bluuebunny/crossref_metadata_2025 huggingface dataset:
The Long Non-Coding RNA SNHG12 as a Mediator of Carboplatin Resistance in Ovarian Cancer via Epigenetic Mechanisms
Authors: Abildgaard Cecilie , do Canto Luisa Matos , Rainho Cláudia Aparecida , Marchi Fabio Albuquerque , Calanca Naiade , Waldstrøm Marianne , Steffensen Karina Dahl , Rogatto Silvia Regina
Published: March 2022

Genetic and epigenetic changes contribute to intratumor heterogeneity and chemotherapy resistance in several tumor types. LncRNAs have been implicated, directly or indirectly, in the epigenetic regulation of gene expression. We investigated lncRNAs that potentially mediate carboplatin-resistance of cell subpopulations, influencing the progression of ovarian cancer (OC). Four carboplatin-sensitive OC cell lines (IGROV1, OVCAR3, OVCAR4, and OVCAR5), their derivative resistant cells, and two inherently carboplatin-resistant cell lines (OVCAR8 and Ovc316) were subjected to RNA sequencing and global DNA methylation analysis. Integrative and cross-validation analyses were performed using external (The Cancer Genome Atlas, TCGA dataset, n = 111 OC samples) and internal datasets (n = 39 OC samples) to identify lncRNA candidates. A total of 4255 differentially expressed genes (DEGs) and 14529 differentially methylated CpG positions (DMPs) were identified comparing sensitive and resistant OC cell lines. The comparison of DEGs between OC cell lines and TCGA-OC dataset revealed 570 genes, including 50 lncRNAs, associated with carboplatin resistance. Eleven lncRNAs showed DMPs, including the SNHG12. Knockdown of SNHG12 in Ovc316 and OVCAR8 cells increased their sensitivity to carboplatin. The results suggest that the lncRNA SNHG12 contributes to carboplatin resistance in OC and is a potential therapeutic target. We demonstrated that SNHG12 is functionally related to epigenetic mechanisms.
Pneumatosis Intestinalis Induced by Anticancer Treatment: A Systematic Review
Authors: Gazzaniga Gianluca , Villa Federica , Tosi Federica , Pizzutilo Elio Gregory , Colla Stefano , D’Onghia Stefano , Di Sanza Giusy , Fornasier Giulia , Gringeri Michele , Lucatelli Maria Victoria , Mosini Giulia , Pani Arianna , Siena Salvatore , Scaglione Francesco , Sartore-Bianchi Andrea
Published: March 2022

Pneumatosis intestinalis (PI) is a rare condition due to the presence of gas within the bowel wall; it is mainly caused by endoscopic procedures, infections and other gastrointestinal diseases. Oncological therapies have been reported to be a cause of PI as well, but their role is not clearly defined. This systematic review investigates the concurrency of PI and antitumor therapy in cancer patients, considering both solid tumors and onco-hematological ones. We performed a literature review of PubMed, Embase and the Web of Science up to September 2021 according to the PRISMA guidelines. A total of 62 papers reporting 88 different episodes were included. PI was mainly reported with targeted therapies (sunitinib and bevacizumab above all) within the first 12 weeks of treatment. This adverse event mostly occurred in the metastatic setting, but in 10 cases, it also occurred also in the neoadjuvant and adjuvant setting. PI was mostly localized in the large intestine, being fatal in 11 cases, while in the remaining cases, symptoms were usually mild, or even absent. A significant risk of PI reoccurrence after drug reintroduction was also reported (6/18 patients), with no fatal outcomes. Potential pharmacological mechanisms underlying PI pathogenesis are also discussed. In conclusion, although uncommonly, PI can occur during oncological therapies and may lead to life-threatening complications; therefore, consideration of its occurrence among other adverse events is warranted in the presence of clinical suspicion.
Outcomes of Patients with Metastatic Melanoma—A Single-Institution Retrospective Analysis
Authors: Szatkowska Lidia , Sieczek Jan , Tekiela Katarzyna , Ziętek Marcin , Stachyra-Strawa Paulina , Cisek Paweł , Matkowski Rafał
Published: March 2022

Background: This study assessed risk factors and the results of treatment with anti-PD-1 antibodies and BRAF/MEK inhibitors for advanced malignant melanoma. Methods: A retrospective analysis was performed on 52 patients treated with immunotherapy and BRAF/MEK inhibitors for disseminated malignant melanoma. Results: The median follow-up was 31 months (6–108 months). The median PFS1 was 6 months (1–44 months). Second-line systemic treatment was applied in 27 patients (52%). The median PFS2 was 2 months (0–27 months), and the median OS was 31 months (6–108 months). Among the analyzed risk factors, only the presence of the BRAF mutation was statistically significant for disease recurrence after surgery. In patients undergoing anti-BRAF/MEK therapy, the median PFS1 was 7 months, and in patients undergoing mono-immunotherapy, 4 months. The 12- and 24-month PFS1 rates in the group treated with BRAF inhibitors were 29 and 7%, respectively, and in patients treated with mono-immunotherapy 13 and 0%, respectively (Z = 1.998, p = 0.04). The type of treatment used had no effect on OS (Z = 0.237, p > 0.05). Conclusion: Patients with the V600 mutation should be closely monitored. In the event of disease recurrence, treatment with BRAF/MEK inhibitors should be considered. The type of treatment used has no effect on OS.
Context-Aware Saliency Guided Radiomics: Application to Prediction of Outcome and HPV-Status from Multi-Center PET/CT Images of Head and Neck Cancer
Authors: Lv Wenbing , Xu Hui , Han Xu , Zhang Hao , Ma Jianhua , Rahmim Arman , Lu Lijun
Published: March 2022

