bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical assessment of combination therapy of EGFR tyrosine kinase inhibitors in a highly heterogeneous tumor model
Authors: Ikeuchi Hiroshi , Hirose Takeshi , Ikegami Masachika , Takamochi Kazuya , Suzuki Kenji , Mano Hiroyuki , Kohsaka Shinji
Published: March 2022

The development of tyrosine kinase inhibitors (TKIs) has improved the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The current research priority is to provide viable treatments for patients who have drug-resistant EGFR mutations. We evaluated the drug sensitivity of various EGFR mutants to monotherapies and combination therapies of EGFR-TKIs. In vitro, the transforming potential and drug sensitivity of 357 EGFR variants were assessed. In vivo, we tested the sensitivity of EGFR variants to different regimens of EGFR-TKIs by examining changes in the proportion of each variant within the tumor. Out of 357 variants thoroughly examined for transforming activities, 144 (40.3%) and 282 (79.0%) transformed 3T3 and Ba/F3 cells, respectively. Among the latter variants, 50 (17.7%) were found to be resistant or only partly resistant to osimertinib or afatinib. Four of 25 afatinib-resistant variants (16%) were sensitive to osimertinib, whereas 25 of 46 osimertinib-resistant variants (54.3%) were sensitive to afatinib. Despite the lack of a synergistic impact, TKI combination treatment effectively reduced in vivo the heterogeneous tumors composed of 3T3 cells with different EGFR variants. Regimens starting with afatinib and subsequently switched to osimertinib suppressed tumor development more efficiently than the opposite combination. Combination EGFR-TKI treatment may decrease tumor growth and prevent the development of resistant variants. This work created an experimental model of a heterogeneous tumor to find the best combination therapy regimen and proposes a basic notion of EGFR-TKI combination therapy to enhance the prognosis of NSCLC patients.
Ventilation-to-perfusion relationships and right-to-left shunt during neonatal intensive care in infants with congenital diaphragmatic hernia
Authors: Dassios Theodore , Shareef Arattu Thodika Fahad M. , Williams Emma , Davenport Mark , Nicolaides Kypros H. , Greenough Anne
Published: March 2022

Background

We aimed to explore the postnatal evolution of ventilation/perfusion ratio (VA/Q) and right-to-left shunt in infants with congenital diaphragmatic hernia (CDH) and whether these indices predicted survival to discharge.

Methods

Retrospective cohort study at King’s College Hospital, London, UK of infants admitted with CDH in 10 years (2011–2021). The non-invasive method of the oxyhaemoglobin dissociation curve was used to determine the VA/Q and shunt in the first 24 h of life, pre-operation, pre-extubation and in the deceased infants, before death.

Results

Eighty-two infants with CDH (71 left-sided) were included with a median (IQR) gestation of 38.1(34.8–39.0) weeks. Fifty-three (65%) survived to discharge from neonatal care. The median (IQR) VA/Q in the first 24 h was lower in the deceased infants [0.09(0.07–0.12)] compared to the ones who survived [0.28(0.19–0.38), p < 0.001]. In the infants who survived, the VA/Q was lower in the first 24 h [0.28 (0.19–0.38)] compared to pre-operation [0.41 (0.3–0.49), p < 0.001] and lower pre-operation compared to pre-extubation [0.48 (0.39–0.55), p = 0.027]. The shunt was not different in infants who survived compared to the infants who did not.

Conclusions

Ventilation-to-perfusion ratio was lower in infants who died in the neonatal period compared to the ones that survived and improved in surviving infants over the immediate postnatal period.

Impact

The non-invasive method of the oxyhaemoglobin dissociation curve was used to determine the ventilation/perfusion ratio VA/Q in infants with congenital diaphragmatic hernia (CDH) in the first 24 h of life, pre-operation, pre-extubation and in the deceased infants, before death.

The VA/Q in the first 24 h of life was lower in the infants who did not survive to discharge from neonatal care compared to the ones who survived.

In the infants who survived, the VA/Q improved over the immediate postnatal period.

The non-invasive calculation of VA/Q can provide valuable information relating to survival to discharge.
Decreased efficacy of antimicrobial agents in a polymicrobial environment
Authors: O’Brien Thomas James , Figueroa Wendy , Welch Martin
Published: March 2022

The airways of people with cystic fibrosis (CF) often harbour diverse polymicrobial communities. These airway infections can be impossible to resolve through antibiotic intervention, even though isolates of the individual species present are susceptible to the treatment when tested in vitro. In this work, we investigate how polymicrobial cultures comprised of key CF-associated pathogens respond to challenge with species-specific antimicrobial agents; colistin (targets Pseudomonas aeruginosa), fusidic acid (targets Staphylococcus aureus), and fluconazole (targets Candida albicans). We found that growth in a polymicrobial environment protects the target microorganism (sometimes by several orders of magnitude) from the effect(s) of the antimicrobial agent. This decreased antimicrobial efficacy was found to have both non-heritable (physiological) and heritable (genetic) components. Whole-genome sequencing of the colistin-resistant P. aeruginosa isolates revealed single nucleotide polymorphisms and indels in genes encoding lipopolysaccharide (LPS) biosynthesis and/or pilus biogenesis, indicating that a previously undescribed colistin resistance mechanism was in operation. This was subsequently confirmed through further genetic analyses. Our findings indicate that the polymicrobial nature of the CF airways is likely to have a significant impact on the clinical response to antimicrobial therapy.
Amyloid β / PKC-dependent alterations in NMDA receptor composition are detected in early stages of Alzheimer´s disease
Authors: Ortiz-Sanz Carolina , Balantzategi Uxue , Quintela-López Tania , Ruiz Asier , Luchena Celia , Zuazo-Ibarra Jone , Capetillo-Zarate Estibaliz , Matute Carlos , Zugaza José L. , Alberdi Elena
Published: March 2022

