bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrometeorological Trends in a Low-Gradient Forested Watershed on the Southeastern Atlantic Coastal Plain in the USA
Authors: Amatya Devendra M. , Callahan Timothy J. , Mukherjee Sourav , Harrison Charles A. , Trettin Carl C. , Wałęga Andrzej , Młyński Dariusz , Emmett Kristen D.
Published: February 2024

Hydrology and meteorological data from relatively undisturbed watersheds aid in identifying effects on ecosystem services, tracking hydroclimatic trends, and reducing model uncertainties. Sustainable forest, water, and infrastructure management depends on assessing the impacts of extreme events and land use change on flooding, droughts, and biogeochemical processes. For example, global climate models predict more frequent high-intensity storms and longer dry periods for the southeastern USA. We summarized 17 years (2005–2021) of hydrometeorological data recorded in the 52 km2, third-order Turkey Creek watershed at the Santee Experimental Forest (SEF), Southeastern Coastal Plain, USA. This is a non-tidal headwater system of the Charleston Harbor estuary. The study period included a wide range of weather conditions; annual precipitation (P) and potential evapotranspiration (PET) ranged from 994 mm and 1212 mm in 2007 to 2243 mm and 1063 in 2015, respectively. The annual runoff coefficient (ROC) varied from 0.09 in 2007 (with water table (WT) as deep as 2.4 m below surface) to 0.52 in 2015 (with frequently ponded WT conditions), with an average of 0.22. Although the average P (1470 mm) was 11% higher than the historic 1964–1976 average (1320 mm), no significant (α= 0.05) trend was found in the annual P (p = 0.11), ROC (p = 0.17) or runoff (p = 0.27). Runoff occurred on 76.4% of all days in the study period, exceeding 20 mm/day for 1.25% of all days, mostly due to intense storms in the summer and lower ET demand in the winter. No-flow conditions were common during most of the summer growing season. WT recharge occurred during water-surplus conditions, and storm-event base flow contributed 23–47% of the total runoff as estimated using a hydrograph separation method. Storm-event peak discharge in the Turkey Creek was dominated by shallow subsurface runoff and was correlated with 48 h precipitation totals. Estimated precipitation intensity–duration–frequency and flood frequency relationships were found to be larger than those found by NOAA for the 1893–2002 period (for durations ≥ 3 h), and by USGS regional frequencies (for ≥10-year return intervals), respectively, for the same location. We recommend an integrated analysis of these data together with available water quality data to (1) assess the impacts of rising tides on the hydroperiod and biogeochemical processes in riparian forests of the estuary headwaters, (2) validate rainfall–runoff models including watershed scale models to assess land use and climate change on hydrology and water quality, and (3) inform watershed restoration goals, strategies, and infrastructure design in coastal watersheds.
Functional Method for Analyzing Open-Space Ratios around Individual Buildings and Its Implementation with GIS
Authors: Okabe Kayo , Okabe Atsuyuki
Published: February 2024

An open-space ratio is often used as a first basic metric to examine the distribution of open space in urbanized areas. Originally, the open-space ratio was defined as the ratio of the area of open space (unbuilt area) to the area of its building site. In recent years, residents have become more concerned with the open-space ratios in the broader neighborhoods of their individual buildings than with their own building sites. To address this concern, this paper proposes a method for dealing with the open-space ratio in the variable x-meter buffer zone around each building, called the open-space ratio function, and implements it using standard GIS operators. The function and its implemented analytical tool can answer the following questions. First, this function shows how the ratio varies with respect to the bandwidth to discuss the modifiable area unit problem. Second, as the ratio changes, the function shows in which bandwidth zone the ratio is the highest, indicating the best open-space environment zone. Third, in the pairwise comparison for housing selection, the function shows in which bandwidth zone a specific house is better than another. Fourth, the function shows in which bandwidth zone the variance among all buildings in a region is the greatest. Fifth, in this zone, buildings are clustered in terms of open-space ratio. The resulting clusters are the most distinct. Sixth, to examine the open-space ratio around a clump of buildings (such as a housing complex), the function shows how to obtain clumps. Seventh, it is shown how the open-space function provides a wide range of applicability without changing the mathematical formulation. Finally, this paper shows how to implement the function in a simple computational method using operators and a processing modeler provided by the standard GIS without additional software.
Genomic Regions and Candidate Genes Affecting Response to Heat Stress with Newcastle Virus Infection in Commercial Layer Chicks Using Chicken 600K Single Nucleotide Polymorphism Array
Authors: Wang Ying , Saelao Perot , Chanthavixay Ganrea , Gallardo Rodrigo A. , Wolc Anna , Fulton Janet E. , Dekkers Jack M. , Lamont Susan J. , Kelly Terra R. , Zhou Huaijun
Published: February 2024