Purpose: This multi-center study aims to investigate the prognostic value of context-aware saliency-guided radiomics in 18F-FDG PET/CT images of head and neck cancer (HNC). Methods: 806 HNC patients (training vs. validation vs. external testing: 500 vs. 97 vs. 209) from 9 centers were collected from The Cancer Imaging Archive (TCIA). There were 100/384 and 60/123 oropharyngeal carcinoma (OPC) patients with human papillomavirus (HPV) status in training and testing cohorts, respectively. Six types of images were used for radiomics feature extraction and further model construction, namely (i) the original image (Origin), (ii) a context-aware saliency map (SalMap), (iii, iv) high- or low-saliency regions in the original image (highSal or lowSal), (v) a saliency-weighted image (SalxImg), and finally, (vi) a fused PET-CT image (FusedImg). Four outcomes were evaluated, i.e., recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), and disease-free survival (DFS), respectively. Multivariate Cox analysis and logistic regression were adopted to construct radiomics scores for the prediction of outcome (Rad_Ocm) and HPV-status (Rad_HPV), respectively. Besides, the prognostic value of their integration (Rad_Ocm_HPV) was also investigated. Results: In the external testing cohort, compared with the Origin model, SalMap and SalxImg achieved the highest C-indices for RFS (0.621 vs. 0.559) and MFS (0.785 vs. 0.739) predictions, respectively, while FusedImg performed the best for both OS (0.685 vs. 0.659) and DFS (0.641 vs. 0.582) predictions. In the OPC HPV testing cohort, FusedImg showed higher AUC for HPV-status prediction compared with the Origin model (0.653 vs. 0.484). In the OPC testing cohort, compared with Rad_Ocm or Rad_HPV alone, Rad_Ocm_HPV performed the best for OS and DFS predictions with C-indices of 0.702 (p = 0.002) and 0.684 (p = 0.006), respectively. Conclusion: Saliency-guided radiomics showed enhanced performance for both outcome and HPV-status predictions relative to conventional radiomics. The radiomics-predicted HPV status also showed complementary prognostic value.
Effect and Tolerability of Immunotherapy in Patients with NSCLC with or without Brain Metastasis
Authors: Bjørnhart Birgitte , Hansen Karin Holmskov , Asmussen Jon Thor , Jørgensen Trine Lembrecht , Herrstedt Jørn , Schytte Tine
Published: March 2022

Sparse data exist on immune checkpoint inhibition (ICI) in NSCLC patients with brain metastasis (BM), especially for those with no local therapy (LT) (whole brain radiation therapy (WBRT), stereotactic RT (SRT) or neurosurgery) preceding ICI. Our aims were to investigate the prevalence of BM, rate of intracranial response (ICR), and survival and quality of life (QoL) in real-life patients with advanced NSCLC undergoing palliative ICI. This was a prospective non-randomized study (NCT03870464) with magnetic resonance imaging of the brain (MR-C) performed at baseline resulting in a clinical decision to administer LT or not. ICR evaluation (MR-C) at week 8–9 (mRECIST criteria) for group A (LT) and group B (untreated) was assessed. Change in QoL was assessed using EQ-5D-5L. Of 159 included patients, 45 (28%) had baseline BM. Median follow-up was 23.2 months (IQR 16.4–30.2). Of patients in group A (21) and B (16), 16/37 (43%) had symptomatic BM. ICR was 8/21, 38% (complete or partial response) for group A versus 8/16, 50% for group B. No statistical difference in median overall survival of patients with BM (group A: 12.3 (5.2-NR), group B: 20.5 months (4.9-NR)) and without (22.4 months (95% 16.2–26.3)) was obtained. Baseline QoL was comparable regardless of BM, but an improved QoL (at week 9) was found in those without BM. Patients with NSCLC and BM receiving ICI had long-term survival comparable to those without BM.
MicroRNAs and Progesterone Receptor Signaling in Endometriosis Pathophysiology
Authors: Nothnick Warren B.
Published: March 2022

Endometriosis is a significant disease characterized by infertility and pelvic pain in which endometrial stromal and glandular tissue grow in ectopic locations. Altered responsiveness to progesterone is a contributing factor to endometriosis pathophysiology, but the precise mechanisms are poorly understood. Progesterone resistance influences both the eutopic and ectopic (endometriotic lesion) endometrium. An inability of the eutopic endometrium to properly respond to progesterone is believed to contribute to the infertility associated with the disease, while an altered responsiveness of endometriotic lesion tissue may contribute to the survival of the ectopic tissue and associated symptoms. Women with endometriosis express altered levels of several endometrial progesterone target genes which may be due to the abnormal expression and/or function of progesterone receptors and/or chaperone proteins, as well as inflammation, genetics, and epigenetics. MiRNAs are a class of epigenetic modulators proposed to play a role in endometriosis pathophysiology, including the modulation of progesterone signaling. In this paper, we summarize the role of progesterone receptors and progesterone signaling in endometriosis pathophysiology, review miRNAs, which are over-expressed in endometriosis tissues and fluids, and follow this with a discussion on the potential regulation of key progesterone signaling components by these miRNAs, concluding with suggestions for future research endeavors in this area.
The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth
Authors: Allen Sophie L. , Seabright Alex P. , Quinlan Jonathan I. , Dhaliwal Amritpal , Williams Felicity R. , Fine Nicholas H. F. , Hodson David J. , Armstrong Matthew J. , Elsharkaway Ahmed M. , Greig Carolyn A. , Lai Yu-Chiang , Lord Janet M. , Lavery Gareth G. , Breen Leigh
Published: March 2022

