bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐point‐NGS analysis of cancer genes in cell‐free DNA of metastatic cancer patients
Authors: Palmieri Maria , Baldassarri Margherita , Fava Francesca , Fabbiani Alessandra , Gelli Elisa , Tita Rossella , Torre Pamela , Petrioli Roberto , Hadijstilianou Theodora , Galimberti Daniela , Cinotti Elisa , Bengala Carmelo , Mandalà Marco , Piu Pietro , Miano Salvatora Tindara , Martellucci Ignazio , Vannini Agnese , Pinto Anna Maria , Mencarelli Maria Antonietta , Marsili Stefania , Renieri Alessandra , Frullanti Elisa
Published: January 2020

Background

Although the efficacy of molecularly target agents in vitro, their use in routine setting is limited mainly to the use of anti‐HER2 and antiEGFR agents in vivo. Moreover, core biopsy of a single cancer site may not be representative of the whole expanding clones and cancer molecular profile at relapse may differ with respect to the primary tumor.

Methods

We assessed the status of a large panel of cancer driver genes by cell‐free DNA (cfDNA) analysis in a cohort of 68 patients with 13 different solid tumors at disease progression. Whenever possible, a second cfDNA analysis was performed after a mean of 2.5 months, in order to confirm the identified clone(s) and to check the correlation with clinical evolution.

Results

The approach was able to identify clones plausibly involved in the disease progression mechanism in about 65% of cases. A mean of 1.4 mutated genes (range 1‐3) for each tumor was found. Point mutations in TP53, PIK3CA, and KRAS and copy number variations in FGFR3 were the gene alterations more commonly observed, with a rate of 48%, 20%, 16%, and 20%, respectively. Two‐points‐Next‐Generation Sequencing (NGS) analysis demonstrated statistically significant correlation between allele frequency variation and clinical outcome (P = .026).

Conclusions

Irrespective of the primary tumor mutational burden, few mutated genes are present at disease progression. Clinical outcome is consistent with variation of allele frequency of specific clones indicating that cfDNA two‐point‐NGS analysis of cancer driver genes could be an efficacy tool for precision oncology.
Proteomic changes in skeletal muscle of aged rats in response to resistance training
Authors: de Sousa Neto Ivo Vieira , Carvalho Marcia Mendes , Marqueti Rita de Cassia , Almeida Jeeser Alves , Oliveira Kléber de S. , Barin Fabrício R. , Petriz Bernardo , de Araújo Heloisa Sobreiro Selistre , Franco Octávio Luiz , Durigan João Luiz Quaglioti
Published: January 2020

Sarcopenia is a multifactorial process defined by loss of strength and skeletal muscle mass, which leads to a reduction in muscle cross‐sectional area (CSA). Although resistance training (RT) has been indicated as a tool to counteract sarcopenia, the protein profile associated with skeletal muscle adaptations remains to be determined. We investigated the effects of 12 weeks of RT on the skeletal muscle proteome profile and CSA of young and older rats. Twenty‐four animals were divided into four groups: young sedentary or trained and older sedentary or trained (six animals per group). A 12‐week RT protocol was performed, which consisted of climbing a vertical ladder. The proteins from the gastrocnemius were analysed by LC‐ESI‐MS/MS. One‐hundred and thirty‐one proteins were identified, of which 28 were assessed between the groups. Ageing induced an increase in proteins associated with the glycolytic pathway, transport and stress response, which represent crucial mechanisms for muscle adaptation. RT upregulated metabolic enzymes, anti‐oxidant activity and transport proteins, besides increasing hypertrophy, regardless of age, suggesting a beneficial adaptation to mitigate age‐related sarcopenia. RT reduced muscle atrophy through the regulation of stress response and by increasing proteins related to energy production and transport, which in turn might protect tissue damage arising from exercise and ageing.

Significance of the study

Protein abundance levels related to the metabolic process and stress response were increased in the aged muscle. RT proved to be an important intervention capable of inducing significant effects on muscle proteome regardless of ageing, due to upregulation of glycolytic enzymes, and anti‐oxidant and transport proteins. This effect could lead to a beneficial adaptation in muscle structure, cellular function and overall homeostasis maintenance. This study contributes to better understanding of the basic biology of ageing and clarifies more profoundly the molecular networks behind physiological adaptations promoted by exercise training. Therefore, the results open new perspectives and insights for studies based on transcriptomics, metabolomics and functional assays.
A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins
Authors: Ban Željka , Griesbeck Stefanie , Tomić Sanja , Nitsch Jörn , Marder Todd B. , Piantanida Ivo
Published: January 2020

Invited for the cover of this issue are the groups of Todd B. Marder at the Julius‐Maximilians‐Universität Würzburg and Ivo Piantanida at the Ruder Boškovic Institute. The image depicts the molecular structure of a bis‐triarylborane‐based chromophore that is simultaneously detecting ds‐DNA and proteins. Read the full text of the article at 10.1002/chem.201903936.
Ring Enlargement of Three‐Membered Heterocycles by Treatment with In Situ Formed Tricyanomethane
Authors: Banert Klaus , Chityala Madhu , Korb Marcus
Published: January 2020

