bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Brain Volumes Are Relevant during Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: Lessons from a Case Report
Authors: De Masi Roberto , Orlando Stefania , Armenise Silvia , Spagnolo Pantaleo , Capra Ruggero , Costa Maria Carmela
Published: November 2022

This is a case report concerning a Natalizumab-associated Progressive Multifocal Leukoencephalopathy (PML) with cerebellar localization and wakefulness disturbances. Awakening and clinical improvement dramatically occurred as soon as the immune reconstitution inflammatory syndrome (IRIS) took place, being it mild in nature and colocalizing with the PML lesion. In these ideal experimental conditions, we applied brain magnetic resonance imaging post-analysis in order to know changes in brain volumes underlying the pathological process over the infection period. White matter volume increased with a decrease in grey matter during IRIS. Conversely, we found a constant increase in cerebrospinal fluid volume throughout the duration of PML, suggesting a widespread abiotrophic effect, far from the lesion. Furthermore, brain parenchymal fraction significantly decreased as expected while the total brain volume remained stable at all times. Neurodegeneration is the main contributor to the steady disability in Natalizumab-associated PML. This process is thought to be widespread and inflammatory in nature as well as sustained by IRIS and humoral factors derived from the PML lesion.
EMT Molecular Signatures of Pancreatic Neuroendocrine Neoplasms
Authors: Venugopal Abhirami , Michalczyk Agnes , Khasraw Mustafa , Ackland M. Leigh
Published: November 2022

Neuroendocrine neoplasms (NENs) are relatively rare neoplasms occurring predominantly in the gastrointestinal tract and pancreas. Their heterogeneity poses challenges for diagnosis and treatment. There is a paucity of markers for characterisation of NEN tumours. For routine diagnosis, immunohistochemistry of the NEN-specific markers CgA and synaptophysin and the proliferation marker Ki-67 are used. These parameters, however, are qualitative and lack the capacity to fully define the tumour phenotype. Molecules of epithelial–mesenchymal transition (EMT) are potential candidates for improved tumour characterisation. Using qRT-PCR, we measured mRNA levels of 27 tumour markers, including 25 EMT-associated markers, in tumour tissue and matched non-tumour tissues for 13 patients with pancreatic NENs. Tissue from patients with three different grades of tumour had distinctly different mRNA profiles. Of the 25 EMT-associated markers analysed, 17 were higher in G3 tissue relative to matched non-tumour tissue, including CD14, CD24, CD31, CD44, CD45, CD56, CK6, CK7, CK13, CK20, NSE, CDX2, CgA, DAXX, PCNA, laminin and Ki-67. The differences in levels of seven EMT-associated markers, Ki-67, DAXX, CD24, CD44, vimentin, laminin and PDX1 plus CgA and NSE (neuroendocrine markers) enabled a distinct molecular signature for each tumour grade to be generated. EMT molecules differentially expressed in three tumour grades have potential for use in tumour stratification and prognostication and as therapeutic targets for treatment of neuroendocrine cancers, following validation with additional samples.
Helicobacter pylori in the Oral Cavity: Current Evidence and Potential Survival Strategies
Authors: Zhang Lin , Chen Xi , Ren Biao , Zhou Xuedong , Cheng Lei
Published: November 2022

Helicobacter pylori (H. pylori) is transmitted primarily through the oral–oral route and fecal–oral route. The oral cavity had therefore been hypothesized as an extragastric reservoir of H. pylori, owing to the presence of H. pylori DNA and particular antigens in distinct niches of the oral cavity. This bacterium in the oral cavity may contribute to the progression of periodontitis and is associated with a variety of oral diseases, gastric eradication failure, and reinfection. However, the conditions in the oral cavity do not appear to be ideal for H. pylori survival, and little is known about its biological function in the oral cavity. It is critical to clarify the survival strategies of H. pylori to better comprehend the role and function of this bacterium in the oral cavity. In this review, we attempt to analyze the evidence indicating the existence of living oral H. pylori, as well as potential survival strategies, including the formation of a favorable microenvironment, the interaction between H. pylori and oral microorganisms, and the transition to a non-growing state. Further research on oral H. pylori is necessary to develop improved therapies for the prevention and treatment of H. pylori infection.
In Silico Identification of Multi-Target Ligands as Promising Hit Compounds for Neurodegenerative Diseases Drug Development
Authors: Alov Petko , Stoimenov Hristo , Lessigiarska Iglika , Pencheva Tania , Tzvetkov Nikolay T. , Pajeva Ilza , Tsakovska Ivanka
Published: November 2022

The conventional treatment of neurodegenerative diseases (NDDs) is based on the “one molecule—one target” paradigm. To combat the multifactorial nature of NDDs, the focus is now shifted toward the development of small-molecule-based compounds that can modulate more than one protein target, known as “multi-target-directed ligands” (MTDLs), while having low affinity for proteins that are irrelevant for the therapy. The in silico approaches have demonstrated a potential to be a suitable tool for the identification of MTDLs as promising drug candidates with reduction in cost and time for research and development. In this study more than 650,000 compounds were screened by a series of in silico approaches to identify drug-like compounds with predicted activity simultaneously towards three important proteins in the NDDs symptomatic treatment: acetylcholinesterase (AChE), histone deacetylase 2 (HDAC2), and monoamine oxidase B (MAO-B). The compounds with affinities below 5.0 µM for all studied targets were additionally filtered to remove known non-specifically binding or unstable compounds. The selected four hits underwent subsequent refinement through in silico blood-brain barrier penetration estimation, safety evaluation, and molecular dynamics simulations resulting in two hit compounds that constitute a rational basis for further development of multi-target active compounds against NDDs.
Fine Mapping and Candidate Gene Analysis of Pm36, a Wild Emmer-Derived Powdery Mildew Resistance Locus in Durum Wheat
Authors: Nigro Domenica , Blanco Antonio , Piarulli Luciana , Signorile Massimo Antonio , Colasuonno Pasqualina , Blanco Emanuela , Simeone Rosanna
Published: November 2022