Sarcopenia is a common complication affecting liver disease patients, yet the underlying mechanisms remain unclear. We aimed to elucidate the cellular mechanisms that drive sarcopenia progression using an in vitro model of liver disease. C2C12 myotubes were serum and amino acid starved for 1-h and subsequently conditioned with fasted ex vivo serum from four non-cirrhotic non-alcoholic fatty liver disease patients (NAFLD), four decompensated end-stage liver disease patients (ESLD) and four age-matched healthy controls (CON) for 4- or 24-h. After 4-h C2C12 myotubes were treated with an anabolic stimulus (5 mM leucine) for 30-min. Myotube diameter was reduced following treatment with serum from ESLD compared with CON (−45%) and NAFLD (−35%; p < 0.001 for both). A reduction in maximal mitochondrial respiration (24% and 29%, respectively), coupling efficiency (~12%) and mitophagy (~13%) was identified in myotubes conditioned with NAFLD and ESLD serum compared with CON (p < 0.05 for both). Myostatin (43%, p = 0.04) and MuRF-1 (41%, p = 0.03) protein content was elevated in myotubes treated with ESLD serum compared with CON. Here we highlight a novel, experimental platform to further probe changes in circulating markers associated with liver disease that may drive sarcopenia and develop targeted therapeutic interventions.
Emerging Roles and Mechanism of m6A Methylation in Cardiometabolic Diseases
Authors: Xu Zujie , Lv Binbin , Qin Ying , Zhang Bing
Published: March 2022

Cardiometabolic diseases (CMDs) are currently the leading cause of death and disability worldwide, and their underlying regulatory mechanisms remain largely unknown. N6-methyladenosine (m6A) methylation, the most common and abundant epigenetic modification of eukaryotic mRNA, is regulated by m6A methyltransferase, demethylase, and the m6A binding protein, which affect the transcription, cleavage, translation, and degradation of target mRNA. m6A methylation plays a vital role in the physiological and pathological processes of CMDs. In this review, we summarize the role played by m6A methylation in CMDs, including obesity, hypertension, pulmonary hypertension, ischemic heart disease, myocardial hypertrophy, heart failure, and atherosclerosis. We also describe mechanisms that potentially involve the participation of m6A methylation, such as those driving calcium homeostasis, circadian rhythm, lipid metabolism, autophagy, macrophage response, and inflammation. m6A methylation and its regulators are expected to be targets for the treatment of CMDs.
Suitability of Human Mesenchymal Stem Cells Derived from Fetal Umbilical Cord (Wharton’s Jelly) as an Alternative In Vitro Model for Acute Drug Toxicity Screening
Authors: Christodoulou Ioannis , Goulielmaki Maria , Kritikos Andreas , Zoumpourlis Panagiotis , Koliakos Georgios , Zoumpourlis Vassilis
Published: March 2022

Preclinical toxicity screening is the first and most crucial test that assesses the safety of new candidate drugs before their consideration for further evaluation in clinical trials. In vitro drug screening using stem cells has lately arisen as a promising alternative to the “gold standard” of animal testing, but their suitability and performance characteristics in toxicological studies have so far not been comprehensively investigated. In this study, we focused on the evaluation of human mesenchymal stem cells isolated from the matrix (Wharton’s jelly) of fetal umbilical cord (WJSCs), which bear enhanced in vitro applicability due to their unique biological characteristics. In order to determine their suitability for drug-related cytotoxicity assessment, we adopted a high-throughput methodology that evaluated their sensitivity to a selected panel of chemicals in different culture environments. Cytotoxicity was measured within 48 h by means of MTS and/or NRU viability assays, and was compared directly (in vitro) or indirectly (in silico) to adult human mesenchymal stem cells and to reference cell lines of human and murine origin. Our data clearly suggest that human WJSCs can serve as a robust in vitro alternative for acute drug toxicity screening by uniquely combining rapid and versatile assay setup with high-throughput analysis, good representation of human toxicology, high reproducibility, and low cost.
Reticulocalbin 2 as a Potential Biomarker and Therapeutic Target for Atherosclerosis
Authors: Li Jing , Taylor Angela M. , Manichaikul Ani , Angle John F. , Shi Weibin
Published: March 2022

Vascular inflammation initiated by oxidized lipoproteins drives initiation, progression, and even rupture of atherosclerotic plaques. Yet, to date, no biomarker is directly linked to oxidized lipid-induced vascular inflammation. Reticulocalbin 2 (RCN2) is a key regulator of basal and oxidized lipid-induced cytokine production in arterial wall cells. We evaluated the potential of circulating RCN2 to identify subjects with or at risk of developing atherosclerosis. Immunohistochemical analysis revealed abundant RCN2 expression in the endothelium and adventitia of normal arteries and in atherosclerotic lesions of both humans and mice. Atherosclerosis-susceptible C57BL/6 (B6) mice had higher plasma Rcn2 levels than resistant C3H mice. High-fat diet feeding raised plasma Rcn2 levels of both strains. In humans, patients with coronary artery disease (CAD) or peripheral artery disease (PAD) showed elevated serum RCN2 levels compared to healthy controls. In a cohort of 92 CAD patients, serum RCN2 exhibited a significant inverse correlation with HDL cholesterol and K+ levels and a trend toward association with white blood cell account, Na+, statin treatment, and diastolic blood pressure. HDL treatment suppressed Rcn2 expression in endothelial cells. This study suggests that circulating RCN2 is a potential non-invasive biomarker for identifying individuals with atherosclerosis and HDL protects against atherosclerosis by downregulation of RCN2 expression in endothelial cells.
L-Type Cav1.3 Calcium Channels Are Required for Beta-Adrenergic Triggered Automaticity in Dormant Mouse Sinoatrial Pacemaker Cells
Authors: Louradour Julien , Bortolotti Olivier , Torre Eleonora , Bidaud Isabelle , Lamb Ned , Fernandez Anne , Le Guennec Jean-Yves , Mangoni Matteo E. , Mesirca Pietro
Published: March 2022

