bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular Tissue Specific miRNA Profiles Reveal Novel Correlations with Risk Factors in Coronary Artery Disease
Authors: Neiburga Katrīna , Vilne Baiba , Bauer Sabine , Bongiovanni Dario , Ziegler Tilman , Lachmann Mark , Wengert Simon , Hawe Johann , Güldener Ulrich , Westerlund Annie , Li Ling , Pang Shichao , Yang Chuhua , Saar Kathrin , Huebner Norbert , Maegdefessel Lars , DigiMed Bayern Consortium  , Lange Rüdiger , Krane Markus , Schunkert Heribert , von Scheidt Moritz
Published: November 2021

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant tissues and their relation to cardiovascular risk factors. Tissue-specific miRs derived from Arteria mammaria interna (IMA) from 192 coronary artery disease (CAD) patients undergoing coronary artery bypass grafting (CABG) were analyzed. The aims of the study were 1) to establish a reference atlas which can be utilized for identification of novel diagnostic biomarkers and potential therapeutic targets, and 2) to relate these miRs to cardiovascular risk factors. Overall, 393 individual miRs showed sufficient expression levels and passed quality control for further analysis. We identified 17 miRs–miR-10b-3p, miR-10-5p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, miR-199a-3p, miR-199b-3p, miR-212-3p, miR-363-3p, miR-548d-5p, miR-744-5p, miR-3117-3p, miR-5683 and miR-5701–significantly correlated with cardiovascular risk factors (correlation coefficient >0.2 in both directions, p-value (p < 0.006, false discovery rate (FDR) <0.05). Of particular interest, miR-5701 was positively correlated with hypertension, hypercholesterolemia, and diabetes. In addition, we found that miR-629-5p and miR-98-5p were significantly correlated with acute myocardial infarction. We provide a first atlas of miR profiles in IMA samples from CAD patients. In perspective, these miRs might play an important role in improved risk assessment, mechanistic disease understanding and local therapy of CAD.
The Small Molecule Alpha-Synuclein Aggregator, FN075, Enhances Alpha-Synuclein Pathology in Subclinical AAV Rat Models
Authors: Kelly Rachel , Cairns Andrew G. , Ådén Jörgen , Almqvist Fredrik , Bemelmans Alexis-Pierre , Brouillet Emmanuel , Patton Tommy , McKernan Declan P. , Dowd Eilís
Published: November 2021

Animal models of Parkinson’s disease, in which the human α-synuclein transgene is overexpressed in the nigrostriatal pathway using viral vectors, are widely considered to be the most relevant models of the human condition. However, although highly valid, these models have major limitations related to reliability and variability, with many animals exhibiting pronounced α-synuclein expression failing to demonstrate nigrostriatal neurodegeneration or motor dysfunction. Therefore, the aim of this study was to determine if sequential intra-nigral administration of AAV-α-synuclein followed by the small α-synuclein aggregating molecule, FN075, would enhance or precipitate the associated α-synucleinopathy, nigrostriatal pathology and motor dysfunction in subclinical models. Rats were given unilateral intra-nigral injections of AAV-α-synuclein (either wild-type or A53T mutant) followed four weeks later by a unilateral intra-nigral injection of FN075, after which they underwent behavioral testing for lateralized motor functionality until they were sacrificed for immunohistological assessment at 20 weeks after AAV administration. In line with expectations, both of the AAV vectors induced widespread overexpression of human α-synuclein in the substantia nigra and striatum. Sequential administration of FN075 significantly enhanced the α-synuclein pathology with increased density and accumulation of the pathological form of the protein phosphorylated at serine 129 (pS129-α-synuclein). However, despite this enhanced α-synuclein pathology, FN075 did not precipitate nigrostriatal degeneration or motor dysfunction in these subclinical AAV models. In conclusion, FN075 holds significant promise as an approach to enhancing the α-synuclein pathology in viral overexpression models, but further studies are required to determine if alternative administration regimes for this molecule could improve the reliability and variability in these models.
Solving the Puzzle: What Is the Role of Progestogens in Neovascularization?
Authors: Xia Zhi , Xiao Jian , Chen Qiong
Published: November 2021

Ovarian sex steroids can modulate new vessel formation and development, and the clarification of the underlying mechanism will provide insight into neovascularization-related physiological changes and pathological conditions. Unlike estrogen, which mainly promotes neovascularization through activating classic post-receptor signaling pathways, progesterone (P4) regulates a variety of downstream factors with angiogenic or antiangiogenic effects, exerting various influences on neovascularization. Furthermore, diverse progestins, the synthetic progesterone receptor (PR) agonists structurally related to P4, have been used in numerous studies, which could contribute to unequal actions. As a result, there have been many conflicting observations in the past, making it difficult for researchers to define the exact role of progestogens (PR agonists including naturally occurring P4 and synthetic progestins). This review summarizes available evidence for progestogen-mediated neovascularization under physiological and pathological circumstances, and attempts to elaborate their functional characteristics and regulatory patterns from a comprehensive perspective.
Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs
Authors: Pinet Louise , Assrir Nadine , van Heijenoort Carine
Published: November 2021