Although the chemistry of elusive tricyanomethane (cyanoform) has been studied during a period of more than 150 years, this compound has very rarely been utilized in the synthesis or modification of heterocycles. Three‐membered heterocycles, such as epoxides, thiirane, aziridines, or 2H‐azirines, are now treated with tricyanomethane, which is generated in situ by heating azidomethylidene‐malonodinitrile in tetrahydrofuran at 45 °C or by adding sulfuric acid to potassium tricyanomethanide. This leads to ring expansion with formation of 2‐(dicyanomethylidene)oxazolidine derivatives or creation of the corresponding thiazolidine, imidazolidine, or imidazoline compounds and opens up a new access to these push–pull‐substituted olefinic products. The regio‐ and stereochemistry of the ring‐enlargement processes are discussed, and the proposed reaction mechanisms were confirmed by using 15N‐labeled substrates. It turns out that different mechanisms are operating; however, tricyanomethanide is always acting as a nitrogen‐centered nucleophile, which is quite unusual if compared to other reactions of this species.
“Will you treat me? I'm suicidal!” The effect of patient gender, suicidal severity, and therapist characteristics on the therapist's likelihood to treat a hypothetical suicidal patient
Authors: Almaliah‐Rauscher Sharon , Ettinger Noa , Levi‐Belz Yossi , Gvion Yari
Published: January 2020

The purpose of our study was to broaden the understanding regarding mental health professionals' willingness to treat and likeliness to refer suicidal patients to other professionals. More specifically, our aim was to examine the effect of the patient's gender and suicidal severity, as well as the mental health professionals' personal and professional characteristics, on the willingness to treat and likeliness to refer. A total of 331 mental health professionals were randomly exposed to one of four case descriptions of a hypothetical patient in a crisis. The cases shared a common background story; however, they differed in terms of the patient's gender and suicidal condition (high vs. low). The exposure was followed by questionnaires aimed to reflect the subject's evaluation of the patient's suicidal severity, the subject's sense of competence and responsibility, willingness to treat or likeliness to refer, emotional contagion, and depression. The results indicate a lower willingness to treat and higher likelihood to refer suicidal patients compared with depressed patients. In addition, subjects exposed to the high suicidality cases showed a greater willingness to treat and refer female patients compared with male patients. A sense of competence was found as the strongest predictor of mental health professionals' willingness to treat and likelihood to refer, and emotional contagion was found as a predictor of likelihood to refer. It is important that mental health professionals be aware of the low tendency to treat suicidal patients especially if they are male. Further research should explore suitable training programmes and their application in the mental health curriculum.
Hitting the Jackpot – development of gas chromatography–mass spectrometry (GC–MS) and other rapid screening methods for the analysis of 18 fentanyl‐derived synthetic opioids
Authors: Gilbert Nicolas , Antonides Lysbeth H. , Schofield Christopher J. , Costello Andrew , Kilkelly Brenda , Cain Alan R. , Dalziel Paula R.V. , Horner Karen , Mewis Ryan E. , Sutcliffe Oliver B.
Published: January 2020

In recent years, the occurrence of synthetic opioid fentanyl and its derivatives has grown significantly in forensic casework. This study presents the synthesis and analysis of 18 fentalogs, selected based on information received from local law enforcement. This study provides colorimetric tests, thin‐layer chromatography (TLC) which can potentially be utilized for presumptive screening of the target compounds, as bulk powders or as trace‐level adulterants. The fully validated confirmatory GC–MS method (employing SIM mode) allows the identification of the 18 derivatives, five commonly encountered controlled substances and four adulterants, within 20 minutes. The cross‐validated method described herein provides a sensitive screening and quantitation method for the illicit (and potentially harmful) components at trace levels (LOD = 0.007–0.822 μg/mL and LOQ = 0.023–2.742 μg/mL respectively). Spectral data [1H‐NMR, 13C‐NMR, 19F‐NMR, FT‐IR, and HRMS] and assignments for the synthesized reference materials are also provided in the Supplementary Information for laboratories engaged in the routine analysis of fentanyl and its derivatives.
Improving Spin Probe Methodologies to Investigate Supramolecular Assemblies
Authors: Lucarini Marco
Published: January 2020

In this report, our work describing the use of spin probes in the field of supramolecular chemistry and how electron spin resonance (EPR) has been used for detecting and identifying supramolecular assemblies is shortly reviewed. Selected examples are reported, including paramagnetic host–guest complexes, self‐assembled systems doped with spin probes, spin‐labelled macrocycles and open shell mechanically interlocked structures (MIMs) such as rotaxanes, in which the dumbbell, the wheel or both are tagged with nitroxide radicals.
Electrochemical Tracing of Butein Using Carbon Nanoparticles Interfaced Electrode Processed from Biowaste
Authors: Kanagavalli Pandiyaraj , Radhakrishnan Sivaprakasam , Pandey Gaurav , Ravichandiran Velayutham , Perumal Pazhani Gururaja , Veerapandian Murugan , Hegde Gurumurthy
Published: January 2020

Nanoparticles of carbon derivatized from pyrolysis of biowaste oil palm leaves were processed as electrochemical transducer material at the interface of glassy carbon electrode. This modified electrode exhibits convincing electron‐transfer property for voltammetric and chronoamperometric quantification of clinically important phytochemical, butein, without the use of external redox mediator and enzyme. A reversible two‐electron transfer redox property observed from butein is distinct at the electrode interface and the current density is found to be superior in phosphate buffered saline electrolyte at pH 7.0. Carbon nanoparticles interfaced electrode system displayed a good stability and sensitivity for butein with a detection limit of 7.6 μM and a dynamic detection concentration ranging from 10 to 100 μM. This bio‐waste translated carbon nanoparticle represent a promising electrode material for various flavonoids detection useful for biological studies.
Mucosal dysbiosis in patients with gastrointestinal follicular lymphoma
Authors: Zeze Keizo , Hirano Atsushi , Torisu Takehiro , Esaki Motohiro , Shibata Hiroki , Moriyama Tomohiko , Umeno Junji , Fujioka Shin , Okamoto Yasuharu , Fuyuno Yuta , Matsuno Yuichi , Kitazono Takanari
Published: January 2020