Powdery mildew (PM) is an economically important foliar disease of cultivated cereals worldwide. The cultivation of disease-resistant varieties is considered the most efficient, sustainable and economical strategy for disease management. The objectives of the current study were to fine map the chromosomal region harboring the wild emmer PM resistance locus Pm36 and to identify candidate genes by exploiting the improved tetraploid wheat genomic resources. A set of backcross inbred lines (BILs) of durum wheat were genotyped with the SNP 25K chip array and comparison of the PM-resistant and susceptible lines defined a 1.5 cM region (physical interval of 1.08 Mb) harboring Pm36. The genetic map constructed with F2:3 progenies derived by crossing the PM resistant line 5BIL-42 and the durum parent Latino, restricted to 0.3 cM the genetic distance between Pm36 and the SNP marker IWB22904 (physical distance 0.515 Mb). The distribution of the marker interval including Pm36 in a tetraploid wheat collection indicated that the positive allele was largely present in the domesticated and wild emmer Triticum turgidum spp. dicoccum and ssp. dicoccoides. Ten high-confidence protein coding genes were identified in the Pm36 region of the emmer, durum and bread wheat reference genomes, while three added genes showed no homologous in the emmer genome. The tightly linked markers can be used for marker-assisted selection in wheat breeding programs, and as starting point for the Pm36 map-based cloning.
FOXO1 Is a Key Mediator of Glucocorticoid-Induced Expression of Tristetraprolin in MDA-MB-231 Breast Cancer Cells
Authors: Jeon Do Yong , Jeong So Yeon , Lee Ju Won , Kim Jeonghwan , Kim Jee Hyun , Chu Hun Su , Jeong Won Jin , Lee Byung Ju , Ahn Byungyong , Kim Junil , Choi Seong Hee , Park Jeong Woo
Published: November 2022

The mRNA destabilizing factor tristetraprolin (TTP) functions as a tumor suppressor by down-regulating cancer-associated genes. TTP expression is significantly reduced in various cancers, which contributes to cancer processes. Enforced expression of TTP impairs tumorigenesis and abolishes maintenance of the malignant state, emphasizing the need to identify a TTP inducer in cancer cells. To search for novel candidate agents for inducing TTP in cancer cells, we screened a library containing 1019 natural compounds using MCF-7 breast cancer cells transfected with a reporter vector containing the TTP promoter upstream of the luciferase gene. We identified one molecule, of which the enantiomers are betamethasone 21-phosphate (BTM-21-P) and dexamethasone 21-phosphate (BTM-21-P), as a potent inducer of TTP in cancer cells. We confirmed that BTM-21-P, DXM-21-P, and dexamethasone (DXM) induced the expression of TTP in MDA-MB-231 cells in a glucocorticoid receptor (GR)-dependent manner. To identify potential pathways linking BTM-21-P and DXM-21-P to TTP induction, we performed an RNA sequencing-based transcriptome analysis of MDA-MB-231 cells at 3 h after treatment with these compounds. A heat map analysis of FPKM expression showed a similar expression pattern between cells treated with the two compounds. The KEGG pathway analysis results revealed that the upregulated DEGs were strongly associated with several pathways, including the Hippo signaling pathway, PI3K-Akt signaling pathway, FOXO signaling pathway, NF-κB signaling pathway, and p53 signaling pathway. Inhibition of the FOXO pathway using a FOXO1 inhibitor blocked the effects of BTM-21-P and DXM-21-P on the induction of TTP in MDA-MB-231 cells. We found that DXM enhanced the binding of FOXO1 to the TTP promoter in a GR-dependent manner. In conclusion, we identified a natural compound of which the enantiomers are DXM-21-P and BTM-21-P as a potent inducer of TTP in breast cancer cells. We also present new insights into the role of FOXO1 in the DXM-21-P- and BTM-21-P-induced expression of TTP in cancer cells.
In Silico Discovery of Anticancer Peptides from Sanghuang
Authors: Liu Minghao , Lv Jiachen , Chen Liyuan , Li Wannan , Han Weiwei
Published: November 2022

Anticancer peptide (ACP) is a short peptide with less than 50 amino acids that has been discovered in a variety of foods. It has been demonstrated that traditional Chinese medicine or food can help treat cancer in some cases, which suggests that ACP may be one of the therapeutic ingredients. Studies on the anti-cancer properties of Sanghuangporus sanghuang have concentrated on polysaccharides, flavonoids, triterpenoids, etc. The function of peptides has not received much attention. The purpose of this study is to use computer mining techniques to search for potential anticancer peptides from 62 proteins of Sanghuang. We used mACPpred to perform sequence scans after theoretical trypsin hydrolysis and discovered nine fragments with an anticancer probability of over 0.60. The study used AlphaFold 2 to perform structural modeling of the first three ACPs discovered, which had blast results from the Cancer PPD database. Using reverse docking technology, we found the target proteins and interacting residues of two ACPs with an unknown mechanism. Reverse docking results predicted the binding modes of the ACPs and their target protein. In addition, we determined the active part of ACPs by quantum chemical calculation. Our study provides a framework for the future discovery of functional peptides from foods. The ACPs discovered have the potential to be used as drugs in oncology clinical treatment after further research.
Bioluminescence Production by Turnip Yellows Virus Infectious Clones: A New Way to Monitor Plant Virus Infection
Authors: Boissinot Sylvaine , Ducousso Marie , Brault Véronique , Drucker Martin
Published: November 2022