ErbBs are receptor tyrosine kinases involved not only in development, but also in a wide variety of diseases, particularly cancer. Their extracellular, transmembrane, juxtamembrane, and kinase folded domains were described extensively over the past 20 years, structurally and functionally. However, their whole C-terminal tails (CTs) following the kinase domain were only described at atomic resolution in the last 4 years. They were shown to be intrinsically disordered. The CTs are known to be tyrosine-phosphorylated when the activated homo- or hetero-dimers of ErbBs are formed. Their phosphorylation triggers interaction with phosphotyrosine binding (PTB) or Src Homology 2 (SH2) domains and activates several signaling pathways controling cellular motility, proliferation, adhesion, and apoptosis. Beyond this passive role of phosphorylated domain and site display for partners, recent structural and function studies unveiled active roles in regulation of phosphorylation and interaction: the CT regulates activity of the kinase domain; different phosphorylation states have different compaction levels, potentially modulating the succession of phosphorylation events; and prolines have an important role in structure, dynamics, and possibly regulatory interactions. Here, we review both the canonical role of the disordered CT domains of ErbBs as phosphotyrosine display domains and the recent findings that expand the known range of their regulation functions linked to specific structural and dynamic features.
Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity
Authors: Udrea Ana Maria , Gradisteanu Pircalabioru Gratiela , Boboc Anca Andreea , Mares Catalina , Dinache Andra , Mernea Maria , Avram Speranta
Published: November 2021

Diabetes represents a major health problem, involving a severe imbalance of blood sugar levels, which can disturb the nerves, eyes, kidneys, and other organs. Diabes management involves several synthetic drugs focused on improving insulin sensitivity, increasing insulin production, and decreasing blood glucose levels, but with unclear molecular mechanisms and severe side effects. Natural chemicals extracted from several plants such as Gymnema sylvestre, Momordica charantia or Ophiopogon planiscapus Niger have aroused great interest for their anti-diabetes activity, but also their hypolipidemic and anti-obesity activity. Here, we focused on the anti-diabetic activity of a few natural and synthetic compounds, in correlation with their pharmacokinetic/pharmacodynamic profiles, especially with their blood-brain barrier (BBB) permeability. We reviewed studies that used bioinformatics methods such as predicted BBB, molecular docking, molecular dynamics and quantitative structure-activity relationship (QSAR) to elucidate the proper action mechanisms of antidiabetic compounds. Currently, it is evident that BBB damage plays a significant role in diabetes disorders, but the molecular mechanisms are not clear. Here, we presented the efficacy of natural (gymnemic acids, quercetin, resveratrol) and synthetic (TAK-242, propofol, or APX3330) compounds in reducing diabetes symptoms and improving BBB dysfunctions. Bioinformatics tools can be helpful in the quest for chemical compounds with effective anti-diabetic activity that can enhance the druggability of molecular targets and provide a deeper understanding of diabetes mechanisms.
Treating Cancers Using Nature’s Medicine: Significance and Challenges
Authors: Samuel Samson , Kubatka Peter , Büsselberg Dietrich
Published: November 2021

There was a time when plant-derived natural formulations were the cornerstone of ancient therapeutic approaches for treating many illnesses [...]
Two-Step Approach Using Degradable Magnesium to Inhibit Surface Biofilm and Subsequently Kill Planktonic Bacteria
Authors: Wong Pei-Chun , Wang Ren-Yi , Lu Long-Sheng , Wang Wei-Ru , Jang Jason Shian-Ching , Wu Jia-Lin , Su Tai-Yuan , Chang Ling-Hua
Published: November 2021

Bacterial infection remains a great risk in medical implantation surgery. In this paper, we found that degradable metals may be a feasible alternative option of antibacterial implantation materials. It is known that the spalling mechanism of magnesium (Mg) during degradation leads to Mg ions-induced alkaline environment, which is harmful to planktonic bacteria. In this study, we showed that alkaline pH environment is almost harmless to those adhesive bacteria protected in well-formed biofilms. Moreover, experimental results demonstrated that the biofilm formed in the place where Mg spalls are destroyed, releasing the covered bacteria to be planktonic in the alkaline environment. As a result, the colonization of biofilms continues to shrink during the degradation of Mg. It implies that if degradable metal is employed as implantation material, even if bacterial infection occurs, it may be possibly cured without second surgery.
Wnt/β-Catenin Pathway in Experimental Model of Fibromyalgia: Role of Hidrox®
Authors: D’Amico Ramona , Cordaro Marika , Siracusa Rosalba , Impellizzeri Daniela , Trovato Salinaro Angela , Scuto Maria , Ontario Maria Laura , Crea Roberto , Cuzzocrea Salvatore , Di Paola Rosanna , Fusco Roberta , Calabrese Vittorio
Published: November 2021

Fibromyalgia (FM) is a chronic condition characterized by persistent widespread pain that negatively affects the quality of life of patients. The WNT/β-catenin signaling pathway seems to be involved in central sensitization and different pain states. The objective of this study was to investigate the beneficial effects of a new compound called Hidrox® (HD), containing 40–50% hydroxytyrosol, in counteracting the pain associated with FM. An FM-like model was induced in rats by subcutaneous injections of reserpine (1 mg/kg) for three consecutive days. Later, HD (10 mg/kg) was administered orally to the animals for seven days. Reserpine injections induced WNT/β-catenin pathway activation, release of pro-inflammatory mediators as well as a significant increase in oxidative stress. Daily treatment with HD was able to modulate the WNT/β-catenin and Nrf2 pathways and consequently attenuate the behavioral deficits and microglia activation induced by reserpine injection. These results indicate that nutritional consumption of HD can be considered as a new therapeutic approach for human FM.
Immunotherapy in Breast Cancer: When, How, and What Challenges?
Authors: Henriques Beatriz , Mendes Fernando , Martins Diana
Published: November 2021

