bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring Atmospheric Atomic Mercury by Optical Techniques
Authors: Svanberg Sune
Published: July 2023

Mercury is a serious neurotoxic agent, and the control and monitoring of emissions are important. Optical spectroscopy is a powerful technique for measurement of mercury, which in the atmosphere predominantly appears in atomic form. The mercury resonance line close to 254 nm can be utilized in long-path absorption measurements of average concentrations or in light detection and ranging (lidar) studies, where range-resolved concentration values can be obtained. In addition, point monitors often use optical detection, frequently after pre-concentration, as well as for mercury compounds in conjunction with denuders, which transfer the compounds into atomic mercury. The present review discusses mercury measurement methods with respect to merits and sensitivity to interference. The main focus is on remote-sensing techniques, and many examples from industrial and mining monitoring are given. Further, mercury emissions related to the extraction of geothermal energy are discussed. Finally, an example from archaeology—the Qin tomb in Xi’an—is presented. Advanced measurement techniques can help in shaping an environment largely free from mercury contamination. Further, the aspect of mercury being an important geophysical tracer gas can also be exploited.
The Future Impact of Shipping Emissions on Air Quality in Europe under Climate Change
Authors: Russo Michael , Carvalho David , Jalkanen Jukka-Pekka , Monteiro Alexandra
Published: July 2023

Ship engine combustion emits several atmospheric pollutants, such as PM, SOx, and NOx, which can have adverse health effects and are significant contributors to decreased air quality. Due to the distribution of maritime transport activity routes in the EU, a large portion of the population is exposed to shipping emissions throughout Europe. Therefore, in light of the European Commission long-term objective of “zero-waste, zero-emission” for maritime transport, the focus of this study was to quantify the impact of shipping emissions in the present, as well as the future, considering both emissions projection for the shipping sector and a climate change scenario. The WRF-CHIMERE modelling system was used to quantify the impact of shipping in Europe. To obtain the current and future contributions of maritime transport to the total pollutant concentrations, simulations were divided into two present (baseline and without shipping) and three future scenarios (shipping projection, climate change, and shipping projection and climate change). The results indicate that the current and future impacts of shipping emissions on pollutant concentrations are similar in some regions (NO2 for Northern Europe and SO2 for Southern Europe), which is due to the enforcement of emission control areas for those pollutants. However, efforts towards lowering emissions from the shipping sector are negated in the south of this domain due to the concentration changes caused by the climate change scenario. In light of these changes, the introduction of a NECA is proposed for the Mediterranean, which would help us to make great strides to reduce the impact of the shipping sector in the region and aid in counteracting the effects of climate change.
Plurisubharmonic Interpolation and Plurisubharmonic Geodesics
Authors: Rashkovskii Alexander
Published: July 2023

We give a short survey on plurisubharmonic interpolation, with a focus on the possibility of connecting two given plurisubharmonic functions by plurisubharmonic geodesics.
General New Results on (ϕ,F)−Contractions in b−Metric-like-Spaces
Authors: Zoto Kastriot , Gardašević-Filipović Milanka , Vardhami Ilir , Mitrović Zoran , Radenović Stojan
Published: July 2023

Thispaper recognizes a general approach related to recent fixed point results about the classes of interpolative and hybrid contractions in metric space and general metric spaces. Considering auxiliary functions, so called Wardowski functions, and a rich set of implicit relations, we introduce types of (αvq,ϕ,F)−contractions and r−order hybrid (αvq,ϕ,F)−contractions in the setting of b−metric-like spaces. They generate and simplify many forms of contractions widely used in the literature. The resulting theorems significantly extend, generalize, and unify an excellent work on fixed point theory.
Joint Discrete Universality in the Selberg–Steuding Class
Authors: Kačinskaitė Roma , Laurinčikas Antanas , Žemaitienė Brigita
Published: July 2023

In the paper, we consider the approximation of analytic functions by shifts from the wide class S˜ of L-functions. This class was introduced by A. Selberg, supplemented by J. Steuding, and is defined axiomatically. We prove the so-called joint discrete universality theorem for the function L(s)∈S˜. Using the linear independence over Q of the multiset (hjlogp:p∈P),j=1,…,r;2π for positive hj, we obtain that there are many infinite shifts L(s+ikh1),…,L(s+ikhr), k=0,1,…, approximating every collection f1(s),…,fr(s) of analytic non-vanishing functions defined in the strip {s∈C:σL<σ<1}, where σL is a degree of the function L(s). For the proof, the probabilistic approach based on weak convergence of probability measures in the space of analytic functions is applied.
Cancer Drug Delivery Systems Using Bacterial Toxin Translocation Mechanisms
Authors: Yin Linxiang , Thaker Hatim
Published: July 2023

