bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitation Technologies for Chronic Conditions: Will We Sink or Swim?
Authors: LaMarca Amber , Tse Ivy , Keysor Julie
Published: October 2023

Introduction: Chronic conditions such as stroke, Parkinson’s disease, spinal cord injury, multiple sclerosis, vestibular disorders, chronic pain, arthritis, diabetes, chronic obstructive pulmonary disease (COPD), and heart disease are leading causes of disability among middle-aged and older adults. While evidence-based treatment can optimize clinical outcomes, few people with chronic conditions engage in the recommended levels of exercise for clinical improvement and successful management of their condition. Rehabilitation technologies that can augment therapeutic care—i.e., exoskeletons, virtual/augmented reality, and remote monitoring—offer the opportunity to bring evidence-based rehabilitation into homes. Successful integration of rehabilitation techniques at home could help recovery and access and foster long term self-management. However, widespread uptake of technology in rehabilitation is still limited, leaving many technologies developed but not adopted. Methods: In this narrative review, clinical need, efficacy, and obstacles and suggestions for implementation are discussed. The use of three technologies is reviewed in the management of the most prevalent chronic diseases that utilize rehabilitation services, including common neurological, musculoskeletal, metabolic, pulmonary, and cardiac conditions. The technologies are (i) exoskeletons, (ii) virtual and augmented reality, and (iii) remote monitoring. Results: Effectiveness evidence backing the use of technology in rehabilitation is growing but remains limited by high heterogeneity, lack of long-term outcomes, and lack of adoption outcomes. Conclusion: While rehabilitation technologies bring opportunities to bridge the gap between clinics and homes, there are many challenges with adoption. Hybrid effectiveness and implementation trials are a possible path to successful technology development and adoption.
Fair Healthcare Practices in Orthopedics Assessed with a New Framework
Authors: Moldovan Flaviu , Moldovan Liviu
Published: October 2023

Background and Objectives: Healthcare systems are supported by the European ideology to develop their egalitarian concerns and to encourage the correct and fair behavior of medical staff. By integrating fair healthcare practices into sustainability, this requirement is addressed. In this research, our objective is to develop and validate, in the current activity of healthcare facilities, a new instrument for evaluating fair healthcare practices as a component of social responsibility integrated into sustainability. Materials and Methods: The research methods consist of deciding the domains of a new framework that integrates fair healthcare practices; the collection of the most recent fair healthcare practices reported by healthcare facilities around the world; elaboration of the contents and evaluation grids of the indicators; the integration of indicators related to fair healthcare practices in the matrix of the new framework for sustainable development; validation of the theoretical model at an orthopedic hospital. Results: The theoretical model of the new framework is composed of five domains: organizational management, provision of sustainable medical care services, economic, environmental, and social. The last domain is developed on the structure of the seven subdomains of the social responsibility standard ISO 26000. The seven indicators that describe fair healthcare practices are attitudes of the profession towards accreditation, effective intervention application, promoting a culture of patient safety, characteristics that affect the effectiveness of transfers, effective healthcare practices, feedback to medical staff, safety checklists. The new reference framework was implemented and validated in practice at an emergency hospital with an orthopedic profile. Conclusions: The practical implementation highlighted the usefulness of the new reference framework, its compatibility, and the possibility of integration with the reference frameworks for the evaluation of European hospitals, with the national legislation for the accreditation of hospitals and outpatient units, as well as with the ISO 9001 standard regarding the implementation of quality management systems. Its added value consists in promoting sustainable development by orienting staff, patients, and interested parties towards sustainability.
Characterization and Degradation Analysis of Pigments in Paintings by Martiros Sarian: Attenuated Total Reflection Fourier Transform Infrared Spectroscopic Imaging and X-ray Fluorescence Approach
Authors: Liu Guan-Lin , Kazarian Sergei G.
Published: October 2023

This paper presents a preliminary scientific investigation of pigments used by Martiros Sarian, a prominent Armenian artist known for his vibrant and evocative paintings. The study focuses on five of Sarian’s paintings from different periods of his career, namely, Morning in Stavrino, Arabian Dancer, Caravan, Yerevan Zangu River, and Kirovakan, dated between 1909 and 1948. Non-destructive techniques, including micro-attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic imaging and X-ray fluorescence (XRF), were employed to characterize the pigments in the samples extracted from these paintings. The results reveal the presence of various pigments, including ultramarine blue, cobalt blue, cobalt cerulean blue, viridian, emerald green, cobalt green, celadonite green, cadmium yellow, chrome yellow, Venetian red, yellow ochre, red ochre, lead white, zinc white, and calcium carbonate. Additionally, metal carboxylates and oxalates, degradation products associated with the paint layers, were observed and discussed. The findings contribute to a better understanding of Sarian’s artistic technique and provide valuable insights for the conservation and restoration of his artworks.
The Endophytic Entomopathogenic Fungus Beauveria bassiana Alleviates Adverse Effects of Salt Stress in Potato Plants
Authors: Tomilova Oksana G. , Kryukova Natalia A. , Efimova Marina V. , Kolomeichuk Liliya V. , Kovtun Irina S. , Glupov Victor V.
Published: October 2023