Breast Cancer (BC) is the second most frequent cause of cancer death among women worldwide and, although there have been significant advances in BC therapies, a significant percentage of patients develop metastasis and disease recurrence. Since BC was demonstrated to be an immunogenic tumor, immunotherapy has broken through as a significant therapy strategy against BC. Over the years, immunotherapy has improved the survival rate of HER2+ BC patients due to the approval of some monoclonal antibodies (mAbs) such as Trastuzumab, Pertuzumab and, recently, Margetuximab, along with the antibody-drug conjugates (ADC) Trastuzumab-Emtansine (T-DM1) and Trastuzumab Deruxtecan. Immune checkpoint inhibitors (ICI) showed promising efficacy in triple-negative breast cancer (TNBC) treatment, namely Atezolizumab and Pembrolizumab. Despite the success of immunotherapy, some patients do not respond to immunotherapy or those who respond to the treatment relapse or progress. The main causes of these adverse events are the complex, intrinsic or extrinsic resistance mechanisms. In this review, we address the different immunotherapy approaches approved for BC and some of the mechanisms responsible for resistance to immunotherapy.
The Potential Role of Cytokine Storm Pathway in the Clinical Course of Viral Respiratory Pandemic
Authors: Murdaca Giuseppe , Paladin Francesca , Tonacci Alessandro , Isola Stefania , Allegra Alessandro , Gangemi Sebastiano
Published: November 2021

The “cytokine storm” (CS) consists of a spectrum of different immune dysregulation disorders characterized by constitutional symptoms, systemic inflammation and multiorgan dysfunction triggered by an uncontrolled immune response. Particularly in respiratory virus infections, the cytokine storm plays a primary role in the pathogenesis of respiratory disease and the clinical outcome of respiratory diseases, leading to complications such as alveolar edema and hypoxia. In this review, we wanted to analyze the different pathogenetic mechanisms involved in the various respiratory viral pandemics (COVID-19; SARS; MERS; H1N1 influenza A and Spanish flu) which have affected humans in this and last century, with particular attention to the phenomenon of the “cytokine storm” which determines the clinical severity of the respiratory disease and consequently its lethality.
A DNA Electrochemical Sensor via Terminal Protection of Small-Molecule-Linked DNA for Highly Sensitive Protein Detection
Authors: Ouyang Ping , Fang Chenxin , Han Jialun , Zhang Jingjing , Yang Yuxing , Qing Yang , Chen Yubing , Shang Wenyan , Du Jie
Published: November 2021

The qualitative and quantitative determination of marker protein is of great significance in the life sciences and in medicine. Here, we developed an electrochemical DNA biosensor for protein detection based on DNA self-assembly and the terminal protecting effects of small-molecule-linked DNA. This strategy is demonstrated using the small molecule biotin and its receptor protein streptavidin (SA). We immobilized DNA with a designed structure and sequence on the surface of the gold electrode, and we named it M1-Biotin DNA. M1-Biotin DNA selectively combines with SA to generate M1-Biotin-SA DNA and protects M1-Biotin DNA from digestion by EXO III; therefore, M1-Biotin DNA remains intact on the electrode surface. M1-Biotin-SA DNA was modified with methylene blue (MB); the MB reporter molecule is located near the surface of the gold electrode, which generates a substantial electrochemical signal during the detection of SA. Through this strategy, we can exploit the presence or absence of an electrochemical signal to provide qualitative target protein determination as well as the strength of the electrochemical signal to quantitatively analyze the target protein concentration. This strategy has been proven to be used for the quantitative analysis of the interaction between biotin and streptavidin (SA). Under optimal conditions, the detection limit of the proposed biosensor is as low as 18.8 pM, and the linear range is from 0.5 nM to 5 μM, showing high sensitivity. The detection ability of this DNA biosensor in complex serum samples has also been studied. At the same time, we detected the folate receptor (FR) to confirm that this strategy can be used to detect other proteins. Therefore, this electrochemical DNA biosensor provides a sensitive, low-cost, and fast target protein detection platform, which may provide a reliable and powerful tool for early disease diagnosis.
Technological Devices and Their Effect on Preschool Children’s Eating Habits in Communities of Mixed Socioeconomic Status in Istanbul; a Pilot Cross-Sectional Study
Authors: Kristo Aleksandra S. , Çinar Nur , Kucuknil Stefanos L. , Sikalidis Angelos K.
Published: November 2021