Recent advances in targeted cancer therapy hold great promise for both research and clinical applications and push the boundaries in finding new treatments for various currently incurable cancers. However, these therapies require specific cell-targeting mechanisms for the efficient delivery of drug cargo across the cell membrane to reach intracellular targets and avoid diffusion to unwanted tissues. Traditional drug delivery systems suffer from a limited ability to travel across the barriers posed by cell membranes and, therefore, there is a need for high doses, which are associated with adverse reactions and safety concerns. Bacterial toxins have evolved naturally to specifically target cell subtypes via their receptor binding module, penetrating the cell membrane efficiently through the membrane translocation process and then successfully delivering the toxic cargo into the host cytosol. They have, thus, been harnessed for the delivery of various drugs. In this review, we focus on bacterial toxin translocation mechanisms and recent progress in the targeted delivery systems of cancer therapy drugs that have been inspired by the receptor binding and membrane translocation processes of the anthrax toxin protective antigen, diphtheria toxin, and Pseudomonas exotoxin A. We also discuss the challenges and limitations of these studies that should be addressed before bacterial toxin-based drug delivery systems can become a viable new generation of drug delivery approaches in clinical translation.
Comprehensive Analysis for Anti-Cancer Target-Indication Prioritization of Placental Growth Factor Inhibitor (PGF) by Use of Omics and Patient Survival Data
Authors: Kim Nari , Ko Yousun , Shin Youngbin , Park Jisuk , Lee Amy Junghyun , Kim Kyung Won , Pyo Junhee
Published: July 2023

The expression of the placental growth factor (PGF) in cancer cells and the tumor microenvironment can contribute to the induction of angiogenesis, supporting cancer cell metabolism by ensuring an adequate blood supply. Angiogenesis is a key component of cancer metabolism as it facilitates the delivery of nutrients and oxygen to rapidly growing tumor cells. PGF is recognized as a novel target for anti-cancer treatment due to its ability to overcome resistance to existing angiogenesis inhibitors and its impact on the tumor microenvironment. We aimed to integrate bioinformatics evidence using various data sources and analytic tools for target-indication identification of the PGF target and prioritize the indication across various cancer types as an initial step of drug development. The data analysis included PGF gene function, molecular pathway, protein interaction, gene expression and mutation across cancer type, survival prognosis and tumor immune infiltration association with PGF. The overall evaluation was conducted given the totality of evidence, to target the PGF gene to treat the cancer where the PGF level was highly expressed in a certain tumor type with poor survival prognosis as well as possibly associated with poor tumor infiltration level. PGF showed a significant impact on overall survival in several cancers through univariate or multivariate survival analysis. The cancers considered as target diseases for PGF inhibitors, due to their potential effects on PGF, are adrenocortical carcinoma, kidney cancers, liver hepatocellular carcinoma, stomach adenocarcinoma, and uveal melanoma.
Mitochondrial Neurodegenerative Diseases: Three Mitochondrial Ribosomal Proteins as Intermediate Stage in the Pathway That Associates Damaged Genes with Alzheimer’s and Parkinson’s
Authors: Del Giudice Luigi , Pontieri Paola , Aletta Mariarosaria , Calcagnile Matteo
Published: July 2023

Currently, numerous research endeavors are dedicated to unraveling the intricate nature of neurodegenerative diseases. These conditions are characterized by the gradual and progressive impairment of specific neuronal systems that exhibit anatomical or physiological connections. In particular, in the last twenty years, remarkable efforts have been made to elucidate neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. However, despite extensive research endeavors, no cure or effective treatment has been discovered thus far. With the emergence of studies shedding light on the contribution of mitochondria to the onset and advancement of mitochondrial neurodegenerative disorders, researchers are now directing their investigations toward the development of therapies. These therapies include molecules designed to protect mitochondria and neurons from the detrimental effects of aging, as well as mutant proteins. Our objective is to discuss and evaluate the recent discovery of three mitochondrial ribosomal proteins linked to Alzheimer's and Parkinson's diseases. These proteins represent an intermediate stage in the pathway connecting damaged genes to the two mitochondrial neurological pathologies. This discovery potentially could open new avenues for the production of medicinal substances with curative potential for the treatment of these diseases.
Berberine and Its Study as an Antidiabetic Compound
Authors: Utami Ayudiah Rizki , Maksum Iman Permana , Deawati Yusi
Published: July 2023

Diabetes mellitus (DM) is a metabolic disorder that causes hyperglycemia conditions and leads to various chronic complications that causes death. The prevalence of diabetes is predicted to continue to increase, and with the high toxicity levels of current diabetes drugs, the exploration of natural compounds as alternative diabetes treatment has been widely carried out, one of which is berberine. Berberine and several other alkaloid compounds, including some of its derivatives, have shown many bioactivities, such as neuraminidase and hepatoprotective activity. Berberine also exhibits antidiabetic activity. As an antidiabetic compound, berberine is known to reduce blood glucose levels, increase insulin secretion, and weaken glucose tolerance and insulin resistance by activating the AMPK pathway. Apart from being an antidiabetic compound, berberine also exhibits various other activities such as being anti-adipogenic, anti-hyperlipidemic, anti-inflammatory, and antioxidant. Many studies have been conducted on berberine, but its exact mechanism still needs to be clarified and requires further investigation. This review will discuss berberine and its mechanism as a natural compound with various activities, mainly as an antidiabetic.
CpG ODN/Mangiferin Dual Delivery through Calcium Alginate Hydrogels Inhibits Immune-Mediated Osteoclastogenesis and Promotes Alveolar Bone Regeneration in Mice
Authors: Gu Yingzhi , Hu Yang , Huang Shengyuan , Ruiz Sunniva , Kawai Toshihisa , Bai Yuxing , Han Xiaozhe
Published: July 2023

