bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative metabolomics and transcriptomics analysis reveals novel therapeutic vulnerabilities in lung cancer
Authors: Thaiparambil Jose , Dong Jianrong , Grimm Sandra L. , Perera Dimuthu , Ambati Chandra Shekar R. , Putluri Vasanta , Robertson Matthew J. , Patel Tajhal D. , Mistretta Brandon , Gunaratne Preethi H. , Kim Min P. , Yustein Jason T. , Putluri Nagireddy , Coarfa Cristian , El‐Zein Randa 
Published: June 2022

AbstractBackgroundNon‐small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi‐modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite‐related gene signature and altered metabolic pathways associated with LUAD and LUSC.MethodsWe integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co‐expression was used to identify modules of metabolites that were altered between normal and tumor.ResultsWe identified unique metabolite‐related gene signatures specific for LUAD and LUSC and key pathways aberrantly regulated at both transcriptional and metabolic levels. Differential co‐expression analysis revealed that loss of coherence between metabolites in tumors is a major characteristic in both LUAD and LUSC. We identified one metabolic onco‐module gained in LUAD, characterized by nine metabolites and 57 metabolic genes. Multi‐omics integrative analysis revealed a 28 metabolic gene signature associated with poor survival in LUAD, with six metabolite‐related genes as individual prognostic markers.ConclusionsWe demonstrated the clinical utility of this integrated metabolic gene signature in LUAD by using it to guide repurposing of AZD‐6482, a PI3Kβ inhibitor which significantly inhibited three genes from the 28‐gene signature. Overall, we have integrated metabolomics and transcriptomics analyses to show that LUAD and LUSC have distinct profiles, inferred gene signatures with prognostic value for patient survival, and identified therapeutic targets and repurposed drugs for potential use in NSCLC treatment.
Single Entity Electrochemical Detection of As‐prepared Metallic and Dielectric Nanoparticle Stochastic Impacts in a Phosphonium Ionic Liquid
Authors: Ahmadinasab Nazanin , Stockmann Talia Jane 
Published: June 2022

AbstractInvited for this issue's Front Cover is the group of Dr. Talia Jane Stockmann from Memorial University of Newfoundland (Canada). The cover picture shows a platinum nanoparticle stochastic impact at a carbon fiber ultramicroelectrode along with the associated, recorded signal in an ionic liquid medium. Read the full text of the Research Article at 10.1002/celc.202200162.
H2, B−H, and Si−H Bond Activation and Facile Protonolysis Driven by Pt‐Base Metal Cooperation
Authors: Govindarajan Ramadoss , Deolka Shubham , Khaskin Eugene , Fayzullin Robert R. , Pal Shrinwantu , Vasylevskyi Serhii , Khusnutdinova Julia R. 
Published: June 2022

AbstractWe report a series of heterobimetallic Pt/Zn and Pt/Ca complexes to study the effect of proximity of a dicationic base metal on the organometallic Pt species. Varying degrees of Pt⋅⋅⋅Zn and Zn interaction with the bridging Me group are achieved, showcasing snapshots of a hypothetical process of retrotransmetalation from Pt to Zn. In contrast, only weak interactions were observed for Ca with a Pt‐bound Me group. Activation of H2, B−H and Si−H bonds leads to the formation of hydride‐bridged Pt−H−Zn complexes, which is not observed in the absence of Zn, pointing out the importance of metal‐metal cooperation. Reactivity of PtMe2/M2+ with terminal acetylene, water and methanol is also studied, leading to facile protonation of one of the Me groups at the Pt center only when Zn is present. This study sheds light on various ways in which the presence of a 2+ metal cation significantly affects the reactivity of a common organoplatinum complex.
Carboxymethyl‐β‐cyclodextrin and histidine‐zeolitic imidazolate framework‐8 used for enantioseparation of three basic drugs in open‐tubular capillary electrochromatography
Authors: Miao Pandeng , Gan Jie , Zhang Jian , Ma Mingxuan , Li Xiaoqi , Du Yingxiang , Feng Zijie , Zhang Liu 
Published: June 2022

