solved and underline difficulties associated with the development of new drugs from Nature's warehouse.
Federated learning based caching in fog computing for future smart cities
Authors: Sharma Sushant , Gupta Nitin
Published: September 2020

Edge devices in the Internet of Things (IoT) networks are responsible for the continuous generation and communication of massive chunks of transient data to the fog devices for data processing. However, resources at the fog nodes are limited. Therefore, objective of the work is efficient caching, which is achieved using Federated Learning (FL), where the data used for learning is not gathered centrally but remains where it is produced. Therefore, the heavy transmission of the data to the fog nodes for learning is not required. Simulation results depict the advantages of using this approach over other centralized approaches.
CircMMP1 promotes the progression of glioma through miR‐433/HMGB3 axis in vitro and in vivo
Authors: Yin Kai , Liu Xianzhi
Published: September 2020

Circular RNAs (circRNAs) are non‐coding RNAs that have shown to regulate the progression of human diseases, including a variety of cancers. We aimed to investigate the function and the underlying working mechanism of circRNA matrix metallopeptidase 1 (circMMP1; hsa_circ_0024108) in glioma progression. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to examine the expression of circMMP1, microRNA‐433‐3p (written as “miR‐433”) and high mobility group box 3 (HMGB3). Nanoparticle tracking analysis (NTA) was used to analyze the relative concentration and size distribution of serum exosomes. Cell proliferation was analyzed via cell counting kit‐8 (CCK8) assay and colony formation assay. Transwell migration and invasion assays were used to examine the metastasis ability of glioma cells. Cell apoptosis was assessed by flow cytometry. Dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to verify the interactions of circMMP1/miR‐433 and miR‐433/HMGB3 messenger RNA (mRNA). Xenograft mouse model was built to clarify the role of circMMP1 in vivo. The results showed that high serum exosomal circMMP1 level might predict poor prognosis of glioma patients. CircMMP1 promoted the proliferation and motility and impeded the apoptosis of glioma cells. MiR‐433 was a direct target of circMMP1, and circMMP1 silencing‐mediated influences in glioma cells were partly alleviated by the knockdown of miR‐433. MiR‐433 directly interacted with HMGB3 mRNA, and HMGB3 overexpression partly counteracted the effects of miR‐433 up‐regulation in glioma cells. CircMMP1 enhanced HMGB3 level through sponging miR‐433 in glioma cells. CircMMP1 silencing suppressed the progression of glioma in vivo. CircMMP1 promoted the progression of glioma through acting as a competitive endogenous RNA (ceRNA) of miR‐433 to up‐regulate HMGB3. CircMMP1 level in serum exosomes might be a potential marker for the diagnosis of glioma patients. Targeting circMMP1/miR‐433/HMGB3 signaling might be a novel insight for glioma treatment.
Vitamin D: Brain and Behavior
Authors: Eyles Darryl Walter
Published: September 2020

It has been 20 years since we first proposed vitamin D as a “possible” neurosteroid.(1) Our work over the last two decades, particularly results from our cellular and animal models, has confirmed the numerous ways in which vitamin D differentiates the developing brain. As a result, vitamin D can now confidently take its place among all other steroids known to regulate brain development.(2) Others have concentrated on the possible neuroprotective functions of vitamin D in adult brains. Here these data are integrated, and possible mechanisms outlined for the various roles vitamin D appears to play in both developing and mature brains and how such actions shape behavior. There is now also good evidence linking gestational and/or neonatal vitamin D deficiency with an increased risk of neurodevelopmental disorders, such as schizophrenia and autism, and adult vitamin D deficiency with certain degenerative conditions. In this mini‐review, the focus is on what we have learned over these past 20 years regarding the genomic and nongenomic actions of vitamin D in shaping brain development, neurophysiology, and behavior in animal models. © 2020 The Author. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Two neuroendocrine G protein‐coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives
Authors: Costanzi Eva , Simioni Carolina , Conti Ilaria , Laface Ilaria , Varano Gabriele , Brenna Cinzia , Neri Luca M.
Published: September 2020