The immune system plays an important role in the skeletal system during bone repair and regeneration. The controlled release of biological factors from the immune system could facilitate and optimize the bone remodeling process through the regulation of the activities of bone cells. This study aimed to determine the effect of the controlled delivery of immunomodulatory biologicals on bone regeneration. Immunostimulatory cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) and glucosylxanthone Mangiferin (MAG)-embedded microbeads were incubated with P. gingivalis-challenged splenocytes, or co-cultured with RAW264.7 cells. The effect of CpG ODN/MAG-containing microbeads on bone regeneration was then tested in vivo in a mouse alveolar bone defect model. The results demonstrated that MAG significantly antagonized P. gingivalis proliferation and reduced the live/dead cell ratio. After the addition of CpG ODN + MAG microbeads, anti-inflammatory cytokines IL-10 and IL-4 were upregulated on day 2 but not day 4, whereas pro-inflammatory cytokine IL-1β responses showed no difference at both timepoints. RANKL production by splenocytes and TRAP+ cell formation of RAW264.7 cells were inhibited by the addition of CpG ODN + MAG microbeads. Alveolar bony defects, filled with CpG ODN + MAG microbeads, showed significantly increased new bone after 4 weeks. In summary, this study evaluated a new hydrogel-based regimen for the local delivery and controlled release of biologicals to repair and regenerate alveolar bony defects. The combined CpG ODN + MAG treatment may promote alveolar bone regeneration through the anti-microbial/anti-inflammatory effects and the inhibition of RANKL-mediated osteoclastogenesis.
Quantitative, Targeted Analysis of Gut Microbiota Derived Metabolites Provides Novel Biomarkers of Early Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients
Authors: Balint Lavinia , Socaciu Carmen , Socaciu Andreea Iulia , Vlad Adrian , Gadalean Florica , Bob Flaviu , Milas Oana , Cretu Octavian Marius , Suteanu-Simulescu Anca , Glavan Mihaela , Ienciu Silvia , Mogos Maria , Jianu Dragos Catalin , Petrica Ligia
Published: July 2023

Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes mellitus (T2DM), as it progresses silently to end-stage renal disease (ESRD). The discovery of novel biomarkers of early DKD becomes acute, as its incidence is reaching catastrophic proportions. Our study aimed to quantify previously identified metabolites from serum and urine through untargeted ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques, such as the following: arginine, dimethylarginine, hippuric acid, indoxyl sulfate, p-cresyl sulfate, L-acetylcarnitine, butenoylcarnitine and sorbitol. The study concept was based on the targeted analysis of selected metabolites, using the serum and urine of 20 healthy subjects and 90 T2DM patients with DKD in different stages (normoalbuminuria—uACR < 30 mg/g; microalbuminuria—uACR 30–300 mg/g; macroalbuminuria—uACR > 300 mg/g). The quantitative evaluation of metabolites was performed with pure standards, followed by the validation methods such as the limit of detection (LOD) and the limit of quantification (LOQ). The following metabolites from this study resulted as possible biomarkers of early DKD: in serum—arginine, dimethylarginine, hippuric acid, indoxyl sulfate, butenoylcarnitine and sorbitol and in urine—p-cresyl sulfate.
Exploration of Bis-Cinnamido-Polyamines as Intrinsic Antimicrobial Agents and Antibiotic Enhancers
Authors: Cadelis Melissa M. , Kim Jisoo , Rouvier Florent , Gill Evangelene S. , Fraser Kyle , Bourguet-Kondracki Marie-Lise , Brunel Jean Michel , Copp Brent R.
Published: July 2023

The marine natural product ianthelliformisamine C is a bis-cinnamido substituted spermine derivative that exhibits intrinsic antimicrobial properties and can enhance the action of doxycycline towards the Gram-negative bacterium Pseudomonas aeruginosa. As part of a study to explore the structure–activity requirements of these activities, we have synthesized a set of analogues that vary in the presence/absence of methoxyl group and bromine atoms and in the polyamine chain length. Intrinsic antimicrobial activity towards Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) and the fungus Cryptococcus neoformans was observed for only the longest polyamine chain examples of non-brominated analogues while all examples bearing either one or two bromine atoms were active. Weak to no activity was typically observed towards Gram-negative bacteria, with exceptions being the longest polyamine chain examples 13f, 14f and 16f against Escherichia coli (MIC 1.56, 7.2 and 5.3 µM, respectively). Many of these longer polyamine-chain analogues also exhibited cytotoxic and/or red blood cell hemolytic properties, diminishing their potential as antimicrobial lead compounds. Two of the non-toxic, non-halogenated analogues, 13b and 13d, exhibited a strong ability to enhance the action of doxycycline against P. aeruginosa, with >64-fold and >32-fold enhancement, respectively. These results suggest that any future efforts to optimize the antibiotic-enhancing properties of cinnamido-polyamines should explore a wider range of aromatic ring substituents that do not include bromine or methoxyl groups.
Unique Biomarkers of Collagen Type III Remodeling Reflect Different Information Regarding Pathological Kidney Tissue Alterations in Patients with IgA Nephropathy
Authors: Sparding Nadja , Neprasova Michaela , Maixnerova Dita , Genovese Federica , Karsdal Morten Asser , Kollar Marek , Koprivova Helena , Hruskova Zdenka , Tesar Vladimir
Published: July 2023

