bluuebunny/crossref_metadata_2025 huggingface dataset:
Electromagnetic Fields Generated by the IteraCoil Device Differentiate Mesenchymal Stem Progenitor Cells Into the Osteogenic Lineage
Authors: Haroutunian Gagik Greg , Tsaghikian Ashot , Fedorova Elena , Chaurasia Pratima , Gusella Gabriele Luca , Mosoian Arevik
Published: April 2022

Rapid advances in mesenchymal stem progenitor cells (MSPCs) have rendered impetus into the area of cell therapy and regenerative medicine. The main promise of future stem cell therapies is their reliance on autologous stem cells derived from adipose tissue, which also includes treatments of bone fractures and degeneration. The effectiveness of different electric devices utilized to reprogram MSPCs toward osteogenic differentiation has provided varying degrees of effectiveness for clinical use. Adipose tissue‐derived MSPCs were flow‐cytometrically characterized and further differentiated into osteoblasts by culturing either in growth medium with pro‐osteogenic supplements or without supplements with alternating electromagnetic field (EMF) generated by IteraCoil. IteraCoil is a multi‐solenoid coil with a specific complex geometry that creates a 3D‐EMF with desired parameters without directly applying electrodes to the cells and tissues. The flow‐cytometric analysis of highly enriched (≥95%) adipose‐derived MSPCs (CD34−, CD73+, CD90+, and CD105+) was utilized for the study. Osteoblasts and chondrocyte differentiations were then assessed by specific staining and quantified using ImageJ (National Institutes of Health). The osteoblastic differentiation of MSPCs cultured in regular medium and exposed to EMF at 0.05 and 1 kHz frequencies was compared with MSPCs cultured in a pro‐osteogenic supplemented medium. In this study, we demonstrated that EMF from IteraCoil might have affected the signaling pathways that induce the osteogenic differentiation of human adipose‐derived MSPCs in the absence of exogenous osteogenic factors. Therefore, EMF‐generated osteogenic differentiation of reprogrammed adipose‐derived autologous MSPCs may treat the loss of osteoblasts and osteoporosis and open new avenues for the development of regenerative cellular therapy. © 2022 Bioelectromagnetics Society.
Case of possible encephalopathy following receiving the first dose of Iranian COVID‐19Vaccine; COVIran Barakat
Authors: Fallahi Mohammad Javad , Esmaeilzadeh Shahri Navid , Khodamoradi Zohre , Meymandi Nia Moazameh , Sehatpour Faezeh , Mahmoudi Laleh
Published: April 2022

We report a case of possible encephalopathy after receiving the first dose of Iran's COVIran Barekat vaccine. The patient had no history of neurological or mental illness. Clinical examinations and radiology reports were performed and differential diagnoses were analyzed by the treatment team. Finally, the possible association between vaccination and encephalopathy was concluded.
On the edge—A diagnostic odyssey
Authors: McLean Hailey , Palmquist Rachel , Nadauld Lincoln D. , Malone Jenkins Sabrina , Bonkowsky Joshua , Filloux Francis
Published: April 2022

The diagnostic odyssey of a child with epileptic encephalopathy was resolved by rapid whole genome sequencing. This identified a rare form of pyridoxine responsive epilepsy due to a pathogenic variant in PLPBP. Access to such potentially life‐changing diagnostic technology needs to expand in a thoughtful and equitable manner.
Applying Magnetic‐Responsive Nanocatalyst‐Liquid Interface for Active Molecule Manipulation to Boost Catalysis Beyond Diffusion Limit
Authors: Mohamed‐Ibrahim Nur Amalina binte , Kheng Boong Siew , Zhong Ang Zhi , Shiuan Ng Li , Tan Jia Ying Charlene , Chong Carice , Kwee Lee Hiang
Published: April 2022

Efficient nanocatalysis requires swift delivery of reactants to catalytic sites, but the presence of diffusion‐dominated, hydrodynamic boundary layers on all heterogeneous catalysts impedes fast chemical transformation. Here, efficient nanocatalysis is achieved by applying a magnetic‐responsive nanocatalyst‐liquid interface to create a vortex‐like flow that rapidly pulls reactants from bulk solution to the catalyst, beyond the diffusion limit. Consequently, our design attains a >90 % degradation efficiency in <5 min with reaction kinetics tunable via the nanocatalyst spin rate. The spinning nanocatalyst notably exhibits reaction kinetics and molecule transfer rates >10‐fold and 30‐fold faster than traditional homogenization methods, respectively. This unique molecule delivery design will complement recent advances in active catalytic nanomaterials to realize ideal nanocatalysis in emerging chemical, energy, and environmental applications.
Towards a Generalized ORR Mechanism in M2+‐Containing DMSO: Oxygen Reduction and Evolution in Ca2+‐Containing DMSO on Atomically Smooth and Rough Pt
Authors: Koellisch‐Mirbach Andreas , Bawol Pawel Peter , Park Inhee , Baltruschat Helmut
Published: April 2022