Recent studies have shown that G protein‐coupled receptors (GPCRs), the largest signal‐conveying receptor family, are targets for mutations occurring frequently in different cancer types. GPCR alterations associated with cancer development represent significant challenges for the discovery and the advancement of targeted therapeutics. Among the different molecules that can activate GPCRs, we focused on two molecules that exert their biological actions regulating many typical features of tumorigenesis such as cellular proliferation, survival, and invasion: somatostatin and melatonin. The modulation of signaling pathways, that involves these two molecules, opens an interesting scenario for cancer therapy, with the opportunity to act at different molecular levels. Therefore, the aim of this review is the analysis of the biological activity and the therapeutic potential of somatostatin and melatonin, displaying a high affinity for GPCRs, that interfere with cancer development and maintenance.
Factors inducing transdifferentiation of myoblasts into adipocytes
Authors: Wang Liyi , Shan Tizhong
Published: September 2020

Fat infiltration in skeletal muscle is observed in several myopathies, is associated with muscular dysfunction, and is strongly correlated with insulin resistance, diabetes, obesity, and aging. In animal production, skeletal muscle fat (also known as intermuscular and intramuscular fat) is positively related to meat quality including tenderness, flavor, and juiciness. Thus, understanding the cell origin and regulation mechanism of skeletal muscle fat infiltration is important for developing therapies against human myopathies as well as for improving meat quality. Notably, age, sarcopenia, oxidative stress, injury, and regeneration can activate adipogenic differentiation potential in myoblasts and affect fat accumulation in skeletal muscle. In addition, several transcriptional and nutritional factors can directly induce transdifferentiation of myoblasts into adipocytes. In this review, we focused on the recent progress in understanding the muscle‐to‐adipocyte differentiation and summarized and discussed the genetic, nutritional, and physiological factors that can induce transdifferentiation of myoblasts into adipocytes. Moreover, the regulatory roles and mechanisms of these factors during the transdifferentiation process were also discussed.
Characterization of cachexia in the human fibrosarcoma HT‐1080 mouse tumour model
Authors: Bernardo Barbara , Joaquim Stephanie , Garren Jeonifer , Boucher Magalie , Houle Christopher , LaCarubba Brianna , Qiao Shuxi , Wu Zhidan , Esquejo Ryan M. , Peloquin Matthew , Kim Hanna , Breen Danna M.
Published: September 2020

Background

Cancer cachexia is a complex metabolic disease with unmet medical need. Although many rodent models are available, none are identical to the human disease. Therefore, the development of new preclinical models that simulate some of the physiological, biochemical, and clinical characteristics of the human disease is valuable. The HT‐1080 human fibrosarcoma tumour cell line was reported to induce cachexia in mice. Therefore, the purpose of this work was to determine how well the HT‐1080 tumour model could recapitulate human cachexia and to examine its technical performance. Furthermore, the efficacy of ghrelin receptor activation via anamorelin treatment was evaluated, because it is one of few clinically validated mechanisms.

Methods

Female severe combined immunodeficient mice were implanted subcutaneously or heterotopically (renal capsule) with HT‐1080 tumour cells. The cachectic phenotype was evaluated during tumour development, including body weight, body composition, food intake, muscle function (force and fatigue), grip strength, and physical activity measurements. Heterotopic and subcutaneous tumour histology was also compared. Energy balance was evaluated at standard and thermoneutral housing temperatures in the subcutaneous model. The effect of anamorelin (ghrelin analogue) treatment was also examined.

Results

The HT‐1080 tumour model had excellent technical performance and was reproducible across multiple experimental conditions. Heterotopic and subcutaneous tumour cell implantation resulted in similar cachexia phenotypes independent of housing temperature. Tumour weight and histology was comparable between both routes of administration with minimal inflammation. Subcutaneous HT‐1080 tumour‐bearing mice presented with weight loss (decreased fat mass and skeletal muscle mass/fibre cross‐sectional area), reduced food intake, impaired muscle function (reduced force and grip strength), and decreased spontaneous activity and voluntary wheel running. Key circulating inflammatory biomarkers were produced by the tumour, including growth differentiation factor 15, Activin A, interleukin 6, and TNF alpha. Anamorelin prevented but did not reverse anorexia and weight loss in the subcutaneous model.

