bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Mechanisms of Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury
Authors: Shimizu Nobutaka , Saito Tetsuichi , Wada Naoki , Hashimoto Mamoru , Shimizu Takahiro , Kwon Joonbeom , Cho Kang Jun , Saito Motoaki , Karnup Sergei , de Groat William C. , Yoshimura Naoki
Published: April 2023

This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder–urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.
The Triad Na+ Activated Na+ Channel (Nax)—Salt Inducible KINASE (SIK) and (Na+ + K+)-ATPase: Targeting the Villains to Treat Salt Resistant and Sensitive Hypertension
Authors: Gonsalez Sabrina R. , Gomes Dayene S. , de Souza Alessandro M. , Ferrão Fernanda M. , Vallotton Zoe , Gogulamudi Venkateswara R. , Lowe Jennifer , Casarini Dulce E. , Prieto Minolfa C. , Lara Lucienne S.
Published: April 2023

The Na+-activated Na+ channel (Nax) and salt-inducible kinase (SIK) are stimulated by increases in local Na+ concentration, affecting (Na+ + K+)-ATPase activity. To test the hypothesis that the triad Nax/SIK/(Na+ + K+)-ATPase contributes to kidney injury and salt-sensitive hypertension (HTN), uninephrectomized male Wistar rats (200 g; n = 20) were randomly divided into 4 groups based on a salt diet (normal salt diet; NSD—0.5% NaCl—or high-salt diet; HSD—4% NaCl) and subcutaneous administration of saline (0.9% NaCl) or deoxycorticosterone acetate (DOCA, 8 mg/kg), as follows: Control (CTRL), CTRL-Salt, DOCA, and DOCA-Salt, respectively. After 28 days, the following were measured: kidney function, blood pressure, (Na+ + K+)-ATPase and SIK1 kidney activities, and Nax and SIK1 renal expression levels. SIK isoforms in kidneys of CTRL rats were present in the glomerulus and tubular epithelia; they were not altered by HSD and/or HTN. CTRL-Salt rats remained normotensive but presented slight kidney function decay. HSD rats displayed augmentation of the Nax/SIK/(Na+ + K+)-ATPase pathway. HTN, kidney injury, and kidney function decay were present in all DOCA rats; these were aggravated by HSD. DOCA rats presented unaltered (Na+ + K+)-ATPase activity, diminished total SIK activity, and augmented SIK1 and Nax content in the kidney cortex. DOCA-Salt rats expressed SIK1 activity and downregulation in (Na+ + K+)-ATPase activity in the kidney cortex despite augmented Nax content. The data of this study indicate that the (Na+ + K+)-ATPase activity response to SIK is attenuated in rats under HSD, independent of HTN, as a mechanism contributing to kidney injury and salt-sensitive HTN.
The Evaluation of SHAPE-MaP RNA Structure Probing Protocols Reveals a Novel Role of Mn2+ in the Detection of 2′-OH Adducts
Authors: Grzywacz Kamilla , Chełkowska-Pauszek Agnieszka , Plucinska-Jankowska Marianna , Żywicki Marek
Published: April 2023

Chemical probing, for decades, has been one of the most popular tools for studying the secondary structure of RNA molecules. Recently, protocols for simultaneous analysis of multiple RNAs have been developed, enabling in vivo transcriptome-wide interrogation of the RNA structure dynamics. One of the most popular methods is the selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP). In this study, we describe the evaluation of this protocol by addressing the influence of the reverse transcription enzymes, buffer conditions, and chemical probes on the properties of the cDNA library and the quality of mutational profiling-derived structural signals. Our results reveal a SuperScript IV (SSIV) reverse transcriptase as a more efficient enzyme for mutational profiling of SHAPE adducts and shed new light on the role of Mn2+ cations in the modulation of SSIV readthrough efficiency.
Potential Role of AGR2 for Mammalian Skin Wound Healing
Authors: Kosykh Anastasiya V. , Tereshina Maria B. , Gurskaya Nadya G.
Published: April 2023

The limited ability of mammals to regenerate has garnered significant attention, particularly in regard to skin wound healing (WH), which is a critical step for regeneration. In human adults, skin WH results in the formation of scars following injury or trauma, regardless of severity. This differs significantly from the scarless WH observed in the fetal skin of mammals or anamniotes. This review investigates the role of molecular players involved in scarless WH, which are lost or repressed in adult mammalian WH systems. Specifically, we analyze the physiological role of Anterior Gradient (AGR) family proteins at different stages of the WH regulatory network. AGR is activated in the regeneration of lower vertebrates at the stage of wound closure and, accordingly, is important for WH. Mammalian AGR2 is expressed during scarless WH in embryonic skin, while in adults, the activity of this gene is normally inhibited and is observed only in the mucous epithelium of the digestive tract, which is capable of full regeneration. The combination of AGR2 unique potencies in postnatal mammals makes it possible to consider it as a promising candidate for enhancing WH processes.
Vortex Glass—Vortex Liquid Transition in BaFe2(As1-xPx)2 and CaKFe4As4 Superconductors from Multi-Harmonic AC Magnetic Susceptibility Studies
Authors: Ivan Ion , Ionescu Alina M. , Crisan Daniel N. , Crisan Adrian
Published: April 2023