We used the NanoLuc luciferase bioluminescent reporter system to detect turnip yellows virus (TuYV) in infected plants. For this, TuYV was genetically tagged by replacing the C-terminal part of the RT protein with full-length NanoLuc (TuYV-NL) or with the N-terminal domain of split NanoLuc (TuYV-N65-NL). Wild-type and recombinant viruses were agro-infiltrated in Nicotiana benthamiana, Montia perfoliata, and Arabidopsis thaliana. ELISA confirmed systemic infection and similar accumulation of the recombinant viruses in N. benthamiana and M. perfoliata but reduced systemic infection and lower accumulation in A. thaliana. RT-PCR analysis indicated that the recombinant sequences were stable in N. benthamiana and M. perfoliata but not in A. thaliana. Bioluminescence imaging detected TuYV-NL in inoculated and systemically infected leaves. For the detection of split NanoLuc, we constructed transgenic N. benthamiana plants expressing the C-terminal domain of split NanoLuc. Bioluminescence imaging of these plants after agro-infiltration with TuYV-N65-NL allowed the detection of the virus in systemically infected leaves. Taken together, our results show that NanoLuc luciferase can be used to monitor infection with TuYV.
The Origin, Function, Distribution, Quantification, and Research Advances of Extracellular DNA
Authors: Yang Kaixin , Wang Lishuang , Cao Xinghong , Gu Zhaorui , Zhao Guowei , Ran Mengqu , Yan Yunjun , Yan Jinyong , Xu Li , Gao Chunhui , Yang Min
Published: November 2022

In nature, DNA is ubiquitous, existing not only inside but also outside of the cells of organisms. Intracellular DNA (iDNA) plays an essential role in different stages of biological growth, and it is defined as the carrier of genetic information. In addition, extracellular DNA (eDNA) is not enclosed in living cells, accounting for a large proportion of total DNA in the environment. Both the lysis-dependent and lysis-independent pathways are involved in eDNA release, and the released DNA has diverse environmental functions. This review provides an insight into the origin as well as the multiple ecological functions of eDNA. Furthermore, the main research advancements of eDNA in the various ecological environments and the various model microorganisms are summarized. Furthermore, the major methods for eDNA extraction and quantification are evaluated.
Influence of Selective Extraction/Isolation of Heme/Hemoglobin with Hydrophobic Imidazolium Ionic Liquids on the Precision and Accuracy of Cotinine ELISA Test
Authors: Flieger Jolanta , Tatarczak-Michalewska Małgorzata , Flieger Wojciech , Baj Jacek , Buszewicz Grzegorz , Teresiński Grzegorz , Maciejewski Ryszard , Wawrzykowski Jacek , Przygodzka Dominika , Lutsyk Valery , Płaziński Wojciech
Published: November 2022

In this study, ionic liquids were used for the selective extraction/isolation of hemoglobin from human serum for cotinine determination using the ELISA Kit. The suitability of hydrophobic imidazolium-based ionic liquids was tested, of which OMIM BF4 (1-methyl-3-octylimidazolium tetrafluoroborate) turned out to be the most suitable for direct extraction of hemoglobin into an ionic liquid without the use of any additional reagent at one extraction step. Hemoglobin was separated quantitatively (95% recovery) from the remaining types of proteins remaining in the aqueous phase. Quantum mechanical calculations showed that the interaction of the iron atom in the heme group and the nitrogen atom of the ionic liquid cation is responsible for the transfer of hemoglobin whereas molecular dynamics simulations demonstrated that the non-covalent interactions between heme and solvent are more favorable in the case of OMIM BF4 in comparison to water. The opposite trend was found for cotinine. Selective isolation of the heme/hemoglobin improved the ELISA test’s accuracy, depending on the cotinine level, from 15% to 30%.
Track Structure-Based Simulations on DNA Damage Induced by Diverse Isotopes
Authors: Kundrát Pavel , Friedland Werner , Baiocco Giorgio
Published: November 2022

Diverse isotopes such as 2H, 3He, 10Be, 11C and 14C occur in nuclear reactions in ion beam radiotherapy, in cosmic ray shielding, or are intentionally accelerated in dating techniques. However, only a few studies have specifically addressed the biological effects of diverse isotopes and were limited to energies of several MeV/u. A database of simulations with the PARTRAC biophysical tool is presented for H, He, Li, Be, B and C isotopes at energies from 0.5 GeV/u down to stopping. The doses deposited to a cell nucleus and also the yields per unit dose of single- and double-strand breaks and their clusters induced in cellular DNA are predicted to vary among diverse isotopes of the same element at energies < 1 MeV/u, especially for isotopes of H and He. The results may affect the risk estimates for astronauts in deep space missions or the models of biological effectiveness of ion beams and indicate that radiation protection in 14C or 10Be dating techniques may be based on knowledge gathered with 12C or 9Be.
TBPEH-TBPB Initiate the Radical Addition of Benzaldehyde and Allyl Esters
Authors: Sun Binlong , Tian Xiaoyu , Yang Sen , Wang Yingying , Shao Yingying , Fu Xinhao , Wang Wenyuan , Tu Minting , Chen Yang , Wu Junhui , Wu Changyuan , Tan Chengxia
Published: November 2022