Heat stress results in significant economic losses to the poultry industry. Genetics plays an important role in chickens adapting to the warm environment. Physiological parameters such as hematochemical parameters change in response to heat stress in chickens. To explore the genetics of heat stress resilience in chickens, a genome-wide association study (GWAS) was conducted using Hy-Line Brown layer chicks subjected to either high ambient temperature or combined high temperature and Newcastle disease virus infection. Hematochemical parameters were measured during three treatment phases: acute heat stress, chronic heat stress, and chronic heat stress combined with NDV infection. Significant changes in blood parameters were recorded for 11 parameters (sodium (Na+, potassium (K+), ionized calcium (iCa2+), glucose (Glu), pH, carbon dioxide partial pressure (PCO2), oxygen partial pressure (PO2), total carbon dioxide (TCO2), bicarbonate (HCO3), base excess (BE), and oxygen saturation (sO2)) across the three treatments. The GWAS revealed 39 significant SNPs (p < 0.05) for seven parameters, located on Gallus gallus chromosomes (GGA) 1, 3, 4, 6, 11, and 12. The significant genomic regions were further investigated to examine if the genes within the regions were associated with the corresponding traits under heat stress. A candidate gene list including genes in the identified genomic regions that were also differentially expressed in chicken tissues under heat stress was generated. Understanding the correlation between genetic variants and resilience to heat stress is an important step towards improving heat tolerance in poultry.
Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease
Authors: Angelopoulou Efthalia , Koros Christos , Hatzimanolis Alexandros , Stefanis Leonidas , Scarmeas Nikolaos , Papageorgiou Sokratis G.
Published: February 2024

The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer’s disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline.
Beyond Amyloid: A Machine Learning-Driven Approach Reveals Properties of Potent GSK-3β Inhibitors Targeting Neurofibrillary Tangles
Authors: Nwadiugwu Martin , Onwuekwe Ikenna , Ezeanolue Echezona , Deng Hongwen
Published: February 2024

Current treatments for Alzheimer’s disease (AD) focus on slowing memory and cognitive decline, but none offer curative outcomes. This study aims to explore and curate the common properties of active, drug-like molecules that modulate glycogen synthase kinase 3β (GSK-3β), a well-documented kinase with increased activity in tau hyperphosphorylation and neurofibrillary tangles—hallmarks of AD pathology. Leveraging quantitative structure–activity relationship (QSAR) data from the PubChem and ChEMBL databases, we employed seven machine learning models: logistic regression (LogR), k-nearest neighbors (KNN), random forest (RF), support vector machine (SVM), extreme gradient boosting (XGB), neural networks (NNs), and ensemble majority voting. Our goal was to correctly predict active and inactive compounds that inhibit GSK-3β activity and identify their key properties. Among the six individual models, the NN demonstrated the highest performance with a 79% AUC-ROC on unbalanced external validation data, while the SVM model was superior in accurately classifying the compounds. The SVM and RF models surpassed NN in terms of Kappa values, and the ensemble majority voting model demonstrated slightly better accuracy to the NN on the external validation data. Feature importance analysis revealed that hydrogen bonds, phenol groups, and specific electronic characteristics are important features of molecular descriptors that positively correlate with active GSK-3β inhibition. Conversely, structural features like imidazole rings, sulfides, and methoxy groups showed a negative correlation. Our study highlights the significance of structural, electronic, and physicochemical descriptors in screening active candidates against GSK-3β. These predictive features could prove useful in therapeutic strategies to understand the important properties of GSK-3β candidate inhibitors that may potentially benefit non-amyloid-based AD treatments targeting neurofibrillary tangles.
Mast Cells in Autism Spectrum Disorder—The Enigma to Be Solved?
Authors: Kovacheva Eleonora , Gevezova Maria , Maes Michael , Sarafian Victoria
Published: February 2024

Autism Spectrum Disorder (ASD) is a disturbance of neurodevelopment with a complicated pathogenesis and unidentified etiology. Many children with ASD have a history of “allergic symptoms”, often in the absence of mast cell (MC)-positive tests. Activation of MCs by various stimuli may release molecules related to inflammation and neurotoxicity, contributing to the development of ASD. The aim of the present paper is to enrich the current knowledge on the relationship between MCs and ASD by discussing key molecules and immune pathways associated with MCs in the pathogenesis of autism. Cytokines, essential marker molecules for MC degranulation and therapeutic targets, are also highlighted. Understanding the relationship between ASD and the activation of MCs, as well as the involved molecules and interactions, are the main points contributing to solving the enigma. Key molecules, associated with MCs, may provide new insights to the discovery of drug targets for modeling inflammation in ASD.
Polyelectrolyte Microcapsules: An Extended Release System for the Antiarrhythmic Complex of Allapinin with Glycyrrhizic Acid Salt
Authors: Salikhov Shavkat I. , Musin Egor V. , Kim Aleksandr L. , Oshchepkova Yulia I. , Tikhonenko Sergey A.
Published: February 2024