For practical applications of superconductors, understanding the vortex matter and dynamics is of paramount importance. An important issue in this context is the transition of the vortex glass, which is a true superconducting phase, into a vortex liquid phase having a linear dissipation. By using multi-harmonic susceptibility studies, we have investigated the vortex glass—vortex liquid phase transitions in CaKFe4As4 and BaFe2(As0.68P0.32)2 single crystals. The principle of our method relates the on-set of the third-harmonic susceptibility response with the appearance of a vortex-glass phase in which the dissipation is non-linear. Similar to the high-critical temperature cuprate superconductors, we have shown that even in these iron-based superconductors with significant lower critical temperatures, such phase transition can be treated as a melting in the sense of Lindemann’s approach, considering an anisotropic Ginzburg-Landau model. The experimental data are consistent with a temperature-dependent London penetration depth given by a 3D XY fluctuations model. The fitting parameters allowed us to extrapolate the vortex melting lines down to the temperature of liquid hydrogen, and such extrapolation showed that CaKFe4As4 is a very promising superconducting material for high field applications in liquid hydrogen, with a melting field at 20 K of the order of 100 T.
Mechanisms of Oxidative Stress in Metabolic Syndrome
Authors: Masenga Sepiso K. , Kabwe Lombe S. , Chakulya Martin , Kirabo Annet
Published: April 2023

Metabolic syndrome is a cluster of conditions associated with the risk of diabetes mellitus type 2 and cardiovascular diseases (CVDs). Metabolic syndrome is closely related to obesity. Increased adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving metabolic syndrome components, namely insulin resistance, hypertension, and hyperlipidemia. An increasing number of studies confirm the importance of oxidative stress and chronic inflammation in the etiology of metabolic syndrome. However, few studies have reviewed the mechanisms underlying the role of oxidative stress in contributing to metabolic syndrome. In this review, we highlight mechanisms by which reactive oxygen species (ROS) increase mitochondrial dysfunction, protein damage, lipid peroxidation, and impair antioxidant function in metabolic syndrome. Biomarkers of oxidative stress can be used in disease diagnosis and evaluation of severity.
SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea
Authors: Díaz-García Elena , García-Sánchez Aldara , Sánz-Rubio David , Alfaro Enrique , López-Fernández Cristina , Casitas Raquel , Mañas Baena Eva , Cano-Pumarega Irene , Cubero Pablo , Marin-Oto Marta , López-Collazo Eduardo , Marin José María , García-Río Francisco , Cubillos-Zapata Carolina
Published: April 2023

Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-β) plays a crucial role in the development and progression of atherosclerosis. In this context, the central regulator of TGF-β pathway, SMAD4 (small mother against decapentaplegic homolog 4), has been previously reported to be augmented in OSA patients, which levels were even higher in patients with concomitant cardiometabolic diseases. Here, we analyzed soluble and intracellular SMAD4 levels in plasma and monocytes from OSA patients and non-apneic subjects, with or without early subclinical atherosclerosis (eSA). In addition, we used in vitro and ex vivo models to explore the mechanisms underlying SMAD4 upregulation and release. Our study confirmed elevated sSMAD4 levels in OSA patients and identified that its levels were even higher in those OSA patients with eSA. Moreover, we demonstrated that SMAD4 is overexpressed in OSA monocytes and that intermittent hypoxia contributes to SMAD4 upregulation and release in a process mediated by NLRP3. In conclusion, this study highlights the potential role of sSMAD4 as a biomarker for atherosclerosis risk in OSA patients and provides new insights into the mechanisms underlying its upregulation and release to the extracellular space.
The Effect of Sorbent Composition on Sorption Properties of Materials Based on Ti-Ca-Mg Phosphates
Authors: Mudruk Natalia , Maslova Marina
Published: April 2023

Individual titanium and calcium–magnesium phosphates are widely known as effective sorbents. The sorption processes on these phosphates are based on different mechanisms. The sorption efficiency towards different cations depends on the phase composition of the sorbent. Composite materials with various ratio Ti:(Ca+Mg) have been synthesized. The sorption properties of samples obtained towards Cs+, Sr2+, Co2+, Cd2+, Zn2+, Cu2+, and Pb2+ have been studied to establish the effect of sorbent composition on metal removal. The adsorption isotherms have been analyzed using the Langmuir, Freundlich, and Redlich–Peterson models. The composition of sorbents has no effect on the level of removal of readily hydrolyzable Pb2+ and Cu2+ cations. Removal of lead occurs preferentially via the precipitation of metal phosphates and hydroxides. Copper precipitates as hydroxide in case of a high share of Ca-Mg phosphates in the composite sorbent. The removal of cesium proceeds according to the ion exchange mechanism only. For Cd2+, Co2+, Sr2+, and Zn2+ cations, the sorption efficiency on the composite materials synthesized is found to increase with the increase in titanium phosphate’s share in the sample. All composite sorbents synthesized demonstrated a considerable increase in the level of purification of solutions studied compared with individual Ti and Ca-Mg phosphates due to the synergism of the components.
The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children
Authors: Gavrilovici Cristina , Dusa Cristian Petru , Iliescu Halitchi Codruta , Lupu Vasile Valeriu , Spoiala Elena Lia , Bogos Roxana Alexandra , Mocanu Adriana , Gafencu Mihai , Lupu Ancuta , Stoica Cristina , Starcea Iuliana Magdalena
Published: April 2023

