bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Characterisation of Epstein–Barr Virus in Classical Hodgkin Lymphoma
Authors: Begić Valerija , Korać Petra , Gašparov Slavko , Rozman Marija , Simicic Petra , Zidovec-Lepej Snjezana
Published: December 2022

Hodgkin lymphomas (HLs) are a heterogeneous group of lymphoid neoplasia associated with Epstein–Barr virus (EBV) infection. EBV, considered to be an important etiological co-factor in approximately 1% of human malignancies, can be classified into two genotypes based on EBNA-2, EBNA-3A and EBNA-3C sequences, and into genetic variants based on the sequence variation of the gene coding for the LMP1 protein. Here, we present the results on the distribution of EBV genotypes 1 and 2 as well as LMP1 gene variants in 50 patients with EBV-positive classical HL selected from a cohort of 289 histologically verified cases collected over a 9-year period in a tertiary clinical center in the Southeast of Europe. The population-based sequencing of the EBNA-3C gene showed the exclusive presence of EBV genotype 1 in all cHL samples. The analysis of EBV LMP1 variant distribution showed a predominance of the wild-type strain B95-8 and the Mediterranean subtype with 30 bp deletion. These findings could contribute to the understanding of EBV immunobiology in cHL as well as to the development of a prophylactic and therapeutic vaccine.
Direct or Indirect ESPT Mechanism in CFP psamFP488? A Theoretical-Computational Investigation
Authors: Donati Greta , Rega Nadia
Published: December 2022

Fluorescent Proteins are widely studied for their multiple applications in technological and biotechnological fields. Despite this, they continue to represent a challenge in terms of a complete understanding of all the non-equilibrium photo-induced processes that rule their properties. In this context, a theoretical-computational approach can support experimental results in unveiling and understanding the processes taking place after electronic excitation. A non-standard cyan fluorescent protein, psamFP488, is characterized by an absorption maximum that is blue-shifted in comparison to other cyan fluorescent proteins. This protein is characterized by an extended Stokes shift and an ultrafast (170 fs) excited state proton transfer. In this work, a theoretical-computational study, including excited state ab initio dynamics, is performed to help understanding the reaction mechanism and propose new hypotheses on the role of the residues surrounding the chromophore. Our results suggest that the proton transfer could be indirect toward the acceptor (Glu167) and involves other residues surrounding the chromophore, despite the ultrafast kinetics.
NFκB-Mediated Mechanisms Drive PEDF Expression and Function in Pre- and Post-Menopausal Oestrogen Levels in Breast Cancer
Authors: Brook Naomi , Gill Jespal , Dharmarajan Arun , Chan Arlene , Dass Crispin R.
Published: December 2022

Pigment epithelium-derived factor (PEDF) protein regulates normal bone, with anti-tumour roles in bone and breast cancer (BC). Pre- and post-menopausal oestrogen levels may regulate PEDF expression and function in BC, though the mechanisms behind this remain unknown. In this study, in vitro models simulating pre- and post-menopausal bone microenvironments were used to evaluate if PEDF regulates pro-metastatic biomarker expression and downstream functional effects on BC cells. PEDF treatment reduced phosphorylated-nuclear factor-κB p65 subunit (p-NFκB-p65), tumour necrosis factor-α (TNFα), C-X-C chemokine receptor type-4 (CXCR4), and urokinase plasminogen activator receptor (uPAR) in oestrogen receptor (ER)+/human epidermal growth factor receptor-2 (HER2)- BC cells under post-menopausal oestrogen conditions. In triple negative BC (TNBC) cells, PEDF treatment reduced pNFκB-p65 and uPAR expression under pre-menopausal oestrogen conditions. A potential reciprocal regulatory axis between p-NFκB-65 and PEDF in BC was identified, which was BC subtype-specific and differentially regulated by menopausal oestrogen conditions. The effects of PEDF treatment and NFκB inhibition on BC cell function under menopausal conditions were also compared. PEDF treatment exhibited superior anti-viability effects, while combined PEDF and NFκB-p65 inhibitor treatment was superior in reducing BC cell colony formation in a subtype-specific manner. Lastly, immunohistochemical evaluation of p-NFκB-p65 and PEDF expression in human BC and bone metastases specimens revealed an inverse correlation between nuclear PEDF and NFκB expression in bone metastases. We propose that menopausal status is associated with a PEDF/NFκB reciprocal regulatory axis, which drives PEDF expression and anti-metastatic function in a subtype-specific manner. Altogether, our findings identify pre-menopausal TNBC and post-menopausal ER+/HER2- BC patients as target populations for future PEDF research.
Degradation of Chemical Components of Thermally Modified Robinia pseudoacacia L. Wood and Its Effect on the Change in Mechanical Properties
Authors: Sikora Adam , Hájková Kateřina , Jurczyková Tereza
Published: December 2022