The considerable decrease in crop productivity associated with the expansion of saline soils is an acute problem in agriculture. Endophytic fungi positively affect plant fitness under salinity conditions. The effects of potato inoculation with the conidia of the Beauveria bassiana strain Sar-31 on growth (the weight of fresh and dry biomass, shoot and root length, numbers of stolons and leaves, and the leaf surface) and physiological indices (the concentration of pigments, free proline and malondialdehyde, and antioxidant enzymes’ activity) were evaluated under moderate chloride salinity (100 mM). The results indicated that the plant’s association with the fungus mitigated the negative impact of salinity probably because of the activation of antioxidant enzymes and accumulation of free proline in potato tissues. Moreover, under the influence of B. bassiana Sar-31, the number of stolons significantly increased, which is one of the main characteristics of potato as an agricultural crop. Thus, Sar-31 may be a promising candidate for further investigation of its ability to stimulate growth and increase the stress tolerance of potato plants.
Portable Technology for Obtaining Plasma-Activated Water to Stimulate the Growth of Spruce and Strawberry Plants
Authors: Danileyko Yury K. , Belov Sergej V. , Egorov Aleksej B. , Lukanin Vladimir I. , Apasheva Ludmila M. , Ovcharenko Elena N. , Lobanov Anton V. , Astashev Maxim E. , Simakin Alexander V. , Shkirin Alexey V. , Konchekov Evgeny M. , Zakharov Dmitry A. , Stepanova Eugenia V. , Paskhin Mark O. , Kazantseva Dina V. , Pobedonostsev Roman V. , Sukhov Vladimir , Dorokhov Alexey S. , Izmailov Andrey Yu.
Published: October 2023

A method for stimulating the growth of spruce and strawberry in the early phases of development is proposed. A technology for obtaining plasma-activated water (PAW) with the help of a glow discharge plasma generator was developed. The method is proposed for increasing the shelf life of PAW by adding an aqueous colloid of polyvinylpyrralidone (PVP) polymer. It is shown that after treatment with a PAW + PVP mixture, the seeds have a higher percentage of germination, the plants develop faster in the early stages, and they are more viable. At the physicochemical level, after seed treatment with PAW + PVP, higher rates of metabolite outflow from seeds are observed. At the biological level, seed treatment with PAW + PVP leads to a slight decrease in the activity of antioxidant enzymes and a higher content of chlorophylls in the leaves, and a slightly higher assimilation rate is observed. In the leaves, there is higher content of the growth hormone indole-3-acetic acid (IAA), whereas the content of the growth-inhibiting hormone abscisic acid decreases. The use of a stimulating drug based on the composition of an aqueous solution activated by plasma and polyvinylpyrrolidone (PAW + PVP) polymer can be an effective means of a single pre-sowing treatment of spruce seeds in solving the problem of reforestation and strawberry during plant propagation.
A Comparative Analysis of Lung Cancer Incidence and Tobacco Consumption in Canada, Norway and Sweden: A Population-Based Study
Authors: Chen Jing
Published: October 2023

Risk factors for developing lung cancer include tobacco smoking, exposure to second-hand smoke, radon gas, asbestos and other carcinogens, as well as air pollution and aging. Canada, Norway and Sweden are three Arctic countries that are very similar in socioeconomic status, similar in the social determinants of health and many environmental factors, including current smoking rates. However, lung cancer incidence rates differ significantly among the three countries. Since tobacco smoking is the principal risk factor for developing lung cancer, and there is a long lag time between tobacco consumption and lung cancer incidence at the population average level, a comparative analysis is conducted with historical data available publicly in the three countries to demonstrate how tobacco consumption in the past impacts lung cancer incidence decades late. The analysis shows that lung cancer incidence rates increase proportionally with the increasing tobacco consumption rates with a lag time of 20–30 years. On average, one more cigarette smoked per person per day can increase lung cancer cases by 2 to 5 per 100,000 population.
Automated Generation of Room Usage Semantics from Point Cloud Data
Authors: Cai Guoray , Pan Yimu
Published: October 2023

Room usage semantics in models of large indoor environments such as public buildings and business complex are critical in many practical applications, such as health and safety regulations, compliance, and emergency response. Existing models such as IndoorGML have very limited semantic information at room level, and it remains difficult to capture semantic knowledge of rooms in an efficient way. In this paper, we formulate the task of generating rooms usage semantics as a special case of room classification problems. Although methods for room classification tasks have been developed in the field of social robotics studies and indoor maps, they do not deal with room usage and occupancy aspects of semantics, and they ignore the value of furniture objects in understanding room usage. We propose a method for generating room usage semantics based on the spatial configuration of room objects (e.g., furniture, walls, windows, doors). This method uses deep learning architecture to support a room usage classifier that can learn spatial configuration features directly from semantically labelled point cloud (SLPC) data that represent room scenes with furniture objects in place. We experimentally assessed the capacity of our method in classifying rooms in office buildings using the Stanford 3D (S3DIS) dataset. The results showed that our method was able to achieve an overall accuracy of 91% on top-level room categories (e.g., offices, conference rooms, lounges, storage) and above 97% accuracy in recognizing offices and conference rooms. We further show that our classifier can distinguish fine-grained categories of of offices and conference rooms such as shared offices, single-occupancy offices, large conference rooms, and small conference rooms, with comparable intelligence to human coders. In general, our method performs better on rooms with a richer variety of objects than on rooms with few or no furniture objects.
A Hybrid Discrete Artificial Bee Colony Algorithm Based on Label Similarity for Solving Point-Feature Label Placement Problem
Authors: Cao Wen , Xu Jiaqi , Zhang Yong , Zhao Siqi , Xu Chu , Wu Xiaofeng
Published: October 2023