The use of technological devices is increasing in all age groups, especially in preschool-aged children. However, there is a limiting number of studies investigating the relationship between the use of technological devices, eating behavior, and weight status in preschool children. The aim of this study was (1) to describe total usage of technological devices, (2) to evaluate level of exclusive use of such devices by children, (3) to investigate children’s eating behaviors and diet in relation to screen time and type. A cross-sectional study was conducted with 104 children aged 2–5 years in Küçükçekmece and Bakırköy, Istanbul. Data collection consisted of a validated parental questionnaire on demographics and the child’s use of technology and eating behavior, while associations in children were examined using logistic regression analysis. The analysis of the obtained data uncovered a strong association between children’s TV and tablet/smart phone use and the foods consumed by children when using these devices (p = 0.0001; p = 0.012). Also, there was a significant association between children’s eating habits and TV, and tablet/smart phone durations of use (p = 0.015; p = 0.025), but not with computer duration of use (p > 0.05). Obesity and associated health problems can arise as results of suboptimal eating behavior, such as the ones observed in our study, which are also intensified with an increased duration of use of technological devices. The attitude of families towards prudent use of technological equipment is of great importance in impacting present and future health.
Influence of the Visitor Walking on Airflow and the Bioaerosol Particles in Typical Open Tomb Chambers: An Experimental and Case Study
Authors: Liu Zhijian , Wu Minnan , Cao Hongwei , Wang Yongxin , Rong Rui , Zhu Hangyao
Published: November 2021

Effective maintenance of ancient buildings is paid more and more attention worldwide. Many ancient buildings with high inheritance value were gradually destroyed, especially for murals in the open tombs. The bioaerosol particles (BPs) are the major source of contamination in murals and visitor walking could increase this hazard. In order to study the impact of visitors walking on the air flow and the distribution of BPs in the typical tomb chambers, the k-ε and Lagrangian discrete phase model were adopted. The walking visitor was described by the dynamic mesh, and the concentration of BPs in the simulation was verified by experimental sampling. The distribution and migration mechanism of contamination in the chamber were dynamically analyzed. The results indicate that the denser vortex generated when a visitor was walking, and the concentration of BPs changed obviously. Therefore, the number of BPs deposited on some precious murals increased and the contamination location shifted in the direction of visitor walking. In addition, the deposition time of BPs was lagging which would cause potential risk. This research can provide scientific basis for reducing murals contamination during visitor visiting and a reference for the maintenance of ancient buildings.
Role and Merits of Green Based Nanocarriers in Cancer Treatment
Authors: Elbagory Abdulrahman M. , Marima Rahaba Makgotso , Dlamini Zodwa
Published: November 2021

The use of nanocarriers for biomedical applications has been gaining interests from researchers worldwide for the delivery of therapeutics in a controlled manner. These “smart” vehicles enhance the dissolution and the bioavailability of drugs and enable their delivery to the target site. Taking the potential toxicity into consideration, the incorporation of natural “green” materials, derived from plants or microbial sources, in the nanocarriers fabrication, improve their safety and biocompatibility. These green components can be used as a mechanical platform or as targeting ligand for the payload or can play a role in the synthesis of nanoparticles. Several studies reported the use of green based nanocarriers for the treatment of diseases such as cancer. This review article provides a critical analysis of the different types of green nanocarriers and their synthesis mechanisms, characterization, and their role in improving drug delivery of anticancer drugs to achieve precision cancer treatment. Current evidence suggests that green-based nanocarriers can constitute an effective treatment against cancer.
Epidemiology of Kaposi’s Sarcoma
Authors: Grabar Sophie , Costagliola Dominique
Published: November 2021

Kaposi’s sarcoma is an angioproliferative tumor caused by human herpesvirus 8 in the context of immunodeficiency, such as that induced by HIV infection or immunosuppressive therapy. Its incidence has dramatically fallen in patients living with HIV (PLHIV) since the introduction of potent antiretroviral combinations 25 years ago due to the restoration of immunity and better control of HIV replication. However, KS is still one of the most frequently occurring cancers in PLHIV, in particular in men who have sex with men and in sub-Saharan Africa, where it is still endemic. Even in the context of restored immunity, the risk of KS is still more than 30 times higher in PLHIV than in the general population. Recent evidence indicates that early initiation of antiretroviral treatment, which is recommended by current guidelines, may reduce the risk of KS but it needs to be accompanied by early access to care. This review mainly focuses on the recent epidemiological features of KS in the context of HIV infection.
The Role of Protein SUMOylation in Human Hepatocellular Carcinoma: A Potential Target of New Drug Discovery and Development
Authors: Yuan Hongchao , Lu Yuanjun , Chan Yau-Tuen , Zhang Cheng , Wang Ning , Feng Yibin
Published: November 2021

Small ubiquitin-like modifier (SUMO) is a highly conserved post-translational modification protein, mainly found in eukaryotes. They are widely expressed in different tissues, including the liver. As an essential post-translational modification, SUMOylation is involved in many necessary regulations in cells. It plays a vital role in DNA repair, transcription regulation, protein stability and cell cycle progression. Increasing shreds of evidence show that SUMOylation is closely related to Hepatocellular carcinoma (HCC). The high expression of SUMOs in the inflammatory hepatic tissue may lead to the carcinogenesis of HCC. At the same time, SUMOs will upregulate the proliferation and survival of HCC, migration, invasion and metastasis of HCC, tumour microenvironment as well as drug resistance. This study reviewed the role of SUMOylation in liver cancer. In addition, it also discussed natural compounds that modulate SUMO and target SUMO drugs in clinical trials. Considering the critical role of SUMO protein in the occurrence of HCC, the drug regulation of SUMOylation may become a potential target for treatment, prognostic monitoring and adjuvant chemotherapy of HCC.
Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone
Authors: Lin Qun , Fang Xiaolin , Liang Gehao , Luo Qing , Cen Yinghuan , Shi Yu , Jia Shijie , Li Juanmei , Yang Wenqian , Sanders Andrew J. , Gong Chang , Jiang Wenguo
Published: November 2021