Because the pathogenesis of gastrointestinal follicular lymphoma (GI‐FL) remains unclear, no standardized treatment strategy has been established. Of the gastrointestinal lymphomas, gastric mucosa‐associated lymphoid tissue lymphomas are strongly associated with Helicobacter pylori; hence, the microbiota may be involved in GI‐FL pathogenesis. However, the association between GI‐FL and the microbiota remains uninvestigated. Therefore, we compared the mucosal microbiotas of GI‐FL patients with those of controls to identify microbiota changes in GI‐FL patients. Mucosal biopsy samples were obtained from the second portion of the duodenum from 20 GI‐FL patients with duodenal lesions and 20 controls. Subsequent 16S rRNA gene sequencing was performed on these samples. QIIME pipeline and LEfSe software were used to analyze the microbiota. The GI‐FL patients had significantly lower alpha diversity (P = .049) than did the controls, with significant differences in the microbial composition (P = .023) evaluated by the beta diversity metrics between the two groups. Comparing the taxonomic compositions indicated that the genera Sporomusa, Rothia, and Prevotella and the family Gemellaceae were significantly less abundant in the GI‐FL patients than in the controls. GI‐FL patients presented altered duodenal mucosal microbial compositions, suggesting that the microbiota might be involved in the GI‐FL pathogenesis.
Downregulation of uPAR promotes urokinase translocation into the nucleus and epithelial to mesenchymal transition in neuroblastoma
Authors: Semina Ekaterina V. , Rubina Kseniya A. , Shmakova Anna A. , Rysenkova Karina D. , Klimovich Polina S. , Aleksanrushkina Natalya A. , Sysoeva Veronika Y. , Karagyaur Maxim N. , Tkachuk Vsevolod A.
Published: January 2020

The urokinase system is involved in a variety of physiological processes, such as fibrinolysis, matrix remodeling, wound healing, and regeneration. Upon binding to its cognate receptor urokinase‐type plasminogen activator receptor (uPAR), urokinase‐type plasminogen activator (uPA) catalyzes the conversion of plasminogen to plasmin and the activation of matrix metalloproteases. Apart from this, uPA–uPAR interaction can lead to the activation of transcription factors, mitogen‐activated protein kinase signaling pathways and RTK cascades. Elevated expression of uPA and uPAR is markedly associated with cancer progression and metastasis and correlates with a poor prognosis in clinics. Targeting the urokinase system has proved to be effective in experimental models in vitro and in vivo, however, in clinics the inhibition of the uPA/uPAR system has fallen short of expectations, suggesting that the question of the functional relevance of uPA/uPAR system is far from being moot. Recently, using CRISPR/Cas9 technology, we have shown that uPAR knockout decreases the proliferation of neuroblastoma Neuro2a cells in vitro. In the present study we demonstrate that uPAR expression is essential for maintaining the epithelial phenotype in Neuro2a cells and that uPAR silencing promotes epithelial‐mesenchymal transition (EMT) and increased cell migration. Accordingly, uPAR knockout results in the downregulation of epithelial markers (E‐cadherin, occludin, and claudin‐5) and in the increase of mesenchymal markers (N‐cadherin, α‐smooth muscle actin, and interleukin‐6). In search of the molecular mechanism underlying these changes, we identified uPA as a key component. Two key insights emerged as a result of this work: in the absence of uPAR, uPA is translocated into the nucleus where it is presumably involved in the activation of transcription factors (nuclear factor κB and Snail) resulting in EMT. In uPAR‐expressing cells, uPAR functions as a uPA “trap” that binds uPA on the cell surface and promotes controlled uPA internalization and degradation in lysosomes.
Impairment of motor but not anxiety‐like behavior caused by the increase of dopamine during development is sustained in zebrafish larvae at later stages
Authors: de Souza Lima Ana Carolina Monteiro , de Alvarenga Kevin Augusto Farias , Codo Beatriz Campos , Sacramento Erika Kelmer , Rosa Daniela Valadão Freitas , Souza Renan Pedra , Romano‐Silva Marco Aurélio , Souza Bruno Rezende
Published: January 2020