Background: Sinoatrial node cells (SANC) automaticity is generated by functional association between the activity of plasmalemmal ion channels and local diastolic intracellular Ca2+ release (LCR) from ryanodine receptors. Strikingly, most isolated SANC exhibit a “dormant” state, whereas only a fraction shows regular firing as observed in intact SAN. Recent studies showed that β-adrenergic stimulation can initiate spontaneous firing in dormant SANC, though this mechanism is not entirely understood. Methods: To investigate the role of L-type Cav1.3 Ca2+ channels in the adrenergic regulation of automaticity in dormant SANC, we used a knock-in mouse strain in which the sensitivity of L-type Cav1.2 α1 subunits to dihydropyridines (DHPs) was inactivated (Cav1.2DHP−/−), enabling the selective pharmacological inhibition of Cav1.3 by DHPs. Results: In dormant SANC, β-adrenergic stimulation with isoproterenol (ISO) induced spontaneous action potentials (AP) and Ca2+ transients, which were completely arrested with concomitant perfusion of the DHP nifedipine. In spontaneously firing SANC at baseline, Cav1.3 inhibition completely reversed the effect of β-adrenergic stimulation on AP and the frequency of Ca2+ transients. Confocal calcium imaging of SANC showed that the β-adrenergic-induced synchronization of LCRs is regulated by the activity of Cav1.3 channels. Conclusions: Our study shows a novel role of Cav1.3 channels in initiating and maintaining automaticity in dormant SANC upon β-adrenergic stimulation.
Evolution of the Degenerated Y-Chromosome of the Swamp Guppy, Micropoecilia picta
Authors: Nanda Indrajit , Schories Susanne , Simeonov Ivan , Adolfi Mateus Contar , Du Kang , Steinlein Claus , Alsheimer Manfred , Haaf Thomas , Schartl Manfred
Published: March 2022

The conspicuous colour sexual dimorphism of guppies has made them paradigmatic study objects for sex-linked traits and sex chromosome evolution. Both the X- and Y-chromosomes of the common guppy (Poecilia reticulata) are genetically active and homomorphic, with a large homologous part and a small sex specific region. This feature is considered to emulate the initial stage of sex chromosome evolution. A similar situation has been documented in the related Endler’s and Oropuche guppies (P. wingei, P. obscura) indicating a common origin of the Y in this group. A recent molecular study in the swamp guppy (Micropoecilia. picta) reported a low SNP density on the Y, indicating Y-chromosome deterioration. We performed a series of cytological studies on M. picta to show that the Y-chromosome is quite small compared to the X and has accumulated a high content of heterochromatin. Furthermore, the Y-chromosome stands out in displaying CpG clusters around the centromeric region. These cytological findings evidently illustrate that the Y-chromosome in M. picta is indeed highly degenerated. Immunostaining for SYCP3 and MLH1 in pachytene meiocytes revealed that a substantial part of the Y remains associated with the X. A specific MLH1 hotspot site was persistently marked at the distal end of the associated XY structure. These results unveil a landmark of a recombining pseudoautosomal region on the otherwise strongly degenerated Y chromosome of M. picta. Hormone treatments of females revealed that, unexpectedly, no sexually antagonistic color gene is Y-linked in M. picta. All these differences to the Poecilia group of guppies indicate that the trajectories associated with the evolution of sex chromosomes are not in parallel.
High-Performance Bidirectional Chemical Sensor Platform Using Double-Gate Ion-Sensitive Field-Effect Transistor with Microwave-Assisted Ni-Silicide Schottky-Barrier Source/Drain
Authors: Kim Yeong-Ung , Cho Won-Ju
Published: March 2022

This study proposes a bidirectional chemical sensor platform using ambipolar double-gate ion-sensitive field-effect transistors (ISFET) with microwave-assisted Ni-silicide Schottky-barrier (SB) source and drain (S/D) on a fully depleted silicon-on-insulator (FDSOI) substrate. The microwave-assisted Ni-silicide SB S/D offer bidirectional turn-on characteristics for both p- and n-type channel operations. The p- and n-type operations are characterized by high noise resistance as well as improved mobility and excellent drift performance, respectively. These features enable sensing regardless of the gate voltage polarity, thus contributing to the use of detection channels based on various target substances, such as cells, antigen-antibodies, DNA, and RNA. Additionally, the capacitive coupling effect existing between the top and bottom gates help achieve self-amplified pH sensitivity exceeding the Nernst limit of 59.14 mV/pH without any additional amplification circuitry. The ambipolar FET sensor performance was evaluated for bidirectional electrical characteristics, pH detection in the single-gate and double-gate modes, and reliability in continuous and repetitive operations. Considering the excellent characteristics confirmed through evaluation, the proposed ambipolar chemical sensor platform is expected to be applicable to various fields including biosensors. And through linkage with subsequent studies, various medical applications and precision detector operations for specific markers will be possible.
Visible and Near Infrared Image Fusion Using Base Tone Compression and Detail Transform Fusion
Authors: Son Dong-Min , Kwon Hyuk-Ju , Lee Sung-Hak
Published: March 2022