Conclusions

The subcutaneous HT‐1080 tumour model displays many of the perturbations of energy balance and physical performance described in human cachexia, consistent with the production of key inflammatory factors. Anamorelin was most effective when administered early in disease progression. The HT‐1080 tumour model is valuable for studying potential therapeutic targets for the treatment of cachexia.
Pollen wall patterns as a model for biological self‐assembly
Authors: Radja Asja
Published: September 2020

We are still far from being able to predict organisms' shapes purely from their genetic codes. While it is imperative to identify which encoded macromolecules contribute to a phenotype, determining how macromolecules self‐assemble independently of the genetic code may be equally crucial for understanding shape development. Pollen grains are typically single‐celled microgametophytes that have decorated walls of various shapes and patterns. The accumulation of morphological data and a comprehensive understanding of the wall development makes this system ripe for mathematical and physical modeling. Therefore, pollen walls are an excellent system for identifying both the genetic products and the physical processes that result in a huge diversity of extracellular morphologies. In this piece, I highlight the current understanding of pollen wall biology relevant for quantification studies and enumerate the modellable aspects of pollen wall patterning and specific approaches that one may take to elucidate how pollen grains build their beautifully patterned walls.
Andrographolide exerts anti-inflammatory effects in Mycobacterium tuberculosis-infected macrophages by regulating the Notch1/Akt/NF-κB axis
Authors: He Weigang , Sun Jinxia , Zhang Qingwen , Li Yinhong , Fu Yan , Zheng Yuejuan , Jiang Xin
Published: September 2020

Tuberculosis is a serious public health problem aggravated by the slow progress in the development of new anti-tuberculosis drugs. The hyper-reactive TB patients have suffered from chronic inflammation which could cause deleterious effects on their bodies. Therefore, it is imperative to develop an adjunctive therapy based on inflammatory modulation during Mycobacterium tuberculosis (Mtb) infection. The present study aims to investigate the immune regulatory effects of Andrographolide (Andro) on Mtb-infected macrophages and its underlying mechanisms. The results showed that Andro inhibits the production of IL-1β and other inflammatory cytokines in a dose-dependent manner. The down-regulation of IL-1β expression causes the declining expression of IL-8 and MCP-1 in lung epithelial cells which were co-cultured with Mtb-infected macrophages. The inhibition of the activation of NF-κB pathway, but not the inhibition of MAPK signaling pathway, accounts for the anti-inflammatory role of Andro. Further studies elucidated that Andro could evoke the activation of autophagy to degrade NLRP3, which ultimately inhibited inflammasome activation and subsequent IL-1β production. Finally, the relevant results demonstrated that Andro inhibited the Notch1 pathway to down-regulate the phosphorylation of Akt/mTOR and NF-κB p65 subunit. Taken together, Andro has been found to suppress the Notch1/Akt/NF-κB signaling pathway. Both Akt inhibition-induced autophagy and inhibition of the NF-κB pathway contributed to restraining the activation of NLRP3 inflammasome and subsequent IL-1β production. Then, the decreased production of IL-1β influenced chemokine expression in lung epithelial cells. Based on these results, anti-inflammatory effect of Andro in TB infection is merit further investigation.
Heterogeneous response of global precipitation concentration to global warming
Authors: Dong Qing , Wang Weiguang , Kunkel Kenneth E. , Shao Quanxi , Xing Wanqiu , Wei Jia
Published: September 2020

This study investigated the change in precipitation concentration due to global warming based on the output of one experiment (a scenario of 1% CO2 increase per year) from 12 general circulation models provided by the Coupled Model Intercomparison Project Phase 5 (CMIP5). Two different indices were used to describe precipitation concentration: (a) concentration index (CI), which measures the evenness of total precipitation on wet days, and (b) precipitation concentration degree (PCD), which measures the evenness of the annual precipitation distributions over time. We found that widespread increases in CI were distributed over all land areas except for some arid areas, indicating a less uniform distribution of precipitation on wet days in a warming climate caused by CO2 increasing. We also found that the spatial patterns of changes in PCD are complex, with large regional differences. All of the results suggest a global‐scale readjustment of precipitation distribution in magnitude and timing. This kind of readjustment may have significant impacts on climatic and hydrological events and thus cause severe ecological and environmental damage.
Comparison of the ability of Child‐Pugh score, MELD score, and ICG‐R15 to assess preoperative hepatic functional reserve in patients with hepatocellular carcinoma
Authors: Wang Yan‐Yan , Zhao Xin‐Hua , Ma Liang , Ye Jia‐Zhou , Wu Fei‐Xiang , Tang Juan , You Xue‐Mei , Xiang Bang‐De , Li Le‐Qun
Published: September 2020

Background

Assessing hepatic functional reserve before hepatectomy is beneficial to reduce the incidence of posthepatectomy liver failure (PHLF). This study aimed to compare the ability of the Child‐Pugh score, model for end‐stage liver disease (MELD) score, and retention test at 15 minutes (indocyanine green [ICG]‐R15) to assess hepatic functional reserve.

