bluuebunny/crossref_metadata_2025 huggingface dataset:
Weighing the influence of race and obesity on outcomes in patients with early‐stage breast cancer
Authors: Taylor Caitlin E. , Meisel Jane Lowe
Published: December 2020

The association between obesity and an increased risk of several cancers, including postmenopausal breast cancer, is well established. In this issue of Cancer, Nyrop et al evaluate disparities in obesity and the possible treatment implications of such disparities among Black and White women with early‐stage, hormone receptor–positive breast cancer. The authors highlight the importance of recognizing racial disparities among obesity trends and emphasize the need to address comorbidities early in breast cancer management for patients of all racial and ethnic backgrounds.
Decorating a Loose Defect‐free Hybrid Selective Layer on a Smooth Intermediary: An Effective Way for Unexpected Performances of Nanofiber‐based Forward Osmosis Membranes
Authors: Li Nan , Han Yu , Yu Feiyue , Wang Wei , Liu Qin , Qian Xiaoming , Xu Zhiwei , Deng Hui , Shan Mingjing
Published: December 2020

A novel composite forward osmosis (FO) membrane was fabricated by introducing a chitosan (CS) sublayer between nanofibers and polyamide (PA) layer, which was beneficial to forming thin and defect‐free PA layer and improved binding strength between substrate and the selective layer. Results exhibited low reverse salt flux (0.73 gMH) while maintained high water flux (85.4 LMH), which were better than that in other reports. In order to further improve permeability of membranes, oxidized multiwall carbon nanotubes (OMWNTs) were added into PA layer based on the optimized sublayer. The crosslinking degree of PA layer was reduced, leading to loose PA layers, which promoted the increase of water flux. After modifying, water flux reached 96.9 LMH without sacrificing salt rejection. It was worth mentioning that PAN/CS composite FO membrane, which could adjust microstructure of support layer and selective layer respectively, may provide a promising way for preparing membranes with anticipated separation performance.
Simultaneous Ca2+ Imaging and Optogenetic Stimulation of Cortical Astrocytes in Adult Murine Brain Slices
Authors: Balachandar Lakshmini , Montejo Karla A. , Castano Eleane , Perez Melissa , Moncion Carolina , Chambers Jeremy W. , Lujan J. Luis , Diaz Jorge Riera
Published: December 2020

Astrocytes are actively involved in a neuroprotective role in the brain, which includes scavenging reactive oxygen species to minimize tissue damage. They also modulate neuroinflammation and reactive gliosis prevalent in several brain disorders like epilepsy, Alzheimer's, and Parkinson's disease. In animal models, targeted manipulation of astrocytic function via modulation of their calcium (Ca2+) oscillations by incorporating light‐sensitive cation channels like Channelrhodopsin‐2 (ChR2) offers a promising avenue in influencing the long‐term progression of these disorders. However, using adult animals for Ca2+ imaging poses major challenges, including accelerated deterioration of in situ slice health and age‐ related changes. Additionally, optogenetic preparations necessitate usage of a red‐shifted Ca2+ indicator like Rhod‐2 AM to avoid overlapping light issues between ChR2 and the Ca2+ indicator during simultaneous optogenetic stimulation and imaging. In this article, we provide an experimental setting that uses live adult murine brain slices (2‐5 months) from a knock‐in model expressing Channelrhodopsin‐2 (ChR2(C128S)) in cortical astrocytes, loaded with Rhod‐2 AM to elicit robust Ca2+ response to light stimulation. We have developed and standardized a protocol for brain extraction, sectioning, Rhod‐2 AM loading, maintenance of slice health, and Ca2+ imaging during light stimulation. This has been successfully applied to optogenetically control adult cortical astrocytes, which exhibit synchronous patterns of Ca2+ activity upon light stimulation, drastically different from resting spontaneous activity. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Experimental preparation, setup, slice preparation and Rhod‐2 AM staining

Basic Protocol 2: Image acquisition and analysis
Green Preparation of Thin Films of Polybenzimidazole on Flat and Hollow Fiber Supports: Application to Hydrogen Separation
Authors: Sánchez‐Laínez Javier , Etxeberria‐Benavides Miren , David Oana , Téllez Carlos , Coronas Joaquín
Published: December 2020

This work shows the preparation of thin films, with thickness from 70 nm to 1 μm, of meta‐polybenzimidazole (m‐PBI) on polyimide P84 supports. Ethanolic solutions of m‐PBI were used to coat flat and hollow fiber supports of asymmetric P84 with m‐PBI in a process where the coating and drying was performed at room temperature. A solution of NaOH in EtOH allowed the dissolution of the m‐PBI powder, providing the perfect coating solution to build thin films of m‐PBI without damaging the polymeric support. It also meant a green alternative, avoiding the use of toxic solvents, such as dimethylacetamide. The resulting membranes have been tested for the separation of H2 mixtures at high temperature at different setups to allow checking their reproducibility. With 100 nm thickness the membranes showed their best gas separation performance. For flat membranes at 180 °C and 3 bar feed pressure a H2 permeance of 48.5 GPU was obtained, with respective H2/CO2 and H2/N2 selectivities of 33.3 and 55.8. Besides, the hollow fibers under a feed pressure of 6 bar and tested at the same temperature showed near 90 GPU of H2 with a H2/CO2 selectivity of 13.5 in the one‐fiber module and over 39 GPU of H2 with a H2/CO2 selectivity of 20.2 in the five‐fiber module. Finally, the stability of the membranes was proved for 22 days at 180 °C.
Rapid detection of SARS‐CoV‐2‐specific memory T‐cell immunity in recovered COVID‐19 cases
Authors: Lineburg Katie E , Srihari Sriganesh , Altaf Mohammed , Swaminathan Srividhya , Panikkar Archana , Raju Jyothy , Crooks Pauline , Ambalathingal George R , Martins Jose Paulo , Matthews Katherine K , Neller Michelle A , Khanna Rajiv , Smith Corey
Published: December 2020

Objectives

There is emerging evidence that SARS‐CoV‐2‐specific memory T‐cell responses are likely to provide critical long‐term protection against COVID‐19. Strategies to rapidly assess T‐cell responses are therefore likely to be important for assessing immunity in the global population.

