bluuebunny/crossref_metadata_2025 huggingface dataset:
Somatostatin Containing δ-Cell Number Is Reduced in Type-2 Diabetes
Authors: Kothegala Lakshmi , Miranda Caroline , Singh Meetu , Krieger Jean-Philippe , Gandasi Nikhil R.
Published: February 2023

Recent developments suggest that increased glucagon and decreased somatostatin secretion from the pancreas contribute to hyperglycaemia in type-2 diabetes (T2D) patients. There is a huge need to understand changes in glucagon and somatostatin secretion to develop potential anti-diabetic drugs. To further describe the role of somatostatin in the pathogenesis of T2D, reliable means to detect islet δ-cells and somatostatin secretion are necessary. In this study, we first tested currently available anti-somatostatin antibodies against a mouse model that fluorescently labels δ-cells. We found that these antibodies only label 10–15% of the fluorescently labelled δ-cells in pancreatic islets. We further tested six antibodies (newly developed) that can label both somatostatin 14 (SST14) and 28 (SST28) and found that four of them were able to detect above 70% of the fluorescent cells in the transgenic islets. This is quite efficient compared to the commercially available antibodies. Using one of these antibodies (SST10G5), we compared the cytoarchitecture of mouse and human pancreatic islets and found fewer δ-cells in the periphery of human islets. Interestingly, the δ-cell number was also reduced in islets from T2D donors compared to non-diabetic donors. Finally, with the aim to measure SST secretion from pancreatic islets, one of the candidate antibodies was used to develop a direct-ELISA-based SST assay. Using this novel assay, we could detect SST secretion under low and high glucose conditions from the pancreatic islets, both in mice and humans. Overall, using antibody-based tools provided by Mercodia AB, our study indicates reduced δ-cell numbers and SST secretion in diabetic islets.
Molecular Frontiers in Transplantation-Induced Ischemia–Reperfusion Injury
Authors: Thuillier Raphael
Published: February 2023

This Special Issue aims to summarize the most up-to-date research on ischemia–reperfusion and organ transplantation [...]
Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair
Authors: Uzieliene Ilona , Bironaite Daiva , Pachaleva Jolita , Bagdonas Edvardas , Sobolev Arkadij , Tsai Wei-Bor , Kvedaras Giedrius , Bernotiene Eiva
Published: February 2023

The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.
Triac Treatment Prevents Neurodevelopmental and Locomotor Impairments in Thyroid Hormone Transporter Mct8/Oatp1c1 Deficient Mice
Authors: Chen Jiesi , Salveridou Eva , Liebmann Lutz , Sundaram Sivaraj M. , Doycheva Denica , Markova Boyka , Hübner Christian A. , Boelen Anita , Visser W. Edward , Heuer Heike , Mayerl Steffen
Published: February 2023

Patients with inactive thyroid hormone (TH) transporter MCT8 display intellectual disability due to compromised central TH transport and action. As a therapeutic strategy, application of thyromimetic, MCT8-independent compounds Triac (3,5,3′-triiodothyroacetic acid), and Ditpa (3,5-diiodo-thyropropionic acid) was proposed. Here, we directly compared their thyromimetic potential in Mct8/Oatp1c1 double knock-out mice (Dko) modeling human MCT8 deficiency. Dko mice received either Triac (50 ng/g or 400 ng/g) or Ditpa (400 ng/g or 4000 ng/g) daily during the first three postnatal weeks. Saline-injected Wt and Dko mice served as controls. A second cohort of Dko mice received Triac (400 ng/g) daily between postnatal weeks 3 and 6. Thyromimetic effects were assessed at different postnatal stages by immunofluorescence, ISH, qPCR, electrophysiological recordings, and behavior tests. Triac treatment (400 ng/g) induced normalized myelination, cortical GABAergic interneuron differentiation, electrophysiological parameters, and locomotor performance only when administered during the first three postnatal weeks. Ditpa (4000 ng/g) application to Dko mice during the first three postnatal weeks resulted in normal myelination and cerebellar development but only mildly improved neuronal parameters and locomotor function. Together, Triac is highly-effective and more efficient than Ditpa in promoting CNS maturation and function in Dko mice yet needs to be initiated directly after birth for the most beneficial effects.
Nanostrategies for Therapeutic and Diagnostic Targeting of Gastrin-Releasing Peptide Receptor
Authors: Rurarz Beata Paulina , Bukowczyk Małgorzata , Gibka Natalia , Piastowska-Ciesielska Agnieszka Wanda , Karczmarczyk Urszula , Ulański Piotr
Published: February 2023

Advances in nanomedicine bring the attention of researchers to the molecular targets that can play a major role in the development of novel therapeutic and diagnostic modalities for cancer management. The choice of a proper molecular target can decide the efficacy of the treatment and endorse the personalized medicine approach. Gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled membrane receptor, well known to be overexpressed in numerous malignancies including pancreatic, prostate, breast, lung, colon, cervical, and gastrointestinal cancers. Therefore, many research groups express a deep interest in targeting GRPR with their nanoformulations. A broad spectrum of the GRPR ligands has been described in the literature, which allows tuning of the properties of the final formulation, particularly in the field of the ligand affinity to the receptor and internalization possibilities. Hereby, the recent advances in the field of applications of various nanoplatforms that are able to reach the GRPR-expressing cells are reviewed.
Circulating miR-122-5p, miR-92a-3p, and miR-18a-5p as Potential Biomarkers in Human Liver Transplantation Follow-Up
Authors: Morsiani Cristina , Collura Salvatore , Sevini Federica , Ciurca Erika , Bertuzzo Valentina Rosa , Franceschi Claudio , Grazi Gian Luca , Cescon Matteo , Capri Miriam
Published: February 2023