AbstractMetal organic frameworks (MOFs) have drawn broad attention as a novel stationary phase due to their highly porous structure, modifiable pores, large specific surface areas, and satisfactory stability. In this paper, histidine‐zeolitic imidazolate framework‐8 (His‐ZIF‐8) synthesized at room temperature was physically coated to the internal surface of the capillary column and the carboxymethyl‐β‐cyclodextrin (CM‐β‐CD) as the chiral selector was chemically bonded to the His‐ZIF‐8@capillary column. The prepared CM‐β‐CD@His‐ZIF‐8@capillary column was used for the enantioseparation of amlodipine, propranolol, and atenolol in capillary electrochromatography. In contrast to the CM‐β‐CD@capillary column without His‐ZIF‐8, the CM‐β‐CD@His‐ZIF‐8@capillary column reveals significantly improved enantiodiscrimination performance for amlodipine (Rs: 0 → 2.29), propranolol (Rs: 0 → 1.69), and atenolol (Rs: 0 → 0.79). His‐ZIF‐8 concentration, buffer pH, buffer concentration, and the proportion of organic modifier were evaluated in detail with enantiomerically separating chiral molecules. The repeatability of intraday, day‐to‐day, and column‐to‐column have been discussed; the result was preferable, and the relative standard deviation (RSD) of separation parameters was <6.7%.
A correlation for average droplet diameter in rotating packed beds
Authors: Golshan Shahab , Shams Alireza , Rabiee Roshanak , Jafari Rouzbeh , Chaouki Jamal , Blais Bruno 
Published: June 2022

AbstractA rotating packed bed (RPB) is a novel process intensification technology that increases mass transfer rate using a strong centrifugal acceleration. Inside an RPB, the inlet jet of the liquid absorbent is broken into tiny droplets. It is reported that RPBs provide 11 times larger mass transfer area compared to equal‐sized packed beds and two to three orders of magnitude higher mass transfer compared to equal‐sized stirred tanks. The novelty of the technology and lack of research, however, undermines the adoption of RPBs where a low mass transfer rate is the main bottleneck. In this work, we study the effect of bed size on the average droplet diameter in RPBs and investigate scale‐up criteria to preserve the average droplet diameter at a large scale. Furthermore, we develop a correlation for the average droplet diameter using the experimental data and simulation results obtained using a volume of fluid (VOF) method. This correlation is obtained from dimensional analysis. The effects of rotating speed, absorbent flow rate, wire mesh packing diameter, bed diameter, absorbent viscosity, density, and surface tension are included in the dataset. Among these parameters, rotating speed, centrifugal force, and surface tension have the highest correlation coefficients (R2 = 0.88, 0.83, and 0.42, respectively) with the average droplet diameter.
Length‐Dependent Collective Vibrational Dynamics in Alpha‐Helices
Authors: Zhang Zhenyu , Chen Mu , Zhan Lijian , Zheng Fei , Si Wei , Sha Jingjie , Chen Yunfei 
Published: June 2022

AbstractThe front cover artwork is provided by Prof. Yunfei Chen's group at the Southeast University. The image shows collective vibrational motions of alpha‐helices inside a protein. Studying the vibrations allows connecting protein structure and function, and therefore benefits de novo protein design. Read the full text of the Research Article at 10.1002/cphc.202200082.
Metabolism and Excretion of Nirmatrelvir in Humans Using Quantitative Fluorine Nuclear Magnetic Resonance Spectroscopy: A Novel Approach for Accelerating Drug Development
Authors: Singh Ravi Shankar P. , Walker Gregory S. , Kadar Eugene P. , Cox Loretta M. , Eng Heather , Sharma Raman , Bergman Arthur J. , Van Eyck Lien , Hackman Frances , Toussi Sima S. , Kalgutkar Amit S. , Obach R. Scott 
Published: June 2022

