bluuebunny/crossref_metadata_2025 huggingface dataset:
Nesting Habitat Selection and Suitable Breeding Habitat of Blue-Crowned Laughingthrush: Implication on Its Habitat Conservation
Authors: Huang Xinjie , Tian Shan , Liu Zhengxiao , Xu Jiliang
Published: June 2023

Understanding the impact of human disturbance on the breeding habitat selection of endangered species is critical to improving their conservation. Blue-crowned Laughingthrush Pterorhinus courtoisi (Ménégaux, 1923) syn. Garrulax courtoisi (Passeriformes: Leiotrichidae) is an endangered species in China. To explore the nesting habitat selection of the Blue-crowned Laughingthrush and its response to human disturbance during the breeding period, we conducted a field survey at its nesting sites in Wuyuan County and Dexing City, Jiangxi Province, from March to July 2021 and in June 2022. At the home range scale (200 m) the results of a principal component analysis (PCA) showed that this species had a clear preference for infrastructure construction, grassland, farmland and bare land. At the microhabitat scale (12.26 m), we compared the ecological parameters of a nest plot and control plot using a Kruskal–Wallis H test and found that there were significant differences in the vegetation coverage, crown breadth, shrub coverage, herb maximum height, herb average height and herb species number of the nesting area between the two groups. Ensemble species distribution models showed that the suitable habitat of the Blue-crowned Laughingthrush covered an area of 108.67 km2. Distance to waterways, deciduous broadleaved forests and roads were the main factors impacting the habitat distribution of the Blue-crowned Laughingthrush. Our study suggests that (1) it is highly important to improve the protection of breeding sites and suitable living areas close to the settlements and preserve a certain nesting habitat selection space for the Blue-crowned Laughingthrush during the breeding period; and (2) it is necessary to continue to monitor the potential suitable breeding habitat. This study provides a scientific basis for the protection of the Blue-crowned Laughingthrush by local forestry bureaus and conservation departments in the future.
Phenotypic Diversity Analysis in Elaeagnus angustifolia Populations in Gansu Province, China
Authors: Shi Rongrong , Zhu Zhu , Shi Ningrui , Li Yongmei , Dang Jun , Wang Yanli , Ma Yonglong , Xu Xiangyun , Liu Ting
Published: June 2023

As a highly resistant urban ornamental plant, Elaeagnus angustifolia L. is often used in dry land, saline-alkali land shelter forest, and landscape horticulture. It is the main windbreak and sand-fixing tree species in Gansu Province, China. The special geographical and climatic environment makes the distribution and growth of E. angustifolia in Gansu Province show different degrees of difference. In order to evaluate the phenotypic diversity of E. angustifolia in different populations and its variation patterns under different geographical and climatic conditions, 35 phenotypic traits (trunk, branch, leaf, and flower related traits) of 90 plants from 10 populations in Gansu Province were measured and analyzed. The results showed the following: (1) E. angustifolia has rich phenotypic variation. The variation is greater among populations. The traits with the largest and smallest coefficients of variation were “under-branch height” and “flower diameter”, respectively. The variation in the Qilihe population was the largest, and the variation in the Ganzhou population was the smallest. The diversity of flowers and leaves is relatively higher. (2) Correlation analysis showed that most of traits were closely related. Leaf traits showed a gradient variation law dominated by altitude and precipitation. Flower traits were affected by the synergistic effects of various geographical and climatic factors. (3) The results of the principal component analysis (PCA) showed that the primary traits affecting the phenotypic diversity of E. angustifolia were leaf size and branch length among the related traits of trunk, branch, leaf, and flower. (4) Cluster analysis showed that 90 E. angustifolia plants were clustered into four clusters that were not completely clustered according to geographical distance and may be randomly affected by genotypic or environmental factors. These results will lay a foundation for further analysis of the genetic mechanism of phenotypic traits of E. angustifolia and also provide a reference for the collection, preservation, and variety improvement of E. angustifolia germplasm resources.
PKD1 Nonsense Variant in a Lagotto Romagnolo Family with Polycystic Kidney Disease
Authors: Drögemüller Michaela , Klein Nadine , Steffensen Rikke Lill , Keiner Miriam , Jagannathan Vidhya , Leeb Tosso
Published: June 2023

A female Lagotto Romagnolo dog with polycystic kidney disease (PKD) and her progeny, including PKD-affected offspring, were studied. All affected dogs appeared clinically inconspicuous, while sonography revealed the presence of renal cysts. The PKD-affected index female was used for breeding and produced two litters with six affected offspring of both sexes and seven unaffected offspring. The pedigrees suggested an autosomal dominant mode of inheritance of the trait. A trio whole genome sequencing analysis of the index female and her unaffected parents identified a de novo heterozygous nonsense variant in the coding region of the PKD1 gene. This variant, NM_001006650.1:c.7195G>T, is predicted to truncate 44% of the open reading frame of the wild-type PKD1 protein, NP_001006651.1:p.(Glu2399*). The finding of a de novo variant in an excellent functional candidate gene strongly suggests that the PKD1 nonsense variant caused the observed phenotype in the affected dogs. Perfect co-segregation of the mutant allele with the PKD phenotype in two litters supports the hypothesized causality. To the best of our knowledge, this is the second description of a PKD1-related canine form of autosomal dominant PKD that may serve as an animal model for similar hepatorenal fibrocystic disorders in humans.
Mathematical Simulation of Honeycomb Weathering via Moisture Transport and Salt Deposition
Authors: Safonov Alexander , Minchenkov Kirill
Published: June 2023