Kidney fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix (ECM) remodeling. Collagen type III is one of the main ECM components of the interstitial matrix of the kidney. We hypothesized that measuring three biomarkers of collagen type III reflecting different aspects of this protein turnover (C3M, C3C, and PRO-C3) may provide different information about the fibrotic burden in patients with IgA nephropathy (IgAN). We examined a cohort of 134 patients with IgAN. The three collagen type III biomarkers were measured in serum (S) and in urine (U) samples taken on the same day before kidney biopsy was performed. Biopsies were evaluated for interstitial fibrosis and tubular atrophy, according to the Banff and MEST-C scores. S-PRO-C3 and S-C3C correlated with the degree of fibrosis in the biopsy, whereas U-C3M/Cr had an inverse correlation with fibrosis. U-C3M/Cr had the highest discrimination ability for advanced fibrosis, which was maintained after adjustment for the other collagen type III biomarkers, proteinuria, and serum creatinine. The data presented in this study indicate that measuring the different fragments of the same ECM protein and in different matrices provides a variety of information regarding pathological kidney tissue alterations in patients with IgAN.
The Metallodrug BOLD-100 Is a Potent Inhibitor of SARS-CoV-2 Replication and Has Broad-Acting Antiviral Activity
Authors: Labach Daniel S. , Kohio Hinissan P. , Tse Edwin A. , Paparisto Ermela , Friesen Nicole J. , Pankovich Jim , Bazett Mark , Barr Stephen D.
Published: July 2023

The COVID-19 pandemic has highlighted an urgent need to discover and test new drugs to treat patients. Metal-based drugs are known to interact with DNA and/or a variety of proteins such as enzymes and transcription factors, some of which have been shown to exhibit anticancer and antimicrobial effects. BOLD-100 (sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]dihydrate) is a novel ruthenium-based drug currently being evaluated in a Phase 1b/2a clinical trial for the treatment of advanced gastrointestinal cancer. Given that metal-based drugs are known to exhibit antimicrobial activities, we asked if BOLD-100 exhibits antiviral activity towards SARS-CoV-2. We demonstrated that BOLD-100 potently inhibits SARS-CoV-2 replication and cytopathic effects in vitro. An RNA sequencing analysis showed that BOLD-100 inhibits virus-induced transcriptional changes in infected cells. In addition, we showed that the antiviral activity of BOLD-100 is not specific for SARS-CoV-2, but also inhibits the replication of the evolutionarily divergent viruses Human Immunodeficiency Virus type 1 and Human Adenovirus type 5. This study identifies BOLD-100 as a potentially novel broad-acting antiviral drug.
Abnormal Expression of Prolyl Oligopeptidase (POP) and Its Catalytic Products Ac-SDKP Contributes to the Ovarian Fibrosis Change in Polycystic Ovary Syndrome (PCOS) Mice
Authors: Han Suo , Wang Shimeng , Fan Xiang , Chen Mengchi , Wang Xiaojie , Huang Yingtong , Zhang Hongdan , Ma Yinyin , Wang Jing , Zhang Chunping
Published: July 2023

Polycystic ovary syndrome (PCOS) is an endocrine disorder and metabolic syndrome. Ovarian fibrosis pathological change in PCOS has gradually attracted people’s attention. In this study, we constructed a PCOS mouse model through the use of dehydroepiandrosterone. Sirius red staining showed that the ovarian tissues in PCOS mice had obvious fibrosis. Prolyl oligopeptidase (POP) is a serine protease and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is its catalytic product. Studies show that abnormal expression and activity of POP and Ac-SDKP are closely related to tissue fibrosis. It was found that the expression of POP and Ac-SDKP was decreased in the ovaries of PCOS mice. Further studies showed that POP and Ac-SDKP promoted the expression of matrix metalloproteinases 2 (MMP-2) expression and decreased the expression of transforming growth factor beta 1 (TGF-β1) in granulosa cells. Hyperandrogenemia is a typical symptom of PCOS. We found that testosterone induced the low expression of POP and MMP2 and high expression of TGF-β1 in granulosa cells. POP overexpression and Ac-SDKP treatment inhibited the effect of testosterone on TGF-β1 and MMP2 in vitro and inhibited ovarian fibrosis in the PCOS mouse model. In conclusion, PCOS ovarian tissue showed obvious fibrosis. Low expression of POP and Ac-SDKP and changes in fibrotic factors contribute to the ovarian pathological fibrosis induced by androgen.
The Significance of CXCL1 and CXCR1 as Potential Biomarkers of Colorectal Cancer
Authors: Łukaszewicz-Zając Marta , Zajkowska Monika , Pączek Sara , Kulczyńska-Przybik Agnieszka , Safiejko Kamil , Juchimiuk Marcin , Kozłowski Leszek , Mroczko Barbara
Published: July 2023