The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in Ca2+ containing dimethyl sulfoxide (DMSO) on atomically smooth Pt(111) and Pt(100) and rough Pt surfaces is reported. As demonstrated by cyclic voltammetry and XPS, the bromine adlayer used to protect Pt single crystals against ambient air and solvent vapor is desorbed in DMSO and does not affect the following measurements. Cyclic voltammetry, differential electrochemical mass spectrometry (DEMS), and rotating ring disk electrode (RRDE) investigations with variation of the electrode surface roughness and atomically surface structure show, that on Pt electrodes the CaO2 adsorbate layer formation determines the ORR product distribution. On Pt electrodes, calcium peroxide is formed on the clean electrode, whereas calcium superoxide is formed at the adsorbate covered electrode. We furthermore identified four key parameters, which strongly affect the ORR product distribution: 1) The electrode oxide interaction: A strong interaction increases superoxide contribution; 2) The alkaline earth metal oxide interaction: A strong interaction increases peroxide contribution; 3) The electrode surface area: A large electrode surface area increases peroxide contribution; 4) Electrode surface defects: Defects increase superoxide contribution. Finally, reviewing earlier results of our group, we provide a more general mechanism for the oxygen reduction alkaline earth metal cation containing DMSO, for a variety of electrode materials.
Peroxynitrite‐Promoted Persulfide Prodrugs with Protective Potential against Paracetamol Poisoning
Authors: Xu Ya‐Wen , Xu Bi‐Xin , Wang Jiankun , Jin Hao‐Wen , Xu Si‐Tao , Wang Guangji , Zhen Le
Published: April 2022

The newly emerging persulfide prodrugs provide additional options for the profound study of persulfide, a fascinating molecule expected to intervene in biological functions and even diseases. Peroxynitrite is often the culprit in pathological processes characterized by oxidative stress, while the persulfide prodrug responsive to it is still pending. To enrich the family of redox‐activated prodrugs, we designed prodrugs with a 2‐oxo‐2‐phenylacetamide trigger, which achieved the release of persulfide via 1, 6‐N,S‐relay. The degradation of prodrugs and the formation of persulfides were confirmed to be peroxynitrite‐responsible by the qualitative and quantitative studies based on LC‐MS/MS methods and a spectrophotometry‐based tag‐switch strategy. Furthermore, these prodrugs showed potent peroxynitrite scavenging activity, cellular therapeutic potential against paracetamol poisoning in HepG2 and oxidative stress in H9c2, as well as desirable in vitro metabolic properties.
Boron‐Locked Starazine – A Soluble and Fluorescent Analogue of Starphene
Authors: Feng Yi , Zhou Jiadong , Qiu Honglin , Schnitzlein Matthias , Hu Jingtao , Liu Linlin , Würthner Frank , Xie Zengqi
Published: April 2022

A starlike heterocyclic molecule containing an electron‐deficient nonaaza‐core structure and three peripheral isoquinolines locked by three tetracoordinate borons, namely isoquinoline‐nona‐starazine (QNSA), is synthesized by using readily available reactants through a rather straightforward approach. This new heteroatom‐rich QNSA possesses a quasi‐planar π‐backbone structure, and bears phenyl substituents on borons which protrude on both sides of the π‐backbones endowing it with good solubility in common organic solvents. Contrasting to its starphene analogue, QNSA shows intense fluorescence with a quantum yield (PLQY) of up to 62 % in dilute solution.
Reactivity of Diphenylberyllium as a Brønsted Base and Its Synthetic Application
Authors: Thomas‐Hargreaves Lewis R. , Berthold Chantsalmaa , Augustinov William , Müller Matthias , Ivlev Sergei I. , Buchner Magnus R.
Published: April 2022

Diphenylberyllium [Be3Ph6] is shown here to react cleanly as a Brønsted base with a vast variety of protic compounds. Through the addition of the simple molecules tBuOH, HNPh2 and HPPh2, as well as the more complex 1,3‐bis‐(2,6‐diisopropylphenyl)imidazolinium chloride, one or two phenyl groups in diphenylberyllium were protonated. As a result, the long‐postulated structures of [Be3(OtBu)6] and [Be(μ‐NPh2)Ph]2 have finally been verified and shown to be static in solution. Additionally [Be(μ‐PPh2)(HPPh2)Ph]2 was generated, which is only the second beryllium‐phospanide to be prepared; the stark differences between its behaviour and that of the analogous amide were also examined. The first crystalline example of a beryllium Grignard reagent with a non‐bulky aryl group has also been prepared; it is stabilised with an N‐heterocyclic carbene.
A Mesoionic Diselenolene Anion and the Corresponding Radical Dianion
Authors: Dong Zhaowen , Sienkiewicz Andrzej , Suleymanov Abdusalom A. , Berton Cesare , Fadaei‐Tirani Farzaneh , Scopelliti Rosario , Severin Kay
Published: April 2022

Dichalcogenolenes are archetypal redox non‐innocent ligands with numerous applications. Herein, a diselenolene ligand with fundamentally different electronic properties is described. A mesoionic diselenolene was prepared by selenation of a C2‐protected imidazolium salt. This ligand is diamagnetic, which is in contrast to the paramagnetic nature of standard dichalcogenolene monoanions. The new ligand is also redox‐active, as demonstrated by isolation of a stable diselenolene radical dianion. The unique electronic properties of the new ligand give rise to unusual coordination chemistry. Thus, preparation of a hexacoordinate aluminum tris(diselenolene) complex and a Lewis acidic aluminate complex with two ligand‐centered unpaired electrons was achieved.
New enantioselective liquid chromatography method development and validation of dipeptidyl peptidase IV inhibitors using a macrocyclic glycopeptide (vancomycin) chiral stationary phase under polar ionic mode condition
Authors: Arnipalli Manikanta Swamy , Nimmu Narendra varma , Boddapati S. N. Murthy , Challa Gangu Naidu , Jaweria Syed , Kola A. Emmanuel
Published: April 2022