Honeycomb weathering is a common phenomenon found on various rock surfaces all around the world. However, honeycomb formation mechanisms are still poorly understood. In this study, we propose a model describing moisture transport within the sandstone and erosion resulting from salt deposition during evaporation of moisture off the rock surface. The moisture transport model is based on the non-linear diffusion equation, where the volumetric moisture content is a combined parameter accounting for the moisture and gas (vapor) content. The moisture transport model accounts for the several-orders-of-magnitude decrease in moisture diffusivity, observed during drying. It was assumed that erosion occurs when the evaporation front is located close to the rock surface. The depth of erosion is proportional to the moisture flow rate through the drying surface. The ABAQUS finite-element software suite was used for numerical solution of the non-linear diffusion equation. The iterative scheme of erosion simulation for different drying cycles was implemented using the Python programming language. Computations were conducted in the 2D setting for the square model with dimensions of 50 mm × 50 mm. Simulation results demonstrate the possibility of obtaining various landform shapes (honeycombs, tafoni) by varying only the value of the distribution of moisture content at the bottom side, simulating the rate of internal wetting of rock.
First Report of Rose Bent Neck Caused by Sclerotinia sclerotiorum on Commercial Cut Roses (Rosa hybrida L.)
Authors: Muñoz Melissa , Behnke Logan E. , Faust James E. , Schnabel Guido
Published: June 2023

Cut roses are highly valuable ornamentals and their profitability depends on the flower postharvest performance. Bent neck symptoms in roses make them unmarketable and are typically related to physiological disorders, bacteria accumulation in the vase solution, and Botrytis cinerea infection. Unusual bent neck symptoms were observed in 4.7% of ‘Orange Crush’ roses from two commercial shipments, resulting in complete flower collapse. This research was aimed to determine the causal agent of the bent neck symptoms. Following incubation in a humid chamber, symptomatic roses evolved in water-soaked lesions with the presence of white mycelium and sclerotia development. Fungal isolations and molecular characterization were performed and Sclerotinia sclerotiorum was identified as the causal agent of rose bent neck. Therefore, when bent neck symptoms are observed, S. sclerotiorum incidence should be considered to avoid possible outbreaks.
Physical Activity Intensity Measurement and Health: State of the Art and Future Directions for Scientific Research
Authors: Rey-López Juan Pablo , Lee Dong Hoon , Ferrari Gerson , Giovannucci Edward , Rezende Leandro F. M.
Published: June 2023

Physical activity guidelines for health recommend any type of unstructured physical activity for health promotion. Adults should perform at least 150–300 min per week of moderate intensity or 75–150 min per week of vigorous intensity activities, or an equivalent combination of the two intensities. However, the relationship between physical activity intensity and longevity remains a debated topic, with conflicting perspectives offered by epidemiologists, clinical exercise physiologists or anthropologists. This paper addresses the current known role of physical activity intensity (in particular vigorous versus moderate intensity) on mortality and the existing problems of measurement. Given the diversity of existing proposals to categorize physical activity intensity, we call for a common methodology. Device-based physical activity measurements (e.g., wrist accelerometers) have been proposed as a valid method to measure physical activity intensity. An appraisal of the results reported in the literature, however, highlights that wrist accelerometers have not yet demonstrated sufficient criterion validity when they are compared to indirect calorimetry. Novel biosensors and wrist accelerometers will help us understand how different metrics of physical activity relates to human health, however, all these technologies are not enough mature to provide personalized applications for healthcare or sports performance.
Controlling Traffic Congestion in Urbanised City: A Framework Using Agent-Based Modelling and Simulation Approach
Authors: Shaharuddin Raihanah Adawiyah , Misro Md Yushalify
Published: June 2023

Urbanised city transportation simulation needs a wide range of factors to reflect the influence of certain real-life events accurately. The vehicle composition and the timing of the traffic light signal scheduling play an important role in controlling the traffic flow and facilitate road users, particularly in densely populated urban cities. Since road capacity in urban cities changes throughout the day, an optimal traffic light signal duration might be different. Hence, in this paper, the effect of vehicle composition and traffic light phases on traffic flow during peak and off-peak hours in Georgetown, Penang, one of the highly populated cities in Malaysia, is investigated. Through Agent-Based Modelling (ABM), this complex system is simulated by integrating the driver’s behaviour into the model using the GIS and Agent-Based Modelling Architecture (GAMA) simulation platform. The result of predicted traffic flow varies significantly depending on the vehicle composition while the duration of the traffic signal timing has little impact on traffic flow during peak hours. However, during off-peak hour, it is suggested that 20 s duration of green light provides the highest flow compared to 30 s and 40 s duration of green light. This concludes that the planning for traffic light phasing should consider multiple factors since the vehicle composition and traffic light timing for an effective traffic flow varies according to the volume of road users.
The Regulated Secretion and Models of Intracellular Transport: The Goblet Cell as an Example
Authors: Mironov Alexander A. , Beznoussenko Galina V.
Published: June 2023