The CXCL1/CXCR2 and CXCL8-CXCR1/CXCR2 axes are under intensive investigation as they appear to regulate the progression and invasion of colorectal cancer (CRC). Growing evidence demonstrates the elevated expression of these proteins in CRC. However, a majority of relevant studies have been performed on CRC tissues using immunohistochemical techniques. Our study is the first to evaluate the diagnostic significance of serum CXCL1 and CXCR1 levels in CRC patients in comparison to well-established tumor markers, such as the carcinoembryonic antigen (CEA), and markers of inflammation, such as C-reactive protein (CRP). Thus, the aim of our study was to assess whether circulating serum levels of CXCL1 and CXCR1 might be candidates for novel biomarkers in the diagnosis and progression of CRC. The study was performed on 76 subjects, including patients with CRC and healthy volunteers as a control group. Serum concentrations of CXCL1, CXCR1, and the classical tumor marker (CEA) were measured using immunoenzyme assays, while CRP levels were assessed with the immunoturbidimetric method. Serum CXCL1 levels were statistically significantly increased in CRC patients when compared to healthy subjects, and similar results were found for CEA and CRP levels. The percentage of elevated concentrations of CXCL1 and CXCR1 was higher than that of the classical tumor biomarker and increased in the combined measurement of these proteins with CEA. In addition, among all proteins tested, serum CXCL1 seems to be the best indicator in the differentiation between CRC patients with nodal involvement and patients without the presence of lymph node metastasis. Our preliminary results indicate the role of serum CXCL1 and CXCR1 in the diagnosis of CRC, particularly in the combined measurement with CEA.
Compensatory Increase of Serum Hepassocin Protects Hyperthyroidism-Induced Hepatic Dysfunction
Authors: Wang Chih-Chen , Lin Ching-Han , Chou Hsuan-Wen , Wang Chung-Teng , Liang Yu-Cheng , Wu Hung-Tsung , Ou Horng-Yih
Published: July 2023

Hepatic dysfunction is commonly observed in subjects with hyperthyroidism. Hepassocin is a hepatokine playing an important role in metabolic diseases and exhibiting a hepatic protective effect. Nevertheless, the relationship between hepassocin and hyperthyroidism was still unknown. In the present study, a total of 36 subjects with Graves’ disease were enrolled, and we found that the alanine aminotransferase (ALT) levels were significantly decreased in parallel with the decrement in serum hepassocin concentrations at 6 months after standard treatment for hyperthyroidism. In addition, HepG2 cell line was used to investigate the role of hepassocin in hyperthyroidism-induced hepatic dysfunction. Treatment of hepassocin recombinant protein in HepG2 cells dose-dependently decreased triiodothyronine (T3)-induced ALT and aspartate aminotransferase (AST) elevation. Moreover, hepassocin significantly increased the expression of phosphoenolpyruvate carboxykinase (PEPCK) in a dose-dependent manner. Deletion of hepassocin in HepG2 cells reversed the effects of T3 on PEPCK expressions. Furthermore, we found that T3 increased the expression of hepassocin through a hepatocyte nuclear factor 1α-dependent pathway. Taken together, these results indicated a compensatory increase in serum hepassocin might have a protective role in hyperthyroidism-induced hepatic dysfunction.
Melatonin Preserves Fluidity in Cell and Mitochondrial Membranes against Hepatic Ischemia–Reperfusion
Authors: Esteban-Zubero Eduardo , López-Pingarrón Laura , Ramírez José Manuel , Reyes-Gonzales Marcos César , Azúa-Romeo Francisco Javier , Soria-Aznar Marisol , Agil Ahmad , García José Joaquín
Published: July 2023

We evaluated the in vivo effects of melatonin treatment on oxidative damage in the liver in an experimental model of ischemia–reperfusion. A total of 37 male Sprague-Dawley rats were randomly divided into four groups: control, ischemia, ischemia + reperfusion, and ischemia + reperfusion + melatonin. Hepatic ischemia was maintained for 20 min, and the clamp was removed to initiate vascular reperfusion for 30 min. Melatonin (50 mg/kg body weight) was intraperitoneally administered. Fluidity was measured by polarization changes in 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene-p-toluene sulfonate). After 20 min of ischemia, no significant changes were observed in cell and mitochondrial membrane fluidity levels, lipid peroxidation, and protein carbonylation. However, after 30 min of reperfusion, membrane fluidity decreased compared to controls. Increases in lipid and protein oxidation were also seen in hepatic homogenates of animals exposed to reperfusion. Melatonin injected 30 min before ischemia and reperfusion fully prevented membrane rigidity and both lipid and protein oxidation. Livers from ischemia–reperfusion showed histopathological alterations and positive labeling with antibodies to oxidized lipids and proteins. Melatonin reduced the severity of these morphological changes and protected against in vivo ischemia–reperfusion-induced toxicity in the liver. Therefore, melatonin might be a candidate for co-treatment for patients with hepatic vascular occlusion followed by reperfusion.
Super-Resolution Imaging Reveals the Nanoscale Distributions of Dystroglycan and Integrin Itga7 in Zebrafish Muscle Fibers
Authors: Shivanna Komala , Astumian Mary , Raut Prakash , Ngo Vinh-Nhan , Hess Samuel T. , Henry Clarissa
Published: July 2023

Cell signaling is determined partially by the localization and abundance of proteins. Dystroglycan and integrin are both transmembrane receptors that connect the cytoskeleton inside muscle cells to the extracellular matrix outside muscle cells, maintaining proper adhesion and function of muscle. The position and abundance of Dystroglycan relative to integrins is thought to be important for muscle adhesion and function. The subcellular localization and quantification of these receptor proteins can be determined at the nanometer scale by FPALM super-resolution microscopy. We used FPALM to determine localizations of Dystroglycan and integrin proteins in muscle fibers of intact zebrafish (Danio rerio). Results were consistent with confocal imaging data, but illuminate further details at the nanoscale and show the feasibility of using FPALM to quantify interactions of two proteins in a whole organism.
Wing Kinematics-Based Flight Control Strategy in Insect-Inspired Flight Systems: Deep Reinforcement Learning Gives Solutions and Inspires Controller Design in Flapping MAVs
Authors: Xue Yujing , Cai Xuefei , Xu Ru , Liu Hao
Published: July 2023