The artificial bee colony algorithm (ABC) is a promising metaheuristic algorithm for continuous optimization problems, but it performs poorly in solving discrete problems. To address this issue, this paper proposes a hybrid discrete artificial bee colony (HDABC) algorithm based on label similarity for the point-feature label placement (PFLP) problem. Firstly, to better adapt to PFLP, we have modified the update mechanism for employed bees and onlooker bees. Employed bees learn the label position of the better individuals, while onlooker bees perform dynamic probability searches using two neighborhood operators. Additionally, the onlooker bees’ selection method selects the most promising solutions based on label similarity, which improves the algorithm’s search capabilities. Finally, the Metropolis acceptance strategy is replaced by the original greedy acceptance strategy to avoid the premature convergence problem. Systematic experiments are conducted to verify the effectiveness of the neighborhood solution generation method, the selection operation based on label similarity, and the Metropolis acceptance strategy in this paper. In addition, experimental comparisons were made at different instances and label densities. The experimental results show that the algorithm proposed in this paper is better or more competitive with the compared algorithm.
The Dynamics of Nerve Degeneration and Regeneration in a Healthy Milieu and in Diabetes
Authors: Dahlin Lars B.
Published: October 2023

Appropriate animal models, mimicking conditions of both health and disease, are needed to understand not only the biology and the physiology of neurons and other cells under normal conditions but also under stress conditions, like nerve injuries and neuropathy. In such conditions, understanding how genes and different factors are activated through the well-orchestrated programs in neurons and other related cells is crucial. Knowledge about key players associated with nerve regeneration intended for axonal outgrowth, migration of Schwann cells with respect to suitable substrates, invasion of macrophages, appropriate conditioning of extracellular matrix, activation of fibroblasts, formation of endothelial cells and blood vessels, and activation of other players in healthy and diabetic conditions is relevant. Appropriate physical and chemical attractions and repulsions are needed for an optimal and directed regeneration and are investigated in various nerve injury and repair/reconstruction models using healthy and diabetic rat models with relevant blood glucose levels. Understanding dynamic processes constantly occurring in neuropathies, like diabetic neuropathy, with concomitant degeneration and regeneration, requires advanced technology and bioinformatics for an integrated view of the behavior of different cell types based on genomics, transcriptomics, proteomics, and imaging at different visualization levels. Single-cell-transcriptional profile analysis of different cells may reveal any heterogeneity among key players in peripheral nerves in health and disease.
Prevalence of Congenital Color Vision Deficiency in Southern Taiwan and Detection of Female Carriers by Visual Pigment Gene Analysis
Authors: Kuo Hsi-Kung , Tsao Shih-Ting , Wu Pei-Chang
Published: October 2023

This study aimed to investigate the prevalence of color vision deficiencies (CVDs) and determine whether carriers could be detected by analyzing the visual pigment genes. Materials and Methods: The data of students who underwent routine CVD screening using the Ishihara color test in Kaohsiung, Southern Taiwan were analyzed. Furthermore, the DNA samples of 80 randomly selected females and four obligate carriers were analyzed. The most upstream genes, downstream genes, and the most downstream genes in the red/green pigment gene arrays were amplified separately using polymerase chain reaction (PCR), and exon 5 of each gene was analyzed. The prevalence of congenital red–green CVD in this study was 3.46% in males and 0.14% in females. The PCR analysis of the first gene, downstream gene, and last gene revealed normal patterns in 73 normal cases. Seven unusual patterns were detected in two proton carriers and five deutan carriers. Among the randomly selected females, 8.8% (7/80) were CVD carriers. The prevalence of CVD among male Taiwanese students in this study was 3.46%. Female carriers of congenital CVD can be identified by molecular analysis of the visual pigment genes. The proportion of CVD carriers among the randomly selected females was 8.8%, which was slightly higher than expected and further studies are warranted.
Plasma miR-486-5p Expression Is Upregulated in Atrial Fibrillation Patients with Broader Low-Voltage Areas
Authors: Cebro-Márquez María , Rodríguez-Mañero Moisés , Serrano-Cruz Valentina , Vilar-Sánchez Marta E. , González-Melchor Laila , García-Seara Javier , Martínez-Sande José Luis , Aragón-Herrera Alana , Martínez-Monzonís María Amparo , González-Juanatey José Ramón , Lage Ricardo , Moscoso Isabel
Published: October 2023

