bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural network robust control of a 3‐DOF hydraulic manipulator with asymptotic tracking
Authors: Ge Yaowen , Zhou Jin , Deng Wenxiang , Yao Jianyong , Xie Lei
Published: June 2022

Multiaxial hydraulic manipulators are complicated systems with highly nonlinear dynamics and various modeling uncertainties, which hinders the development of high‐performance controller. In this paper, a neural network feedforward with a robust integral of the sign of the error (RISE) feedback is proposed for high precise tracking control of hydraulic manipulator systems. The established nonlinear model takes three‐axis dynamic coupling, hydraulic actuator dynamics, and nonlinear friction effects into consideration. A radial basis function neural network (RBFNN) is synthesized to approximate the uncertain system dynamics and external disturbance, which can greatly reduce the dependence on accurate system model. In addition, a continuous RISE feedback law is judiciously integrated to deal with the residual unknown dynamics. Since the major unknown dynamics can be estimated by the RBFNN and then compensated in the feedforward design, the high‐gain feedback issue in RISE feedback control will be avoided. The proposed RISE‐based neural network robust controller theoretically guarantees an excellent semi‐global asymptotic stability. Comparative simulation is performed on a 3‐DOF hydraulic manipulator, and the obtained results verify the effectiveness of the proposed controller.
Encapsulation of Pseudomonas aeruginosa elastase inside the P22 virus‐like particle for controlling enzyme–substrate interactions
Authors: Patterson Dustin , Draper Derek , Anazia Kara , Hjorth Christy , Bird Jessica , Fancher Shandis , Azghani Ali
Published: June 2022

Controlling interactions between enzymes and interaction partners, such as substrates, is important for applications in cellular biology and molecular biochemistry. A strategy for controlling enzyme access with substrate interaction partners is to exploit encapsulation of enzymes inside nanoparticles to limit the accessibility of the enzymes to large macromolecules, but allow free exchange of small‐molecule substrates. The research here evaluates the encapsulation of Pseudomonas aeruginosa elastase inside the bacteriophage P22 virus‐like particle (VLP) to examine the ability to allow free soluble substrates access to the enzyme while blocking large macromolecular substrate interactions. The results show that the active elastase protease can be encapsulated inside the P22 VLP, which blocks its ability to disrupt cell monolayers, but allows soluble substrates to be catalytically cleaved, supporting the viability of this approach for future investigations.
Microbial maintenance energy quantified and modeled with microcalorimetry
Authors: Hunt Kristopher A. , von Netzer Frederick , Gorman‐Lewis Drew , Stahl David A.
Published: June 2022

Refining the energetic costs of cellular maintenance is essential for predicting microbial growth and survival in the environment. Here, we evaluate a simple batch culture method to quantify energy partitioning between growth and maintenance using microcalorimetry and thermodynamic modeling. The constants derived from the batch culture system were comparable to those that have been reported from meta‐analyses of data derived from chemostat studies. The model accurately predicted temperature‐dependent biomass yield and the upper temperature limit of growth for Desulfovibrio alaskensis G20, suggesting the method may have broad application. An Arrhenius temperature dependence for the specific energy consumption rate, inferred from substrate consumption and heat evolution, was observed over the entire viable temperature range. By combining this relationship for specific energy consumption rates and observed specific growth rates, the model describes an increase in nongrowth associated maintenance at higher temperatures and the corresponding decrease in energy available for growth. This analytical and thermodynamic formulation suggests that simply monitoring heat evolution in batch culture could be a useful complement to the recognized limitations of estimating maintenance using extrapolation to zero growth in chemostats.
The effect of acrylic silane crosslinker on room‐temperature cured acrylate binder for road markings
Authors: Jang Dong Gyu , Lim Won‐Bin , Bae Ji‐Hong , Lee Ju‐Hong , Min Jin‐Gyu , Kim Ju‐Won , Yoon Keun‐Byoung , Huh PilHo
Published: June 2022

An acrylic binder with excellent physical properties is prepared using copolymer of methyl methacrylate (MMA) and butyl acrylate monomer (BAM), 2‐hydroxyethyl methacrylate (2‐HEMA), 3‐(trimethoxysilyl)propyl methacrylate (TMSPMA), and additives. The obtained acrylic resins are subjected to a redox initiator system (ROIS) for room temperature curing. The effects of the TMSPMA concentration and [acryl‐copolymer]/[2‐HEMA] ratio on backbone content are studied in terms of traffic marking paint. The mechanical and morphological properties are thoroughly evaluated using universal testing machine (UTM), UV spectrum, and SEM. With increasing TMSPMA content, the adhesive strength and transmittance of the cured resins increase up to a limiting value of TMSPMA content because of the optimizing crosslink network in backbone structure. The introduction of TMSPMA may be effectively attributed to strong adhesive and high transparency of an acrylic resin series. Consequently, acrylic resins with optimal TMSPMA content can be mostly utilized as a high‐performance binder in the traffic marking paint field.
Navigate Title IX obligations in hybrid learning, working environments
Authors: Davis‐Brantley Tiffany
Published: June 2022

In a world fundamentally altered by the COVID‐19 pandemic, the virtual sphere has become an integral element of delivering educational services.
Use interactive process to determine if accommodations for long COVID create fundamental alterations
Authors: Masinter Michael R.
Published: June 2022