Methods

A total of 185 patients with hepatocellular carcinoma (HCC) undergoing hepatectomy were enrolled in this study. The ability of Child‐Pugh score, MELD score, and ICG‐R15 predicting severe PHLF were compared.

Results

A total of 23 patients (12.4%) developed severe PHLF. Multivariate analyses identified that platelet count, ICG‐R15, clinically significant portal hypertension, and major resection were independent factors for predicting severe PHLF. The area under the receiver operating characteristic curve of ICG‐R15 for predicting severe PHLF was higher than that of both Child‐Pugh score and MELD score. With an optimal cutoff value of 7.1%, the sensitivity and specificity of ICG‐R15 for predicting severe PHLF were 52.2% and 89.5%, respectively. Both the incidence of severe PHLF and mortality in patients with ICG‐R15 >7.1% were significantly higher than the figures for patients with ICG‐R15 ≤7.1%.

Conclusion

ICG‐R15 is more accurate than the Child‐Pugh score and MELD score in predicting hepatic functional reserve before hepatectomy.
Active surveillance or early resection for ground‐glass nodules that need preoperative localization
Authors: Tsai Ping‐Chung , Hsu Po‐Kuei , Yeh Yi‐Chen , Chen Chun‐Ku , Chang Ying‐Yueh , Huang Chien‐Sheng , Hsu Han‐Shui
Published: September 2020

Introduction

Few studies have investigated the impact of active surveillance on pathological outcome ground‐glass nodules (GGNs). We focused on GGNs that needed preoperative localization before resection and compared the pathological results between GGNs that underwent early resection or active surveillance.

Methods

We retrospectively reviewed data of resected GGNs between January 2017 and December 2018. GGNs were classified by early resection (Group A) and active surveillance (Group B). Group B was subclassified as no (Group B1) and with (Group B2) growth, and intergroup comparison of pathological results was undertaken.

Results

In total, 509 GGNs (124, 275, and 110 in Groups A, B1, and B2, respectively) were included. Malignancy (primary lung cancer) ratios were 68% and 72% in Groups A and B (p = .312) and 65% and 92% in Groups B1 and B2, respectively (p < .001). The ratios of invasive carcinoma were 21.4%, 9.6%, and 35.6% in Groups A, B1, and B2, respectively. Predictors for invasive carcinoma included history of lung cancer, GGN size ≥ 10 mm, solid size ≥ 6 mm, and GGN growth.

Conclusions

The pathological findings were similar for GGNs in the early resection and active surveillance groups. However, rates of malignancy and invasive carcinoma increased in the group that manifested growth during active surveillance.
Therapeutic Effects of Intranasal Tofacitinib on Chronic Rhinosinusitis with Nasal Polyps in Mice
Authors: Joo Yeon‐Hee , Cho Hyun‐Jin , Jeon Yung Jin , Kim Jin Hyun , Jung Myeong Hee , Jeon Sea‐Yuong , Suh Young Sun , Park Jung Je , Kim Sang‐Wook
Published: September 2020

Objectives

The Janus kinase/signal transducer and activator of transcription (JAK–STAT) pathway play a key role in immune modulation, especially in the polarization of T helper cells. JAK inhibitors reduce inflammation by inhibiting the phosphorylation of STAT. We investigated whether a JAK inhibitor, tofacitinib, can reduce inflammation in a mouse model of chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods

An eosinophilic CRSwNP model was induced using 4‐week‐old BALB/c mice. The therapeutic effects of topical tofacitinib were compared with the effects of triamcinolone acetonide (TAC). Polyp formation and eosinophilic infiltration were assessed by histology. Levels of phosphorylated STAT (pSTAT), eosinophil cationic protein, and eotaxin were measured by immunohistochemistry. Gene expression levels of GATA‐3 was measured using quantitative PCR. The production of cytokines in sinonasal tissues, including interleukin IL‐4, IL‐5, IL‐12, and interferon‐γ, were measured using enzyme‐linked immunosorbent assays (ELISA).