Amyloid beta (Aβ)-mediated synapse dysfunction is an early event in Alzheimer’s disease (AD) pathogenesis and previous studies suggest that NMDA receptor (NMDAR) dysregulation may contribute to these pathological effects. Although Aβ peptides impair NMDAR expression and activity, the mechanisms mediating these alterations in the early stages of AD are unclear. Here, we observed that NMDAR subunit NR2B and PSD-95 levels were aberrantly upregulated and correlated with Aβ42 load in human postsynaptic fractions of the prefrontal cortex in early stages of AD patients, as well as in the hippocampus of 3xTg-AD mice. Importantly, NR2B and PSD95 dysregulation was revealed by an increased expression of both proteins in Aβ-injected mouse hippocampi. In cultured neurons, Aβ oligomers increased the NR2B-containing NMDAR density in neuronal membranes and the NMDA-induced intracellular Ca2+ increase, in addition to colocalization in dendrites of NR2B subunit and PSD95. Mechanistically, Aβ oligomers required integrin β1 to promote synaptic location and function of NR2B-containing NMDARs and PSD95 by phosphorylation through classic PKCs. These results provide evidence that Aβ oligomers modify the contribution of NR2B to NMDAR composition and function in the early stages of AD through an integrin β1 and PKC-dependent pathway. These data reveal a novel role of Aβ oligomers in synaptic dysfunction that may be relevant to early-stage AD pathogenesis.
Pyruvate kinase L/R links metabolism dysfunction to neuroendocrine differentiation of prostate cancer by ZBTB10 deficiency
Authors: Wen Yu-Ching , Chen Wei-Yu , Tram Van Thi Ngoc , Yeh Hsiu-Lien , Chen Wei-Hao , Jiang Kuo-Ching , Abou-Kheir Wassim , Huang Jiaoti , Hsiao Michael , Liu Yen-Nien
Published: March 2022

Neuroendocrine differentiation (NED) frequently occurs in androgen-deprivation therapy (ADT)-resistant prostate cancer (PCa) and is typically associated with metabolic pathway alterations, acquisition of lineage plasticity, and malignancy. There is no conventional therapeutic approach for PCa patients with NED pathologic features because the molecular targets are unknown. Here, we evaluated the regulatory mechanism of NED-associated metabolic reprogramming induced by ADT. We detected that the loss of the androgen-responsive transcription factor, zinc finger, and BTB domain containing 10 (ZBTB10), can activate pyruvate kinase L/R (PKLR) to enhance a NED response that is associated with glucose uptake by PCa cells. PKLR exhibits a tumor-promoting effect in PCa after ADT, but ZBTB10 can compensate for the glucose metabolism and NED capacity of PKLR through the direct transcriptional downregulation of PKLR. Targeting PKLR by drug repurposing with FDA-approved compounds can reduce the aggressiveness and NED of ADT-resistant PCa. We demonstrated that PKLR acts as a modulator to activate NED in PCa enhancement by loss of ZBTB10, thereby enabling PCa cells to mount a glycolysis response essential for therapeutic resistance. Our findings highlight the broad relation between NED and metabolic dysfunction to provide gene expression-based biomarkers for NEPC treatment.
End-point RT-PCR based on a conservation landscape for SARS-COV-2 detection
Authors: Cruz-Rangel Armando , Gómez-Romero Laura , Cisneros-Villanueva Mireya , de Anda Jáuregui G. , Luna-Pineda Victor , Cedro-Tanda Alberto , Campos-Romero Abraham , Mendoza-Vargas Alfredo , Reyes-Grajeda J. P. , Hidalgo-Miranda Alfredo ,   COVID-19 Consortium INMEGEN, Herrera Luis A. , Hidalgo-Miranda Alfredo , Mendoza-Vargas Alfredo , Reyes-Grajeda Juan P. , Vadillo-Ortega Felipe , Cedro-Tanda Alberto , Peñaloza Fernando , Frías-Jimenez Emmanuel , Ruiz Rosaura , Angulo Ofelia , Cisneros-Villanueva Mireya , Hernandez-Morales Jose S. , Moreno Bernardo , Hernández-Cruz Irwin A. , Herrera César A. , García Francisco , González-Woge Miguel A. , Munguía-Garza Paulina , Luna-Maldonado Fernando , Sanchez-Vizcarra Antonia , Osnaya Vincent G. , Medina-Molotla Nelly , Alfaro-Mora Yair , Caceres-Gutiérrez Rodrigo E. , Tolentino-Garcia Laura , Moreno-Camacho José Luis , Rodriguez-Gallegos Jorge , Esparza Marco A. Luna-Ruiz , Rojas Miguel Ángel Fernández , Rosas-Escobar Patricia , Román-González Sergio A. , Escobar-Arrazola Marco A. , Canseco-Mendez Julio C. , Ortiz-Soriano Diana R. , Dominguez-Ortiz Julieta , Gonzalez-Barrera Ana D. , Aparicio-Bautista Diana I. , Rodriguez Martinez Griselda , Rangel Armando Cruz , Herrera Luis A. , Vadillo-Ortega Felipe
Published: March 2022