Atrial fibrillation (AF) is the most common arrhythmia worldwide, affecting 1% of the population over 60 years old. The incidence and prevalence of AF are increasing globally, representing a relevant health problem, suggesting that more advanced strategies for predicting risk stage are highly needed. miRNAs mediate several processes involved in AF. Our aim was to identify miRNAs with a prognostic value as biomarkers in patients referred for AF ablation and its association with LVA extent, based on low-voltage area (LVA) maps. In this study, we recruited 44 AF patients referred for catheter ablation. We measured the expression of 84 miRNAs in plasma from peripheral blood in 3 different groups based on LVA extent. Expression analysis showed that miR-486-5p was significantly increased in patients with broader LVA (4-fold, p = 0.0002; 5-fold, p = 0.0001). Receiver operating characteristic curve analysis showed that miR-486-5p expression could predict atrium LVA (AUC, 0.8958; p = 0.0015). Also, miR-486-5p plasma levels were associated with AF-type (AUC, 0.7137; p = 0.0453). In addition, miR-486-5p expression was positively correlated with LVA percentage, left atrial (LA) area, and LA volume (r = 0.322, p = 0.037; r = 0.372, p = 0.015; r = 0.319, p = 0.045, respectively). These findings suggest that miR-486-5p expression might have prognostic significance in LVA extent in patients with AF.
Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead
Authors: Datta Sayantap , Cao Wangjia , Skillman Mikayla , Wu Mingfu
Published: October 2023

Hypoplastic left heart syndrome (HLHS) is a lethal congenital heart disease (CHD) affecting 8–25 per 100,000 neonates globally. Clinical interventions, primarily surgical, have improved the life expectancy of the affected subjects substantially over the years. However, the etiological basis of HLHS remains fundamentally unclear to this day. Based upon the existing paradigm of studies, HLHS exhibits a multifactorial mode of etiology mediated by a complicated course of genetic and signaling cascade. This review presents a detailed outline of the HLHS phenotype, the prenatal and postnatal risks, and the signaling and molecular mechanisms driving HLHS pathogenesis. The review discusses the potential limitations and future perspectives of studies that can be undertaken to address the existing scientific gap. Mechanistic studies to explain HLHS etiology will potentially elucidate novel druggable targets and empower the development of therapeutic regimens against HLHS in the future.
Differential Expression of Proteins Associated with Bipolar Disorder as Identified Using the PeptideShaker Software
Authors: Seregin Alexander A. , Smirnova Liudmila P. , Dmitrieva Elena M. , Zavialova Maria G. , Simutkin German G. , Ivanova Svetlana A.
Published: October 2023

The prevalence of bipolar disorder (BD) in modern society is growing rapidly, but due to the lack of paraclinical criteria, its differential diagnosis with other mental disorders is somewhat challenging. In this regard, the relevance of proteomic studies is increasing due to the development of methods for processing large data arrays; this contributes to the discovery of protein patterns of pathological processes and the creation of new methods of diagnosis and treatment. It seems promising to search for proteins involved in the pathogenesis of BD in an easily accessible material—blood serum. Sera from BD patients and healthy individuals were purified via affinity chromatography to isolate 14 major proteins and separated using 1D SDS-PAGE. After trypsinolysis, the proteins in the samples were identified via HPLC/mass spectrometry. Mass spectrometric data were processed using the OMSSA and X!Tandem search algorithms using the UniProtKB database, and the results were analyzed using PeptideShaker. Differences in proteomes were assessed via an unlabeled NSAF-based analysis using a two-tailed Bonferroni-adjusted t-test. When comparing the blood serum proteomes of BD patients and healthy individuals, 10 proteins showed significant differences in NSAF values. Of these, four proteins were predominantly present in BD patients with the maximum NSAF value: 14-3-3 protein zeta/delta; ectonucleoside triphosphate diphosphohydrolase 7; transforming growth factor-beta-induced protein ig-h3; and B-cell CLL/lymphoma 9 protein. Further exploration of the role of these proteins in BD is warranted; conducting such studies will help develop new paraclinical criteria and discover new targets for BD drug therapy.
Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder
Authors: Fernández-Pereira Carlos , Penedo Maria Aránzazu , Rivera-Baltanás Tania , Pérez-Márquez Tania , Alves-Villar Marta , Fernández-Martínez Rafael , Veiga César , Salgado-Barreira Ángel , Prieto-González José María , Ortolano Saida , Olivares José Manuel , Agís-Balboa Roberto Carlos
Published: October 2023

The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.
Dysbiotic Gut Microbiota-Derived Metabolites and Their Role in Non-Communicable Diseases
Authors: Tan Jian , Taitz Jemma , Nanan Ralph , Grau Georges , Macia Laurence
Published: October 2023