Bone metastasis from triple-negative breast cancer (TNBC) frequently results in poorer prognosis than other types of breast cancer due to the delay in diagnosis and intervention, lack of effective treatments and more skeletal-related complications. In the present study, we identified CTNND1 as a most reduced molecule in metastatic bone lesion from TNBC by way of high throughput sequencing of TNBC samples. In vivo experiments revealed that knockdown of CTNND1 enhanced tumor cells metastasis to bones and also increased neutrophils infiltration in bones. In vitro, we demonstrated that knockdown of CTNND1 accelerated epithelial–mesenchymal transformation (EMT) of tumor cells and their recruitment to bones. The involvement by CTNND1 in EMT and bone homing was achieved by upregulating CXCR4 via activating the PI3K/AKT/HIF-1αpathway. Moreover, TNBC cells with reduced expression of CTNND1 elicited cytotoxic T-cells responses through accelerating neutrophils infiltration by secreting more GM-CSF and IL-8. Clinically, patients with triple-negative breast cancer and lower level of CTNND1 had shorter overall survival (OS) and distant metastasis-free survival (DMFS). It was concluded that downregulation of CTNND1 played a critical role in facilitating bone metastasis of TNBC and that CTNND1 might be a potential biomarker for predicting the risk of bone metastases in TNBC.
Reply to Stummer, W.; Thomas, C. Comment on “Hosmann et al. 5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)—Experience at Two Specialized Centers. Cancers 2021, 13, 2540”
Authors: Hosmann Arthur , Millesi Matthias , Wadiura Lisa I. , Kiesel Barbara , Mercea Petra A. , Mischkulnig Mario , Borkovec Martin , Furtner Julia , Roetzer Thomas , Wolfsberger Stefan , Phillips Joanna J. , Berghoff Anna S. , Hervey-Jumper Shawn , Berger Mitchel S. , Widhalm Georg
Published: November 2021

We greatly appreciate Dr. Stummer’s and Dr. Thomas’s interest in our study and their important comments [...]
Fracture Risk Evaluation of Bone Metastases: A Burning Issue
Authors: Confavreux Cyrille B. , Follet Helene , Mitton David , Pialat Jean Baptiste , Clézardin Philippe
Published: November 2021

Major progress has been achieved to treat cancer patients and survival has improved considerably, even for stage-IV bone metastatic patients. Locomotive health has become a crucial issue for patient autonomy and quality of life. The centerpiece of the reflection lies in the fracture risk evaluation of bone metastasis to guide physician decision regarding physical activity, antiresorptive agent prescription, and local intervention by radiotherapy, surgery, and interventional radiology. A key mandatory step, since bone metastases may be asymptomatic and disseminated throughout the skeleton, is to identify the bone metastasis location by cartography, especially within weight-bearing bones. For every location, the fracture risk evaluation relies on qualitative approaches using imagery and scores such as Mirels and spinal instability neoplastic score (SINS). This approach, however, has important limitations and there is a need to develop new tools for bone metastatic and myeloma fracture risk evaluation. Personalized numerical simulation qCT-based imaging constitutes one of these emerging tools to assess bone tumoral strength and estimate the femoral and vertebral fracture risk. The next generation of numerical simulation and artificial intelligence will take into account multiple loadings to integrate movement and obtain conditions even closer to real-life, in order to guide patient rehabilitation and activity within a personalized-medicine approach.
Water Splitting with Enhanced Efficiency Using a Nickel-Based Co-Catalyst at a Cupric Oxide Photocathode
Authors: Lo Vecchio Carmelo , Trocino Stefano , Giacoppo Giosuè , Barbera Orazio , Baglio Vincenzo , Díez-García María I. , Contreras Maxime , Gómez Roberto , Aricò Antonino Salvatore
Published: November 2021

Homemade non-critical raw materials such as Ni or NiCu co-catalysts were added at the photocathode of a tandem cell, constituted by photoelectrodes made of earth-abundant materials, to generate green solar hydrogen from photoelectrochemical water splitting. Oxygen evolving at the Ti-and-P-doped hematite/TCO-based photoanode and hydrogen at the cupric oxide/GDL-based photocathode are separated by an anion exchange polymer electrolyte membrane placed between them. The effect of the aforementioned co-catalysts was studied in a complete PEC cell in the presence of the ionomer dispersion and the anionic membrane to evaluate their impact under practical conditions. Notably, different amounts of Ni or NiCu co-catalysts were used to improve the hydrogen evolution reaction (HER) kinetics and the overall solar-to-hydrogen (STH) efficiency of the photoelectrochemical cells. At −0.6 V, in the bias-assisted region, the photocurrent density reaches about 2 mA cm−2 for a cell with 12 µg cm−2 of Ni loading, followed by 1.75 mA cm−2 for the cell configuration based on 8 µg cm−2 of NiCu. For the best-performing cell, enthalpy efficiency at −0.4 V reaches a first maximum value of 2.03%. In contrast, the throughput efficiency, which is a ratio between the power output and the total power input (solar + electric) provided by an external source, calculated at −1.225 V, reaches a maximum of 10.75%. This value is approximately three times higher than the best results obtained in our previous studies without the use of co-catalysts at the photocathode.
Degradation of Dibutyl Phthalate Plasticizer in Water by High-Performance Iro2-Ta2O5/Ti Electrocatalytic Electrode
Authors: Xu Jia-Ming , Chou Shu-Hsien , Zhang Ying , Kumar Mohanraj , Shen Shan-Yi
Published: November 2021