The direct separation of dipeptidyl peptidase IV (DPP‐4) inhibitors such as Sitagliptin (STG), Linagliptin (LIG), and Saxagliptin (SAG) enantiomers in normal phase conditions have been achieved on immobilized polysaccharide‐based chiral stationary phases (CSPs), as well as on the macrocyclic glycopeptide vancomycin chiral stationary phase (Chirobiotic V2) under polar ionic mode. The enantiomers of these targets could be separated completely (resolution factor Rs > 2) using the Chirobiotic V2 column in polar ionic mode with the mobile phase (MeOH/AcOH/TEA 100/0.3/0.1 v/v/v) in an isocratic elution at 1.0 ml min−1. The effect of the mobile phase composition on separation, including buffer salts, acid–base modifiers, and analyte structures, was evaluated. The developed technique was validated in the polar ionic mode according to the International Conference on Harmonization (ICH) Q2R1 guidelines in terms of accuracy, precision, selectivity, linearity, limit of detection (LOD), and limit of quantification (LOQ). The calibration curve was linear in a concentration range from LOQ to 3.75 μg/ml. The LOD and LOQ of STG, LIG, and SAG were 0.15 and 0.45, 0.15 and 0.50, 0.16 and 0.50, respectively. The proposed method is said to be selective, accurate, and precise. Finally, the validated method was used successfully for the quantitative determination of DPP‐4 enantiomers in pharmaceutical analytes.
Synthesis, in vitro Antileishmanial Efficacy and Hit/Lead Identification of Nitrofurantoin‐Triazole Hybrids
Authors: Zuma Nonkululeko H. , Aucamp Janine , Viljoen Maryna , N'Da David D.
Published: April 2022

Leishmaniasis is a vector‐borne neglected parasitic infection affecting thousands of individuals, mostly among populations in low‐ to moderate‐income developing countries. In the absence of protective vaccines, the management of the disease banks solely on chemotherapy. However, the clinical usefulness of current antileishmanial drugs is threatened by their toxicity and the emergence of multidrug‐resistant strains of the causative pathogens. This emphasizes the imperative for the development of new and effective antileishmanial agents. In this regard, we synthesized and evaluated in vitro the antileishmanial activity and cytotoxicity profile of a series of nitrofurantoin‐triazole hybrids. The nitrofurantoin derivative 1 featuring propargyl moiety was distinctively the most active of all, was nontoxic to human cells and possessed submicromolar cellular activity selectively directed towards the pathogens of the life threatening visceral leishmaniasis. Hence it was identified as potential antileishmanial lead for further investigation into its prospective to act as alternative to therapies.
Estimation of coefficient of variation using linear moments and calibration approach for nonsensitive and sensitive variables
Authors: Shahzad Usman , Ahmad Ishfaq , Hanif Muhammad , Al‐Noor Nadia H.
Published: April 2022

Assessment of coefficient of variation (CV) is of major importance in numerous examinations. However, the appearance of extreme observations raises concerns about the outcomes of CV estimates based on conventional moments. So, motivated by some recent developments in finite sampling theory, we propose some new estimators of CV based on the properties of linear moments (L‐moments and Trimmed L‐moments), which are highly robust whenever outliers or extreme observations appear in a dataset. The proposed estimators are initially established on the premise that the variable of interest is nonsensitive which deals with the subjects that do not embarrass respondents when asked about them explicitly. These estimators are also applied to situations where the variable of interest is associated with sensitive issues that cause measurement errors resulting from nonresponse or unreliable reporting where such issues can be mitigated by increasing respondent participation by scrambled response models which obscure the true value of the sensitive variable. Four models are considered for this article: additive, multiplicative, mixed, and combined additive‐multiplicative models. Finally, in both nonsensitive and sensitive settings, real‐life data sets are employed to undertake simulation‐based analysis. In all cases, the proposed estimators considerably increased efficiency.
Introducing Alternative Algorithms for the Determination of the Distribution of Relaxation Times
Authors: Bergmann Tobias G. , Schlüter Nicolas
Published: April 2022

Impedance spectroscopy is a powerful characterization method to evaluate the performance of electrochemical systems. However, overlapping signals in the resulting impedance spectra oftentimes cause misinterpretation of the data. The distribution of relaxation times (DRT) method overcomes this problem by transferring the impedance data from the frequency domain into the time domain, which yields DRT spectra with an increased resolution. Unfortunately, the determination of the DRT is an ill‐posed problem, and appropriate mathematical regularizations become inevitable to find suitable solutions. The Tikhonov algorithm is a widespread method for computing DRT data, but it leads to unlikely spectra due to necessary boundaries. Therefore, we introduce the application of three alternative algorithms (Gold, Richardson Lucy, Sparse Spike) for the determination of stable DRT solutions and compare their performances. As the promising Sparse Spike deconvolution has a limited scope when using one single regularization parameter, we furthermore replaced the scalar regularization parameter with a vector. The resulting method is able to calculate well‐resolved DRT spectra.
Impact of Obesity on Postprandial Triglyceride Contribution to Glucose Homeostasis, Assessed with a Semimechanistic Model
Authors: Leohr Jennifer , Kjellsson Maria C.
Published: April 2022

