bluuebunny/crossref_metadata_2025 huggingface dataset:
Population Pharmacokinetics of Tofacitinib in Patients With Moderate to Severe Ulcerative Colitis
Authors: Vong Camille , Martin Steven W. , Deng Chenhui , Xie Rujia , Ito Kaori , Su Chinyu , Sandborn William J. , Mukherjee Arnab
Published: January 2021

Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We characterized tofacitinib pharmacokinetics in patients with moderate to severe UC, and the effects of covariates on variability in pharmacokinetic parameter estimates. Data were pooled from 1 8‐week phase 2 and 2 8‐week phase 3 induction studies, and a 52‐week phase 3 maintenance study (N = 1096). Population pharmacokinetic analysis was conducted using nonlinear mixed‐effects modeling. Potential predictors of apparent oral clearance (CL/F) and volume of distribution (V/F) were evaluated. The PK was described by a 1‐compartment model parameterized in terms of CL/F (26.3 L/hour [h]) and V/F (115.8 L), with first‐order absorption (Ka; 9.85 h−1) and lag time (0.236 h). The derived elimination half‐life was approximately 3.05 h. In the final model, baseline creatinine clearance, sex, and race (Asian vs non‐Asian) were significant covariates for CL/F; significant covariates for V/F were age, sex, and body weight; baseline albumin and baseline Mayo score were not significant covariates. CL/F between‐patient variability was estimated at 22%. Tofacitinib exposure did not change significantly over the duration of induction/maintenance treatment in patients with UC. Although statistically significant covariate effects on CL/F and V/F were observed, the magnitude of the effects are not clinically significant. Therefore, dose adjustment/restrictions for age, body weight, sex, race, or baseline disease severity are not required during tofacitinib treatment. ClinicalTrials.gov numbers: NCT00787202, NCT01465763, NCT01458951, NCT01458574.
Hybrid feature selection model based on relief‐based algorithms and regulizer algorithms for cancer classification
Authors: Manhrawy Ibrahim I.M. , Qaraad Mohammed , El‐Kafrawy Passent
Published: January 2021

Cancer is a group of diseases that involve abnormal cell growth with the potential to spread to other parts of the body. Cancer microarray data usually include a small number of samples with a large number of gene expression levels as features. Gene expression or microarray is a technology that monitors the expression of the large number of genes in parallel that make it useful in cancer classification, high dimensionality in cancer microarray data results in the overfitting problem. This article proposes novel hybrid feature selection model called the RBARegulizer model, which is based on two types of feature selection techniques, two RBAs algorithms (ReliefF, MultiSURF) for feature‐ranking filters to the most important one's genes, and three regulizer algorithms (Lasso, Elastic Net, Elastic Net CV) to reduce the feature subset, remove the noisy and irrelevant feature to improve the performance and accuracy of cancer (microarray) data classification. For evaluating the model, the different three classifiers SVM, MLP, and random forest with four high‐dimensional microarray data for different cancer types were applied. The experimental type shows that our model overcomes the overfitting problem of cancer microarray data. Moreover, the results show that RBARegulizer model is perfect in improving the accuracy of cancer microarray data classification.
Investigating memory prefetcher performance over parallel applications: From real to simulated
Authors: Girelli Valéria S. , Moreira Francis B. , Serpa Matheus S. , Carastan‐Santos Danilo , Navaux Philippe O. A.
Published: January 2021

Memory prefetcher algorithms are widely used in processors to mitigate the performance gap between the processors and the memory subsystem. The complexities behind the architectures and prefetcher algorithms, however, not only hinder the development of accurate architecture simulators, but also hinder understanding the prefetcher's contribution to performance, on both a real hardware and in a simulated environment. In this paper, we contribute to shed light on the memory prefetcher's role in the performance of parallel High‐Performance Computing applications, considering the prefetcher algorithms offered by both the real hardware and the simulators. We performed a careful experimental investigation, executing the NAS parallel benchmark (NPB) on a real Skylake machine, and as well in a simulated environment with the ZSim and Sniper simulators, taking into account the prefetcher algorithms offered by both Skylake and the simulators. Our experimental results show that: (i) prefetching from the L3 to L2 cache presents better performance gains, (ii) the memory contention in the parallel execution constrains the prefetcher's effect, (iii) Skylake's parallel memory contention is poorly simulated by ZSim and Sniper, and (iv) Skylake's noninclusive L3 cache hinders the accurate simulation of NPB with the Sniper's prefetchers.
Implantable Optofluidic Systems for Wireless In Vivo Photopharmacology
Authors: Qazi Raza , Yeon Kim Choong , Kang Inho , Binazarov Dauren , McCall Jordan G. , Jeong Jae‐Woong
Published: January 2021

The front cover artwork is provided by the Jeong Group at the School of Electrical Engineering at Korea Advanced Institute of Science and Technology (KAIST; South Korea). The image illustrates an ultrathin, soft and biocompatible optofluidic probe, which can deliver both light and drugs for in vivo photopharmacology. Read the full text of the Minireview at 10.1002/cptc.2020000217.
Investigation of dental elastomers as oral mucosa simulant materials
Authors: Choi Joanne Jung Eun , Chen Shiyao , Waddell John Neil
Published: January 2021

Objective

To measure mechanical properties of dental soft liners in tensional stress to identify their suitability as human oral mucosa simulant materials.