Dibutyl phthalate (DBP) in the presence of a wastewater system is harmful to the environment and interferes with the human’s endocrine system. For wastewater treatment, DBP is very difficult to be decomposed by biotechniques and many catalytic processes have been developed. Among them, the electrocatalytic oxidation (EO) technique has been proven to possess high degradation efficiency of various organic compounds in wastewater. In this study, an electrocatalytic electrode of iridium-tantalum/titanium (IrO2-Ta2O5/Ti) was employed as the anode and graphite as the cathode to decompose DBP substances in the water. According to experimental results, the high removal efficiency of DBP and total organic carbon (TOC) of 90% and 56%, respectively, could be obtained under a voltage gradient of 10 V/cm for 60 min. Compared with other photocatalysis degradation, the IrO2-Ta2O5/Ti electrode could shorten about half the treatment time and electric power based on the same removal efficiency of DBP (i.e., photocatalysis requires 0.225~0.99 KWh). Results also indicated that the production of hydroxyl radical (•OH) in the electrocatalytic electrode played a key role for decomposing the DBP. Moreover, the pH and conductivity of water containing DBP were slightly changed and eventually remained in a stable state during the EO treatment. In addition, the removal efficiency of DBP could still remain about 90% after using the IrO2-Ta2O5/Ti electrode three times and the surface structure of the IrO2-Ta2O5/Ti electrode was stable.
Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments
Authors: Shenoy Gautam N. , Bhatta Maulasri , Bankert Richard B.
Published: November 2021

Exosomes are a subset of extracellular vesicles (EVs) that are released by cells and play a variety of physiological roles including regulation of the immune system. Exosomes are heterogeneous and present in vast numbers in tumor microenvironments. A large subset of these vesicles has been demonstrated to be immunosuppressive. In this review, we focus on the suppression of T cell function by exosomes in human tumor microenvironments. We start with a brief introduction to exosomes, with emphasis on their biogenesis, isolation and characterization. Next, we discuss the immunosuppressive effect of exosomes on T cells, reviewing in vitro studies demonstrating the role of different proteins, nucleic acids and lipids known to be associated with exosome-mediated suppression of T cell function. Here, we also discuss initial proof-of-principle studies that established the potential for rescuing T cell function by blocking or targeting exosomes. In the final section, we review different in vivo models that were utilized to study as well as target exosome-mediated immunosuppression, highlighting the Xenomimetic mouse (X-mouse) model and the Omental Tumor Xenograft (OTX) model that were featured in a recent study to evaluate the efficacy of a novel phosphatidylserine-binding molecule for targeting immunosuppressive tumor-associated exosomes.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic–Pathologic Correlations
Authors: Palicelli Andrea , Bonacini Martina , Croci Stefania , Magi-Galluzzi Cristina , Cañete-Portillo Sofia , Chaux Alcides , Bisagni Alessandra , Zanetti Eleonora , De Biase Dario , Melli Beatrice , Sanguedolce Francesca , Zanelli Magda , Bonasoni Maria Paola , De Marco Loredana , Soriano Alessandra , Ascani Stefano , Zizzo Maurizio , Castro Ruiz Carolina , De Leo Antonio , Giordano Guido , Landriscina Matteo , Carrieri Giuseppe , Cormio Luigi , Berney Daniel M. , Gandhi Jatin , Santandrea Giacomo , Gelli Maria Carolina , Tafuni Alessandro , Ragazzi Moira
Published: November 2021

Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), and clinical trials. Despite some controversial results and study limitations, PD-L1 expression by tumor cells may be related to clinic–pathologic features of adverse outcome, including advanced tumor stage (high pT, presence of lymph node, and distant metastases), positivity of surgical margins, high Grade Group, and castration resistance. Different PD-L1 positivity rates may be observed in matched primary PCs and various metastatic sites of the same patients. Over-fixation, type/duration of decalcification, and PD-L1 antibody clone may influence the immunohistochemical analysis of PD-L1 on bone metastases. PD-L1 seemed expressed more frequently by castration-resistant PCs (49%) as compared to hormone-sensitive PCs (17%). Some series found that PD-L1 positivity was associated with decreased time to castration resistance. Treatment with ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone may increase PD-L1 expression. Correlation of PD-L1 positivity with overall survival and outcomes related to tumor recurrence were rarely investigated; the few analyzed series produced conflicting results and sometimes showed limitations. Further studies are required. The testing and scoring of PD-L1 should be standardized.
Expanding the Evidence of a Semi-Dominant Inheritance in GDF2 Associated with Pulmonary Arterial Hypertension
Authors: Gallego Natalia , Cruz-Utrilla Alejandro , Guillén Inmaculada , Bonora Amparo Moya , Ochoa Nuria , Arias Pedro , Lapunzina Pablo , Escribano-Subias Pilar , Nevado Julián , Tenorio-Castaño Jair
Published: November 2021