End-point RT-PCR is a suitable alternative diagnostic technique since it is cheaper than RT-qPCR tests and can be implemented on a massive scale in low- and middle-income countries. In this work, a bioinformatic approach to guide the design of PCR primers was developed, and an alternative diagnostic test based on end-point PCR was designed. End-point PCR primers were designed through conservation analysis based on kmer frequency in SARS-CoV-2 and human respiratory pathogen genomes. Highly conserved regions were identified for primer design, and the resulting PCR primers were used to amplify 871 nasopharyngeal human samples with a previous RT-qPCR based SARS-CoV-2 diagnosis. The diagnostic test showed high accuracy in identifying SARS-CoV-2-positive samples including B.1.1.7, P.1, B.1.427/B.1.429 and B.1.617.2/ AY samples with a detection limit of 7.2 viral copies/µL. In addition, this test could discern SARS-CoV-2 infection from other viral infections with COVID-19-like symptomatology. The designed end-point PCR diagnostic test to detect SARS-CoV-2 is a suitable alternative to RT-qPCR. Since the proposed bioinformatic approach can be easily applied in thousands of viral genomes and over highly divergent strains, it can be used as a PCR design tool as new SARS-CoV-2 variants emerge. Therefore, this end-point PCR test could be employed in epidemiological surveillance to detect new SARS-CoV-2 variants as they emerge and propagate.
Classification of ransomware using different types of neural networks
Authors: Madani Houria , Ouerdi Noura , Boumesaoud Ahmed , Azizi Abdelmalek
Published: March 2022

Malware threat the security of computers and Internet. Among the diversity of malware, we have “ransomware”. Its main objective is to prevent and block access to user data and computers in exchange for a ransom, once paid, the data will be liberated. Researchers and developers are rushing to find reliable and safe techniques and methods to detect Ransomware to protect the Internet user from such threats. Among the techniques generally used to detect malware are machine learning techniques. In this paper, we will discuss the different types of neural networks, the related work of each type, aiming at the classification of malware in general and ransomware in particular. After this study, we will talk about the adopted methodology for the implementation of our neural network model (multilayer perceptron). We tested this model, firstly, with the binary detection whether it is malware or goodware, and secondly, with the classification of the nine families of Ransomware by taking the vector of our previous work and we will make a comparison of the accuracy rate of the instances that are correctly classified.
A novel lipase with dual localisation in Trypanosoma brucei
Authors: Monic S.G. , Lamy A. , Thonnus M. , Bizarra-Rebelo T. , Bringaud F. , Smith T. K. , Figueiredo L. M. , Rivière L.
Published: March 2022

Phospholipases are esterases involved in lipid catabolism. In pathogenic micro-organisms (bacteria, fungi, parasites) they often play a critical role in virulence and pathogenicity. A few phospholipases (PL) have been characterised so far at the gene and protein level in unicellular parasites including African trypanosomes (AT). They could play a role in different processes such as host–pathogen interaction, antigenic variation, intermediary metabolism. By mining the genome database of AT we found putative new phospholipase candidate genes and here we provided biochemical evidence that one of these has lipolytic activity. This protein has a unique non-canonical glycosome targeting signal responsible for its dual localisation in the cytosol and the peroxisomes-related organelles named glycosomes. We also show that this new phospholipase is excreted by these pathogens and that antibodies directed against this protein are generated during an experimental infection withT. brucei gambiense, a subspecies responsible for infection in humans. This feature makes this protein a possible tool for diagnosis.
Terrestrial arthropods broadly possess endogenous phytohormones auxin and cytokinins
Authors: Tokuda Makoto , Suzuki Yoshihito , Fujita Shohei , Matsuda Hiroki , Adachi-Fukunaga Shuhei , Elsayed Ayman Khamis
Published: March 2022

Some herbivorous insects possess the ability to synthesize phytohormones and are considered to use them for manipulating their host plants, but how these insects acquired the ability remains unclear. We investigated endogenous levels of auxin (IAA) and cytokinins (iP and tZ), including their ribosides (iPR and tZR), in various terrestrial arthropod taxa. Surprisingly, IAA was detected in all arthropods analysed. In contrast, tZ and/or tZR was detected only in some taxa. Endogenous levels of IAA were not significantly different among groups with different feeding habits, but gall inducers possessed significantly higher levels of iPR, tZ and tZR. Ancestral state reconstruction of the ability to synthesize tZ and tZR revealed that the trait has only been acquired in taxa containing gall inducers. Our results strongly suggest critical role of the cytokinin synthetic ability in the evolution of gall-inducing habit and IAA has some function in arthropods.
Identifying and extracting bark key features of 42 tree species using convolutional neural networks and class activation mapping
Authors: Kim Tae Kyung , Hong Jeonghyun , Ryu Daun , Kim Sukyung , Byeon Si Yeon , Huh Woojin , Kim Kunhyo , Baek Gyu Heon , Kim Hyun Seok
Published: March 2022