Methods

Eleven different dental elastomers were subjected to tensile testing to obtain their tensile strength and elastic moduli (n = 15/group) according to the ISO‐527 method. Fractured surfaces of one specimen per sample group were examined under the light microscope and scanning electron microscope (SEM). Energy‐dispersive X‐ray spectroscopy (EDS) was performed for the elemental analysis or chemical characterization of each sample group. The obtained data were quantitatively and qualitatively analysed. They were also statistically analysed using SPSS version 25.

Results

The tensile strength of dental elastomers ranged from 0.43 MPa (±0.09) to 7.41 MPa (±1.11) and had statistically significant differences between tested groups (p = 0.001). Vertex soft heat‐cure soft liner, GC impression silicones and Silagum soft liners were found to have tensile strengths close to that of the oral mucosa reported by previous studies. SEM analysis revealed that the elastomers with higher filler contents showed rough fractured surface with plucking of particles after tensile fracture.

Conclusion

This is the first study assessing the suitability of dental elastomers as human oral mucosa simulant materials which can be used for in vitro, mathematical modeling and finite element analysis (FEA) to study masticatory force distribution in oral mucosa. Out of 11 studied, six (Vertex Soft, GC heavy and Light body, Molloplast B, Algin X Ultra and Exaclear) dental elastomers showed similar mechanical properties to the Theil embalmed gingival tissues. Vertex Soft, GC Light body, and Molloplast B may be used for the majority of oral mucosal model when considering tensile strength as the primary factor for mechanical stimulation.
Investigation of Sr0.7Ca0.3FeO3 Oxygen Carriers with Variable Cobalt B‐Site Substitution
Authors: Popczun Eric J. , Jia Ting , Natesakhawat Sittichai , Marin Chris M. , Nguyen‐Phan Thuy‐Duong , Duan Yuhua , Lekse Jonathan W.
Published: January 2021

A‐site and B‐site substitutions are effective methods towards improving well‐studied oxygen carrier materials that are vital for emerging gasification technologies. Such materials include SrFeO3, which greatly benefits from the inclusion of calcium and/or cobalt, and Sr0.8Ca0.2Fe0.4Co0.6O3 has been regarded as the best‐performing composition. In this study, systems with higher calcium and lower cobalt contents are investigated with a view to lessening the societal and economic burdens of these dual‐doped carriers. Density functional theory calculations are performed to illustrate the Fe−O bonding and relaxation contributions to the oxygen vacancy formation energy in Sr1‐xCaxFe1‐yCoyO3 systems (x=0.1875, 0.25, 0.3125; y=0.125, 0.25, 0.375, 0.5) and determine that increased calcium A‐site substitution requires the use of less cobalt B‐site doping to reach the same oxygen vacancy formation. These findings are experimentally validated in situ and ex situ characterization of bulk Sr0.7Ca0.3Fe1‐yCoyO3 materials. Sr0.7Ca0.3Fe0.7Co0.3O3 is found to have similar O2 adsorption/desorption rates and storage capacity to Sr0.8Ca0.2Fe0.4Co0.6O3 in air/N2 cycling experiments. Additionally, both materials are outperformed by Sr0.7Ca0.3Fe1‐yCoyO3 systems with y=0–0.10 at 400–500 °C, which cycle 1.5 wt% O2 in under ten minutes.
IL‐6 receptor blockade for allograft dysfunction after lung transplantation in a patient with COPA syndrome
Authors: Riddell Peter , Moshkelgosha Sajad , Levy Liran , Chang Nina , Pal Prodipto , Halloran Kieran , Halloran Phil , Parkes Michael , Singer Lianne G , Keshavjee Shaf , Martinu Tereza , Juvet Stephen C
Published: January 2021

Objective

COPA syndrome is a genetic disorder of retrograde cis‐Golgi vesicle transport that leads to upregulation of pro‐inflammatory cytokines (mainly IL‐1β and IL‐6) and the development of interstitial lung disease (ILD). The impact of COPA syndrome on post‐lung transplant (LTx) outcome is unknown but potentially detrimental. In this case report, we describe progressive allograft dysfunction following LTx for COPA‐ILD. Following the failure of standard immunosuppressive approaches, detailed cytokine analysis was performed with the intention of personalising therapy.

Methods

Multiplexed cytokine analysis was performed on serum and bronchoalveolar lavage (BAL) fluid obtained pre‐ and post‐LTx. Peripheral blood mononuclear cells (PMBCs) obtained pre‐ and post‐LTx were stimulated with PMA, LPS and anti‐CD3/CD28 antibodies. Post‐LTx endobronchial biopsies underwent microarray‐based gene expression analysis. Results were compared to non‐COPA LTx recipients and non‐LTx healthy controls.

Results

Multiplexed cytokine analysis showed rising type I/II IFNs, and IL‐6 in BAL post‐LTx that decreased following treatment of acute rejection but rebounded with further clinical deterioration. In vitro stimulation of PMBCs suggested that myeloid cells were driving deterioration, through IL‐6 signalling pathways. Tocilizumab (IL‐6 receptor antibody) administration for 3 months (4 mg kg−1, monthly) effectively suppressed IL‐6 levels in BAL. Mucosal gene expression profile following tocilizumab suggested greater similarity to normal.