Currently, emphasis is placed on using environmentally friendly materials both from a structural point of view and the application of protective means. For this reason, it is advisable to deal with the thermal modification of wood, which does not require the application of protective substances, to increase its service life. The main reason for the thermal modification of black locust is that although black locust grows abundantly in our country, it has no industrial use. It is mainly used outdoors, where thermal modification could increase its resistance. This article deals with the thermal modification of black locust wood (Robinia pseudoacacia L.) and the impact of this modification on the chemical components of the wood with an overlap in the change in mechanical properties compared to untreated wood. Static (LOP, MOR, and MOE) and dynamic (IBS) bending properties were evaluated as representative mechanical properties. At the same time, the impact of thermal modification on the representation of chemical components of wood (cellulose, lignin, hemicellulose) was also tested. As a result of the heat treatment, the mechanical properties gradually decreased as the temperature increased. The highest decrease in mechanical values found at 210 °C was 43.7% for LOP and 45.1% for MOR. Thermal modification caused a decrease in the content of wood polysaccharides (the decrease in hemicelluloses content was 33.2% and the drop in cellulose was about 29.9% in samples treated at 210 °C), but the relative amount of lignin in the wood subjected to increased temperature was higher due to autocondensation, and mainly because of polysaccharide loss. Based on the correlations between chemical and mechanical changes caused by thermal modification, it is possible to observe the effects of reducing the proportions of chemical components and changes in their characteristic properties (DP, TCI) on the reduction in mechanical properties. The results of this research serve to better understand the behavior of black locust wood during thermal modification, which can primarily be used to increase its application use.
Role of EZH2 in Uterine Gland Development
Authors: Ni Nan , Jalufka Frank L. , Fang Xin , McCreedy Dylan A. , Li Qinglei
Published: December 2022

Enhancer of zeste homolog 2 (EZH2) is a core component of polycomb repressive complex 2 that plays a vital role in transcriptional repression of gene expression. Conditional ablation of EZH2 using progesterone receptor (Pgr)-Cre in the mouse uterus has uncovered its roles in regulating uterine epithelial cell growth and stratification, suppressing decidual myofibroblast activation, and maintaining normal female fertility. However, it is unclear whether EZH2 plays a role in the development of uterine glands, which are required for pregnancy success. Herein, we created mice with conditional deletion of Ezh2 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre recombinase that is expressed in mesenchyme-derived cells of the female reproductive tract. Strikingly, these mice showed marked defects in uterine adenogenesis. Unlike Ezh2 Pgr-Cre conditional knockout mice, deletion of Ezh2 using Amhr2-Cre did not lead to the differentiation of basal-like cells in the uterus. The deficient uterine adenogenesis was accompanied by impaired uterine function and pregnancy loss. Transcriptomic profiling using next generation sequencing revealed dysregulation of genes associated with signaling pathways that play fundamental roles in development and disease. In summary, this study has identified an unrecognized role of EZH2 in uterine gland development, a postnatal event critical for pregnancy success and female fertility.
Recent Developments in ZnS-Based Nanostructures Photocatalysts for Wastewater Treatment
Authors: Isac Luminita , Enesca Alexandru
Published: December 2022

The continuous growth of the world population has led to the constant increase of environmental pollution, with serious consequences for human health. Toxic, non-biodegradable, and recalcitrant organic pollutants (e.g., dyes, pharmaceuticals, pesticides) are discharged into water resources from various industries, such as textiles, leather, pharmaceuticals, plastics, etc. Consequently, the treatment of industrial wastewater, via a sustainable technology, represents a great challenge for worldwide research. Photocatalytic technology, an innovative technique based on advanced oxidation process (AOP), is considered a green technology with promising prospects in the remediation of global environmental issues. In photocatalysis, a very important role is attributed to the photocatalyst, usually a semiconductor material with high solar light absorption capacity and conductivity for photogenerated-charge carriers. Zinc sulfide (ZnS), as n-type semiconductor with different morphologies and band gap energies (Eg = 3.2–3.71 eV), is recognized as a promising photocatalyst for the removal of organic pollutants from wastewater, especially under UV light irradiation. This review deals with the recent developments (the last five years) in ZnS nanostructures (0D, 1D, 3D) and ZnS-based heterojunctions (n-n, n-p, Z scheme) used as photocatalysts for organic pollutants’ degradation under simulated (UV, Vis) and sunlight irradiation in wastewater treatment. The effects of different synthesis parameters (precursors’ type and concentration, capping agents’ dosages, reaction time and temperature, metal doping, ZnS concentration in heterostructures, etc.) and properties (particle size, morphology, band gap energy, and surface properties) on the photocatalytic performance of ZnS-based photocatalysts for various organic pollutants’ degradation are extensively discussed.
Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol
Authors: Terracina Sergio , Petrella Carla , Francati Silvia , Lucarelli Marco , Barbato Christian , Minni Antonio , Ralli Massimo , Greco Antonio , Tarani Luigi , Fiore Marco , Ferraguti Giampiero
Published: December 2022

Both physiological and pathological aging processes induce brain alterations especially affecting the speed of processing, working memory, conceptual reasoning and executive functions. Many therapeutic approaches to reduce the impact of brain aging on cognitive functioning have been tested; unfortunately, there are no satisfactory results as a single therapy. As aging is partly contributed by free radical reactions, it has been proposed that exogenous antioxidants could have a positive impact on both aging and its associated manifestations. The aim of this report is to provide a summary and a subsequent review of the literature evidence on the role of antioxidants in preventing and improving cognition in the aging brain. Manipulation of endogenous cellular defense mechanisms through nutritional antioxidants or pharmacological compounds represents an innovative approach to therapeutic intervention in diseases causing brain tissue damage, such as neurodegeneration. Coherently with this notion, antioxidants, especially those derived from the Mediterranean diet such as hydroxytyrosol and resveratrol, seem to be able to delay and modulate the cognitive brain aging processes and decrease the occurrence of its effects on the brain. The potential preventive activity of antioxidants should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability, able to bypass the blood-brain barrier limitation, and that are well standardized.
Single-Cell RNA Sequencing for the Detection of Clonotypic V(D)J Rearrangements in Multiple Myeloma
Authors: Matera Antonio , Marella Alessio , Maeda Akihiro , Da Vià Matteo C. , Lazzaroni Francesca , Fabris Sonia , Pioggia Stefania , Porretti Laura , Colombo Federico , Torricelli Federica , Neri Antonino , Taiana Elisa , Fabbiano Giuseppina , Traini Valentina , Genuardi Elisa , Drandi Daniela , Bolli Niccolò , Lionetti Marta
Published: December 2022