Allapinin has antiarrhythmic activity and can be used to prevent and treat various supraventricular and ventricular arrhythmias. Nevertheless, it is highly toxic and has a number of side effects associated with non-specific accumulation in various tissues. The complex of this substance with the monoammonium salt of glycyrrhizic acid (Al:MASGA) has less toxicity and improved antiarrhythmic activity. However, the encapsulation of Al:MASGA in polyelectrolyte microcapsules (PMC) for prolonged release will reduce the residual adverse effects of this drug. In this work, the possibility of encapsulating the allapinin–MASGA complex in polyelectrolyte microcapsules based on polyallylamine and polystyrene sulfonate was investigated. The encapsulation methods of the allapinin–MASGA in polyelectrolyte microcapsules by adsorption and coprecipitation were compared. It was found that the coprecipitation method did not result in the encapsulation of Al:MASGA. The sorption method facilitated the encapsulation of up to 80% of the original substance content in solution in PMC. The release of the encapsulated substance was further investigated, and it was shown that the release of the encapsulated Al:MASGA was independent of the substance content in the capsules, but at pH 5, a two-fold decrease in the rate of drug release was observed.
The Impact of Salinity on Crop Yields and the Confrontational Behavior of Transcriptional Regulators, Nanoparticles, and Antioxidant Defensive Mechanisms under Stressful Conditions: A Review
Authors: Ahmed Mostafa , Tóth Zoltán , Decsi Kincső
Published: February 2024

One of the most significant environmental challenges to crop growth and yield worldwide is soil salinization. Salinity lowers soil solution water potential, causes ionic disequilibrium and specific ion effects, and increases reactive oxygen species (ROS) buildup, causing several physiological and biochemical issues in plants. Plants have developed biological and molecular methods to combat salt stress. Salt-signaling mechanisms regulated by phytohormones may provide additional defense in salty conditions. That discovery helped identify the molecular pathways that underlie zinc-oxide nanoparticle (ZnO-NP)-based salt tolerance in certain plants. It emphasized the need to study processes like transcriptional regulation that govern plants’ many physiological responses to such harsh conditions. ZnO-NPs have shown the capability to reduce salinity stress by working with transcription factors (TFs) like AP2/EREBP, WRKYs, NACs, and bZIPs that are released or triggered to stimulate plant cell osmotic pressure-regulating hormones and chemicals. In addition, ZnO-NPs have been shown to reduce the expression of stress markers such as malondialdehyde (MDA) and hydrogen peroxide (H2O2) while also affecting transcriptional factors. Those systems helped maintain protein integrity, selective permeability, photosynthesis, and other physiological processes in salt-stressed plants. This review examined how salt stress affects crop yield and suggested that ZnO-NPs could reduce plant salinity stress instead of osmolytes and plant hormones.
Analysis of the AIRE Gene Promoter in Patients Affected by Autoimmune Polyendocrine Syndromes
Authors: Cudini Annamaria , Nardella Caterina , Bellacchio Emanuele , Palma Alessia , Delfino Domenico Vittorio , Betterle Corrado , Cappa Marco , Fierabracci Alessandra
Published: February 2024

Autoimmune polyglandular syndromes (APS) are classified into four main categories, APS1–APS4. APS1 is caused by AIRE gene loss of function mutations, while the genetic background of the other APS remains to be clarified. Here, we investigated the potential association between AIRE gene promoter Single Nucleotide Polymorphisms (SNPs) and susceptibility to APS. We sequenced the AIRE gene promoter of 74 APS patients, also analyzing their clinical and autoantibody profile, and we further conducted molecular modeling studies on the identified SNPs. Overall, we found 6 SNPs (-230Y, -655R, -261M, -380S, -191M, -402S) of the AIRE promoter in patients’ DNA. Interestingly, folding free energy calculations highlighted that all identified SNPs, except for -261M, modify the stability of the nucleic acid structure. A rather similar percentage of APS3 and APS4 patients had polymorphisms in the AIRE promoter. Conversely, there was no association between APS2 and AIRE promoter polymorphisms. Further AIRE promoter SNPs were found in 4 out of 5 patients with APS1 clinical diagnosis that did not harbor AIRE loss of function mutations. We hypothesize that AIRE promoter polymorphisms could contribute to APS predisposition, although this should be validated through genetic screening in larger patient cohorts and in vitro and in vivo functional studies.
Targeted Suicide Gene Therapy with Retroviral Replicating Vectors for Experimental Canine Cancers
Authors: Sonoda-Fukuda Emiko , Takeuchi Yuya , Ogawa Nao , Noguchi Shunsuke , Takarada Toru , Kasahara Noriyuki , Kubo Shuji
Published: February 2024