Vesicoureteral reflux (VUR) is the most frequent congenital urinary tract malformation and an important risk factor for urinary tract infections (UTIs). Up to 50% of children with VUR may develop reflux nephropathy (RN), and the diagnosis and monitoring of renal scars are invasive and costly procedures, so it is paramount to find a non-invasive and accurate method to predict the risk of renal damage. Neutrophil gelatinase-associated lipocalin (NGAL) has already proven to be a good predictive biomarker in acute kidney injuries, but there are few studies that have investigated the role of NGAL in primary VUR in children. Our aim is to review the predictive value of urine NGAL (uNGAL) as a non-invasive biomarker of RN in children with primary VUR, as well as its ability to predict the evolution of chronic kidney disease (CKD). Based on our analysis of the available original studies, uNGAL can be an accurate and reliable biomarker of RN and its progression to CKD. Some studies suggested a good correlation between VUR severity and uNGAL levels, but other studies found no significant correlation. The relationship between VUR severity and uNGAL levels is likely complex and influenced by factors such as UTIs, the timing of the urine sample collection, and the age and overall health of the patient.
Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0
Authors: Sereno Denis
Published: April 2023

Infectious diseases caused by parasites (malaria, leishmaniasis, trypanosomiasis, filariasis…), viruses (chikungunya, dengue, phlebovirus, etc [...]
Overexpression of miR-4669 Enhances Tumor Aggressiveness and Generates an Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma: Its Clinical Value as a Predictive Biomarker
Authors: Nakano Toshiaki , Chen Chao-Long , Chen I-Hsuan , Tseng Hui-Peng , Chiang Kuei-Chen , Lai Chia-Yun , Hsu Li-Wen , Goto Shigeru , Lin Chih-Che , Cheng Yu-Fan
Published: April 2023

Accumulating evidence suggests the involvement of tumor-derived exosomes in the development and recurrence of hepatocellular carcinoma (HCC). We previously identified miR-4669 as a highly expressed microRNA in circulating exosomes obtained from patients with post-transplant HCC recurrence. This study aimed to explore how overexpression of miR-4669 affects HCC development and recurrence. The impact of miR-4669 overexpression in Hep3B cells on tumor cell behavior and the tumor microenvironment was evaluated in vitro. In addition, the clinical value of exosomal miR-4669 for the prediction of treatment response to HCC downstaging therapies and following post-transplant HCC recurrence was explored. Overexpression of miR-4669 enhanced migration ability and led to acquired sorafenib resistance with an elevation of sirtuin 1 and long noncoding RNA associated with microvascular invasion. Active release of tumor-derived exosomes and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) contributed to generating an immunosuppressive tumor microenvironment through the induction of M2 macrophage polarization. The retrospective analysis demonstrated the clinical value of exosomal miR-4669 for predicting treatment response to HCC downstaging therapies and for risk assessment of post-transplant HCC recurrence. In summary, the present data demonstrate the impact of exosomal miR-4669 on HCC recurrence through the enhancement of tumor aggressiveness and generation of an immunosuppressive tumor microenvironment.
Health Properties of Plant Bioactive Compounds: Immune, Antioxidant, and Metabolic Effects
Authors: Cruz-Chamorro Ivan , Carrillo-Vico Antonio
Published: April 2023

In recent decades, people in the industrialized world have increased the demand for meat-free foods motivated by health, environmental, and animal welfare reasons [...]
Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853
Authors: Chen Leifeng , Zhang Lin , He Haihua , Shao Fei , Gao Yibo , He Jie
Published: April 2023

Pancreatic cancer (PC) is a deadly malignant digestive tumor with poor prognoses and a lack of effective treatment options. Cuproptosis, a recently identified copper-dependent programmed cell death type, has been implicated in multiple cancers. Long non-coding RNAs (lncRNAs) are also linked to the progression of PC. However, the role and prognostic values of cuproptosis-related lncRNAs in pancreatic adenocarcinoma (PAAD) remain unclear. In this study, we systemically analyzed the differential expressions and prognostic values of 672 cuproptosis-related lncRNAs in PAAD. Based on this, a prognostic signature including four lncRNAs (LINC00853, AC099850.3, AC010719.1, and AC006504.7) was constructed and was able to divide PAAD patients into high- and low-risk groups with significantly different prognoses. Next, we focused on lncRNA LINC00853. The differential expressions of LINC00853 between normal tissue and PAAD samples were validated by qRT-PCR. LINC00853 was knocked down by siRNA in PC cell lines BxPC-3 and PANC-1 and the oncogenic role of LINC00853 was validated by CCK8, colony formation, and EdU assays. Subsequently, LINC00853 knockdown cells were subjected to tumor xenograft tests and exhibited decreased tumor growth in nude mice. Mechanistically, knockdown of LINC00853 significantly reduced cellular glycolysis and enhanced cellular mitochondrial respiration levels in PC cells. Moreover, knockdown of LINC00853 decreased the protein level of a glycolytic kinase PFKFB3. Finally, glycolysis tests and functional tests using LINC00853 and HA-PFKFB3 indicated that the effects of LINC00853 on glycolysis and cell proliferation were mediated by PFKFB3. In conclusion, our systemic analyses have highlighted the important roles of cuproptosis-related lncRNAs in PAAD while the prognostic signature based on them showed excellent performance in PAAD patients and is expected to provide clinical guidance for individualized treatment. In addition, our findings provide a novel mechanism by which the LINC00853-PFKFB3 axis critically regulates aerobic glycolysis and cell proliferation in PC cells.
The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis
Authors: Podyacheva Ekaterina , Toropova Yana
Published: April 2023