Although the worst of the COVID‐19 pandemic appears to be over, its impact on higher education administrators will continue through the effects of long COVID‐19 and through continued fear of illness. Recent guidance from the Office for Civil Rights and the Department of Justice (bit.ly/3IPSbYh) notes that long COVID, an occasional consequence of even mild COVID infections, can be a disability if it substantially limits a major life activity, and therefore can be expected to trigger requests for academic adjustments and reasonable accommodations. The guidance notes that common symptoms associated with long COVID include, but are not limited to, fatigue; difficulty thinking or concentrating, sometimes referred to as brain fog; depression; anxiety; and heart palpitations, all of which may directly interfere with the ability to think and learn.
The development of reputational capital – How social media influencers differ from traditional celebrities
Authors: Hess Alexandra C. , Dodds Sarah , Rahman Nadia
Published: June 2022

Social media influencers (SMI) have grown in importance as a promotional channel. However, little is known about how they build reputational capital and thus endorsement effectiveness, particularly compared to traditional celebrity endorsers. From a consumers' perspective, this research investigates both types of endorsers in different stages of the Celebrity Capital Life Cycle (CCLC). Across three studies, we find that parasocial relationships and interactions with consumers are paramount for SMIs reputational capital and endorsement effectiveness, yet not critical for traditional celebrities. Further, a consumer's perceived weak parasocial relationship/interaction with SMIs can be detrimental to their effectiveness yet has little impact on traditional celebrities' influence. We find that the positive effect of a SMI with high parasocial relationship/interaction with consumers on Word of Mouth (i.e., endorsers effectiveness) is mediated by expectation fulfillment and brand endorsers' credibility (i.e., reputation capital). This research discovers how important parasocial relationships with consumers are for SMIs in comparison to traditional celebrities; importantly this is the first research that empirically identifies how SMIs can gain and maintain reputation capital and subsequently be more effective as brand endorsers. Our findings have important implications for marketing professionals who are managing SMIs.
Clinical outcomes following single access transfemoral transcatheter aortic valve implantation
Authors: Aroney Nicholas P. , Patterson Tiffany , Kalogeropoulos Andreas , Allen Christopher J. , Hurrell Harriet , Chehab Omar , Grapsa Julia , Rajani Ronak , Prendergast Bernard , Redwood Simon
Published: June 2022

Objectives

We describe the first experience using calcification of anatomical landmarks to obviate the need for transcatheter aortic valve implantation (TAVI) alignment aortography and secondary TAVI access.

Background

TAVI alignment conventionally involves secondary femoral access for contrast aortography using a second catheter. Secondary femoral access accounts for up to 25% of all vascular complications. Heavily calcified aortic leaflets are often visible fluoroscopically and can act as markers for TAVI alignment.

Methods

We considered 100 consecutive patients for transfemoral TAVI. The first group was considered for a conventional dual access technique and the subsequent group was considered for a single access technique. Relevant baseline, and procedural and outcome measures were recorded.

Results

Baseline characteristics were comparable between groups. Balloon‐expandable transcatheter heart valves (THV) were used in all cases. THV implantation was successful in 100% of cases with no procedural or in‐hospital mortality. Procedural time and contrast use were lower in the single access group. There were no Valve Academic Research Consortium (VARC)‐2 major vascular complications with the single access technique.

Conclusions

This is the first study describing the use of calcification of anatomical landmarks to obviate the need for secondary TAVI access. Notable observations included successful device implantation in all cases, no VARC‐2 major vascular complications, comparable rates of paravalvular leak and permanent pacemaker requirement, shorter procedural times, and lower contrast use. Single access TAVI is a viable alternative technique to minimize vascular access, contrast use, and procedural duration in experienced centers and with selected patients, allowing successful device implantation and low complication rates while further streamlining TAVI workflow.
Case of non‐secretory multiple myeloma eventually diagnosed by 18F‐FDG PET/CT
Authors: Haratake Daisuke , Kanno Keishi , Ichinohe Tatsuo , Ito Masanori
Published: June 2022

Non‐secretory multiple myeloma (NSMM) is a rare type of multiple myeloma characterized by the absence of the M protein, making its diagnosis challenging. Here, we report a 67‐year‐old female patient eventually diagnosed as NSMM with positron emission tomography‐computed tomography (PET/CT) imaging as a clue.
Graphical introduction to principal components analysis
Authors: Brereton Richard G.
Published: June 2022

Principal components analysis is introduced graphically using a small 3 × 2 matrix, showing the relationship between the original dataset, scores and loadings.
Acene Size‐Dependent Transition of The Radical Centers From the Metal to The Acene Parts In Monocationic Dinuclear (Diethynylacene)diyl Complexes
Authors: Tanaka Yuya , Kawano Reo , Akita Munetaka
Published: June 2022