Multiple myeloma (MM) has a highly heterogeneous genetic background, which complicates its molecular tracking over time. Nevertheless, each MM patient’s malignant plasma cells (PCs) share unique V(D)J rearranged sequences at immunoglobulin loci, which represent ideal disease biomarkers. Because the tumor-specific V(D)J sequence is highly expressed in bulk RNA in MM patients, we wondered whether it can be identified by single-cell RNA sequencing (scRNA-seq). To this end we analyzed CD138+ cells purified from bone marrow aspirates of 19 samples with PC dyscrasias by both a standard method based on bulk DNA and by an implementation of the standard 10x Genomics protocol to detect expressed V(D)J sequences. A dominant clonotype was easily identified in each sample, accounting on average for 83.65% of V(D)J-rearranged cells. Compared with standard methods, scRNA-seq analysis proved highly concordant and even more effective in identifying clonal productive rearrangements, by-passing limitations related to the misannealing of consensus primers in hypermutated regions. We next validated its accuracy to track 5 clonal cells with absolute sensitivity in a virtual sample containing 3180 polyclonal cells. This shows that single-cell V(D)J analysis may be used to find rare clonal cells, laying the foundations for functional single-cell dissection of minimal residual disease.
Changes in TRPV1 Expression as Well as Substance P and Vasoactive Intestinal Peptide Levels Are Associated with Recurrence of Pterygium
Authors: İlhan Hatice Deniz , Ünal Betül , Ayaz Yusuf , Erin Nuray
Published: December 2022

Pterygium, a disease of the ocular surface, is characterized by the proliferation and invasion of fibrovascular tissue. Chronic inflammation contributes to pterygium occurrence. Sensory neuropeptides of TRPV1-positive nerve fibers are involved in inflammation and corneal wound healing. The possible association between TRPV1 in nerve fibers and neuropeptides such as Substance P (SP) and Vasoactive Intestinal Peptide (VIP) in the recurrence of pterygium has not been examined before. The pterygia from 64 patients were used to determine changes in SP and VIP levels using 10 min acetic-acid extraction that yielded mainly neuronal peptides. There was a sufficient amount of pterygium tissues from the 35 patients for further immunohistochemical analysis of TRPV1 and S100, which is a glial marker to visualize nerve fibers. SP and VIP levels increased markedly in cases with primary and secondary recurrences, and there was a close correlation between SP and VIP levels. TRPV1 expression increased in the epithelium, while stromal expression decreased in recurrences. Nerve fibers were demonstrated mainly in the stroma, and serial sections confirmed the localization of TRPV1 with the nerve fibers. These results together with previous findings demonstrated that the increased epithelial expression of TRPV1 in recurrent pterygia might be involved in the pathogenesis, and the inhibition of epithelial TRPV1 activity may prevent recurrence.
Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma
Authors: Maruoka Hiroshi , Tanaka Tomohito , Murakami Hikaru , Tsuchihashi Hiromitsu , Toji Akihiko , Nunode Misa , Daimon Atsushi , Miyamoto Shunsuke , Nishie Ruri , Ueda Shoko , Hashida Sousuke , Terada Shinichi , Konishi Hiromi , Kogata Yuhei , Taniguchi Kohei , Komura Kazumasa , Ohmichi Masahide
Published: December 2022

Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC.
Transcriptional Regulation of zma-MIR528a by Action of Nitrate and Auxin in Maize
Authors: Luján-Soto Eduardo , Aguirre de la Cruz Paola I. , Juárez-González Vasti T. , Reyes José L. , Sanchez María de la Paz , Dinkova Tzvetanka D.
Published: December 2022

In recent years, miR528, a monocot-specific miRNA, has been assigned multifaceted roles during development and stress response in several plant species. However, the transcription regulation and the molecular mechanisms controlling MIR528 expression in maize are still poorly explored. Here we analyzed the zma-MIR528a promoter region and found conserved transcription factor binding sites related to diverse signaling pathways, including the nitrate (TGA1/4) and auxin (AuxRE) response networks. Accumulation of both pre-miR528a and mature miR528 was up-regulated by exogenous nitrate and auxin treatments during imbibition, germination, and maize seedling establishment. Functional promoter analyses demonstrated that TGA1/4 and AuxRE sites are required for transcriptional induction by both stimuli. Overall, our findings of the nitrogen- and auxin-induced zma-MIR528a expression through cis-regulatory elements in its promoter contribute to the knowledge of miR528 regulome.
Lhb−/−Lhr−/− Double Mutant Mice Phenocopy Lhb−/− or Lhr−/− Single Mutants and Display Defects in Leydig Cells and Steroidogenesis
Authors: Liu Zhenghui , Larsen Mark , Lei Zhenmin , Rao C. V. , Kumar T. Rajendra
Published: December 2022