Methods

Here, we have developed a rapid immune‐monitoring strategy to assess virus‐specific memory T‐cell responses in the peripheral blood of COVID‐19 convalescent individuals. We validated SARS‐CoV‐2‐specific memory T‐cell responses detected in whole blood using in vitro expansion with SARS‐CoV‐2 proteins.

Results

T‐cell immunity characterised by the production of IFN‐γ and IL‐2 could be consistently detected in the whole blood of recovered participants. T cells predominantly recognised structural SARS‐CoV‐2 proteins. In vitro expansion demonstrated that while CD8+ T cells recognised nucleocapsid protein, spike protein and ORF3a, CD4+ T cells more broadly targeted multiple SARS‐CoV‐2 proteins.

Conclusion

These observations provide a timely monitoring approach for identifying SARS‐CoV‐2 cellular immunity and may serve as a diagnostic for the stratification of risk in immunocompromised and other at‐risk individuals.
Determination of antiretroviral drugs for buyers’ club in Switzerland using capillary electrophoresis methods
Authors: Guichard Nicolas , Tobolkina Elena , El Morabit Lamyae , Bonnabry Pascal , Vernaz Nathalie , Rudaz Serge
Published: December 2020

Human immunodeficiency virus‐acquired immunodeficiency syndrome continues to be a major global public health issue, having claimed almost 33 million lives to date. Due to the high cost of antiretroviral treatment, access to these drugs remains difficult for vulnerable populations, such as migrants and people living in prisons, who often do not have health insurance. These factors lead to poorer health outcomes and higher transmission rates. The personal importation scheme for unapproved generics from foreign countries is one option to access affordable human immunodeficiency virus treatment. However, the risk of importing falsified medicine remains high, and the quality control of unapproved drugs is lacking. In this context, three CE methods for the analysis of nine antiviral drugs found in commercial pharmaceutical formulations were evaluated. The selected compounds were emtricitabine, tenofovir disoproxil, tenofovir alafenamide, rilpivirine, efavirenz, raltegravir, dolutegravir, abacavir, and lamivudine. The developed methods were successfully applied to determine the active pharmaceutical ingredients of commercial formulations and unapproved generics. The quality control of unapproved generics by CE is an attractive approach due to its good standard of quality, low cost, ecofriendliness, and ease of implementation.
Measurement of the Temperature Influence on the Current Distribution in Lithium‐Ion Batteries
Authors: Paarmann Sabine , Cloos Lisa , Technau Jakob , Wetzel Thomas
Published: December 2020

Herein, a comprehensive experimental studies on the interdependence of temperature and current distribution in lithium‐ion batteries is presented. Initially, a method for measuring the current distribution on a single cell is presented and verified by comparison with measurements on a parallel circuit. The presented method is straightforward and robust. It provides accurate quantitative and reproducible results. They are consistent with literature and show a higher current with increasing temperature. This temperature dependency is more pronounced at lower temperatures. Furthermore, it offers the opportunity to determine the influence of the temperature on the current distribution more precisely. Finally, this publication correlates the normalized current with temperature quantitatively using an Arrhenius‐like approach according to .
New approach to an overlooked flap: Technique to augment venous drainage of the infrahyoid myocutaneous flap
Authors: Lyu Xiaoming , Liu Shuming , Zheng Lei , Huang Mingwei , Zhang Jianguo , Zhang Jie
Published: December 2020

Background

To describe a technique in which the anterior jugular vein is preserved in the infrahyoid myocutaneous flap (IHMCF) to augment skin paddle venous drainage.

Methods

From April 2018 to December 2019, 14 patients with primary oral cancer underwent radical resection and IHMCF reconstruction. Three‐dimensional reconstruction of the anterior jugular vein was used to assess the venous drainage of the skin paddle preoperatively. The anterior jugular vein was preserved during dissection of the flap. Healing of the recipient and donor sites was observed.

Results

Total flap necrosis occurred in one patient and marginal skin paddle necrosis occurred in one patient. No flap complications occurred in the other 12 patients.

Conclusion

This new approach to augment venous drainage of the IHMCF appears to be effective for decreasing risk of flap necrosis.
Dysbiosis of the endometrial microbiota and its association with inflammatory cytokines in endometrial cancer
Authors: Lu Wanting , He Fei , Lin Zheng , Liu Shuang , Tang Li , Huang Yuxiu , Hu Zhijian
Published: December 2020