Flying insects exhibit outperforming stability and control via continuous wing flapping even under severe disturbances in various conditions of wind gust and turbulence. While conventional linear proportional derivative (PD)-based controllers are widely employed in insect-inspired flight systems, they usually fail to deal with large perturbation conditions in terms of the 6-DoF nonlinear control strategy. Here we propose a novel wing kinematics-based controller, which is optimized based on deep reinforcement learning (DRL) to stabilize bumblebee hovering under large perturbations. A high-fidelity Open AI Gym environment is established through coupling a CFD data-driven aerodynamic model and a 6-DoF flight dynamic model. The control policy with an action space of 4 is optimized using the off-policy Soft Actor–Critic (SAC) algorithm with automating entropy adjustment, which is verified to be of feasibility and robustness to achieve fast stabilization of the bumblebee hovering flight under full 6-DoF large disturbances. The 6-DoF wing kinematics-based DRL control strategy may provide an efficient autonomous controller design for bioinspired flapping-wing micro air vehicles.
Electronic Tongue for Direct Assessment of SARS-CoV-2-Free and Infected Human Saliva—A Feasibility Study
Authors: Falk Magnus , Psotta Carolin , Cirovic Stefan , Ohlsson Lars , Shleev Sergey
Published: July 2023

An electronic tongue is a powerful analytical instrument based on an array of non-selective chemical sensors with a partial specificity for data gathering and advanced pattern recognition methods for data analysis. Connecting electronic tongues with electrochemical techniques for data collection has led to various applications, mostly within sensing for food quality and environmental monitoring, but also in biomedical research for the analyses of different bioanalytes in human physiological fluids. In this paper, an electronic tongue consisting of six electrodes (viz., gold, platinum, palladium, titanium, iridium, and glassy carbon) was designed and tested in authentic (undiluted, unpretreated) human saliva samples from eight volunteers, collected before and during the COVID-19 pandemic. Investigations of 11 samples using differential pulse voltammetry and a principal component analysis allowed us to distinguish between SARS-CoV-2-free and infected authentic human saliva. This work, as a proof-of-principle demonstration, provides a new perspective for the use of electronic tongues in the field of enzyme-free electrochemical biosensing, highlighting their potential for future applications in non-invasive biomedical analyses.
An ML-Based Approach to Reconstruct Heart Rate from PPG in Presence of Motion Artifacts
Authors: Vicente-Samper José María , Tamantini Christian , Ávila-Navarro Ernesto , De La Casa-Lillo Miguel Ángel , Zollo Loredana , Sabater-Navarro José María , Cordella Francesca
Published: July 2023

The heart rate (HR) is a widely used clinical variable that provides important information on a physical user’s state. One of the most commonly used methods for ambulatory HR monitoring is photoplethysmography (PPG). The PPG signal retrieved from wearable devices positioned on the user’s wrist can be corrupted when the user is performing tasks involving the motion of the arms, wrist, and fingers. In these cases, the obtained HR is altered as well. This problem increases when trying to monitor people with autism spectrum disorder (ASD), who are very reluctant to use foreign bodies, notably hindering the adequate attachment of the device to the user. This work presents a machine learning approach to reconstruct the user’s HR signal using an own monitoring wristband especially developed for people with ASD. An experiment is carried out, with users performing different daily life activities in order to build a dataset with the measured signals from the monitoring wristband. From these data, an algorithm is applied to obtain a reliable HR value when these people are performing skill improvement activities where intensive wrist movement may corrupt the PPG.
Wearable Insulin Biosensors for Diabetes Management: Advances and Challenges
Authors: Psoma Sotiria D. , Kanthou Chryso
Published: July 2023

We present a critical review of the current progress in wearable insulin biosensors. For over 40 years, glucose biosensors have been used for diabetes management. Measurement of blood glucose is an indirect method for calculating the insulin administration dosage, which is critical for insulin-dependent diabetic patients. Research and development efforts aiming towards continuous-insulin-monitoring biosensors in combination with existing glucose biosensors are expected to offer a more accurate estimation of insulin sensitivity, regulate insulin dosage and facilitate progress towards development of a reliable artificial pancreas, as an ultimate goal in diabetes management and personalised medicine. Conventional laboratory analytical techniques for insulin detection are expensive and time-consuming and lack a real-time monitoring capability. On the other hand, biosensors offer point-of-care testing, continuous monitoring, miniaturisation, high specificity and sensitivity, rapid response time, ease of use and low costs. Current research, future developments and challenges in insulin biosensor technology are reviewed and assessed. Different insulin biosensor categories such as aptamer-based, molecularly imprinted polymer (MIP)-based, label-free and other types are presented among the latest developments in the field. This multidisciplinary field requires engagement between scientists, engineers, clinicians and industry for addressing the challenges for a commercial, reliable, real-time-monitoring wearable insulin biosensor.
Transcranial Direct Current Stimulation Effects on the Neural Substrate of Conceptual Representations
Authors: Bonnì Sonia , Borghi Ilaria , Maiella Michele , Casula Elias Paolo , Koch Giacomo , Caltagirone Carlo , Gainotti Guido
Published: July 2023