Dysbiosis, generally defined as the disruption to gut microbiota composition or function, is observed in most diseases, including allergies, cancer, metabolic diseases, neurological disorders and diseases associated with autoimmunity. Dysbiosis is commonly associated with reduced levels of beneficial gut microbiota-derived metabolites such as short-chain fatty acids (SCFA) and indoles. Supplementation with these beneficial metabolites, or interventions to increase their microbial production, has been shown to ameliorate a variety of inflammatory diseases. Conversely, the production of gut ‘dysbiotic’ metabolites or by-products by the gut microbiota may contribute to disease development. This review summarizes the various ‘dysbiotic’ gut-derived products observed in cardiovascular diseases, cancer, inflammatory bowel disease, metabolic diseases including non-alcoholic steatohepatitis and autoimmune disorders such as multiple sclerosis. The increased production of dysbiotic gut microbial products, including trimethylamine, hydrogen sulphide, products of amino acid metabolism such as p-Cresyl sulphate and phenylacetic acid, and secondary bile acids such as deoxycholic acid, is commonly observed across multiple diseases. The simultaneous increased production of dysbiotic metabolites with the impaired production of beneficial metabolites, commonly associated with a modern lifestyle, may partially explain the high prevalence of inflammatory diseases in western countries.
Proximal Tubular Lats2 Ablation Exacerbates Ischemia/Reperfusion Injury (IRI)-Induced Renal Maladaptive Repair through the Upregulation of P53
Authors: Zhang Chi , Zheng Zhihuang , Xu Kexin , Cheng Guozhe , Wu Huijuan , Liu Jun
Published: October 2023

The Hippo pathway mediates renal maladaptive repair after acute kidney injury (AKI), which has been considered a driving force in the progression to chronic kidney disease (CKD). LATS2, a core kinase of the Hippo pathway, exerts non-Hippo-dependent functions in the regulation of the cell cycle and cell fate, providing new insights into AKI and further repair. However, its role remains unknown. Here, we utilized a proximal tubular Lats2 conditional knockout mouse strain (Lats2-CKO) to evaluate the effect of LATS2 deficiency on ischemia/reperfusion-induced AKI-to-CKD transition. Lats2-CKO mice presented with more severe tubular maladaptive repair, inflammatory infiltration, interstitial fibrosis, and apoptosis following AKI. Importantly, we discovered that Lats2 ablation caused the activation of p53, with increased levels of cellular apoptotic molecules (p21, Bax, and cleaved caspase-3), and decreased levels of anti-apoptotic molecules (Bcl-2 and Bcl-xL). Pifithirin-α (p53 inhibitor) effectively attenuated renal fibrosis, inflammation, and apoptosis in Lats2-CKO mice after AKI. Consistently, in vitro Lats2 overexpression decreased p53, p21, Bax and cleaved caspase 3 expression after hypoxia/reoxygenation (H/R) treatment. Of note, the phosphorylation of MDM2, which promotes the ubiquitination degradation of p53, at site Ser186 was decreased in Lats2-CKO kidneys, but increased by Lats2 overexpression in vitro. Therefore, LATS2 deficiency aggravated ischemia/reperfusion injury (IRI)-induced maladaptive repair via regulating the tubular MDM2-p53 axis in AKI-to-CKD transition.
Comparative Analysis of Plastomes in Elsholtzieae: Phylogenetic Relationships and Potential Molecular Markers
Authors: Tu Xiong-De , Zhao Zhuang , Zhou Cheng-Yuan , Zeng Meng-Yao , Gao Xu-Yong , Li Ming-He , Liu Zhong-Jian , Chen Shi-Pin
Published: October 2023

The Elsholtzieae, comprising ca. 7 genera and 70 species, is a small tribe of Lamiaceae (mint family). Members of Elsholtzieae are of high medicinal, aromatic, culinary, and ornamentals value. Despite the rich diversity and value of Elsholtzieae, few molecular markers or plastomes are available for phylogenetics. In the present study, we employed high-throughput sequencing to assemble two Mosla plastomes, M. dianthera and M. scabra, for the first time, and compared with other plastomes of Elsholtzieae. The plastomes of Elsholtzieae exhibited a quadripartite structure, ranging in size from 148,288 bp to 152,602 bp. Excepting the absence of the pseudogene rps19 in Elsholtzia densa, the exhaustive tally revealed the presence of 132 genes (113 unique genes). Among these, 85 protein-coding genes (CDS), 37 tRNA genes, 8 rRNA genes, and 2 pseudogenes (rps19 and ycf1) were annotated. Comparative analyses showed that the plastomes of these species have minor variations at the gene level. Notably, the E. eriostchya plastid genome exhibited increased GC content regions in the LSC and SSC, resulting in an increased overall GC content of the entire plastid genome. The E. densa plastid genome displayed modified boundaries due to inverted repeat (IR) contraction. The sequences of CDS and intergenic regions (IGS) with elevated variability were identified as potential molecular markers for taxonomic inquiries within Elsholtzieae. Phylogenetic analysis indicated that four genera formed monophyletic entities, with Mosla and Perilla forming a sister clade. This clade was, in turn, sister to Collinsonia, collectively forming a sister group to Elsholtzia. Both CDS, and CDS + IGS could construct a phylogenetic tree with stronger support. These findings facilitate species identification and DNA barcoding investigations in Elsholtzieae and provide a foundation for further exploration and resource utilization within this tribe.
The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission—An Up-to-Date Review
Authors: Pańczyszyn-Trzewik Patrycja , Czechowska Ewelina , Stachowicz Katarzyna , Sowa-Kućma Magdalena
Published: October 2023