The underlying molecular mechanisms involved in the pathogenesis of endometrial cancer (EC) are still not well understood. Our goal was to investigate the composition of the endometrial microbiota and the association with inflammatory cytokines in EC. Endometrial microbiota profiles of women with EC (n = 25) and benign uterine lesions (BUL, n = 25) were assessed by 16S ribosomal RNA gene amplicon sequencing. The expression levels of interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), and interleukin‐17 (IL‐17) mRNA and protein in the endometrial tissues of the two groups were determined by real‐time quantitative polymerase chain reaction and Western blot, respectively. There were significant differences in alpha diversity based on the observed operational taxonomic units (P = .002), Pielou evenness (P = .001), and Shannon index (P < .001) between EC and BUL groups. Significant differences were also found in Bray‐Curtis (P = .001) and unweighted UniFrac (P = .001) beta diversity measures between the two groups. At the genus level, Micrococcus was more abundant in the EC group. Pseudoramibacter_Eubacterium, Rhodobacter, Vogesella, Bilophila, Rheinheimera, and Megamonas were enriched in the BUL group. There were no differences in IL‐8 and IL‐17 protein levels between the two groups, except IL‐6 protein levels. However, the mRNA expression levels of IL‐6, IL‐8, and IL‐17 were significantly different. Moreover, the relative abundances of Micrococcus was positively correlated with IL‐6, and IL‐17 mRNA levels. In conclusion, our results suggested that dysbiosis of endometrial microbiota and the inflammatory cytokines were associated with Micrococcus in EC patients, which might be useful for exploration of the mechanism between the endometrial microbiota and inflammatory responses in future studies.
Social interactions and social preferences in social networks
Authors: Hsieh Chih‐Sheng , Lin Xu
Published: December 2020

We study social interactions when individuals hold altruistic preferences in social networks. Rich network features can be captured in the resulting best response function. The inward network links provide unique information for identifying the altruism effect. We demonstrate that the often ignored altruism is another serious confounding factor of peer effects. Specifically, the estimates of peer effects are approximately 36% smaller after taking into account social preferences. Furthermore, we could identify two types of effects caused by peers' outcomes: the spillover effects and the externality effects, which is impossible in a conventional social interactions model based on the self‐interest hypothesis.
Molecular dynamic simulations, GIAO‐NMR and TD‐DFT spectroscopy analyze for zwitterionic isoleucine (ILE)N, 1 ≤ N ≤ 6, in water solution
Authors: Mendanha Karinna , Prado Richard Costa , Oliveira Leonardo Bruno Assis , Colherinhas Guilherme
Published: December 2020

In this article, we investigate the effects of the isoleucine (ILE)N amino acid chain growth, N = 1.0.6, the ILE conformational effect as well as the solvent presence on the electrical and magnetic spectroscopic properties when these compounds are in aqueous solution. Computational molecular dynamics simulations were performed to include the solvent medium and generate uncorrelated configurations involving solute‐solvent structures. The charge point model for solvent was used to obtain the results for quantum mechanical calculation, in special DFT calculations, for (ILE)N structures. Our results for the magnetic shielding constant obtained via GIAO‐DFT‐NMR calculations show that there is evidence of a magnetic behavior that characterizes the number of peptide bonds and, therefore, how the N isoleucine polypeptide chain is composed. TD‐DFT results also show an absorption band shift to larger wavelengths indicating a dependence on N growth.
The potential therapeutic role of PTR1 gene in non‐healing anthroponotic cutaneous leishmaniasis due to Leishmania tropica
Authors: Sezavar Monireh , Sharifi Iraj , Ghasemi Nejad Almani Pooya , Kazemi Bahram , Davoudi Noushin , Salari Samira , Salarkia Ehsan , Khosravi Ahmad , Bamorovat Mehdi
Published: December 2020

Background

Drug resistance is a common phenomenon frequently observed in countries where leishmaniasis is endemic. Due to the production of the pteridine reductase enzyme (PTR1), drugs lose their efficacy, and consequently, the patient becomes unresponsive to treatment. This study aimed to compare the in vitro effect of meglumine antimoniate (MA) on non‐ healing Leishmania tropica isolates and on MA transfected non‐healing one to PTR1.

Methods

Two non‐healing and one healing isolates of L. tropica were collected from patients who received two courses or one cycle of intralesional MA along with biweekly liquid nitrogen cryotherapy or systemic treatment alone, respectively. After confirmation of L. tropica isolates by polymerase chain reaction (PCR), the recombinant plasmid pcDNA‐rPTR (antisense) was transfected via electroporation and cultured on M199. Isolates in form of promastigotes were treated with different concentrations of MA and read using an enzyme‐linked immunosorbent assay (ELISA) reader and the half inhibitory concentration (IC50) value was calculated. The amastigotes were grown in mouse macrophages and were similarly treated with various concentrations of MA. The culture glass slides were stained, and the mean number of intramacrophage amastigotes and infected macrophages were assessed in triplicate for both stages.

Results

All three transfected isolates displayed a reduction in optical density compared with the promastigotes in respective isolates, although there was no significant difference between non‐healing and healing isolates. In contrast, in the clinical form (amastigotes), there was a significant difference between non‐healing and healing isolates (p < 0.05).

Conclusion

The results indicated that the PTR1 gene reduced the efficacy of the drug, and its inhibition by antisense and could improve the treatment of non‐healing cases. These findings have future implications in the prophylactic and therapeutic modality of non‐ healing Leishmania isolates to drug.
Performance evaluation of immunoassay for infectious diseases on the Alinity i system
Authors: Nam Minjeong , Song Da Young , Song Sang Hoon , Roh Eun Youn , Shin Sue , Park Kyoung Un , Song Eun Young
Published: December 2020

Background

Although a diagnosis of infectious diseases is essential for timely treatment, the performance of diagnostic tests has been hardly evaluated due to variable results that are influenced by multiple factors in different conditions. In the present study, the performance of the Alinity i system, which is a newly developed immunoassay to diagnose infectious diseases, was evaluated.