Results

Topical tofacitinib administration significantly reduced the number of polyp‐like lesions and the degree of eosinophilic infiltration, with an efficacy comparable with that of systemic TAC administration. Similarly, the levels of pSTAT6, eosinophil cationic protein, and eotaxin decreased with tofacitinib treatment. Tofacitinib decreased the gene expression level of GATA‐3. Lastly, tofacitinib significantly decreased IL‐4 and IL‐5 production to a similar extent as that by systemic or topical TAC administration. Tofacitinib, but not TAC, significantly increased the production of interferon‐γ.

Conclusion

Topical tofacitinib administration may be an effective treatment for eosinophilic CRSwNP by inhibiting phosphorylation of STATs.

Level of Evidence

N/A. Laryngoscope, 131:E1400–E1407, 2021
Cell wall epitopes in grasses of different novel ecosystem habitats on post‐industrial sites
Authors: Milewska‐Hendel Anna , Chmura Damian , Wyrwał Karolina , Kurczyńska Ewa U. , Kompała‐Bąba Agnieszka , Jagodziński Andrzej M. , Woźniak Gabriela
Published: September 2020

The post‐industrial habitats provide previously unknown conditions for plant and vegetation development. We asked the question: do the extreme soil substrate conditions cause differences in chemical composition of cell walls of leaves in three grass species: Calamagrostis epigejos (L.) Roth, Phragmites australis (Cav.) Trin. ex Steud, and Molinia caerulea (L.) Moench? With the use of immunohistochemical methods we determined the spatial distribution of selected pectic and AGP (arabinogalactan proteins) epitopes within leaf tissues of grass species growing in two industrial and control (meadow) habitats. Some post‐industrial habitats increase biodiversity. Fast adaptation and divergence cause phenotypic changes. This process has been recently recorded and is called human‐induced rapid evolutionary changes. The levels of pectins and arabinogalactan proteins increased on the post‐industrial habitats in comparison to the control sites. On control habitat, pectic epitope with galactan chain residues (recognised by the LM5 antibody) was not detected in cell walls of Calamagrostis epigejos leaves, but was abundantly present in Phragmites australis leaves. The pectic epitope with arabinan residues (recognized by LM6 antibody) was less represented in cell walls of Molinia caerulea leaves. AGP epitope, recognised by LM2 antibody, was abundant only in Ph. australis. In Molinia caerulea this epitope was not detected. The AGP epitope recognised by JIM13 antibody was observed in all analysed species. The results obtained revealed the response of grass individuals to different environments: a) varied responses to different soil substratum conditions (novel ecosystems), and b) that this reaction is species‐specific with respect to the analysed cell wall components.
Heat kernels and regularity for rough metrics on smooth manifolds
Authors: Bandara Lashi , Bryan Paul
Published: September 2020

We consider rough metrics on smooth manifolds and corresponding Laplacians induced by such metrics. We demonstrate that globally continuous heat kernels exist and are Hölder continuous locally in space and time. This is done via local parabolic Harnack estimates for weak solutions of operators in divergence form with bounded measurable coefficients in weighted Sobolev spaces.
Shear‐Induced Adhesion of Alternating Peptides Prepared by Ugi Four‐Center Three‐Component Reaction
Authors: Ihsan Abu Bin , Taniguchi Masataka , Koyama Yasuhito
Published: September 2020