The requirement of blood-circulating sensitive biomarkers for monitoring liver transplant (LT) is currently a necessary step aiming at the reduction of standard invasive protocols, such as liver biopsy. In this respect, the main objective of this study is to assess circulating microRNA (c-miR) changes in recipients’ blood before and after LT and to correlate their blood levels with gold standard biomarkers and with outcomes such as rejection or complications after graft. An miR profile was initially performed; then, the most deregulated miRs were validated by RT-qPCR in 14 recipients pre- and post-LT and compared to a control group of 24 nontransplanted healthy subjects. MiR-122-5p, miR-92a-3p, miR-18a-5p, and miR-30c-5p, identified in the validation phase, were also analyzed considering an additional 19 serum samples collected from LT recipients and focusing on different follow-up (FU) times. The results showed significant, FU-related changes in c-miRs. In particular, miR-122-5p, miR-92a-3p, and miR-18a-5p revealed the same trend after transplantation and an increase in their level was found in patients with complications, independently from FU times. Conversely, the variations in the standard haemato-biochemical parameters for liver function assessment were not significant in the same FU period, confirming the importance of c-miRs as potential noninvasive biomarkers for monitoring patients’ outcomes.
Notch Signaling in Acute Inflammation and Sepsis
Authors: Gallenstein Nadia , Tichy Lucas , Weigand Markus Alexander , Schenz Judith
Published: February 2023

Notch signaling, a highly conserved pathway in mammals, is crucial for differentiation and homeostasis of immune cells. Besides, this pathway is also directly involved in the transmission of immune signals. Notch signaling per se does not have a clear pro- or anti-inflammatory effect, but rather its impact is highly dependent on the immune cell type and the cellular environment, modulating several inflammatory conditions including sepsis, and therefore significantly impacts the course of disease. In this review, we will discuss the contribution of Notch signaling on the clinical picture of systemic inflammatory diseases, especially sepsis. Specifically, we will review its role during immune cell development and its contribution to the modulation of organ-specific immune responses. Finally, we will evaluate to what extent manipulation of the Notch signaling pathway could be a future therapeutic strategy.
The Terminal Extensions of Dbp7 Influence Growth and 60S Ribosomal Subunit Biogenesis in Saccharomyces cerevisiae
Authors: Contreras Julia , Ruiz-Blanco Óscar , Dominique Carine , Humbert Odile , Henry Yves , Henras Anthony K. , de la Cruz Jesús , Villalobo Eduardo
Published: February 2023

Ribosome synthesis is a complex process that involves a large set of protein trans-acting factors, among them DEx(D/H)-box helicases. These are enzymes that carry out remodelling activities onto RNAs by hydrolysing ATP. The nucleolar DEGD-box protein Dbp7 is required for the biogenesis of large 60S ribosomal subunits. Recently, we have shown that Dbp7 is an RNA helicase that regulates the dynamic base-pairing between the snR190 small nucleolar RNA and the precursors of the ribosomal RNA within early pre-60S ribosomal particles. As the rest of DEx(D/H)-box proteins, Dbp7 has a modular organization formed by a helicase core region, which contains conserved motifs, and variable, non-conserved N- and C-terminal extensions. The role of these extensions remains unknown. Herein, we show that the N-terminal domain of Dbp7 is necessary for efficient nuclear import of the protein. Indeed, a basic bipartite nuclear localization signal (NLS) could be identified in its N-terminal domain. Removal of this putative NLS impairs, but does not abolish, Dbp7 nuclear import. Both N- and C-terminal domains are required for normal growth and 60S ribosomal subunit synthesis. Furthermore, we have studied the role of these domains in the association of Dbp7 with pre-ribosomal particles. Altogether, our results show that the N- and C-terminal domains of Dbp7 are important for the optimal function of this protein during ribosome biogenesis.
Development and Evaluation of the Magnetic Properties of a New Manganese (II) Complex: A Potential MRI Contrast Agent
Authors: Reale Giovanni , Calderoni Francesca , Ghirardi Teresa , Porto Francesca , Illuminati Federica , Marvelli Lorenza , Martini Petra , Uccelli Licia , Tonini Eugenia , Del Bianco Lucia , Spizzo Federico , Capozza Martina , Cazzola Emiliano , Carnevale Aldo , Giganti Melchiore , Turra Alessandro , Esposito Juan , Boschi Alessandra
Published: February 2023

Magnetic resonance imaging (MRI) is a non-invasive powerful modern clinical technique that is extensively used for the high-resolution imaging of soft tissues. To obtain high-definition pictures of tissues or of the whole organism this technique is enhanced by the use of contrast agents. Gadolinium-based contrast agents have an excellent safety profile. However, over the last two decades, some specific concerns have surfaced. Mn(II) has different favorable physicochemical characteristics and a good toxicity profile, which makes it a good alternative to the Gd(III)-based MRI contrast agents currently used in clinics. Mn(II)-disubstituted symmetrical complexes containing dithiocarbamates ligands were prepared under a nitrogen atmosphere. The magnetic measurements on Mn complexes were carried out with MRI phantom measurements at 1.5 T with a clinical magnetic resonance. Relaxivity values, contrast, and stability were evaluated by appropriate sequences. Studies conducted to evaluate the properties of paramagnetic imaging in water using a clinical magnetic resonance showed that the contrast, produced by the complex [Mn(II)(L’)2] × 2H2O (L’ = 1.4-dioxa-8-azaspiro[4.5]decane-8-carbodithioate), is comparable to that produced by gadolinium complexes currently used in medicine as a paramagnetic contrast agent.
Novel Therapeutic Potential of Retinoid-Related Orphan Receptor α in Cardiovascular Diseases
Authors: Chen Yun , Zhang Shu-Ping , Gong Wei-Wei , Zheng Yang-Yang , Shen Jie-Ru , Liu Xiao , Gu Yun-Hui , Shi Jia-Hai , Meng Guo-Liang
Published: February 2023