Methods

We evaluated the precision, linearity, correlation, and carryover of 16 analytes (HAV Ab IgG, HBsAg, HBeAg, anti‐HBc, anti‐HBe, anti‐HBs, anti‐HCV, HIV Ag/Ab, EBV VCA IgM, EBV VCA IgG, EBV EBNA IgG, CMV IgM, CMV IgG, Toxoplasma IgG, Rubella IgG, and Syphilis TP) of Alinity i by comparison with ARCHITECT i2000SR system following the rationale of the Clinical and Laboratory Standards Institute (CLSI).

Results

For quantitative tests, the coefficients of variation (CV) % of repeatability and intermediate precision were between 0% and 4.18%. The coefficients of the linearity (r2) over a widely tested analytical range were ≥ 0.990 and the correlation between Alinity i and the ARCHITECT i2000SR system was strong (r ≥ 0.994). For qualitative tests, the agreement between Alinity i and the ARCHITECT i2000SR system was excellent (kappa coefficient 1) with 100% sensitivity and specificity. Carryover rates for all analytes were less than 1.0% (−0.11% ~ 0.21%).

Conclusion

The Alinity i system showed good analytical performance and favorable comparability with the ARCHITECT i2000SR. It could be suitable as a routine immunoassay analyzer for screening and diagnosis of infectious disease.
Model‐Based Selection and Recommendation for Subcutaneous Abatacept Dose in Patients With Polyarticular Juvenile Idiopathic Arthritis
Authors: Gandhi Yash , Passarell Julie A. , Roy Amit , Murthy Bindu
Published: December 2020

The selective T‐cell costimulation modulator abatacept is approved for treatment of adult rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA; 6‐17 years [intravenous] and 2‐17 years [subcutaneous]). An extrapolation approach was taken to determine subcutaneous weight‐tiered doses of abatacept to evaluate in patients with pJIA. Population pharmacokinetic (PPK) and exposure‐response (E‐R) analyses were conducted to determine whether the weight‐tiered subcutaneous regimen provides near‐maximal efficacy and is therapeutically comparable to the intravenous regimen in patients with pJIA aged 2‐17 years. Combined study data from intravenous or subcutaneous abatacept were used to assess clinically relevant exposure outcomes. The PPK model was developed with data from 13 phase 2/3 studies in RA and pJIA; the E‐R model for the American College of Rheumatology pediatric scores (JIA‐ACR 30/50/70/100 responses) in month 4 was developed with data from 2 phase 3 pJIA studies. Predefined covariates were investigated in both analyses. PPK model‐predicted exposures were steady‐state peak, trough (Cminss), and time‐averaged concentrations. Abatacept PK was characterized by a linear 2‐compartment model (zero‐order intravenous infusion, first‐order subcutaneous absorption, first‐order elimination); body weight was the only clinically relevant covariate. Cminss was the best exposure predictor for the JIA‐ACR response: log odds for response increased in proportion to log‐transformed Cminss; JIA‐ACR30 approached a plateau when Cminss ≥ 10 μg/mL. The PPK and E‐R analyses demonstrated that the weight‐tiered subcutaneous and intravenous abatacept dosing regimens provide near‐maximal efficacy and are clinically comparable across children with pJIA who are > 2 years old.
The effect of imaging modality (magnetic resonance imaging vs. computed tomography) and patient position (supine vs. prone) on target and organ at risk doses in partial breast irradiation
Authors: Brown Emily , Dundas Kylie , Surjan Yolanda , Miller Daniela , Lim Karen , Boxer Miriam , Ahern Verity , Papadatos George , Batumalai Vikneswary , Harvey Jennifer , Lee Debra , Delaney Geoff P. , Holloway Lois
Published: December 2020

Introduction

Conventionally computed tomography (CT) has been used to delineate target volumes in radiotherapy; however, magnetic resonance imaging (MRI) is being continually integrated into clinical practice; therefore, the investigation into targets derived from MRI is warranted. The purpose of this study was to evaluate the impact of imaging modality (MRI vs. CT) and patient positioning (supine vs. prone) on planning target volumes (PTVs) and organs at risk (OARs) for partial breast irradiation (PBI).

Methods

A retrospective data set, of 35 patients, was accessed where each patient had undergone MRI and CT imaging for tangential whole breast radiotherapy in both the supine and prone position. PTVs were defined from seroma cavity (SC) volumes delineated on each respective image, resulting in 4 PTVs per patient. PBI plans were generated with 6MV external beam radiotherapy (EBRT) using the TROG 06.02 protocol guidelines. A prescription of 38.5Gy in 10 fractions was used for all cases. The impact analysis of imaging modality and patient positioning included dose to PTVs, and OARs based on agreed criteria. Statistical analysis was conducted though Mann–Whitey U, Fisher’s exact and chi‐squared testing (P < 0.005).

Results

Twenty‐four patients were eligible for imaging analysis. However, positioning analysis could only be investigated on 19 of these data sets. No statistically significant difference was found in OAR doses based on imaging modality. Supine patient position resulted in lower contralateral breast dose (0.10Gy ± 0.35 vs. 0.33Gy ± 0.78, p = 0.011). Prone positioning resulted in a lower dose to ipsilateral lung volumes (10.85Gy ± 11.37 vs. 3.41Gy ± 3.93, P = <0.001).