Transport models are extremely important to map thousands of proteins and their interactions inside a cell. The transport pathways of luminal and at least initially soluble secretory proteins synthesized in the endoplasmic reticulum can be divided into two groups: the so-called constitutive secretory pathway and regulated secretion (RS) pathway, in which the RS proteins pass through the Golgi complex and are accumulated into storage/secretion granules (SGs). Their contents are released when stimuli trigger the fusion of SGs with the plasma membrane (PM). In specialized exocrine, endocrine, and nerve cells, the RS proteins pass through the baso-lateral plasmalemma. In polarized cells, the RS proteins secrete through the apical PM. This exocytosis of the RS proteins increases in response to external stimuli. Here, we analyze RS in goblet cells to try to understand the transport model that can be used for the explanation of the literature data related to the intracellular transport of their mucins.
Preconditioned Chorionic Villus Mesenchymal Stem/Stromal Cells (CVMSCs) Minimize the Invasive Phenotypes of Breast Cancer Cell Line MDA231 In Vitro
Authors: Subayyil Abdullah Al , Basmaeil Yasser S. , Kulayb Hayaa Bin , Alrodayyan Maha , Alhaber Lama Abdulaziz A. , Almanaa Taghreed N. , Khatlani Tanvir
Published: June 2023

Among the newer choices of targeted therapies against cancer, stem cell therapy is gaining importance because of their antitumor properties. Stem cells suppress growth, metastasis, and angiogenesis, and induce apoptosis in cancer cells. In this study, we have examined the impact of the cellular component and the secretome of preconditioned and naïve placenta-derived Chorionic Villus Mesenchymal Stem Cells (CVMSCs) on the functional characteristics of the Human Breast Cancer cell line MDA231. MDA231 cells were treated with preconditioned CVMSCs and their conditioned media (CM), followed by an evaluation of their functional activities and modulation in gene and protein expression. Human Mammary Epithelial Cells (HMECs) were used as a control. CM obtained from the preconditioned CVMSCs significantly altered the proliferation of MDA231 cells, yet no change in other phenotypes, such as adhesion, migration, and invasion, were observed at various concentrations and time points tested. However, the cellular component of preconditioned CVMSCs significantly inhibited several phenotypes of MDA231 cells, including proliferation, migration, and invasion. CVMSCs-treated MDA231 cells exhibited modulation in the expression of various genes involved in apoptosis, oncogenesis, and Epithelial to Mesenchymal Transition (EMT), explaining the changes in the invasive behavior of MDA231 cells. These studies reveal that preconditioned CVMSCs may make useful candidate in a stem cell-based therapy against cancer.
Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy
Authors: Zhou Maggie Y. , Bui Nam Q. , Charville Gregory W. , Ganjoo Kristen N. , Pan Minggui
Published: June 2023

Well-differentiated/de-differentiated liposarcoma (WDLPS/DDLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS); however, treatment options remain limited. WDLPS and DDLPS both exhibit the characteristic amplification of chromosome region 12q13-15, which contains the genes CDK4 and MDM2. DDLPS exhibits higher amplification ratios of these two and carries additional genomic lesions, including the amplification of chromosome region 1p32 and chromosome region 6q23, which may explain the more aggressive biology of DDLPS. WDLPS does not respond to systemic chemotherapy and is primarily managed with local therapy, including multiple resections and debulking procedures whenever clinically feasible. In contrast, DDLPS can respond to chemotherapy drugs and drug combinations, including doxorubicin (or doxorubicin in combination with ifosfamide), gemcitabine (or gemcitabine in combination with docetaxel), trabectedin, eribulin, and pazopanib. However, the response rate is generally low, and the response duration is usually short. This review highlights the clinical trials with developmental therapeutics that have been completed or are ongoing, including CDK4/6 inhibitors, MDM2 inhibitors, and immune checkpoint inhibitors. This review will also discuss the current landscape in assessing biomarkers for identifying tumors sensitive to immune checkpoint inhibitors.
Targeting Mitochondrial Metabolic Dysfunction in Pulmonary Hypertension: Toward New Therapeutic Approaches?
Authors: Riou Marianne , Enache Irina , Sauer François , Charles Anne-Laure , Geny Bernard
Published: June 2023

Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary vascular remodeling leading to right heart failure and death. To date, despite the three therapeutic approaches targeting the three major endothelial dysfunction pathways based on the prostacyclin, nitric oxide/cyclic guanosine monophosphate, and endothelin pathways, PAH remains a serious disease. As such, new targets and therapeutic agents are needed. Mitochondrial metabolic dysfunction is one of the mechanisms involved in PAH pathogenesis in part through the induction of a Warburg metabolic state of enhanced glycolysis but also through the upregulation of glutaminolysis, tricarboxylic cycle and electron transport chain dysfunction, dysregulation of fatty acid oxidation or mitochondrial dynamics alterations. The aim of this review is to shed light on the main mitochondrial metabolic pathways involved in PAH and to provide an update on the resulting interesting potential therapeutic perspectives.
The 3q Oncogene SEC62 Predicts Response to Neoadjuvant Chemotherapy and Regulates Tumor Cell Migration in Triple Negative Breast Cancer
Authors: Radosa Julia C. , Kasoha Mariz , Doerk Merle , Cullmann Annika , Kaya Askin C. , Linxweiler Maximilian , Radosa Marc P. , Takacs Zoltan , Tirincsi Andrea , Lang Sven , Jung Martin , Puppe Julian , Linxweiler Barbara , Wagner Mathias , Bohle Rainer M. , Solomayer Erich-Franz , Zimmermann Julia S. M.
Published: June 2023