Conclusion

Clinical effectiveness of IL‐6 receptor blockade was not observed. However, we identified IL‐6 upregulation associated with graft injury, effective IL‐6 suppression with tocilizumab and evidence of beneficial effect on molecular transcripts. This mechanistic analysis suggests a role for IL‐6 blockade in post‐LTx care that should be investigated further.
Investigating differences between tamoxifen resistant and sensitive breast cancer cells with flow cytometry
Authors: Bitton Aric , Zheng Yan , Houston Jessica P. , Houston Kevin D.
Published: January 2021

The active metabolite of tamoxifen, 4‐hydroxytamoxifen, functions as an anti‐estrogen in breast cancer cells and thus inhibits proliferation. While tamoxifen continues to be successfully used to treat estrogen‐dependent breast cancer, most patients receiving treatment will develop chemoresistance over time. Two commonly reported biomarkers of tamoxifen resistance are decreased expression of insulin‐like growth factor 1 receptor (IGF‐1R) and increased expression of epidermal growth factor receptor (EGFR). In prior work we have shown that these receptors facilitate chemoresistance and have unique regulatory functions measurable in resistant cell lines compared with nonresistant. Thus, we hypothesized that these receptors and a newly identified biomarker, integrin β1, may be used to search for the presence of resistant breast cancer cells within a population of cells that are sensitive to tamoxifen therapy. We tested this by designing a straightforward cell‐labeling approach to measure differences in the receptor expression of resistant vs. sensitive cells cytometrically. Our results show that separation is possible when observing the expression of IGF‐1R as well as integrin β1. Interestingly, we found no detectable difference in EGFR expression between tamoxifen resistant and ‐sensitive cells when measured with cytometry despite the fact that EGFR is upregulated in resistant cells. Our long‐term goal is to utilize sorting to isolate tamoxifen resistant subpopulations of cells by receptor expression level. Isolating rare resistant cells that reside within a population of drug‐sensitive cells will offer new insights into why chemoresistance occurs.
Analysis of energy‐efficient cooperative spectrum sensing with improved energy detectors and multiple antennas over Nakagami‐q/n fading channels
Authors: Nallagonda Srinivas , Mamidi Ranjeeth , Bhowmick Abhijit
Published: January 2021

Cognitive radio (CR) is an advanced technique used for the utilization of radio spectrum. A CR node uses the radio spectrum of a licensed user (called as primary user, PU) deviously. In this work, a cooperative sensing network (CSN) with improved energy detection (IED)‐based CR nodes is proposed. Each CR node consists of multiple antennas and perform themselves selection diversity (SC) technique. Each CR node senses a PU through erroneous sensing channel and reports its sensing data (1‐bit binary‐decision) to the fusion center (FC) through erroneous reporting channels. At FC, existence of PU (presence or absence) is identified using k‐out‐of‐N fusion rule. The novel expressions for detection probability over noise plus Nakagami‐q/n fading channels are derived and the mathematical frameworks for analysis of throughput and energy‐efficiency of the proposed network are developed. The simulation testbed is also developed and presented in this work to validate the analytically obtained performance characteristics. For several network parameters values, the investigation on comparison between IED and traditional energy detection method for various decision fusion rules is studied. Further, performance characteristics are analytically illustrated for throughput and energy‐efficiency over noise plus Nakagami‐q/n fading channels. The impact of diversity technique and effect of fading severity parameters on the throughput and energy‐efficiency are also investigated. The effect of channel error on total error performance for both proposed and conventional networks is shown. Finally, optimal fusion rule and optimal network parameters values correspond to maximum throughput and maximum energy‐efficiency are also identified.
Limb reduction in squamate reptiles correlates with the reduction of the chondrocranium: A case study on serpentiform anguids
Authors: Yaryhin Oleksandr , Klembara Jozef , Pichugin Yuriy , Kaucka Marketa , Werneburg Ingmar
Published: January 2021

Background

In vertebrates, the skull evolves from a complex network of dermal bones and cartilage—the latter forming the pharyngeal apparatus and the chondrocranium. Squamates are particularly important in this regard as they maintain at least part of the chondrocranium throughout their whole ontogeny until adulthood. Anguid lizards represent a unique group of squamates, which contains limbed and limbless forms and show conspicuous variation of the adult skull.

Results

Based on several emboadryonic stages of the limbless lizards Pseudopus apodus and Anguis fragilis, and by comparing with other squamates, we identified and interpreted major differences in chondrocranial anatomy. Among others, the most important differences are in the orbitotemporal region. P. apodus shows a strikingly similar development of this region to other squamates. Unexpectedly, however, A. fragilis differs considerably in the composition of the orbitotemporal region. In addition, A. fragilis retains a paedomorphic state of the nasal region.

Conclusions

Taxonomic comparisons indicate that even closely related species with reduced limbs show significant differences in chondrocranial anatomy. The Pearson correlation coefficient suggests strong correlation between chondrocranial reduction and limb reduction. We pose the hypothesis that limb reduction could be associated with the reduction in chondrocrania by means of genetic mechanisms.
The effect of three major co‐morbidities on quality of life and outcome of patients with heart failure with reduced ejection fraction
Authors: Benes Jan , Kotrc Martin , Jarolim Petr , Hoskova Lenka , Hegarova Marketa , Dorazilova Zora , Podzimkova Mariana , Binova Jana , Lukasova Marianna , Malek Ivan , Franekova Janka , Jabor Antonin , Kautzner Josef , Melenovsky Vojtech
Published: January 2021

Aims

Diabetes mellitus, chronic obstructive pulmonary disease, and chronic kidney disease are prevalent in patients with heart failure with reduced ejection fraction (HFrEF). We have analysed the impact of co‐morbidities on quality of life (QoL) and outcome.