Many neuropsychiatric disorders are associated with both dopaminergic (DAergic) and developmental hypotheses. Since DAergic receptors are expressed in the developing brain, it is possible that alterations in dopamine (DA) signaling may impair brain development and consequent behavior. In our previous study, using a zebrafish model, we showed that an increase of DA during the 3 to 5 days postfertilization (dpf) developmental window (an important window for GABAergic neuronal differentiation) affects the motor behavior of 5 dpf larvae. In this study, we set out to determine whether these behavioral alterations were sustained in larvae at older stages (7 and 14 dpf). To test this hypothesis, we chronically treated zebrafish larvae from 3 to 5 dpf with DA. After washing the drug, we recorded and analyzed the first 5 and 30 min of the motor behavior of 5, 7, and 14 dpf subjects. We analyzed mobile episodes, distance traveled, time mobile, distance traveled per mobile episode, time in movement per mobile episode, and distance traveled per time mobile. We showed, once again, that an increase of DA during the 3 to 5 dpf developmental window reduces the number of movement episodes initiated by 5 dpf larvae. We also detected a decrease of other motor behavior parameters in 5 dpf DA‐treated larvae. We observed that these alterations are sustained in the 7 dpf larvae. However, we did not see these general locomotor alterations in the 14 dpf larvae. Moreover, we detected a decrease of distance traveled and an increase of time of locomotion per episode in the first 5 min of behavioral analyses in 14 dpf DA‐treated larvae. To test if the alterations in the first 5 min were due to anxiety‐like behavior, we used a light/dark preference paradigm. We recorded 5dpf, 7dpf, and 14dpf larvae for 5 min and analyzed time of freezing, preference for light or dark, number of entries to the dark, percentage of time in the light. We observed that 5dpf larvae treated with DA showed more freezing, less passages to the dark, and more time spent in the light as compared to their control counterparts. But 7dpf and 14dpf larvae did not show these alterations. Taken overall, therefore, our results suggest that DA does play a role in the development of zebrafish motor behavior, and, furthermore, that some behaviors are more sensitive than others to the effects of DAergic imbalances during development.
Design, synthesis, molecular docking, and biological evaluation of novel selenium containing lumefantrine analogues
Authors: Puthran Divyaraj , Poojary Boja , Nayak Soukhyarani Gopal , Purushotham Nikil , Rasheed Mohammed Shafeeulla , Hegde Hemant
Published: January 2020

A new series of 1‐(9‐benzylidene‐2,7‐dichloro‐9H‐fluoren‐4‐yl)‐2‐(methylselanyl)ethanol was synthesized by a simple Knoevenagel condensation of 1‐(2,7‐dichloro‐9H‐fluoren‐4‐yl)‐2‐(methylselanyl)ethanol with different substituted aromatic aldehydes in basic media. These synthesized compounds were confirmed on the basis of their elemental analyses, infrared (IR), 1H NMR, 13C NMR, and mass spectral data and screened for the antibacterial and antifungal activity. The preliminary antibacterial and antifungal screening revealed that the compounds 8c (dichloro), 8d (fluoro), 8e (chloro), 8i (methoxy), and 8l (methyl) displayed moderate to good activity. The antibacterial results of these compounds were further supported by in silico molecular docking studies, for the inhibition of Escherichia coli MurB enzyme (PDB code: 2MBR), wherein they showed higher binding energy and good affinity towards the active pocket of the enzyme compared with that of the standard drug Ciprofloxacin. Thus, the plausible mechanism of their antibacterial activity was owed to their inhibitory action of the bacterial MurB enzyme.
Evaluation of Fibrosis in Intestinal Failure–Associated Liver Disease in the Sustain Registry
Authors: Wang Jennifer , Wamuo Obinnaya , Micic Dejan
Published: January 2020

Background

Intestinal failure–associated liver disease (IFALD) is one of the leading complications in type III intestinal failure (IF). Early recognition of liver‐fibrosis development in IFALD is crucial to the development of strategies aimed at reducing the risk of complications secondary to IFALD. Our aim was to identify patients with advanced fibrosis using a noninvasive index and to study the risk factors for fibrosis development in the Sustain registry.

Methods

Using the Sustain registry, patients requiring >3 months of parenteral nutrition (PN) support were identified. The presence or absence of advanced fibrosis was identified using the Fibrosis‐4 (FIB‐4) index. Risk factors for the presence of a high FIB‐4 score were identified using univariable logistic regression.

Results

Two hundred seventy‐one adult patients were included. Sixty‐three patients (23.2%) were at risk for advanced fibrosis based on the FIB4‐index. Risk factors for advanced fibrosis included short‐bowel syndrome (odds ratios [ORs]: 1.84; 95% confidence interval [CI], 1.03–3.28), receipt of PN for >1 year (OR: 2.6; 95% CI, 1.46–4.64), receipt of PN for >5 years (OR: 3.05; 95% CI, 1.67–5.59), and days of lipid emulsion use (OR: 1.11; 95% CI, 1–1.24). Small‐intestine–remnant length was inversely associated with advanced fibrosis (OR: 0.97, 95% CI, 0.95–0.99).

Conclusion

Advanced fibrosis, as guided by FIB‐4 index, is associated with known risk factors for IFALD. Therefore, the FIB‐4 index is potentially a useful noninvasive tool for identification of individuals at risk for fibrosis in IFALD. Further studies utilizing a gold‐standard fibrosis assessment will be required to validate these results.
Comparing methane ebullition variability across space and time in a Brazilian reservoir
Authors: Linkhorst Annika , Hiller Carolin , DelSontro Tonya , M. Azevedo Guilherme , Barros Nathan , Mendonça Raquel , Sobek Sebastian
Published: January 2020

