bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of hydroxypropyl β‐cyclodextrin hybrid monolithic material as adsorbent for dispersive solid‐phase extraction of fluoroquinolones from environmental water samples
Authors: Zhou Li , Yu Jia
Published: April 2022

In this study, the hydroxypropyl β‐cyclodextrin hybrid monolithic material was fabricated and firstly applied as an adsorbent for dispersive solid‐phase extraction coupled with high‐performance liquid chromatography to detect trace‐level seven fluoroquinolones in water samples. The prepared hydroxypropyl β‐cyclodextrin hybrid monolithic material was characterized by Fourier‐transform infrared spectroscopy, scanning electron microscopy, and adsorption experiments, which showed excellent specific adsorption to the target fluoroquinolones. Under the optimized conditions, the extraction methodology showed satisfactory precision with relative standard deviations between 2.6% and 5.6%, good linearity (R2 ≥ 0.9990), and satisfactory recoveries (82.5–91.8%). The limits of detection and limits of quantification of the method were in the range of 0.4–1.2 and 1.4–4.0 ng/mL, respectively, which confirmed the possibility of quantifying trace levels. Furthermore, the material could be reused at least five times. These results demonstrated that the hydroxypropyl β‐cyclodextrin hybrid monolithic material was a promising adsorbent for fluoroquinolones, and the established method combined dispersive solid‐phase extraction with high‐performance liquid chromatography was suitable for the determination of fluoroquinolones in aqueous samples.
Evaluation of Fetal Cardiac Function in Maternal Gestational Diabetes Mellitus by Speckle‐Tracking Echocardiography
Authors: Huang Peina , Deng Youbin , Feng Ling , Gao Yiping , Cheng Xueqing , Liu Hongyun
Published: April 2022

Objectives

Gestational diabetes mellitus (GDM) is the most common metabolic disease that occurs during pregnancy and may result in fetal cardiac dysfunction. Our study aimed to assess the cardiac function in fetuses of mothers with GDM by a quantitative analysis software based on speckle‐tracking echocardiography.

Methods

Forty‐nine fetuses exposed to GDM and 50 normal fetuses were enrolled, and fetal echocardiography were performed and analyzed in this prospective cross‐sectional study. We compared cardiac systolic function between the two groups using fetal cardiac quantitative analysis software.

Results

In the GDM group, left ventricular (24 ± 4 versus 28 ± 4, P < .001) and right ventricular global longitudinal strain (23 ± 4 versus 26 ± 4, P = .002) and right ventricular free wall strain (26 ± 6 versus 29 ± 5, P = .006) were significantly lower compared with the control group, whereas there was no significant difference in global spherical index (1.2 ± 0.1 versus 1.2 ± 0.1, P = .425). Additionally, 24‐segment transverse fraction shortening of the right ventricle was more impaired than the left, and the segments with reduced fraction shortening were mainly located in the mid and apical sections of the right ventricle, and midsection of the left ventricle.

Conclusion

Fetuses exposed to GDM may have cardiac dysfunction before the onset of cardiac morphologic abnormalities, and the right ventricle is more vulnerable than the left during fetal development.
Medical and Surgical Treatment for Medication‐Induced Tremor: Case Report and Systematic Review
Authors: Amerika Wardell E. , van der Gaag Saskia , Mosch Arne , van der Gaag Niels A. , Hoffmann Carel F.E. , Zutt Rodi , Marinus Johan , Contarino Maria Fiorella
Published: April 2022

Objective

To present a case of refractory medication‐induced tremor successfully treated with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) and to propose a medical and surgical treatment algorithm based on a systematical review of the literature.

Methods

Patient data were retrospectively collected. A systematic search was performed in PubMed, Embase, and Cochrane Library. Subjective and objective data were pooled for analysis by classifying them into 5 predefined categories(no, minimal, moderate, good, and excellent effects).

Results

The patient presented with lithium‐induced bilateral progressive hand tremor lasting 25 years. After DBS, he reported excellent tremor suppression until the last follow‐up (36 months after Vim‐DBS). For the review, 34 of 140 studies were included and evaluated (178 unique subjects, 31 different treatments). A good‐to‐excellent tremor suppression (50%–100%) in at least 50% of subjects was achieved using propranolol (12 studies, 50% of 56 subjects), tetrabenazine (5 studies, 51% of 13 subjects), and metoprolol (4 studies, 75% of 8 subjects). The effect of benztropine and diphenhydramine was none or only minimal to moderate (up to 50% improvement; both: 3 studies, 50% of 4 patients). One article reported minimal‐to‐moderate effectiveness after DBS of the ventral oral posterior nucleus of the thalamus. Methods were highly heterogeneous. All studies scored grade III or IV quality of evidence, which was insufficient for recommendations (level U).

Conclusion

Treatment decision making should be performed on a case‐by‐case basis considering the low level of evidence, and we propose a practically oriented treatment algorithm. Propranolol, tetrabenazine, and metoprolol might be effective. For selected and refractory cases, DBS might be considered.
The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy
Authors: Wenning Gregor K. , Stankovic Iva , Vignatelli Luca , Fanciulli Alessandra , Calandra‐Buonaura Giovanna , Seppi Klaus , Palma Jose‐Alberto , Meissner Wassilios G. , Krismer Florian , Berg Daniela , Cortelli Pietro , Freeman Roy , Halliday Glenda , Höglinger Günter , Lang Anthony , Ling Helen , Litvan Irene , Low Phillip , Miki Yasuo , Panicker Jalesh , Pellecchia Maria Teresa , Quinn Niall , Sakakibara Ryuji , Stamelou Maria , Tolosa Eduardo , Tsuji Shoji , Warner Tom , Poewe Werner , Kaufmann Horacio
Published: April 2022

Background

The second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages.