Cancer in dogs has increased in recent years and is a leading cause of death. We have developed a retroviral replicating vector (RRV) that specifically targets cancer cells for infection and replication. RRV carrying a suicide gene induced synchronized killing of cancer cells when administered with a prodrug after infection. In this study, we evaluated two distinct RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV) in canine tumor models both in vitro and in vivo. Despite low infection rates in normal canine cells, both RRVs efficiently infected and replicated within all the canine tumor cells tested. The efficient intratumoral spread of the RRVs after their intratumoral injection was also demonstrated in nude mouse models of subcutaneous canine tumor xenografts. When both RRVs encoded a yeast cytosine deaminase suicide gene, which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil, they caused tumor-cell-specific 5-FC-induced killing of the canine tumor cells in vitro. Furthermore, in the AZACF- and AZACH-cell subcutaneous tumor xenograft models, both RRVs exerted significant antitumor effects. These results suggest that RRV-mediated suicide gene therapy is a novel therapeutic approach to canine cancers.
Intersecting Pathways: Nonalcoholic Fatty Liver Disease and Psoriasis Duet—A Comprehensive Review
Authors: Costache Daniel , Blejan Horia , Cojocaru Damian , Ioniță Georgiana , Poenaru Marcela , Constantin Maria , Costache Andrei , Căruntu Constantin , Balaban Daniel , Costache Raluca
Published: February 2024

Psoriasis is a chronic, immune-mediated, inflammatory disease that has a major impact on patients’ quality of life. Common psoriasis-associated comorbidities include cardiovascular diseases, psoriatic arthritis, inflammatory bowel syndromes, type-2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is affecting a substantial portion of the population and is closely linked with psoriasis. The interplay involves low-grade chronic inflammation, insulin resistance, and genetic factors. The review presents the pathophysiological connections between psoriasis and nonalcoholic fatty liver disease, emphasizing the role of cytokines, adipokines, and inflammatory cascades. The “hepato-dermal axis” is introduced, highlighting how psoriatic inflammation potentiates hepatic inflammation and vice versa. According to the new guidelines, the preliminary examination for individuals with psoriasis should encompass evaluations of transaminase levels and ultrasound scans as part of the initial assessment for this cohort. Considering the interplay, recent guidelines recommend screening for NAFLD in moderate-to-severe psoriasis cases. Treatment implications arise, particularly with medications impacting liver function. Understanding the intricate relationship between psoriasis and NAFLD provides valuable insights into shared pathogenetic mechanisms. This knowledge has significant clinical implications, guiding screening practices, treatment decisions, and the development of future therapeutic approaches for these chronic conditions.
Biosynthesis and Biodegradation—Eco-Concept for Polymer Materials
Authors: Rydz Joanna , Sikorska Wanda , Musioł Marta
Published: February 2024

Polymers have become essential for various aspects of modern life, including packaging, transportation, and electronics [...]
Molecular Behavior of α-Synuclein Is Associated with Membrane Transport, Lipid Metabolism, and Ubiquitin–Proteasome Pathways in Lewy Body Disease
Authors: Kon Tomoya , Lee Seojin , Martinez-Valbuena Ivan , Yoshida Koji , Tanikawa Satoshi , Lang Anthony E. , Kovacs Gabor G.
Published: February 2024

Lewy body diseases (LBDs) feature α-synuclein (α-syn)-containing Lewy bodies, with misfolded α-syn potentially propagating as seeds. Using a seeding amplification assay, we previously reported distinct α-syn seeding in LBD cases based on the area under seeding curves. This study revealed that LBD cases showing different α-syn seeding kinetics have distinct proteomics profiles, emphasizing disruptions in mitochondria and lipid metabolism in high-seeder cases. Though the mechanisms underlying LBD development are intricate, the factors influencing α-syn seeding activity remain elusive. To address this and complement our previous findings, we conducted targeted transcriptome analyses in the substantia nigra using the nanoString nCounter assay together with histopathological evaluations in high (n = 4) and low (n = 3) nigral α-syn seeders. Neuropathological findings (particularly the substantia nigra) were consistent between these groups and were characterized by neocortical LBD associated with Alzheimer’s disease neuropathologic change. Among the 1811 genes assessed, we identified the top 20 upregulated and downregulated genes and pathways in α-syn high seeders compared with low seeders. Notably, alterations were observed in genes and pathways related to transmembrane transporters, lipid metabolism, and the ubiquitin–proteasome system in the high α-syn seeders. In conclusion, our findings suggest that the molecular behavior of α-syn is the driving force in the neurodegenerative process affecting the substantia nigra through these identified pathways. These insights highlight their potential as therapeutic targets for attenuating LBD progression.
Enhanced Reduction of Ferredoxin in PGR5-Deficient Mutant of Arabidopsis thaliana Stimulated Ferredoxin-Dependent Cyclic Electron Flow around Photosystem I
Authors: Maekawa Shu , Ohnishi Miho , Wada Shinya , Ifuku Kentaro , Miyake Chikahiro
Published: February 2024