In the mouse, two distinct populations of Leydig cells arise during testis development. Fetal Leydig cells arise from a stem cell population and produce T required for masculinization. It is debated whether they persist in the adult testis. A second adult Leydig stem cell population gives rise to progenitor-immature-mature adult type Leydig cells that produce T in response to LH to maintain spermatogenesis. In testis of adult null male mice lacking either only LH (Lhb−/−) or LHR (Lhr−/−), mature Leydig cells are absent but fetal Leydig cells persist. Thus, it is not clear whether other ligands signal via LHRs in Lhb null mice or LH signals via other receptors in the absence of LHR in Lhr null mice. Moreover, it is not clear whether truncated LHR isoforms generated from the same Lhr gene promoter encode functionally relevant LH receptors. To determine the in vivo roles of LH-LHR signaling pathway in the Leydig cell lineage, we generated double null mutant mice lacking both LH Ligand and all forms of LHR. Phenotypic analysis indicated testis morpho-histological characteristics are identical among double null and single mutants which all showed poorly developed interstitium with a reduction in Leydig cell number and absence of late stage spermatids. Gene expression analyses confirmed that the majority of the T biosynthesis pathway enzyme-encoding mRNAs expressed in Leydig cells were all suppressed. Expression of thrombospondin-2, a fetal Leydig cell marker gene was upregulated in single and double null mutants indicating that fetal Leydig cells originate and develop independent of LH-LHR signaling pathway in vivo. Serum and intratesticular T levels were similarly suppressed in single and double mutants. Consequently, expression of AR-regulated genes in Sertoli and germ cells were similarly affected in single and double mutants without any evidence of any additive effect in the combined absence of both LH and LHR. Our studies unequivocally provide genetic evidence that in the mouse testis, fetal Leydig cells do not require LH-LHR signaling pathway and a one-to-one LH ligand-LHR signaling pathway exists in vivo to regulate adult Leydig cell lineage and spermatogenesis.
Preferred Migration of Mitochondria toward Cells and Tissues with Mitochondrial Damage
Authors: Lee Seo-Eun , Kang Young Cheol , Kim Yujin , Kim Soomin , Yu Shin-Hye , Park Jong Hyeok , Kim In-Hyeon , Kim Hyeon-Young , Han Kyuboem , Lee Hong Kyu , Kim Sung-Hwan , Kim Chun-Hyung
Published: December 2022

Mitochondria are organelles that play a vital role in cellular survival by supplying ATP and metabolic substrates via oxidative phosphorylation and the Krebs cycle. Hence, mitochondrial dysfunction contributes to many human diseases, including metabolic syndromes, neurodegenerative diseases, cancer, and aging. Mitochondrial transfer between cells has been shown to occur naturally, and mitochondrial transplantation is beneficial for treating mitochondrial dysfunction. In this study, the migration of mitochondria was tracked in vitro and in vivo using mitochondria conjugated with green fluorescent protein (MTGFP). When MTGFP were used in a coculture model, they were selectively internalized into lung fibroblasts, and this selectivity depended on the mitochondrial functional states of the receiving fibroblasts. Compared with MTGFP injected intravenously into normal mice, MTGFP injected into bleomycin-induced idiopathic pulmonary fibrosis model mice localized more abundantly in the lung tissue, indicating that mitochondrial homing to injured tissue occurred. This study shows for the first time that exogenous mitochondria are preferentially trafficked to cells and tissues in which mitochondria are damaged, which has implications for the delivery of therapeutic agents to injured or diseased sites.
Bioassay-Guided Isolation of Anthelmintic Components from Semen pharbitidis, and the Mechanism of Action of Pharbitin
Authors: Liu Maoxuan , Lu Jing-Guang , Yang Ming-Rong , Jiang Zhi-Hong , Wan Xiaochun , Luyten Walter
Published: December 2022

Parasitic helminths continue to pose problems in human and veterinary medicine, as well as in agriculture. Semen pharbitidis, the seeds of Pharbitis nil (Linn.) Choisy (Convolvulaceae), is a well-known traditional Chinese medicinal botanical preparation widely used for treating intestinal parasites in China owing to its desirable efficacy. However, the anthelmintic compounds in Semen pharbitidis and their mechanism of action have not been investigated yet. This study aimed to identify the compounds active against helminths from Semen pharbitidis, and to establish the mechanism of action of these active compounds. Bioassay-guided fractionation was used to identify the anthelmintic compounds from Semen pharbitidis. The anthelmintic assay was performed by monitoring Caenorhabditis elegans (C. elegans) motility with a WMicrotracker instrument. Active compounds were identified by high-resolution mass spectrometry. Several (analogues of) fragments of the anthelmintic compounds were purchased and tested to explore the structure–activity relationship, and to find more potent compounds. A panel of C. elegans mutant strains resistant to major currently used anthelmintic drugs was used to explore the mechanism of action of the active compounds. The bioassay-guided isolation from an ethanol extract of Semen pharbitidis led to a group of glycosides, namely pharbitin (IC50: 41.0 ± 9.4 μg/mL). Hit expansion for pharbitin fragments yielded two potent analogues: 2-bromohexadecanoic acid (IC50: 1.6 ± 0.7 μM) and myristoleic acid (IC50: 35.2 ± 7.6 μM). One drug-resistant mutant ZZ37 unc-63 (x37) demonstrated a ~17-fold increased resistance to pharbitin compared with wild-type worms. Collectively, we provide further experimental scientific evidence to support the traditional use of Semen pharbitidis for the treatment of intestinal parasites. The anthelmintic activity of Semen pharbitidis is due to pharbitin, whose target could be UNC-63 in C. elegans.
Anti-Inflammatory Mechanisms of Dietary Flavones: Tapping into Nature to Control Chronic Inflammation in Obesity and Cancer
Authors: Kariagina Anastasia , Doseff Andrea I.
Published: December 2022