The integrated glucose‐insulin model is a semimechanistic model describing glucose and insulin after a glucose challenge. Similarly, a semiphysiologic model of the postprandial triglyceride (TG) response in chylomicrons and VLDL‐V6 was recently published. We have developed the triglyceride‐insulin‐glucose‐GLP‐1 (TIGG) model by integrating these models and active GLP‐1. The aim was to characterize, using the TIGG model, the postprandial response over 13 hours following a high‐fat meal in 3 study populations based on body mass index categories: lean, obese, and very obese. Differential glucose and lipid regulation were observed between the lean population and obese or very obese populations. A population comparison revealed further that fasting glucose and insulin were elevated in obese and very obese when compared with lean; and euglycemia was achieved at different times postmeal between the obese and very obese populations. Postprandial insulin was incrementally elevated in the obese and very obese populations compared with lean. Postprandial chylomicrons TGs were similar across populations, whereas the postprandial TGs in VLDL‐V6 were increased in the obese and very obese populations compared with lean. Postprandial active GLP‐1 was diminished in the very obese population compared with lean or obese. The TIGG model described the response following a high‐fat meal in individuals who are lean, obese, and very obese and provided insight into the possible regulation of glucose homeostasis in the extended period after the meal by utilizing lipids. The TIGG‐model is the first model to integrate glucose and insulin regulation, incretin effect, and postprandial TGs response in chylomicrons and VLDL‐V6.
Regulation of Drug Transport Proteins—From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium
Authors: Brouwer Kim L.R. , Evers Raymond , Hayden Elizabeth , Hu Shuiying , Li Cindy Yanfei , Meyer zu Schwabedissen Henriette E. , Neuhoff Sibylle , Oswald Stefan , Piquette‐Miller Micheline , Saran Chitra , Sjöstedt Noora , Sprowl Jason A. , Stahl Simone H. , Yue Wei
Published: April 2022

Membrane transport proteins are involved in the absorption, disposition, efficacy, and/or toxicity of many drugs. Numerous mechanisms (e.g., nuclear receptors, epigenetic gene regulation, microRNAs, alternative splicing, post‐translational modifications, and trafficking) regulate transport protein levels, localization, and function. Various factors associated with disease, medications, and dietary constituents, for example, may alter the regulation and activity of transport proteins in the intestine, liver, kidneys, brain, lungs, placenta, and other important sites, such as tumor tissue. This white paper reviews key mechanisms and regulatory factors that alter the function of clinically relevant transport proteins involved in drug disposition. Current considerations with in vitro and in vivo models that are used to investigate transporter regulation are discussed, including strengths, limitations, and the inherent challenges in predicting the impact of changes due to regulation of one transporter on compensatory pathways and overall drug disposition. In addition, translation and scaling of in vitro observations to in vivo outcomes are considered. The importance of incorporating altered transporter regulation in modeling and simulation approaches to predict the clinical impact on drug disposition is also discussed. Regulation of transporters is highly complex and, therefore, identification of knowledge gaps will aid in directing future research to expand our understanding of clinically relevant molecular mechanisms of transporter regulation. This information is critical to the development of tools and approaches to improve therapeutic outcomes by predicting more accurately the impact of regulation‐mediated changes in transporter function on drug disposition and response.
A Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Novel Insulin Dimer
Authors: Walford Geoffrey A. , Duncan Kelly E. , Hernandez Moises , Vaddady Pavan , Hompesch Marcus , Morrow Linda , Stoch S. Aubrey
Published: April 2022

Insulin molecules of size much greater than natural insulin have been synthesized and studied with the intention of widening the therapeutic window between adequate glycemic control and hypoglycemia as compared with conventional insulins. MK‐1092 is a synthetic insulin dimer with favorable properties demonstrated in preclinical studies. Here, we report the results of the first‐in‐human, randomized, double‐blind, active‐control, single ascending dose trial of MK‐1092, conducted in healthy adults, adults with type 1 diabetes (T1D), and adults with type 2 diabetes (T2D). MK‐1092 was well tolerated in all study populations, and no dose‐related adverse events were identified across the evaluated dose range (4–64 nmol/kg). Circulating concentrations of MK‐1092 were approximately dose‐proportional. Maximum glucose infusion rate (GIR) and 24‐hour time‐weighted average GIR were evaluated under euglycemic clamp conditions. These pharmacodynamic measurements were approximately dose‐proportional in all study populations; at similar doses, the GIR parameters were lower in adults with T2D than in healthy adults or adults with T1D, likely due to the influence of insulin resistance. At doses ≥ 16 nmol/kg, MK‐1092 had similar or greater effects than glargine 3 nmol/kg (0.5 units/kg) on increasing GIR in each study population and on suppressing free fatty acids and ketone generation in adults with T1D. MK‐1092 did not prevent a subsequent high dose of lispro from increasing the GIR in healthy adults. Additional studies in adults with T1D and T2D are needed to further evaluate the safety, tolerability, and efficacy profile of MK‐1092 and its potential for differentiation from more conventional insulins. (ClinicalTrials.gov: NCT03170544)
A novel reduced switch single‐phase five‐level inverter
Authors: Bogineni Jayachandra , Nakka Jayaram
Published: April 2022