The molecular entity responsible for catalyzing ferredoxin (Fd)-dependent cyclic electron flow around photosystem I (Fd-CEF) remains unidentified. To reveal the in vivo molecular mechanism of Fd-CEF, evaluating ferredoxin reduction–oxidation kinetics proves to be a reliable indicator of Fd-CEF activity. Recent research has demonstrated that the expression of Fd-CEF activity is contingent upon the oxidation of plastoquinone. Moreover, chloroplast NAD(P)H dehydrogenase does not catalyze Fd-CEF in Arabidopsis thaliana. In this study, we analyzed the impact of reduced Fd on Fd-CEF activity by comparing wild-type and pgr5-deficient mutants (pgr5hope1). PGR5 has been proposed as the mediator of Fd-CEF, and pgr5hope1 exhibited a comparable CO2 assimilation rate and the same reduction–oxidation level of PQ as the wild type. However, P700 oxidation was suppressed with highly reduced Fd in pgr5hope1, unlike in the wild type. As anticipated, the Fd-CEF activity was enhanced in pgr5hope1 compared to the wild type, and its activity further increased with the oxidation of PQ due to the elevated CO2 assimilation rate. This in vivo research clearly demonstrates that the expression of Fd-CEF activity requires not only reduced Fd but also oxidized PQ. Importantly, PGR5 was found to not catalyze Fd-CEF, challenging previous assumptions about its role in this process.
Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy
Authors: Zhang Teng , Qian Cheng , Song Mengyao , Tang Yu , Zhou Yueke , Dong Guanglu , Shen Qiuhong , Chen Wenxing , Wang Aiyun , Shen Sanbing , Zhao Yang , Lu Yin
Published: February 2024

Since its inception, induced pluripotent stem cell (iPSC) technology has been hailed as a powerful tool for comprehending disease etiology and advancing drug screening across various domains. While earlier iPSC-based disease modeling and drug assessment primarily operated at the cellular level, recent years have witnessed a significant shift towards organoid-based investigations. Organoids derived from iPSCs offer distinct advantages, particularly in enabling the observation of disease progression and drug metabolism in an in vivo-like environment, surpassing the capabilities of iPSC-derived cells. Furthermore, iPSC-based cell therapy has emerged as a focal point of clinical interest. In this review, we provide an extensive overview of non-integrative reprogramming methods that have evolved since the inception of iPSC technology. We also deliver a comprehensive examination of iPSC-derived organoids, spanning the realms of the nervous system, cardiovascular system, and oncology, as well as systematically elucidate recent advancements in iPSC-related cell therapies.
Combined PIK3CA and SOX2 Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading
Authors: Montoro-Jiménez Irene , Granda-Díaz Rocío , Menéndez Sofía T. , Prieto-Fernández Llara , Otero-Rosales María , Álvarez-González Miguel , García-de-la-Fuente Vanessa , Rodríguez Aida , Rodrigo Juan P. , Álvarez-Teijeiro Saúl , García-Pedrero Juana M. , Hermida-Prado Francisco
Published: February 2024

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.
Bioluminescence of (R)-Cypridina Luciferin with Cypridina Luciferase
Authors: Kanie Shusei , Wu Chun , Kihira Kiyohito , Yasuno Rie , Mitani Yasuo , Ohmiya Yoshihiro
Published: February 2024

Cypridina luciferin (CypL) is a marine natural product that functions as the luminous substrate for the enzyme Cypridina luciferase (CypLase). CypL has two enantiomers, (R)- and (S)-CypL, due to its one chiral center at the sec-butyl moiety. Previous studies reported that (S)-CypL or racemic CypL with CypLase produced light, but the luminescence of (R)-CypL with CypLase has not been investigated. Here, we examined the luminescence of (R)-CypL, which had undergone chiral separation from the enantiomeric mixture, with a recombinant CypLase. Our luminescence measurements demonstrated that (R)-CypL with CypLase produced light, indicating that (R)-CypL must be considered as the luminous substrate for CypLase, as in the case of (S)-CypL, rather than a competitive inhibitor for CypLase. Additionally, we found that the maximum luminescence intensity from the reaction of (R)-CypL with CypLase was approximately 10 fold lower than that of (S)-CypL with CypLase, but our kinetic analysis of CypLase showed that the Km value of CypLase for (R)-CypL was approximately 3 fold lower than that for (S)-CypL. Furthermore, the chiral high-performance liquid chromatography (HPLC) analysis of the reaction mixture of racemic CypL with CypLase showed that (R)-CypL was consumed more slowly than (S)-CypL. These results indicate that the turnover rate of CypLase for (R)-CypL was lower than that for (S)-CypL, which caused the less efficient luminescence of (R)-CypL with CypLase.
A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging
Authors: Digpal Ronneil , Arkill Kenton P. , Doherty Regan , Yates Joseph , Milne Lorna K. , Broomes Nicole , Katsamenis Orestis L. , Macdonald Jason , Ditchfield Adam , Narata Ana Paula , Darekar Angela , Carare Roxana O. , Fabian Mark , Galea Ian , Bulters Diederik
Published: February 2024

Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, p = 0.001 and p = 0.002), endothelial cell markers (CD34 and CD31, p = 0.007 and p = 0.003), glycans (Alcian blue, p = 0.003) and wall thickness (p = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown.
Integrated Metabolome and Transcriptome Analysis of Gibberellins Mediated the Circadian Rhythm of Leaf Elongation by Regulating Lignin Synthesis in Maize
Authors: Yao Qingqing , Feng Ying , Wang Jiajie , Zhang Yushi , Yi Fei , Li Zhaohu , Zhang Mingcai
Published: February 2024

Plant growth exhibits rhythmic characteristics, and gibberellins (GAs) are involved in regulating cell growth, but it is still unclear how GAs crosstalk with circadian rhythm to regulate cell elongation. The study analyzed growth characteristics of wild-type (WT), zmga3ox and zmga3ox with GA3 seedlings. We integrated metabolomes and transcriptomes to study the interaction between GAs and circadian rhythm in mediating leaf elongation. The rates of leaf growth were higher in WT than zmga3ox, and zmga3ox cell length was shorter when proliferated in darkness than light, and GA3 restored zmga3ox leaf growth. The differentially expressed genes (DEGs) between WT and zmga3ox were mainly enriched in hormone signaling and cell wall synthesis, while DEGs in zmga3ox were restored to WT by GA3. Moreover, the number of circadian DEGs that reached the peak expression in darkness was more than light, and the upregulated circadian DEGs were mainly enriched in cell wall synthesis. The differentially accumulated metabolites (DAMs) were mainly attributed to flavonoids and phenolic acid. Twenty-two DAMs showed rhythmic accumulation, especially enriched in lignin synthesis. The circadian DEGs ZmMYBr41/87 and ZmHB34/70 were identified as regulators of ZmHCT8 and ZmBM1, which were enzymes in lignin synthesis. Furthermore, GAs regulated ZmMYBr41/87 and ZmHB34/70 to modulate lignin biosynthesis for mediating leaf rhythmic growth.
The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity
Authors: Cho Eun-Hwa , In Chi-Bum , Lee Gyu-Won , Hong Seung-Wan , Seo Eun-Hye , Lee Won Hyung , Kim Seong-Hyop
Published: February 2024

This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype.
Efficacy and Safety of Thermal Ablation after Endoscopic Mucosal Resection: A Systematic Review and Network Meta-Analysis
Authors: Haghbin Hossein , Zakirkhodjaev Nuruddinkhodja , Fatima Rawish , Kamal Faisal , Aziz Muhammad
Published: February 2024

(1) Background: Large colonic polyps during colonoscopy can be managed by Endoscopic mucosal resection (EMR). To decrease the polyp recurrence rate, thermal ablation methods like argon plasma coagulation (APC) and snare tip soft coagulation (STSC) have been introduced. We performed this network meta-analysis to assess the efficacy and safety of these modalities. (2) Methods: We performed a comprehensive literature review, through 5 January 2024, of databases including Embase, PubMed, SciELO, KCI, Cochrane Central, and Web of Science. Using a random effects model, we conducted a frequentist approach network meta-analysis. The risk ratio (RR) with 95% confidence interval (CI) was calculated. Safety and efficacy endpoints including rates of recurrence, bleeding, perforation, and post polypectomy syndrome were compared. (3) Results: Our search yielded a total of 13 studies with 2686 patients. Compared to placebo, both APC (RR: 0.33 CI: 0.20–0.54, p < 0.01) and STSC (RR: 0.27, CI: 0.21–0.34, p < 0.01) showed decreased recurrence rates. On ranking, STSC showed the lowest recurrence rate, followed by APC and placebo. Regarding individual adverse events, there was no statistically significant difference between either of the thermal ablation methods and placebo. (4) Conclusions: We demonstrated the efficacy and safety of thermal ablation after EMR for decreasing recurrence of adenoma.
First Italian Experience with the Oxinium Metal-Backed Fixed-Bearing Medial Journey II Unicompartmental Knee System: Promising Short-Term Outcomes of 145 Cases
Authors: D’Amario Federico , De Berardinis Luca , Zanon Giacomo , Qordja Fjorela , Vitale Umberto , Gigante Antonio Pompilio
Published: February 2024