Typically human absorption, distribution, metabolism, and excretion (ADME) studies are executed using radiolabeled (e.g., carbon‐14) material, the synthesis of which is a time‐consuming activity. In this study, we were able to assess the metabolism and excretion of unlabeled nirmatrelvir (PF‐07321332) within the first‐in‐human study via a novel application of quantitative fluorine (19F) nuclear magnetic resonance (NMR) spectroscopy in place of a standard radiolabel ADME study. Six healthy participants received a single 300‐mg oral dose of nirmatrelvir (in combination with ritonavir), and excreta were collected up to 10 days. Virtually all drug‐related material was recovered within 5 days, and mass balance was achieved with 84.9 ± 8.9% (range = 70.7–95.5%) of the administered dose recovered in urine and feces. The excretion of fluorine‐containing material in urine and feces was 47.0% and 33.7%, respectively. Unchanged nirmatrelvir represented 82.5% of the normalized drug‐related material with a carboxylic acid metabolite M5, derived from hydrolysis of the P2 amide bond, present at 12.1% of dose. Nirmatrelvir was the only drug‐related entity observed in plasma. Approximately 4.2% of the dose was excreted as metabolite M8 (measured by liquid chromatography–mass spectrometry), which was 19F NMR silent due to hydrolysis of the trifluoroacetamide moiety. Hydrolysis of nirmatrelvir to M5 and M8 was shown to occur in cultures of human gut microflora. This successful demonstration of quantitative 19F NMR spectroscopy to establish the mass‐balance, excretion, and metabolic profile of nirmatrelvir offers an advantageous means to execute human ADME studies for fluorine‐containing compounds early in drug development.
Implementing of aMMP‐8 point‐of‐care test with a modified new disease classification in Finnish adolescent cohorts
Authors: Heikkinen Anna M. , Raivisto Teija , Räisänen Ismo , Tervahartiala Taina , Bostanci Nagihan , Sorsa Timo 
Published: June 2022

AbstractObjectivesPeriodontitis is a multifactorial biofilm‐induced inflammatory disease; however, clinical and radiographic information reflects events that have already occurred. aMMP‐8 lateral‐flow chairside or point‐of‐care‐test (POC‐test) results have also come to complement the overall status of the patient's current situation. The current study aimed to clarify the usefulness of aMMP‐8 chairside‐test (aMMP‐8 POCT) results to alert the initial or early periodontitis in adolescents, a potential periodontitis risk group with cut off 20 ng/ml in Stage I periodontitis, according to the current periodontitis classification system.Material and MethodsA total of 117 adolescents were aMMP‐8 POC tested for aMMP‐8 levels and examined for the full mouth and were interviewed for questions concerning health behavior.ResultsOf all 117 participants, N = 38 (32.5%) was aMMP‐8 POCT positive, and N = 34 (29.1%) had at least one 4 mm periodontal deepened pocket; however, only N = 16 (13.7%) had both characteristics. The subclinical stage (N = 47) could not be classified either as gingivitis or Stage I. Of the participants, who did not have any deepened periodontal pockets, 18 tested negative.ConclusionsStage I is preceded by antecedent stages that should be tackled by oral healthcare prevention and personalized treatment modalities by professionals. Elevated (>20 ng/ml), positive aMMP‐8 POCT results can be regarded as initial alarmer such as emerging risk. This should be utilized in the preventive personalized interventions by oral health professionals.
60°phase difference current control‐based open‐phase fault‐tolerant operation strategy for open‐end winding permanent synchronous motor
Authors: Zhong Liping , Hu Song 
Published: June 2022

AbstractAs the most favorable candidate of electric vehicle drive system, the fault tolerance of open‐end winding permanent synchronous motor (OEW‐PMSM) fed by dual inverter with common DC bus is of great significance because it is related to the reliability and safety of the system. Aiming at the most common fault of open‐phase, a fault‐tolerant operation strategy based on 60° phase difference current control is proposed by making full use of the characteristics that each phase of OEW‐PMSM can be controlled independently. Through this method, the same stator rotating magnetic field can be generated before and after the open‐phase fault without reconfiguring the controller, so as to reduce the torque ripple after the fault and ensure the continuous and stable fault‐tolerant operation of the motor. In addition, this method can reduce the switching times by 50%. The proposed method can reduce the switching loss by 50% compared with the ordinary modulation method, reduce the switching loss, and will not produce large zero sequence current. Experimental results show that the fault‐tolerant performance of this strategy is significantly improved compared with the traditional methods.
Singular solitons interaction of dust ion acoustic waves in the framework of Korteweg de Vries and Modified Korteweg‐de Vries equations with (r,q) distributed electrons
Authors: Ghosh Uday Narayan 
Published: June 2022