Depression is a serious neuropsychiatric disease affecting an increasing number of people worldwide. Cognitive deficits (including inattention, poor memory, and decision-making difficulties) are common in the clinical picture of depression. Cognitive impairment has been hypothesized to be one of the most important components of major depressive disorder (MDD; referred to as clinical depression), although typical cognitive symptoms are less frequent in people with depression than in people with schizophrenia or bipolar disorder (BD; sometimes referred to as manic-depressive disorder). The importance of α-Klotho in the aging process has been well-documented. Growing evidence points to the role of α-Klotho in regulating other biological functions, including responses to oxidative stress and the modulation of synaptic plasticity. It has been proven that a Klotho deficit may contribute to the development of various nervous system pathologies, such as behavioral disorders or neurodegeneration. Given the growing evidence of the role of α-Klotho in depression and cognitive impairment, it is assumed that this protein may be a molecular link between them. Here, we provide a research review of the role of α-Klotho in depression and cognitive impairment. Furthermore, we propose potential mechanisms (related to oxidative stress and glutamatergic transmission) that may be important in α-Klotho-mediated regulation of mental and cognitive function.
Necrotic Cells from Head and Neck Carcinomas Release Biomolecules That Are Activating Toll-like Receptor 3
Authors: Vasiljevic Tea , Tarle Marko , Hat Koraljka , Luksic Ivica , Mikulandra Martina , Busson Pierre , Matijevic Glavan Tanja
Published: October 2023

Tumor necrosis is a recurrent characteristic of head and neck squamous cell carcinomas (HNSCCs). There is a need for more investigations on the influence of biomolecules released by these necrotic foci in the HNSCC tumor microenvironment. It is suspected that a fraction of the biomolecules released by necrotic cells are damage-associated molecular patterns (DAMPs), which are known to be natural endogenous ligands of Toll-like receptors (TLRs), including, among others, proteins and nucleic acids. However, there has been no direct demonstration that biomolecules released by HNSCC necrotic cells can activate TLRs. Our aim was to investigate whether some of these molecules could behave as agonists of the TLR3, either in vitro or in vivo. We chose a functional approach based on reporter cell exhibiting artificial TLR3 expression and downstream release of secreted alkaline phosphatase. The production of biomolecules activating TLR3 was first investigated in vitro using three HNSCC cell lines subjected to various pronecrotic stimuli (external irradiation, serum starvation, hypoxia and oxidative stress). TLR3 agonists were also investigated in necrotic tumor fluids from five oral cancer patients and three mouse tumor grafts. The release of biomolecules activating TLR3 was demonstrated for all three HNSCC cell lines. External irradiation was the most consistently efficient stimulus, and corresponding TLR3 agonists were conveyed in extracellular vesicles. TLR3-stimulating activity was detected in the fluids from all five patients and three mouse tumor grafts. In most cases, this activity was greatly reduced by RNAse pretreatment or TLR3 blocking antibodies. Our data indicate that TLR3 agonists are consistently present in necrotic fluids from HNSCC cells and mainly made of dsRNA fragments. These endogenous agonists may induce TLR3, which might lead to a protumorigenic effect. Regarding methodological aspects, our study demonstrates that direct investigations—including functional testing—can be performed on necrotic fluids from patient tumors.
Gut Microbiota Patterns in Patients with Non-Alcoholic Fatty Liver Disease: A Comprehensive Assessment Using Three Analysis Methods
Authors: Korobeinikova Anna V. , Zlobovskaya Olga A. , Sheptulina Anna F. , Ashniev German A. , Bobrova Maria M. , Yafarova Adel A. , Akasheva Dariga U. , Kabieva Shuanat Sh. , Bakoev Siroj Yu. , Zagaynova Anjelica V. , Lukashina Maria V. , Abramov Ivan A. , Pokrovskaya Mariya S. , Doludin Yurii V. , Tolkacheva Larisa R. , Kurnosov Alexander S. , Zyatenkova Elena V. , Lavrenova Evgeniya A. , Efimova Irina A. , Glazunova Evgeniya V. , Kiselev Anton R. , Shipulin German A. , Kontsevaya Anna V. , Keskinov Anton A. , Yudin Vladimir S. , Makarov Valentin V. , Drapkina Oxana M. , Yudin Sergey M.
Published: October 2023

Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in Collinsella sp. and Oscillospiraceae for the control samples and enrichment in Lachnospiraceae (and in particular Dorea sp.) and Veillonellaceae in NAFLD. The families, Bifidobacteriaceae, Lactobacillaceae, and Enterococcaceae (particularly Enterococcus faecium and Enterococcus faecalis), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in Candida krusei and a decrease in Bacteroides uniformis for NAFLD patients were detected using MALDI-TOF-MS. An increase in Gracilibacteraceae, Chitinophagaceae, Pirellulaceae, Erysipelatoclostridiaceae, Muribaculaceae, and Comamonadaceae, and a decrease in Acidaminococcaceae in NAFLD were observed with 16S NGS, and enrichment in Fusobacterium nucleatum was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.
The PKG Inhibitor CN238 Affords Functional Protection of Photoreceptors and Ganglion Cells against Retinal Degeneration
Authors: Tolone Arianna , Haq Wadood , Fachinger Alexandra , Roy Akanksha , Kesh Sandeep , Rentsch Andreas , Wucherpfennig Sophie , Zhu Yu , Groten John , Schwede Frank , Tomar Tushar , Herberg Friedrich W. , Nache Vasilica , Paquet-Durand François
Published: October 2023