The retinoid-related orphan receptor α (RORα) is one subfamily of nuclear hormone receptors (NRs). This review summarizes the understanding and potential effects of RORα in the cardiovascular system and then analyzes current advances, limitations and challenges, and further strategy for RORα-related drugs in cardiovascular diseases. Besides regulating circadian rhythm, RORα also influences a wide range of physiological and pathological processes in the cardiovascular system, including atherosclerosis, hypoxia or ischemia, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, hypertension, and myocardial hypertrophy. In terms of mechanism, RORα was involved in the regulation of inflammation, apoptosis, autophagy, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial function. Besides natural ligands for RORα, several synthetic RORα agonists or antagonists have been developed. This review mainly summarizes protective roles and possible mechanisms of RORα against cardiovascular diseases. However, there are also several limitations and challenges of current research on RORα, especially the difficulties on the transformability from the bench to the bedside. By the aid of multidisciplinary research, breakthrough progress on RORα-related drugs to combat cardiovascular disorder may appear.
A Highly Expressed Antennae Odorant-Binding Protein Involved in Recognition of Herbivore-Induced Plant Volatiles in Dastarcus helophoroides
Authors: Yi Shan-Cheng , Wu Yu-Hang , Yang Rui-Nan , Li Dong-Zhen , Abdelnabby Hazem , Wang Man-Qun
Published: February 2023

Natural enemies such as parasitoids and parasites depend on sensitive olfactory to search for their specific hosts. Herbivore-induced plant volatiles (HIPVs) are vital components in providing host information for many natural enemies of herbivores. However, the olfactory-related proteins involved in the recognition of HIPVs are rarely reported. In this study, we established an exhaustive tissue and developmental expression profile of odorant-binding proteins (OBPs) from Dastarcus helophoroides, an essential natural enemy in the forestry ecosystem. Twenty DhelOBPs displayed various expression patterns in different organs and adult physiological states, suggesting a potential involvement in olfactory perception. In silico AlphaFold2-based modeling and molecular docking showed similar binding energies between six DhelOBPs (DhelOBP4, 5, 6, 14, 18, and 20) and HIPVs from Pinus massoniana. While in vitro fluorescence competitive binding assays showed only recombinant DhelOBP4, the most highly expressed in the antennae of emerging adults could bind to HIPVs with high binding affinities. RNAi-mediated behavioral assays indicated that DhelOBP4 was an essential functional protein for D. helophoroides adults recognizing two behaviorally attractive substances: p-cymene and γ-terpinene. Further binding conformation analyses revealed that Phe 54, Val 56, and Phe 71 might be the key binding sites for DhelOBP4 interacting with HIPVs. In conclusion, our results provide an essential molecular basis for the olfactory perception of D. helophoroides and reliable evidence for recognizing the HIPVs of natural enemies from insect OBPs’ perspective.
CRISPR-Cas9-Mediated Mutation of Methyltransferase METTL4 Results in Embryonic Defects in Silkworm Bombyx mori
Authors: Guo Hao , Chen Feng , Zhou Mingyi , Lan Weiqun , Zhang Wenchang , Shen Guanwang , Lin Ping , Xia Qingyou , Zhao Ping , Li Zhiqing
Published: February 2023

DNA N6-methyladenine (6mA) has recently been found to play regulatory roles in gene expression that links to various biological processes in eukaryotic species. The functional identification of 6mA methyltransferase will be important for understanding the underlying molecular mechanism of epigenetic 6mA methylation. It has been reported that the methyltransferase METTL4 can catalyze the methylation of 6mA; however, the function of METTL4 remains largely unknown. In this study, we aim to investigate the role of the Bombyx mori homolog METTL4 (BmMETTL4) in silkworm, a lepidopteran model insect. By using CRISPR-Cas9 system, we somatically mutated BmMETTL4 in silkworm individuates and found that disruption of BmMETTL4 caused the developmental defect of late silkworm embryo and subsequent lethality. We performed RNA-Seq and identified that there were 3192 differentially expressed genes in BmMETTL4 mutant including 1743 up-regulated and 1449 down-regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that genes involved in molecular structure, chitin binding, and serine hydrolase activity were significantly affected by BmMETTL4 mutation. We further found that the expression of cuticular protein genes and collagens were clearly decreased while collagenases were highly increased, which had great contributions to the abnormal embryo and decreased hatchability of silkworm. Taken together, these results demonstrated a critical role of 6mA methyltransferase BmMETTL4 in regulating embryonic development of silkworm.
Antibacterial Effects of X-ray and MRI Contrast Media: An In Vitro Pilot Study
Authors: Brönnimann Michael P. , Hirzberger Lea , Keller Peter M. , Gsell-Albert Monika
Published: February 2023