In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter predictive of oncological outcomes (progression-free and overall survival). An approach to the evaluation of predictive markers enabling therapy individualization is the identification of tumor driver genetic mutations. This study was conducted to investigate the role of SEC62, harbored at 3q26 and identified as a driver of breast cancer pathogenesis, in TNBC. We analyzed SEC62 expression in The Cancer Genome Atlas database, and immunohistologically investigated SEC62 expression in pre- and post-NACT tissue samples from 64 patients with TNBC treated at the Department of Gynecology and Obstetrics/Saarland University Hospital/Homburg between January 2010 and December 2018 and compared the effect of SEC62 on tumor cell migration and proliferation in functional assays. SEC62 expression dynamics correlated positively with the response to NACT (p ≤ 0.01) and oncological outcomes (p ≤ 0.01). SEC62 expression stimulated tumor cell migration (p ≤ 0.01). The study findings indicate that SEC62 is overexpressed in TNBC and serves as a predictive marker for the response to NACT, a prognostic marker for oncological outcomes, and a migration-stimulating oncogene in TNBC.
Evaluation of the Antiviral Efficacy of Subcutaneous Nafamostat Formulated with Glycyrrhizic Acid against SARS-CoV-2 in a Murine Model
Authors: Jeong Ju Hwan , Lee Woong Hee , Min Seong Cheol , Kim Beom Kyu , Park On Bi , Chokkakula Santosh , Ahn Seong Ju , Oh Sol , Park Ji-Hyun , Jung Ji Won , Jung Ji Min , Kim Eung-Gook , Song Min-Suk
Published: June 2023

The ongoing COVID-19 pandemic highlights the urgent need for effective antiviral agents and vaccines. Drug repositioning, which involves modifying existing drugs, offers a promising approach for expediting the development of novel therapeutics. In this study, we developed a new drug, MDB-MDB-601a-NM, by modifying the existing drug nafamostat (NM) with the incorporation of glycyrrhizic acid (GA). We assessed the pharmacokinetic profiles of MDB-601a-NM and nafamostat in Sprague-Dawley rats, revealing rapid clearance of nafamostat and sustained drug concentration of MDB-601a-NM after subcutaneous administration. Single-dose toxicity studies showed potential toxicity and persistent swelling at the injection site with high-dose administration of MDB-601a-NM. Furthermore, we evaluated the efficacy of MDB-601a-NM in protecting against SARS-CoV-2 infection using the K18 hACE-2 transgenic mouse model. Mice treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM exhibited improved protectivity in terms of weight loss and survival rates compared to the nafamostat-treated group. Histopathological analysis revealed dose-dependent improvements in histopathological changes and enhanced inhibitory efficacy in MDB-601a-NM-treated groups. Notably, no viral replication was detected in the brain tissue when mice were treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM. Our developed MDB-601a-NM, a modified Nafamostat with glycyrrhizic acid, shows improved protectivity against SARS-CoV-2 infection. Its sustained drug concentration after subcutaneous administration and dose-dependent improvements makes it a promising therapeutic option.
Pharmacological Analysis of GABAA Receptor and Sigma1R Chaperone Interaction: Research Report I―Investigation of the Anxiolytic, Anticonvulsant and Hypnotic Effects of Allosteric GABAA Receptors’ Ligands
Authors: Voronin Mikhail V. , Shangin Stanislav V. , Litvinova Svetlana A. , Abramova Elena V. , Kurbanov Rustam D. , Rybina Inna V. , Vakhitova Yulia V. , Seredenin Sergei B.
Published: June 2023

Two groups of facts have been established in previous drug development studies of the non-benzodiazepine anxiolytic fabomotizole. First, fabomotizole prevents stress-induced decrease in binding ability of the GABAA receptor’s benzodiazepine site. Second, fabomotizole is a Sigma1R chaperone agonist, and exposure to Sigma1R antagonists blocks its anxiolytic effect. To prove our main hypothesis of Sigma1R involvement in GABAA receptor-dependent pharmacological effects, we performed a series of experiments on BALB/c and ICR mice using Sigma1R ligands to study anxiolytic effects of benzodiazepine tranquilizers diazepam (1 mg/kg i.p.) and phenazepam (0.1 mg/kg i.p.) in the elevated plus maze test, the anticonvulsant effects of diazepam (1 mg/kg i.p.) in the pentylenetetrazole-induced seizure model, and the hypnotic effects of pentobarbital (50 mg/kg i.p.). Sigma1R antagonists BD-1047 (1, 10, and 20 mg/kg i.p.), NE-100 (1 and 3 mg/kg i.p.), and Sigma1R agonist PRE-084 (1, 5, and 20 mg/kg i.p.) were used in the experiments. Sigma1R antagonists have been found to attenuate while Sigma1R agonists can enhance GABAARs-dependent pharmacological effects.
New Insights on the Activity and Selectivity of MAO-B Inhibitors through In Silico Methods
Authors: Pacureanu Liliana , Bora Alina , Crisan Luminita
Published: June 2023