The significance of automatic plant identification has already been recognized by academia and industry. There were several attempts to utilize leaves and flowers for identification; however, bark also could be beneficial, especially for trees, due to its consistency throughout the seasons and its easy accessibility, even in high crown conditions. Previous studies regarding bark identification have mostly contributed quantitatively to increasing classification accuracy. However, ever since computer vision algorithms surpassed the identification ability of humans, an open question arises as to how machines successfully interpret and unravel the complicated patterns of barks. Here, we trained two convolutional neural networks (CNNs) with distinct architectures using a large-scale bark image dataset and applied class activation mapping (CAM) aggregation to investigate diagnostic keys for identifying each species. CNNs could identify the barks of 42 species with > 90% accuracy, and the overall accuracies showed a small difference between the two models. Diagnostic keys matched with salient shapes, which were also easily recognized by human eyes, and were typified as blisters, horizontal and vertical stripes, lenticels of various shapes, and vertical crevices and clefts. The two models exhibited disparate quality in the diagnostic features: the old and less complex model showed more general and well-matching patterns, while the better-performing model with much deeper layers indicated local patterns less relevant to barks. CNNs were also capable of predicting untrained species by 41.98% and 48.67% within the correct genus and family, respectively. Our methodologies and findings are potentially applicable to identify and visualize crucial traits of other plant organs.
A viability assay combining palladium compound treatment with quantitative PCR to detect viable Mycobacterium avium subsp. paratuberculosis cells
Authors: Cechova Martina , Beinhauerova Monika , Babak Vladimir , Kralik Petr
Published: March 2022

Mycobacterium aviumsubsp. paratuberculosis(MAP) is a pathogenic bacterium causing the paratuberculosis, chronic and infectious disease common particularly in wild and domestic ruminants. Currently, culture techniques to detect viable MAP are still used most commonly, although these require a long incubation period. Consequently, a faster molecular method for assessing MAP cell viability based on cell membrane integrity was introduced consisting of sample treatment with the intercalation dye propidium monoazide (PMA) followed by quantitative PCR (qPCR). However, the PMA-qPCR assay is complicated by demanding procedures involving work in a darkroom and on ice. In this study, we therefore optimized a viability assay combining sample treatment with palladium (Pd) compounds as an alternative viability marker to PMA, which does not require such laborious procedures, with subsequent qPCR. The optimized Pd-qPCR conditions consisting of 90 min exposure to 30 µM bis(benzonitrile)dichloropalladium(II) or 30 µM palladium(II)acetate at 5 °C and using ultrapure water as a resuspension medium resulted in differences in quantification cycle (Cq) values between treated live and dead MAP cells of 8.5 and 7.9, respectively, corresponding to approximately 2.5 log units. In addition, Pd-qPCR proved to be superior to PMA-qPCR in distinguishing between live and dead MAP cells. The Pd-qPCR viability assay thus has the potential to replace time-consuming culture methods and demanding PMA-qPCR in the detection and quantification of viable MAP cells with possible application in food, feed, clinical and environmental samples.
Dissipated electroosmotic EMHD hybrid nanofluid flow through the micro-channel
Authors: Bilal M. , Asghar I. , Ramzan M. , Nisar K. S. , Aty A.-H Abdel , Yahia I. S. , Ghazwani H. A. S.
Published: March 2022

The main objective of the present study is to explore the effects of electromagnetohydrodynamics electroosmotic flow of hybrid nanofluid through circular cylindrical microchannels. An analysis of hybrid nanofluid consisting of four different nanomaterials i.e., single and multiwall carbon nanotubes, silver, and copper is carried out. Yamada–Ota model is employed for the single and multi wall carbon nanotubes, whereas, Xue model is used for the Silver and Copper hybrid nanofluid for specifying the thermal conductivity. The imposed pressure gradient, electromagnetic field and electroosmosis actuated the fluid flow. The flow of heat transfer and Nusselt number with the account of various effects of Joule heating and viscous dissipation under the circumstances of constant heat flux are discussed graphically. The governing system of equations is molded into a system of coupled, nonlinear ordinary differential equations. The shooting technique is used to extract the numerical solutions of the converted system of equations. Also, the outturn of different parameters like Hartman number, the strength of lateral direction electric field, EDL (electric double layer) electrokinetic width, Joule heating parameters on the temperature, and velocity are investigated. The conversion of simple fluid to hybrid nanofluid has greatly alteration in the present model. It has enhanced the thermal properties of fluid. It is also noted that $$SWCNT-MWCNT$$

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based hybrid nanofluid has most influential impact on Nusselt number, temperature distribution and velocity of the fluid. This attempt is useful for the designing of effectual electromagnetic appliances and exquisite.
Acid red 18 removal from aqueous solution by nanocrystalline granular ferric hydroxide (GFH); optimization by response surface methodology & genetic-algorithm
Authors: Hamidi Farshad , Dehghani Mohammad Hadi , Kasraee Mahboobeh , Salari Mehdi , Shiri Leila , Mahvi Amir Hossein
Published: March 2022

The need for fresh water is more than before by population growth, and industrial development have affected the quality of water supplies, one of the important reason for water contamination is synthetic dyes and their extensive use in industries. Adsorption has been considered as a common methods for dye removal from waters. In this study, Acid Red18 removal in batch mode by using Granular Ferric Hydroxide (GFH) was investigated. The GFH characterized by XRD, FESEM and FTIR analysis. Experiments were designed using RSM-CCD method. The maximum removal efficiency was obtained 78.59% at pH = 5, GFH dosage = 2 g/l, AR18 concentration = 77.5 mg/l and 85 min of contact time. Optimization with RSM and Genetic Algorithm carried out and is similar together. The non-linear adsorption Isotherm and kinetic fitted with Freundlich (R2 = 0.978) and pseudo-second-order (R2 = 0.989) models, respectively. Thermodynamic studies showed that the AR18 adsorption is endothermic process and GFH nature was found spontaneous.
A role for the periplasmic adaptor protein AcrA in vetting substrate access to the RND efflux transporter AcrB
Authors: Alav Ilyas , Bavro Vassiliy N. , Blair Jessica M. A.
Published: March 2022