Conventional multilevel inverters (MLI) incorporate many independent dc sources and switches, which adds to the overall system's cost and complexity. This article presents a detailed analysis of a reduced switch single‐phase five‐level inverter for medium‐ and high‐power applications. The comparison of the proposed topology with traditional and recently developed MLI topologies shows that the topology proposed has a smaller number of circuit elements, isolated dc sources, and voltage stress of half of the supply voltage on 50% of switches. Reducing the number of components and sources reduces the complexity and total cost of the inverter. These reduced switches voltage stresses increase the overall system reliability. The MATLAB/SIMULINK simulations for different load changes were carried out for analysis in software mode. The scaled‐down prototype is used for the validation of simulation analysis. The components comparison was also carried out to list the advantages of this topology over other MLI configurations.
Posttranslational modification of Aurora A‐NSD2 loop contributes to drug resistance in t(4;14) multiple myeloma
Authors: Jiang Hongmei , Wang Yixuan , Wang Jingjing , Wang Yafei , Wang Sheng , He Enyang , Guo Jing , Xie Ying , Wang Jingya , Li Xin , Peng Ziyi , Wang Mengqi , Hou Jian , Liu Zhiqiang
Published: April 2022

Background

t(4;14)(p16;q32) cytogenetic abnormality renders high level of histone methyltransferase NSD2 in multiple myeloma (MM) patients, and predicts poor clinical prognosis, but mechanisms of NSD2 in promoting chemoresistance have not been well elucidated.

Methods

An epigenetics compound library containing 181 compounds was used to screen inhibitors possessing a prior synergistic effect with bortezomib (BTZ) in vitro. Molecular biology techniques were applied to uncover underlying mechanisms. Transcriptome profile assay was performed by RNA‐seq. NSG mouse‐based xenograft model and intra‐bone model were applied to qualify the synergistic effect in vivo.

Results

We identified an Aurora kinase A inhibitor (MLN8237) possessed a significant synergistic effect with BTZ on t(4;14) positive MM cells. Aurora A protein level positively correlated with NSD2 level, and gain‐ and loss‐of‐functions of Aurora A correspondingly altered NSD2 protein and H3K36me2 levels. Mechanistically, Aurora A phosphorylated NSD2 at S56 residue to protect the protein from cleavage and degradation, thus methylation of Aurora A and phosphorylation of NSD2 bilaterally formed a positive regulating loop. Transcriptome profile assay of MM cells with AURKA depletion identified IL6R, STC2 and TCEA2 as the downstream target genes responsible for BTZ‐resistance (BR). Clinically, higher expressions of these genes correlated with poorer outcomes of MM patients. Combined administration of MLN8237 and BTZ significantly suppressed tumour growth in LP‐1 cells derived xenografts, and remarkably alleviated bone lesion in femurs of NSG mice.

Conclusions

Aurora A phosphorylates NSD2 at S56 residue to enhance NSD2 methyltransferase activity and form a positive regulating loop in promoting MM chemoresistance, thus pharmacologically targeting Aurora A sensitizes t(4;14) positive MM to the proteasome inhibitors treatment. Our study uncovers a previously unknown reason of MM patients with t(4;14) engendering chemoresistance, and provides a theoretical basis for developing new treatment strategy for MM patients with different genomic backgrounds.
Relevance of polyclonal plasma cells and post‐therapy immunomodulation in measurable residual disease assessment in multiple myeloma
Authors: Das Nupur , Dahiya Meetu , Gupta Ritu , Kumar Lalit , Sharma Atul , Rai Sandeep , Singh Saroj , Prajapati Vijay K. , Sahoo Ranjit K. , Gogia Ajay
Published: April 2022

Background

Immunophenotypic profile and post‐therapy alteration in antigenic expression were evaluated in normal, reactive, and aberrant plasma cells (NPC, RPC, and APC) for impact on measurable residual disease (MRD) assessment in multiple myeloma (MM).

Methods

Samples from non‐MM staging marrow (n = 30), Hodgkin's lymphoma (n = 30) and MM (n = 724) were prospectively evaluated for expression profiles of NPC, RPC, and APC using antigens recommended in consensus guidelines.

Results

Polyclonal NPC‐RPC demonstrated aberrations for all antigens evaluated with a higher frequency of aberrancies in post‐therapy samples compared to treatment naïve samples (p < 0.001%). Immunomodulation in APC was observed in 79% of post‐therapy samples with a change in expression of 1, 2, and ≥3 antigens in 19.9%, 15.6%, and 43.5% samples, respectively. In 13.4% of samples, APC showed no aberrancy and aberrant status was assigned based on cytoplasmic light chain restriction (cyLCR) alone. 9% samples with an admixture of NPC and APC displayed normal cytoplasmic kappa to lambda ratio (cyKLR) when the percentage of APC of total PC (neoplastic plasma cell index, NPCI), was below 25% and 50% for kappa and lambda restricted cases, respectively.