AbstractTwo nonlinear evolution equations (NLEEs), namely, Korteweg‐de Vries (KdV) and modified Korteweg‐de Vries (MKdV) are derived from the dust hydrodynamic model of collisionless, unmagnetized dusty plasma with electrons following double spectral velocity distribution, that is, (r,q) distribution. Regular as well as singular analytic solutions of derived KdV equations and MKdV equations are obtained separately with the aid of the Hirota Bilinear method. Two singular soliton solutions of both KdV and MKdV equations are obtained separately. The efficiency and interactive approach of the heuristic Hirota Bilinear method leads to multiple singular soliton solutions for its beautiful algebraic technique which generates solitons solutions as well as singular solitons explicitly. Then the significance of multi singular soliton interaction has been studied for KdV singular solitons and for MKdV singular solitons in the critical parameter set.
Methoxido‐Bridged Lacunary Heterocubane Oxidovanadium(IV) Cluster with Azo Ligands: Synthesis, X‐ray Structure, Magnetic Properties, and Antiproliferative Activity
Authors: Roy Satabdi , Böhme Michael , Lima Sudhir , Mohanty Monalisa , Banerjee Atanu , Buchholz Axel , Plass Winfried , Rathnam Sharan , Banerjee Indranil , Kaminsky Werner , Dinda Rupam 
Published: June 2022

AbstractThe new μ3‐methoxido bridged trinuclear vanadium(IV) complexes [VIV3O3(μ3‐OMe)(μ2‐OMe)3(L1,2)2] (1 and 2) have been synthesized using the azo ligands 1‐(2‐(thiazol‐2‐yl)diazenyl)naphthalene‐2‐ol (HL1) and 2‐(2‐(thiazol‐2‐yl)diazenyl)‐4‐methylphenol (HL2). X‐ray crystallography revealed a trinuclear structure with a lacunary heterocubane {(VO)3(μ3‐OMe)(μ2‐OMe)3}2+ core unit for complex 1, which contains a central μ3‐methoxido bridge. All three vanadium centers are in a slightly distorted octahedral coordination environment. Magnetic and theoretical studies reveal an antiferromagnetic coupling between the three vanadium(IV) centers within the triangular arrangement in 1. The complexes were also screened for in vitro cytotoxicity study against HeLa and HT‐29 cancer cell lines. The results indicated that both the complexes are cytotoxic but possess varying specificity towards different cell types.
Paper‐based Wearable Electrochemical Sensors: A New Generation of Analytical Devices
Authors: Deroco Patricia Batista , Wachholz Junior Dagwin , Kubota Lauro Tatsuo 
Published: June 2022

AbstractOver the past few years, the emergence of electrochemical wearable sensors has attracted considerable attention because of their promising application in point‐of‐care testing due to some features such as high sensitivity, simplicity, miniaturization, and low fabrication cost. Recent developments in new fabrication approaches and innovative substrates have resulted in sensors able to real‐time and on‐body measurements. Wearable electrochemical sensors have also been combined with paper‐based substrates and directly used on human skin for different applications for non‐invasive analyses. Furthermore, wearable electrochemical sensors enable monitoring analytes in different biofluids without complex procedures, such as pre‐treatment or sample manipulation. The coupling of IoT to various wearable sensors has also attracted attention due to real‐time data collection and handling in remote and resource‐limited conditions. This mini‐review presents the significant advances in developing wearable electrochemical devices, such as sampling, data collection, connection protocols, and power sources, and discusses some critical challenges for higher performance in this field. We also present an overview of the application of paper as an intelligent substrate for electrochemical wearable sensors and discuss their advantages and drawbacks. Lastly, conclude by highlighting the future advances in wearable sensors and diagnostics by coupling real‐time and on‐body measurements to multiplexed detection of different biomarkers simultaneously, reducing the cost and time of classical analysis to provide fast and complete overall physiological conditions to the wearer.
An energy‐aware and lightweight routing algorithm using clustering and mobile sinks in wireless sensor networks
Authors: Adabi Sepideh , Mohammadifar Ali , Ebrahimi Nezhad Mohammad Mahdi 
Published: June 2022