Controlling radical localization/delocalization is important for functional materials. The present paper describes synthesis and results of electrochemical, spectroscopic, and theoretical studies of diruthenium (p‐diethynylacene)diyl complexes, Me3Si‐(C≡C)2‐Ru(dppe)2‐C≡C−Ar‐C≡C−Ru(dppe)2‐(C≡C)2‐SiMe3 (1–6) (dppe: 1,2‐bis(diphenylphosphino)ethane), and their monocationic radical species ([1]+–[6]+). The HOMO‐LUMO energy gaps can be finely tuned by the acene rings in the bridging ligands installed, as indicated by the absorption maxima of the electronic spectra of 1–6 ranging from the UV region even to the NIR region. The cationic species [1]+–[6]+ show two characteristic NIR bands, which are ascribed to the charge resonance (CR) and π‐π* transition bands, as revealed by spectroelectrochemistry. Expansion of the acene rings in [1]+–[6]+ causes (1) blue shifts of the CR bands and red shifts of the π‐π* transition bands and (2) charge localization on the acene parts as evidenced by the ESR, DFT and TD‐DFT analyses. Notably, the monocationic complexes of the larger acene derivatives are characterized as the non‐classical acene‐localized radicals.
Carba Analogues of Flupirtine and Retigabine with Improved Oxidation Resistance and Reduced Risk of Quinoid Metabolite Formation
Authors: Wurm Konrad W. , Bartz Frieda‐Marie , Schulig Lukas , Bodtke Anja , Bednarski Patrick J. , Link Andreas
Published: June 2022

The KV7 potassium channel openers flupirtine and retigabine have been valuable options in the therapy of pain and epilepsy. However, as a result of adverse reactions, both drugs are currently no longer in therapeutic use. The flupirtine‐induced liver injury and the retigabine linked tissue discolouration do not appear related at first glance; nevertheless, both events can be attributed to the triaminoaryl scaffold, which is affected by oxidation leading to elusive reactive quinone diimine or azaquinone diimine metabolites. Since the mechanism of action, i. e. KV7 channel opening, seems not to be involved in toxicity, this study aimed to further develop safer replacements for flupirtine and retigabine. In a ligand‐based design strategy, replacing amino substituents of the triaminoaryl core with alkyl substituents led to carba analogues with improved oxidation resistance and negligible risk of quinoid metabolite formation. In addition to these improved safety features, some of the novel analogues exhibited significantly improved KV7.2/3 channel opening activity, indicated by an up to 13‐fold increase in potency and an efficacy of up to 176 % compared to flupirtine, thus being attractive candidates for further development.
Post‐Marketing Requirements for Cancer Drugs Approved by the European Medicines Agency, 2004–2014
Authors: Cherla Avi , Mossialos Elias , Salcher‐Konrad Maximilian , Kesselheim Aaron S. , Naci Huseyin
Published: June 2022

To address unresolved questions about drug safety and efficacy at the time of approval, the European Medicines Agency (EMA) may require that manufacturers conduct additional studies during the postmarketing period. As a growing proportion of new cancer drugs are approved on the basis of limited evidence of clinical benefit, timely completion of postmarketing requirements is important. We used publicly available regulatory documents to evaluate key characteristics of pivotal studies supporting EMA‐approved cancer drugs from 2004–2014 and assessed completion rates of postmarketing data collection requirements after a minimum of 5 years. From 2004–2014, 79% (45/57) of EMA‐approved cancer drugs had to fulfill postmarketing requirements. Pivotal trials supporting the approval of cancer drugs with postmarketing requirements were less likely to have randomized designs (41/61, 67% vs. 11/11, 100%), include an active comparator (20/61, 33% vs. 10/11, 91%), or measure overall survival as the primary study end point (18/61, 30% vs. 6/11, 55%) compared with pivotal trials for drugs without postmarketing requirements. Among 200 postmarketing requirements, almost half were designed to assess drug safety. After a minimum of 5 years, 60% (121/200) of requirements were completed, 10% (19/200) were ongoing, and 30% (60/200) were delayed. About half (40/75, 53%) of postmarketing requirements for new clinical studies were completed on time. Delays in the completion of postmarketing requirements often did not impact the likelihood of drugs receiving permanent marketing authorization (87%, 39/45) after 5 years. Our findings highlight the need for EMA to better enforce its authority to require timely completion of postmarketing requirements and studies.
Assessing Prolongation of the Corrected QT Interval with Bedaquiline and Delamanid Coadministration to Predict the Cardiac Safety of Simplified Dosing Regimens
Authors: Tanneau Lénaïg , Karlsson Mats O. , Rosenkranz Susan L. , Cramer Yoninah S. , Shenje Justin , Upton Caryn M. , Morganroth Joel , Diacon Andreas H. , Maartens Gary , Dooley Kelly E. , Svensson Elin M.
Published: June 2022

Delamanid and bedaquiline are two drugs approved to treat drug‐resistant tuberculosis, and each have been associated with corrected QT interval (QTc) prolongation. We aimed to investigate the relationships between the drugs' plasma concentrations and the prolongation of observed QT interval corrected using Fridericia’s formula (QTcF) and to evaluate their combined effects on QTcF, using a model‐based population approach. Furthermore, we predicted the safety profiles of once daily regimens. Data were obtained from a trial where participants were randomized 1:1:1 to receive delamanid, bedaquiline, or delamanid + bedaquiline. The effect on QTcF of delamanid and/or its metabolite (DM‐6705) and the pharmacodynamic interactions under coadministration were explored based on a published model between bedaquiline's metabolite (M2) and QTcF. The metabolites of each drug were found to be responsible for the drug‐related QTcF prolongation. The final drug‐effect model included a competitive interaction between M2 and DM‐6705 acting on the same cardiac receptor and thereby reducing each other's apparent potency, by 28% (95% confidence interval (CI), 22–40%) for M2 and 33% (95% CI, 24–54%) for DM‐6705. The generated combined effect was not greater but close to “additivity” in the analyzed concentration range. Predictions with the final model suggested a similar QT prolonging potential with simplified, once‐daily dosing regimens compared with the approved regimens, with a maximum median change from baseline QTcF increase of 20 milliseconds in both regimens. The concentrations–QTcF relationship of the combination of bedaquiline and delamanid was best described by a competitive binding model involving the two main metabolites. Model predictions demonstrated that QTcF prolongation with simplified once daily regimens would be comparable to currently used dosing regimens.
Characterization of new psychoactive substances by integrating benchtop NMR to multi‐technique databases
Authors: Castaing‐Cordier Thomas , Benavides Restrepo Alejandra , Dubois Damien , Ladroue Virginie , Besacier Fabrice , Buleté Audrey , Charvoz Céline , Goupille Anais , Jacquemin Denis , Giraudeau Patrick , Farjon Jonathan
Published: June 2022