Objective

To develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence‐based and consensus‐based methodology.

Methods

We identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference.

Results

The criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow.

Conclusions

This set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
A broadband circularly polarized e‐shaped patch antenna
Authors: Han Zhu‐Bin , Li Jian‐ying , Li Zhi‐Ying , Qi Yang‐Xiao , Li Dong
Published: April 2022

We proposed a broadband e‐shaped circularly polarized (CP) patch antenna with single‐point feed, and the feed point is located at the center of the antenna. The structure of this new antenna includes a ground plate and an e‐shaped patch placed on a substrate. The measured impedance bandwidth of the proposed antenna is approximately 17.89% (3.47–4.15 GHz), and the measured 3‐dB axial ratio bandwidth (ARBW) is about 9.47% (3.63–3.99 GHz). The antenna can achieve the gain of 8.4 to 8.7 dBi within the ARBW. And at the center frequency (3.8 GHz), right‐hand CP to left‐hand CP isolation of the antenna can reach −33 dB.
A low‐cost greenhouse‐based high‐throughput phenotyping platform for genetic studies: A case study in maize under inoculation with plant growth‐promoting bacteria
Authors: Yassue Rafael Massahiro , Galli Giovanni , Borsato Ronaldo , Cheng Hao , Morota Gota , Fritsche‐Neto Roberto
Published: April 2022

Greenhouse‐based high‐throughput phenotyping (HTP) presents a useful approach for studying novel plant growth‐promoting bacteria (PGPB). Despite the potential of this approach to leverage genetic variability for breeding new maize (Zea Mays L.) cultivars exhibiting highly stable symbiosis with PGPB, greenhouse‐based HTP platforms are not yet widely used because they are highly expensive; hence, it is challenging to perform HTP studies under a limited budget. In this study, we built a low‐cost greenhouse‐based HTP platform to collect growth‐related image‐derived phenotypes. We assessed 360 inbred maize lines with or without PGPB inoculation under nitrogen‐limited conditions. Plant height, canopy coverage, and canopy volume obtained from photogrammetry were evaluated five times during early maize development. A plant biomass index was constructed as a function of plant height and canopy coverage. Inoculation with PGPB promoted plant growth in early developmental stages. Phenotypic correlations between the image‐derived phenotypes and manual measurements were at least 0.47 in the later stages of plant development. The genomic heritability estimates of the image‐derived phenotypes ranged from 0.23 to 0.54. Moderate‐to‐strong genomic correlations between the plant biomass index and shoot dry mass (0.24–0.47) and between HTP‐based plant height and manually measured plant height (0.55–0.68) across the developmental stages showed the utility of our HTP platform. Collectively, our results demonstrate the usefulness of the low‐cost HTP platform for large‐scale genetic and management studies to capture plant growth.
Assessment of porphyrogenicity of drugs and chemicals in selected hepatic cell culture models through a fluorescence‐based screening assay
Authors: Ma Christopher D. , Van Horn Cynthia G. , Wan Meimei , Bishop Colin , Bonkovsky Herbert L.
Published: April 2022

Compounds that induce 5‐aminolevulinic acid [ALA] synthase‐1 and/or cytochromes P‐450 may induce acute porphyric attacks in patients with the acute hepatic porphyrias [AHPs]. Currently, there is no simple, robust model used to assess and predict the porphyrogenicity of drugs and chemicals. Our aim was to develop a fluorescence‐based in vitro assay for this purpose. We studied four different hepatic cell culture models: HepG2 cells, LMH cells, 3D HepG2 organoids, and 3D organoids of primary liver cells from people without known disease [normal human controls]. We took advantage of the fluorescent properties of protoporphyrin IX [PP], the last intermediate of the heme biosynthesis pathway, performing fluorescence spectrometry to measure the intensity of fluorescence emitted by these cells treated with selected compounds of importance to patients with AHPs. Among the four cell culture models, the LMH cells produced the highest fluorescence readings, suggesting that these cells retain more robust heme biosynthesis enzymes or that the other cell models may have lost their inducibility of ALA synthase‐1 [ALAS‐1]. Allyl isopropyl acetamide [AIA], a known potent porphyrogen and inducer of ALAS‐1, was used as a positive control to help predict porphyrogenicity for tested compounds. Among the tested compounds (acetaminophen, acetylsalicylic acid, β‐estradiol, hydroxychloroquine sulfate, alpha‐methyldopa, D (‐) norgestrel, phenobarbital, phenytoin, sulfamethoxazole, sulfisoxazole, sodium valproate, and valsartan), concentrations greater than 0.314 mM for norgestrel, phenobarbital, phenytoin, and sodium valproate produced fluorescence readings higher than the reading produced by the positive AIA control. Porphyrin accumulation was also measured by HPLC to confirm the validity of the assay. We conclude that LMH cell cultures in multi‐well plates are an inexpensive, robust, and simple system to predict the porphyrogenicity of existing or novel compounds that may exacerbate the AHPs.
Toward cheaper light harvesting systems: Using earth‐abundant metal oxide nanoparticles in self‐assembled peptide‐porphyrin nanofibers
Authors: Lamba Saurabh , Kihara Shinji , Chan Eddie Wai Chi , McGillivray Duncan , Waterhouse Geoffrey I. N. , Travas‐Sejdic Jadranka , Sarojini Vijayalekshmi
Published: April 2022