The World Health Organization has identified oncological diseases as one of the most serious health concerns of the current century. Current research on oncogenesis is focused on the molecular mechanisms of energy-biochemical reprogramming in cancer cell metabolism, including processes contributing to the Warburg effect and the pro-oncogenic and anti-oncogenic roles of sirtuins (SIRTs) and poly-(ADP-ribose) polymerases (PARPs). However, a clear understanding of the interaction between NAD+, SIRTs in cancer development, as well as their effects on carcinogenesis, has not been established, and literature data vary greatly. This work aims to provide a summary and structure of the available information on NAD+, SIRTs interactions in both stimulating and countering carcinogenesis, and to discuss potential approaches for pharmacological modulation of these interactions to achieve an anticancer effect.
The miR166d/TaCPK7-D Signaling Module Is a Critical Mediator of Wheat (Triticum aestivum L.) Tolerance to K+ Deficiency
Authors: Lei Xiaotong , Chen Miaomiao , Xu Ke , Sun Ruoxi , Zhao Sihang , Wu Ningjing , Zhang Shuhua , Yang Xueju , Xiao Kai , Zhao Yong
Published: April 2023

It is well established that potassium (K+) is an essential nutrient for wheat (Triticum aestivum L.) growth and development. Several microRNAs (miRNAs), including miR166, are reportedly vital roles related to plant growth and stress responses. In this study, a K+ starvation-responsive miRNA (miR166d) was identified, which showed increased expression in the roots of wheat seedlings exposed to low-K+ stress. The overexpression of miR166d considerably increased the tolerance of transgenic Arabidopsis plants to K+ deprivation treatment. Furthermore, disrupting miR166d expression via virus-induced gene silencing (VIGS) adversely affected wheat adaptation to low-K+ stress. Additionally, miR166d directly targeted the calcium-dependent protein kinase 7-D gene (TaCPK7-D) in wheat. The TaCPK7-D gene expression was decreased in wheat seedling roots following K+ starvation treatment. Silencing TaCPK7-D in wheat increased K+ uptake under K+ starvation. Moreover, we observed that the miR166d/TaCPK7-D module could affect wheat tolerance to K+ starvation stress by regulating TaAKT1 and TaHAK1 expression. Taken together, our results indicate that miR166d is vital for K+ uptake and K+ starvation tolerance of wheat via regulation of TaCPK7-D.
Small RNA MTS1338 Configures a Stress Resistance Signature in Mycobacterium tuberculosis
Authors: Martini Billy A. , Grigorov Artem S. , Skvortsova Yulia V. , Bychenko Oksana S. , Salina Elena G. , Azhikina Tatyana L.
Published: April 2023

In the course of evolution, Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, has developed sophisticated strategies to evade host immune response, including the synthesis of small non-coding RNAs (sRNAs), which regulate post-transcriptional pathways involved in the stress adaptation of mycobacteria. sRNA MTS1338 is upregulated in Mtb during its infection of cultured macrophages and in the model of chronic tuberculosis, suggesting involvement in host–pathogen interactions. Here, we analyzed the role of MTS1338 in the Mtb response to macrophage-like stresses in vitro. The Mtb strain overexpressing MTS1338 demonstrated enhanced survival ability under low pH, nitrosative, and oxidative stress conditions simulating the antimicrobial environment inside macrophages. Transcriptomic analysis revealed that in MTS1338-overexpressing Mtb, the stress factors led to the activation of a number of transcriptional regulators, toxin–antitoxin modules, and stress chaperones, about half of which coincided with the genes induced in Mtb phagocytosed by macrophages. We determined the MTS1338 “core regulon”, consisting of 11 genes that were activated in all conditions under MTS1338 overexpression. Our findings indicate that MTS1338 is a stress-induced sRNA that promotes Mtb survival in macrophages by triggering adaptive transcriptional mechanisms in response to host antimicrobial defense reactions.
A Promising Way to Overcome Temozolomide Resistance through Inhibition of Protein Neddylation in Glioblastoma Cell Lines
Authors: Brandt Barbara , Németh Marica , Berta Gergely , Szünstein Máté , Heffer Marija , Rauch Tibor A. , Pap Marianna
Published: April 2023