Methods and results

A total of 397 patients (58.8 ± 11.0 years, 73.6% with New York Heart Association functional class ≥3) with stable advanced HFrEF were followed for a median of 1106 (inter‐quartile range 379–2606) days, and 68% of patients (270 patients) experienced an adverse outcome (death, urgent heart transplantation, and implantation of mechanical circulatory support). Chronic obstructive pulmonary disease was present in 16.4%, diabetes mellitus in 44.3%, and chronic kidney disease in 34.5% of patients; 33.5% of patients had none, 40.0% had one, 21.9% had two, and 3.8% of patient had three co‐morbidities. Patients with more co‐morbidities reported similar QoL (assessed by Minnesota Living with Heart Failure Questionnaire, 45.46 ± 22.21/49.07 ± 21.69/47.52 ± 23.54/46.77 ± 23.60 in patients with zero to three co‐morbidities, P for trend = 0.51). Multivariable regression analysis revealed that furosemide daily dose, systolic blood pressure, New York Heart Association functional class, and body mass index, but not the number of co‐morbidities, were significantly (P < 0.05) associated with QoL. Increasing co‐morbidity burden was associated with worse survival (P < 0.0001), lower degree of angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker treatment (P = 0.001), and increasing levels of BNP (mean of 685, 912, 1053, and 985 ng/L for patients with zero to three co‐morbidities, P for trend = 0.008) and cardiac troponin (sm‐cTnI, P for trend = 0.0496), which remained significant (P < 0.05) after the adjustment for left ventricular ejection fraction, left ventricular end‐diastolic diameter, right ventricular dysfunction grade, body mass index, and estimated glomerular filtration rate.

Conclusions

In stable advanced HFrEF patients, co‐morbidities are not associated with impaired QoL, but negatively affect the prognosis both directly and indirectly through lower level of HF pharmacotherapy and increased myocardial stress and injury.
Unsymmetrical Dinuclear RuII Complexes with Bridging Polydentate Nitrogen Ligands as Potential Water Oxidation Catalysts
Authors: de Palo Alice , La Ganga Giuseppina , Nastasi Francesco , Guelfi Massimo , Bortoluzzi Marco , Pampaloni Guido , Puntoriero Fausto , Campagna Sebastiano , Marchetti Fabio
Published: January 2021

Mononuclear RuII complex [RuCl(κ3N‐tpm)(κ2N‐bptz)]Cl, [1]Cl [tpm=tris(1‐ pyrazolyl)methane; bptz=3,6‐di(2‐pyridyl)‐1,2,4,5‐tetrazine], and dinuclear complexes [RuCl(κ3N‐tpm)(μ‐κ2N:κ2N‐bptz)Ru(κ2N‐bipy)2][PF6]3, [3][PF6]3, [RuCl(η6‐p‐cymene)(μ‐κ2N:κ2N‐dpp)Ru(κ2N‐bipy)2][PF6]2, [4][PF6]2, and [RuCl(η6‐p‐cymene)(μ‐κ2N:κ2N‐dpp)Ru(κ2N‐biqn)2][PF6]3, [5][PF6]3 [dpp=2,3‐bis(2′‐pyridyl)‐pyrazine; bipy=2,2′‐bipyridine; biqn=2,2′‐quinoline], incorporating both potentially catalytic and photosensitive subunits, were synthesized and characterized by means of elemental analysis, mass spectrometry, and spectroscopic methods. The molecular structures of the new compounds were also investigated and compared by means of DFT calculations. The absorption spectra of all the compounds are dominated by metal‐to‐ligand charge‐transfer bands in the visible (which in most cases largely extend over the red portion of the spectrum) and ligand‐centered bands in the UV region. The oxidation behavior is based on metal‐centered RuII to RuIII oxidation processes, which in phosphate buffer solution are followed by a catalytic water oxidation wave for [1]Cl and [3][PF6]3. For these compounds, the mechanism of water oxidation is proposed to consist in water nucleophilic attack, according to chemical experiments with Ce(IV) salts, so demonstrating for the first time that the bptz ligand can be profitably used to build ruthenium(II) complexes with catalytic properties. On the contrary, no catalytic process is observed for 4 and 5, most likely due to the high positive potential for RuII oxidation induced by the presence of the p‐cymene moiety.
The Use of Phospholipids to Make Pharmaceutical Form Line Extensions
Authors: van Hoogevest Peter , Tiemessen Harry , Metselaar Josbert M. , Drescher Simon , Fahr Alfred
Published: January 2021

This review describes the use of phospholipid excipients to make Pharmaceutical Form (Dosage Form) Line Extensions of existing drugs as part of a Product Life Cycle Management. Product examples and development candidates, which show the versatility of phospholipids as key excipients in formulations to develop line extension drug products for any administration route by reformulating existing products, are provided. The resulting patented products enable the application of a drug substance for another administration route or show an increased efficacy and/or reduced toxicity of the formulated drug substances, or enable a more convenient use, through reduction of dosing frequency, or adapt a product for regulatory requirements for specific patient populations. Parenteral line extensions for lipophilic drugs using non‐toxic phospholipid‐based solubilising formulations are clearly an alternative to products with solubilising synthetic detergents with the risk for allergic and anaphylactic reactions. This review draws the attention to academic and industrial formulation scientist to consider using phospholipid excipients to reformulate existing products to improve the product properties by an active product life cycle management. Phospholipids are suitable for this purpose because they are biocompatible, biodegradable, non‐toxic, and available at large scale and of pharmaceutical grade. Besides, they are well known to regulatory authorities.
The Asymmetric Difluoro‐Reformatsky Reaction
Authors: Braun Manfred
Published: January 2021