This study aims to develop a spatial dual-sensor module for acquiring visible and near-infrared images in the same space without time shifting and to synthesize the captured images. The proposed method synthesizes visible and near-infrared images using contourlet transform, principal component analysis, and iCAM06, while the blending method uses color information in a visible image and detailed information in an infrared image. The contourlet transform obtains detailed information and can decompose an image into directional images, making it better in obtaining detailed information than decomposition algorithms. The global tone information is enhanced by iCAM06, which is used for high-dynamic range imaging. The result of the blended images shows a clear appearance through both the compressed tone information of the visible image and the details of the infrared image.
Cardiac Remodeling and Its Determinants in Anorexia Nervosa Adolescents: Impact of Weight Recovery
Authors: Paysal Justine , Thireau Jérôme , Terral Daniel , Rochette Emmanuelle , Obert Philippe , Merlin Etienne , Nottin Stéphane
Published: March 2022

Cardiovascular alterations in anorexia nervosa (AN) adolescents include bradycardia and decreased systolic blood pressure and left ventricular mass. However, their determinants remain poorly understood. We assessed the associations between morphological and functional left ventricular (LV) remodeling, autonomic control by heart rate variability (HRV) analysis, thyroid hormones and brain natriuretic peptide (BNP) levels in AN female adolescents without or with weight recovery (WR). Fifty-nine female adolescents including 16 AN patients without WR (mean age 13.9 years (10–16)), 10 AN patients with WR (15.7 years (12–18)) and 33 controls (14.1 years (10–18)) underwent night heart rate (HR) recording to measure HRV (and especially SD1/SD2, the ratio between instantaneous (SD1) and long-term (SD2) standard deviation of R-R intervals, reflecting sympatho-vagal balance), speckle tracking echocardiography to assess LV global longitudinal strain (GLS) and blood test for dosage of tri-iodothyronine (T3) hormone and NT-proBNP. Compared to controls, AN patients without WR presented with lower HR (55 ± 7 vs. 68 ± 6 bpm; p < 0.001), parasympathetic hyperactivity, and higher GLS (−19.2 ± 1.8 vs. −16.9 ± 2.8%; p = 0.009). These alterations were partly abolished in AN patients with WR. In a multivariate regression analysis, T3 was the main factor explaining the variance of SD1/SD2, a sympatho-vagal balance marker. NT-proBNP levels were not correlated with cardiac alterations. AN patients had parasympathetic hyperactivity linked with their rate of T3, and a higher GLS. These alterations were partly restored in AN patients with WR.
Surgical Management of Pre-Chiasmatic Intraorbital Optic Nerve Gliomas in Children after Loss of Visual Function—Resection from Bulbus to Chiasm
Authors: Zipfel Julian , Tellermann Jonas , Besch Dorothea , Bertelmann Eckart , Ebinger Martin , Driever Pablo Hernáiz , Schittenhelm Jens , Beschorner Rudi , Koch Arend , Thomale Ulrich-Wilhelm , Schuhmann Martin Ulrich
Published: March 2022

Optic pathway gliomas in children carry significant morbidity and therapeutic challenges. For the subgroup of pre-chiasmatic gliomas, intraorbital and intradural resection is a curative option after blindness. We present a two-center cohort using different surgical approaches. A retrospective analysis was performed, including 10 children. Mean age at surgery was 6.8 years. Interval between diagnosis and surgery was 1–74 (mean 24 ± 5.5, median 10) months. Indications for surgery were exophthalmos, pain, tumor progression, or a combination. Eight patients underwent an extradural trans-orbital-roof approach to resect the intra-orbital tumor, including the optic canal part plus intradural pre-chiasmatic resection. Gross total resection was achieved in 7/8, and none had a recurrence. One residual behind the bulbus showed progression, treated by chemotherapy. In two patients, a combined supra-orbital mini-craniotomy plus orbital frame osteotomy was used for intraorbital tumor resection + intradural pre-chiasmatic dissection. In these two patients, remnants of the optic nerve within the optic canal remained stable. No patient had a chiasmatic functional affection nor permanent oculomotor deficits. In selected patients, a surgical resection from bulb to chiasm ± removal of optic canal tumor was safe without long-term sequela and with an excellent cosmetic result. Surgery normalizes exophthalmos and provides an effective tumor control.
A Cross-Temporal Meta-Analysis of Changes in Left-Behind Children’s Mental Health in China
Authors: Zhang Xiaoyi , Dai Zhoudao , Antwi Collins Opoku , Ren Jun
Published: March 2022