Tert-butylperoxy-2-ethylhexanoate (TBPEH) and tert-butyl peroxybenzoate (TBPB) promote the radical acylation of allyl ester with benzaldehyde to synthesize new carbonyl-containing compounds under solvent-free and metal-free conditions. This reaction is compatible with electron-donating and halogen groups and has excellent atom utilization and chemical selectivity. Furthermore, the synthetic compounds can further apply to the preparation of lactone, piperidine, tetrazole and oxazole.
Diffusiophoresis of a Nonionic Micelle in Salt Gradients; Roles of Preferential Hydration and Salt-Induced Surfactant Aggregation
Authors: Cruz Barrios Eliandreina , Penino Kyra V. , Annunziata Onofrio
Published: November 2022

Diffusiophoresis is the migration of a colloidal particle in water driven by concentration gradients of cosolutes such as salts. We have experimentally characterized the diffusiophoresis of tyloxapol micelles in the presence of MgSO4, a strong salting-out agent. Specifically, we determined the multicomponent-diffusion coefficients using Rayleigh interferometry, cloud points, and dynamic-light-scattering diffusion coefficients on the ternary tyloxapol–MgSO4–water system at 25 °C. Our experimental results show that micelle diffusiophoresis occurs from a high to a low salt concentration (positive diffusiophoresis). Moreover, our data were used to characterize the effect of salt concentration on micelle size and salt osmotic diffusion, which occurs from a high to a low surfactant concentration. Although micelle diffusiophoresis can be attributed to the preferential hydration of the polyethylene glycol surface groups, salting-out salts also promote an increase in the size of micellar aggregates, ultimately leading to phase separation at high salt concentration. This complicates diffusiophoresis description, as it is not clear how salt-induced surfactant aggregation contributes to micelle diffusiophoresis. We, therefore, developed a two-state aggregation model that successfully describes the observed effect of salt concentration on the size of tyloxapol micelles, in the case of MgSO4 and the previously reported case of Na2SO4. Our model was then used to theoretically evaluate the contribution of salt-induced aggregation to diffusiophoresis. Our analysis indicates that salt-induced aggregation promotes micelle diffusiophoresis from a low to a high salt concentration (negative diffusiophoresis). However, we also determined that this mechanism marginally contributes to overall diffusiophoresis, implying that preferential hydration is the main mechanism causing micelle diffusiophoresis. Our results suggest that sulfate salts may be exploited to induce the diffusiophoresis of PEG-functionalized particles such as micelles, with potential applications to microfluidics, enhanced oil recovery, and controlled-release technologies.
Integrated Transcriptome and Metabolome Analysis to Identify Sugarcane Gene Defense against Fall Armyworm (Spodoptera frugiperda) Herbivory
Authors: Li Ao-Mei , Wang Miao , Chen Zhong-Liang , Qin Cui-Xian , Liao Fen , Wu Zhen , He Wei-Zhong , Lakshmanan Prakash , Pan You-Qiang , Huang Dong-Liang
Published: November 2022

Sugarcane is the most important sugar crop, contributing ≥80% to total sugar production around the world. Spodoptera frugiperda is one of the main pests of sugarcane, potentially causing severe yield and sugar loss. The identification of key defense factors against S. frugiperda herbivory can provide targets for improving sugarcane resistance to insect pests by molecular breeding. In this work, we used one of the main sugarcane pests, S. frugiperda, as the tested insect to attack sugarcane. Integrated transcriptome and metabolomic analyses were performed to explore the changes in gene expression and metabolic processes that occurred in sugarcane leaf after continuous herbivory by S. frugiperda larvae for 72 h. The transcriptome analysis demonstrated that sugarcane pest herbivory enhanced several herbivory-induced responses, including carbohydrate metabolism, secondary metabolites and amino acid metabolism, plant hormone signaling transduction, pathogen responses, and transcription factors. Further metabolome analysis verified the inducement of specific metabolites of amino acids and secondary metabolites by insect herbivory. Finally, association analysis of the transcriptome and metabolome by the Pearson correlation coefficient method brought into focus the target defense genes against insect herbivory in sugarcane. These genes include amidase and lipoxygenase in amino acid metabolism, peroxidase in phenylpropanoid biosynthesis, and pathogenesis-related protein 1 in plant hormone signal transduction. A putative regulatory model was proposed to illustrate the sugarcane defense mechanism against insect attack. This work will accelerate the dissection of the mechanism underlying insect herbivory in sugarcane and provide targets for improving sugarcane variety resistance to insect herbivory by molecular breeding.
Cell-Specific Transport and Thyroid Hormone Receptor Isoform Selectivity Account for Hepatocyte-Targeted Thyromimetic Action of MGL-3196
Authors: Hönes Georg Sebastian , Sivakumar Ramona Gowry , Hoppe Christoph , König Jörg , Führer Dagmar , Moeller Lars Christian
Published: November 2022

