bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights from a Bibliometrics-Based Analysis of Publishing and Research Trends on Cerium Oxide from 1990 to 2020
Authors: Fleming Charlotte L. , Wong Jessie , Golzan Mojtaba , Gunawan Cindy , McGrath Kristine C.
Published: January 2023

The purpose of this study is to evaluate the literature for research trends on cerium oxide from 1990 to 2020 and identify gaps in knowledge in the emerging application(s) of CeONP. Bibliometric methods were used to identify themes in database searches from PubMed, Scopus and Web of Science Core Collection using SWIFT-Review, VOSviewer and SciMAT software programs. A systematic review was completed on published cerium oxide literature extracted from the Scopus database (n = 17,115), identifying themes relevant to its industrial, environmental and biomedical applications. A total of 172 publications were included in the systematic analysis and categorized into four time periods with research themes identified; “doping additives” (n = 5, 1990–1997), “catalysts” (n = 32, 1998–2005), “reactive oxygen species” (n = 66, 2006–2013) and “pathology” (n = 69, 2014–2020). China and the USA showed the highest number of citations and publications for cerium oxide research from 1990 to 2020. Longitudinal analysis showed CeONP has been extensively used for various applications due to its catalytic properties. In conclusion, this study showed the trend in research in CeONP over the past three decades with advancements in nanoparticle engineering like doping, and more recently surface modification or functionalization to further enhanced its antioxidant abilities. As a result of recent nanoparticle engineering developments, research into CeONP biological effects have highlighted its therapeutic potential for a range of human pathologies such as Alzheimer’s disease. Whilst research over the past three decades show the versatility of cerium oxide in industrial and environmental applications, there are still research opportunities to investigate the potential beneficial effects of CeONP in its application(s) on human health.
Deep Molecular Response Achieved with Chemotherapy, Dasatinib and Interferon α in Patients with Lymphoid Blast Crisis of Chronic Myeloid Leukaemia
Authors: Vráblová Lucia , Divoký Vladimír , Kořalková Pavla , Poláková Kateřina Machová , Kriegová Eva , Janská Romana , Grohmann Jan , Holzerová Milena , Papajík Tomáš , Faber Edgar
Published: January 2023

The treatment outcome in patients with chronic myeloid leukaemia (CML) in blast crisis (BC) is unsatisfactory despite the use of allogeneic stem cell transplantation (ASCT). Moreover, in some patients ASCT is contraindicated, with limited treatment options. We report the case series of two patients with lymphoid BC CML in whom ASCT was not approachable. The first patient developed BC two months after diagnosis in association with dic(7;9)(p11.2;p11.2) and T315I mutation. Blast crisis with central nervous system leukemic involvement and K611N mutation of the SETD2 gene developed abruptly in the second patient five years after ceasing treatment with nilotinib in major molecular response (MMR) at the patient’s request. Both underwent one course of chemotherapy in combination with rituximab and imatinib, followed by dasatinib and interferon α (INFα) treatment in the first and dasatinib alone in the second case. Deep molecular response (DMR; MR 4.0) was achieved within a short time in both cases. It is probable that DMR was caused by a specific immune response to CML cells, described in both agents. The challenging medical condition that prompted these case series, and the subsequent results, suggest a re-visit to the use of a combination of well-known drugs as an area for further investigation.
Protective Effects of Lactobacillus gasseri against High-Cholesterol Diet-Induced Fatty Liver and Regulation of Host Gene Expression Profiles
Authors: He Tianhua , Lykov Nikita , Luo Xu , Wang Huiling , Du Zhanxiang , Chen Ziyi , Chen Shitian , Zhu Lin , Zhao Ye , Tzeng Chimeng
Published: January 2023