A considerable body of research using the Mental Health Test (MHT) has explored the psychological repercussions of the physical separation of children from one or both parents as they pursue better economic prospects in cities. Generally, these studies compare the mental health status (MHS) between left-behind children (LBC) and non-left-behind children (NLBC). That notwithstanding, little is known about the real policy impact of these studies on the ground over the years. Using a relevant search strategy and selection criteria, we identified qualified studies (N = 102: 2004 to 2019). Cross-temporal meta-analysis (CTMA) was performed on these studies for dynamic trends. Our results demonstrate: (1) a slight but significant change in MHS of both LBC and NLBC, with LBC being significantly worse off over time; (2) a significant deterioration in MHS of LBC over time, particularly among left-behind boys (LBBs); (3) a stable and significant decline in MHS of left-behind junior high and elementary school students, respectively; and (4) a more substantial degradation in MHS of LBC with both parents absent compared with LBC with a parent present. The findings reveal that the efforts of, and collaboration among, researchers, policy experts and politicians are producing results. Nevertheless, more targeted research is needed to unearth the underlying issues that generate the differences among subpopulations of LBC to better inform pragmatic interventions for collective psychological wellness of LBC.
Electrochemical Deposition of Hydroxyapatite on Stainless Steel Coated with Tantalum/Tantalum Nitride Using Simulated Body Fluid as an Electrolytic Medium
Authors: Uribe Rafael , Uvillús Andrea , Fernández Lenys , Bonilla Omar , Jara Angélica , González Gema
Published: March 2022

In the present work the electrochemical deposition of hydroxyapatite using simulated body fluid (SBF) as an electrolytic medium was carried out on Ta and Ta/TaN coatings on BIOLINE stainless steel SS316LVM (SS). The electrochemical deposition performed on each substrate for 3000 and 6000 s, at different potentials were determined from cyclic voltammetry. The best conditions found were −1.4 V for bare SS and −1.7 V for Ta/TaN coating. The structural characterization was carried out by SEM, FTIR, XRD, and contact angle measurements. The electrochemical characterization was done by electrochemical impedance (EIS), which allowed us to know the capacitive and resistive character of the substrates. The substrate (Ta/TaN)/SS at −1.7 V 6000 s presented the largest formation of a nonstoichiometric hydroxyapatite with a uniform distribution on the substrate, implying that Ta–OH is formed on the tantalum metallic surface, due to formation of the passivation layer of tantalum oxide. These groups attract Ca2+ ions and PO43− ions absorbed on the surface will form the precursors of the apatite crystals that finally transform to hydroxyapatite. The electrodeposition of HAp the double layer Ta/TaN resulted in a more uniform and denser layer than SS alone.
Simulation Analysis on Flow Field of Paint Mist Recovery with Single Nozzle for Ship Outer Panel Spraying Robot
Authors: Yi Zhengyao , Mi Siyao , Tong Tianqi , Li Kai , Feng Bingxing
Published: March 2022

In this paper, we design a kind of negative pressure vacuum recovery hood, arranged at the front of the spray gun nozzle by CFD simulation; this addresses the paint mist pollution problem of the robot spraying on the outer plate of the ship, and the nozzle is arranged at the center of the recovery hood. Three vacuum recovery hood schemes are designed as follows: Scheme A, a hemispherical recovery hood with a diameter of 1.2 m; Scheme B, with a diameter of 1.6 m; Scheme C, with a diameter of 2.0 m. The recovery vacuum suction holes of the three recovery hoods are arranged differently. Firstly, a mathematical model of the spraying jet for the case of 0.48 mm diameter nozzle was established, and the established nozzle jet flow field model was verified to be feasible through case simulation analysis and experimental comparison. Secondly, a detailed discussion and analysis of the simulation process was conducted focusing on Scheme A. During the simulation of Scheme A, it was found that: the air velocity at the inlet surface and the kinetic energy of the paint mist had a large impact on the simulation effect, so it is necessary to try to further improve the structure of the recovery hood. Finally, the further simulation analysis of Scheme B and Scheme C shows that Scheme C > Scheme B > Scheme A in terms of the paint mist recovery effect. It can be seen that the use of Scheme C as a shipyard robotic spray paint mist recovery shows better results, which provides a theoretical scheme for shipyards to achieve paint mist anti-fouling as soon as possible.
In Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and Related Compounds
Authors: Aminpour Maral , Cannariato Marco , Preto Jordane , Safaeeardebili M. Ehsan , Moracchiato Alexia , Doria Domiziano , Donato Francesca , Zizzi Eric Adriano , Deriu Marco Agostino , Scheim David E. , Santin Alessandro D. , Tuszynski Jack Adam
Published: March 2022

Some clinical studies have indicated activity of ivermectin, a macrocyclic lactone, against COVID-19, but a biological mechanism initially proposed for this anti-viral effect is not applicable at physiological concentrations. This in silico investigation explores potential modes of action of ivermectin and 14 related compounds, by which the infectivity and morbidity of the SARS-CoV-2 virus may be limited. Binding affinity computations were performed for these agents on several docking sites each for models of (1) the spike glycoprotein of the virus, (2) the CD147 receptor, which has been identified as a secondary attachment point for the virus, and (3) the alpha-7 nicotinic acetylcholine receptor (α7nAChr), an indicated point of viral penetration of neuronal tissue as well as an activation site for the cholinergic anti-inflammatory pathway controlled by the vagus nerve. Binding affinities were calculated for these multiple docking sites and binding modes of each compound. Our results indicate the high affinity of ivermectin, and even higher affinities for some of the other compounds evaluated, for all three of these molecular targets. These results suggest biological mechanisms by which ivermectin may limit the infectivity and morbidity of the SARS-CoV-2 virus and stimulate an α7nAChr-mediated anti-inflammatory pathway that could limit cytokine production by immune cells.
Effect of the Use of a Cream with Leucine and Lactic Acid Associated with Electrostimulation in Contouring and Facial Tonus: A Randomized Clinical Controlled Trial
Authors: da Silva Carolina , Costa Giselle , Aguiar Andreo , Camargo Mariana , Fernandes Karen , Oliveira Marcio , da Silva Rubens
Published: March 2022