Flavones are natural phytochemicals broadly distributed in our diet. Their anti-inflammatory properties provide unique opportunities to control the innate immune system and inflammation. Here, we review the role of flavones in chronic inflammation with an emphasis on their impact on the molecular mechanisms underlying inflammatory diseases including obesity and cancer. Flavones can influence the innate immune cell repertoire restoring the immune landscape. Flavones impinge on NF-κB, STAT, COX-2, or NLRP3 inflammasome pathways reestablishing immune homeostasis. Devoid of adverse side effects, flavones could present alternative opportunities for the treatment and prevention of chronic inflammation that contributes to obesity and cancer.
3–(2–Pyridyl)pyrazole Based Luminescent 1D-Coordination Polymers and Polymorphic Complexes of Various Lanthanide Chlorides Including Orange-Emitting Cerium(III)
Authors: Youssef Heba , Sedykh Alexander E. , Becker Jonathan , Taydakov Ilya V. , Müller-Buschbaum Klaus
Published: December 2022

A series of 18 lanthanide-containing 1D-coordination polymers 1∞[Ln2(2–PyPzH)4Cl6], Ln = La, Nd, Sm, dinuclear polymorphic complexes α–, β–[Ln2(2–PyPzH)4Cl6], Ln = Sm, Eu, Gd, α–[Tb2(2–PyPzH)4Cl6], and [Gd2(2–PyPzH)3(2–PyPz)Cl5], mononuclear complexes [Ce(2–PyPzH)3Cl3], [Ln(2–PyPzH)2Cl3], Ln = Tb, Dy, Ho, and Er, and salt-like complexes [Gd3(2–PyPzH)8Cl8]Cl and [PyH][Tb(2–PyPzH)2Cl4] were obtained from the reaction of the respective lanthanide chloride with the 3–(2–pyridyl)pyrazole (2–PyPzH) ligand at different temperatures. An antenna effect through ligand-to-metal energy transfer was observed for several products, leading to the highest luminescence efficiency displayed by a quantum yield of 92% in [Tb(2–PyPzH)2Cl3]. The Ce3+ ion in the complex [Ce(2–PyPzH)3Cl3] exhibits a bright and orange 5d-based broadband emission with a maximum at around 600 nm, marking an example of a strong reduction of the 5d-excited states of Ce(III). The absorption spectroscopy shows ion-specific 4f–4f transitions, which can be assigned to Nd3+, Sm3+, Eu3+, Dy3+, Ho3+, and Er3+ in a wide spectral range from UV–VIS to the NIR region.
Efficient and Rapid Removal of Pb(II) and Cu(II) Heavy Metals from Aqueous Solutions by MgO Nanorods
Authors: Ghoniem Monira G. , Ben Aissa Mohamed Ali , Ali Fatima Adam Mohamed , Khairy Mohamed
Published: December 2022

In this study, the adsorption capability of MgO nanorods for the quick and effective elimination of Cu(II) and Pb(II) heavy metals from wastewater was examined. The MgO nanorods were produced via simple coprecipitation process. Various characterization techniques were used to investigate the morphological and chemical properties of the as-prepared nanomaterial. Moreover, the influences of initial heavy-metal ion concentration, pH, and contact time were investigated to evaluate the removal efficiency of the nanomaterials. The adsorption process followed pseudo-second order and Langmuir adsorption isotherm models, according to kinetics and isotherm investigations, respectively. MgO nanoparticles exhibited a high adsorption capacity for Cu(II) (234.34 mg/g) and Pb(II) (221.26 mg/g). The existence of interfering ions in the aqueous solution leads to a decrease in the adsorption capacity. Surface complexation was determined as the key contributor to the adsorption of Cu(II) and Pb(II) heavy-metal ions onto MgO nanorods. Notably, regeneration experiments demonstrate the potential applicability of MgO nanorods for the elimination of Pb(II) and Cu(II) from aqueous solution.
Developing a Novel Immune-Related Seven-Gene Signature and Immune Infiltration Pattern in Patients with COVID-19 and Cardiovascular Disease
Authors: Fu Yajuan , Zhang Juan , Xu Lingbo , Zhang Hui , Ma Shengchao , Gao Yujing , Jiang Yideng
Published: December 2022