Some radiological contrast agents have been shown to have effects on bacterial growth. In this study, the antibacterial effect and mechanism of action of iodinated X-ray contrast agents (Ultravist 370, Iopamiro 300, Telebrix Gastro 300 and Visipaque) and complexed lanthanide MRI contrast solutions (MultiHance and Dotarem) were tested against six different microorganisms. Bacteria with high and low concentrations were exposed to media containing different contrast media for various lengths of time and at pH 7.0 and 5.5. The antibacterial effect of the media was examined in further tests using agar disk diffusion analysis and the microdilution inhibition method. Bactericidal effects were found for microorganisms at low concentrations and low pH. Reductions were confirmed for Staphylococcus aureus and Escherichia coli.
Integrated Transcriptome and Metabolome Analyses Provide Insights into the Coloring Mechanism of Dark-red and Yellow Fruits in Chinese Cherry [Cerasus pseudocerasus (Lindl.) G. Don]
Authors: Wang Yan , Wang Zhiyi , Zhang Jing , Liu Zhenshan , Wang Hao , Tu Hongxia , Zhou Jingting , Luo Xirui , Chen Qing , He Wen , Yang Shaofeng , Li Mengyao , Lin Yuanxiu , Zhang Yunting , Zhang Yong , Luo Ya , Tang Haoru , Wang Xiaorong
Published: February 2023

Chinese cherry [Cerasus pseudocerasus (Lindl.) G. Don] is an important fruit tree from China that has excellent ornamental, economic, and nutritional values with various colors. The dark-red or red coloration of fruit, an attractive trait for consumers, is determined by anthocyanin pigmentation. In this study, the coloring patterns during fruit development in dark-red and yellow Chinese cherry fruits were firstly illustrated by integrated transcriptome and widely-targeted metabolome analyses. Anthocyanin accumulation in dark-red fruits was significantly higher compared with yellow fruits from the color conversion period, being positively correlated to the color ratio. Based on transcriptome analysis, eight structural genes (CpCHS, CpCHI, CpF3H, CpF3’H, CpDFR, CpANS, CpUFGT, and CpGST) were significantly upregulated in dark-red fruits from the color conversion period, especially CpANS, CpUFGT, and CpGST. On contrary, the expression level of CpLAR were considerably higher in yellow fruits than in dark-red fruits, especially at the early stage. Eight regulatory genes (CpMYB4, CpMYB10, CpMYB20, CpMYB306, bHLH1, CpNAC10, CpERF106, and CpbZIP4) were also identified as determinants of fruit color in Chinese cherry. Liquid chromatography-tandem mass spectrometry identified 33 and 3 differential expressed metabolites related to anthocyanins and procyanidins between mature dark-red and yellow fruits. Cyanidin-3-O-rutinoside was the predominant anthocyanin compound in both fruits, while it was 6.23-fold higher in dark-red than in yellow fruits. More accumulated flavanol and procyanidin contents resulted in less anthocyanin content in flavonoid pathway in yellow fruits due to the higher expression level of CpLAR. These findings can help understand the coloring mechanism of dark-red and yellow fruits in Chinese cherry, and provide genetic basis for breeding new cultivars.
Quality of E-Tax System and Tax Compliance Intention: The Mediating Role of User Satisfaction
Authors: Saptono Prianto Budi , Hodžić Sabina , Khozen Ismail , Mahmud Gustofan , Pratiwi Intan , Purwanto Dwi , Aditama Muhamad Akbar , Haq Nisa’ul , Khodijah Siti
Published: February 2023

The effectiveness of the e-tax system in encouraging tax compliance has been largely unexplored. Thus, the current study aims to examine the interrelationship between technological predictors in explaining tax compliance intention among certified tax professionals. Based on the literature on information system success and tax compliance intention, this paper proposed an expanded conceptual framework that incorporates convenience and perception of reduced compliance costs as predictors and satisfaction as a mediator. The data were collected from 650 tax professionals who used e-Filing and 492 who used e-Form through an online survey and analyzed using hierarchical multiple regression. The empirical results suggest that participants’ perceived service quality of e-Filing services and perceptions of reduced compliance costs positively influence users’ willingness to comply with tax regulations. The latter predictor is also, and only, significant among e-Form users. The empirical results also provide statistical evidence for the mediating role of satisfaction in the relationship between all predictors and tax compliance intention. This study encourages tax policymakers and e-tax filing providers to improve their services to increase user satisfaction and tax compliance.
Differences in Disability Perception in Systemic Sclerosis: A Mirror Survey of Patients and Health Care Providers
Authors: Kirren Quentin , Daste Camille , Foissac Frantz , Abdoul Hendy , Alami Sophie , Carrier Marie-Eve , Kwakkenbos Linda , Lefèvre-Colau Marie-Martine , Rannou François , Papelard Agathe , Roren Alexandra , Thombs Brett D. , Mouthon Luc , Nguyen Christelle
Published: February 2023