New psychoactive substances (NPS) have become a serious threat for public health due to their ability to be sold in the street or on internet. NPS are either derived from commercial drugs which are misused (recreational rather than medical use) or whose structure is slightly modified. To regulate NPS, it is essential to accurately characterize them, either to recognize molecules that were previously identified or to quickly elucidate the structure of unknown ones. Most approaches rely on the determination of the exact mass obtained by high‐resolution mass spectrometry requiring expensive equipment. This motivated us to develop a workflow in which the elucidation is assisted with databases and does not need the exact mass. This workflow combines 1D and 2D NMR measurements performed on a benchtop spectrometer with IR spectroscopy, for creating a multi‐technique database to characterize pure and mixed NPS. The experimental database was created with 57 entries mostly coming from seizures, mainly cathinones, cannabinoids, amphetamines, arylcyclohexylamines, and fentanyl. A blind validation of the workflow was carried out on a set of six unknown seizures. In the first three cases, AF, AB‐FUBINACA, and a mixture of 2C‐I and 2C‐E could be straightforwardly identified with the help of their reference spectra in the database. The two next samples were elucidated for the first time with the help of the database to reveal NEK and MPHP substances. Finally, a precise quantification of each characterized NPS was obtained in order to track NPS trafficking networks.
A Three‐Way Regioselective Synthesis of Amino Acid Decorated Imidazole, Purine and Pyrimidine Derivatives by Multicomponent Chemistry Starting from Prebiotic Diaminomaleonitrile
Authors: Bizzarri Bruno Mattia , Fanelli Angelica , Cesarini Silvia , Saladino Raffaele
Published: June 2022

Amino acid decorated imidazole, pyrimidine and purine derivatives, resembling analogues of peptide nucleic acid's building blocks, have been synthesized by a three‐way multicomponent chemistry of diaminomaleonitrile, one of the most studied chemical precursors in prebiotic chemistry. The regioselectivity of the multicomponent reaction between diaminomaleonitrile, trimethyl orthoacetate and a selected panel of α‐amino acids, was controlled by the energy source used for triggering the condensation. Imidazole derivatives were obtained under thermal condition, while photochemical and combined photothermal conditions afforded pyrimidine and purine derivatives, respectively. The three synthetic pathways were independent of each other, the type of product being controlled by the chemical intermediates prevailing in the reaction mixture. In addition to the synthetic potential of these multicomponent reactions in the preparation of a large variety of heterocycles, the control of the synthesis of peptide nucleic acid's building blocks, simply by changing the nature of the energy source, further enlarged the chemical complexity available in prebiotic conditions for the emergence of pristine pre‐genetic codes.
The impact of geopolitical tensions on international higher education
Authors: Dennis Marguerite J.
Published: June 2022

Prior to the invasion of Ukraine by Russia in February 2022, geopolitical tensions had impacted the politics and economies of countries worldwide. And the international higher education sector has, for years, also been impacted by global geopolitical shifts and tensions. International student mobility, college and university collaborations, branch campus agreements, and faculty research have been shaped, in part, by changes in country realignments.
Mission‐centric decision support in cybersecurity via Bayesian Privilege Attack Graph
Authors: Javorník Michal , Husák Martin
Published: June 2022

We present an approach to decision support in cybersecurity with respect to cyber threats and stakeholders' requirements. We approach situations in which cybersecurity experts need to take actions to mitigate the risks, such as temporarily putting an IT system out of operation, but need to consult them with other stakeholders. We propose a decision support system that uses a mission decomposition model representing the organization's functional and security requirements on its IT infrastructure. Based on the cybersecurity state assessment, that is, discovery of vulnerabilities and attacker's position, the decision support system calculates the resilience metrics for each IT infrastructure's configuration, that is, how likely are they to not be disrupted. The calculation is enabled by two novel formal models, Privilege‐Exploit Attack Graph and Bayesian Privilege Attack Graph, which reduce complex attack graphs into a comprehensible bipartite graph. Moreover, they illustrate the impact of exploiting the vulnerabilities and attackers gaining the privileges. The system recommends the most resilient mission configurations that are comprehensible to both cybersecurity experts and non‐technical stakeholders, who may then choose which configuration to apply. Our approach is illustrated in a case study of a real‐world medical information system.
Thermal modelling of cylindrical Lithium‐Ion batteries to study the impact of structural components
Authors: Rathod Dhanashri , Ghosh Nitika , Panigrahi Bijaya Kiten , Garg Akhil , Kumari Pooja
Published: June 2022