Evidence has supported the use of leucine as a promising agent for the maintenance of muscle tone. This study aimed to assess the combined effect of leucine and cream-based lactic acid (novel cosmetic product), associated with the use of surface electrical stimulation to improve contour and facial tonus in women. A total of 23 women were randomly allocated into two groups: Experimental (EG)—use of the leucine-based cream and lactic acid + electrostimulation for facial toning (mean intensity 13 Hz and protocol in progression); and placebo (GP)—use of the placebo cream (without the addition of leucine and lactic acid) + stimulation with the same protocol as the EG. Each group used their cream daily and underwent the intervention protocol three x/week with stimulation for 40 min, for a total of 8 weeks. Three main outcomes were reported: angular variation of facial contour by means of photogrammetry, muscle tone through the electromyographic activity of the masseter and zygomatic muscles during rest and functional tasks of biting and smiling. A significant effect of the intervention and between the groups was obtained for the experimental group against the placebo group for facial contour and muscle tone. An increased muscular activity of the masseter (average 28%) when smiling, and a reduction of zygomatic activity (in average 41%) when biting were found. The use of cream containing leucine and lactic acid combined with electrostimulation contributes to the improvement of facial contour and muscle tone when biting and smiling.
Optical Temperature Sensor Capabilities of the Green Upconverted Luminescence of Er3+ in La3NbO7 Ceramic Powders
Authors: Hernández-Rodríguez Miguel A. , Egaña Alvaro , Rodríguez-Mendoza Ulises R. , Lavín Victor , Muñoz-Santiuste Juan E.
Published: March 2022

We present a study of the Er3+ upconverted luminescence in erbium doped Lanthanum Niobium Oxide, La3NbO7, ceramic powder, prepared by solid state reaction. This study focuses on the analysis of the feasibility of this system as a temperature sensor. Efficient UC luminescence was observed under the 975 nm excitation showing intense green, red and NIR (850 nm) emission bands. The NIR luminescence centred at about 850 nm and lying on the first biological window is mainly insensitive to the temperature. In contrast, the upconverted green bands, associated with the (2H11/2,4S3/2) →4I15/2 transitions, showed a high sensibility to temperature. Their temperature dependence was studied from RT up to 525 K, paying special attention to the physiological range of temperature (303–318 K). The high thermal sensitivities obtained, in comparison with other Er3+ and Er3+-Yb3+ based optical temperature sensors in such ranges, suggest the potential application of this phosphor in thermal sensing, suitable for both biological systems and other industrial applications requiring higher temperatures.
Second-Order Raman Scattering in Ferroelectric Ceramic Solid Solutions LiNbxTa1−xO3
Authors: Sidorov Nikolay , Palatnikov Mikhail , Pyatyshev Alexander , Sverbil Pavel
Published: March 2022

In the second-order Raman spectra of ceramic solid solutions, LiNbxTa1−xO3 weak overtone bands of fully symmetric fundamental polar excitations were observed for the first time. The frequencies of the two bands exceeded the value of the overtone frequency corresponding to the fully symmetrical vibration 4A1(z). The possibility of the existence of phonon bound states of the antipolar type in the vibrational spectrum of LiNbxTa1−xO3 ceramics is predicted.
Scintillation Properties of Pr-Doped Lanthanum Pyrosilicate Single Crystals
Authors: Kantuptim Prom , Kato Takumi , Nakauchi Daisuke , Kawaguchi Noriaki , Yanagida Takayuki
Published: March 2022

Five samples of lanthanum pyrosilicate (La2Si2O7) single crystals with 0.5–10.0% Praseodymium (Pr)-doping concentrations were synthesized by the floating-zone method. Photoluminescence and scintillation properties of these crystals were investigated in this study for the first time. The multiple emissions from electron transitions of Pr3+ were observed on both a photoluminescence emission map and scintillation spectra, including the desired emission band of Pr3+ 5d–4f transition at 250–310 nm. The major photoluminescence and scintillation decay times were approximately 19 and 26 ns, respectively. When compared with commercial scintillators such as Tl-doped cesium iodide (CsI), the Pr-doped La2Si2O7 samples presented a respectively low afterglow level of 32 ppm after 20 ms of X-ray irradiation. Under 662 keV γ-ray irradiation from 137Cs, the 3.0% Pr-doped La2Si2O7 sample presented a scintillation light yield of 3200 ph/MeV, which was the best value among the tested samples.
Chemical Characterization of Taif Rose (Rosa damascena Mill var. trigentipetala) Waste Methanolic Extract and Its Hepatoprotective and Antioxidant Effects against Cadmium Chloride (CdCl2)-Induced Hepatotoxicity and Potential Anticancer Activities against Liver Cancer Cells (HepG2)
Authors: Hamza Reham Z. , Al-Yasi Hatim M. , Ali Esmat F. , Fawzy Mustafa A. , Abdelkader Tharwat G. , Galal Tarek M.
Published: March 2022