(1) Background: Unicompartmental knee arthroplasty (UKA) provides a viable alternative to total knee arthroplasty (TKA) in patients with isolated medial osteoarthritis (OA). From 2007 to 2021, 23% of all primary knee arthroplasties in Italy were UKAs. We retrospectively evaluated clinical outcomes and satisfaction in patients implanted with a new oxinium metal-backed fixed-bearing medial unicompartmental prosthesis at a 24-month follow-up. (2) Methods: From December 2020 to December 2021, 145 patients were treated by a single surgeon at a single institution using the hypoallergenic Journey II prosthesis. Clinical outcome measures included the Knee Society Knee Score (KSKS), Knee Society Function Score (KSFS), Oxford Knee Society (OKS) score, University of California Los Angeles Activity Score (UCLA), the Physical Component Summary (PCS), and the Mental Component Summary (MCS), and were calculated preoperatively and at 12 and 24 months. The Forgotten Joint Score-12 (FJS-12) was calculated at 12 and 24 months. Patient satisfaction was collected at 24 months. The scores were compared using the Friedman test. (3) Results: All clinical scores improved significantly from baseline to 24 months (p < 0.0001), except for the FJS-12, which from 12 to 24 months did not improve significantly (p = 0.041). Patient satisfaction was 9.32 ± 0.74 out of 10. No patient experienced complications or required revision surgery. (4) Conclusions: The Journey II unicompartmental prosthesis is a valuable treatment option for end-stage medial OA, improving knee function, providing pain relief, and ensuring high patient satisfaction at 24 months.
FGFR3 Mutations in Urothelial Carcinoma: A Single-Center Study Using Next-Generation Sequencing
Authors: Yu Seong Hyeon , Kim Sung sun , Kim Shinseung , Lee Hyungki , Kang Taek Won
Published: February 2024

Background: Mutations of fibroblast growth factor receptor 3 (FGFR3) are associated with urothelial carcinoma (UC) oncogenesis and are considered an important therapeutic target. Therefore, we evaluated the FGFR3 mutation rate and its clinical significance in urothelial carcinoma (UC) using next-generation sequencing. Methods: A total of 123 patients with UC who were treated at Chonnam National University Hospital (Gwang-ju, Korea) from January 2018 to December 2020 were enrolled. We performed NGS using the Oncomine panel with tumor specimens and blood samples corresponding to each specimen. We analyzed the FGFR3 mutation results according to the type of UC and the effects on early recurrence and progression. Results: The mean age of the patients was 71.39 ± 9.33 years, and 103 patients (83.7%) were male. Overall, the FGFR3 mutation rate was 30.1% (37 patients). The FGFR3 mutation rate was the highest in the non-muscle-invasive bladder cancer (NMIBC) group (45.1%), followed by the muscle-invasive bladder cancer (22.7%) and upper tract UC (UTUC) (14.3%) groups. Patients with FGFR3 mutations had a significantly lower disease stage (p = 0.019) but a high-risk of NMIBC (p < 0.001). Conclusions: Our results revealed that FGFR3 mutations were more prevalent in patients with NMIBC and lower stage UC and associated with a high-risk of NMIBC. Large multicenter studies are needed to clarify the clinical significance of FGFR3 mutations in UC.
CT-Assessment of Epicardial Fat Identifies Increased Inflammation at the Level of the Left Coronary Circulation in Patients with Atrial Fibrillation
Authors: Gerculy Renáta , Benedek Imre , Kovács István , Rat Nóra , Halațiu Vasile Bogdan , Rodean Ioana , Bordi Lehel , Blîndu Emanuel , Roșca Aurelian , Mátyás Botond-Barna , Szabó Evelin , Parajkó Zsolt , Benedek Theodora
Published: February 2024

Background: Atrial fibrillation (AF) can often be triggered by an inflammatory substrate. Perivascular inflammation may be assessed nowadays using coronary computed tomography angiography (CCTA) imaging. The new pericoronary fat attenuation index (FAI HU) and the FAI Score have prognostic value for predicting future cardiovascular events. Our purpose was to investigate the correlation between pericoronary fat inflammation and the presence of AF among patients with coronary artery disease. Patients and methods: Eighty-one patients (mean age 64.75 ± 7.84 years) who underwent 128-slice CCTA were included in this study and divided into two groups: group 1 comprised thirty-six patients with documented AF and group 2 comprised forty-five patients without a known history of AF. Results: There were no significant differences in the absolute value of fat attenuation between the study groups (p > 0.05). However, the mean FAI Score was significantly higher in patients with AF (15.53 ± 10.29 vs. 11.09 ± 6.70, p < 0.05). Regional analysis of coronary inflammation indicated a higher level of this process, especially at the level of the left anterior descending artery (13.17 ± 7.91 in group 1 vs. 8.80 ± 4.75 in group 2, p = 0.008). Conclusions: Patients with AF present a higher level of perivascular inflammation, especially in the region of the left coronary circulation, and this seems to be associated with a higher risk of AF development.
Expanding the Armamentarium of Donor Sites in Microvascular Head and Neck Reconstruction
Authors: Lee Z-Hye , Canzi Ana , Yu Jessie , Chang Edward I.
Published: February 2024