Temperature has a profound impact on the performance of lithium‐ion batteries. The temperature distribution in the cylindrical cell during charging and discharging cycles is governed by physical features of materials such as thermal conductivity and specific heat capacity. The cells must operate at their optimal temperature. The eight thermal models were build by finite element analysis on the COMSOL Multiphysics 5.6 software. With inputs and average characteristics such as open‐circuit voltage (OCV), state of charge (SOC), thermal conductivities, specific heat capacities, and density of the materials employed, the software develops a two‐dimensional thermal model. The thermal model is designed to work with a cylindrical 18 650 lithium‐ion battery. The cell's initial temperature is 298.15 K. After the simulation, the results are interpolated to the 1500s. The thermal distribution in the axial and radial directions is investigated, with the conclusion that certain elements have a greater impact on the cell temperature distribution. The results show that the temperature distributions of the cell are greatly influenced by the steel case around the cylindrical structure, steel needle, electrolyte filled in between the cavities, and relief valve.
Access to technology to support telehealth in areas without specialty care for liver disease
Authors: Henson Jacqueline B. , Wegermann Kara , Patel Yuval A. , Wilder Julius M. , Muir Andrew J.
Published: June 2022

Background and Aims:

Telehealth may be a successful strategy to increase access to specialty care for liver disease, but whether the areas with low access to care and a high burden of liver‐related mortality have the necessary technology access to support a video‐based telehealth strategy to expand access to care is unknown.

Approach and Results:

Access to liver disease specialty care was defined at the county level as <160.9 km (100 miles) from a liver transplant (LT) center or presence of local gastroenterology (GI). Liver‐related mortality rates were compared by access to care, and access to technology was compared by degree of access to care and burden of liver‐related mortality. Counties with low access to liver disease specialty care had higher rates of mortality from liver disease, and this was highest in areas both >160.9 km from an LT center and without local GI. These counties were more rural, had higher poverty, and had decreased access to devices and internet at broadband speeds. Technology access was lowest in areas with low access to care and the highest burden of liver‐related mortality.

Conclusions:

Areas with poor access to liver disease specialty care have a greater burden of liver‐related mortality, and many of their residents lack access to technology. Therefore, a telehealth strategy based solely on patient device ownership and internet access will exclude a large proportion of individuals in the areas of highest need. Further work should be done at the local and state levels to design optimal strategies to reach their populations of need.
Contemporary management of pain in cirrhosis: Toward precision therapy for pain
Authors: Holman Alexis , Parikh Neehar , Clauw Dan J. , Williams David A. , Tapper Elliot B.
Published: June 2022

Chronic pain is highly prevalent in patients with cirrhosis and is associated with poor health‐related quality of life and poor functional status. However, there is limited guidance on appropriate pain management in this population, and pharmacologic treatment can be harmful, leading to adverse outcomes, such as gastrointestinal bleeding, renal injury, falls, and hepatic encephalopathy. Chronic pain can be categorized mechanistically into three pain types: nociceptive, neuropathic, and nociplastic, each responsive to different therapies. By discussing the identification, etiology, and treatment of these three mechanistic pain descriptors with a focus on specific challenges in patients with cirrhosis, we provide a framework for better tailoring treatments, including nonpharmacologic therapies, to patients' needs.
BCR/ABL1ΔE7‐8‐9 isoform contributes to tyrosine kinase inhibitor resistance in chronic myeloid leukemia
Authors: Tan Yanhong , Zhang Lingli , Zhu Guiyang , Yang Yuchao , Guo Wenzheng , Chen Lanhui , Chang Jianmei , Xu Yang , Muyey Daniel Muteb , Wang Hongwei
Published: June 2022

In chronic myeloid leukemia (CML) patients, the involvement of the BCR/ABL1 isoform in tyrosine kinase inhibitors (TKIs) resistance has attracted lots of attention. In this work, a novel isoform that encoded truncated protein due to the deletion of ABL1 exon7, 8, and 9 was reported and named BCR/ABL1ΔE7‐8‐9 here. This isoform was detected only in 10.2% of CML patients with inadequate responses to TKIs. BCR/ABL1Δexon7‐8‐9 isoform promoted S phase cell proliferation and reduced the expression of fusion gene and ABL1 phosphorylation level more slowly than that of control cells after TKIs treatment. The novel isoform has the qualities of a functional tyrosine kinase, localized in the cytoplasm, and could not be imported into the nucleus by TKIs. These results indicated that BCR/ABL1Δexon7‐8‐9 showed poorer sensitivity to imatinib and nilotinib than wild‐type BCR/ABL1. According to molecular docking studies, nilotinib and imatinib present different binding sites and have a lower binding capacity with BCR/ABL1ΔE7‐8‐9 protein than the wild type. Our findings suggested that the novel isoform BCR/ABL1ΔE7‐8‐9 may contribute to TKIs resistance in CML due to its weakened TKIs binding ability. It enriched the mechanism of spliceosome involved in TKIs resistance. Monitoring the expression of BCR/ABL1ΔE7‐8‐9 helps guide the treatment of CML patients in the clinic.
Adverse childhood experiences and maternal self‐efficacy: Examining the mediating role of intimate partner violence and the moderating role of caste membership in rural India
Authors: Jiwani Zishan , Drylewski Grace , Sharma Shipra , Ahun Marilyn , Thapa Shobhali , Steele Miriam
Published: June 2022