Tripartite resistance-nodulation-division (RND) efflux pumps, such as AcrAB-TolC of Salmonella Typhimurium, contribute to antibiotic resistance and comprise an inner membrane RND-transporter, an outer membrane factor, and a periplasmic adaptor protein (PAP). The role of the PAP in the assembly and active transport process remains poorly understood. Here, we identify the functionally critical residues involved in PAP-RND-transporter binding between AcrA and AcrB and show that the corresponding RND-binding residues in the closely related PAP AcrE, are also important for its interaction with AcrB. We also report a residue in the membrane-proximal domain of AcrA, that when mutated, differentially affects the transport of substrates utilising different AcrB efflux channels, namely channels 1 and 2. This supports a potential role for the PAP in sensing the substrate-occupied state of the proximal binding pocket of the transporter and substrate vetting. Understanding the PAP’s role in the assembly and function of tripartite RND pumps can guide novel ways to inhibit their function to combat antibiotic resistance.
Condensation and growth of amorphous aluminosilicate nanoparticles via an aggregation process
Authors: Dupuis Romain , Hahn Seung Ho , van Duin Adri C. T. , Pellenq Roland J.-M. , Poulesquen Arnaud
Published: March 2022

The precipitation of zeolite nanoparticles involves the initial formation of metastable precursors such as amorphous entities that crystallize through non-classical pathways.
The low overpotential regime of acidic water oxidation part I: the importance of O2 detection
Authors: Scott Soren B. , Rao Reshma R. , Moon Choongman , Sørensen Jakob E. , Kibsgaard Jakob , Shao-Horn Yang , Chorkendorff Ib
Published: March 2022

By measuring O2 with high sensitivity, we open a mechanistic window into water oxidation on RuOx in acid.
β-Ga2O3 heterojunction field-effect transistors prepared via UV laser-assisted p-doping of two-dimensional WSe2
Authors: Moon Sanghyun , Bae Jinho , Kim Jihyun
Published: March 2022

A WSe2/β-Ga2O3 p–n heterojunction FET, fabricated by the area-selective p-doping of ambipolar WSe2via the self-limited formation of WOX with high electron affinity using a UV laser, exhibited outstanding p–n diode and JFET characteristics.
Influence of charge transfer strength on emission bandwidth for multiple-resonance emitters via systematically tuning the acceptor–donor assembly
Authors: Huang Jing-Wei , Hsu Yu-Chieh , Wu Xiugang , Wang Sai , Gan Xiang-Qin , Zheng Wei-Qiong , Zhang Hu , Gong Yin-Zhi , Hung Wen-Yi , Chou Pi-Tai , Zhu Weiguo
Published: March 2022

Tuning the acceptor–donor assembly strategy, which is to lock the benzophenone acceptor and stepwise change the donors, demonstrates that charge transfer dominates the full width at half maximum of the multiple resonance (MR) emitters.
A susceptible multifunctional fluorescent probe based on levulinic acid for the practical detection of SO2
Authors: Chen Shijun , Wang Lin , Zhou Shunchao , He Xie , Wu Yuanyuan , Hou Shicong , Ma Xiaodong
Published: March 2022

The application of a multifunctional, sensitive, fluorescent SO2 probe is demonstrated.
Regiospecific construction of m-alkenyl benzaldehyde from β-bromoenal and vinyl borate
Authors: Xin Xiaolan , Liu Yilin , Zhou Lu , Li You , Luo Han , Liu Lei , Bai Ruopeng , Lan Yu , Li Baosheng
Published: March 2022

A practical method can be used to assemble four simple molecules into an aromatic system, by which m-alkenyl benzaldehydes can be synthesized with regiospecificity. Moreover, new AIE molecules can be obtained by coupling the products in one pot.
High ZT in p-type thermoelectric (Bi,Sb)2Te3 with built-in nanopores
Authors: Zhuang Hua-Lu , Hu Haihua , Pei Jun , Su Bin , Li Jing-Wei , Jiang Yilin , Han Zhanran , Li Jing-Feng
Published: March 2022

Nanopores with modified surfaces introduced by simultaneously adding BiI3 and Zn significantly improved the ZT value of (Bi,Sb)2Te3.
A multi-functional porous cobalt catalyst for the selective hydrogenative ring-opening and rearrangement of furfural to cyclopentanol
Authors: Li Xing-Long , Zhu Rui
Published: March 2022

Multi-functional Co-400 catalyst via the simple reduction of commercially available Co3O4 for the conversion of furfural to cyclopentanol was developed.
Stretchable solvent-free ionic conductor with self-wrinkling microstructures for ultrasensitive strain sensor
Authors: Ou Ying , Zhao Tingting , Zhang Yang , Zhao Guanghui , Dong Lijie
Published: March 2022

A solvent-free ionic conductor with self-wrinkling microstructure, which has high strain sensitivity with GF of 7.03, has been developed in this work. Moreover, this ionic conductor also exhibited self-healable ability and adhesion characteristics.
Application of nanotechnology in the diagnosis and treatment of acute pancreatitis
Authors: Jia WeiLu , Xu LinFeng , Xu WenJing , Yang Meng , Zhang YeWei
Published: March 2022

Acute pancreatitis (AP) is a common digestive system disease. We summarize the reported applications of different nanoplatforms in AP diagnosis and treatment to provide guidance for further clinical applications of nanotechnology.
Structure–activity relationship studies on an antitumor marine macrolide using aplyronine a–swinholide A hybrid
Authors: Ohyoshi Takayuki , Takano Atsuhiro , Kikuchi Imari , Ogura Tomotaka , Namiki Mayu , Miyazaki Yuto , Hirano Takahiro , Konishi Shota , Ebihara Yuta , Takeno Koichi , Hayakawa Ichiro , Kigoshi Hideo
Published: March 2022