Differences in disability perception between patients and care providers may impact outcomes. We aimed to explore differences in disability perception between patients and care providers in systemic sclerosis (SSc). We conducted a cross-sectional internet-based mirror survey. SSc patients participating in the online SPIN Cohort and care providers affiliated with 15 scientific societies were surveyed using the Cochin Scleroderma International Classification of Functioning, Disability and Health (ICF)-65 questionnaire, including 65 items (from 0 to 10), representing 9 domains of disability. Mean differences between patients and care providers were calculated. Care providers’ characteristics associated with a mean difference ≥ 2 of 10 points were assessed in multivariate analysis. Answers were analyzed for 109 patients and 105 care providers. The mean age of patients was 55.9 (14.7) years and the disease duration was 10.1 (7.5) years. For all domains of the ICF-65, care providers’ rates were higher than those of patients. The mean difference was 2.4 (1.0) of 10 points. Care providers’ characteristics associated with this difference were organ-based specialty (OR = 7.0 [2.3–21.2]), younger age (OR = 2.7 [1.0–7.1]) and following patients with disease duration ≥5 years (OR = 3.0 [1.1–8.7]). We found systematic differences in disability perception between patients and care providers in SSc.
Retinal Pigment Epithelial Abnormality and Choroidal Large Vascular Flow Imbalance Are Associated with Choriocapillaris Flow Deficits in Age-Related Macular Degeneration in Fellow Eyes
Authors: Nagai Norihiro , Mushiga Yasuaki , Ozawa Yoko
Published: February 2023

Choriocapillaris flow deficits detected on optical coherence tomography angiographs were retrospectively analyzed. In 38 age-related macular degeneration (AMD) fellow eyes, without fundus findings (26 men, 71.7 ± 1.9 years old), and 22 control eyes (11 men, 69.4 ± 1.8), the choriocapillaris flow area (CCFA) ratio and coefficient of variation (CV) of the CCFA ratio (which represented the heterogeneity of the ratio), negatively and positively correlated with age (all p < 0.01), respectively. Moreover, the respective mean values were lower (p = 0.0031) and greater (p = 0.002) in AMD fellow eyes than in the control eyes. The high-risk condition of AMD fellow eyes was defined by a CCFA ratio <58.5%, and the CV of the CCFA ratio ≥0.165 (odds ratio (OR), 5.408; 95% confidence interval (CI): 1.117–21.118, p = 0.035, after adjusting for age and sex) was related to the presence of fundus autofluorescence abnormality (OR, 16.440; 95% CI, 1.262–214.240; p = 0.033) and asymmetrically dilated choroidal large vasculature (OR, 4.176; 95% CI, 1.057–16.503; p = 0.042), after adjusting for age and sex. The presence of fundus autofluorescence abnormality indicated a retinal pigment epithelium (RPE) abnormality. The RPE volume was reduced in the latter eye group, particularly in the thinner choroidal vasculature. In addition to aging, RPE abnormality and choroidal large vascular flow imbalances were associated with exacerbated heterogeneous choriocapillaris flow deficits in AMD fellow eyes without macular neovascularization.
Big Endothelin-1 as a Predictor of Reverse Remodeling and Prognosis in Dilated Cardiomyopathy
Authors: Feng Jiayu , Liang Lin , Chen Yuyi , Tian Pengchao , Zhao Xuemei , Huang Boping , Wu Yihang , Wang Jing , Guan Jingyuan , Huang Liyan , Li Xinqing , Zhang Yuhui , Zhang Jian
Published: February 2023

This study aimed to investigate the predictive value of Big endothelin-1(ET-1) for left ventricular reverse remodeling (LVRR) and prognosis in patients with dilated cardiomyopathy (DCM). Patients with DCM and a left ventricular ejection fraction (LVEF) ≤ 50% from 2008 to 2017 were included. LVRR was defined as the LVEF increased by at least 10% or follow-up LVEF increased to at least 50% with a minimum improvement of 5%; meanwhile, the index of left ventricular end-diastolic diameter (LVEDDi) decreased by at least 10% or LVEDDi decreased to ≤33 mm/m2. The composite outcome for prognostic analysis consisted of death and heart transplantations. Of the 375 patients included (median age 47 years, 21.1% female), 135 patients (36%) had LVRR after a median of 14 months of treatment. An independent association was found between Big ET-1 at baseline and LVRR in the multivariate model (OR 0.70, 95% CI 0.55–0.89, p = 0.003, per log increase). Big ET-1, body mass index, systolic blood pressure, diagnosis of type 2 diabetes mellitus (T2DM) and treatment with ACEI/ARB were significant predictors for LVRR after stepwise selection. Adding Big ET-1 to the model improved the discrimination (∆AUC = 0.037, p = 0.042 and reclassification (IDI, 3.29%; p = 0.002; NRI, 35%; p = 0.002) for identifying patients with LVRR. During a median follow-up of 39 (27–68) months, Big ET-1 was also independently associated with the composite outcome of death and heart transplantations (HR 1.45, 95% CI 1.13–1.85, p = 0.003, per log increase). In conclusion, Big ET-1 was an independent predictor for LVRR and had prognostic implications, which might help to improve the risk stratification of patients with DCM.
Temporomandibular Disorders Related Pain among Sleep & Awake Bruxers: A Comparison among Sexes and Age
Authors: Winocur Ephraim , Wieckiewicz Mieszko
Published: February 2023

According to the current international consensus [...]
Depression in Chinese Patients with Cleft Lip and/or Palate: A Preliminary Study
Authors: Xia Weiyao , Yang Renjie , Zong Yuan , Yang Yichun , Xie Zhuojun , Chi Ting , Shi Bing , Gong Caixia , Huang Hanyao
Published: February 2023