Cheap artificial light harvesting systems, which competently harvest solar energy and promote efficient energy transfer, are highly sought after in the renewable sector. We report the synthesis of self‐assembled peptide‐porphyrin fibers (SJ 6) fabricated with iron(III) oxide (Fe3O4) nanoparticles as feasible electron acceptors. Charge‐complementarity between the negatively charged peptide (20E) and the protonated Zn‐tetraphenyl porphyrin (ZnTPyP) led to an ordered assembly of the ZnTPyP molecules, enabling efficient light harvesting. X‐ray diffraction data indicates a more ordered structure in SJ 6 compared to 20E and ZnTPyP. The incorporation of Fe3O4 nanoparticles into SJ 6 showed significant fluorescence quenching, indicating efficient electron flow from the donor to the acceptor. The SJ 6‐nFe3O4 system performed the light reaction of photosynthesis as confirmed by the reduction of 1 mM NAD+ to 0.180 mM NADH upon exposure to visible light (Xe lamp λ > 420 nm) for 1 h. The photochemical regeneration of NADH using the SJ 6‐nFe3O4 system was coupled to glutamate dehydrogenase‐catalyzed conversion of α‐ketoglutarate to L‐glutamate. These results confirm the successful synthesis of an artificial light harvesting peptide‐porphyrin system with Fe3O4 nanoparticles as promising low‐cost electron separators.
Model‐informed drug development of voxelotor in sickle cell disease: Population pharmacokinetics in whole blood and plasma
Authors: Savic Radojka M. , Green Michelle L. , Jorga Karin , Zager Michael , Washington Carla B.
Published: April 2022

Oxbryta (voxelotor) is a small‐molecule inhibitor of sickle hemoglobin (Hb) polymerization approved for patients with sickle cell disease (SCD) aged greater than or equal to 12 years at a dose of 1500 mg once daily (q.d.). Voxelotor binds preferentially to Hb, and voxelotor partitioning into red blood cells is an effective predictor of Hb occupancy. The objectives of these analyses were to develop a population pharmacokinetic (PopPK) model for voxelotor in both plasma and whole blood in adults and adolescents to support the dose selection for optimal target engagement and to identify covariates that have a significant effect on voxelotor pharmacokinetics (PK) in plasma and whole blood. An integrated plasma and whole blood PopPK model with two compartments, first‐order absorption and elimination, and a site‐of‐action effect compartment adequately described the concentration‐time profiles of voxelotor in plasma and whole blood in patients treated up to 72 weeks. Covariates with significant effects on voxelotor PK included baseline blood volume on apparent volume of the central compartment and time‐varying hematocrit and dose on whole blood partitioning, indicating that clinical markers of voxelotor effect can, in turn, influence its PK. Furthermore, the model confirmed that voxelotor PK in plasma and whole blood is linear with dose and time and comparable for adults and adolescents. No clinically important covariate effects on voxelotor PK that warranted dose adjustment were identified in this analysis. Overall, the PopPK analyses contributed significantly to the voxelotor label and support 1500 mg q.d. as the therapeutic dose in adults and adolescents with SCD.
Prediction of CYP‐mediated DDIs involving inhibition: Approaches to address the requirements for system qualification of the Simcyp Simulator
Authors: Kilford Peter J. , Chen Kuan‐Fu , Crewe Kim , Gardner Iain , Hatley Oliver , Ke Alice Ban , Neuhoff Sibylle , Zhang Mian , Rowland Yeo Karen
Published: April 2022

Physiologically‐based pharmacokinetic (PBPK) modeling is being increasingly used in drug development to avoid unnecessary clinical drug–drug interaction (DDI) studies and inform drug labels. Thus, regulatory agencies are recommending, or indeed requesting, more rigorous demonstration of the prediction accuracy of PBPK platforms in the area of their intended use. We describe a framework for qualification of the Simcyp Simulator with respect to competitive and mechanism‐based inhibition (MBI) of CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4/5. Initially, a DDI matrix, consisting of a range of weak, moderate, and strong inhibitors and substrates with varying fraction metabolized by specific CYP enzymes that were susceptible to different degrees of inhibition, were identified. Simulations were run with 123 clinical DDI studies involving competitive inhibition and 78 clinical DDI studies involving MBI. For competitive inhibition, the overall prediction accuracy was good with an average fold error (AFE) of 0.91 and 0.92 for changes in the maximum plasma concentration (Cmax) and area under the plasma concentration (AUC) time profile, respectively, as a consequence of the DDI. For MBI, an AFE of 1.03 was determined for both Cmax and AUC. The prediction accuracy was generally comparable across all CYP enzymes, irrespective of the isozyme and mechanism of inhibition. These findings provide confidence in application of the Simcyp Simulator (V19 R1) for assessment of the DDI potential of drugs in development either as inhibitors or victim drugs of CYP‐mediated interactions. The approach described herein and the identified DDI matrix can be used to qualify subsequent versions of the platform.
Nanoscale Memristor‐Based Spike Timing‐Dependent Plasticity Learning in a Radix‐X Quantized Retinal Neural Network
Authors: Kim Young Hwan , Eshraghian Jason K. , Goo Yong Sook , Cho Kyoungrok
Published: April 2022