Fatty liver is one of the most pervasive liver diseases worldwide. Probiotics play an important role in the progression of liver disease, but their effects on host regulation are poorly understood. This study investigated the protective effects of lactobacillus gasseri (L. gasseri) against high-cholesterol diet (HCD)-induced fatty liver injury using a zebrafish larvae model. Liver pathology, lipid accumulation, oxidative stress and hepatic inflammation were evaluated to demonstrate the changes in a spectrum of hepatic injury. Moreover, multiple indexes on host gene expression profiles were comprehensively characterized by RNA screening. The results showed that treatment with L. gasseri ameliorated HCD-induced morphological and histological alterations, lipid regulations, oxidative stress and macrophage aggregation in the liver of zebrafish larvae. Furthermore, the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed that the core pathways of L. gasseri regulation were interleukin-17 (IL-17) signaling, phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, the regulation of lipolysis and adipocytes and fatty acid elongation and estrogen signaling. The genes at key junction nodes, hsp90aa1.1, kyat3, hsd17b7, irs2a, myl9b, ptgs2b, cdk21 and papss2a were significantly regulated by L. gasseri administration. To conclude, the current research extends our understanding of the protective effects of L. gasseri against fatty liver and provides potential therapeutic options for fatty liver treatment.
eIF4A1 Is a Prognostic Marker and Actionable Target in Human Hepatocellular Carcinoma
Authors: Steinmann Sara M. , Sánchez-Martín Anabel , Tanzer Elisabeth , Cigliano Antonio , Pes Giovanni M. , Simile Maria M. , Desaubry Laurent , Marin Jose J.G. , Evert Matthias , Calvisi Diego F.
Published: January 2023

Hepatocellular carcinoma (HCC) is a primary liver tumor with high lethality and increasing incidence worldwide. While tumor resection or liver transplantation is effective in the early stages of the disease, the therapeutic options for advanced HCC remain limited and the benefits are temporary. Thus, novel therapeutic targets and more efficacious treatments against this deadly cancer are urgently needed. Here, we investigated the pathogenetic and therapeutic role of eukaryotic initiation factor 4A1 (eIF4A1) in this tumor type. We observed consistent eIF4A1 upregulation in HCC lesions compared with non-tumorous surrounding liver tissues. In addition, eIF4A1 levels were negatively correlated with the prognosis of HCC patients. In HCC lines, the exposure to various eIF4A inhibitors triggered a remarkable decline in proliferation and augmented apoptosis, paralleled by the inhibition of several oncogenic pathways. Significantly, anti-growth effects were achieved at nanomolar concentrations of the eIF4A1 inhibitors and were further increased by the simultaneous administration of the pan mTOR inhibitor, Rapalink-1. In conclusion, our results highlight the pathogenetic relevance of eIF4A1 in HCC and recommend further evaluation of the potential usefulness of pharmacological combinations based on eIF4A and mTOR inhibitors in treating this aggressive tumor.
Moutan Cortex Extract Modulates Macrophage Activation via Lipopolysaccharide-Induced Calcium Signaling and ER Stress-CHOP Pathway
Authors: Kim Hyun-Ju , Kim Do-Hoon , Park Wansu
Published: January 2023