Conclusions

PBI plans with PTVs derived from MRI exhibited no clinically significant differences when compared to plans created from CT in relation to plan compliance and OAR dose. Patient position requires careful consideration regardless of imaging modality chosen. Although there was no proven superiority of MRI derived target volumes, it indicates that MRI could be considered for PBI target delineation.
Physicochemical Properties and Biological Performance of Polymethacrylate Based Gene Delivery Vector Systems: Influence of Amino Functionalities
Authors: Haladjova Emi , Chrysostomou Varvara , Petrova Maria , Ugrinova Iva , Pispas Stergios , Rangelov Stanislav
Published: December 2020

Physicochemical characteristics and biological performance of polyplexes based on two identical copolymers bearing tertiary amino or quaternary ammonium groups are evaluated and compared. Poly(2‐(dimethylamino)ethyl methacrylate)‐b‐poly(oligo(ethylene glycol) methyl ether methacrylate) block copolymer (PDMAEMA‐b‐POEGMA) is synthesized by reversible addition fragmentation chain transfer polymerization. The tertiary amines of PDMAEMA are converted to quaternary ammonium groups by quaternization with methyl iodide. The two copolymers spontaneously formed well‐defined polyplexes with DNA. The size, zeta potential, molar mass, aggregation number, and morphology of the polyplex particles are determined. The parent PDMAEMA‐b‐POEGMA exhibits larger buffering capacity, whereas the corresponding quaternized copolymer (QPDMAEMA‐b‐POEGMA) displays stronger binding affinity to DNA, yielding invariably larger in size and molar mass particles bearing greater number of DNA molecules per particle. Experiments revealed that QPDMAEMA‐b‐POEGMA is more effective in transfecting pEGFP‐N1 than the parent copolymer, attributed to the larger size, molar mass, and DNA cargo, as well as to the effective cellular traffic, which dominated over the enhanced ability for endo‐lysosomal escape of PDMAEMA‐b‐POEGMA.
Chemical exchange rotation transfer imaging of phosphocreatine in muscle
Authors: Zu Zhongliang , Lin Eugene C. , Louie Elizabeth A. , Jiang Xiaoyu , Lankford Christopher L. , Damon Bruce , Does Mark D. , Gore John C. , Gochberg Daniel F.
Published: December 2020

In chemical exchange saturation transfer (CEST) imaging, the signal at 2.6 ppm from the water resonance in muscle has been assigned to phosphocreatine (PCr). However, this signal has limited specificity for PCr since the signal is also sensitive to exchange with protein and macromolecular protons when using some conventional quantification methods, and will vary with changes in the water longitudinal relaxation rate. Correcting for these effects while maintaining reasonable acquisition times is challenging. As an alternative approach to overcome these problems, here we evaluate chemical exchange rotation transfer (CERT) imaging of PCr in muscle at 9.4 T. Specifically, the CERT metric, AREXdouble,cpw at 2.6 ppm, was measured in solutions containing the main muscle metabolites, in tissue homogenates with controlled PCr content, and in vivo in rat leg muscles. PCr dominates CERT metrics around 2.6 ppm (although with nontrivial confounding baseline contributions), indicating that CERT is well‐suited to PCr specific imaging, and has the added benefit of requiring a relatively small number of acquisitions.
Gamma Secretase Inhibitors in Cancer: A Current Perspective on Clinical Performance
Authors: McCaw Tyler R. , Inga Evelyn , Chen Herbert , Jaskula-Sztul Renata , Dudeja Vikas , Bibb James A. , Ren Bin , Rose J. Bart
Published: December 2020

Gamma secretase inhibitors (GSIs), initially developed as Alzheimer's therapies, have been repurposed as anticancer agents given their inhibition of Notch receptor cleavage. The success of GSIs in preclinical models has been ascribed to induction of cancer stem-like cell differentiation and apoptosis, while also impairing epithelial-to-mesenchymal transition and sensitizing cells to traditional chemoradiotherapies. The promise of these agents has yet to be realized in the clinic, however, as GSIs have failed to demonstrate clinical benefit in most solid tumors with the notable exceptions of CNS malignancies and desmoid tumors. Disappointing clinical performance to date reflects important questions that remain to be answered. For example, what is the net impact of these agents on antitumor immune responses, and will they require concurrent targeting of tumor-intrinsic compensatory pathways? Addressing these limitations in our current understanding of GSI mechanisms will undoubtedly facilitate their rational incorporation into combinatorial strategies and provide a valuable tool with which to combat Notch-dependent cancers. In the present review, we provide a current understanding of GSI mechanisms, discuss clinical performance to date, and suggest areas for future investigation that might maximize the utility of these agents.

Implications for Practice

The performance of gamma secretase inhibitors (GSIs) in clinical trials generally has not reflected their encouraging performance in preclinical studies. This review provides a current perspective on the clinical performance of GSIs across various solid tumor types alongside putative mechanisms of antitumor activity. Through exploration of outstanding gaps in knowledge as well as reasons for success in certain cancer types, the authors identify areas for future investigation that will likely enable incorporation of GSIs into rational combinatorial strategies for superior tumor control and patient outcomes.
Partially bio‐based furyl‐functionalized organosoluble poly(ether ether ketone)s
Authors: Kuhire Sachin S , Talanikar Aniket A , Tawade Bhausaheb V , Nagane Samadhan S , Wadgaonkar Prakash P
Published: December 2020