The human retina sends visual signals to the brain's visual cortex from photoreceptors (rod and cone cells) through various synaptic pathways and performs crucial early vision processing before signals are passed to higher brain regions. Herein, an artificial retina system implemented based on the leaky integrate‐and‐fire spiking neuron model is presented. The architecture of the proposed retina system consists of a multilayer convolutional neural network (CNN), and the system uses spike timing‐dependent plasticity (STDP) as a feedforward learning rule. In addition, the system integrates a feedback plasticity learning rule to expedite learning convergence. The system weights are implemented using nanoscale memristor arrays, taking on a constrained (radix‐X) range of conductance states. The proposed system produces an output image of 25 × 25 pixels, corresponding to the output retina ganglion cells that act as the interface between the retina and the visual cortex, using an input image of 100 × 100 pixels.
Dual autoimmune diseases: Rheumatoid arthritis with systemic lupus erythematosus and Type 1 diabetes mellitus with multiple sclerosis
Authors: Ahmad Rizwan , Ahsan Haseeb
Published: April 2022

Autoantibodies and inflammation are the hallmarks of autoimmune diseases (ADs). Organ‐specific and nonorgan‐specific ADs are divided according to whether the autoimmune reaction is directed against a specific tissue (e.g., thyroid in Hashimoto's thyroiditis) or widely expressed antigens (e.g., cell nuclei in systemic lupus erythematosus [SLE]). SLE is distinguished by the presence of circulating autoantibodies and immune complex deposition, both of which can induce inflammatory damage to many organs. Rheumatoid arthritis (RA), sometimes called inflammatory arthritis, is a systemic AD that affects the joints and causes synovitis. Multiple sclerosis (MS) is a central nervous system inflammatory disease with various neurological and autoimmune symptoms. Links have been reported between RA and SLE as well as between Type 1 diabetes mellitus and MS. Identification of shared genes and biological processes could aid in the discovery of possible treatment targets in these dual ADs. This review article explores the molecular nature and familial inheritance of dual ADs.
Construction of boric acid‐functionalized metal–organic frameworks for glycopeptide recognition in the serum of cervical cancer patients
Authors: Rao Dongping , Wang Baichun , Zhong Huizhen , Yan Yinghua , Ding Chuan‐Fan
Published: April 2022

Rationale

Cervical cancer is one of the most common malignant tumors in women, and it is essential to explore potential biomarkers such as glycopeptides closely related to cancer in physiological samples of cervical cancer patients. Sample pretreatment is required before direct detection using mass spectrometry because there are certain limitations. Meanwhile, it is still highly desired to promote the functionalization and application of metal–organic framework (MOF)‐derived materials.

Methods

Using a post‐synthesis modification method, a novel type of boric acid‐functionalized MOF probe (designated as UiO‐66@PEI@Au@B(OH)2) is prepared for recognition of glycopeptides. The results are obtained using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry and nano‐liquid chromarography–tandem mass spectrometry.

Results

The UiO‐66@PEI@Au@B(OH)2 probe exhibits a low detection limit (0.6 fmol μL−1), an excellent recovery rate, comparatively good reusability and selectivity (HRP digests:BSA digests = 1:500). When UiO‐66@PEI@Au@B(OH)2 is used to selectively capture glycopeptides from the serum of a healthy person and a cervical cancer patient, 101 glycopeptides corresponding to 54 glycoproteins and 108 glycopeptides corresponding to 57 glycoproteins are detected, respectively.

Conclusions

The successful preparation of UiO‐66@PEI@Au@B(OH)2 provides a path for the investigation of the functionalization of MOF‐derived materials. The excellent performance of UiO‐66@PEI@Au@B(OH)2 not only demonstrates the huge potential of functionalized MOFs in the glycoproteome, but also opens up new phases of the application of MOF‐based materials.
Preoperative positioning planning for a robot‐assisted minimally invasive surgical system based on accuracy and safety
Authors: Su Peng , Li Jiang , Yue Chao , Liu Tian , Liu Baoguo , Li Jian
Published: April 2022

Background

Minimally invasive robot‐assisted techniques are being used increasingly in surgical procedures, and the preoperative preparation for this kind of operation is more complicated than traditional operations.

Method

Taking the placement requirements of minimally invasive thyroid surgery as the research object, taking the kinematic performance and safety of the manipulator as the optimization goal, a set of indexes and pendulums for evaluating the accuracy and safety of the manipulators are proposed accordingly.

Results

The optimal preoperative positioning scheme is obtained based on Non dominated sorting genetic algorithm‐ II multi‐objective genetic algorithm. Meanwhile, compared with the optimization results of Gaot genetics and the positional scheme given by the surgeon based on experience, the advantages of the scheme are proved to be obvious.