Moutan Cortex, Paeonia suffruticosa root, has long been used as a medicine for the treatment of inflammatory diseases. The aim of this study was to evaluate the modulative properties of Moutan Cortex water extract (CP) on endoplasmic reticulum (ER) stress-related macrophage activation via the calcium-CHOP pathway. RAW 264.7 mouse macrophages were activated by lipopolysaccharide (LPS), and the levels of various inflammatory mediators from RAW 264.7 were evaluated. The multiplex cytokine assay was used to investigate both cytokines and growth factors, and RT-PCR was used to investigate the expressions of inflammation-related genes, such as CHOP. Data represent the levels of NO and cytosolic calcium in LPS-stimulated RAW 264.7 were significantly inhibited by CP as well as hydrogen peroxide (p < 0.05). Minutely, NO production in LPS-stimulated RAW 264.7 incubated with CP at concentrations of 25, 50, 100, and 200 µg/mL for 24 h was 97.32 ± 1.55%, 95.86 ± 2.26%, 94.64 ± 1.83%, and 92.69 ± 2.31% of the control value (LPS only), respectively (p < 0.05). Calcium release in LPS-stimulated RAW 264.7 incubated with CP at concentrations of 25, 50, 100, and 200 µg/mL for 18 h was 95.78 ± 1.64%, 95.41 ± 1.14%, 94.54 ± 2.76%, and 90.89 ± 3.34% of the control value, respectively (p < 0.05). Hydrogen peroxide production in LPS-stimulated RAW 264.7 incubated with CP at concentrations of 25, 50, 100, and 200 µg/mL for 24 h was 79.15 ± 7.16%, 63.83 ± 4.03%, 46.27 ± 4.38%, and 40.66 ± 4.03% of the control value, respectively (p < 0.05). It is interesting that the production of IL-6, TNF-α, G-CSF, MIP-1α, MIP-2, and M-CSF in LPS-stimulated RAW 264.7 were significantly inhibited by CP (p < 0.05), while the production of LIX, LIF, RANTES, and MIP-1β showed a meaningful decrease. CP at concentrations of 25, 50, 100, and 200 µg/mL significantly reduced the transcription of Chop, Camk2α, NOS, STAT1, STAT3, Ptgs2, Jak2, c-Jun, Fas, c-Fos, TLR3, and TLR9 in LPS-stimulated RAW 264.7 (p < 0.05). CP at concentrations of 25, 50, and 100 µg/mL significantly reduced the phosphorylation of STAT3, p38 MAPK, and IκB-α in LPS-stimulated RAW 264.7 (p < 0.05). These results suggest that CP might modulate macrophage activation via LPS-induced calcium signaling and the ER stress-CHOP pathway.
Serum and Urine Biomarkers Related to Kidney Fibrosis Predict Kidney Outcome in Czech Patients with IgA Nephropathy
Authors: Neprasova Michaela , Maixnerova Dita , Sparding Nadja , Genovese Federica , Karsdal Morten Asser , Koprivova Helena , Kollar Marek , Suchanek Miloslav , Hruskova Zdenka , Tesar Vladimir
Published: January 2023

We evaluated biomarkers related to kidney fibrosis for the outcome of patients with IgA nephropathy (IgAN). Clinical parameters (estimated glomerular filtration rate, hypertension, proteinuria) and histological findings were assessed in 134 patients with IgAN at the time of diagnosis and followed up prospectively (mean follow-up time, 56.5 months). We measured biomarkers of collagen and laminin turnover in serum and urine collected at the time of kidney biopsy using a novel enzyme-linked immunosorbent assay. Linear discriminant analysis and logistic regression models were used to predict the patient’s kidney outcome. Five serum and urine biomarkers of laminin and collagen turnover (sLG1M, sPRO-C3, sPRO-C6, uPRO-C6/Cr, uC3M/Cr) could significantly differentiae IgAN patients with a worse prognosis. Clinical parameters (glomerular filtration rate (GFR), proteinuria) distinguished patients at risk of IgAN progression with a specificity of 87.3% and a sensitivity of 45.2% (area under the curve-AUC 0.751). The addition of the biomarkers significantly increased the prognostic ability with a specificity of 85.1% and a sensitivity of 73.3% (AUC 0.905). We have identified three serum (sLG1M, sPRO-C3, sPRO-C6) and two urinary markers (uPRO-C6/Cr, u-C3M /Cr) that significantly improve the prognostic ability of markers of kidney function to identify an IgAN patient’s risk of progressing to ESKD.
TZD-Based Hybrid Molecules Act as Dual Anti-Mycobacterium tuberculosis and Anti-Toxoplasma gondii Agents
Authors: Dzitko Katarzyna , Kaproń Barbara , Paneth Agata , Bekier Adrian , Plech Tomasz , Paneth Piotr , Trotsko Nazar
Published: January 2023