Background: patients with pre-existence of cardiovascular disease (CVD) are vulnerable to coronavirus disease 2019 (COVID-19), and COVID-19 will cause long-term burden of CVD. However, the common pathogenic mechanisms are not fully elucidated. More detailed knowledge of linking biological molecules and the role of immune signature would allow more valuable and specific clinical management. Methods: the gene expression profiles of CVD and COVID-19 were retrieved from the GEO database. Common differentially expressed genes (DEGs) were screened with the Limma R package and the WGCNA algorithm, and then functional enrichment analysis, protein-protein interaction network, hub genes, and small therapeutic molecules analyses were performed. The hub immune-related genes (HIRGs) were intersected, and their associations with immune cells, expressional correlation, evaluated performance, and potential signal pathways were further investigated. Results: In total, 57 common DEGs were identified as a shared transcriptional signature between CVD and COVID-19, and 12 hub genes were screened using five topological algorithms. There are common altered immune responses in the response of these two diseases, and seven HIRGs, including C5AR1, MMP9, CYBB, FPR2, CSF1R, TLR2, and TLR4, were identified, with positive correlation to altered macrophages and neutrophils. Nine small molecular agents (SMAs) were detected as promising therapeutic drugs. These seven HIRGs mainly participated in the inflammatory immune response through activation of Il2 stat5 signaling and Tnfa signaling via nfκb pathways, and ROC curves confirmed their good discriminatory capacity in the two diseases. Conclusions: this study established the co-expression network and identified a new immune-related seven-gene signature as therapeutic targets, which may provide new insights into pathogenic mechanisms and novel clinical management strategies.
Healthcare Utilization and Outcomes in Atrial Fibrillation Patients Treated by Drug Therapy versus a Catheter Ablation Strategy—A Middle European Propensity Score Matched Cohort Study
Authors: Martinek Martin , Crijns Harry J. G. M. , Essers Barbara A. B. , Wiesinger Rene , Pruckner Gerald
Published: December 2022

Background and Aims: Atrial fibrillation (AF) is the most prevalent arrhythmia, associated with increased mortality and morbidity and causing relevant costs. Treatment options consist of catheter ablation (PVI) and rate or rhythm control drugs (non-PVI). Methods: We analyze inpatient and outpatient data from the Upper Austrian Health Insurance Fund. Data of patients with a first hospitalization for AF in the years 2005 to 2018 were examined, using propensity score matching (PSM) including all CHA2DS2-VASc variables and working “collar”. Results: Out of 21,791 AF patients, PSM identified 1013 well-matching pairs (PVI and non-PVI). Over a ten-year period, the PVI treatment strategy group reveals significantly higher inpatient and outpatient expenditures (€2200/year). Positive economic effects can be demonstrated by a 5.1 percentage points (pp) higher employment rate and fewer retirements (7.6pp). Of utmost important is the 5.8pp all-cause mortality reduction over 10 years in the PVI treatment strategy. Conclusions: A PVI based treatment strategy results in higher healthcare expenditures vs. drug therapy alone. Most of these higher costs were caused by the PVI procedures during this period. Thus, more effective and efficient methods are needed to further reduce costs for the intervention and prevent repeat procedures. The benefit of a PVI treatment strategy is seen in higher employment rates, which are crucial from a societal perspective and should be a strong argument for caregivers. We show a significant reduction in all-cause mortality, which we partly attribute to the PVI procedure itself, to a stricter risk factor assessment and treatment, and a tighter medical adherence.
Acquired von Willebrand Syndrome Secondary to Normally Functioning Mechanical Aortic Valve and High-Output Cardiac State
Authors: Yang Xinglin , Zhang Jinghong , Lai Yamin , Yan Xuemin , Guo Xiaoxiao , Han Jianhua , Liu Jihai , Wang Jiangshan , Zhu Huadong
Published: December 2022

Acquired von Willebrand syndrome (AVWS) is caused by an acquired deficiency of von Willebrand factor (VWF), a multimeric protein required for primary hemostasis. For patients with heart valve diseases, high gradient across the malfunctioning valves could cause elevated shear stress and damage the most effective large VWF, eventually resulting in AVWS. However, AVWS has not been reported in association with normally functioning mechanical valves. Herein, we reported a 74-year-old female who suffered from recurrent gastrointestinal bleeding with a history of mechanical aortic and mitral valve replacement. This patient’s function/antigen ratio of VWF was decreased and gel electrophoresis revealed the loss of large VWF, which confirmed the diagnosis of AVWS. Echocardiogram showed that the function of the prostheses was normal. However, the gradient across aortic valve was increased due to a high cardiac state which is secondary to chronic anemia, resulting in the disruption of large VWF multimers and exacerbation of gastrointestinal (GI) bleeding. After managing the patient’s anemia with transfusion, the gradient across the aortic valve had improved, with the resolution of GI bleeding. This is the first case report of AVWS that is associated with a normally functioning mechanical valve. AVWS should be considered one of the differential diagnoses if patients present with unexplained GI bleeding on the background of having prosthetic heart valves. The management of the underlying condition is essential.
Impact of Short-Acting Disopyramide on Left Ventricular Mechanics Evaluated by Strain Analysis in Patients with Hypertrophic Obstructive Cardiomyopathy
Authors: Yedidya Idit , Elbaz Greener Gabby , Vaturi Mordehay , Sagie Alik , Amir Offer , Carasso Shemy , Monakier Daniel
Published: December 2022