Hereditary retinal degeneration (RD) is often associated with excessive cGMP signalling in photoreceptors. Previous research has shown that inhibition of cGMP-dependent protein kinase G (PKG) can reduce photoreceptor loss in two different RD animal models. In this study, we identified a PKG inhibitor, the cGMP analogue CN238, which preserved photoreceptor viability and functionality in rd1 and rd10 mutant mice. Surprisingly, in explanted retinae, CN238 also protected retinal ganglion cells from axotomy-induced retrograde degeneration and preserved their functionality. Furthermore, kinase activity-dependent protein phosphorylation of the PKG target Kv1.6 was reduced in CN238-treated rd10 retinal explants. Ca2+-imaging on rd10 acute retinal explants revealed delayed retinal ganglion cell repolarization with CN238 treatment, suggesting a PKG-dependent modulation of Kv1-channels. Together, these results highlight the strong neuroprotective capacity of PKG inhibitors for both photoreceptors and retinal ganglion cells, illustrating their broad potential for the treatment of retinal diseases and possibly neurodegenerative diseases in general.
Regulation Mechanism of Dopamine Receptor 1 in Low Temperature Response of Marsupenaeus japonicus
Authors: Ren Xianyun , Bian Xueqiong , Shao Huixin , Jia Shaoting , Yu Zhenxing , Liu Ping , Li Jian , Li Jitao
Published: October 2023

Dopamine receptors (DARs) are important transmembrane receptors responsible for receiving extracellular signals in the DAR-mediated signaling pathway, and are involved in a variety of physiological functions. Herein, the D1 DAR gene from Marsupenaeus japonicus (MjDAD1) was identified and characterized. The protein encoded by MjDAD1 has the typical structure and functional domains of the G-protein coupled receptor family. MjDAD1 expression was significantly upregulated in the gills and hepatopancreas after low temperature stress. Moreover, double-stranded RNA-mediated silencing of MjDAD1 significantly changed the levels of protein kinases (PKA and PKC), second messengers (cyclic AMP (cAMP), cyclic cGMP, calmodulin, and diacyl glycerol), and G-protein effectors (adenylate cyclase and phospholipase C). Furthermore, MjDAD1 silencing increased the apoptosis rate of gill and hepatopancreas cells. Thus, following binding to their specific receptors, G-protein effectors are activated by MjDAD1, leading to DAD1-cAMP/PKA pathway-mediated regulation of caspase-dependent mitochondrial apoptosis. We suggest that MjDAD1 is indispensable for the environmental adaptation of M. japonicus.
Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation
Authors: Greaves Ronda F. , Kumar Monish , Mawad Nazha , Francescon Alberto , Le Chris , O’Connell Michele , Chi James , Pitt James
Published: October 2023

There are mixed reports on the inclusion and use of 21 deoxycortisol (21DF) as the primary decision marker for classical 21-hydroxylase deficiency. We hypothesize that this may be due to insufficient recognition of the presence and chromatographic separation of isomeric steroids. The aim of this study was to determine the comparative utility of 21DF for screening and diagnosis of CAH due to classical 21-hydroxylase deficiency using a second-tier LC–MS/MS method that included the separation of isomeric steroids to 17OHP and 21DF. For each baby sample, one 3.2 mm dried blood spot was eluted in a methanolic solution containing isotopically matched internal standards. Data were interrogated by univariate and receiver operator characteristic analysis. Steroid profile results were generated for 924 non-CAH baby samples (median gestational age 37 weeks, range 22 to 43 weeks) and 17 babies with 21-hydroxylase deficiency. The ROC curves demonstrated 21DF to have the best sensitivity and specificity for the diagnosis of classical 21-hydroxylase deficiency with an AUC = 1.0. The heatmap showed the very strong correlation (r = 0.83) between 17OHP and 21DF. Our data support 21DF as a robust marker for CAH due to 21-hydroxylase deficiency. We recommend that 21DF be incorporated into routine newborn screening panels as part of the second-tier LC–MS/MS method, follow-up plasma steroid panels, and external quality assurance material.
DAEM: A Data- and Application-Aware Error Analysis Methodology for Approximate Adders
Authors: Hanif Muhammad Abdullah , Hafiz Rehan , Shafique Muhammad
Published: October 2023

Approximate adders are some of the fundamental arithmetic operators that are being employed in error-resilient applications, to achieve performance/energy/area gains. This improvement usually comes at the cost of some accuracy and, therefore, requires prior error analysis, to select an approximate adder variant that provides acceptable accuracy. Most of the state-of-the-art error analysis techniques for approximate adders assume input bits and operands to be independent of one another, while some also assume the operands to be uniformly distributed. In this paper, we analyze the impact of these assumptions on the accuracy of error estimation techniques, and we highlight the need to address these assumptions, to achieve better and more realistic quality estimates. Based on our analysis, we propose DAEM, a data- and application-aware error analysis methodology for approximate adders. Unlike existing error analysis models, we neither assume the adder operands to be uniformly distributed nor assume them to be independent. Specifically, we use 2D joint input probability mass functions (PMFs), populated using sample data, in order to incorporate the data and application knowledge in the analysis. These 2D joint input PMFs, along with 2D error maps of approximate adders, are used to estimate the error PMF of an adder network. The error PMF is then utilized to compute different error measures, such as the mean squared error (MSE) and mean error distance (MED). We evaluate the proposed error analysis methodology on audio and video processing applications, and we demonstrate that our methodology provides error estimates having a better correlation with the simulation results, as compared to the state-of-the-art techniques.
Remote Moderated Usability Testing of a Mobile Phone App for Remote Monitoring of Pregnant Women at High Risk of Preeclampsia in Karachi, Pakistan
Authors: Shahil-Feroz Anam , Yasmin Haleema , Saleem Sarah , Bhutta Zulfiqar , Seto Emily
Published: October 2023