The potent greenhouse gas methane (CH4) is readily emitted from tropical reservoirs, often via ebullition (bubbles). This highly stochastic emission pathway varies in space and time, however, hampering efforts to accurately assess total CH4 emissions from water bodies. We systematically studied both the spatial and temporal scales of ebullition variability in a river inflow bay of a tropical Brazilian reservoir. We conducted multiple highly resolved spatial surveys of CH4 ebullition using a hydroacoustic approach supplemented with bubble traps over a 12‐month and a 2‐week timescale to evaluate which scale of variation was more important. To quantify the spatial and temporal variability of CH4 ebullition, we used the quartile coefficients of dispersion at each point in space and time and compared their frequency distributions across the various temporal and spatial scales. We found that CH4 ebullition varied more temporally than spatially and that the intra‐annual variability was stronger than daily variability within 2 weeks. We also found that CH4 ebullition was positively related to water temperature increase and pressure decrease, but no consistent relationship with water column depth or sediment characteristics was found, further highlighting that temporal drivers of emissions were stronger than spatial drivers. Annual estimates of CH4 ebullition from our study area may vary by 75–174% if ebullition is not resolved in time and space, but at a minimum we recommend conducting spatially resolved measurements at least once during each major hydrologic season in tropical regions (i.e., in dry and rainy season when water levels are falling and rising, respectively).
A Novel Model Integration Network Inference Algorithm with Clustering and Hub Genes Finding
Authors: Li Wenchao , Zhang Wei , Zhang Jianming
Published: January 2020

Gene regulatory network Inference with high accuracy based on gene expression data sets is one of the most challenging problems in computational biology. To improve the accuracy of gene regulatory network inference and find hub genes, we proposed a novel model integration network inference method with clustering and hub genes finding called MINICHG. The method is divided into three main steps: (1) using single models inference results based on three machine learning algorithms to construct feature matrix; (2) using k‐means to cluster gene pairs according to feature matrix; (3) hub genes finding. MINICHG integrates RF(Random Forest), GBDT (Gradient Boosting Decision Tree) and Pearson Correlation results with a novel weighted strategy in a semi‐unsupervised way. The designed optimization scheme in MINICHG considering sparse gold standard data characteristics is suitable for most gene regulatory network reconstruction. We evaluated the proposed method on simulated data sets from five Dream4 multifactorial data sets and Dream5 in silico data set and real data set from E.coli. The performance was better than other network inference methods with high accuracy and robustness.
Challenges and Learning Opportunities of Pre‐Registration Physiotherapy Placements in First Contact Settings: The Perspectives of Musculoskeletal First Contact Physiotherapists
Authors: Bassett Andrew Mark , Jackson Jo
Published: January 2020

Objectives

As musculoskeletal first contact physiotherapy is rolled out into primary healthcare in Britain, this could offer up new practice‐based educational opportunities for pre‐registration physiotherapy students. Thus, the present study sought to explore the perceived challenges and learning opportunities of pre‐registration physiotherapy placements in musculoskeletal first contact physiotherapy settings from first contact physiotherapists' perspectives.

Methods

Using a qualitative strategy, 15 musculoskeletal first contact physiotherapists from different geographical locations in Britain, participated in telephone mediated semi‐structured interviews. Participants were self‐selected through a Chartered Society of Physiotherapy fortnightly bulletin and online forum for first contact physiotherapists, or recruited via snowball sampling. Interview transcripts were analysed according to framework analysis ‐ and the findings were member‐checked by proxy.

Results

Three core themes emerged: operational challenges, challenges for pre‐registration physiotherapy students and learning opportunities for pre‐registration physiotherapy students. Operational challenges included: ensuring sufficient support from first contact physiotherapy practice educators; financial cost implications of placements, and; lack of capacity within the existing first contact physiotherapy workforce to provide placements. Challenges for physiotherapy students involved: time pressures and stressors of a first contact physiotherapy placement; identifying red flags, and; complexity of patient presentations. Identified learning opportunities for physiotherapy students were: experience of a specialised physiotherapy role in a primary healthcare setting; bringing awareness of first contact physiotherapy as a potential career pathway, and; experience multidisciplinary team working in primary care.

Conclusions

By seeking the perspectives of first contact physiotherapists, this study provides the first step for the development of placements in an emerging practice area.
SETTING THE TONE FOR 2020
Authors: Atwood Stephen P.
Published: January 2020

Happy New Year, and welcome to the first 2020 issue of ID. I sincerely hope that all of you found time to be with family and recharge yourselves over the holiday period. In past editorials, I've spoken about the value of taking downtime or scheduling time off for personal endeavors.
Mechanical behavior of porous solid considering mesoscopic elastic buckling
Authors: Zhang Hao‐Yue , Hu Xiao‐Xong , Zhao Gao‐Feng
Published: January 2020

In this work, the elastic buckling of porous solids was investigated using a lattice spring model (LSM). The capability of the LSM to solve elastic buckling problems was comprehensively verified by comparing well‐established numerical and analytical solutions. Following this, the buckling of a porous solid was studied, in which two porous structures were considered, ie, the random porous model and the Voronoi porous model. The results reveal that both the porosity and the shape of the pores influence the elastic buckling bearing capacity of the porous solid. Finally, the mechanical responses of a porous solid with an extra high porosity (0.85) were numerically investigated. Our numerical results demonstrated that the nonlinear elastic response of the porous solid might come from its mesoscale elastic buckling. This work shows the ability and promise of using the LSM as a fundamental numerical tool for the deep investigation of the buckling mechanical behavior of porous solids.
Interpersonal leader responses to secondary trauma in nonprofit human service organizations
Authors: Silard Anthony
Published: January 2020