To facilitate the identification of novel MAO-B inhibitors, we elaborated a consolidated computational approach, including a pharmacophoric atom-based 3D quantitative structure–activity relationship (QSAR) model, activity cliffs, fingerprint, and molecular docking analysis on a dataset of 126 molecules. An AAHR.2 hypothesis with two hydrogen bond acceptors (A), one hydrophobic (H), and one aromatic ring (R) supplied a statistically significant 3D QSAR model reflected by the parameters: R2 = 0.900 (training set); Q2 = 0.774 and Pearson’s R = 0.884 (test set), stability s = 0.736. Hydrophobic and electron-withdrawing fields portrayed the relationships between structural characteristics and inhibitory activity. The quinolin-2-one scaffold has a key role in selectivity towards MAO-B with an AUC of 0.962, as retrieved by ECFP4 analysis. Two activity cliffs showing meaningful potency variation in the MAO-B chemical space were observed. The docking study revealed interactions with crucial residues TYR:435, TYR:326, CYS:172, and GLN:206 responsible for MAO-B activity. Molecular docking is in consensus with and complementary to pharmacophoric 3D QSAR, ECFP4, and MM-GBSA analysis. The computational scenario provided here will assist chemists in quickly designing and predicting new potent and selective candidates as MAO-B inhibitors for MAO-B-driven diseases. This approach can also be used to identify MAO-B inhibitors from other libraries or screen top molecules for other targets involved in suitable diseases.
Metastatic Dissemination: Role of Tumor-Derived Extracellular Vesicles and Their Use as Clinical Biomarkers
Authors: Giusti Ilaria , Poppa Giuseppina , Di Fazio Giulia , D’Ascenzo Sandra , Dolo Vincenza
Published: June 2023

Cancer is a major cause of mortality in humans; often, rather than the primary tumor, it is the presence of metastases that are the cause of death. Extracellular vesicles (EVs) are small structures released by both normal and cancer cells; regarding the latter, they have been demonstrated to modulate almost all cancer-related processes, such as invasion, angiogenesis induction, drug resistance, and immune evasion. In the last years, it has become clear how EVs are widely involved in metastatic dissemination as well as in pre-metastatic niche (PMN) formation. Indeed, in order to achieve a successful metastatic process, i.e., penetration by cancer cells into distant tissues, the shaping of a favorable environment into those distant tissue, i.e., PMN formation, is mandatory. This process consists of an alteration that takes place in a distant organ and paves the way for the engraftment and growth of circulating tumor cells derived from the tumor primary site. This review focuses on the role of EVs in pre-metastatic niche formation and metastatic dissemination, also reporting the last studies suggesting the EVs role as biomarkers of metastatic diseases, possibly in a liquid biopsy approach.
Exploring a Nuclear-Selective Radioisotope Delivery System for Efficient Targeted Alpha Therapy
Authors: Iizuka Yuki , Manabe Yoshiyuki , Ooe Kazuhiro , Toyoshima Atsushi , Yin Xiaojie , Haba Hiromitsu , Kabayama Kazuya , Fukase Koichi
Published: June 2023

Targeted alpha therapy (TAT) has garnered significant interest as an innovative cancer therapy. Owing to their high energy and short range, achieving selective α-particle accumulation in target tumor cells is crucial for obtaining high potency without adverse effects. To meet this demand, we fabricated an innovative radiolabeled antibody, specifically designed to selectively deliver 211At (α-particle emitter) to the nuclei of cancer cells. The developed 211At-labeled antibody exhibited a superior effect compared to its conventional counterparts. This study paves the way for organelle-selective drug delivery.
Sleep Deprivation and Gut Microbiota Dysbiosis: Current Understandings and Implications
Authors: Sun Jingyi , Fang Dan , Wang Zhiqiang , Liu Yuan
Published: June 2023

Gut microbiota comprises the microbial communities inhabiting our gastrointestinal (GI) tracts. Accordingly, these complex communities play a fundamental role in many host processes and are closely implicated in human health and diseases. Sleep deprivation (SD) has become increasingly common in modern society, partly owing to the rising pressure of work and the diversification of entertainment. It is well documented that sleep loss is a significant cause of various adverse outcomes on human health including immune-related and metabolic diseases. Furthermore, accumulating evidence suggests that gut microbiota dysbiosis is associated with these SD-induced human diseases. In this review, we summarize the gut microbiota dysbiosis caused by SD and the succedent diseases ranging from the immune system and metabolic system to various organs and highlight the critical roles of gut microbiota in these diseases. The implications and possible strategies to alleviate SD-related human diseases are also provided.
The Disorganization of Retinal Inner Layers Is Correlated to Müller Cells Impairment in Diabetic Macular Edema: An Imaging and Omics Study
Authors: Midena Edoardo , Torresin Tommaso , Schiavon Stefano , Danieli Luca , Polo Chiara , Pilotto Elisabetta , Midena Giulia , Frizziero Luisa
Published: June 2023

The disorganization of retinal inner layers (DRIL) is an optical coherence tomography (OCT) biomarker strictly associated with visual outcomes in patients with diabetic macular edema (DME) whose pathophysiology is still unclear. The aim of this study was to characterize in vivo, using retinal imaging and liquid biopsy, DRIL in eyes with DME. This was an observational cross-sectional study. Patients affected by center-involved DME were enrolled. All patients underwent spectral domain optical coherence tomography (SD-OCT) and proteomic analysis of aqueous humor (AH). The presence of DRIL at OCT was analyzed by two masked retinal experts. Fifty-seven biochemical biomarkers were analyzed from AH samples. Nineteen eyes of nineteen DME patients were enrolled. DRIL was present in 10 patients (52.63%). No statistically significant difference was found between DME eyes with and without DRIL, considering the AH concentration of all the analyzed biomarkers except for glial fibrillary acidic protein (GFAP), a biomarker of Müller cells dysfunction (p = 0.02). In conclusion, DRIL, in DME eyes, seems to strictly depend on a major dysfunction of Müller cells, explaining its role not only as imaging biomarker, but also as visual function Müller cells-related parameter.
Bombyx mori Ecdysone Receptor B1 May Inhibit BmNPV Infection by Triggering Apoptosis
Authors: Su Zhihao , Zhao Chunxiao , Huang Xinming , Lv Junli , Zhao Ziqin , Zheng Kaiyi , Sun Xia , Qin Sheng , Wang Xueyang , Jin Byung-Rae , Wu Yangchun
Published: June 2023