Background: Disopyramide is a class Ia antiarrhythmic drug that has been used for the second-line treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of the study was to assess the impact of short-acting disopyramide in patients with hypertrophic obstructive cardiomyopathy (HOCM) using two-dimensional speckle-tracking echocardiography. Methods: This prospective study included patients with HOCM on chronic treatment with short-acting disopyramide. Two sequential comprehensive echocardiographic examinations were performed: after temporary disopyramide suspension and 2.5 h after disopyramide intake. Results: 19 patients were included in the study. The effect of disopyramide on the left ventricle was not uniform. After the intake of disopyramide, the mean global strain peak was −17 ± 2% before disopyramide intake and −14 ± 2% after (p < 0.0001). There was a significant reduction in strain in the basal septal (p = 0.015), basal inferior (p = 0.019), basal posterior (p = 0.05), apical anterior (p = 0.0001), and apical lateral segments (p = 0.021). In all other segments, there was no significant change. Disopyramide also caused a significant accentuation of the base-apex strain gradients (p = 0.036). No change was noted in circumferential and left atrial strain. While the left ventricular ejection fraction and outflow gradients did not change, the significant reduction in global and segmental longitudinal strain demonstrated the acute negative inotropic effect of disopyramide on the myocardium in patients with HOCM. Conclusion: A strain analysis may be a useful tool to assess the negative inotropic effect of cardiovascular medication on the left ventricle in patients with HOCM.
Autologous Platelet-Rich Plasma (PRP) for Treating Androgenetic Alopecia: A Novel Treatment Protocol Standardized on 2 Cases
Authors: Maletic Ana , Dumic-Cule Ivo , Brlek Petar , Zic Rado , Primorac Dragan
Published: December 2022

Platelet-rich plasma (PRP) treatment has emerged in recent years as a valuable, effective, and affordable treatment for androgenetic alopecia. Androgenetic alopecia is the most common type of alopecia, affecting both men and women, and is characterized by diminished hair follicles mainly pronounced in the frontal region and vertex. A considerable variety of PRP treatment regimens have been described so far, but there is no consensus on the standardization of PRP preparation or administration protocol. Our study was conducted on two patients to test the efficacy of a new PRP application protocol of only two treatments by using a combination of a PRP collecting device and a conventional kit. Efficacy of treatment was assessed after a 6-month follow-up by artificial intelligence (AI)-driven software on microscopic images of treated regions. An average number of hairs, cumulative hair thickness, and the number of follicular units increased in the vertex region of both patients by 30/59%, 35/53%, and 14/48%, respectively. The novel treatment regimen showed significant effectiveness in only six months.
A Clinical Study of Alveolar Bone Tissue Engineering Using Autologous Bone Marrow Stromal Cells: Effect of Optimized Cell-Processing Protocol on Efficacy
Authors: Kagami Hideaki , Inoue Minoru , Agata Hideki , Asahina Izumi , Nagamura-Inoue Tokiko , Taguri Masataka , Tojo Arinobu
Published: December 2022

(1) Objectives: The effect of cell-processing protocols on the clinical efficacy of bone tissue engineering is not well-known. To maximize efficacy, we optimized the cell-processing protocol for bone-marrow-derived mesenchymal stromal cells for bone tissue engineering. In this study, the efficacy of bone tissue engineering using this modified protocol was compared to that of the original protocol. (2) Materials and Methods: This single-arm clinical study included 15 patients. Cells were obtained from bone marrow aspirates and expanded in culture flasks containing basic fibroblast growth factor. The cells were seeded onto β-tricalcium phosphate granules and induced into osteogenic cells for two weeks. Then, the cell–scaffold composites were transplanted into patients with severe atrophic alveolar bone. Radiographic evaluations and bone biopsies were performed. The results were compared with those of a previous clinical study that used the original protocol. (3) Results: Panoramic X-ray and computed tomography showed bone regeneration at the transplantation site in all cases. The average bone area in the biopsy samples at 4 months was 44.0%, which was comparable to that in a previous clinical study at 6 months (41.9%) but with much less deviation. No side effects related to cell transplantation were observed. In regenerated bone, 100% of the implants were integrated. (4) Conclusions: Compared to the original protocol, the non-inferiority of this protocol was proven. The introduction of an optimized cell-processing protocol resulted in a comparable quality of regenerated bone, with less fluctuation. Optimized cell-processing protocols may contribute to stable bone regeneration.
Application of nnU-Net for Automatic Segmentation of Lung Lesions on CT Images and Its Implication for Radiomic Models
Authors: Ferrante Matteo , Rinaldi Lisa , Botta Francesca , Hu Xiaobin , Dolp Andreas , Minotti Marta , De Piano Francesca , Funicelli Gianluigi , Volpe Stefania , Bellerba Federica , De Marco Paolo , Raimondi Sara , Rizzo Stefania , Shi Kuangyu , Cremonesi Marta , Jereczek-Fossa Barbara A. , Spaggiari Lorenzo , De Marinis Filippo , Orecchia Roberto , Origgi Daniela
Published: December 2022

Radiomics investigates the predictive role of quantitative parameters calculated from radiological images. In oncology, tumour segmentation constitutes a crucial step of the radiomic workflow. Manual segmentation is time-consuming and prone to inter-observer variability. In this study, a state-of-the-art deep-learning network for automatic segmentation (nnU-Net) was applied to computed tomography images of lung tumour patients, and its impact on the performance of survival radiomic models was assessed. In total, 899 patients were included, from two proprietary and one public datasets. Different network architectures (2D, 3D) were trained and tested on different combinations of the datasets. Automatic segmentations were compared to reference manual segmentations performed by physicians using the DICE similarity coefficient. Subsequently, the accuracy of radiomic models for survival classification based on either manual or automatic segmentations were compared, considering both hand-crafted and deep-learning features. The best agreement between automatic and manual contours (DICE = 0.78 ± 0.12) was achieved averaging 2D and 3D predictions and applying customised post-processing. The accuracy of the survival classifier (ranging between 0.65 and 0.78) was not statistically different when using manual versus automatic contours, both with hand-crafted and deep features. These results support the promising role nnU-Net can play in automatic segmentation, accelerating the radiomic workflow without impairing the models’ accuracy. Further investigations on different clinical endpoints and populations are encouraged to confirm and generalise these findings.
Effects of Running in Minimal and Conventional Footwear on Medial Tibiofemoral Cartilage Failure Probability in Habitual and Non-Habitual Users
Authors: Sinclair Jonathan , Huang Guohao , Taylor Paul John , Chockalingam Nachiappan , Fan Yifang
Published: December 2022