Secondary trauma is concerned with the intrapersonal affective responses an individual can experience during or subsequent to an interaction(s) with another person who recounts his or her personal stories of abuse, trauma, or disempowerment. Secondary trauma can engender a host of detrimental intrapersonal effects on nonprofit staff who express empathy toward clients experiencing primary trauma. I explore the interpersonal‐level responses to secondary trauma‐affected staff available to the leaders of nonprofit human service organizations. These secondary trauma‐sensitive leader behaviors, I theorize, will reduce the prevalence of secondary trauma in nonprofit organizations and generate follower engagement.
LIGHT/TNFSF14 regulates estrogen deficiency‐induced bone loss
Authors: Brunetti Giacomina , Storlino Giuseppina , Oranger Angela , Colaianni Graziana , Faienza Maria F , Ingravallo Giuseppe , Di Comite Mariasevera , Reseland Janne E , Celi Monica , Tarantino Umberto , Passeri Giovanni , Ware Carl F , Grano Maria , Colucci Silvia
Published: January 2020

Bone loss induced by ovariectomy is due to the direct activity on bone cells and mesenchymal cells and to the dysregulated activity of bone marrow cells, including immune cells and stromal cells, but the underlying mechanisms are not completely known. Here, we demonstrate that ovariectomy induces the T‐cell co‐stimulatory cytokine LIGHT, which stimulates both osteoblastogenesis and osteoclastogenesis by modulating osteoclastogenic cytokine expression, including TNF, osteoprotegerin, and the receptor activator of nuclear factor‐κB ligand (RANKL). Predictably, LIGHT‐deficient (Tnfsf14−/−) mice are protected from ovariectomy‐dependent bone loss, whereas trabecular bone mass increases in mice deficient in both LIGHT and T and B lymphocytes (Rag
−/−Tnfsf14
−/−) and is associated with an inversion of the TNF and RANKL/OPG ratio. Furthermore, women with postmenopausal osteoporosis display high levels of LIGHT in circulating T cells and monocytes. Taken together, these results indicate that LIGHT mediates bone loss induced by ovariectomy, suggesting that patients with postmenopausal osteoporosis may benefit from LIGHT antagonism. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Radiation‐induced tissue damage and response
Authors: McBride William H , Schaue Dörthe
Published: January 2020

Normal tissue responses to ionizing radiation have been a major subject for study since the discovery of X‐rays at the end of the 19th century. Shortly thereafter, time–dose relationships were established for some normal tissue endpoints that led to investigations into how the size of dose per fraction and the quality of radiation affected outcome. The assessment of the radiosensitivity of bone marrow stem cells using colony‐forming assays by Till and McCulloch prompted the establishment of in situ clonogenic assays for other tissues that added to the radiobiology toolbox. These clonogenic and functional endpoints enabled mathematical modeling to be performed that elucidated how tissue structure, and in particular turnover time, impacted clinically relevant fractionated radiation schedules. More recently, lineage tracing technology, advanced imaging and single cell sequencing have shed further light on the behavior of cells within stem, and other, cellular compartments, both in homeostasis and after radiation damage. The discovery of heterogeneity within the stem cell compartment and plasticity in response to injury have added new dimensions to the consideration of radiation‐induced tissue damage. Clinically, radiobiology of the 20th century garnered wisdom relevant to photon treatments delivered to a fairly wide field at around 2 Gy per fraction, 5 days per week, for 5–7 weeks. Recently, the scope of radiobiology has been extended by advances in technology, imaging and computing, as well as by the use of charged particles. These allow radiation to be delivered more precisely to tumors while minimizing the amount of normal tissue receiving high doses. One result has been an increase in the use of schedules with higher doses per fraction given in a shorter time frame (hypofractionation). We are unable to cover these new technologies in detail in this review, just as we must omit low‐dose stochastic effects, and many aspects of dose, dose rate and radiation quality. We argue that structural diversity and plasticity within tissue compartments provides a general context for discussion of most radiation responses, while acknowledging many omissions. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Autopsy and postnatal follow‐up of prenatally diagnosed ventricular outpouchings
Authors: Zheng Min , Sun Lin , Liu Xiaowei , Wang Xin , He Yihua
Published: January 2020

Objectives

Prenatal ventricular outpouchings (VOs), which include congenital ventricular aneurysms (CAs) and congenital ventricular diverticula (CD), are very rare. We describe the features and outcomes of prenatal VOs diagnosed over a 4‐year period.

Methods

Retrospective cohort study of cases of prenatal diagnoses of CAs and CD at our center between June 2014 and January 2018. The prenatal and postnatal echocardiogram data were reviewed, and telephone follow‐up was conducted of liveborn cases.

Results

A total of 25 VOs were identified. Two were lost to follow‐up, 15 chose termination of pregnancy, and eight resulted in livebirths. Only two cases underwent autopsy: Histopathology showed that the CA wall was substituted by collagen fibers. At follow‐up, none of the eight liveborn babies experienced adverse events, and three VOs near the tricuspid annulus almost disappeared, though one was extremely large.

Conclusions

In our center, all liveborn babies with VO had good prognoses. We hypothesize that VOs located near the right ventricular annulus may be caused by prenatally unbalanced pressure, given their decrease in size after birth when the right heart pressure declines.
Pneumonia‐related ideations, care‐seeking, and treatment behaviors among children under 2 years with pneumonia symptoms in northwestern Nigeria
Authors: Anaba Udochisom , Hutchinson Paul L. , Abegunde Dele , White Johansson Emily
Published: January 2020

Background

Prompt treatment of pediatric pneumonia symptoms is a cornerstone of child survival programs but remains a challenge in Nigeria. Psychosocial influences, or ideations, directly influence pathways to care but have not been previously measured or examined for pediatric pneumonia.