Conclusion

The panorama and high frequency of antigenic aberrations on polyclonal PC signify the importance of MRD assay validation on a large cohort under normal and reactive conditions. Frequent Immunophenotypic shifts in APC re‐confirm the redundancy of baseline immunophenotype for MRD evaluation. Small clones of APC may be missed by assessment of cyKLR alone and therefore, surface marker aberrancy supported by cyLCR is required for definitive assignment of residual APC.
Swarm intelligence‐based deep ensemble learning machine for efficient channel estimation in MIMO communication systems
Authors: Manasa B.M.R. , P. Venugopal
Published: April 2022

Multiple‐input multiple‐output (MIMO) technology is much significant for achieving high data rates while considering the multiuser communication. For this purpose, the estimation of Channel State Information (CSI) is performed by the pilot. But, the estimated CSI cannot be applied for downlinks while processing an extremely high speed mobile data as it gets outdated because of the rapid channel variation. Estimating the channel in the MIMO systems is highly difficult on using non‐stationary channel characteristics under the high mobility environments. Channel estimation with received signal‐to‐noise ratio (SNR) feedback ensures an effective performance in the practical wireless MIMO systems. This paper plans to develop an intelligent deep learning strategy to solve the channel estimation problem in MIMO system. The main goal of the proposed model is to estimate the MIMO channel coefficients at a transmitter based on the received SNR feedback information from a receiver using the swarm intelligence‐based deep ensemble learning machine (SI‐DELM). For both the scenarios, the SI‐DELM is developed, in which the convolution neural network (NN) with three classifiers is used. Here, the fully connected layers of CNN are replaced by the NN, recurrent neural network (RNN), and deep neural network (DNN). In the SI‐DEL‐based channel estimation, the hyper parameter tuning is performed by the adaptive iteration assisted mixture ratio‐based cat swarm optimization (AIMR‐CSO) for minimizing the mean square error (MSE) and bit error rate (BER) of the estimated channel. Finally, by performing numerical simulations, the efficiency and better performance of the suggested model is revealed by conducting the comparison between proposed and conventional models.
Fuzzy preference ranking organization method for enrichment evaluation‐based node cooperation technique for improving QoS in MANETs
Authors: Mylsamy Rajkumar , Jayaprakash Karthika
Published: April 2022

Cooperation between mobile nodes is the predominant factor required for achieving reliable data dissemination in mobile ad hoc networks (MANETs), since non‐cooperative nodes crumbles the routing process and degrades network performance. The degree of non‐cooperation rendered by mobile nodes need to be accurately identified by exploring feasible and comprehensive number of criteria to achieve maximized cooperation in uncertain MANET. In this paper, fuzzy preference ranking organization method for enrichment evaluation (FPROMETHEE)‐based node cooperation technique is proposed with the merits of trapezoidal fuzzy interval numbers that aids in the selection of high trustworthy mobile nodes for attaining maximized data delivery. This FPROMETHEE technique utilizes complex and multiple criteria for potential ranking in the presence of finite number of mobile nodes. It prevented the bias of information that is more common during the judgmental process associated with the cooperation estimation of mobile nodes. It includes information about the relative weights of criteria and decision maker's preferences for estimating the trust of mobile nodes to include or isolate them from the routing path. It is also useful in handling the degree of uncertainly involved in the process of routing without compromising Quality of Service (QoS) level in the network. The simulation experiments of the proposed FPROMETHEE technique conducted using ns‐2 simulator confirmed its predominance in enhancing the packet dissemination rate, throughput, energy consumptions, total overhead, and packet loss rate for different number of mobile nodes, malicious nodes, and pairs of source and destination nodes.
An interest‐based access control scheme via edge verification in Named Data Networking
Authors: Tao Yu , Zhu Yi
Published: April 2022

Named Data Networking (NDN) is a disruptive future architecture, in which content delivery can be significantly improved through named routing and distributed caching. However, distributed caching also leads to serious access control problems. Once a content is disseminated to the network, any entity can fetch it regardless of owning the access permission or not. To protect the authorized content, current solutions are mainly designed based on data packet encryption, but redundant in‐network traffic is still a challenge due to illegal interest‐data exchange. Focus on this problem, an Interest‐Based Access Control scheme via Edge Verification (IBAC‐EV) is proposed in this paper. In IBAC‐EV, the producer authorizes the user to sign interest packet. By checking the signature, the edge router can forbid unsubscribed users to enter network through discarding interest packets. Simulation results show that IBAC‐EV can effectively reduce the in‐network traffic. Moreover, by using proxy signature algorithm, it simplifies the complexity of key management and alleviates the storage overhead on the edge router.
Performance evaluation of multiuser Internet of Things wireless‐powered relaying networks with transceiver hardware imperfections over Nakagami‐m fading channels
Authors: Kharwar Preeti , Yadav Suneel , Purohit Neetesh
Published: April 2022

We investigate the performance of multiuser Internet of Things (IoT) relay networks in the presence of transceiver hardware impairments. In particular,
IoT users communicate with a destination via a simultaneous wireless information and power transfer (SWIPT) amplify‐and‐forward relay. We exploit both time‐switching (TS) and power‐splitting (PS) protocols at the SWIPT‐aided relay terminal. Specifically, we derive the exact outage probability (OP) expressions for both TS and PS schemes under transceiver hardware imperfections over Nakagami‐m fading channels. In addition, we derive the asymptotic OP expressions for both TS and PS schemes in the high signal‐to‐noise ratio regime. From which, the diversity order of
can be achieved, where
denotes the fading severity parameter for the channel between
IoT users and relay. Furthermore, we present a tight upper bound for the ergodic capacity (EC) under both TS and PS schemes with transceiver hardware impairments over Nakagami‐m fading channels. Moreover, our results demonstrate the impact of number of IoT users, fading severity parameters, TS factor, PS factor, and energy conversion efficiency, on the system performance. We also validate our analytical findings via numerical and simulation results.
The importance of marshes providing soil stabilization to resist fast‐flow erosion in case of a dike breach
Authors: Marin‐Diaz Beatriz , Govers Laura L. , van der Wal Daphne , Olff Han , Bouma Tjeerd J.
Published: April 2022