Maternal self‐efficacy (MSE) is associated with healthy functioning in mothers and children globally. Maternal exposure to adverse childhood experiences (ACEs) and intimate partner violence (IPV) is known to negatively impact MSE in high‐income countries; however, the association has not been examined in low‐and‐middle‐income countries, such as India, which face socioeconomic risks including poverty, illiteracy, and discrimination based on caste membership. The present study examines the mediating role of IPV in the association between ACEs (specifically—emotional, physical, and sexual abuse, neglect, household dysfunction, and discrimination) and MSE and tests caste membership as a moderator. A community‐based, cross‐sectional survey was performed with 316 mothers with at least one child between 0 and 24 months in a rural area in the North Indian state of Uttar Pradesh. A structural equation framework was used to test the moderated‐mediation model. Results from the moderated‐mediation model indicate that greater ACEs exposure was associated with lower MSE and this association was mediated by IPV exposure for low‐caste but not high‐caste mothers, even after controlling for wealth and literacy. These findings add to existing evidence on ACEs exposure as a significant burden for rural Indian mothers, negatively impacting parenting outcomes such as MSE. The critical role of caste membership is also highlighted, providing implications for future research.
A data optimization and processing method for complex micro‐electronics system in the IoT environment
Authors: Sun Yang
Published: June 2022

With the rapid development of network technologies nowadays, the Internet of Things (IoT) has become a comment trend in most situations. In this trend, the complex micro‐electronics system is the most benefited one. Generally, the traditional evaluation and design of the micro‐electronics system is to establish an approximate model based on the statistical theory with a large error probability. Now, with the benefits of IoT, new methods can be applied. In this paper, we mainly use the IoT enabled Back Propagation (BP) neural network to establish the reliability evaluation and analysis model of micro‐electronic complex system. Firstly, the life cycle of micro‐electronic components and mechanical parts obeys exponential distribution and Weibull distribution in the IoT environment respectively. Then the reliability of each piece under different working time and the overall reliability of the system is calculated according to the failure rate of each part. Secondly, the numerical simulation results show that the error of the reliability value between the BP reliability evaluation model and the basic reliability model is very small, which verifies the accuracy and feasibility of the model, and predicts the reliability of the system. The research shows that this method can predict the overall reliability from the reliability of components, improve the accuracy of reliability evaluation, solve the problem that it is difficult to obtain the analytical expression of distribution model based on statistical theory, and reduce the complexity of the model.
William Carlos Williams’ “The Young Housewife”: A Postcritical Reading vis‐à‐vis Shel Silverstein's The Giving Tree
Authors: Norton Sue
Published: June 2022

Using the framework of Rita Felski in her 2015 book The Limits of Critique, this essay offers a postcritical analysis of William Carlos Williams’ 1915 poem “The Young Housewife.” Its intention is to show how Williams’ poem or any poem can be approached through a variety of critical lenses, but that these may get in the way of more immediate, rewarding ways of reading. Shel Silverstein's well‐known 1964 short book The Giving Tree is similar at the level of “plot” to “The Young Housewife.” Taken in tandem, these two texts neatly exemplify the value of postcritical/non‐resistant reading.
Implementation of pharmacist‐led HIV pre‐exposure prophylaxis management to increase access to care at an academic internal medicine practice
Authors: Miller Trisha A. , Halza Katherine , Hovis Zachary
Published: June 2022

Introduction

The ongoing human immunodeficiency virus (HIV) epidemic continues to require attention to reduce the number of new infections. HIV pre‐exposure prophylaxis (PrEP) has emerged as a highly effective strategy. Although its overall use in the United States has increased since initial approval, it is still underutilized, especially in populations disproportionately affected by HIV. One method for overcoming barriers to PrEP uptake includes utilizing pharmacists to increase access to care.

Methods

For this initiative, a pharmacist‐led PrEP service within a primary care practice was developed utilizing a collaborative practice agreement to enable ordering medications, lab tests, and immunizations. Following the sustainable initial implementation at the first site, expansion occurred to a second location. Data on referrals, patient demographics, and PrEP persistence were collected. Challenges, lessons learned, and future opportunities were also considered.

Results

Since initiating services at both practice sites, a total of 76 patients were referred from August 2018 through March 2022. The majority of patients had their sex listed as male (96%) within the electronic health record and was white (69.7%). The mean age of patients was 33 years (range, 20‐71). Of those who engaged with pharmacist‐led PrEP management, 33.9% (20/59) were retained in care for at least 1 year. There were no occurrences of seroconversion during pharmacist management. Throughout the course of implementation, areas of improvement were identified and addressed for process improvement.

Conclusion

Our experience supports that pharmacist‐led PrEP management in an outpatient primary care practice is a sustainable option to address certain barriers to care. However, the ability for pharmacist‐provided services may be limited by state pharmacy practice laws and/or lack of reimbursement opportunities for clinical services. Developing innovative practice models that integrate pharmacists in a variety of settings is imperative for further reducing HIV transmission.
Depth estimation of tumor invasion in early gastric cancer using scattering of circularly polarized light: Monte Carlo Simulation study
Authors: Nishizawa Nozomi , Kuchimaru Takahiro
Published: June 2022