A new series of partially bio‐based (co)poly(ether ether ketone)s bearing pendent furyl groups was synthesized by nucleophilic aromatic substitution polycondensation of varying molar proportions of 4,4′‐(furan‐2‐ylmethylene)bis(2‐methoxyphenol) and bisphenol‐A with 4,4′‐difluorobenzophenone. The chemical structures, compositions and random nature of (co)poly(ether ether ketone)s were confirmed by NMR spectroscopy. Inherent viscosities and number‐average molecular weights of the (co)poly(ether ether ketone)s were in the range 0.74–2.90 dL g−1and 33 500–46 300 g mol−1, respectively, indicating the formation of reasonably high molecular weight polymers. (Co)poly(ether ether ketone)s were readily soluble in common organic solvents and could be cast into tough, transparent and flexible films from chloroform solutions. (Co)poly(ether ether ketone)s exhibited 10% weight loss and glass transition temperatures in the range 429–464 and 152–156 °C, respectively. A representative copoly(ether ether ketone) was crosslinked with 1,1′‐(methylenedi‐1,4‐phenylene)bismaleimide via Diels–Alder reaction to form a crosslinked polymer which showed improved mechanical properties and was recycled twice without significant loss of mechanical properties. Diels–Alder/retro Diels–Alder reaction was demonstrated by studies of sol–gel transformation, solubility tests, DSC and stress–strain measurements. © 2020 Society of Chemical Industry
Scalable, safer and greener syntheses of vinylimidazoles via reactive distillation of hydroxyethylimidazole intermediates
Authors: Alshaikh Ali , O'Harra Kathryn E , Liu Xiaoyang , Whitley John W , Mittenthal Max S , Taylor Wesley F , Turner C Heath , Bara Jason E
Published: December 2020

1‐Vinylimidazole has been extensively utilized by the polymer science community, due to its high reactivity for free radical polymerization and the variety of uses for both neutral polyvinylimidazole and cationic polyvinylimidazolium forms. While much rarer, 4‐vinylimidazoles and 2‐vinylimidazoles are less synthetically accessible. In comparison to conventional methods for the synthesis of vinylimidazole derivatives from energy‐intensive reaction conditions utilizing hazardous, gaseous precursors, herein we demonstrate a simple and versatile two‐step method applied to the synthesis of seven 1‐vinylimidazoles with different substituents as well as an initial demonstration of a facile method to synthesize the rare compound 1‐methyl‐2‐vinylimidazole. The process relies upon the synthesis of N‐hydroxyethylimidazole precursors via a ring‐opening reaction from substituted imidazoles with ethylene carbonate, a ‘green’ substance formed from CO2 and ethylene oxide. For the synthesis of 1‐methyl‐2‐vinylimidazole, the hydroxyethylimidazole intermediate is conveniently formed from 1,2‐dimethylimidazole and paraformaldehyde. These hydroxyethylimidazoles are subsequently dehydrated to the corresponding 1‐ or 2‐vinylimidazole forms using a base‐catalyzed reactive distillation. The optimization of process conditions is discussed, and properties of the vinylimidazole derivatives were computationally studied using density functional theory calculations. This work reveals scalable synthetic methods for previously inaccessible vinylimidazole compounds which can enable the design of new polymers. © 2020 Society of Chemical Industry
Registration of the wheat D‐genome nested association mapping (DNAM) population
Authors: Strauss Nikayla M. , Wiersma Andrew , DeMacon Patricia , Klarquist Emily , Carter Arron , Campbell Kimberly A. Garland , Olson Eric
Published: December 2020

Modern wheat is lacking diversity in the D genome due to the genetic bottleneck from the hybridization between tetraploid Triticum turgidum L. and diploid Aegilops tauschii Coss. The D‐genome nested association mapping (DNAM) population (Reg. no. MP‐14, NSL 536301 MAP) was developed to expand D‐genome variation in hexaploid wheat (Triticum aestivum L.). The DNAM population is a wheat nested association mapping population developed with direct crosses between the hard‐white winter Kansas State University breeding line KS05HW14‐3 and Ae. tauschii accessions TA10187, TA1693, TA10171, TA1662, TA1617, TA1615, TA1642, and TA1718. In total, there are 1,164 BC₂F₄ recombinant inbred lines (RILs) in 19 families. The DNAM was originally created for introgression of novel stem rust resistance genes but has since been used to identify resistance to other fungal pathogens. A subset of 420 lines were selected for important agronomic traits, including height and threshability, and named the DNAM Core RILs. Research with the DNAM has potential to provide novel genes that can be introgressed into elite cultivars, as well as knowledge and understanding of the D genome in wheat.
Fabrication of natural colorimetric indicators for monitoring freshness of ready‐to‐cook idli batter
Authors: Gaikwad Pratik S. , Yadav Binod K. , Sugumar Anandakumar
Published: December 2020

Natural colorimetric indicators have been fabricated using annatto and pomegranate extract powder and compared with chemical colorimetric indicator fabricated using bromophenol blue (BPB) to monitor the freshness of ready‐to‐cook (RTC) idli batter. The fabricated colorimetric indicator labels work on increasing headspace carbon dioxide (CO2) concentration and decreasing pH of stored batter, where indicators showed visible color change from lightest to darkest for spoiled samples. The headspace CO2 concentration of RTC idli batter increased from 0.15 ± 0.05 to 18.07 ± 0.21% (v/v) and pH decreased from 6.7 ± 0.06 to 4.5 ± 0.06 at optimum storage condition (35 ± 1°C) up to 24 h. The percent titratable acidity (% TA) increased from 0.44 ± 0.02 to 0.90 ± 0.02% up to 24 h. The viable lactic acid bacteria count (LABC) and total bacterial count (TBC) increased while yeast and mold count (YMC) was decreased with increasing fermentation time up to 24 h for batter stored at optimum condition. The color change of indicators was quantitatively measured with captured red, green, and blue (RGB) images. Pixel intensity for natural and chemical colorimetric indicators were decreased with increasing fermentation time. The leaching of chemical dye was observed on stored batter, and natural colorimetric indicators are nontoxic and successfully used as “on package sticker” for monitoring freshness of RTC idli batter.
Theoretical study on the atmospheric degradation mechanism and subsequent products of E,E‐2,4‐hexadienal with hydroxyl radical
Authors: Sun Yanan , Yao Junfang , Tang Yizhen , Zhang Yunju , Wu Wenzhong , Sun Jingyu
Published: December 2020