Aplyronine A–swinholide A hybrid, a simplified analog of aplyronine A, was designed and synthesized for structure–activity relationship studies.
Molecular engineering of organic small-molecule photothermal agents by changing the donor group for photothermal therapy and photoacoustic imaging of tumors
Authors: Deng Guowei , Chen Hongyu , Wang Jiexue , Chen Kexiang , Li Lu , Zhang Shilu , Sun Kang , Li Zhonghui , Liu Jun
Published: March 2022

A series of PTT agents based on ‘D–π–A’-type chromophores with different electron-donating groups were constructed to optimize their photothermal performance at 808 nm after nanogel loading.
Long‐time target tracking algorithm based on re‐detection multi‐feature fusion
Authors: Qu Junsuo , Tang Chenxue , Zhang Yuan , Zhou Kai , Razi Abolfazl
Published: March 2022

This paper considers the problem of long‐term target tracking in complex scenes when tracking failures are unavoidable due to illumination change, target deformation, scale change, motion blur, and other factors. More specifically, a target tracking algorithm, called re‐detection multi‐feature fusion, is proposed based on the fusion of scale‐adaptive kernel correlation filtering and re‐detection. The target tracking algorithm trains three kernel correlation filters based on the histogram of oriented gradients, colour name, and local binary pattern features and then obtains the fusion weight of response graphs corresponding to different features based on average peak correlation energy criterion and uses weighted average to complete the position estimation of the tracked target. In order to deal with the problem that the target is occluded and disappears in the tracking process, a random fern classifier is trained to perform re‐detection when the target is occluded. After comparing the OTB‐50 target tracking dataset, the experimental results show that the proposed tracker can track the target well in the occlusion attribute video sequence in the OTB‐100 test dataset and has a certain improvement in tracking accuracy and success rate compared with the traditional correlation filter tracker.
An adaptive‐impedance fault current limiter for accelerating fault current suppression in MMC‐HVDC systems
Authors: Duan Pan , Fu Zhengzheng , Yang Ming , Sima Wenxia
Published: March 2022

DC fault clearance is one of the critical issues for the modular‐multilevel‐converter‐based high voltage direct current (MMC‐HVDC) systems. Employing a hybrid DC circuit breaker (H‐DCCB) to isolate the faulty line is a typical method to achieve fast fault clearance. However, the H‐DCCB has to interrupt the fault current and absorb the energy up to tens of megawatts in several milliseconds. Through theoretical analysis of the interruption process using the H‐DCCB, reducing the equivalent inductance of the fault circuit during the fault falling stage is recommended to accelerate the fault current suppression for the H‐DCCBs. This paper proposes a novel adaptive‐impedance fault current limiter (AFCL), which contains two coupled DC reactors and an energy absorption branch (EAB). The proposed AFCL can automatically limit the fault current during the current rising stage and works as a DC reactor with a fixed equivalent inductance through a two‐state model analysis. Meanwhile, the AFCL contributes to accelerating the decline of the current by adaptively reducing the inductance of the discharge circuit. Consequently, the fault current suppression time and the energy absorbed by the H‐DCCB are reduced. Simulation case studies and hardware experiments are carried out to verify the performance and practicality of the proposed AFCL.
The bow‐tie antenna: Performance limitations and improvements
Authors: Gonçalves Licursi de Mello Rafael , Lepage Anne Claire , Begaud Xavier
Published: March 2022

The simple planar shape and wideband input impedance of the bow‐tie antenna make it suitable to diverse wideband applications. However, the radiation pattern of this kind of antenna is not stable and the gain in the broadside direction deteriorates with increasing frequencies. In this article, the operation of both the triangular and the rounded‐edge versions of the bow‐tie antenna is thoroughly investigated and the performance thereof is compared. A technique to maximise such performance, which consists of inserting radially aligned grooves in the radiators' ends, is presented. The bandwidth, defined by a broadside gain of at least 2 dBi and a reflection coefficient magnitude of less than −10 dB, is improved from 85.7% to 97.9% in simulations. Such an improvement is validated through the measurement of two prototypes, in which the presented technique also increases the broadside gain in up to 1.5 dB, with no significant change in the shapes of the radiation patterns and in the reflection coefficient magnitude.
Biochemical Characterization of the Pharmacological Effects of Yagari in Experimentally Induced Benign Prostatic Hyperplasia
Authors: Agatemor Uzuazokaro Mark-Maria , Nwodo Okwesili Fred Chiligue
Published: March 2022

Benign prostatic hyperplasia is a progressive pathologic condition common in ageing men, constituting a health burden. Benign prostatic hyperplasia is characterized by the proliferation of prostatic tissues, prostate enlargement, and lower urinary tract symptoms. The use of herbal medicine in the management and treatment of benign prostatic hyperplasia has shown some promise. The efficacy and potency of some polyherbal extracts have been scientifically proven in the management and treatment of diseases, while many others are yet to be investigated. The aim of this study was to determine the effect of the herbal mixture Yagari on experimentally induced benign prostatic hyperplasia in rats and to identify its pharmacologically active agents. The effect of the herbal mixture on experimentally induced benign prostatic hyperplasia in rats was determined using 36 male Wistar rats grouped randomly into 6 groups of 6 rats each. The test rats were treated subcutaneously using a combination of dihydrotestosterone and estradiol valerate in a 10:1 ratio for 28 days according to the standard method. The test rats were thereafter treated with the herbal mixture for 21 days. Prostate-specific antigen, inflammatory cytokines, assay of prostate function hormonal and prostate function enzyme activities, and kidney function test were evaluated in the blood samples collected by ocular puncture applying standard methods. Prostates were harvested and examined for histopathological changes. Biological activity-guided fractionation of Yagari in a silica gel column was carried out and using phospholipase A2 activity as a biomarker. The identity of the bioactive compounds was determined using mass spectroscopy and nuclear magnetic resonance. The herbal mixture showed a positive effect on prostatic hyperplasia by decreasing urinary obstruction through the inhibition of 5-alpha reductase, anti-inflammatory activity, and decreased level of sex hormones. Characterization by spectral studies revealed apigenin (4´,5,7-trihydroxyflavone, molecular weight).
Synthesis of Bifacial Peptide Nucleic Acids with Diketopiperazine Backbones
Authors: Bong Dennis , Devari Shekaraiah , Bhunia Debmalya
Published: March 2022