Bombyx mori nucleopolyhedrovirus (BmNPV) is a serious threat to sericulture. Nevertheless, no effective control strategy is currently available. The innate immunity of silkworm is critical in the antiviral process. Exploring its molecular mechanism provides theoretical support for the prevention and treatment of BmNPV. Insect hormone receptors play an essential role in regulating host immunity. We found a correlation between Bombyx mori ecdysone receptor B1 (BmEcR-B1) and BmNPV infection, whereas the underlying mechanism remains unclear. In this study, the expression patterns and sequence characteristics of BmEcR-B1 and its isoform, BmEcR-A, were initially analyzed. BmEcR-B1 was found to be more critical than BmEcR-A in silkworm development and responses to BmNPV. Moreover, RNAi and an overexpression in BmN cells showed BmEcR-B1 had antiviral effects in the presence of 20-hydroxyecdysone (20E); Otherwise, it had no antiviral activity. Furthermore, BmEcR-B1 was required for 20E-induced apoptosis, which significantly suppressed virus infection. Finally, feeding 20E had no significant negative impacts on larval growth and the cocoon shell, suggesting the regulation of this pathway has practical value in controlling BmNPV in sericulture. The findings of this study provide important theoretical support for understanding the mechanism of the silkworm innate immune system in response to BmNPV infection.
A Review on Digestive System of Rhynchophorus ferrugineus as Potential Target to Develop Control Strategies
Authors: Seman-Kamarulzaman Ahmad-Faris , Pariamiskal Faizatul Atikah , Azidi Amiratul Nabihah , Hassan Maizom
Published: June 2023

Rhynchophorus ferrugineus, commonly known as red palm weevil (RPW), is a high-risk insect pest that has become a threat to many important palm species. There are several dominant factors that lead to the successful infestation of RPW, including its stealthy lifestyle, highly chitinized mouthpart, and high fecundity rate. Due to that, millions of dollars of losses have been suffered by many countries invaded by RPW. Several methods have been designed to control its invasion, including the usage of insecticides, but many cause resistance and environmental pollution. Therefore, an environmentally friendly insecticide that targets specific systems or pathways in RPW is urgently needed. One of the potential targets is the digestive system of RPW, as it is the major interface between the insect and its plant host. The related knowledge of RPW’s digestive system, such as the anatomy, microflora, transcriptomic analysis, and proteomic analysis, is important to understand its effects on RPW’s survival. Several data from different omics regarding the digestive systems of RPW have been published in separate reports. Some of the potential targets have been reported to be inhibited by certain potential insecticides, while other targets have not yet been tested with any inhibitors. Hence, this review may lead to a better understanding on managing infestations of RPW using the system biology approach for its digestive system.
Determining Field Insecticide Efficacy on Whiteflies with Maximum Dose Bioassays
Authors: Cremonez Paulo S. G. , Perier Jermaine D. , Simmons Alvin M. , Riley David G.
Published: June 2023

We conducted a rapid bioassay method to assess insecticide efficacy for controlling adult sweetpotato whitefly Bemisia tabaci in squash and cucumber crops before insecticide applications. The study aimed to evaluate the accuracy of a 24-hour laboratory bioassay in determining maximum dose insecticide efficacy in the field. Ten insecticides were evaluated using leaf-dip bioassays, and their effectiveness was tested across eight cucurbit field experiments in Georgia, USA, during the 2021 and 2022 field seasons. The maximum dose, defined as the highest labeled rate of an insecticide diluted in the equivalent of 935 L ha−1 of water, was used for all bioassays. Adult survival observed in the bioassay was compared to adult field count-based survival 24 h after treatment. A low concentration (1/10 rate) was used for imidacloprid, flupyradifurone, pyriproxyfen, and cyantraniliprole to assess insecticide tolerance in the whitefly population. Overall, significant positive correlation between laboratory bioassay and field efficacy was reported, explaining 50–91% of the observed variation. The addition of the low dosage was helpful, indicating that no rate response was consistent with susceptibility to the tested insecticide, while a rate response was associated with a loss of susceptibility between 2021 and 2022.
Reply to Wostyn, P. Could Young Cerebrospinal Fluid Combat Glaucoma? Comment on “Lee et al. Association between Optic Nerve Sheath Diameter and Lamina Cribrosa Morphology in Normal-Tension Glaucoma. J. Clin. Med. 2023, 12, 360”
Authors: Lee Seung Hyen , Kim Tae-Woo , Lee Eun Ji , Kil Hyunkyung
Published: June 2023

We are pleased to see that Peter Wostyn has contributed a Comment: “Could Young Cerebrospinal Fluid Combat Glaucoma?" [...]
BILE: A Literature Review Based Novel Clinical Classification and Treatment Algorithm of Iatrogenic Bile Duct Injuries
Authors: Symeonidis Dimitrios , Tepetes Konstantinos , Tzovaras George , Samara Athina A. , Zacharoulis Dimitrios
Published: June 2023