E,E‐2,4‐hexadienal is probably a precursor of secondary organic aerosol (SOA) and plays an important role in the atmospheric chemistry. Its main degradation routs are the reactions with OH, Cl, NO3 as well as photolysis. Atmospheric hydroxyl radical, as the most important oxidant, generally controls the removal of volatile organic compounds in the atmosphere. Thus, the quantum chemical calculations are used to investigate the reaction mechanism of E,E‐2,4‐hexadienal with hydroxyl radical, which would give us a better understanding for the main degradation products. The reaction paths of E,E‐2,4‐hexadienal with OH radical have been calculated accurately by using the BMC‐CCSD//M06‐2X/6‐311G (d, p) level at atmospheric pressure and room temperature. There are six hydrogen abstraction and four carbon addition paths at the first stages of this reaction. Due to the low energy barrier and exothermic reaction, the ten paths would contribute to the total reaction. Furthermore, the peroxy (RO2) and alkoxy (RO) radicals from the most important adduct IM1(CH3CHOHCHCHCHCHO) would be formed in the atmospheric environment. Hence, the reaction mechanism of the peroxy radical (CH3CHOHCHO2CHCHCHO) with NO, NO2, HO2, and self‐reaction have been also studied by using the same quantum chemical methods. And the reaction paths of alkoxy radical (CH3CHOHCHOCHCHCHO) have been also originally studied. It is found that the subsequent reactions play a key role in the cycling of atmospheric radicals, production of ozone, and SOA formation. What is more, the reaction mechanism of this study accords with the reported experimental observations. Meanwhile, the theoretical rate constant of 1.05 × 10−10 cm3 molecule−1 s−1 of E,E‐2,4‐hexadienal with OH reaction at 298 K is close to experimental data. The atmospheric lifetime of E,E‐2,4‐hexadienal with OH radical is about 2.6 h at 298 K. This study provides insight into the transformation of E,E‐2,4‐hexadienal in the atmospheric environment.
On the estimation bias in first‐order bifurcating autoregressive models
Authors: Elbayoumi Tamer M. , Mostafa Sayed A.
Published: December 2020

In this paper, we study the bias of the least squares (LS) estimation for the stationary first‐order bifurcating autoregressive (BAR(1)) model which is commonly used to model binary tree‐structured data that appear in many applications, most famously cell‐lineage applications. We first show that the LS estimator can have large bias for both small and moderate sized samples and that this bias is dependent on the values of both the autoregressive parameter (the target parameter) and the correlation between model errors. We also provide a first‐order approximation to the bias of the LS estimator and show, empirically, that this approximation can accurately describe the bias as a function of the autoregressive parameter and the errors correlation over wide combinations of their values. Then we study two approaches for correcting the bias of the LS estimator, namely, bootstrap bias correction and bias correction through linear bias functions. Both single and double bootstrap bias‐corrected versions of the LS estimator are defined and studied empirically in comparison with a linear‐bias‐correcting estimator as well as the standard LS estimator. The empirical results, based on both simulated and real data, demonstrate that both the linear‐bias‐correcting estimator and the bootstrap bias‐correcting estimators can be quite effective in reducing the bias of the LS estimator and that the bootstrap estimators are more effective near the boundaries of the range of the autoregressive parameter. We also discuss the extension of these methods to higher order BAR models.
Glycemic Control for Critically Ill Patients Using Zone Model Predictive Control
Authors: Wu Sha , Furutani Eiko , Sugawara Tomonori , Asaga Takehiko , Shirakami Gotaro
Published: December 2020

Hyperglycemia in critically ill patients leads to severe complications and even death. It was shown that keeping blood glucose (BG) within the range of 80–110 mg/dl (4.4–6.1 mmol/l) reduces mortality and morbidity in intensive care units (ICUs), and many researches for achieving such BG control have been performed. However, maintaining BG within such range is not easy mainly due to the time variability of insulin sensitivity in ICU patients. In this study, regarding hypoglycemia prevention as important, we improve our glycemic control system utilizing zone model predictive control, which is a control strategy to keep the controlled variable within a target range and has been applied to avoid hypoglycemia for type 1 diabetes mellitus. Then, we assess the performance of the glycemic control system on ICU virtual patients created from clinical ICU data. The modified glycemic control system achieves 68% of BG measurements within the range of 80–110 mg/dl and only 1.3% of BG measurements below 80 mg/dl, which suggests the effectiveness and safety of the system. © 2020 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
ColAtt‐Net: In Reducing the Ambiguity of Pedestrian Orientations on Attribute‐Aware Semantic Segmentation Task
Authors: Sulistiyo Mahmud Dwi , Kawanishi Yasutomo , Deguchi Daisuke , Ide Ichiro , Hirayama Takatsugu , Murase Hiroshi
Published: December 2020