Methods

A two‐stage cluster‐sample cross‐sectional population‐based survey was conducted in Kebbi, Sokoto, and Zamfara States in September 2019. Across 108 enumeration areas, all households were enumerated to census pregnant women and randomly sample women with children under 2 years (“under‐twos”) for inclusion. Respondents were asked about pediatric pneumonia and other health‐related behaviors and ideations developed using the Ideation Model of Strategic Communication and Behavior Change. Prevalence ratios for predictors of care‐seeking from formal medical sources and antibiotic treatment for pneumonia symptoms among under‐twos were calculated using mixed‐effects Poisson regression models with robust error variance.

Results

Among 350 under‐twos with pneumonia symptoms, 33.8% were taken to formal medical care and 38.0% used antibiotics. Women who positively viewed treatment efficacy and those who positively viewed health services quality had 1.35 (95% CI: 1.00‐1.82; P = .050) and 2.13 (95% CI: 1.35‐3.35; P = .001) times higher likelihood of attending formal medical sources, while women viewing peers as mostly attending drug shops had 29% lower likelihood. Perceived treatment efficacy and illness susceptibility were also significant predictors for antibiotic use.

Conclusions

Program interventions focusing on increasing pneumonia knowledge alone may not be sufficient to improve care‐seeking and treatment rates and should expand to address perceived and actual poor‐quality health services and maternal beliefs about treatment efficacy, social norms, illness severity, and susceptibility.
The anti‐anaphylactoid effects of Piperine through regulating MAS‐related G protein‐coupled receptor X2 activation
Authors: Qiao Chuchu , Hu Shiling , Che Delu , Wang Jue , Gao Jiapan , Ma Ruiping , Jiang Wenjun , Zhang Tao , Liu Rui
Published: January 2020

Mast cells play an important role in inflammatory and allergic diseases. MAS‐related G protein‐coupled receptor X2 (MRGPRX2) is a novel G protein‐coupled receptor in mast cells that mediates drug‐induced anaphylactoid reactions. Piperine has been reported to have anti‐inflammatory and anti‐allergic pharmacological activities. However, whether the pharmacological effects are regulated by MRGPRX2 has not yet been reported. The purpose of this study was to assess the anti‐anaphylactoid effect of Piperine and to explore its potential mechanism. The anti‐anaphylactoid effect of Piperine was assessed by an in vivo mouse hindpaw extravasation model. Mast cell intracellular calcium mobilization was measured by a calcium imaging assay. An enzyme immunoassay was used to evaluate the release of pro‐inflammatory factors from stimulated mast cells. Activated mast cell related signals were assessed by western blot. A cell membrane chromatography assay was used to determine the binding characteristics of Piperine and MRGPRX2. The results showed that Piperine suppressed mast cell intracellular Ca2+ mobilization, inhibited cytokines and chemokines release, and down‐regulated the phosphorylation level of phospholipase Cγ1, protein kinase C, inositol 1,4,5‐triphate receptor, P38, protein kinase B, and ERK. Meanwhile, Piperine can bind to MRGPRX2 as a specific antagonist. Hence, Piperine can be served as a novel therapeutic drug candidate for MRGPRX2‐mediated anaphylactoid reactions.
Ginger and avocado as nutraceuticals for obesity and its comorbidities
Authors: Tramontin Natalia dos Santos , Luciano Thais F. , Marques Scherolin de Oliveira , de Souza Claudio T. , Muller Alexandre P.
Published: January 2020

Obesity is a worldwide epidemic and is one of the factors involved in the etiology of type 2 diabetes mellitus. Obesity induces low‐grade inflammation and oxidative stress. The treatment for obesity involves changes in diet, physical activity, and even medication and surgery. Currently, the use of nutraceutical compounds is associated with health benefits. Ginger and avocado are used for many people all around the world; however, its effect as a nutraceutical compound is less known by the general population. For this reason, we searched information of the literature to point its effects on distinct mechanisms of defense against the obesity its comorbidities. The present review aimed showing that these nutraceuticals may be useful in obesity treatment. Reports have shown that ginger and avocado induce antioxidant and anti‐inflammatory effects by improving enzymatic activity and modulating obesity‐related impairments in the anti‐inflammatory system in different tissues, without side effects. Furthermore, ginger and avocado were found to be effective in reversing the harmful effects of obesity on blood lipids. In conclusion, on the basis of the positive effects of ginger and avocado in in vitro, animal, and human studies, these nutraceuticals may be useful in obesity treatment.
The multifarious roles of heterogeneous ribonucleoprotein A1 in viral infections
Authors: Kaur Ramandeep , Lal Sunil K.
Published: January 2020