The structural motif of α,α‐difluoro‐substituted carboxyl and carbonyl groups with hydroxy‐ or amino‐substituents at the stereogenic carbon in β‐position is found frequently in drugs and biologically active compounds. A straightforward method for obtaining those targets in high enantiomeric purity is given by asymmetric difluoro‐Reformatsky and imino‐difluoro‐Reformatsky reactions that lead to α,α‐difluorinated β‐hydroxy‐ and β‐amino‐carboxylates or β‐lactams. Three concepts that open a route to this type of compounds are discussed here. Firstly, chiral substrates are able to induce stereoselectivity in the formation of the newly created stereogenic center. Secondly, covalently bound and removable chiral auxiliaries are used in asymmetric syntheses and, thirdly, chiral additives and ligands at the metal direct the addition of the zinc enolate, the Reformatsky reagent, to aldehydes or imines in an enantioselective manner. The review closes with a short discussion of more recently developed difluoro‐aldol reactions that may be considered as alternatives to the Reformatsky procedure.
Machine learning for mobile network payment security evaluation system
Authors: Wang Fei , Yang Nan , Shakeel P. Mohamed , Saravanan Vijayalakshmi
Published: January 2021

In the recent past, different types of Mobile Network payments gateways have been explosively growing, which allows consumers to access services using various types of mobile devices. The demanding, challenging factors in the mobile network payment gateway security evaluation system includes malware detection, multi‐factor authentication, and fraudulent detection in payment systems. In this paper, Machine Learning‐Assisted Secure Mobile Electronic Payment Framework (ML‐SMEPF) is proposed to detect the presence of malware, authentication issues, and fraud detection in mobile transactions. Here, the Efficient Random Oracle Model is introduced to detect the presence of malware on a host system and multi‐factor authentication challenges posed during mobile payments. Mutual Mobile Authentication model is incorporated with ML‐SMEPF, to identify the type of fraud detection which ensures a safe and secure mobile payment platform. The simulation analysis is performed based on accuracy ratio, security factor, performance, and cost factor proves the reliability of the proposed framework.
Comparative petioler anatomy of tribe Mentheae subfamily Nepetoideae, Lamiaceae from Pakistan
Authors: Jehanzeb Sahira , Zafar Muhammad , Ahmad Mushtaq , Sultana Shazia , Zaman Wajid , Ullah Fazal
Published: January 2021

The current study was carried out to investigate the anatomical characteristics of the petiole of eight species of tribe Mentheae collected from different phytogeographical regions of Pakistan. The transverse section was cut using Shandon Microtome (Finesse 325) to prepare slides. Cluster analysis was carried out to represent the agglomeration schedule of species viewed from the cluster point of view. The distinguishing anatomical characteristics of petioles were noted including petiole shapes, number and shape of vascular bundles, number of vessels, layers of collenchyma, and sclerenchyma. Prunella vulgaris and Salvia plebeia were observed with sclerenchyma cells arranged outside the vascular bundle. The comparative anatomical characteristics of petiole provide valuable information in identifying the tribe Mentheae species. Petiole anatomy plays a significant role in future taxonomic and phylogenetic studies. The aim of the present study was to evaluate the taxonomical importance of the petiole anatomy in the tribe Mentheae. This work will be helpful for the taxonomist and the taxonomic importance of the petiole anatomy in this tribe specifically, and generally will provide baseline to the other studies in family Lamiaceae.
Oxidative stress and endoplasmic reticulum stress contribute to L. paracasei subsp. paracasei M5L exopolysaccharide‐induced apoptosis in HT‐29 cells
Authors: Song Wei , Hu Panpan , Guo Shouli , Hu Jinhong , Song Chen , Wang Tianyi , Gao Zihan , Yue Tianli
Published: January 2021

Colorectal cancer is the third most malignant cancer occurring around the world. Effective prevention and treatment have been increasingly the focus of global attention. Long‐term diet of fermented dairy inhibits proliferation of colon cancer cell, which is considered that not only live lactic acid bacteria but also the secreted exopolysaccharides exert the function. In this scenario, this study aimed to investigate the mechanism of growth inhibition on HT‐29 cells induced in vitro by exopolysaccharides isolated from Lactobacillus paracasei subsp. paracasei M5L (M5‐EPSs).

HT‐29 cells which were treated by a set of concentrations of M5‐EPSs have been investigated of cell viability, characteristic changes, cell cycle distribution, and redox system. The results demonstrated that M5‐EPSs treatments induced HT‐29 cell apoptosis and resulted in upregulation of ROS levels and downregulation of antioxidant enzyme activities, leading to an imbalance in the oxidation system in HT‐29 cells. In response to M5‐EPSs, endogenous ER stress (ERS) markers, including GRP78, ATF4, and CHOP, were transcriptionally altered so that activating the ERS in HT‐29 cells. After NAC treatment, the oxidative stress was inhibited, and the expression of GRP78 and CHOP was significantly decreased, indicating that oxidative stress can significantly affect the ERS pathway. Furthermore, it suggested that the occurrence of apoptosis was associated with Bcl‐2 gene family.