Conclusion

The scheme showed good performance in the comparison and proved the feasibility of the positional scheme in preoperative planning.
Omicron – The new SARS‐CoV‐2 challenge?
Authors: Lino A. , Cardoso M. A. , Martins‐Lopes P. , Gonçalves H. M. R.
Published: April 2022

SARS‐CoV‐2 virus has infected nearly 300 M people worldwide and has been associated with over 6 M deaths by March 2022. Since the virus emergence in December 2019 in Wuhan, several new mutations have been described. The World Health Organization has developed a working name for these emerging variants according to their impact on the worldwide population. In this context a high alert has been paid to variants of concern (VOC) due to their high infectiousness and transmissibility patterns. The most recent VOC, Omicron (B.1.1.529), has become dominant in the shortest time ever and has placed Europe under an overwhelming and unprecedented number of new cases. This variant has numerous mutations in regions that are associated with higher transmissibility, stronger viral binding, affinity and antibody escape. Moreover, the mutations and deletions present in the spike protein suggest that the SARS‐CoV‐2 specific attachment inhibitors may not be the best option for Omicron therapy. Omicron is the dominant variant circulating worldwide and, at the end of February 2022, it was responsible for nearly all sequences reported to GISAID. Omicron is made up of several sublineages, where the most common are BA.1 and BA.2 (or Nextstrain clade 21K and 21L, respectively). At a global level, it is possible to say that the proportion of BA.2 has been increasing relative to BA.1 and in some countries it has been replacing it at high rates. In order to better assess the Omicron effectiveness on antibody escape, spread and infectious ability it is of the highest relevance to maintain a worldwide tight surveillance. Even though this variant has been associated with a lower death rate, it is important to highlight that the number of people becoming infected is concerning and that further unpredictable mutations may emerge as the number of infected people rises.
Bisphosphonates on Smooth TiO2: Modeling and Characterization
Authors: Dias Leonardo F. G. , Rheinheimer João P. C. , Gomes Orisson P. , Noeske Michael , Stamboroski Stephani , Bronze‐Uhle Erika S. , Mainardi Maria C. , Cavalcanti Welchy L. , Neto Augusto B. , Lisboa‐Filho Paulo N.
Published: April 2022

This paper presents insights into surfaces properties of sputter‐deposited titania modified with bisphosphonates, including zeta potential measurements in a pH range. Functionalization was investigated through simulation and experimental approaches to model the adsorbate and evaluate structure‐response relationships. Molecules of etidronic, alendronic, and risedronic acids were investigated through density functional theory. The molecules vary their reactivity through similar structures considering different scenarios. X‐ray photoelectron spectroscopy of titania/BP systems demonstrated that functionalization occurs in a short time and resulted in a predominantly “side‐on” adsorbate configuration after two hours of immersion. Zeta potential showed the predominancy of negative charges deprotonated free phosphonates. Water contact angle demonstrated that titania surfaces are hydrophilic after overnight functionalization. Atomic force measurements of bisphosphonates layers suggested that the molecular anions follow the surface topography, unchanging the surface roughness.
Detection of L‐Aspartic Acid and L‐Glutamic Acid in Water Using a Fluorescent Nanoparticle Constructed by Pillar[5]arene‐Based Molecular Recognition
Authors: Shi Bingbing , Zhao Xing‐Xing , Chai Yongping , Qin Peng , Qu Wen‐Juan , Lin Qi , Zhang You‐Ming
Published: April 2022

Aspartic acid and glutamic acid show critical impact in the central nervous system as excitatory neurotransmitters. The selective detection of aspartic acid and glutamic acid has a wide range of potential applications in the field of biomedicine. In this work, we report the highly selective detection of L‐Aspartic acid (L‐Asp) and L‐Glutamic acid (L‐Glu) in water is achieved by using a fluorescent nanoparticle constructed by a water‐soluble pillar[5]arene‐based host‐guest interactions. These nanoparticles show strong fluorescent emission in water. After the addition of L‐Asp or L‐Glu to a solution of the fluorescent nanoparticles, these nanoparticles transformed to nanosheets with weak fluorescent emission, resulting the highly selective detection of aspartic acid and glutamic acid in water. The detection limits of the fluorescent nanoparticles toward L‐Asp and L‐Glu were calculated to be 2.09×10−7 M and 4.03×10−7 M, respectively. This work provide an efficiency way for highly sensitive detection of L‐Asp and L‐Glu in water.
A comparison of integrated and designated ELD models on second and third graders' oral English language proficiency
Authors: Edelman Emily R. , Amirazizi Samira A. , Feinberg Daniel K. , Quirk Matthew , Scheller Jennifer , Pagán Carlos R. , Persoon Jamie
Published: April 2022

This article reports on a longitudinal, quasi‐experimental comparison of two English language development (ELD) models implemented from kindergarten through Grade 3 to support oral English language development among Spanish‐speaking English language learners (ELLs). Specifically, the study examined oral English language proficiency among students who received only integrated English language development (I‐ELD; n = 39) and students who received I‐ELD with 30 minutes of daily designated ELD (D‐ELD) entailing four specific routines and strategies (n = 65). The study also compared oral proficiency with English‐only speakers (EO) from the same school (n = 47). Oral language proficiency was measured by the IDEA Proficiency Test (IPT I‐Oral; Ballard & Tighe, 2017). A repeated‐measures analysis of variance (ANOVA) across Grades 2 and 3 indicated significant (p < .001; η2 = 0.53) increases in oral proficiency for ELL students who received D‐ELD. A follow‐up analysis of covariance (ANCOVA) indicated significant positive effects (p < .001; η2 = 0.19) of the D‐ELD approach on ELL students' oral proficiency compared to only I‐ELD in Grade 3. The ANCOVA also found no significant (p > .05) differences in oral proficiency between ELL students who received D‐ELD and EO students in Grade 3, indicating similar oral English skills. The D‐ELD model's instructional strategies and practical implications are discussed.
Protective effect of lupeol on arthritis induced by type II collagen via the suppression of P13K/AKT signaling pathway in Sprague dawley rats
Authors: Song Tiebing , Shi Renhong , Vijayalakshmi Annamalai , Lei Bin
Published: April 2022