This study examined the effects of minimal and conventional running footwear on medial tibiofemoral cartilage mechanics and longitudinal failure probability. The current investigation examined twenty males who habitually ran in minimal footwear and 20 males who habitually ran in conventional footwear. Kinematic data during overground running were collected using a motion-capture system and ground reaction forces using a force plate. Medial tibiofemoral loading was examined using musculoskeletal simulation and cartilage failure probability via probabilistic modelling. In habitual minimal footwear users, peak medial tibiofemoral cartilage force, stress and strain were significantly greater in conventional (force = 7.43 BW, stress = 5.12 MPa and strain = 0.30), compared to minimal footwear (force = 7.11 BW, stress 4.65 MPa and strain = 0.28), though no significant differences in these parameters were evident in non-habitual minimal footwear users (conventional: force = 7.50 BW, stress = 5.05 MPa and strain = 0.30; minimal: force = 7.40 BW, stress = 4.77 MPa and strain = 0.29). However, in both habitual and non-habitual minimal footwear users, the probability of medial tibiofemoral cartilage failure was significantly greater in conventional (habitual = 47.19% and non-habitual = 50.00%) compared to minimal footwear (habitual = 33.18% and non-habitual = 32.81%) users. The observations from this investigation show that compared to minimal footwear, conventional footwear appears to have a negative influence on medial tibiofemoral cartilage health.
The Analysis of Facio-Dental Proportions to Determine the Width of Maxillary Anterior Teeth: A Clinical Study
Authors: Ahmed Naseer , Halim Mohamad Syahrizal , Ab-Ghani Zuryati , Abbasi Maria Shakoor , Aslam Ayesha , Safdar Jawad , Das Gotam , Ahmed Abdul Razzaq , Jamayet Nafij Bin
Published: December 2022

The present study aimed to analyze mid horizontal facial third proportions, those being the interpupillary, inner intercanthal, and bizygomatic distance modified with golden proportion, The Preston proportion, golden percentage and 70% recurring esthetic dental proportion were used for determining maxillary anterior teeth width. A total of 230 participants took part in this study. The front dental and facial photographs along dental stone cast which were converted to three-dimensional (3D) models were used for evaluation. The mid horizontal facial third proportions showed no significant relationship with maxillary anterior teeth width without modification with dental proportions. Whereas, with modification, no statistically significant difference was found between inner-intercanthal distance by golden percentage and width of central incisors. The bizygomatic distance was greater than intercanine distance. While the interpupillary distance by golden proportion was found to be consistent with intercanine distance in female participants. The modified anterior teeth width was significantly different from measured values, when determined by using the three mid facial proportions with Preston and 70% recurring esthetic dental (RED) proportion. Furthermore, the measured width of maxillary anterior teeth showed no difference when plaster dental casts widths were compared with 3D models. The interpupillary, inner-intercanthal, and bizygomatic distance should not be directly used to determine maxillary anterior teeth width. While maxillary anterior teeth width can be determined by modifying the inner inter-canthal distance with golden percentage and interpupillary distance with golden proportion. Moreover, the midfacial third proportions modified with Preston and 70% recurrent esthetic dental proportion were found to be unreliable for the determination of maxillary anterior teeth widths.
A Smart Glove Digital System Promotes Restoration of Upper Limb Motor Function and Enhances Cortical Hemodynamic Changes in Subacute Stroke Patients with Mild to Moderate Weakness: A Randomized Controlled Trial
Authors: Shin Seyoung , Lee Hwang-Jae , Chang Won Hyuk , Ko Sung Hwa , Shin Yong-Il , Kim Yun-Hee
Published: December 2022

This study was a randomized controlled trial to examine the effects of the RAPAEL® Smart Glove digital training system on upper extremity function and cortical hemodynamic changes in subacute stroke patients. Of 48 patients, 20 experimental and 16 controls completed the study. In addition to conventional occupational therapy (OT), the experimental group received game-based digital hand motor training with the RAPAEL® Smart Glove digital system, while the control group received extra OT for 30 min. The Fugl-Meyer assessment (UFMA) and Jebsen-Tayler hand function test (JTT) were assessed before (T0), immediately after (T1), and four weeks after intervention (T2). Cortical hemodynamics (oxyhemoglobin [OxyHb] concentration) were measured by functional near-infrared spectroscopy. The experimental group had significantly better improvements in UFMA (T1-T0 mean [SD]; Experimental 13.50 [7.49]; Control 8.00 [4.44]; p = 0.014) and JTT (Experimental 21.10 [20.84]; Control 5.63 [5.06]; p = 0.012). The OxyHb concentration change over the ipsilesional primary sensorimotor cortex during the affected wrist movement was greater in the experimental group (T1, Experimental 0.7943 × 10−4 μmol/L; Control −0.3269 × 10−4 μmol/L; p = 0.025). This study demonstrated a beneficial effect of game-based virtual reality training with the RAPAEL® Smart Glove digital system with conventional OT on upper extremity motor function in subacute stroke patients.