We report a synthesis of bifacial peptide nucleic acids (bPNAs) with novel diketopiperazine (DKP) backbones that display unnatural melamine (M) bases, as well as native bases. To examine the structure–function scope of DKP bPNAs, we synthesized a set of bPNAs by using diaminopropionic acid, diaminobutyric acid, ornithine, and lysine derivatives to display the base-tripling motifs, which result in one, two, three, or four carbons linking the alpha carbon to the side-chain amine. Thermal denaturation of DNA hybrids with these bPNAs revealed that the optimal side-chain linkage was four carbons, corresponding to the lysine derivative. Accordingly, monomers displaying two bases per side-chain were prepared through double reductive alkylation of the ε-amine of Fmoc-lysine with acetaldehyde derivatives of adenine, cytidine, uridine, and melamine. With these building blocks in hand, DKP bPNAs were prepared to display a combination of native and synthetic (melamine) bases. Preliminary melting studies indicate binding signatures of cytidine- and melamine-displaying bPNAs to T-rich DNAs of noncanonical structure, though full characterization of this behavior is ongoing. The convenient and potentially scalable method described enables rapid access to DNA-binding scaffolds of low (<1 kD) molecular weight and previously established cell permeability. We expect that this straightforward and efficient approach to nucleic acid binders will enable studies on noncanonical nucleic acid hybridization.
Pressurized Natural Deep Eutectic Solvent Extraction of Galanthamine and Related Alkaloids from Narcissus pseudonarcissus
Authors: Rachmaniah Orchidea , Wilson Erica G. , Choi Young Hae , Witkamp Geert-Jan , Verpoorte Robert
Published: March 2022

The isolation of a compound from a natural source involves many organic and mostly toxic solvents for extraction and purification. Natural deep eutectic solvents have been shown to be
efficient options for the extraction of natural products. They have the advantage of being composed of abundantly available common primary metabolites, being nontoxic and environmentally
safe solvents. The aim of this study was to develop a natural deep eutectic solvent-based extraction method for galanthamine, an important therapeutic agent for the treatment of Alzheimerʼs
disease. This alkaloid can be produced by synthesis or by extraction from Narcissus bulbs. To develop an efficient extraction method, a number of different natural deep eutectic
solvents was first tested for their solubilization capacity of galanthamine bromide salt. Promising results were obtained for ionic liquids, as well as some amphoteric and acidic natural
deep eutectic solvents. In a two-cycle extraction process, the best solvents were tested for the extraction of galanthamine from bulbs. The ionic liquids produced poor yields, and the best
results were obtained with some acid and sugar mixtures, among which malic acid-sucrose-water (1 : 1 : 5) proved to be the best, showing similar yields to that of the exhaustive Soxhlet
extraction with methanol. Furthermore, the natural deep eutectic solvent was more selective for galanthamine.
Characteristics of older-patient-specif ic oncological trials: a cross-sectional analysis of ClinicalTrials.gov
Authors: Yang Yun , Xie Mingxing , Zhang Li , Yu Kaixu , Li He , Sun Wei , Feng Zishan , Tang Yun , Ma Haotian , Wang Qingpeng , Wu Gang , Yang Kunyu , Wu Bian
Published: March 2022

Background

clinical trials dedicated to the older patients with cancer are essential to help to define optimal cancer therapy for this rapidly growing population. Our study aimed to analyse the characteristics and the evolution of older-patient-specific oncological trials registered in ClinicalTrials.gov.

Methods

a dataset of 61,120 oncological trials registered in ClinicalTrials.gov between 2000 and 2019 was downloaded. Characteristics of older-patient-specific trials were compared with characteristics of age-unspecified trials. Chronological shifts in older-patient-specific trials were also analysed.

Results

of the 49,273 interventional trials eligible for analysis, only 490 (1.0%) were older-patient-specific. More than half of the older-patient-specific trials were phase 2 and enrolled less than 100 patients. Compared with age-unspecified trials, older-patient-specific trials were less likely to be funded by industry (26.9 vs 37.1%), and more likely to be conducted in Europe (44.5 vs 28.3%). During the two time periods between 2000 and 2009, and 2010 and 2019, the proportion of supportive care-oriented trials increased from 1.9 to 13.9%. Concerningly, the use of clinically meaningful end points in older patients such as disease-specific survival, patient-reported outcomes and functional status as a primary end point was uncommon (0.4, 8.1 and 7.3%, respectively). There was no correlation between the number of trials for a given cancer type and relative incidence and mortality. 196/490 (40.0%) of the trials were conducted for patients with haematological cancer.