To explore the therapeutic value of lupeol on collagen‐induced arthritis (CIA) in rats, a rheumatoid arthritis model. Lupeol is well known pentacyclic triterpene found in various plant sources, which possess anti‐inflammatory and antioxidant actions. The current study was assessed the anti‐arthritic potential of lupeol and its molecular mechanisms as compared with indomethacin (Indo) in collagen‐induced arthritis CIA rats. The rats were randomly alienated into five groups: Control, CIA alone, CIA + lupeol (10 mg/kg bw), CIA + Indomethacin (3 mg/kg bw), and lupeol (10 mg/kg bw) alone. The paw volume, biochemical, hematological parameters, inflammatory enzymes, and cytokines were measured. As well protein expression of apoptotic proteins, and histopathological of ankle joint were examined. Inflammatory markers, cytokines, histological changes, paw volume, and inflammation were intensely reduced and enhanced apoptosis by lupeol. Alterations in hematological parameters, rheumatoid factor, C‐reactive protein, and ceruloplasmin in arthritis were reverted by lupeol. Protein expressions of Bcl‐2, and P13K/Akt signaling were declined, whereas the Bax, caspssae‐3, and caspase‐9 were elevated. These results highlighted that lupeol suppresses P13K/Akt signaling and has a promising anti‐arthritic potential for collagen‐induced rheumatic arthritis treatment. Hence lupeol would be suggested as an alternative natural source with potent anti‐inflammatory and apoptotic actions for chronic inflammatory disorders.
Deltamethrin induces apoptosis in cerebrum neurons of quail via promoting endoplasmic reticulum stress and mitochondrial dysfunction
Authors: Li Siyu , Wu Pengfei , Han Bing , Yang Qingyue , Wang Xiaoqiao , Li Jiayi , Deng Ning , Han Biqi , Liao Yuge , Liu Yan , Zhang Zhigang
Published: April 2022

Deltamethrin (DLM) is a widely used and highly effective insecticide. DLM exposure is harmful to animal and human. Quail, as a bird model, has been widely used in the field of toxicology. However, there is little information available in the literature about quail cerebrum damage caused by DLM. Here, we investigated the effect of DLM on quail cerebrum neurons. Four groups of healthy quails were assigned (10 quails in each group), respectively given 0, 15, 30, and 45 mg/kg DLM by gavage for 12 weeks. Through the measurements of quail cerebrum, it was found that DLM exposure induced obvious histological changes, oxidative stress, and neurons apoptosis. To further explore the possible molecular mechanisms, we performed real‐time quantitative PCR to detect the expression of endoplasmic reticulum (ER) stress‐related mRNA such as glucose regulated protein 78 kD, activating transcription factor 6, inositol requiring enzyme, and protein kinase RNA (PKR)‐like ER kinase. In addition, we detected ATP content in quail cerebrum to evaluate the functional status of mitochondria. The study showed that DLM exposure significantly increased the expression of ER stress‐related mRNA and decreased ATP content in quail cerebrum tissues. These results suggest that chronic exposure to DLM induces apoptosis of quail cerebrum neurons via promoting ER stress and mitochondrial dysfunction. Furthermore, our results provide a novel explanation for DLM‐induced apoptosis of avian cerebrum neurons.
A novel approach to consider triaxial tensile stresses within the framework of a failure criterion
Authors: Roetsch Karl , Horst Thomas
Published: April 2022

For use in micromechanical simulations of continuous fiber reinforced polymers, a more general form of the paraboloid failure criterion by Stassi‐D'Alia for matrix failure was developed with explicit consideration of the hydrostatic tension strength. Regarding polymers, limits for hydrostatic tensile strength based on isotropic linear elasticity could be derived. The comparison of the newly developed extended paraboloid criterion with experimental data for yielding as well as for material separation (fracture) shows good agreement.
Socio-Technical Innovation Bundles Tailored to Distinct Agri-Food Systems
Authors: Barrett Christopher B. , Benton Tim , Fanzo Jessica , Herrero Mario , Nelson Rebecca J. , Bageant Elizabeth , Buckler Edward , Cooper Karen , Culotta Isabella , Fan Shenggen , Gandhi Rikin , James Steven , Kahn Mark , Lawson-Lartego Laté , Liu Jiali , Marshall Quinn , Mason-D’Croz Daniel , Mathys Alexander , Mathys Cynthia , Mazariegos-Anastassiou Veronica , Miller Alesha , Misra Kamakhya , Mude Andrew , Shen Jianbo , Sibanda Lindiwe Majele , Song Claire , Steiner Roy , Thornton Philip , Wood Stephen
Published: April 2022

Scientific discovery is neither linear nor predictable. The time it takes to develop breakthrough technologies varies enormously among application domains. Some basic scientific discoveries remain elusive and will need continued, concerted funding and attention in the years and decades ahead. In some cases, the stumbling block is the scientific advancement per se, when important discoveries along the path towards technological readiness have not yet been made.
Artificial Intelligence in Education and Ethics
Authors: du Boulay Benedict
Published: April 2022