Semantic segmentation has become one of the trending topics in the world of computer vision and deep learning. Recently, due to an increasing demand to solve a semantic segmentation task simultaneously with attribute recognition of objects, a new task named attribute‐aware semantic segmentation has been introduced. Since the task requires to handle pixel‐wise object class estimation with its attributes such as a pedestrian's body orientation, previous works had difficulties to handle ambiguous attributes such as body orientations in object‐level, especially when segmenting the pedestrians with their attributes correctly. This paper proposes the ColAtt‐Net that is an attribute‐aware semantic segmentation model augmented by a column‐wise mask branch to predict the pedestrians' orientations in the horizontal perspective of the input image. We firmly assume that the pedestrians captured by a car‐mounted camera are distributed horizontally so that for each column of the input image, the pedestrian pixels can be labeled with one orientation uniformly. In the proposed method, we split the output of the base semantic segmentation model into two branches; one branch for segmenting the object categories, while the other one, as the novel column‐wise attribute branch, is to map the recognition of pedestrian's orientations that are distributed horizontally. This method successfully enhances the performance of attribute‐aware semantic segmentation by reducing the ambiguity on segmenting the pedestrian's orientation. Improvements on the pedestrian orientation segmentation are confidently shown by the proposed method in the experimental results, both in quantitative and qualitative views. This paper also discusses how the improved performance becomes an advantage in the autonomous driving system. © 2020 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Design and Analysis of Dual‐Magnet BLDCM for Momentum Wheel
Authors: Xiao Yunfeng , Xu Kang , Liu Qiang
Published: December 2020

To obtain the larger output torque and the higher stability speed accuracy, a novel dual‐magnet brushless DC motor is proposed, and its structure is introduced. The mathematical model is established by the equivalent surface current method, and the magnetic circuit is analyzed by finite element method. The radial and tangential air gap magnetic flux densities of the dual‐magnet scheme are larger and less than that of the ironless stator and the Halbach array schemes, respectively. The theoretical calculation and simulation results are verified by prototype experiments. © 2020 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Modigliani's studio practice revealed by MA‐XRF and non‐invasive spectral imaging techniques
Authors: Genty‐Vincent Anaïs , Laval Eric , Senot Marie‐Amélie , Menu Michel
Published: December 2020

Amedeo Modigliani (1884–1920) is an artist highly valued by the public. However, his works have been little studied by natural scientists. The project “Modigliani and His Secrets” follows two closely correlated purposes: a better knowledge of the materiality of the works and a better understanding of the studio practice of the artist. The corpus (25 paintings and 3 sculptures, works belonging to French museums) covers the entire work of Modigliani in France from 1908 to 1920. The present article will focus on the beginning of Modigliani's artistic life through the analyses of two paintings dated from 1909 to 1913. The same multi‐analytical approach was implemented for each painting. It enables us to determine Modigliani's color palette, but also to unveil pentimenti and previous compositions. Complementary two‐dimensional imaging techniques operating in different spectral ranges (MA‐XRF, SWIR reflectance hyperspectral, X‐ray radiography…) were successful examining Modigliani's masterpieces to reveal the artistic know‐how and intentional strategy of the cursed and legendary artist.
Placenta accreta spectrum disorders—experience of management in a German tertiary perinatal centre
Authors: Bluth Anja , Schindelhauer Axel , Nitzsche Katharina , Wimberger Pauline , Birdir Cahit
Published: December 2020

Purpose

Placenta accreta spectrum (PAS) disorders can cause major intrapartum haemorrhage. The optimal management approach is not yet defined. We analysed available cases from a tertiary perinatal centre to compare the outcome of different individual management strategies.

Methods

A monocentric retrospective analysis was performed in patients with clinically confirmed diagnosis of PAS between 07/2012 and 12/2019. Electronic patient and ultrasound databases were examined for perinatal findings, peripartum morbidity including blood loss and management approaches such as (1) vaginal delivery and curettage, (2) caesarean section with placental removal versus left in situ and (3) planned, immediate or delayed hysterectomy.

Results

46 cases were identified with an incidence of 2.49 per 1000 births. Median diagnosis of placenta accreta (56%), increta (39%) or percreta (4%) was made in 35 weeks of gestation. Prenatal detection rate was 33% for all cases and 78% for placenta increta. 33% showed an association with placenta praevia, 41% with previous caesarean section and 52% with previous curettage. Caesarean section rate was 65% and hysterectomy rate 39%. In 9% of the cases, the placenta primarily remained in situ. 54% of patients required blood transfusion. Blood loss did not differ between cases with versus without prenatal diagnosis (p = 0.327). In known cases, an attempt to remove the placenta did not show impact on blood loss (p = 0.417).

Conclusion

PAS should be managed in an optimal setting and with a well-coordinated team. Experience with different approaches should be proven in prospective multicentre studies to prepare recommendations for expected and unexpected need for management.
Comparative ultrastructure of the radiolar crown in Sabellida (Annelida)
Authors: Tilic Ekin , Rouse Greg W. , Bartolomaeus Thomas
Published: December 2020

Three major clades of tube-dwelling annelids are grouped within Sabellida: Fabriciidae, Serpulidae and Sabellidae. The most characteristic feature of these animals is the often spectacularly colorful and flower-like radiolar crown. Holding up such delicate, feathery appendages in water currents requires some sort of internal stabilization. Each of the above-mentioned family-ranked groups has overcome this problem in a different way. Herein we describe the arrangement, composition and ultrastructure of radiolar tissues for fabriciids, sabellids and serpulids using transmission electron microscopy, histology and immunohistochemistry. Our sampling of 12 species spans most of the phylogenetic lineages across Sabellida and, from within Sabellidae, includes representatives of Myxicolinae, Sabellinae and the enigmatic sabellin Caobangia. We further characterize the ultrastructure of the chordoid cells that make up the supporting cellular axis in Sabellidae and discuss the evolution of radiolar tissues within Sabellida in light of the recently published phylogeny of the group.