There is no effective therapy for the lately increased incidence of glioblastoma multiforme (GBM)—the most common primary brain tumor characterized by a high degree of invasiveness and genetic heterogeneity. Currently, DNA alkylating agent temozolomide (TMZ) is the standard chemotherapy. Nevertheless, TMZ resistance is a major problem in the treatment of GBM due to numerous molecular mechanisms related to DNA damage repair, epigenetic alterations, cellular drug efflux, apoptosis-autophagy, and overactive protein neddylation. Low molecular weight inhibitors of NEDD8-activating enzyme (NAE), such as MLN4924, attenuate protein neddylation and present a promising low-toxicity anticancer agent. The aim of our study was to find an effective combination treatment with TMZ and MLN4924 in our TMZ-resistant GBM cell lines and study the effect of these combination treatments on different protein expressions such as O6-methylguanine methyltransferase (MGMT) and p53. The combination treatment successfully decreased cell viability and sensitized TMZ-resistant cells to TMZ, foreshadowing a new treatment strategy for GBM.
Critical Overview on Regenerative Medicine: New Insights into the Role of Stem Cells and Innovative Biomaterials
Authors: Tatullo Marco , Zavan Barbara , Piattelli Adriano
Published: April 2023

Regenerative medicine represents a novel and intriguing field of medicine [...]
Immunopathogenesis of Nipah Virus Infection and Associated Immune Responses
Authors: Brown Brent , Gravier Tanya , Fricke Ingo , Al-Sheboul Suhaila A. , Carp Theodor-Nicolae , Leow Chiuan Yee , Imarogbe Chinua , Arabpour Javad
Published: April 2023

Pandemics in the last two centuries have been initiated by causal pathogens that include Severe Acute Coronavirus 2 (SARS-CoV-2) and Influenza (e.g., the H1N1 pandemic of 2009). The latter is considered to have initiated two prior pandemics in 1918 and 1977, known as the “Spanish Flu” and “Russian Flu”, respectively. Here, we discuss other emerging infections that could be potential public health threats. These include Henipaviruses, which are members of the family Paramyxoviridae that infect bats and other mammals. Paramyxoviridae also include Parainfluenza and Mumps viruses (Rubulavirus) but also Respiratory Syncytial virus (RSV) (Pneumovirus). Additionally included is the Measles virus, recorded for the first time in writing in 1657 (Morbillivirus). In humans and animals, these may cause encephalitis or respiratory diseases. Recently, two more highly pathogenic class 4 viral pathogens emerged. These were named Hendra Henipavirus (HeV) and Nipah Henipavirus (NiV). Nipah virus is a negative-sense single-stranded ribonucleic acid ((−) ssRNA) virus within the family Paramyxoviridae. There are currently no known therapeutics or treatment regimens licensed as effective in humans, with development ongoing. Nipah virus is a lethal emerging zoonotic disease that has been neglected since its characterization in 1999 until recently. Nipah virus infection occurs predominantly in isolated regions of Malaysia, Bangladesh, and India in small outbreaks. Factors that affect animal–human disease transmission include viral mutation, direct contact, amplifying reservoirs, food, close contact, and host cell mutations. There are different strains of Nipah virus, and small outbreaks in humans limit known research and surveillance on this pathogen. The small size of outbreaks in rural areas is suggestive of low transmission. Person-to-person transmission may occur. The role that zoonotic (animal–human) or host immune system cellular factors perform therefore requires analysis. Mortality estimates for NiV infection range from 38–100% (averaging 58.2% in early 2019). It is therefore critical to outline treatments and prevention for NiV disease in future research. The final stages of the disease severely affect key organ systems, particularly the central nervous system and brain. Therefore, here we clarify the pathogenesis, biochemical mechanisms, and all research in context with known immune cell proteins and genetic factors.
Generation of Nonlinear Substitutions by Simulated Annealing Algorithm
Authors: Kuznetsov Alexandr , Karpinski Mikolaj , Ziubina Ruslana , Kandiy Sergey , Frontoni Emanuele , Peliukh Oleksandr , Veselska Olga , Kozak Ruslan
Published: April 2023

The problem of nonlinear substitution generation (S-boxes) is investigated in many related works in symmetric key cryptography. In particular, the strength of symmetric ciphers to linear cryptanalysis is directly related to the nonlinearity of substitution. In addition to being highly nonlinear, S-boxes must be random, i.e., must not contain hidden mathematical constructs that facilitate algebraic cryptanalysis. The generation of such substitutions is a complex combinatorial optimization problem. Probabilistic algorithms are used to solve it, for instance the simulated annealing algorithm, which is well-fitted to a discrete search space. We propose a new cost function based on Walsh–Hadamard spectrum computation, and investigate the search efficiency of S-boxes using a simulated annealing algorithm. For this purpose, we conduct numerous experiments with different input parameters: initial temperature, cooling coefficient, number of internal and external loops. As the results of the research show, applying the new cost function allows for the rapid generation of nonlinear substitutions. To find 8-bit bijective S-boxes with nonlinearity 104, we need about 83,000 iterations. At the same time, the probability of finding the target result is 100%.
Is Users’ Trust during Automated Driving Different When Using an Ambient Light HMI, Compared to an Auditory HMI?
Authors: Gonçalves Rafael Cirino , Louw Tyron , Lee Yee Mun , Madigan Ruth , Kuo Jonny , Lenné Mike , Merat Natasha
Published: April 2023