(1) Objectives: To investigate the difference in prevalence of depression between patients with CL/P (cleft lip and/or palate) and analyze the possible demographic factors that affect the prevalence of depression in Chinese patients with CL/P. (2) Methods: Patients with CL (cleft lip only), CP (cleft palate), and CLP (cleft lip and palate) were included in the study group. Non-CL/P individuals were included in the control group. The Patient Health Questionnaire (PHQ-9) was used to screen the depression of Chinese patients with CL/P. The different proportions of different depression groups between the CL/P group and the control groups were tested by the Fisher–Freeman–Halton test and Bonferroni correction. The scores between the study groups and the control group were analyzed by one-way ANOVA. In the study groups, demographic and clinical data of the patients, including diagnosis (CL, CP, CLP), gender, age, the only child or not, and region were collected to analyze whether they were the possible factors affecting depression through one-way independent-samples t-test. Pearson correlation analysis was used to analyze the correlation between monthly family income and depression. (3) Results: 111 and 80 valid questionnaires were collected from the study and control groups, respectively. The mean PHQ-9 score of the study group (5.459 ± 6.082) was relatively higher than the control group (4.362 ± 3.384), and the difference in proportions of depression groups was statistically significant between the CL/P group and the control group (p = 0.01), especially in the mild depression (p < 0.05) and moderately severe depression groups (p < 0.05). Statistically significant differences in PHQ-9 scores were observed between the individuals of different genders (p = 0.036) and ages (p = 0.007) in patients with CL/P, the individuals who were the only child or not in patients with CL (p = 0.007), and the individuals of different ages in patients with CP (p = 0.016). (4) Conclusions: The prevalence of depression in Chinese patients with CL/P was different compared with those without CL/P, while gender, age, the only child or not, and region played significant roles in affecting depression psychology.
Higher Leukocyte Count Is Associated with Lower Presence of Carotid Lipid-Rich Necrotic Core: A Sub-Study in the Plaque at RISK (PARISK) Study
Authors: van Velzen Twan Jowan , Stolp Jeffrey , van Dam-Nolen Dianne , Kassem Mohamed , Hendrikse Jeroen , Kooi Marianne Eline , Bos Daniel , Nederkoorn Paul J.
Published: February 2023

Background: Increasing evidence suggests that inflammation inside the vessel wall has a prominent role in atherosclerosis. In carotid atherosclerosis in particular, vulnerable plaque characteristics are strongly linked to an increased stroke risk. An association between leukocytes and plaque characteristics has not been investigated before and could help with gaining knowledge on the role of inflammation in plaque vulnerability, which could contribute to a new target for intervention. In this study, we investigated the association of the leukocyte count with carotid vulnerable plaque characteristics. Methods: All patients from the Plaque At RISK (PARISK) study whom had complete data on their leukocyte count and CTA- and MRI-based plaque characteristics were included. Univariable logistic regression was used to detect associations of the leukocyte count with the separate plaque characteristics (intra-plaque haemorrhage (IPH), lipid-rich-necrotic core (LRNC), thin or ruptured fibrous cap (TRFC), plaque ulceration and plaque calcifications). Subsequently, other known risk factors for stroke were included as covariates in a multivariable logistic regression model. Results: 161 patients were eligible for inclusion in this study. Forty-six (28.6%) of these patients were female with a mean age of 70 [IQR 64–74]. An association was found between a higher leukocyte count and lower prevalence of LRNC (OR 0.818 (95% CI 0.687–0.975)) while adjusting for covariates. No associations were found between the leucocyte count and the presence of IPH, TRFC, plaque ulceration or calcifications. Conclusions: The leukocyte count is inversely associated with the presence of LRNC in the atherosclerotic carotid plaque in patients with a recently symptomatic carotid stenosis. The exact role of leukocytes and inflammation in plaque vulnerability deserves further attention.
Norepinephrine May Exacerbate Septic Acute Kidney Injury: A Narrative Review
Authors: Al-Husinat Lou’i , Alsabbah Alameen , Hmaid Amer Abu , Athamneh Razan , Adwan Majd , Hourani Mohammad N. , Almakhadmeh Seif , Modanat Zaid Jehad Al , Ismail Mohammed I. A , Varrassi Giustino
Published: February 2023

Sepsis, the most serious complication of infection, occurs when a cascade of potentially life-threatening inflammatory responses is triggered. Potentially life-threatening septic shock is a complication of sepsis that occurs when hemodynamic instability occurs. Septic shock may cause organ failure, most commonly involving the kidneys. The pathophysiology and hemodynamic mechanisms of acute kidney injury in the case of sepsis or septic shock remain to be elucidated, but previous studies have suggested multiple possible mechanisms or the interplay of multiple mechanisms. Norepinephrine is used as the first-line vasopressor in the management of septic shock. Studies have reported different hemodynamic effects of norepinephrine on renal circulation, with some suggesting that it could possibly exacerbate acute kidney injury caused by septic shock. This narrative review briefly covers the updates on sepsis and septic shock regarding definitions, statistics, diagnosis, and management, with an explanation of the putative pathophysiological mechanisms and hemodynamic changes, as well as updated evidence. Sepsis-associated acute kidney injury remains a major burden on the healthcare system. This review aims to improve the real-world clinical understanding of the possible adverse outcomes of norepinephrine use in sepsis-associated acute kidney injury.
The Local Release of Teriparatide Incorporated in 45S5 Bioglass Promotes a Beneficial Effect on Osteogenic Cells and Bone Repair in Calvarial Defects in Ovariectomized Rats
Authors: de Araújo Juliani Caroline Ribeiro , Sobral Silva Leonardo Alvares , de Barros Lima Vinicius Almeida , Bastos Campos Tiago Moreira , Lisboa Filho Paulo Noronha , Okamoto Roberta , de Vasconcellos Luana Marotta Reis
Published: February 2023