The development of new peptide‐based glues has been strongly urged from the viewpoints of industrial applications and biomedical engineering. However, the large‐scale synthesis of polypeptides with an ordered sequence is highly challenging, which strictly restricts materials resources for the research and development of polypeptides. In this work, the framework of adhesive alternating peptides has been designed to be glycine (Gly)‐N‐substituted valine (Val) as the dipeptide repeating sequence, considering the peptapeptide repeating sequence of viscoelastic natural elastin as a motif. The alternating peptides are prepared via three‐component polymerization exploiting Ugi four‐center three‐component reaction as the elemental polymerization reaction. The adhesive strength (SAdh) values of the polymers are evaluated by a shear adhesive test method using two glass plates. Alternating peptides with Gly‐N‐benzylated Val dipeptide repeating units exhibit the optimal adhesive properties such as much higher SAdh than that of conventional fibrin glue and a unique readhesion capability. It is indicated that the remarkably high SAdh would be attributed to the shear‐induced structural change of single polymer chain, the slow relaxation of extended structure, and the weak interchain interactions. Due to the favorable adhesive properties of alternating peptides, these adhesives may be highly suitable for real‐world applications.
Monte Carlo simulated beam quality and perturbation correction factors for ionization chambers in monoenergetic proton beams
Authors: Kretschmer Jana , Dulkys Anna , Brodbek Leonie , Stelljes Tenzin Sonam , Looe Hui Khee , Poppe Björn
Published: September 2020

Purpose

Beam quality correction factors provided in current codes of practice for proton beams are approximated using the water‐to‐air mass stopping power ratio and by assuming the proton beam quality related perturbation correction factors to be unity. The aim of this work is to use Monte Carlo simulations to calculate energy dependent beam quality and perturbation correction factors for a set of nine ionization chambers in proton beams.

Methods

The Monte Carlo code EGSnrc was used to determine the ratio of the absorbed dose to water and the absorbed dose to the sensitive air volume of ionization chambers related to the reference photon beam quality (60Co). For proton beams, the quantity was simulated with GATE/Geant4 for five monoenergetic beam energies between 70 MeV and 250 MeV. The perturbation correction factors for the air cavity, chamber wall, chamber stem, central electrode, and displacement effect in proton radiation were investigated separately. Additionally, the correction factors of cylindrical chambers were investigated with and without consideration of the effective point of measurement.

Results

The perturbation factors were shown to deviate from unity for the investigated chambers, contradicting the assumptions made in dosimetry protocols. The beam quality correction factors for both plane‐parallel and cylindrical chambers positioned with the effective point of measurement at the measurement depth were constant within 0.8%. An increase of the beam quality correction factors determined for cylindrical ionization chambers placed with their reference point at the measurement depth with decreasing energy is attributed to the displacement perturbation correction factors , which were up to 1.045 ± 0.1% for the lowest energy and 1.005 ± 0.1% for the highest energy investigated. Besides , the largest perturbation was found for the chamber wall where the smallest determined was 0.981 ± 0.3%.

Conclusions

Beam quality correction factors applied in dosimetry with cylindrical chambers in monoenergetic proton beams strongly depend on the positioning method used. We found perturbation correction factors different from unity. Consequently, the approximation of ionization chamber perturbations in proton beams by the respective water‐to‐air mass stopping power ratio shall be revised.
Patient acceptability of the physiotherapy first contact practitioner role in primary care: A realist informed qualitative study
Authors: Morris Leah , Moule Pam , Pearson Jennifer , Foster Dave , Walsh Nicola
Published: September 2020

Background

Approximately 30% of general practitioner (GP) consultations are due to musculoskeletal disorders (MSKDs). Physiotherapists are trained to assess, diagnose and treat MSKDs and provide an alternative to GP consultation for primary care patients as first contact physiotherapists (FCPs).

Aim

To explore patient perceived acceptability of the FCP role using realist methods to understand what works for whom, how, why and in what circumstances.

Methods

A realist evaluation was undertaken, which involved three stages: forming the theory area framework; testing the theory framework and refining the programme theory. The theory framework was formed through realist synthesis. Realist interviews tested this framework. Data were collected from two GP practice case study sites and interviews were undertaken at each site. N = 20 participants were interviewed in total. In each practice, this constituted patients (n = 5), GPs (n = 1), FCPs (n = 2), receptionists (n = 1) and practice managers (n = 1). Interview data were analysed against preliminary hypotheses and, where appropriate, new theory areas were created.

Results

The evaluation highlighted that acceptability of the FCP role was influenced by ‘expectations’, ‘accessibility’ and ‘promoting the role’. Whilst some findings were shared by both practices, different contexts resulted in unique practice findings.

Conclusion

Patients were predominantly accepting of FCPs, nevertheless, there was a scope to increase acceptability through an implementation strategy that considered the contexts of the individual patient, as well as wider practice contexts.