Salt marshes provide valuable ecosystem services including coastal protection by reducing wave loading on dikes and seawalls. If the topsoil is erosion resistant to fast‐flowing water, it may also reduce breach depth if a dike fails. In this experiment, we quantified the topsoil erosion resistance from marshes and bare tidal flats with different soil types to understand the extent to which they can help reduce breach depth. Intact soil samples were collected from 11 locations in the Netherlands at different tidal elevations and then exposed for 3 h to 2.3 m/s currents. To the samples that remained stable after flow exposure, an artificial crack was made to test their stability following soil disturbance. All samples from the tidal flats were completely eroded, regardless of sediment type. In contrast, all samples from well‐established marsh plateaus were stable as long as no disturbances were made, including those with sandy subsoils. After creating artificial cracks, samples with a thin cohesive top layer on top of sandy subsoil collapsed, while marshes with silty subsoils remained stable. Pioneer marshes on sandy substrate without a cohesive top layer were the only vegetated soils that completely eroded. The lower erosion of marshes with either sandy or silty soils compared to bare tidal flats was best explained by the presence of a top layer with belowground biomass, high organic content, high water content, and low bulk density. When analyzing the erodibility of marshes only, fine root density was the best predictor of erosion resistance. This study demonstrates the importance of preserving, restoring, or creating salt marshes, to obtain a topsoil that is erosion resistant under fast‐flowing water, which helps reduce breach dimensions if a dike fails. The probability of topsoil erosion in established marshes with sandy subsoil is higher than in silty marshes. A silty layer of cohesive sediment on top of the sand provides extra erosion resistance as long as it does not break. Pioneer marshes that have not developed a cohesive top layer are erosion sensitive, especially in sandy soils. For future marsh creations, using fine‐grained sediments or a mixture of sand with silt or clay is recommended.
Weight control beliefs in the treatment of binge‐eating disorder: Why might they matter?
Authors: Laliberte Michele M. , Lucibello Kristen M.
Published: April 2022

Objective

The belief in personal control over weight (BCWeight) is positively associated, while the belief in control over healthy lifestyle with weight acceptance (BCLifestyle) is negatively associated with disordered eating, body dissatisfaction, and low self‐esteem. This study examined how weight control beliefs are impacted by cognitive behavior therapy (CBT) for binge‐eating disorder (BED) that provides evidence and choice regarding weight management options; and assessed whether changes in weight control beliefs are associated with treatment outcomes.

Method

Participants were 57 patients consecutively referred to an outpatient eating disorder clinic from 2013–2017 for BED treatment. Using retrospective self‐reported program‐evaluation data, baseline to post‐CBT changes in weight control beliefs were evaluated, as well as whether these changes were associated with the change in the drive for thinness, body dissatisfaction, fear of loss of control over eating, and self‐esteem.

Results

BCLifestyle significantly increased over CBT; BCWeight significantly decreased. Increases in BCLifestyle were associated with the reduced drive for thinness, body dissatisfaction, and fear of loss of control overeating. Decreases in BCWeight were associated with improved self‐esteem.

Discussion

BED CBT that provides science on weight management options is associated with positive changes in weight control beliefs, which are associated with measures of recovery from BED.

Public Significance Statement

Cognitive behavior therapy (CBT) for binge‐eating disorder decreases the belief that one can and should control one's weight, and increases the belief that one should strive for a healthy lifestyle and accept one's weight. These changes in beliefs are associated with improved treatment outcomes. CBT that gives patients evidence on different weight management options addresses patient obesity concerns and is related to positive change in weight control beliefs.
Individual variability in space use near power lines by a long‐lived territorial raptor
Authors: Marques Ana Teresa , Palma Luís , Lourenço Rui , Cangarato Rogério , Leitão Alexandre , Mascarenhas Miguel , Tavares João Tiago , Tomé Ricardo , Moreira Francisco , Beja Pedro
Published: April 2022

Evaluating species responses to anthropogenic infrastructures and other habitat changes is often used to assess environmental impacts and to guide conservation actions. However, such studies are generally carried out at the population level, disregarding inter‐individual variability. Here, we investigate population‐ and individual‐level responses toward power lines of a territorial raptor, the Bonelli's eagle Aquila fasciata. We used GPS‐PTT tracking data of 17 adult eagles to model space use as a function of distance to transmission and distribution lines, while accounting for other habitat features known to affect this species. At population level, eagles increased the intensity of space use in the proximity of power lines (up to 1,000 m), suggesting an attraction effect. At individual level, some eagles shared the general population attraction pattern, while others showed reduced intensity of space use in the proximity of power lines. These differential responses were unrelated to the sex of individuals, but were affected by the characteristics of the power grid, with a tendency for apparent attraction to be associated with individuals occupying home ranges with a denser network of transmission lines and transmission pylons. However, the study could not rule out the operation of other potentially influential factors, such as individual idiosyncrasies, the spatial distribution of prey availability, and the availability of natural perches and nesting sites. Overall, these results suggest that power lines may drive different behaviors and have differential impacts across individuals, with those attracted to the proximity of power lines potentially facing increased risk of mortality through electrocution and collision, and those avoiding power lines being potentially subject to exclusion effects. More generally, our results reinforce the need to understand individual variability when assessing and mitigating impacts of anthropogenic infrastructures.
Cold‐air pools as microrefugia for ecosystem functions in the face of climate change
Authors: Pastore Melissa A. , Classen Aimée T. , D'Amato Anthony W. , Foster Jane R. , Adair E. Carol
Published: April 2022