With the increase in the population’s life expectancy, there has also been an increase in the rate of osteoporosis, which has expanded the search for strategies to regenerate bone tissue. The ultrasonic sonochemical technique was chosen for the functionalization of the 45S5 bioglass. The samples after the sonochemical process were divided into (a) functionalized bioglass (BG) and (b) functionalized bioglass with 10% teriparatide (BGT). Isolated mesenchymal cells (hMSC) from femurs of ovariectomized rats were differentiated into osteoblasts and submitted to in vitro tests. Bilateral ovariectomy (OVX) and sham ovariectomy (Sham) surgeries were performed in fifty-five female Wistar rats. After a period of 60 days, critical bone defects of 5.0 mm were created in the calvaria of these animals. For biomechanical evaluation, critical bone defects of 3.0 mm were performed in the tibias of some of these rats. The groups were divided into the clot (control) group, the BG group, and the BGT group. After the sonochemical process, the samples showed modified chemical topographic and morphological characteristics, indicating that the surface was chemically altered by the functionalization of the particles. The cell environment was conducive to cell adhesion and differentiation, and the BG and BGT groups did not show cytotoxicity. In addition, the experimental groups exhibited characteristics of new bone formation with the presence of bone tissue in both periods, with the BGT group and the OVX group statistically differing from the other groups (p < 0.05) in both periods. Local treatment with the drug teriparatide in ovariectomized animals promoted positive effects on bone tissue, and longitudinal studies should be carried out to provide additional information on the biological performance of the mutual action between the bioglass and the release of the drug teriparatide.
Application of the Gini Index on the Evaluation of the Environmental Heterogeneity and Habitat Suitability Index for Larval Gobies
Authors: Zhai Lu , Wan Rong , Tian Siquan , Li Zengguang , Song Pengbo , Lin Jun
Published: February 2023

Spatial environmental heterogeneity in the Yangtze River Estuary (YRE) is always mentioned but rarely quantified and included in the evaluation process. This study introduced the habitat suitability index evaluation model based on the Gini index (HSIgini) to evaluate the optimal ranges of suitable environmental factors for three typical estuarine gobies, i.e., Rhinogobius giurinus, Acentrogobius pflaumii, Odontamblyopus rubicundus, and their habitat quality. The evaluation was carried out based on field surveys conducted in the spring and summer of 2018–2020. The Lorentz curve and Gini index were used to evaluate the spatial environmental heterogeneities in the YRE. The spatial heterogeneity of environmental factors in the Yangtze Estuary ranged from 0.62 to 0.05, with the highest Gini index for salinity and the lowest for temperature. The combination of environmental factors had significant spatial effects on habitat, with temperature showing mainly seasonal effects. The study indicated that the YRE is a good habitat for gobies and that there is spatial and seasonal differentiation in the habitats of different species, greatly reducing interspecific competition. Environmental heterogeneity is important for biological processes and should be incorporated into the modeling of bio–environmental relationships in future research to provide a basis for environmental and biological conservation and management.
Salivary-Based Cell-Free Mitochondrial DNA Level Is an Independent Prognostic Biomarker for Patients with Head and Neck Squamous Cell Carcinoma
Authors: Sayal Lana , Hamadah Omar , AlMasri Aroub , Idrees Majdy , Kassem Issam , Habbal Wafa , Alsalamah Buthainah , Kujan Omar
Published: February 2023

Changes in the copy numbers of cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) have shown promising diagnostic utilities among patients with head and neck squamous cell carcinoma (HNSCC). Considering the absence of objective prognostic tools for HNSCC surveillance, this study aimed to assess the utility of saliva-based cf-nDNA and cf-mtDNA in predicting the overall survival of patients with HNSCC. The study included ninety-four patients with a confirmed HNSCC diagnosis with a mean follow-up time of 32.04 months (±19.1). A saliva-based liquid biopsy was collected from each patient. A multiplex quantitative PCR was used to determine the absolute number of cf-nDNA and cf-mtDNA. The Kaplan–Meier estimator and Cox proportional hazards regression models were used to assess overall survival. The absolute copy numbers of cf-nDNA and cf-mtDNA were statistically significantly higher among the deceased patients than among the censored ones (p < 0.05). Individuals with elevated levels of cf-nDNA or cf-mtDNA were associated with a significantly poorer overall survival (p ≤ 0.05). A univariate analysis showed that only the absolute copy number of cf-mtDNA was the sole predictor of overall survival. However, the multivariate analysis showed that all the absolute copy numbers of cf-nDNA, the absolute copy numbers of cf-mtDNA, and the stage of HNSCC were predictors of overall survival. Our study confirms that saliva is a reliable and non-invasive source of data that can be used to predict the overall survival of patients with HNSCC, where cf-mtDNA levels act as the sole predictor.
The Role of Somatostatin Analogues in the Control of Diarrhea and Flushing as Markers of Carcinoid Syndrome: A Systematic Review and Meta-Analysis
Authors: Alexandraki Krystallenia I. , Angelousi Anna , Chatzellis Eleftherios , Chrisoulidou Alexandra , Kalogeris Nikolaos , Kanakis Georgios , Savvidis Christos , Vassiliadi Dimitra , Spyroglou Ariadni , Kostopoulos Georgios , Markussis Vyron , Toulis Konstantinos , Tsagarakis Stylianos , Kaltsas Gregory A.
Published: February 2023