The aim of this study was to compare the success of two different Human Machine Interfaces (HMIs) in attracting drivers’ attention when they were engaged in a Non-Driving-Related Task (NDRT) during SAE Level 3 driving. We also assessed the value of each on drivers’ perceived safety and trust. A driving simulator experiment was used to investigate drivers’ response to a non-safety-critical transition of control and five cut-in events (one hard; deceleration of 2.4 m/s2, and 4 subtle; deceleration of ~1.16 m/s2) over the course of the automated drive. The experiment used two types of HMI to trigger a takeover request (TOR): one Light-band display that flashed whenever the drivers needed to takeover control; and one auditory warning. Results showed that drivers’ levels of trust in automation were similar for both HMI conditions, in all scenarios, except during a hard cut-in event. Regarding the HMI’s capabilities to support a takeover process, the study found no differences in drivers’ takeover performance or overall gaze distribution. However, with the Light-band HMI, drivers were more likely to focus their attention to the road centre first after a takeover request. Although a high proportion of glances towards the dashboard of the vehicle was seen for both HMIs during the takeover process, the value of these ambient lighting signals for conveying automation status and takeover messages may be useful to help drivers direct their visual attention to the most suitable area after a takeover, such as the forward roadway.
Leveraging RNA Interference to Impact Insecticide Resistance in the Colorado Potato Beetle, Leptinotarsa decemlineata
Authors: Timani Kenan , Bastarache Pierre , Morin Pier Jr
Published: April 2023

The Colorado potato beetle, Leptinotarsa decemlineata Say, is a potato pest that can cause important economic losses to the potato industry worldwide. Diverse strategies have been deployed to target this insect such as biological control, crop rotation, and a variety of insecticides. Regarding the latter, this pest has demonstrated impressive abilities to develop resistance against the compounds used to regulate its spread. Substantial work has been conducted to better characterize the molecular signatures underlying this resistance, with the overarching objective of leveraging this information for the development of novel approaches, including RNAi-based techniques, to limit the damage associated with this insect. This review first describes the various strategies utilized to control L. decemlineata and highlights different examples of reported cases of resistances against insecticides for this insect. The molecular leads identified as potential players modulating insecticide resistance as well as the growing interest towards the use of RNAi aimed at these leads as part of novel means to control the impact of L. decemlineata are described subsequently. Finally, select advantages and limitations of RNAi are addressed to better assess the potential of this technology in the broader context of insecticide resistance for pest management.
Impaired Awareness in People with Severe Alcohol-Related Cognitive Deficits Including Korskoff’s Syndrome: A Network Analysis
Authors: Fidder Hester , Veenhuizen Ruth B. , Gerridzen Ineke J. , van Wieringen Wessel N. , Smalbrugge Martin , Hertogh Cees M. P. M. , van Loon Anouk M.
Published: April 2023

Background: Impaired awareness of one’s own functioning is highly common in people with Korsakoff’s syndrome (KS). However, it is currently unclear how awareness relates to impairments in daily functioning and quality of life (QoL). Methods: We assessed how impaired awareness relates to cognitive, behavioral, physical, and social functioning and QoL by applying a network analysis. We used cross-sectional data from 215 patients with KS or other severe alcohol-related cognitive deficits living in Dutch long-term care facilities (LTCFs). Results: Apathy has the most central position in the network. Higher apathy scores relate positively to reduced cognition and to a greater decline in activities of daily living and negatively to social participation and the use of antipsychotic drugs. Impaired awareness is also a central node. It is positively related to a higher perceived QoL, reduced cognition and apathy, and negatively to social participation and length of stay in the LTCF. Mediated through apathy and social participation, impaired awareness is indirectly related to other neuropsychiatric symptoms. Conclusions: Impaired awareness is closely related to other domains of daily functioning and QoL of people with KS or other severe alcohol-related cognitive deficits living in LTCFs. Apathy plays a central role. Network analysis offers interesting insights to evaluate the interconnection of different symptoms and impairments in brain disorders such as KS.
Korsakoff’s Syndrome and Alzheimer’s Disease—Commonalities and Specificities of Volumetric Brain Alterations within Papez Circuit
Authors: Segobin Shailendra , Ambler Melanie , Laniepce Alice , Platel Hervé , Chételat Gael , Groussard Mathilde , Pitel Anne-Lise
Published: April 2023