Purposes: The management of patients with iatrogenic bile duct injuries (IBDI) is a challenging field, often with dismal medico legal projections. Attempts to classify IBDI have been made repeatedly and the final results were either analytical and extensive but not useful in everyday clinical practice systems, or simple and user friendly but with limited clinical correspondence approaches. The purpose of the present review is to propose a novel, clinical classification system of IBDI by reviewing the relevant literature. Methods: A systematic literature review was conducted by performing bibliographic searches in the available electronic databases, including PubMed, Scopus, and the Cochrane Library. Results: Based on the literature results, we propose a five (5) stage (A, B, C, D and E) classification system for IBDI (BILE Classification). Each stage is correlated with the recommended and most appropriate treatment. Although the proposed classification scheme is clinically oriented, the anatomical correspondence of each IBDI stage has been incorporated as well, using the Strasberg classification. Conclusions: BILE classification represents a novel, simple, and dynamic in nature classification system of IBDI. The proposed classification focuses on the clinical consequences of IBDI and provides an action map that can appropriately guide the treatment plan.
Incidence Rate and Factors Associated with Delirium and Subsyndromal Delirium in Patients with COVID-19 in an Intensive Care Unit
Authors: Perpetuo Lara Helena , Ferreira Wellington , da Silva Danilo Jorge , Jurno Mauro Eduardo , Vale Thiago Cardoso
Published: June 2023

Background: Delirium subsyndrome (SSD) and delirium (DL) are known complications in the intensive care unit (ICU) and are associated with worse clinical outcomes. The aim of this study was to screen for SSD and DL in individuals with COVID-19 admitted to the ICU and to study the associated factors and clinical outcomes. Method: An observational, longitudinal study was conducted in the reference ICU for COVID-19. All admitted individuals with COVID-19 were screened for SSD and DL during their ICU stay using the Intensive Care Delirium Screening Checklist (ICDSC). Individuals with SSD and/or DL were compared to those without SSD and/or DL. Results: Ninety-three patients were evaluated, of which 46.7% had SSD and/or DL. The incidence rate was 4.17 cases/100 person-days. Individuals with SSD and/or DL had higher severity of illness on admission to the ICU, as measured by the APACHE II score (median 16 versus 8 points, p < 0.001). SSD and/or DL were associated with longer ICU and hospital stays (median 19 versus 6 days, p < 0.001 and median 22 versus 7 days, p < 0.001, respectively). Conclusion: Individuals with SSD and/or DL had greater disease severity and longer ICU and hospital stays when compared to those without SSD and/or DL. This reinforces the importance of screening for consciousness disorders in the ICU.
Evaluation of the Cognitive Function of Adults with Severe Hearing Loss Pre- and Post-Cochlear Implantation Using Verbal Fluency Testing
Authors: Baranger Manon , Manera Valeria , Sérignac Chloé , Derreumaux Alexandre , Cancian Elisa , Vandersteen Clair , Gros Auriane , Guevara Nicolas
Published: June 2023

Hearing loss is a major public health problem with significant evidence correlating it with cognitive performance. Verbal fluency tests are commonly used to assess lexical access. They provide a great deal of information about a subject’s cognitive function. The aim of our study was to evaluate phonemic and semantic lexical access abilities in adults with bilateral severe to profound hearing loss and then to re-evaluate a cohort after cochlear implantation. 103 adult subjects underwent phonemic and semantic fluency tests during a cochlear implant candidacy evaluation. Of the total 103 subjects, 43 subjects underwent the same tests at 3 months post-implantation. Our results showed superior performance in phonemic fluency compared to semantic fluency in subjects prior to implantation. Phonemic fluency was positively correlated with semantic fluency. Similarly, individuals with congenital deafness had better semantic lexical access than individuals with acquired deafness. Results at 3 months post-implantation showed an improvement in phonemic fluency. No correlation was found between the evolution of pre- and post-implant fluency and the auditory gain of the cochlear implant, and we found no significant difference between congenital and acquired deafness. Our study shows an improvement in global cognitive function after cochlear implantation without differentiation of the phonemic-semantic pathway.
The Non-Invasive Diagnosis of Chronic Coronary Syndrome: A Focus on Stress Computed Tomography Perfusion and Stress Cardiac Magnetic Resonance
Authors: Groenhoff Léon , De Zan Giulia , Costantini Pietro , Siani Agnese , Ostillio Eleonora , Carriero Serena , Muscogiuri Giuseppe , Bergamaschi Luca , Patti Giuseppe , Pizzi Carmine , Sironi Sandro , Pavon Anna Giulia , Carriero Alessandro , Guglielmo Marco
Published: June 2023

Coronary artery disease is still a major cause of death and morbidity worldwide. In the setting of chronic coronary disease, demonstration of inducible ischemia is mandatory to address treatment. Consequently, scientific and technological efforts were made in response to the request for non-invasive diagnostic tools with better sensitivity and specificity. To date, clinicians have at their disposal a wide range of stress-imaging techniques. Among others, stress cardiac magnetic resonance (S-CMR) and computed tomography perfusion (CTP) techniques both demonstrated their diagnostic efficacy and prognostic value in clinical trials when compared to other non-invasive ischemia-assessing techniques and invasive fractional flow reserve measurement techniques. Standardized protocols for both S-CMR and CTP usually imply the administration of vasodilator agents to induce hyperemia and contrast agents to depict perfusion defects. However, both methods have their own limitations, meaning that optimizing their performance still requires a patient-tailored approach. This review focuses on the characteristics, drawbacks, and future perspectives of these two techniques.
Prognostic Value of Different Levels of Uric Acid in Patients with Coronary Chronic Total Occlusion Undergoing Percutaneous Coronary Intervention
Authors: Ayoub Mohamed , Mashayekhi Kambis , Behnes Michael , Schupp Tobias , Akin Muharrem , Forner Jan , Akin Ibrahim , Neumann Franz-Josef , Westermann Dirk , Rudolph Volker , Toma Aurel
Published: June 2023