Pulmonary arterial hypertension (PAH) sometimes co-exists with hereditary hemorrhagic telangiectasia (HHT). Despite being clinically diagnosable according to Curaçao criteria, HHT can be difficult to diagnose due to its clinically heterogenicity and highly overlapping with PAH. Genetic analysis of the associated genes ACVRL1, ENG, SMAD4 and GDF2 can help to confirm or discard the presumptive diagnosis. As part of the clinical routine and to establish a genetic diagnosis, we have analyzed a cohort of patients with PAH and overlapping HHT features through a customized Next Generation Sequencing (NGS) panel of 21 genes, designed and validated in-house. We detected a homozygous missense variant in GDF2 in a pediatric patient diagnosed with PAH associated with HHT and a missense variant along with a heterozygous deletion in another idiopathic PAH patient (compound heterozygous inheritance). In order to establish variant segregation, we analyzed all available family members. In both cases, parents were carriers for the variants, but neither was affected. Our results expand the clinical spectrum and the inheritance pattern associated with GDF2 pathogenic variants suggesting incomplete penetrance and/or variability of expressivity with a semi-dominant pattern of inheritance.
Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A
Authors: Park Na-Young , Kwak Geon , Doo Hyun-Myung , Kim Hye-Jin , Jang So-Young , Lee Yun-Il , Choi Byung-Ok , Hong Young-Bin
Published: November 2021

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral nerves in CMT patients. In this research, we assessed the potency of farnesol for improving the demyelinating phenotype using an animal model of CMT type 1A. In vitro treatment with farnesol facilitated myelin gene expression and ameliorated the myelination defect caused by PMP22 overexpression, the major causative gene in CMT. In vivo administration of farnesol enhanced the peripheral neuropathic phenotype, as shown by rotarod performance in a mouse model of CMT1A. Electrophysiologically, farnesol-administered CMT1A mice exhibited increased motor nerve conduction velocity and compound muscle action potential compared with control mice. The number and diameter of myelinated axons were also increased by farnesol treatment. The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol’s effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT.
Comprehensive Enhancement of Mechanical, Water-Repellent and Antimicrobial Properties of Regenerated Seaweed and Plant-Based Paper with Chitosan Coating
Authors: Saleh Rabi Ibrahim , Kim Mirae , Cha Chaenyung
Published: November 2021

Regenerated papers made from discarded natural sources, such as seaweeds or non-wood plants, are viewed as promising eco-friendly alternatives relative to conventional wood-based paper. However, due to its limited mechanical strength and higher water absorption than compared to traditional wood paper, it often results in premature structural disintegration. In order to overcome this limitation, this research introduces an efficient and comprehensive strategy of coating seaweed and plant papers with varying concentrations and molecular weights of chitosan. Increased concentration and molecular weight resulted in a greater amount of chitosan deposition, while the highest molecular weight also shows increased dissolution of soluble components of the paper. Since plants and seaweeds contain high anionic polysaccharide contents, the cationic chitosan shows high binding affinity towards paper. The resulting chitosan-coated papers demonstrate significant enhancements in water repellency and mechanical properties. In addition, the chitosan-coated papers also show significant bacterial inhibition effects due to the natural anti-microbial activity of chitosan.
Evaluating the Effect of MgO/Al2O3 Ratio on Thermal Behaviors and Structures of Blast Furnace Slag with Low Carbon Consumption
Authors: Zhan Wenlong , Liu Yi , Shao Tengfei , Han Xiao , Pang Qinghai , Zhang Junhong , He Zhijun
Published: November 2021

In order to clarify the effect of the MgO/Al2O3 ratio on the fluidity of a low-alumina blast furnace slag system, the influence law of slag fluidity with different MgO/Al2O3 ratios was studied based on the composition of blast furnace slag through a viscosity experiment and themodynamic software. By studying the effect of the MgO/Al2O3 ratio on the activation energy of viscous flow of slag combined with FT-IR, the effect of the MgO/Al2O3 ratio on the thermal-stability of low-aluminum slag was interpreted from the microstructure level. Results indicated that the viscosity and the melting temperature of slag both showed a gradual downward trend due to the increase of the MgO/Al2O3 ratio. Besides, the temperature stability of the low aluminum slag became more stable due to the depolymerization of the complex structure of slag. Considering the actual operating conditions of blast furnace, the MgO/Al2O3 ratio of slag was suggested to be controlled to 0.60 and the basicity to be no higher than 1.20 under the conditions of this investigation. Industrial test results showed that the coke rate could be saved as 3.49 kg/t when the MgO/Al2O3 ratio decreased from 0.70 to 0.58.
Cholera Rapid Diagnostic Tests for the Detection of Vibrio cholerae O1: An Updated Meta-Analysis
Authors: Muzembo Basilua Andre , Kitahara Kei , Ohno Ayumu , Debnath Anusuya , Okamoto Keinosuke , Miyoshi Shin-Ichi
Published: November 2021