In conclusion, this study demonstrated that M5‐EPSs can induce HT‐29 cells apoptosis by destroying the redox system through activation of the ERS signaling pathway.
Characteristics of saline lake shale oil reservoir and its influence on shale oil enrichment in the Qianjiang Formation, Qianjiang Depression, Jianghan Basin, China
Authors: Luo Jing , Wang Furong , He Sheng , Sun Zhongliang , Wu Shiqiang
Published: January 2021

The enrichment mechanism and process of shale oil are key issues in the studies on shale oil. To date, a variety of methods have been applied to describe the characteristics of typical shale oil reservoirs and reveal the potential influencing factors on marine and freshwater continental shale. However, geological characteristics and influencing mechanism of saline lake shale oil reservoirs remain poorly understood. Here, we report our investigation on the petrological, organic geochemical, and pore structure characteristics of the 10th cyclothem of the third member (Eq3410) of the saline lake–formed Qianjiang Formation in Jianghan Basin using X‐ray fluorescence spectroscopy, X‐ray diffraction, field emission scanning electron microscopy, low‐temperature nitrogen adsorption, and high‐pressure mercury intrusion. The shales of Eq3410 contain high average carbonate contents (45.53%) and clay minerals (20.89%), as well as anisometric glauberite, quartz, feldspar, rock salt, and pyrite. The main lithofacies are dolomitic mudstone, argillaceous dolomite, and calcareous mudstone. The shale samples tested yield total organic carbon (TOC) and S1 + S2 values of 1.94 wt% and 10.46 mg HC/g rock, respectively, and are primarily types II1 and II2 kerogen with thermal maturities between 0.5 and 1.0%. The abundance of organic matter in calcareous mudstone and dolomitic mudstone facies of the Eq3410 shales was relatively high. Inorganic pores are the dominant pore types, including intercrystalline pores within the carbonate and clay minerals, while mesopores and macropores contribute most to the pore volume. Better pore structures exist in argillaceous dolomite and dolomitic mudstone facies, and their characteristics are mainly affected by the compositions of dolomite, clay minerals, and glauberite and, thus, the TOC and oil contents of the shale oil reservoir.
Food insecurity and adverse pregnancy outcomes among rural Malawian women
Authors: Hood Robert B. , Norris Alison H. , Huber‐Krum Sarah , Garver Sarah , Chapotera Gertrude , Turner Abigail N.
Published: January 2021

Objective

To investigate whether food insecurity is associated with adverse pregnancy outcomes such as miscarriage, stillbirth, and neonatal mortality among women in rural Malawi.

Methods

We analyzed data from the baseline (July 2014 to February 2015) and follow‐up (January 2018 to May 2018) waves of a longitudinal study of reproductive‐age women in rural Malawi. We sampled women from villages from the catchment area of a community hospital in rural Lilongwe district of Malawi using stratified cluster sampling. We classified women as food secure or insecure at baseline. Using unadjusted and adjusted log‐binomial models, we used baseline data to examine the cross‐sectional association between food insecurity and ever experiencing an adverse pregnancy outcome. We used baseline and follow‐up data to assess the longitudinal association between food insecurity and experiencing a new adverse pregnancy outcome during follow‐up. In a subgroup analysis, we repeated the longitudinal analysis after restricting the sample to women who had no adverse pregnancy outcomes at baseline.

Results

We observed no significant cross‐sectional association between baseline food insecurity and ever experiencing an adverse pregnancy outcome (adjusted prevalence ratio: 1.09; 95% confidence interval [CI]: 0.78–1.53). Baseline food insecurity was not associated with experiencing a new adverse pregnancy outcome during follow‐up (adjusted risk ratio [aRR]: 1.14, 95% CI: 0.60–2.20) or in the subgroup analysis (aRR: 1.52, 95% CI: 0.78–2.96).

Conclusions

While food insecurity is a critical issue, in this cohort of rural Malawian women, food insecurity was not associated with adverse pregnancy outcomes.
Phone follow up to families of COVID‐19 patients who died at the hospital: families' grief reactions and clinical psychologists' roles
Authors: Menichetti Delor Julia Paola , Borghi Lidia , Cao di San Marco Eugenia , Fossati Ivan , Vegni Elena
Published: January 2021

A proportion of persons affected by coronavirus disease‐19 (COVID‐19) die and do so in extraordinary circumstances. This can make grief management extremely challenging for families. The Clinical Psychology unit of an Italian hospital offered a bereavement follow‐up call to such families. This study aimed to explore the families' experiences and needs collected during these calls, and the role that the psychologists played through the call. A total of 246 families were called over 3 months. Multiple qualitative methods included: (i) written reports of the calls with relatives of patients who died at the hospital for COVID‐19; (ii) qualitative semi‐structured interviews with psychologists involved in the calls; (iii) observation of psychologists' peer group discussions. A thematic analysis was conducted. Six themes emerged: without death rituals, solitary, unexpected, unfair, unsafe, coexisting with other stressors. Families' reactions were perceived by psychologists as close to a traumatic grief. Families' needs ranged from finding alternative rituals to giving meaning and expressing different emotions. The psychologists played both a social‐institutional and a psychological‐human role through the calls (e.g., they cured disrupted communication or validated feelings and choices). This study highlighted the potential of traumatic grief of families of COVID‐19 victims, and provided indications for supporting them within the space of a short phone call.
Optical incoherent technique for noninvasive assessment of blood flow in tissues: Theoretical model and experimental study
Authors: Lapitan Denis , Rogatkin Dmitry
Published: January 2021