Thyroid hormones (THs) and TH receptor-beta (TRβ) reduce hepatic triglycerides, indicating a therapeutic potential for TH analogs in liver steatosis. To avoid adverse extrahepatic, especially TRα-mediated effects such as tachycardia and bone loss, TH analogs with combined TRβ and hepatocyte specificity are desired. MGL-3196 is a new TH analog that supposedly meets these criteria. Here, we characterize the thyromimetic potential of MGL-3196 in cell-based assays and address its cellular uptake requirements. We studied the contribution of liver-specific organic anion transporters (OATP)1B1 and 1B3 to MGL-3196 action. The TR isoform-specific efficacy of MGL-3196 compared with 3,5,3′-triiodothyronine (T3) was determined with luciferase assays and gene expression analysis in OATP1B1 and OATP1B3 and TRα- or TRβ-expressing cells and in primary murine hepatocytes (PMHs) from wild-type and TRβ knockout mice. We measured the oxygen consumption rate to compare the effects of MGL-3196 and T3 on mitochondrial respiration. We identified OATP1B1 as the primary transporter for MGL-3196. MGL-3196 had a high efficacy (90% that of T3) in activating TRβ, while the activation of TRα was only 25%. The treatment of PMHs with T3 and MGL-3196 at EC50 resulted in a similar induction of Dio1 and repression of Serpina7. In HEK293 cells stably expressing OATP1B1, MGL-3196 had comparable effects on mitochondrial respiration as T3. These data indicate that MGL-3196’s hepatic thyromimetic action, the basis for its therapeutic use, results from a combination of hepatocyte-specific transport by OATP1B1 and the selective activation of TRβ over TRα.
2’-Fucosyllactose Inhibits Coxsackievirus Class A Type 9 Infection by Blocking Virus Attachment and Internalisation
Authors: Lou Fuxing , Hu Ruolan , Chen Yangzhen , Li Mengzhe , An Xiaoping , Song Lihua , Tong Yigang , Fan Huahao
Published: November 2022

Coxsackieviruses, a genus of enteroviruses in the small RNA virus family, cause fatal infectious diseases in humans. Thus far, there are no approved drugs to prevent these diseases. Human milk contains various biologically active components against pathogens. Currently, the potential activity of breast milk components against the coxsackievirus remains unclear. In our study, the inhibitory effect of 16 major human milk components was tested on coxsackievirus class A type 9 isolate (CV-A9), BUCT01; 2’-Fucosyllactose (2’-FL) was identified to be effective. Time-of-addition, attachment internalisation assays, and the addition of 2’-FL at different time points were applied to investigate its specific role in the viral life cycle. Molecular docking was used to predict 2’-FL’s specific cellular targets. The initial screening revealed a significant inhibitory effect (99.97%) against CV-A9 with 10 mg/mL 2’-FL, with no cytotoxicity observed. Compared with the control group, 2’-FL blocked virus entry (85%) as well as inhibited viral attachment (48.4%) and internalisation (51.3%), minimising its infection in rhabdomyosarcoma (RD) cells. The cell pre-incubation with 2’-FL exhibited significant inhibition (73.2–99.9%). Extended incubation between cells with 2’-FL reduced CV-A9 infection (93.9%), suggesting that 2’-FL predominantly targets cells to block infection. Molecular docking results revealed that 2’-FL interacted with the attachment receptor αvβ6 and the internalisation receptor FCGRT and β2M with an affinity of −2.14, −1.87, and −5.43 kcal/mol, respectively. This study lays the foundation for using 2’-FL as a food additive against CV-A9 infections.
Contrast-Free FLIM Reveals Metabolic Changes in Pathological Islets of Langerhans
Authors: Ermakova Polina , Kashirina Alena , Kornilova Irina , Bogomolova Aleksandra , Myalik Darya , Naraliev Nasipbek , Kuchin Denis , Lugovaya Liya , Zagaynova Elena , Zagainov Vladimir , Kashina Aleksandra
Published: November 2022

FLIM (Fluorescence Lifetime Imaging Microscopy) is a powerful tool that could be used in the future to diagnose islet cell recovery after therapy. The identification of appropriate FLIM parameters is required to determine islet quality and islet cell metabolism throughout the organ under various conditions of insulin deficiency. The aim of the work was to identify key FLIM parameters, changes of which are characteristic of pancreatic pathologies. The τm, τ1, τ2, α1, α2 and α1/α2 of free and bound forms of NAD(P)H of the islet cells of animals (rats and pigs) and of humans with and without pathologies were measured and analyzed. The data were confirmed by IHC and histological studies. We identified three FLIM parameters in islet cells from animals with streptozotocin (STZ)-induced diabetes mellitus (DM) and from humans with chronic pancreatitis + type 2 diabetes (T2D), which differ in the same way: τm and α2 take lower values compared to the nonpathological islet cells, while α1/α2 takes higher values. In islet cells from patients with adenocarcinoma (PDAC) and chronic pancreatitis, these parameters had reverse tendency relative to the norm or did not differ. Thus, minimally invasive and non-contrast FLIM methods may, in the future, be used to diagnose pathological islet cells.
Realizing Mathematics of Arrays Operations as Custom Architecture Hardware-Software Co-Design Solutions
Authors: Grout Ian Andrew , Mullin Lenore
Published: November 2022