Conclusion

our study helps us to better understand the current state of older-patient-specific oncological trials and provide insights for future development, resulting in the improvement of the care of older patients with cancer.
Sneering Satire
Authors: Anderson Luvell
Published: March 2022

In ‘“Sneering, or Other Social Pelting”’, Lucy O’Brien understands sneering acts as ways of making feel that are aimed at socially downgrading a target. Sneers are essentially expressions of contempt. Although typically thought of as vicious, O’Brien argues they can also be used virtuously to disrupt social hierarchies, especially when taken up by people with low social status. I examine satire as a potentially effective means of carrying out this virtuous activity. I examine O’Brien’s account while exploring the conditions that must obtain to make satire an efficacious tool for social recalibration.
Continual Improvement of the Reliability of Next-Generation Sequencing-Based ctDNA Analysis: A Long-Term Comparison of ctDNA Detection in China
Authors: Peng Rongxue , Zhang Rui , Li Jinming
Published: March 2022

Background

Since circulating tumor DNA (ctDNA) sequencing is increasingly being applied in clinical management of patients with cancer, its testing accuracy has become a matter of serious concern. To address this issue, a long-term ctDNA analysis proficiency testing (PT) scheme for next-generation sequencing (NGS) was launched in China in 2018, serving as an educational tool for assessing and improving the testing quality of NGS-based ctDNA detection.

Methods

Feedback from participating laboratories across 23 different PT samples containing different variants with varying variant allele frequency was collected between 2018 and 2021. To further show the landscape of changing conditions in accuracy and reliability of NGS-based ctDNA testing, performance was analyzed by evaluating the cfDNA extraction kits, testing panels, target enrichment strategies, and sequencing platforms.

Results

During the 4 years, 2745 results reported from 504 laboratories were evaluated. Only 66.3% of results from laboratories were entirely in concordance with the expected results. Nonetheless, along with an increasing number of participating laboratories, the number of errors occurring in laboratories, and the proportion of laboratories that experienced errors both showed a significant downward trend. No obvious differences in the error rates were found regarding the kit manufacturers or sequencing platform. Moreover, the individual performances of the laboratories improved when they participated in more PT scheme rounds.

Conclusions

These data demonstrated that the performance of individual Chinese laboratories for NGS-based ctDNA analysis continuously improved over time with participation in PT schemes. However, further care must also be taken in standardized operations and validations.
Diversification across mining pools: optimal mining strategies under PoW
Authors: Chatzigiannis Panagiotis , Baldimtsi Foteini , Griva Igor , Li Jiasun
Published: March 2022

Mining is a central operation of all proof-of-work (PoW)-based cryptocurrencies. The vast majority of miners today participate in “mining pools” instead of “solo mining” in order to lower risk and achieve a more steady income. However, this rise of participation in mining pools negatively affects the decentralization levels of most cryptocurrencies. In this work, we look into mining pools from the point of view of a miner: We present an analytical model and implement a computational tool that allows miners to optimally distribute their computational power over multiple pools and PoW cryptocurrencies (i.e. build a mining portfolio), taking into account their risk aversion levels. Our tool allows miners to maximize their risk-adjusted earnings by diversifying across multiple mining pools. Our underlying techniques are drawn from both the areas of financial economy and computer science since we use computer science-based approaches (i.e. optimization techniques) to experimentally prove how parties (and in particular miners) interact with cryptocurrencies in a way of increasing their Sharpe ratio. To showcase our model, we run an experiment in Bitcoin historical data and demonstrate that a miner diversifying over multiple pools, as instructed by our model/tool, receives a higher overall Sharpe ratio (i.e. average excess reward over its standard deviation/volatility).
Consumption of Ultra-Processed Food and Cognitive Decline among Older Adults With Type-2 Diabetes
Authors: Weinstein Galit , Vered Shiraz , Ivancovsky-Wajcman Dana , Ravona-Springer Ramit , Heymann Anthony , Zelber-Sagi Shira , Shahar Danit Rivka , Beeri Michal Schnaider
Published: March 2022

Background

Ultra-processed food (UPF) consumption is related to increased morbidity and mortality. However, knowledge on its association with cognitive function is lacking. In this longitudinal study, we examined the associations between UPF intake and cognitive decline in older adults with type-2 diabetes (T2D).

Methods

The sample included initially nondemented T2D older adults (≥65 years), from the Israel Diabetes and Cognitive Decline study, who had complete information on nutrition at baseline and at least 3 cognitive assessments (mean follow-up 5.3 ± 1.5 years). Nutritional intake was evaluated by a validated Food-Frequency Questionnaire, and foods were categorized as UPF based on NOVA classification. Percent of calories from UPF were calculated from total caloric consumption in total and specific food groups. Mixed effect models were used to examine the link between UPF intake (top vs bottom quartiles) and change in cognitive function overall and in specific domains, adjusting for potential confounders.

Results

Of the total sample (N = 568; mean age 71.3 ± 4.5 years, 60% men), 141 consumed >31% kcal from UPF (top quartile). Greater intake of ultra-processed meat was associated with a faster decline in executive functions and global cognition (β = −0.041 ± 0.013; p = .002 and β = −0.026 ± 0.010; p = .011, respectively). Additionally, consumption of ultra-processed oils/spreads was associated with faster decline in executive functions and global cognition (β = −0.037 ± 0.014; p = .006 and β = −0.028 ± 0.010; p = .009, respectively). Total UPF consumption and UPF-derived from dairy products and bread/pastries/starch were not associated with cognitive change.

Conclusion

This study suggests that a high intake of ultra-processed meat and oils/spreads may be associated with accelerated cognitive decline in older individuals with T2D.