The aim of this study was to shed light on the neural substrate of conceptual representations starting from the construct of higher-order convergence zones and trying to evaluate the unitary or non-unitary nature of this construct. We used the ‘Thematic and Taxonomic Semantic (TTS) task’ to investigate (a) the neural substrate of stimuli belonging to biological and artifact categories, (b) the format of stimuli presentation, i.e., verbal or pictorial, and (c) the relation between stimuli, i.e., categorial or contextual. We administered anodal transcranial direct current stimulation (tDCS) to different brain structures during the execution of the TTS task. Twenty healthy participants were enrolled and divided into two groups, one investigating the role of the anterior temporal lobes (ATL) and the other the temporo-parietal junctions (TPJ). Each participant underwent three sessions of stimulation to facilitate a control condition and to investigate the role of both hemispheres. Results showed that ATL stimulation influenced all conceptual representations in relation to the format of presentation (i.e., left-verbal and right-pictorial). Moreover, ATL stimulation modulated living categories and taxonomic relations specifically, whereas TPJ stimulation did not influence semantic task performances.
Rumination as a Transdiagnostic Phenomenon in the 21st Century: The Flow Model of Rumination
Authors: Wong Stephanie M. Y. , Chen Eric Y. H. , Lee Michelle C. Y. , Suen Y. N. , Hui Christy L. M.
Published: July 2023

Rumination and its related mental phenomena share associated impairments in cognition, such as executive functions and attentional processes across different clinical conditions (e.g., in psychotic disorders). In recent decades, however, the notion of rumination has been increasingly narrowed to the “self-focused” type in depressive disorders. A closer review of the literature shows that rumination may be construed as a broader process characterized by repetitive thoughts about certain mental contents that interfere with one’s daily activities, not only limited to those related to “self”. A further examination of the construct of rumination beyond the narrowly focused depressive rumination would help expand intervention opportunities for mental disorders in today’s context. We first review the development of the clinical construct of rumination with regard to its historical roots and its roles in psychopathology. This builds the foundation for the introduction of the “Flow Model of Rumination (FMR)”, which conceptualizes rumination as a disruption of a smooth flow of mental contents in conscious experience that depends on the coordinated interactions between intention, memory, affect, and external events. The conceptual review concludes with a discussion of the impact of rapid technological advances (such as smartphones) on rumination. Particularly in contemporary societies today, a broader consideration of rumination not only from a cognition viewpoint, but also incorporating a human–device interaction perspective, is necessitated. The implications of the FMR in contemporary mental health practice are discussed.
The Language of Pain in the Hypermobile Ehlers–Danlos Syndrome: Metaphors as a Key to Understanding the Experience of Pain and as a Rehabilitation Tool
Authors: Camerota Filippo , Mariani Rachele , Cordiano Giulia , Di Trani Michela , Lodato Valentina , Ferraris Alessandro , Pasquini Massimo , Celletti Claudia
Published: July 2023

Ehlers–Danlos syndromes are a heterogeneous group of Heritable Connective Tissue Disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Among the different types, the hypermobile Ehlers–Danlos syndrome is the most frequent and includes generalized joint hypermobility as the major diagnostic criterion. Joint hypermobility in hypermobile Ehlers–Danlos syndrome is often associated with pain that does not always allow the use of effective pain-reducing treatments. Patients with hEDS constantly describe their pain in detail. Eighty-nine patients with hEDS diagnoses were recruited and evaluated. They were asked to describe their pain in writing. The texts were examined through Linguistic Inquiry and Word Count. Correlational analyses were conducted between pain perception and language. A comparison of high/low pain perception and the quality of metaphors was carried out. The results showed that language quality varies depending on how much pain is perceived. The greater the pain is perceived, the lesser the positive effects and the greater the negative effects and dehumanizing metaphors are being used. Moreover, a greater pain seems to be related to a verbal experience of greater isolation and less self-care. In conclusion, the use of metaphors is a useful tool for examining illness experience and may help clinicians in the rehabilitation program.
The Processing of Audiovisual Speech Is Linked with Vocabulary in Autistic and Nonautistic Children: An ERP Study
Authors: Dunham-Carr Kacie , Feldman Jacob I. , Simon David M. , Edmunds Sarah R. , Tu Alexander , Kuang Wayne , Conrad Julie G. , Santapuram Pooja , Wallace Mark T. , Woynaroski Tiffany G.
Published: July 2023