Quantitative depth estimation of tumor invasion in early gastric cancer by scattering of circularly polarized light is computationally investigated using the Monte Carlo method. Using the optical parameters of the human stomach wall and its carcinoma, the intensity and circular polarization of light scattered from pseudo‐healthy and cancerous tissues were calculated over a wide spectral range. Large differences in the circular polarization with opposite signs, together with the large intensity, are obtained at wavelengths 600 nm and 950 nm. At these two wavelengths, the sampling depth of the biological tissues can be modulated by tuning the detection angle. In bi‐layered pseudo‐tissues with a cancerous layer on a healthy layer and vice versa, the degree of circular polarization of scattered light shows systematic changes depending on the thickness and depth of the cancerous layer, which indicates the feasibility of in vivo quantitative estimation of cancer progression in early gastric cancer.
Photoacoustic‐triggered nanomedicine delivery to internal organs using a dual‐wavelength laparoscope
Authors: Guo Heng , Chen Qian , Li Tingting , Sun Desheng , Xi Lei
Published: June 2022

Precise drug delivery for internal organs is always an important clinical issue. In this study, we developed a dual‐wavelength optical resolution photoacoustic laparoscope, and achieved precise and efficient delivery of nanomedicine to multiple abdominal organs. The laparoscope integrated 532 and 820 nm light to map the vascular network, and visually deliver the nanoparticles to the targeted area using photoacoustic radiation force, respectively. To achieve endoscopic use, we employed a micro‐electro‐mechanical‐system (MEMS) scanner to realize internal two‐dimensional raster scanning of the optical beams. Using phantom experiments, the lateral resolutions were measured as 3.75 μm for 532 nm, and 5.25 μm for 820 nm, respectively. Besides, we demonstrated the feasibility of targeted drug delivery using mouse‐ear tumor model, normal organs, and colon tumor model. All the experimental results suggested that this strategy can serve as a promising precise drug delivery method for the effective treatment of internal organ diseases.
A Retrospective Analysis of Intravenous vs Oral Antibiotic Step‐Down Therapy for the Treatment of Uncomplicated Streptococcal Bloodstream Infections
Authors: Ramos‐Otero Gerardo P. , Sarangarm Preeyaporn , Walraven Carla
Published: June 2022

Evidence supporting intravenous‐to‐oral (IV‐to‐PO) antibiotic deescalation for uncomplicated streptococcal bloodstream infections (BSIs) are limited. The objective of this study was to compare clinical outcomes of patients treated with IV‐only versus IV‐to‐PO antibiotic therapy for uncomplicated streptococcal BSIs. This was a single‐center, retrospective study of patients aged ≥18 years who received treatment for uncomplicated streptococcal BSIs from January 2017 to December 2019. Patients were excluded if they had a polymicrobial BSI, endocarditis, osteomyelitis, septic arthritis, or received antibiotic therapy for >14 days. The primary outcome was clinical failure, defined as persistent bacteremia, recurrence of bacteremia, or mortality at 30 days. Secondary outcomes included length of hospital stay, all‐cause readmissions, development of Clostridioides difficile infection, and adverse antibiotic reactions. There were 98 patients who met the inclusion criteria: 51 patients in the IV‐to‐PO therapy group and 47 patients who received IV‐only antibiotics. Streptococcus pneumoniae and beta‐hemolytic streptococci were the most common pathogens. Patients received an average of 4.4 days of IV antibiotics before being stepped down to an oral agent. Hospital length of stay (6.3 vs 12.6 days; P < .001) and total antibiotic duration of therapy (11.8 vs 13.9 days; P = .002) were significantly shorter in patients receiving IV‐to‐PO therapy. There were no clinical failures observed in patients who received IV‐to‐PO antibiotic therapy. IV‐to‐PO step‐down therapy for uncomplicated streptococcal BSIs was not associated with worse clinical outcomes compared to patients receiving IV‐only antibiotic therapy.
Dysregulated Th1 cells in lung squamous cell carcinoma
Authors: Wang Jiahui , Zhou Jian , Zhou Qiuru , Qi Ying , Zhang Peng , Yan Cihui , Ren Xiubao
Published: June 2022

Lung squamous cell carcinoma (LUSC) is a common subtype of lung cancer. Th1 cells contribute to antitumor immune responses. However, there are few studies on Th1 cells in LUSC. CD8+ T cells are the main driver of the antitumor immunity, targeting tumor cells killing. Th1 cells play an important auxiliary role in this process. Here, we used single-cell RNA-seq (scRNA-seq) to analyze qualified CD4+ T cells and Th1 cells (defined CD4+ T cells with 1 or more of STAT1+, STAT4+, T-bet+, and IFN-γ+ as Th1 cells) from tissues of 8 LUSC patients. Then, we validated Th1 cells and CD8+ T cells of 32 LUSC patients by multiplex immunofluorescence staining and immunohistochemistry. Finally, we used flow cytometry to detect IFN-γ of CD4+ T cells in human PBMCs coincubated with LUSC-derived supernatant to simulate a tumor inhibitory microenvironment. ScRNA-seq showed IFN-γ+ Th1 cells account for 25.28% of all Th1 cells. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses of differentially expressed genes between IFN-γ+ Th1 cells and IFN-γ– Th1 cells confirmed the decreased IFN-γ is associated with endoplasmic reticulum stress (ER stress). Multiplex immunofluorescence staining and immunohistochemistry proved there was a positive correlation between IFN-γ+ STAT1+ T-bet+ Th1 cells and CD8+ T cells. Flow cytometry showed IFN-γ secreted by Th1 cells is decreased. These findings support the claim that Th1 cells’ function is suppressed in LUSC. Through scRNA-seq, we found that the decreased Th1 cells’ function is associated with ER stress, which requires further study. Overall, these findings may produce a new method for the treatment of LUSC.
Antioxidant, antibacterial, cytotoxicity, and phytochemical potentials of fungal bioactive secondary metabolites
Authors: Sureshkumar Senthuran , Merlin Iniya , Prasai Jiwan R. , Rajapriya Pandy , Pandi Mohan
Published: June 2022