In embedded electronic system applications being developed today, complex datasets are required to be obtained, processed, and communicated. These can be from various sources such as environmental sensors, still image cameras, and video cameras. Once obtained and stored in electronic memory, the data is accessed and processed using suitable mathematical algorithms. How the data are stored, accessed, processed, and communicated will impact on the cost to process the data. Such algorithms are traditionally implemented in software programs that run on a suitable processor. However, different approaches can be considered to create the digital system architecture that would consist of the memory, processing, and communications operations. When considering the mathematics at the centre of the design making processes, this leads to system architectures that can be optimized for the required algorithm or algorithms to realize. Mathematics of Arrays (MoA) is a class of operations that supports n-dimensional array computations using array shapes and indexing of values held within the array. In this article, the concept of MoA is considered for realization in software and hardware using Field Programmable Gate Array (FPGA) and Application Specific Integrated Circuit (ASIC) technologies. The realization of MoA algorithms will be developed along with the design choices that would be required to map a MoA algorithm to hardware, software or hardware-software co-designs.
Modeling the Physiological Parameters of Brewer’s Yeast during Storage with Natural Zeolite-Containing Tuffs Using Artificial Neural Networks
Authors: Shafrai Anton , Permyakova Larisa , Borodulin Dmitriy , Sergeeva Irina
Published: November 2022

Various methods are used to prevent the deterioration of the biotechnological properties of brewer’s yeast during storage. This paper studied the use of artificial neural networks for the mathematical modeling of correcting the biosynthetic activity of brewer’s seed yeast of the C34 race during storage with natural minerals. The input parameters for the artificial neural networks were the suspending medium (water, beer wort, or young beer); the type of the zeolite-containing tuff from Siberian deposits; the tuff content (0.5–4% of the total volume of the suspension); and the duration of storage (3 days). The output parameters were the number of yeast cells with glycogen, budding cells, and dead cells. In the yeast stored with tuffs, the number of budding cells increased by 1.2–2.5 times, and the number of cells with glycogen increased by 9–190% compared to the control sample (without tuff). The presence of kholinskiy zeolite and shivyrtuin tuffs resulted in a significant effect. The artificial neural networks were required for solving the regression tasks and predicting the output parameters based on the input parameters. Four networks were created: ANN1 (mean relative error = 4.869%) modeled the values of all the output parameters; ANN2 (MRE = 1.8381%) modeled the number of cells with glycogen; ANN3 (MRE = 6.2905%) modeled the number of budding cells; and ANN4 (MRE = 4.2191%) modeled the number of dead cells. The optimal parameters for yeast storage were then determined. As a result, the possibility of using ANNs for mathematical modeling of undesired deviations in the physiological parameters of brewer’s seed yeast during storage with natural minerals was proven.
Performance Evaluation of Carrying Capacity of Prestressed Bearers for Railway Turnouts Using Laboratory Experiments in Vietnam
Authors: Dung Tran Anh , Easa Said M.
Published: November 2022

Previous studies have addressed railway turnouts (switches and crossings), but research on the performance of 1000 mm gauge turnouts is limited. At present, wooden sleeper structures are used at turnouts in Vietnam. However, these structures have many disadvantages in the operation process. This paper evaluates the performance of new prestressed bearer (PSB) for turnouts, designed for the 1000 mm gauge, to overcome the disadvantages of a wooden sleeper. Test samples of PSB were manufactured in the factory, and experiments were conducted in the laboratory according to European Standards to evaluate the PSB carrying capacity. The test results show that the proposed structure meets the carrying capacity under the standard test loads. In addition, the results of the static and fatigue tests of the bearers show a considerable reserve in the cross-section capacity. This means that the existing reserve can be used with a larger locomotive axle, and the bearer design can be optimized by arranging the prestressed strands and changing the bearer cross-section’s geometric dimensions. It is hoped that the proposed bearer design will be a viable alternative for designing railway turnouts.
Pollination Effectiveness of the Hoverfly Eristalinus aeneus (Scopoli, 1763) in Diploid and Triploid Associated Watermelon Crop
Authors: Sánchez Manuela , Velásquez Yelitza , González Mónica , Cuevas Julián
Published: November 2022

Watermelon (Citrullus lanatus) is an important crop worldwide. Pollination of this crop is carried out by insects, with honey bees (Apis spp.) and bumble bees (Bombus spp.) as the most used in greenhouse production. Nevertheless, due to the extreme conditions in closed enclosures, these hymenopterans suffer management and behavior problems leading to insufficient pollination. The effectiveness of three release densities (15, 30, and 45 individuals/m2) of Eristalinus aeneus was compared in diploid- and triploid-associated watermelon varieties under protected cultivation. Floral visits, pollen–pistil interaction after pollen transport, yield, and fruit quality were evaluated. The number of floral visits increased with release density in both pistillate and staminate flowers. No significant differences were observed, however, among release densities or between flower types in the duration of the visits. Floral preferences were not found in the behavior of E. aeneus in watermelon. High and medium release densities increased pollen deposition onto the stigma, and consequently the yield of the triploid variety compared to low release density, by 23.8 to 41.8% in 2020 and by 36.3 to 46.7% in 2021. The results of this trial demonstrate the potential of E. aeneus as a managed pollinator in protected cultivation of triploid watermelon.
Transcriptomic Identification and Expression Profile Analysis of Odorant-Degrading Enzymes from the Asian Corn Borer Moth, Ostrinia furnacalis
Authors: Zhang Liya , Shen Yidan , Jiang Xingchuan , Liu Su
Published: November 2022