This chapter traces the ethical issues around applying artificial intelligence (AI) in education from the early days of artificial intelligence in education in the 1970s to the current state of this field, including the increasing sophistication of the system interfaces and the rise in data use and misuse. While in the early days most tools were largely learner-facing, now there are tools that are teacher-facing, supporting their management of the classroom, and administrator-facing, assisting in their management of cohorts of students. Learner-facing tools now take into account the affective and motivational aspects of learning as well as the cognitive. The rise of data collection and its associated analytic tools has enabled the development of dashboards for the dynamic management and reflective understanding of learners, teachers, and administrators. Ethical issues hardly figured in the early days of the field but now they loom large. This is because of the legitimate fears that learners’ and teachers’ autonomy will be compromised, that learner data will be collected and potentially misappropriated for other purposes, and that AI will introduce extra biases into educational decisions and increase existing inequity and also because of the scary reputation that AI has in general.
Impact of phosphorylation of heat shock protein 27 on the expression profile of periodontal ligament fibroblasts during mechanical strain
Authors: Schröder Agnes , Wagner Kathrin , Cieplik Fabian , Spanier Gerrit , Proff Peter , Kirschneck Christian
Published: April 2022

Purpose

Orthodontic tooth movement is a complex process involving the remodeling of extracellular matrix and bone as well as inflammatory processes. During orthodontic treatment, sterile inflammation and mechanical loading favor the production of receptor activator of NF-κB ligand (RANKL). Simultaneously, expression of osteoprotegerin (OPG) is inhibited. This stimulates bone resorption on the pressure side. Recently, heat shock protein 27 (HSP27) was shown to be expressed in the periodontal ligament after force application and to interfere with inflammatory processes.

Methods

We investigated the effects of phosphorylated HSP27 on collagen synthesis (COL1A2 mRNA), inflammation (IL1B mRNA, IL6 mRNA, PTGS2 protein) and bone remodeling (RANKL protein, OPG protein) in human periodontal ligament fibroblasts (PDLF) without and with transfection of a plasmid mimicking permanent phosphorylation of HSP27 using real-time quantitative polymerase chain reaction (RT-qPCR), western blot and enzyme-linked immunosorbent assays (ELISAs). Furthermore, we investigated PDLF-induced osteoclastogenesis after compressive strain in a co-culture model with human macrophages.

Results

In particular, phosphorylated HSP27 increased gene expression of COL1A2 and protein expression of PTGS2, while IL6 mRNA levels were reduced. Furthermore, we observed an increasing effect on the RANKL/OPG ratio and osteoclastogenesis mediated by PDLF.

Conclusion

Phosphorylation of HSP27 may therefore be involved in the regulation of orthodontic tooth movement by impairment of the sterile inflammation response and osteoclastogenesis.
Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial
Authors: Waijer Simke W. , Vart Priya , Cherney David Z. I. , Chertow Glenn M. , Jongs Niels , Langkilde Anna Maria , Mann Johannes F. E. , Mosenzon Ofri , McMurray John J. V. , Rossing Peter , Correa-Rotter Ricardo , Stefansson Bergur V. , Toto Robert D. , Wheeler David C. , Heerspink Hiddo J. L.
Published: April 2022

Aims/hypothesis

In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin reduced the risks of progressive kidney disease, hospitalised heart failure or cardiovascular death, and death from all causes in patients with chronic kidney disease (CKD) with or without type 2 diabetes. Patients with more severe CKD are at higher risk of kidney failure, cardiovascular events and all-cause mortality. In this post hoc analysis, we assessed the efficacy and safety of dapagliflozin according to baseline Kidney Disease Improving Global Outcomes (KDIGO) risk categories.

Methods

DAPA-CKD was a double-blind, placebo-controlled trial that randomised patients with an eGFR of 25–75 ml min−1 [1.73 m]−2 and urinary albumin/creatinine ratio (UACR) of ≥22.6 and <565.0 mg/mmol (200–5000 mg/g) to dapagliflozin 10 mg/day or placebo. The primary endpoint was a composite of ≥50% reduction in eGFR, end-stage kidney disease (ESKD), and death from a kidney or cardiovascular cause. Secondary endpoints included a kidney composite (≥50% reduction in eGFR, ESKD and death from a kidney cause), a cardiovascular composite (heart failure hospitalisation or cardiovascular death), and death from all causes. We used Cox proportional hazards regression analyses to assess relative and absolute effects of dapagliflozin across KDIGO risk categories.

Results

Of the 4304 participants in the DAPA-CKD study, 619 (14.4%) were moderately high risk, 1349 (31.3%) were high risk and 2336 (54.3%) were very high risk when categorised by KDIGO risk categories at baseline. Dapagliflozin reduced the hazard of the primary composite (HR 0.61; 95% CI 0.51, 0.72) and secondary endpoints consistently across KDIGO risk categories (all p for interaction >0.09). Absolute risk reductions for the primary outcome were also consistent irrespective of KDIGO risk category (p for interaction 0.26). Analysing patients with and without type 2 diabetes separately, the relative risk reduction with dapagliflozin in terms of the primary outcome was consistent across subgroups of KDIGO risk categories. The relative frequencies of adverse events and serious adverse events were also similar across KDIGO risk categories.

Conclusion/interpretations

The consistent benefits of dapagliflozin on kidney and cardiovascular outcomes across KDIGO risk categories indicate that dapagliflozin is efficacious and safe across a wide spectrum of kidney disease severity.

Trial registration

ClinicalTrials.gov NCT03036150.

Funding

The study was funded by AstraZeneca.