Viruses are obligate parasites known to interact with a wide variety of host proteins at different stages of infection. Current antiviral treatments target viral proteins and may be compromised due to the emergence of drug resistant viral strains. Targeting viral‐host interactions is now gaining recognition as an alternative approach against viral infections. Recent research has revealed that heterogeneous ribonucleoprotein A1, an RNA‐binding protein, plays an essential functional and regulatory role in the life cycle of many viruses. In this review, we summarize the interactions between heterogeneous ribonucleoprotein A1 (hnRNPA1) and multiple viral proteins during the life cycle of RNA and DNA viruses. hnRNPA1 protein levels are modulated differently, in different viruses, which further dictates its stability, function, and intracellular localization. Multiple reports have emphasized that in Sindbis virus, enteroviruses, porcine endemic diarrhea virus, and rhinovirus infection, hnRNPA1 enhances viral replication and survival. However, in others like hepatitis C virus and human T‐cell lymphotropic virus, it exerts a protective response. The involvement of hnRNPA1 in viral infections highlights its importance as a central regulator of host and viral gene expression. Understanding the nature of these interactions will increase our understanding of specific viral infections and pathogenesis and eventually aid in the development of novel and robust antiviral intervention strategies.
Nonlinear sliding sector design for multi‐input systems with application to helicopter control
Authors: Ozcan S. , Salamci M. U. , Nalbantoglu V.
Published: January 2020

The ability of helicopters to hover and land vertically has spurred an interesting field of research on the development of autonomous flight for these rotatory wing aircrafts. Linear control theory with gain scheduling, which is based on linearizing the system at the equilibrium points, dominated the helicopter autopilot design. Unlike the linear cascaded autopilot structure used in the existing literature, this paper uses state‐dependent linear like structure, including rate‐limited actuator dynamics, with cascaded autopilot topology. This approach allows nonlinear control laws to be implemented throughout the entire flight envelope, providing satisfactory robustness and stability over the various parameter uncertainties and time delays. The cascaded autopilot topology with nonlinear dynamical equations contains a new sliding sector control (SSC) mechanism which is derived for multi‐input nonlinear dynamical systems. The proposed SSC structure for multi‐input nonlinear systems is used in the inner loop of the cascaded autopilot system where the fastest dynamics are required to be controlled for rapid changes in the helicopter dynamical characteristics which enables one to stabilize the helicopter over a wide range of flight conditions. The proposed cascaded autopilot topology with the new SSC mechanism is tested in simulations to assess its robustness and stability properties. To establish its feasibility, the proposed control method is replaced with a suboptimal control method, namely state‐dependent differential Riccati equation (SDDRE) method, for the inner loop and the results of the proposed control architecture are compared with those of SDDRE method.
Developing and supporting the Next Generation Science Standards: The role of policy entrepreneurs
Authors: Hardy Ian , Campbell Todd
Published: January 2020

Drawing upon interviews with key actors involved in the development of and support for the Next Generation Science Standards (NGSS) in the United States, this article shows how a potentially controversial reform came to be actively supported by senior educators. We utilize Kingdon's (2003, Agendas, alternatives, and public policies, 2nd ed.) concept of policy entrepreneurs to highlight how these educators navigated a complex and contested policy and political environment. We reveal the cogency of Kingdon's argument that specific agendas are dependent upon the coupling of particular problems with relevant policies and political support. However, at particular moments in time, the findings also show how those engaged in the NGSS found it beneficial to uncouple federal accountability agendas that would have limited support for the NGSS.
Chemically Prelithiated Hard‐Carbon Anode for High Power and High Capacity Li‐Ion Batteries
Authors: Shen Yifei , Qian Jiangfeng , Yang Hanxi , Zhong Faping , Ai Xinping
Published: January 2020

Hard carbons (HC) have potential high capacities and power capability, prospectively serving as an alternative anode material for Li‐ion batteries (LIB). However, their low initial coulombic efficiency (ICE) and the resulting poor cyclability hinder their practical applications. Herein, a facile and effective approach is developed to prelithiate hard carbons by a spontaneous chemical reaction with lithium naphthalenide (Li‐Naph). Due to the mild reactivity and strong lithiation ability of Li‐Naph, HC anode can be prelithiated rapidly in a few minutes and controllably to a desirable level by tuning the reaction time. The as‐formed prelithiated hard carbon (pHC) has a thinner, denser, and more robust solid electrolyte interface layer consisting of uniformly distributed LiF, thus demonstrating a very high ICE, high power, and stable cyclability. When paired with the current commercial LiCoO2 and LiFePO4 cathodes, the assembled pHC/LiCoO2 and pHC/LiFePO4 full cells exhibit a high ICE of >95.0% and a nearly 100% utilization of electrode‐active materials, confirming a practical application of pHC for a new generation of high capacity and high power LIBs.
Scanning Probe Microscopy of Topological Structure Induced Electronic States of Graphene
Authors: Li Shichao , Liu Mengxi , Qiu Xiaohui
Published: January 2020

Graphene, as the first emerging 2D material, has attracted considerable attention because of its remarkable physical properties and potential applications in future electronic devices. Due to its planar structure and monoatomic thickness, graphene is susceptible to the presence of structural and topological defects in lattices, which can have a pronounced influence on the electrical, optical, thermal, and magnetic properties of this carbon allotrope. To unravel the structural disorders at the atomic scale, characterization techniques such as scanning tunneling microscopy (STM) and atomic force microscopy (AFM) have been widely employed. These techniques enable atomically resolved visualization of the lattice imperfection in graphene, as well as a simultaneous interrogation of the electronic states associated with the structural perturbations. This short review highlights the recent advances in the application of STM and AFM for investigating various defects in graphene, including vacancies, substitutional dopants, non‐hexagonal rings, 1D homo‐ and hetero‐boundaries, and stacking misorientation and faults at interlayers. The understanding of the intrinsic properties of structural and topological defects in graphene is essential for developing graphene‐based functional materials and related devices.