Taif rose (Rosa damascena Mill) is one of the most important economic products of the Taif Governorate, Saudi Arabia. Cadmium chloride (CdCl2) is a common environmental pollutant that is widely used in industries and essentially induces many toxicities, including hepatotoxicity. In this study, the major compounds in the waste of Taif rose extract (WTR) were identified and chemically and biologically evaluated. GC–MS analysis of WTR indicated the presence of many saturated fatty acids, vitamin E, triterpene, dicarboxylic acid, terpene, linoleic acid, diterpenoid, monoterpenoid, flavonoids, phenylpyrazoles, and calcifediol (vitamin D derivative). The assessment of potential anticancer activity against HepG2 cells proved that WTR had a high cell killing effect with IC50 of 100–150 µg/mL. In addition, WTR successfully induced high cell cycle arrest at G0/G1, S, and G2 phases, significant apoptosis, necrosis, and increased autophagic cell death response in the HepG2 line. For the evaluation of its anti-CdCl2 toxicity, 32 male rats were allocated to four groups: control, CdCl2, WTR, and CdCl2 plus WTR. Hepatic functions and antioxidant biomarkers (SOD, CAT, GRx, GPx, and MDA) were examined. Histological changes and TEM variations in the liver were also investigated to indicate liver status. The results proved that WTR alleviated CdCl2 hepatotoxicity by improving all hepatic vitality markers. In conclusion, WTR could be used as a preventive and therapeutic natural agent for the inhibition of hepatic diseases and the improvement of redox status. Additional in vitro and in vivo studies are warranted.
Quantification of Immunohistochemically Stained Cells in Skin Biopsies
Authors: Emmanuel Thomas , Brent Mikkel Bo , Iversen Lars , Johansen Claus
Published: March 2022

Immunohistochemical quantification of inflammatory cells in skin biopsies is a valuable tool for diagnosing skin diseases and assessing treatment response. The quantification of individual cells in biopsies is time-consuming, tedious, and difficult. In this study, we presented and compared two methods for the quantification of CD8+ T cells in skin biopsies from patients with psoriasis using both commercial software (Adobe Photoshop) and open-source software (Qupath). In addition, we provided a detailed, step-by-step description of both methods. The methods are scalable by replacing the CD8 antibody with other antibodies to target different cells. Moreover, we investigated the correlation between quantifying CD8+ cells normalized to area or epidermal length and cell classifications, compared cell classifications in QuPath with threshold classifications in Photoshop, and analyzed the impact of data normalization to epidermal length or area on inflammatory cell densities in skin biopsies from patients with psoriasis. We found a satisfactory correlation between normalizing data to epidermal length and area for psoriasis skin. However, when non-lesional and lesional skin samples were compared, a significant underestimation of inflammatory cell density was found when data were normalized to area instead of epidermal length. Finally, Bland–Altman plots comparing Qupath and Photoshop to quantify inflammatory cell density demonstrated a good agreement between the two methods.
Fluid Biomarkers in Alzheimer’s Disease and Other Neurodegenerative Disorders: Toward Integrative Diagnostic Frameworks and Tailored Treatments
Authors: Giampietri Linda , Belli Elisabetta , Beatino Maria Francesca , Giannoni Sara , Palermo Giovanni , Campese Nicole , Tognoni Gloria , Siciliano Gabriele , Ceravolo Roberto , De Luca Ciro , Baldacci Filippo
Published: March 2022

The diagnosis of neurodegenerative diseases (NDDs) represents an increasing social burden, with the unsolved issue of disease-modifying therapies (DMTs). The failure of clinical trials treating Alzheimer′s Disease (AD) so far highlighted the need for a different approach in drug design and patient selection. Identifying subjects in the prodromal or early symptomatic phase is critical to slow down neurodegeneration, but the implementation of screening programs with this aim will have an ethical and social aftermath. Novel minimally invasive candidate biomarkers (derived from blood, saliva, olfactory brush) or classical cerebrospinal fluid (CSF) biomarkers have been developed in research settings to stratify patients with NDDs. Misfolded protein accumulation, neuroinflammation, and synaptic loss are the pathophysiological hallmarks detected by these biomarkers to refine diagnosis, prognosis, and target engagement of drugs in clinical trials. We reviewed fluid biomarkers of NDDs, considering their potential role as screening, diagnostic, or prognostic tool, and their present-day use in clinical trials (phase II and III). A special focus will be dedicated to novel techniques for the detection of misfolded proteins. Eventually, an applicative diagnostic algorithm will be proposed to translate the research data in clinical practice and select prodromal or early patients to be enrolled in the appropriate DMTs trials for NDDs.
Current Value of Biparametric Prostate MRI with Machine-Learning or Deep-Learning in the Detection, Grading, and Characterization of Prostate Cancer: A Systematic Review
Authors: Michaely Henrik J. , Aringhieri Giacomo , Cioni Dania , Neri Emanuele
Published: March 2022

Prostate cancer detection with magnetic resonance imaging is based on a standardized MRI-protocol according to the PI-RADS guidelines including morphologic imaging, diffusion weighted imaging, and perfusion. To facilitate data acquisition and analysis the contrast-enhanced perfusion is often omitted resulting in a biparametric prostate MRI protocol. The intention of this review is to analyze the current value of biparametric prostate MRI in combination with methods of machine-learning and deep learning in the detection, grading, and characterization of prostate cancer; if available a direct comparison with human radiologist performance was performed. PubMed was systematically queried and 29 appropriate studies were identified and retrieved. The data show that detection of clinically significant prostate cancer and differentiation of prostate cancer from non-cancerous tissue using machine-learning and deep learning is feasible with promising results. Some techniques of machine-learning and deep-learning currently seem to be equally good as human radiologists in terms of classification of single lesion according to the PIRADS score.