The Asian corn borer moth Ostrinia furnacalis is an important lepidopteran pest of maize in Asia. Odorant-degrading enzymes (ODEs), including carboxylesterases (CCEs), glutathione S-transferases (GSTs), cytochrome P450s (CYPs), UDP-glycosyltransferases (UGTs), and aldehyde oxidases (AOXs), are responsible for rapid inactivation of odorant signals in the insect antennae. In this study, we performed a transcriptome assembly for the antennae of O. furnacalis to identify putative ODE genes. Transcriptome sequencing revealed 35,056 unigenes, and 21,012 (59.94%) of these were annotated by searching against the reference sequences in the NCBI non-redundant (NR) protein database. For functional classification, these unigenes were subjected to Gene Ontology (GO), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. We identified 79 genes encoding putative ODEs: 19 CCEs, 17 GSTs, 24 CYPs, 13 UGTs, and 6 AOXs. BLASTX best hit results indicated that these genes shared quite high amino acid identities with their respective orthologs from other lepidopteran species. Reverse transcription-quantitative PCR showed that OfurCCE2, OfurCCE5, and OfurCCE18 were enriched in male antennae, while OfurCCE7 and OfurCCE10 were enriched in female antennae. OfurCCE14 and OfurCCE15 were expressed at near-equal amounts in the antennae of both sexes. Our findings establish a solid foundation for future studies aimed at understanding the olfactory functions of these genes in O. furnacalis.
The Athlete’s Heart and Machine Learning: A Review of Current Implementations and Gaps for Future Research
Authors: Bellfield Ryan A. A. , Ortega-Martorell Sandra , Lip Gregory Y. H. , Oxborough David , Olier Ivan
Published: November 2022

Background: Intense training exercise regimes cause physiological changes within the heart to help cope with the increased stress, known as the “athlete’s heart”. These changes can mask pathological changes, making them harder to diagnose and increasing the risk of an adverse cardiac outcome. Aim: This paper reviews which machine learning techniques (ML) are being used within athlete’s heart research and how they are being implemented, as well as assesses the uptake of these techniques within this area of research. Methods: Searches were carried out on the Scopus and PubMed online datasets and a scoping review was conducted on the studies which were identified. Results: Twenty-eight studies were included within the review, with ML being directly referenced within 16 (57%). A total of 12 different techniques were used, with the most popular being artificial neural networks and the most common implementation being to perform classification tasks. The review also highlighted the subgroups of interest: predictive modelling, reviews, and wearables, with most of the studies being attributed to the predictive modelling subgroup. The most common type of data used was the electrocardiogram (ECG), with echocardiograms being used the second most often. Conclusion: The results show that over the last 11 years, there has been a growing desire of leveraging ML techniques to help further the understanding of the athlete’s heart, whether it be by expanding the knowledge of the physiological changes or by improving the accuracies of models to help improve the treatments and disease management.
Personal Activity Intelligence and Ischemic Heart Disease in a Healthy Population: China Kadoorie Biobank Study
Authors: Hammer Pål , Tari Atefe R. , Franklin Barry A. , Wen Chi-Pang , Wisløff Ulrik , Nauman Javaid
Published: November 2022

Background: Personal Activity Intelligence (PAI) is a physical activity metric that translates heart rate during physical activity into a simple score, where a weekly score of 100 or greater is associated with a lower risk of cardiovascular disease and mortality. Here, we prospectively investigated the association between PAI and ischemic heart disease (IHD) mortality in a large healthy population from China. Methods: Using data from the China Kadoorie Biobank, we studied 443,792 healthy adults (60% women). The weekly PAI score of each participant was estimated based on the questionnaire data and divided into four groups (PAI scores of 0, ≤50, 51–99, or ≥100). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for fatal IHD and nonfatal myocardial infraction (MI) related to PAI were estimated using Cox proportional hazard regression analyses. Results: There were 3050 IHD deaths and 1808 MI events during a median follow-up of 8.2 years (interquartile range, 7.3–9.1; 3.6 million person-years). After adjustments for multiple confounders, a weekly PAI score ≥ 100 was associated with a lower risk of IHD (aHR: 0.91 (95% CI: 0.83–1.00)), compared with the inactive group (0 PAI). The corresponding aHR for MI was 0.94 (95% CI: 0.83–1.05). In participants aged 60 years or older at baseline, the aHR associated with a weekly PAI score ≥ 100 was 0.84 (95% CI, 0.75–0.93) for IHD and 0.84 (95% CI, 0.73–0.98) for MI. Conclusion: Among healthy Chinese adults, a weekly PAI score of 100 or greater was associated with a lower risk of IHD mortality across all age groups; moreover, a high PAI score significantly lowered the risk of MI but only in those 60 years and older at baseline. The present findings extend the scientific evidence that PAI may have prognostic significance in diverse settings for IHD outcomes and suggest that the PAI metric may be useful in delineating the magnitude of weekly physical activity needed to reduce the risk of IHD mortality.
Digital Twins in Radiology
Authors: Pesapane Filippo , Rotili Anna , Penco Silvia , Nicosia Luca , Cassano Enrico
Published: November 2022

A digital twin is a virtual model developed to accurately reflect a physical thing or a system. In radiology, a digital twin of a radiological device enables developers to test its characteristics, make alterations to the design or materials, and test the success or failure of the modifications in a virtual environment. Innovative technologies, such as AI and -omics sciences, may build virtual models for patients that are continuously adjustable based on live-tracked health/lifestyle parameters. Accordingly, healthcare could use digital twins to improve personalized medicine. Furthermore, the accumulation of digital twin models from real-world deployments will enable large cohorts of digital patients that may be used for virtual clinical trials and population studies. Through their further refinement, development, and application into clinical practice, digital twins could be crucial in the era of personalized medicine, revolutionizing how diseases are detected and managed. Although significant challenges remain in the development of digital twins, a structural modification to the current operating models is occurring, and radiologists can guide the introduction of such technology into healthcare.
Effects of Perioperative Oral Management in Patients with Cancer
Authors: Kurasawa Yasuhiro , Iida Akihiko , Narimatsu Kaya , Sekiya Hideki , Maruoka Yutaka , Michiwaki Yukihiro
Published: November 2022