Background: Somatostatin analogues (SSAs) are the cornerstone of treatment for carcinoid syndrome (CS)-related symptoms. The aim of this systematic review and meta-analysis is to evaluate the percentage of patients achieving partial (PR) or complete response (CR) with the use of long-acting SSAs in patients with CS. Methods: A systematic electronic literature search was conducted in PubMed, Cochrane, and Scopus to identify eligible studies. Any clinical trials reporting data on the efficacy of SSAs to alleviate symptoms in adult patients were considered as potentially eligible. Results: A total of 17 studies reported extractable outcomes (PR/CR) for quantitative synthesis. The pooled percentage of patients with PR/CR for diarrhea was estimated to be 0.67 (95% confidence interval (CI): 0.52–0.79, I2 = 83%). Subgroup analyses of specific drugs provided no evidence of a differential response. With regards to flushing, the pooled percentage of patients with PR/CR was estimated to be 0.68 (95% CI: 0.52–0.81, I2 = 86%). Similarly, no evidence of a significant differential response in flushing control was documented. Conclusions: We estimate there is a 67–68% overall reduction in symptoms of CS associated with SSA treatment. However, significant heterogeneity was detected, possibly revealing differences in the disease course, in management and in outcome definition.
Cellular and Humoral Responses in Dialysis Patients after Vaccination with the BNT162b2 or mRNA-1273 Vaccines
Authors: Mavrovouniotis Ilias , Fylaktou Asimina , Stagou Maria , Ouranos Konstantinos , Lioulios Georgios , Evgenikaki Efthimia , Exindari Maria , Gioula Georgia
Published: February 2023

The outbreak of SARS-CoV-2 has raised considerable concern about the detrimental effects it can induce in public health, with the interest of the scientific community being focused on the development of preventive and therapeutic approaches. Patients with end-stage renal disease (ESRD) are amongst vulnerable populations for critical illness owing to the presence of other comorbidities, their defective immune system, and their inability of self-isolation. To date, vaccination constitutes the most promising method to manage viral dispersion. Therefore, it is particularly important to investigate the effectiveness of available vaccines against SARS-CoV-2 in this risk group. Here, we summarize initial experience regarding the humoral and cellular immune responses elicited in dialysis patients after completion of the recommended vaccination regimen, as well as after booster dose administration, with one of the two mRNA vaccines, namely, BNT162b2 and mRNA-1273. In conclusion, a significantly diminished and delayed immune pattern was observed in ESRD patients compared to healthy population, with a peak in antibody titers occurring 3–5 weeks after the second dose. A booster dose significantly augmented the immune response in dialysis patients with either mRNA-based vaccine. Variables adversely correlating with the weak immunogenicity observed in dialysis patients include immunosuppressive therapy, older age, comorbidities, longer time in hemodialysis treatment, and higher body mass index. On the contrary, previous COVID-19 infection and administration of the mRNA-1273 vaccine are deemed to induce a more favorable immune response. Further investigation is needed to thoroughly understand the efficacy of mRNA-based vaccines in hemodialysis patients and define predictive factors that can influence it.
Pregnancy in Patients with Inflammatory Bowel Diseases—A Literature Review
Authors: Grigorescu Raluca Roxana , Husar-Sburlan Ioana Alexandra , Rosulescu Georgiana , Bobirca Anca , Cerban Razvan , Bobirca Florin , Florescu Madalina Marieta
Published: February 2023

In recent years, we have faced an increasing incidence of inflammatory bowel disease (IBD), especially among young people, affecting them during their reproductive years. The paucity of data and reduced knowledge regarding the evolution of the disease during pregnancy and the adverse effects of the therapy on the mother and infant increase voluntary childlessness in this group of patients. Depending on the type of IBD, severity and surgical or medical management, this can negatively affect the pregnancy. C-sections and the risk of low-birth-weight babies are higher in women with IBD, independent of active/inactive disease, while preterm birth, stillbirth and miscarriage are associated with disease activity. In the last period, medicinal therapy has evolved, and new molecules have been developed for better control of the lesions, but the effect on pregnancy and breastfeeding is still controversial. We conducted this review by studying the literature and recent research in order to have a better image of the practical management of IBD during pregnancy.
The Many Roles of Dermoscopy in Melanoma Detection
Authors: (Jitian) Mihulecea Cristina-Raluca , Iancu Gabriela Mariana , Leventer Mihaela , Rotaru Maria
Published: February 2023

Dermoscopy is a non-invasive method of examination that aids the clinician in many ways, especially in early skin cancer detection. Melanoma is one of the most aggressive forms of skin cancer that can affect individuals of any age, having an increasing incidence worldwide. The gold standard for melanoma diagnosis is histopathological examination, but dermoscopy is also very important for its detection. To highlight the many roles of dermoscopy, we analyzed 200 melanocytic lesions. The main objective of this study was to detect through dermoscopy hints of melanomagenesis in the studied lot. The most suspicious were 10 lesions which proved to be melanomas confirmed through histopathology. The second objective of this study was to establish if dermoscopy can aid in estimating the Breslow index (tumoral thickness) of the melanomas and to compare the results to the histopathological examination. We found that the tumoral thickness may be estimated through dermoscopy, but the histopathological examination is superior. To conclude, the aim of this study was to showcase the versatility and many roles of dermoscopy, besides being one of the most important tools for early melanoma diagnosis.