Background: Alzheimer’s disease (AD) and Korsakoff’s syndrome (KS) are two major neurocognitive disorders characterized by amnesia but AD is degenerative while KS is not. The objective is to compare regional volume deficits within the Papez circuit in AD and KS, considering AD progression. Methods: 18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on global cognitive deficits with KS patients and 20 with Severe AD (SAD)), and 70 healthy controls underwent structural MRI. Volumes of the hippocampi, thalami, cingulate gyri, mammillary bodies (MB) and mammillothalamic tracts (MTT) were extracted. Results: For the cingulate gyri, and anterior thalamic nuclei, all patient groups were affected compared to controls but did not differ between each other. Smaller volumes were observed in all patient groups compared to controls in the mediodorsal thalamic nuclei and MB, but these regions were more severely damaged in KS than AD. MTT volumes were damaged in KS only. Hippocampi were affected in all patient groups but more severely in the SAD than in the KS and MAD. Conclusions: There are commonalities in the pattern of volume deficits in KS and AD within the Papez circuit with the anterior thalamic nuclei, cingulate cortex and hippocampus (in MAD only) being damaged to the same extent. The specificity of KS relies on the alteration of the MTT and the severity of the MB shrinkage. Further comparative studies including other imaging modalities and a neuropsychological assessment are required.
Detecting Maritime GPS Spoofing Attacks Based on NMEA Sentence Integrity Monitoring
Authors: Spravil Julian , Hemminghaus Christian , von Rechenberg Merlin , Padilla Elmar , Bauer Jan
Published: April 2023

Today’s maritime transportation relies on global navigation satellite systems (GNSSs) for accurate navigation. The high-precision GNSS receivers on board modern vessels are often considered trustworthy. However, due to technological advances and malicious activities, this assumption is no longer always true. Numerous incidents of tampered GNSS signals have been reported. Furthermore, researchers have demonstrated that manipulations can be carried out even with inexpensive hardware and little expert knowledge, lowering the barrier for malicious attacks with far-reaching consequences. Hence, exclusive trust in GNSS is misplaced, and methods for reliable detection are urgently needed. However, many of the proposed solutions require expensive replacement of existing hardware. In this paper, therefore, we present MAritime Nmea-based Anomaly detection (MANA), a novel low-cost framework for GPS spoofing detection. MANA monitors NMEA-0183 data and advantageously combines several software-based methods. Using simulations supported by real-world experiments that generate an extensive dataset, we investigate our approach and finally evaluate its effectiveness.
Prokaryotic Responses to Estuarine Coalescence Contribute to Planktonic Community Assembly in a Mediterranean Nutrient-Rich Estuary
Authors: Navarro Elisabeth , Santinelli Chiara , Retelletti Brogi Simona , Durrieu Gaël , Radakovitch Olivier , Garnier Cédric , Misson Benjamin
Published: April 2023

In the marine coastal environment, freshwater and seawater coalescing communities are facing a complex set of abiotic and biotic cross-influences. This study aimed at evaluating the respective influences of blending and prokaryotic dynamics on community structure. For that, the surface salinity gradient of a nutrient-rich estuary (Arno River, Mediterranean Sea, Italy) was sampled at regular salinity intervals. When considering the whole length of the estuary and community-scale beta diversity metrics, a relatively smooth transition from freshwater to the sea was observed. Abiotic variability associated with salinity was the predominant constraint on the community structure, and the distribution of most taxa reflected their blending. However, while most of the dissolved substances enriched in freshwater experienced progressive dilution with seawater, heterotrophic prokaryotes demonstrated an important growth at intermediate salinity, interpreted as a heterotrophic assimilation of freshwater inputs by a few opportunistic marine taxa. The distribution of a number of taxa was significantly affected by variations in heterotrophic prokaryotes abundance, suggesting a putative influence of competitive interactions at intermediate salinities. A succession of different bacterial winners was observed from upstream to downstream, as well as losers represented by freshwater copiotrophs accompanied by some marine oligotrophs. Hence, coalescence drove a localized but major functional response of heterotrophic bacteria at intermediate salinity, hidden behind a majority of passively mixed bacterial taxa. This work paves the way for a stronger consideration of the trophic requirements of bacterial taxa to better understand community assembly in estuaries.
Bacterial Contamination of Open Fractures: Pathogens and Antibiotic Resistance Patterns in East China
Authors: Zhong Wanrun , Wang Yanmao , Wang Hongshu , Han Pei , Sun Yi , Chai Yimin , Lu Shengdi , Hu Chengfang
Published: April 2023

Bacterial contamination of soft tissue in open fractures leads to high infection rates. Pathogens and their resistance against therapeutic agents change with time and vary in different regions. The purpose of this study was to characterize the bacterial spectrum present in open fractures and analyze the bacterial resistance to antibiotic agents based on five trauma centers in East China. A retrospective multicenter cohort study was conducted in six major trauma centers in East China from January 2015 to December 2017. Patients who sustained open fractures of the lower extremities were included. The data collected included the mechanism of injury, the Gustilo-Anderson classification, the isolated pathogens and their resistance against therapeutic agents, as well as the prophylactic antibiotics administered. In total, 1348 patients were included in our study, all of whom received antibiotic prophylaxis (cefotiam or cefuroxime) during the first debridement at the emergency room. Wound cultures were taken in 1187 patients (85.8%); the results showed that the positive rate of open fracture was 54.8% (651/1187), and 59% of the bacterial detections occurred in grade III fractures. Most pathogens (72.7%) were sensitive to prophylactic antibiotics, according to the EAST guideline. Quinolones and cotrimoxazole showed the lowest rates of resistance. The updated EAST guidelines for antibiotic prophylaxis in open fracture (2011) have been proven to be adequate for a large portion of patients, and we would like to suggest additional Gram-negative coverage for patients with grade II open fractures based on the results obtained in this setting in East China.
The Role of Cold Atmospheric Plasma in Wound Healing Processes in Critically Ill Patients
Authors: Bolgeo Tatiana , Maconi Antonio , Gardalini Menada , Gatti Denise , Di Matteo Roberta , Lapidari Marco , Longhitano Yaroslava , Savioli Gabriele , Piccioni Andrea , Zanza Christian
Published: April 2023