Laser noninvasive methods for assessment of a tissue blood flow (BF), for example, the Laser Doppler Flowmetry (LDF), are well‐known today. However, in such methods, low‐frequency fluctuations (LFFs) in the registered optical signal caused by blood volume changes inside a tissue have not been studied in details until now. The aim of this study is to investigate the LFFs formation and to justify the LFFs‐based diagnostic technique for cutaneous BF assessment. LFFs are theoretically described and experimentally shown in the input LDF signal inside the frequency range 0 to 10 Hz. They are substantiated as the basis of the new diagnostic method, in which BF is defined as the magnitude of blood volume changes in a tissue per unit time. The hand‐made prototype of the promising diagnostic tool with light emitted diodes is used to validate the technique in experiments in vivo on 16 healthy volunteers in comparison with the LDF method. Experimental results show a good similarity of the recorded BF for both coherent and incoherent method. The proposed technique makes it possible the creation of inexpensive diagnostic equipment for assessment of cutaneous BF without using lasers and coherent light, completely and functionally comparable to LDF devices.
Clioquinol inhibits cell growth in a SERCA2‐dependent manner
Authors: Lv Xiaoguang , Zhang Wei , Xia Shengli , Huang Zhiwei , Shi Ping
Published: January 2021

Clioquinol has been reported to act as a potential therapy for neurodegenerative diseases and cancer. However, the underlying mechanism is unclear. We have previously reported that clioquinol induces S‐phase cell cycle arrest through the elevation of calcium levels in human neurotypic SH‐SY5Y cells. In this study, different types of cells were observed to detect if the effect of clioquinol on intracellular calcium levels is cell type‐specific. The Cell Counting Kit‐8 assay showed that clioquinol exhibited varying degrees of concentration‐dependent cytotoxicity in different cell lines, and that the growth inhibition caused by it was not related to cell source or carcinogenesis. In addition, the inhibition of cell growth by clioquinol was positively associated with its effect on intracellular calcium content ([Ca2+]i). Furthermore, the elevation of [Ca2+]i induced by clioquinol led to S‐phase cell cycle arrest. Similar to our previous studies, the increase in [Ca2+]i was attributed to changes in the expression levels of the calcium pump SERCA2. Comparison of expression levels of SERCA2 between cell lines showed that cells with high levels of SERCA2 were more sensitive to clioquinol. In addition, analysis using UALCAN and the Human Protein Atlas also showed that the expression of SERCA2 in the corresponding human tissues was similar to that of the cells tested in this study, suggesting potential in the application of clioquinol in the future. In summary, our results expand the understanding of the molecular mechanism of clioquinol and provide an important strategy for the rational use of clioquinol.
ZNF667‐AS1, a positively regulating MEGF10, inhibits the progression of uveal melanoma by modulating cellular aggressiveness
Authors: Yang Hai , Cai Min‐Yun , Rong Hua , Ma Li‐Rong , Xu Yue‐Li
Published: January 2021

Zinc finger protein 667‐antisense RNA 1 (ZNF667‐AS1) is a member of the C2H2 zinc finger protein family. However, the exact effect of ZNF667‐AS1 in uveal melanoma (UM) progression has not been elucidated. The biological roles of ZNF667‐AS1 and MEGF10 were assessed using cell counting kit‐8 and flow cytometry. Quantitative reverse‐transcription polymerase chain reaction and Western blot analyses were conducted to measure the expression of subjects. ZNF667‐AS1 expression was significantly decreased in metastasized UM tissues and its low expression was related to poorer prognosis of UM patients. MEGF10 expression was positively associated with ZNF667‐AS1 expression. The inhibitory effect of ZNF667‐AS1 overexpression on UM cellular malignant behaviors could be reversed by MEGF10 knockdown, which was re‐ascertained by the detection of corresponding protein levels (p53, cyclin D1, Bcl‐2, and Bax). In conclusion, ZNF667‐AS1 might play an inhibitory role in the development of UM by regulating cellular aggressiveness, which was partially realized by positively regulating MEGF10.
TGF‐β1 stimulates aromatase expression and estradiol production through SMAD2 and ERK1/2 signaling pathways in human granulosa‐lutein cells
Authors: Cheng Jung‐Chien , Fang Lanlan , Yan Yang , He Jingyan , Guo Yanjie , Jia Qiongqiong , Gao Yibo , Han Xiaoyu , Sun Ying‐Pu
Published: January 2021