AbstractA wireless sensor network (WSN) consists of a number of small sensors which are powered by low‐cost irreplaceable batteries. Therefore, one of the main issues inWSNdesign is to prolong the battery life of the individual sensors. Clustering and utilization of mobile sinks in collaboration with base station (BS) are two common solutions to address energy consumption challenge. Based on these solutions, a new algorithm in name “Energy‐aware Routing algorithm using Clustering and Mobile Sinks (ERCMS)” is proposed in this article. The distinguishing features ofERCMSare as follows: (1) a geometric pattern is applied to divide entire network area into some parts and make cluster in each part. This pattern adjusts the cluster size based on the distance from the sink. Thus, hotspot problem is expected to be reduced, (2) computational load is distributed over sensors, (3) length of messages are controlled and each message is defined in the format with minimum required information, (4) simple mathematics approaches those impose lightweight computations are adopted, and (5) accuracy of mobile sink dispatching procedure is improved in critical conditions of the network. The simulation results show thatERCMSoutperformsDFCR,MDFCR,andTEO‐MCRPin terms of consumed energy, delivery ratio, delay, routing overhead, and throughput.
Cellular mechanisms mediating activity‐dependent extracellular space shrinkage in the retina
Authors: Chiang Pei‐Pei , Kuo Sidney P. , Newman Eric A. 
Published: June 2022

AbstractVolume transmission plays an essential role in CNS function, with neurotransmitters released from synapses diffusing through the extracellular space (ECS) to distant sites. Changes in the ECS volume fraction (α) will influence the diffusion and the concentration of transmitters within the ECS. We have recently shown that neuronal activity evoked by physiological photic stimuli results in rapid decreases in ECSαas large as 10% in the retina. We now characterize the cellular mechanisms responsible for this ECS shrinkage. We find that block of inwardly rectifying K+channels with Ba2+, inhibition of the Na+/K+/2Cl−cotransporter with bumetanide, or block of AQP4 water channels with TGN‐020 do not diminish the light‐evoked ECS decrease. Inhibition of the Na+/HCO3−cotransporter by removing HCO3−from the superfusate, in contrast, reduces the light‐evoked ECS decrease by 95.6%. Inhibition of the monocarboxylate transporter with alpha‐cyano‐4‐hydroxycinnamate (4‐CIN) also reduces the ECS shrinkage, but only by 32.5%. We tested whether the swelling of Müller cells, the principal glial cells of the retina, is responsible for the light‐evoked ECS shrinkage. Light stimulation evoked a 6.3% increase in the volume of the fine processes of Müller cells. This volume increase was reduced by 97.1% when HCO3−was removed from the superfusate. We conclude that a large fraction of the activity‐dependent decrease in ECSαis generated by the activation of the Na+/HCO3−cotransporter in Müller cells. The monocarboxylate transporter may also contribute to the response.
A prospective investigation of serum bile acids with risk of liver cancer, fatal liver disease, and biliary tract cancer
Authors: Farhat Zeinab , Freedman Neal D. , Sampson Joshua N. , Falk Roni T. , Koshiol Jill , Weinstein Stephanie J. , Albanes Demetrius , Sinha Rashmi , Loftfield Erikka 
Published: June 2022

Abstract
Bile acids (BAs), major regulators of the gut microbiota, may play an important role in hepatobiliary cancer etiology. However, few epidemiologic studies have comprehensively examined associations between BAs and liver or biliary tract cancer. In the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) study, we designed 1:1 matched, nested, case–control studies of primary liver cancer (n = 201 cases), fatal liver disease (n = 261 cases), and primary biliary tract cancer (n = 138 cases). Using baseline serum collected ≤30 years before diagnosis or death, we measured concentrations of 15 BAs with liquid chromatography–tandem mass spectrometry. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable conditional logistic regression models, adjusted for age, education, diabetes status, smoking, alcohol intake, and body mass index. We accounted for multiple comparisons using a false discovery rate (FDR) correction. Comparing the highest to the lowest quartile, seven BAs were positively associated with liver cancer risk, including taurocholic acid (TCA) (OR, 5.62; 95% CI, 2.74–11.52; Q trend < 0.0001), taurochenodeoxycholic acid (TCDCA) (OR, 4.77; 95% CI, 2.26–10.08; Q trend < 0.0001), and glycocholic acid (GCA) OR, 5.30; 95% CI, 2.41–11.66; Q trend < 0.0001), and 11 were positively associated with fatal liver disease risk, including TCDCA (OR, 9.65; 95% CI, 4.41–21.14; Q trend < 0.0001), TCA (OR, 7.45; 95% CI, 3.70–14.97; Q trend < 0.0001), and GCA (OR, 6.98; 95% CI, 3.32–14.68; Q trend < 0.0001). For biliary tract cancer, associations were generally >1 but not significant after FDR correction. Conjugated BAs were strongly associated with increased risk of liver cancer and fatal liver disease, suggesting mechanistic links between BA metabolism and liver cancer or death from liver disease.