Graphical abstract
Sleep deprivation prevents counterregulatory adaptation to recurrent hypoglycaemia
Authors: Meyhöfer Svenja , Dembinski Katharina , Schultes Bernd , Born Jan , Wilms Britta , Lehnert Hendrik , Hallschmid Manfred , Meyhöfer Sebastian M.
Published: April 2022

Aims/hypothesis

Attenuated counterregulation after recurrent hypoglycaemia is a major complication of diabetes treatment. As there is previous evidence for the relevance of sleep in metabolic control, we assessed the acute contribution of sleep to the counterregulatory adaptation to recurrent hypoglycaemia.

Methods

Within a balanced crossover design, 15 healthy, normal-weight male participants aged 18–35 years underwent three hyperinsulinaemic–hypoglycaemic clamps with a glucose nadir of 2.5 mmol/l, under two experimental conditions, sleep and sleep deprivation. Participants were exposed to two hypoglycaemic episodes, followed by a third hypoglycaemic clamp after one night of regular 8 h sleep vs sleep deprivation. The counterregulatory response of relevant hormones (glucagon, growth hormone [GH], ACTH, cortisol, adrenaline [epinephrine] and noradrenaline [norepinephrine]) was measured, and autonomic and neuroglycopenic symptoms were assessed.

Results

Sleep deprivation compared with sleep dampened the adaptation to recurrent hypoglycaemia for adrenaline (p=0.004), and this pattern also emerged in an overall analysis including adrenaline, GH and glucagon (p=0.064). After regular sleep, the counterregulatory responses of adrenaline (p=0.005), GH (p=0.029) and glucagon (p=0.009) were attenuated during the 3rd clamp compared with the 1st clamp, but were preserved after sleep deprivation (all p>0.225). Neuroglycopenic and autonomic symptoms during the 3rd clamp compared with the 1st clamp were likewise reduced after sleep (p=0.005 and p=0.019, respectively). In sleep deprivation, neuroglycopenic symptoms increased (p=0.014) and autonomic symptoms were unchanged (p=0.859).

Conclusions/interpretation

The counterregulatory adaptation to recurrent hypoglycaemia is compromised by sleep deprivation between hypoglycaemic episodes, indicating that sleep is essential for the formation of a neurometabolic memory, and may be a potential target of interventions to treat hypoglycaemia unawareness syndrome.

Graphical abstract
Comprehensive interpretation of in vitro micronucleus test results for 292 chemicals: from hazard identification to risk assessment application
Authors: Kuo Byron , Beal Marc A. , Wills John W. , White Paul A. , Marchetti Francesco , Nong Andy , Barton-Maclaren Tara S. , Houck Keith , Yauk Carole L.
Published: April 2022

Risk assessments are increasingly reliant on information from in vitro assays. The in vitro micronucleus test (MNvit) is a genotoxicity test that detects chromosomal abnormalities, including chromosome breakage (clastogenicity) and/or whole chromosome loss (aneugenicity). In this study, MNvit datasets for 292 chemicals, generated by the US EPA’s ToxCast program, were evaluated using a decision tree-based pipeline for hazard identification. Chemicals were tested with 19 concentrations (n = 1) up to 200 µM, in the presence and absence of Aroclor 1254-induced rat liver S9. To identify clastogenic chemicals, %MN values at each concentration were compared to a distribution of batch-specific solvent controls; this was followed by cytotoxicity assessment and benchmark concentration (BMC) analyses. The approach classified 157 substances as positives, 25 as negatives, and 110 as inconclusive. Using the approach described in Bryce et al. (Environ Mol Mutagen 52:280–286, 2011), we identified 15 (5%) aneugens. IVIVE (in vitro to in vivo extrapolation) was employed to convert BMCs into administered equivalent doses (AEDs). Where possible, AEDs were compared to points of departure (PODs) for traditional genotoxicity endpoints; AEDs were generally lower than PODs based on in vivo endpoints. To facilitate interpretation of in vitro MN assay concentration–response data for risk assessment, exposure estimates were utilized to calculate bioactivity exposure ratio (BER) values. BERs for 50 clastogens and two aneugens had AEDs that approached exposure estimates (i.e., BER < 100); these chemicals might be considered priorities for additional testing. This work provides a framework for the use of high-throughput in vitro genotoxicity testing for priority setting and chemical risk assessment.
An Automaton Group with PSPACE-Complete Word Problem
Authors: Wächter Jan Philipp , Weiß Armin
Published: April 2022

We construct an automaton group with a -complete word problem, proving a conjecture due to Steinberg. Additionally, the constructed group has a provably more difficult, namely -complete, compressed word problem and acts over a binary alphabet. Thus, it is optimal in terms of the alphabet size. Our construction directly simulates the computation of a Turing machine in an automaton group and, therefore, seems to be quite versatile. It combines two ideas: the first one is a construction used by D’Angeli, Rodaro and the first author to obtain an inverse automaton semigroup with a -complete word problem and the second one is to utilize a construction used by Barrington to simulate Boolean circuits of bounded degree and logarithmic depth in the group of even permutations over five elements.
A (2,3)-complete intersection fourfold with no decomposition of the diagonal
Authors: Skauli Bjørn
Published: April 2022

We apply the specialization technique based on the decomposition of the diagonal to the intersection of a quadric and cubic hypersurface in $$\mathbb {P}^6$$

P

6

. We find an explicit example defined over $$\mathbb {Q}$$
Q
that is smooth, and does not admit a decomposition of the diagonal, and is therefore not retract rational. The proof uses the specialization of Nicaise and Ottem (Tropical degenerations and stable rationality, 2020), who proved that the very general complete intersection of this type is stably irrational using the motivic volume.