Recent data suggest that uric acid (UA) might be an independent predictor of clinical outcomes following percutaneous coronary intervention (PCI). The predictive value of uric acid in patients undergoing PCI for chronic total occlusions (CTO) is unknown. We included patients with CTO who underwent PCI at our center in 2005 and 2012, with available uric acid levels before angiography. Subjects were divided into groups according to uric acid tertiles (<5.5 mg/dL, 5.6–6.9 mg/dL, and >7.0 mg/dL), and outcomes were compared among the groups. Out of the 1963 patients (mean age 65.2 ± 11 years), 34.7% (n = 682) had uric acid concentrations in the first tertile, 34.3% (n = 673) in the second tertile, and 31% (n = 608) in the third tertile. Median follow-up was 3.0 years. Uric acid levels in the first tertile were associated with significantly lower all-cause mortality, as compared to the third tertile, with an adjusted hazard ratio (HR) of 0.67 (95% confidence interval (CI): 0.49 to 0.92; p = 0.012). No significant differences regarding all-cause mortality were found between patients in the first and second tertiles (HR: 0.96 [95% CI: 0.71 to 1.3; p = 0.78]). High levels of uric acid emerged as an independent predictor of all-cause mortality in patients with chronic total occlusion treated with PCI. Hence, uric acid levels should be incorporated into the risk assessment of patients with CTO.
The Implications of SARS-CoV-2 Infection in a Series of Neuro-Ophthalmological Manifestations—Case Series and Literature Review
Authors: Anton Nicoleta , Bogdănici Camelia Margareta , Brănișteanu Daniel Constantin , Ilie Ovidiu-Dumitru , Pavel Irina Andreea , Doroftei Bogdan
Published: June 2023

The global pandemic impact of the COVID-19 infection included clinical manifestations that affected several organs and systems, with various neuro-ophthalmological manifestations associated with the infection. These are rare and occur either secondary to the presence of the virus or by an autoimmune mechanism secondary to viral antigens. The manifestations are atypical, being present even in the absence of the systemic symptoms typical of a SARS-CoV-2 infection. In this article, we introduce a series of three clinical cases with neuro-ophthalmological manifestations associated with COVID infection that were shown in Ophthalmology Clinic of St. Spiridon Emergency Hospital. Case 1 is that of a 45-year-old male patient with no personal history of general pathology or ophthalmology, with binocular diplopia, painful red eyes, and lacrimal hypersecretion with a sudden onset of about 4 days. Based on the evaluations, a positive diagnosis of orbital cellulitis in both eyes is made. Case 2 is that of a 52-year-old female patient with general PPA (personal pathological antecedents) of SARS-CoV-2 infection 1 month prior to presentation with decreased visual acuity in the right eye and a positive central scotoma, preceded by photopsia and vertigo with balance disorders. The diagnosis is made at the right eye for retrobulbar optic neuritis and post-SARS-CoV-2 infection status. The last clinical case is that of a 55-year-old male patient known to have high blood pressure (HBP) with a sudden, painless decrease in VARE approximately 3 weeks post-SARS-CoV-2 immunization (Pfizer vaccine first dose). The diagnosis is made after consulting all the RE results for central retinal vein thrombosis. Conclusions: Although the cases were quickly and efficiently investigated and the treatment was administered adequately by a multidisciplinary team (cases 1 and 3), the evolution was not favorable in all three situations. Atypical neuro-ophthalmological manifestations can also be present in the absence of systemic symptoms typical of SARS-CoV-2 infection.
Independent Prognostic and Predictive Role of Interstitial Macrophages in Kidney Biopsies of IgA Nephropathy Patients
Authors: Aiello Francesca Bianca , Ranelletti Franco Oreste , Liberatore Marcella , Felaco Paolo , De Luca Graziano , Lamolinara Alessia , Schena Francesco Paolo , Bonomini Mario
Published: June 2023

A relevant percentage of IgAN patients experience a progressive decline in kidney function. According to the KDIGO guidelines, proteinuria and eGFR are the only validated prognostic markers. The role of interstitial macrophages in kidney biopsies of IgAN patients and the outcome of patients treated with renin–angiotensin system inhibitors (RASBs) alone or combined with glucocorticoids were evaluated. Clinical and laboratory records (age, gender, hypertension, hematuria, proteinuria, eGFR, serum creatinine, and therapy), MEST-C parameters of the Oxford classification, C4d deposition, peritubular capillaries, and glomerular and interstitial macrophages in 47 IgAN patients undergoing kidney biopsy consecutively between 2003 and 2016 were examined. A high number of interstitial macrophages significantly correlated with peritubular capillary rarefaction and impairment of kidney function. Cox’s multivariable regression analysis revealed that a value > 19.5 macrophages/HPF behaved as an independent marker of an unfavorable outcome. Patients exhibiting > 19.5 macrophages/HPF treated at the time of diagnosis with RASBs combined with methylprednisolone had an estimated probability of a favorable outcome higher than patients treated with RASBs alone. Thus, a value > 19.5 macrophages/HPF in IgAN biopsies can predict an unfavorable outcome and endorse a well-timed administration of glucocorticoids. Studies evaluating urine biomarkers associated with peritubular capillary rarefaction in patients with marked macrophage infiltration may help personalized treatment decisions.