Explaining individual differences in vocabulary in autism is critical, as understanding and using words to communicate are key predictors of long-term outcomes for autistic individuals. Differences in audiovisual speech processing may explain variability in vocabulary in autism. The efficiency of audiovisual speech processing can be indexed via amplitude suppression, wherein the amplitude of the event-related potential (ERP) is reduced at the P2 component in response to audiovisual speech compared to auditory-only speech. This study used electroencephalography (EEG) to measure P2 amplitudes in response to auditory-only and audiovisual speech and norm-referenced, standardized assessments to measure vocabulary in 25 autistic and 25 nonautistic children to determine whether amplitude suppression (a) differs or (b) explains variability in vocabulary in autistic and nonautistic children. A series of regression analyses evaluated associations between amplitude suppression and vocabulary scores. Both groups demonstrated P2 amplitude suppression, on average, in response to audiovisual speech relative to auditory-only speech. Between-group differences in mean amplitude suppression were nonsignificant. Individual differences in amplitude suppression were positively associated with expressive vocabulary through receptive vocabulary, as evidenced by a significant indirect effect observed across groups. The results suggest that efficiency of audiovisual speech processing may explain variance in vocabulary in autism.
Pareto Optimized Adaptive Learning with Transposed Convolution for Image Fusion Alzheimer’s Disease Classification
Authors: Odusami Modupe , Maskeliūnas Rytis , Damaševičius Robertas
Published: July 2023

Alzheimer’s disease (AD) is a neurological condition that gradually weakens the brain and impairs cognition and memory. Multimodal imaging techniques have become increasingly important in the diagnosis of AD because they can help monitor disease progression over time by providing a more complete picture of the changes in the brain that occur over time in AD. Medical image fusion is crucial in that it combines data from various image modalities into a single, better-understood output. The present study explores the feasibility of employing Pareto optimized deep learning methodologies to integrate Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) images through the utilization of pre-existing models, namely the Visual Geometry Group (VGG) 11, VGG16, and VGG19 architectures. Morphological operations are carried out on MRI and PET images using Analyze 14.0 software and after which PET images are manipulated for the desired angle of alignment with MRI image using GNU Image Manipulation Program (GIMP). To enhance the network’s performance, transposed convolution layer is incorporated into the previously extracted feature maps before image fusion. This process generates feature maps and fusion weights that facilitate the fusion process. This investigation concerns the assessment of the efficacy of three VGG models in capturing significant features from the MRI and PET data. The hyperparameters of the models are tuned using Pareto optimization. The models’ performance is evaluated on the ADNI dataset utilizing the Structure Similarity Index Method (SSIM), Peak Signal-to-Noise Ratio (PSNR), Mean-Square Error (MSE), and Entropy (E). Experimental results show that VGG19 outperforms VGG16 and VGG11 with an average of 0.668, 0.802, and 0.664 SSIM for CN, AD, and MCI stages from ADNI (MRI modality) respectively. Likewise, an average of 0.669, 0.815, and 0.660 SSIM for CN, AD, and MCI stages from ADNI (PET modality) respectively.
Classification of Alzheimer’s Disease Using Maximal Information Coefficient-Based Functional Connectivity with an Extreme Learning Machine
Authors: Chauhan Nishant , Choi Byung-Jae
Published: July 2023

Alzheimer’s disease (AD) is a progressive chronic illness that leads to cognitive decline and dementia. Neuroimaging technologies, such as functional magnetic resonance imaging (fMRI), and deep learning approaches offer promising avenues for AD classification. In this study, we investigate the use of fMRI-based functional connectivity (FC) measures, including the Pearson correlation coefficient (PCC), maximal information coefficient (MIC), and extended maximal information coefficient (eMIC), combined with extreme learning machines (ELM) for AD classification. Our findings demonstrate that employing non-linear techniques, such as MIC and eMIC, as features for classification yields accurate results. Specifically, eMIC-based features achieve a high accuracy of 94% for classifying cognitively normal (CN) and mild cognitive impairment (MCI) individuals, outperforming PCC (81%) and MIC (85%). For MCI and AD classification, MIC achieves higher accuracy (81%) compared to PCC (58%) and eMIC (78%). In CN and AD classification, eMIC exhibits the best accuracy of 95% compared to MIC (90%) and PCC (87%). These results underscore the effectiveness of fMRI-based features derived from non-linear techniques in accurately differentiating AD and MCI individuals from CN individuals, emphasizing the potential of neuroimaging and machine learning methods for improving AD diagnosis and classification.
Neuropsychological Characterization of Autosomal Recessive Intellectual Developmental Disorder 59 Associated with IMPA1 (MRT59)
Authors: Pessoa Andre Luiz Santos , Quesada Andrea Amaro , Nóbrega Paulo Ribeiro , Viana Ana Priscila Oliveira , de Oliveira Kécia Tavares , Figueiredo Thalita , Santos Silvana , Kok Fernando
Published: July 2023

Biallelic loss of function of IMPA1 causes autosomal recessive intellectual developmental disorder 59 (MRT59, OMIM #617323). MRT59 has been reported to present with significant intellectual disability and disruptive behavior, but little is known about the neurocognitive pattern of those patients. Thus, the aims of this study were: (1) to assess the cognitive profile of these patients, and (2) to evaluate their functional dependence levels. Eighteen adults, aged 37 to 89 years, participated in this study: nine MRT59 patients, five heterozygous carriers and four non-carrier family members. All of them were from a consanguineous family living in Northeast Brazil. All IMPA1 patients had the (c.489_493dupGGGCT) pathogenic variant in homozygosis. For cognitive assessment, the WASI battery was applied in nine MRT59 patients and compared to heterozygous carriers and non-carrier family members. Functional dependence was evaluated using the functional independence measure (FIM). Patients showed moderate to severe intellectual disability and severe functional disabilities. Heterozygous carriers did not differ from non-carriers. MRT59 patients should be followed up by health professionals in an interdisciplinary way to understand their cognitive disabilities and functional needs properly.