bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractObjectiveCOPA 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.MethodsMultiplexed 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.ResultsMultiplexed 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.ConclusionClinical 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

AbstractThe 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

SummaryCognitive 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

AbstractBackgroundIn 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.ResultsBased 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.ConclusionsTaxonomic 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

AbstractAimsDiabetes 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 resultsA 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.ConclusionsIn 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

AbstractMononuclear 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

AbstractThis 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

AbstractThe 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

AbstractIn 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

AbstractColorectal 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.
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

AbstractObjectiveTo investigate whether food insecurity is associated with adverse pregnancy outcomes such as miscarriage, stillbirth, and neonatal mortality among women in rural Malawi.MethodsWe 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.ResultsWe 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).ConclusionsWhile food insecurity is a critical issue, in this cohort of rural Malawian women, food insecurity was not associated with adverse pregnancy outcomes.
Optical incoherent technique for noninvasive assessment of blood flow in tissues: Theoretical model and experimental study
Authors: Lapitan Denis , Rogatkin Dmitry 
Published: January 2021

AbstractLaser 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.