Cold‐air pooling is a global phenomenon that frequently sustains low temperatures in sheltered, low‐lying depressions and valleys and drives other key environmental conditions, such as soil temperature, soil moisture, vapor pressure deficit, frost frequency, and winter dynamics. Local climate patterns in areas prone to cold‐air pooling are partly decoupled from regional climates and thus may be buffered from macroscale climate change. There is compelling evidence from studies across the globe that cold‐air pooling impacts plant communities and species distributions, making these decoupled microclimate areas potentially important microrefugia for species under climate warming. Despite interest in the potential for cold‐air pools to enable species persistence under warming, studies investigating the effects of cold‐air pooling on ecosystem processes are scarce. Because local temperatures and vegetation composition are critical drivers of ecosystem processes like carbon cycling and storage, cold‐air pooling may also act to preserve ecosystem functions. We review research exploring the ecological impacts of cold‐air pooling with a focus on vegetation, and then present a new conceptual framework in which cold‐air pooling creates feedbacks between species and ecosystem properties that generate unique hotspots for carbon accrual in some systems relative to areas more vulnerable to regional climate change impacts. Finally, we describe key steps to motivate future research investigating the potential for cold‐air pools to serve as microrefugia for ecosystem functions under climate change.
Biomarker changes as surrogate endpoints in early‐phase trials in heart failure with reduced ejection fraction
Authors: Savarese Gianluigi , Uijl Alicia , Ouwerkerk Wouter , Tromp Jasper , Anker Stefan D. , Dickstein Kenneth , Hage Camilla , Lam Carolyn S.P. , Lang Chim C. , Metra Marco , Ng Leong L. , Orsini Nicola , Samani Nilesh J. , van Veldhuisen Dirk J. , Cleland John G.F. , Voors Adriaan A. , Lund Lars H.
Published: April 2022

Aims

No biomarker has achieved widespread acceptance as a surrogate endpoint for early‐phase heart failure (HF) trials. We assessed whether changes over time in a panel of plasma biomarkers were associated with subsequent morbidity/mortality in HF with reduced ejection fraction (HFrEF).

Methods and results

In 1040 patients with HFrEF from the BIOSTAT‐CHF cohort, we investigated the associations between changes in the plasma concentrations of 30 biomarkers, before (baseline) and after (9 months) attempted optimization of guideline‐recommended therapy, on top of the BIOSTAT risk score and the subsequent risk of HF hospitalization/all‐cause mortality using Cox regression models. C‐statistics were calculated to assess discriminatory power of biomarker changes/month‐nine assessment. Changes in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and WAP four‐disulphide core domain protein HE4 (WAP‐4C) were the only independent predictors of the outcome after adjusting for their baseline plasma concentration, 28 other biomarkers (both baseline and changes), and BIOSTAT risk score at baseline. When adjusting for month‐nine rather than baseline biomarkers concentrations, only changes in NT‐proBNP were independently associated with the outcome. The C‐statistic of the model including the BIOSTAT risk score and NT‐proBNP increased by 4% when changes were considered on top of baseline concentrations and by 1% when changes in NT‐proBNP were considered on top of its month‐nine concentrations and the BIOSTAT risk score.

Conclusions

Among 30 relevant biomarkers, a change over time was significantly and independently associated with HF hospitalization/all‐cause death only for NT‐proBNP. Changes over time were modestly more prognostic than baseline or end‐values alone. Changes in biomarkers should be further explored as potential surrogate endpoints in early phase HF trials.
Hobit and Blimp‐1 regulate TRM abundance after LCMV infection by suppressing tissue exit pathways of TRMprecursors
Authors: Parga‐Vidal Loreto , Taggenbrock Renske L.R.E. , Beumer‐Chuwonpad Ammarina , Aglmous Hajar , Kragten Natasja A.M. , Behr Felix M. , Bovens Astrid A. , van Lier Rene A.W. , Stark Regina , van Gisbergen Klaas P.J.M.
Published: April 2022

Tissue‐resident memory T cells (Trm) are retained in peripheral tissues after infection for enhanced protection against secondary encounter with the same pathogen. We have previously shown that the transcription factor Hobit and its homolog Blimp‐1 drive Trm development after viral infection, but how and when these transcription factors mediate Trm formation remains poorly understood. In particular, the major impact of Blimp‐1 in regulating several aspects of effector T‐cell differentiation impairs study of its specific role in Trm development. Here, we used the restricted expression of Hobit in the Trm lineage to develop mice with a conditional deletion of Blimp‐1 in Trm, allowing us to specifically investigate the role of both transcription factors in Trm differentiation. We found that Hobit and Blimp‐1 were required for the upregulation of CD69 and suppression of CCR7 and S1PR1 on virus‐specific Trm precursors after LCMV infection, underlining a role in their retention within tissues. The early impact of Hobit and Blimp‐1 favored Trm formation and prevented the development of circulating memory T cells. Thus, our findings highlight a role of Hobit and Blimp‐1 at the branching point of circulating and resident memory lineages by suppressing tissue egress of Trm precursors early during infection.