This study assessed the usability of the smartphone app, named “Raabta” from the perspective of pregnant women at high risk of preeclampsia to improve the Raabta app for future implementation. Think-aloud and task-completion techniques were used with a purposive sample of 14 pregnant women at high risk of preeclampsia. The sessions were audio-recorded and later professionally transcribed for thematic analysis. The study generated learnings associated with four themes: improving the clarity of instructions, messaging, and terminology; accessibility for non-tech savvy and illiterate Urdu users; enhancing visuals and icons for user engagement; and simplifying navigation and functionality. Overall, user feedback emphasized the importance of enhancing the clarity of instructions, messaging, and terminology within the Raabta app. Voice messages and visuals were valued by users, particularly among the non-tech savvy and illiterate Urdu users, as they enhance accessibility and enable independent monitoring. Suggestions were made to enhance user engagement through visual improvements such as enhanced graphics and culturally aligned color schemes. Lastly, users highlighted the need for improved navigation both between screens and within screens to enhance the overall user experience. The Raabta app prototype will be modified based on the feedback of the users to address the unique needs of diverse groups.
Vision-Based Structural Monitoring: Application to a Medium-Span Post-Tensioned Concrete Bridge under Vehicular Traffic
Authors: Micozzi Fabio , Morici Michele , Zona Alessandro , Dall’Asta Andrea
Published: October 2023

Video processing for structural monitoring has attracted much attention in recent years thanks to the possibility of measuring displacement time histories in the absence of stationary points close to the structure, using hardware that is simple to operate and with accessible costs. Experimental studies show a unanimous consensus on the potentialities of vision-based monitoring to provide accurate results that can be equivalent to those obtained from accelerometers and displacement transducers. However, past studies mostly involved steel bridges and footbridges while very few applications can be found for concrete bridges, characterised by a stiffer response with lower displacement magnitudes and different frequency contents of their dynamic behaviour. Accordingly, the attention of this experimental study is focused on the application of a vision-based structural monitoring system to a medium-span, post-tensioned, simply supported concrete bridge, a very common typology in many road networks. The objective is to provide evidence on the quality of the results that could be obtained using vision-based monitoring, understanding the role and influence on the accuracy of the measurements of various parameters relevant to the hardware settings and target geometry, highlighting possible difficulties, and providing practical recommendations to achieve optimal results.
T-Wave Oversensing with Contemporary Implantable Cardioverter–Defibrillators
Authors: Strik Marc , Ploux Sylvain , Eschalier Romain , Mondoly Pierre , Fontagne Leslie , Ramirez F. Daniel , Haïssaguerre Michel , Bordachar Pierre
Published: October 2023

Background: Implantable cardioverter–defibrillators (ICDs) need to reliably detect ventricular tachycardia (VT) and ventricular fibrillation (VF) while avoiding T-wave oversensing (TWOS), which is associated with a risk of inappropriate therapies. The incidence of TWOS with endovascular ICDs appears to differ between manufacturers. Objectives: We aimed to evaluate the incidence and clinical consequences of TWOS with contemporary Medtronic and Boston Scientific ICDs. Methods: Consecutive patients implanted with a recent Medtronic or Boston Scientific ICD and remotely monitored at three French centers were included. All transmitted EGMs labelled as VF, VT, non-sustained VT (NSVT), or ventricular oversensing (Medtronic) were screened for TWOS. Results: Among 7589 transmitted episodes from 674 patients with a Boston Scientific ICD, we did not identify a single case of TWOS. Among 16,790 transmitted episodes from 1733 patients with a Medtronic ICD, we identified 60 patients (3.4%) with at least one episode of TWOS. In 46 patients, TWOS was intermittent (NSVT episodes). In the remaining 14 patients, TWOS resulted in 60 sustained episodes (completed counters). No inappropriate therapies were delivered in 12 of these patients because no therapies were programmed (in monitor zones, 11 episodes) or because therapies were inhibited by the morphology discriminator (Wavelet, 19 episodes) or by the anti-TWOS algorithm (26 episodes). Two patients received inappropriate therapies due to TWOS (0.1% of patients with Medtronic ICDs). Conclusion: On review of 24,379 transmitted episodes from 2407 patients with endovascular ICDs, we found no case of TWOS with Boston Scientific devices, whereas TWOS was not uncommon with Medtronic devices. However, the risk of inappropriate therapy with Medtronic ICDs was very low (0.1%) due to the often intermittent nature of this phenomenon, the morphology discriminator, and the anti-TWOS algorithm.