The present study focuses on antioxidant, antibacterial, phytochemical potential, and cytotoxicity of secondary metabolites from Colletotrichum gloeosporioides, Fusarium proliferatum, Alternaria arborescens, and Pestalotiopsis vismiae. The scavenging effect of fungal metabolites was determined by 2, 2‐diphenyl‐1‐picrylhydrazyl (DPPH), H2O2, O2‐, and reducing power assays. Among the four fungi, A. arborescens have higher antioxidant activity of DPPH (81.12%), H2O2 (74.83%), superoxide (75.74%), and reducing power (0.141) with standard ascorbic acid. Fungal metabolites were found to be significantly effective against all tested pathogens. A. arborescens showed significant amounts of phenolic (138.78 ± 3.70 mg/g of gallic acid equivalent), flavonoid (74.16 ± 3.58 mg/g of quercetin equivalent), as well as cytotoxicity effects in a cancer cell line (A549) with inhibitory concentration (IC50 = 35 µg/ml at 24 and 48 h). The live and dead cells were analyzed by acridine orange/ethidium bromide staining methods. In addition, A. arborescens metabolites were characterized through gas chromatography‐mass spectrometry analysis. The major compounds were found to be phenol, 4‐(1,1,3,3‐tetramethylbutyl)‐, acetamide, N‐(3‐methylphenyl)‐, dibutyl phthalate, and benzo[qr]naphtho[2,1,8,7‐fghi] pentacene. The compounds were reported in A. arborescensis up to our knowledge this is the first report. Based on this study, all fungal strains have a significant bioactive capacity with A. arborescens strain exhibiting greater biological properties. Further purification and characterization of A. arborescens bioactive component could lead to an intriguing reservoir of novel pharmacological agents in the future.
Evaluation of green silicone surfactant‐based vortex assisted dispersive liquid‐liquid microextraction for sample preparation of organophosphorus pesticide residues in honey and fruit sample
Authors: Elencovan Vasagee , Yahaya Noorfatimah , Samad Nozlena Abdul , Zain Nur Nadhirah Mohamad
Published: June 2022

A vortex‐assisted surfactant enhanced emulsification liquid‐liquid microextraction based on non‐ionic silicone surfactant was successfully developed for the determination of organophosphorus pesticides in food samples coupled to gas chromatography‐mass spectrometry. A new type of non‐ionic silicone surfactant composed of polysiloxane chains was employed as a green emulsifier to facilitate the emulsification of extraction solvent into the sample matrix, thereby intensifying the mass transfer of target analytes into the organic phase. The variables that affect the extraction were systematically optimized: 80 μl of hexane and 0.5% (v/v) of silicone surfactant were used as extraction solvent and surfactant respectively, the solution was mixed well under vortex agitation for 1 min with the addition of 4% (w/v) sodium sulfate. Under optimum conditions, the linearity of the method was obtained in the range of 0.1–200 μg/kg with a good coefficient of determination varying from 0.9986 to 0.9996. The limit of detection and the limit of quantitation were between 0.008–0.1 and 0.02–0.3 μg/kg, respectively. Application of the proposed method to real samples gave satisfactory recovery values (80%–118%) for the target analytes. The suggested approach has also proven to be convenient, expeditious, and environmentally benign.
The formation of small macro‐aggregates induces soil organic carbon stocks in the restoration process used on cut slopes in alpine regions of China
Authors: Huang Bocong , Zhu Mengke , Liu Zongyang , Sheng Meihua , Chen Mei , Yang Qinqing , Yang Yuxuan , Ai Yingwei
Published: June 2022

Road construction in mountainous areas of China has formed bare slopes on a large scale, which has aggravated soil erosion and carbon loss, and the restoration processes have changed soil structure and fertility. However, there are few reports regarding the differences of soil aggregate dynamics and SOC sequestration under different restoration process for cut slopes. In this study, three types of cut slopes [cut slope restored naturally (CSN); cut slope restored with three‐dimensional mesh (CST); cut slope restored with galvanized wire mesh (CSG)] and natural slope (NS) in alpine regions were selected as the research objects. SOC stocks and their key driving factors were then analyzed. The results showed that CSG was more beneficial to the formation of macro‐aggregates than CSN and CST. There were significant differences in wet‐sieved aggregate stability under different restoration process, where the sort by strength of stability was NS > CSG > CST > CSN. Aggregate size was a more important factor for SOC stocks than restoration process. The increase of SOC stocks was mainly due to that within small macro‐aggregates. RandomForest analysis revealed that the mass proportion of micro‐aggregates was the most important factor affected SOC stocks, while SOC stocks within large macro‐aggregates and small macro‐aggregates and porosity significantly affected SOC stocks. Partial least squares path modelling analysis found the particle size and stability of aggregates had negative total effects on SOC stocks, and SOC content had positive total effect on that. Overall, for the ecological restoration of cut slope in alpine regions, CSG was most beneficial to increase soil aggregate stability and SOC stocks.