Critically ill patients are at risk of skin wounds, which reduce their quality of life, complicate their pharmacological regimens, and prolong their hospital stays in intensive care units (ICUs), while also increasing overall mortality and morbidity rates. Cold atmospheric plasma (CAP) has been proposed as a viable option for many biological and medical applications, given its capacity to reduce wound bacterial contamination and promote wound healing. The aim of this narrative review is to describe how CAP works and its operating mechanisms, as well as reporting its possible applications in critical care settings. The success of CAP in the treatment of wounds, in particular, bedsores or pressure sores, presents an innovative path in the prevention of nosocomial infections and an opportunity of reducing the negative implications of these diseases for the NHS. This narrative review of the literature was conducted following the ‘Scale for the Assessment of Narrative Review Articles’ (SANRA) methodology. Previous literature highlights three biological effects of plasma: inactivation of a wide range of microorganisms, including those that are multi-drug-resistant; increased cell proliferation and angiogenesis with a shorter period of plasma treatment; and apoptosis stimulation with a longer and more intensive treatment. CAP is effective in many areas of the medical field, with no significant adverse effects on healthy cells. However, its use can produce potentially serious side effects and should, therefore, be used under expert supervision and in appropriate doses.
A Useful Method for the Practice of Pneumatic Retinopexy: Slit-Lamp Laser Photocoagulation through the Gas Bubble
Authors: Aykut Aslan , Sevik Mehmet Orkun , Kubat Betül , Dericioğlu Volkan , Şahin Özlem
Published: April 2023

This study aimed to demonstrate the laser retinopexy method through the gas bubble under a slit-lamp biomicroscope using a wide-field contact lens to treat rhegmatogenous retinal detachment (RRD) with pneumatic retinopexy (PR) and report its anatomical and functional results. This single-center, retrospective case series included RRD patients treated with PR using sulfur hexafluoride (SF6). The demographics, preoperative factors, and anatomical and functional outcomes were collected from the patient files. The single-procedure success rate of PR at postoperative 6th months was 70.8% (17/24 eyes), and the final success rate after secondary surgeries was 100%. The BCVA was better in the successful PR eyes at postoperative 3rd (p = 0.011) and 6th month (p = 0.016) than in failed eyes. No single preoperative factor was associated with PR success. The single-procedure success rate of PR using the laser retinopexy method through the gas bubble with a wide-field contact lens system seems comparable to the PR literature.
The Value of Multimodal Imaging in Early Phenotyping of Cardiomyopathies: A Family Case Report
Authors: Iovănescu Maria Livia , Hădăreanu Diana Ruxandra , Militaru Sebastian , Florescu Cristina , Militaru Constantin , Donoiu Ionuț
Published: April 2023

Cardiomyopathies are structural and functional myocardial disorders that are not caused by other specific conditions such as coronary artery disease, arterial hypertension, valvular disease or congenital heart diseases. They are grouped into specific morphological and functional phenotypes, and sub-classified into familial and non-familial forms, with the dilated phenotype being the most frequent. However, there are many overlapping features between these phenotypes, complicating the diagnosis and management of patients. We report here the case of three related patients with different types of cardiomyopathies, emphasizing the importance of a multimodal approach to diagnosis.
Monitoring Events of Market Competitors: A Text Mining Method for Analyzing Massive Firm-Generated Social Media
Authors: Yuan Hua , Deng Wenjun , Ma Baojun , Qian Yu
Published: April 2023

Understanding how competitors act in a market is a critical component of strategic decision-making. In this paper, we propose a method to extract firm events from the textual content generated by firms in the market and explore the competitive relationships among firms based on the spatiotemporal homogeneity of events of different firms. To this end, we first introduce experts to define a series of business events based on the content of corporate-generated texts; then, we propose algorithms to extract and enrich the feature words (triggers) of these business events to form better event classifiers. We subsequently use these classifiers to identify the business events recorded in all online texts published by companies. Finally, based on these results, we can obtain a sequence of activities/events for each firm in the market, which can be used to identify the evolutionary patterns of firms’ behavior in the market, as well as their potential competitive relationships. Considering that competition between companies in the market appears to be continuous at the strategic level, but the implementation of competitive behavior is expressed through their “events” in the market, identifying whether companies are “competing” in the market requires timely observation of the information about “events” in the market. However, obtaining accurate market information is complex and costly. Therefore, this study provides a way to bridge the gap between social media data and market competition “events”.