The field of microsurgical head and neck reconstruction has witnessed tremendous advancements in recent years. While the historic goals of reconstruction were simply to maximize flap survival, optimizing both aesthetic and functional outcomes has now become the priority. With an increased understanding of perforator anatomy, improved technology in instruments and microscopes, and high flap success rates, the reconstructive microsurgeon can push the envelope in harvesting and designing the ideal flap to aid patients following tumor extirpation. Furthermore, with improvements in cancer treatment leading to improved patient survival and prognosis, it becomes increasingly important to have a broader repertoire of donor sites. The present review aims to provide a review of newly emerging soft tissue flap options in head and neck reconstruction. While certainly a number of bony flap options also exist, the present review will focus on soft tissue flaps that can be harvested reliably from a variety of alternate donor sites. From the upper extremity, the ulnar forearm as well as the lateral arm, and from the lower extremity, the profunda artery perforator, medial sural artery perforator, and superficial circumflex iliac perforator flaps will be discussed, and we will provide details to aid reconstructive microsurgeons in incorporating these alternative flaps into their armamentarium.
Anti-Arrhythmic Effects of Heart Failure Guideline-Directed Medical Therapy and Their Role in the Prevention of Sudden Cardiac Death: From Beta-Blockers to Sodium-Glucose Cotransporter 2 Inhibitors and Beyond
Authors: Zaher Wael , Della Rocca Domenico Giovanni , Pannone Luigi , Boveda Serge , de Asmundis Carlo , Chierchia Gian-Battista , Sorgente Antonio
Published: February 2024

Sudden cardiac death (SCD) accounts for a substantial proportion of mortality in heart failure with reduced ejection fraction (HFrEF), frequently triggered by ventricular arrhythmias (VA). This review aims to analyze the pathophysiological mechanisms underlying VA and SCD in HFrEF and evaluate the effectiveness of guideline-directed medical therapy (GDMT) in reducing SCD. Beta-blockers, angiotensin receptor–neprilysin inhibitors, and mineralocorticoid receptor antagonists have shown significant efficacy in reducing SCD risk. While angiotensin-converting enzyme inhibitors and angiotensin receptor blockers exert beneficial impacts on the renin-angiotensin-aldosterone system, their direct role in SCD prevention remains less clear. Emerging treatments like sodium-glucose cotransporter 2 inhibitors show promise but necessitate further research for conclusive evidence. The favorable outcomes of those molecules on VA are notably attributable to sympathetic nervous system modulation, structural remodeling attenuation, and ion channel stabilization. A multidimensional pharmacological approach targeting those pathophysiological mechanisms offers a complete and synergy approach to reducing SCD risk, thereby highlighting the importance of optimizing GDMT for HFrEF. The current landscape of HFrEF pharmacotherapy is evolving, with ongoing research needed to clarify the full extent of the anti-arrhythmic benefits offered by both existing and new treatments.
Atrial Fibrillation Catheter Ablation among Cancer Patients: Utilization Trends and In-Hospital Outcomes
Authors: Margolis Gilad , Goldhaber Ofir , Kazatsker Mark , Kobo Ofer , Roguin Ariel , Leshem Eran
Published: February 2024

Background: Atrial fibrillation (AF) catheter ablation in cancer patients has been evaluated in very few studies. We aimed to investigate utilization trends and in-hospital outcomes of AF catheter ablation among cancer patients in a large US inpatient registry. Methods: Utilizing the National Inpatient Sample (NIS) database, patients who underwent AF catheter ablation between 2012 and 2019 were identified. Sociodemographic, clinical data, in-hospital procedures and outcomes were collected. Baseline characteristics and in-hospital outcomes were compared between patients with and without cancer. Results: An estimated total of 67,915 patients underwent AF catheter ablation between 2012 and 2019 in the US. Of them, 950 (1.4%) had a cancer diagnosis. Patients with a cancer diagnosis were older and had higher Charlson Comorbidity Index, CHA2DS2-VASc and ATRIA bleeding indices scores. A higher rate of total complications was observed in cancer patients (10.5% vs. 7.9, p < 0.001), driven mainly by more bleeding and infectious complications. However, no significant differences in cardiac or neurological complications as well as in-hospital mortality rates were observed and were relatively low in both groups. Conclusions: AF catheter ablation in cancer patients is associated with higher bleeding and infectious complication rates, but not with increased cardiac complications or in-hospital mortality in a US nationwide, all-comer registry.