The rapid diagnosis of cholera contributes to adequate outbreak management. This meta-analysis assesses the diagnostic accuracy of cholera rapid tests (RDTs) to detect Vibrio cholerae O1. Methods: Systematic review and meta-analysis. We searched four databases (Medline, EMBASE, Google Scholar, and Web of Science up to 8 September 2021) for studies that evaluated cholera RDTs for the detection of V. cholerae O1 compared with either stool culture or polymerase chain reaction (PCR). We assessed the studies’ quality using the QUADAS-2 criteria. In addition, in this update, GRADE approach was used to rate the overall certainty of the evidence. We performed a bivariate random-effects meta-analysis to calculate the pooled sensitivity and specificity of cholera RDTs. Results: Overall, 20 studies were included in this meta-analysis. Studies were from Africa (n = 11), Asia (n = 7), and America (Haiti; n = 2). They evaluated eight RDTs (Crystal VC-O1, Crystal VC, Cholkit, Institut Pasteur cholera dipstick, SD Bioline, Artron, Cholera Smart O1, and Smart II Cholera O1). Using direct specimen testing, sensitivity and specificity of RDTs were 90% (95% CI, 86 to 93) and 86% (95% CI, 81 to 90), respectively. Cholera Sensitivity was higher in studies conducted in Africa [92% (95% CI, 89 to 94)] compared with Asia [82% (95% CI, 77 to 87)]. However, specificity [83% (95% CI, 71 to 91)] was lower in Africa compared with Asia [90% (95% CI, 84 to 94)]. GRADE quality of evidence was estimated as moderate. Conclusions: Against culture or PCR, current cholera RDTs have moderate sensitivity and specificity for detecting Vibrio cholerae O1.
Molecular and Cytogenetic Analysis of Romanian Patients with Differences in Sex Development
Authors: Miclea Diana , Alkhzouz Camelia , Bucerzan Simona , Grigorescu-Sido Paula , Popp Radu Anghel , Pascanu Ionela Maria , Cret Victoria , Ghervan Cristina , Blaga Ligia , Zaharie Gabriela
Published: November 2021

Differences in sex development (DSD) are often correlated with a genetic etiology. This study aimed to assess the etiology of DSD patients following a protocol of genetic testing. Materials and methods. This study prospectively investigated a total of 267 patients with DSD who presented to Clinical Emergency Hospital for Children Cluj-Napoca between January 2012 and December 2019. Each patient was clinically, biochemically, and morphologically evaluated. As a first intervention, the genetic test included karyotype + SRY testing. A high value of 17-hydroxyprogesterone was found in 39 patients, in whom strip assay analysis of the CYP21A2 gene was subsequently performed. A total of 35 patients were evaluated by chromosomal microarray technique, and 22 patients were evaluated by the NGS of a gene panel. Results. The karyotype analysis established the diagnosis in 15% of the patients, most of whom presented with sex chromosome abnormalities. Genetic testing of CYP21A2 established a confirmation of the diagnosis in 44% of patients tested. SNP array analysis was particularly useful in patients with syndromic DSD; 20% of patients tested presented with pathogenic CNVs or uniparental disomy. Gene panel sequencing established the diagnosis in 11 of the 22 tested patients (50%), and the androgen receptor gene was most often involved in these patients. The genes that presented as pathogenic or likely pathogenic variants or variants of uncertain significance were RSPO1, FGFR1, WT1, CHD7, AR, NIPBL, AMHR2, AR, EMX2, CYP17A1, NR0B1, GNRHR, GATA4, and ATM genes. Conclusion. An evaluation following a genetic testing protocol that included karyotype and SRY gene testing, CYP21A2 analysis, chromosomal analysis by microarray, and high-throughput sequencing were useful in establishing the diagnosis, with a spectrum of diagnostic yield depending on the technique (between 15 and 50%). Additionally, new genetic variants not previously described in DSD were observed.
Diagnostic Performance of Automated SARS-CoV-2 Antigen Assay in Nasal Swab during COVID-19 Vaccination Campaign
Authors: Altawalah Haya , Alfouzan Wadha , Al-Fadalah Talal , Ezzikouri Sayeh
Published: November 2021

Background: To control the spread of the pandemic brought about by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it is necessary to have an automated reliable diagnostic assay. To date, the RT-PCR (RT-qPCR) has been the recommended laboratory method to diagnose SARS-CoV-2 infection, but there is a need for more automated and reliable tests. The aim of this real-life study was to assess the diagnostic performance of DiaSorin’s LIAISON SARS-CoV-2 antigen (Ag) chemiluminescence immunoassay in detecting SARS-CoV-2 in vaccinated and unvaccinated individuals. Methods: A prospective study was performed on 300 nasopharyngeal swabs randomly collected from 31 May to 6 July 2021. Nasopharyngeal samples were assayed with DiaSorin’s LIAISON SARS-CoV-2 Ag and TaqPath™ COVID-19 multiplex RT-qPCR. Results: Of 300 participants, 150 had a RT-qPCR confirmed SARS-CoV-2 infection of whom 113 (75.33%) were also detected by the DiaSorin LIAISON SARS-CoV-2 Ag. Taking RT-qPCR as a reference, the sensitivity and specificity of the DiaSorin LIAISON SARS-CoV-2 Ag assay were evaluated as 75.33% (95% CI = 67.64–82) and 100% (95% CI = 97.57–100), respectively. When a viral load cut-off was applied for high viral load (median cycle threshold (Ct) < 18.57), the overall sensitivity was increased to 96.55% (95% CI = 88.09–99.58). Interestingly, median RT-qPCR Ct and SARS-CoV-2 Ag values were similar between fully vaccinated and unvaccinated subjects. Conclusions: Automated, quantitative LIAISON SARS-CoV-2 Ag assay shows good performance to identify SARS-CoV-2-infected individuals with moderate to high viral loads. LIAISON SARS-CoV-2 Ag testing could be used as frontline testing for COVID-19 diagnosis and be more suitable for large utilization.