Perioperative oral management (POM) is used to prevent pneumonia in patients with cancer. However, the factors that expose hospitalized patients to increased risk of developing pneumonia remain unclear. For example, no study to date has compared the incidence of pneumonia in hospitalized patients by cancer primary lesion, or POM implementation, or not. We determined which patients were most likely to benefit from POM and examined the effects of POM on pneumonia prevention and mortality. In a total of 9441 patients with cancer who underwent surgery during hospitalization, there were 8208 patients in the No POM group, and 1233 in the POM group. We examined between-group differences in the incidence of pneumonia and associated outcomes during hospitalization. There was no significant between-group difference in the incidence of pneumonitis, however, patients with lung, or head and neck cancers, demonstrated a lower incidence of postoperative pneumonia. Among patients with lung and pancreatic cancers, mortality was significantly lower in the POM group. POM appears effective at reducing the risk of postoperative pneumonia in patients with certain cancers. Further, mortality was significantly lower in patients with lung and pancreatic cancers who received POM; hence, POM may be an effective adjuvant therapy for patients with cancer.
A High Dose, Not Low Dose, of Vitamin D Ameliorates Insulin Resistance in Saudi Women
Authors: AlGhamdi Shareefa , AlHarthi Hanan , Khoja Sawsan , AlJefri Amin , AlShaibi Huda F.
Published: November 2022

Vitamin D has been traditionally seen to be mainly involved in the regulation of bone homeostasis. However, vitamin D has also been clinically linked to various diseases, including metabolic syndrome. The aim of this study was to examine the effect of low and high doses of a vitamin D supplement on the serum levels of 25(OH)D3 and insulin resistance. A total of 120 females were recruited in this study and supplemented weekly with 25,000 IU vitamin D or 50,000 IU vitamin D for three months. Anthropometric measurements were taken at the beginning of the study. Blood samples were collected at the beginning of the study to determine the baseline of the clinical variables and collected again after three months. Insulin resistance was measured using Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). After vitamin D supplementation, a non-significant increase was observed in the serum levels of 25(OH)D3 in the group treated with a low dose of vitamin D (LDVD) and a highly significant increase was seen in the group treated with a high dose of vitamin D (HDVD). In the group treated with a higher dose (HDVD), a significant improvement in insulin sensitivity was observed. The high dose of vitamin D (50,000 IU) supplementation was more effective in both correcting the blood levels of vitamin D and improving the sensitivity of insulin.
Autonomous Robotic Surgery for Immediately Loaded Implant-Supported Maxillary Full-Arch Prosthesis: A Case Report
Authors: Yang Shuo , Chen Jiahao , Li An , Li Ping , Xu Shulan
Published: November 2022

Robotic systems have emerged in dental implant surgery due to their accuracy. Autonomous robotic surgery may offer unprecedented advantages over conventional alternatives. This clinical protocol was used to show the feasibility of autonomous robotic surgery for immediately loaded implant-supported full-arch prostheses in the maxilla. This case report demonstrated the surgical protocol and outcomes in detail, highlighting the pros and cons of the autonomous robotic system. Within the limitations of this study, autonomous robotic surgery could be a feasible alternative to computer-assisted guided implant surgery.
Prediction Value of KREBS Von Den Lungen-6 (KL-6) Biomarker in COVID-19 Patients: A Systematic Review and Meta-Analysis
Authors: Matuszewski Michal , Szarpak Lukasz , Rafique Zubaid , Peacock Frank W. , Pruc Michal , Szwed Piotr , Chirico Francesco , Navolokina Alla , Ladny Jerzy R. , Denegri Andrea
Published: November 2022

The SARS-CoV-2 (COVID-19) pandemic is a major issue that necessitates the use of cutting-edge disease prediction models. The aim of the study was to assess the existing evidence regarding association between Krebs von den Lungen-6 levels and COVID-19 severity. A literature search was performed on Web of Science, PubMed, Scopus and Cochrane Central Register of Controlled Trials databases from 1 January 2020 up to 2 August 2022. The electronic database search was supplemented by searching Google Scholar. In addition, reference lists of relative articles were also reviewed. KL-6 levels among COVID-19 positive vs. negative patients varied and amounted to 443.37 ± 249.33 vs. 205.73 ± 86.8 U/mL (MD = 275.33; 95%CI: 144.57 to 406.09; p < 0.001). The KL-6 level was 402.82 ± 261.16 U/mL in the severe group and was statistically significantly higher than in the non-severe group (297.38 ± 90.46 U/mL; MD = 192.45; 95%CI: 118.19 to 266.72; p < 0.001). The KL-6 level in the mild group was 272.28 ± 95.42 U/mL, compared to 268.04 ± 55.04 U/mL in the moderate COVID-19 group (MD = −12.58; 95%CI: −21.59 to −3.57; p = 0.006). Our meta-analysis indicates a significant association between increased KL-6 levels and SARS-CoV-2 infection. Moreover, KL-6 levels are significantly higher in patients with a more severe course of COVID-19, indicating that KL-6 may be a useful predictor to identify patients at risk for severe COVID-19.