Estradiol (E2), one of the main steroid hormones secreted by the ovaries, plays an important role in maintaining normal female reproductive function. Ovarian granulosa cells are the main source of E2 production because these cells express aromatase, which is encoded by the CYP19A1 gene and catalyzes the final step in E2 biosynthesis from androgens. Transforming growth factor‐beta 1 (TGF‐β1) and its receptors are expressed in human granulosa cells, and TGF‐β1 expression can be detected in human follicular fluid. To date, TGF‐β1 has been shown to regulate various ovarian functions. However, whether aromatase can be regulated by TGF‐β1 in human granulosa cells has not been determined. In the present study, we demonstrate that TGF‐β1 stimulates aromatase expression in primary human granulosa‐lutein cells and in the human ovarian granulose‐like tumor cell line, KGN. We used pharmacological inhibitors and small interfering RNA‐mediated knockdown approaches to reveal that the SMAD2 and ERK1/2 signaling pathways are involved in TGF‐β1‐induced aromatase expression and E2 production. These results not only provide important insights into the molecular mechanisms that mediate TGF‐β1‐induced aromatase expression and E2 production in human granulosa cells but also increase the understanding of the normal physiological roles of TGF‐β1 in the ovary.
Potential COVID‐19 Therapeutic Agents and Vaccines: An Evidence‐Based Review
Authors: Khani Elnaz , Khiali Sajad , Entezari‐Maleki Taher
Published: January 2021

Since the early days of 2020, the severe acute respiratory syndrome coronavirus 2 pandemic has become a global health concern. Currently, some therapies and vaccines have received US Food and Drug Administration approval or emergency use authorization for the management of coronavirus disease 2019. According to the pathophysiology of the disease, several medications have been evaluated in different clinical conditions of the disease. Evidence‐based reviewing and categorizing these medications can guide the clinicians to select the proper medications according to each patient's condition. Therefore, we performed this review to categorize the coronavirus disease 2019 potential therapeutics and vaccines.
Resilient engineering identity development critical to prolonged engagement of Black women in engineering
Authors: Ross Monique S. , Huff James L. , Godwin Allison
Published: January 2021

Background

Social identity theory has been used to understand student and professional engagement in engineering. Engineering identity development, however, can be disrupted by the barriers and challenges associated with the racialized and gendered perceptions of engineering.

Purpose/Hypothesis

This study examined the engineering identity development and resilience of Black women engineers in industry through the exploration of their experiences in the engineering workplace. Many studies document challenges that underrepresented groups face in engineering. This work, instead, focuses on particular supports and empowerment that enabled continued participation in the engineering workforce over time.

Design/Method

This interpretative phenomenological analysis consisted of nine self‐identified Black women engineers currently employed in engineering industry with at least 10 years of work experience and explored the background, pathway into and through engineering, and what it means to be an engineer through 90‐min interviews with each participant.

Results

The results of this study suggest that engineering identity development alone does not contribute to the retention of Black women in the engineering workplace but instead the confluence of race, gender, and role identity that aids in developing a resilient engineering identity.

Conclusions

The formal, informal, and structural educational experiences of Black women engineers are critical to the development of a resilient engineering identity. This identity is dependent on the complexities associated with being Black, a woman, and an engineer.
A theoretical study of inversion barriers and NMR chemical shifts of 3‐pyrazolines (2,3‐dihydro‐1H‐pyrazoles)
Authors: Alkorta Ibon , Elguero José
Published: January 2021

A rather neglected family of heterocyclic compounds, the 3‐pyrazolines or 2,3‐dihydro‐1H‐pyrazoles, has been studied theoretically at the B3LYP/6–311++G(d,p) level to obtain geometries and energies and at the GIAO/B3LYP/6–311++G(d,p) level for NMR chemical shifts. The calculated barriers of inversion of the N‐substituents reproduce adequately the scarce experimental data. The calculated 1H and 13C chemical shifts are consistent with those reported in the literature. A combination of both results, geometries, and 13C chemical shifts, shed light on the conformation of N‐phenyl groups.
The nexus of physical, cognitive, and emotional engagement with academic staff turnover intention: The moderating role of organizational politics
Authors: Lata Lata , Mohamed Zainal Siti Rohaida , Jan Ghulam , Memon Ubedullah
Published: January 2021

The goal of the study is to investigate the effect of physical, cognitive, and emotional engagement on turnover intention among academic staff in public sector universities in Pakistan. The study highlights the buffering effect of organizational politics on employee engagement and turnover intention. The study employs a quantitative research design based around a partial least square analysis of datah gathered from academic staff in public universities in Sindh. The study shows there is a significant negative association between turnover intention, and employees' cognitive and emotional engagement. The findings of the study confirm the buffering effect of organizational politics on physical and emotional engagement and turnover intention. The direct effect of employees' physical engagement on turnover intention was not found to be significant. This study contributes to the conservation of resources theory; it also offers solutions to the problem of staff turnover based on building an organizational culture grounded in justice and teamwork.
Performance and survival implications of sourcing choice sequence across an architectural innovation life cycle
Authors: Park Woo‐Yong , Tangpong Chanchai
Published: January 2021

This study investigates follower firms' make–buy sourcing choices and sequences in response to an architectural innovation by an innovator. We argue that the dynamic trade‐offs among knowledge acquisition, knowledge transformation, and transaction cost reduction underlie the performance impacts of make–buy sourcing choices and sequences across the architectural innovation life cycle. Using the data gathered from the gear‐shifting market of the U.S. bicycle industry, we empirically demonstrate that “buy” is a superior sourcing choice before key market‐winner features (i.e., dominant design) have emerged. After that, “make” becomes a superior choice. We then demonstrate that the “buy‐to‐make” sourcing sequence is associated with superior technological and financial performances in the postdominant design phase of the architectural innovation period, as well as with greater firm survival during the market shakeout in the later period of modular standardization. The theoretical and managerial implications of our findings are also discussed.