Two distinct intracellular pathogens, namely Mycobacterium tuberculosis (Mtb) and Toxoplasma gondii (Tg), cause major public health problems worldwide. In addition, serious and challenging health problems of co-infections of Tg with Mtb have been recorded, especially in developing countries. Due to this fact, as well as the frequent cases of resistance to the current drugs, novel anti-infectious therapeutics, especially those with dual (anti-Tg and anti-Mtb) modes of action, are needed. To address this issue, we explored the anti-Tg potential of thiazolidinedione-based (TZD-based) hybrid molecules with proven anti-Mtb potency. Several TZD hybrids with pyridine-4-carbohydrazone (PCH) or thiosemicarbazone (TSC) structural scaffolds were more effective and more selective than sulfadiazine (SDZ) and trimethoprim (TRI). Furthermore, all of these molecules were more selective than pyrimethamine (PYR). Further studies for the most potent TZD-TSC hybrids 7, 8 and 10 and TZD-PCH hybrid molecule 2 proved that these compounds are non-cytotoxic, non-genotoxic and non-hemolytic. Moreover, they could cross the blood–brain barrier (BBB), which is a critical factor linked with ideal anti-Tg drug development. Finally, since a possible link between Tg infection and the risk of glioblastoma has recently been reported, the cytotoxic potential of TZD hybrids against human glioblastoma cells was also evaluated. TZD-PCH hybrid molecule 2 was found to be the most effective, with an IC50 of 19.36 ± 1.13 µg/mL against T98G cells.
Therapeutic Potential and Limitation of Serotonin Type 7 Receptor Modulation
Authors: Fukuyama Kouji , Motomura Eishi , Okada Motohiro
Published: January 2023

Although a number of mood-stabilising atypical antipsychotics and antidepressants modulate serotonin type 7 receptor (5-HT7), the detailed contributions of 5-HT7 function to clinical efficacy and pathophysiology have not been fully understood. The mood-stabilising antipsychotic agent, lurasidone, and the serotonin partial agonist reuptake inhibitor, vortioxetine, exhibit higher binding affinity to 5-HT7 than other conventional antipsychotics and antidepressants. To date, the initially expected rapid onset of antidepressant effects—in comparison with conventional antidepressants or mood-stabilising antipsychotics—due to 5-HT7 inhibition has not been observed with lurasidone and vortioxetine; however, several clinical studies suggest that 5-HT7 inhibition likely contributes to quality of life of patients with schizophrenia and mood disorders via the improvement of cognition. Furthermore, recent preclinical studies reported that 5-HT7 inhibition might mitigate antipsychotic-induced weight gain and metabolic complication by blocking other monoamine receptors. Further preclinical studies for the development of 5-HT7 modulation against neurodevelopmental disorders and neurodegenerative diseases have been ongoing. To date, various findings from various preclinical studies indicate the possibility that 5-HT7 modifications can provide two independent strategies. The first is that 5-HT7 inhibition ameliorates the dysfunction of inter-neuronal transmission in mature networks. The other is that activation of 5-HT7 can improve transmission dysfunction due to microstructure abnormality in the neurotransmission network—which could be unaffected by conventional therapeutic agents—via modulating intracellular signalling during the neurodevelopmental stage or via loss of neural networks with aging. This review attempts to describe the current and novel clinical applications of 5-HT7 modulation based on preclinical findings.
Celiac Disease Genetics, Pathogenesis, and Standard Therapy for Japanese Patients
Authors: Tamai Tasuku , Ihara Kenji
Published: January 2023

Celiac disease is an autoimmune disease primarily affecting the small intestine that is caused by the ingestion of gluten in genetically susceptible individuals. The development of celiac disease is based on a complex immune response to gluten proteins. The global average prevalence in the general population is about 1%. In recent years, it has become clear that celiac disease is not less common in Asian countries than in Western countries but often remains undiagnosed. Although the number of patients with celiac disease in Asia is expected to increase with improving disease recognition and advances in diagnostic techniques, there remain few reports of celiac disease in the Far East region of Asia, especially in Japan. In this paper, we outline the epidemiology, diagnosis, and treatment of celiac disease. In addition, we summarize the reported Japanese cases of celiac disease with an overview in Japan.
Mesenchymal Stem Cells and Their Exocytotic Vesicles
Authors: Cai Hao , Guo Haidong
Published: January 2023

Mesenchymal stem cells (MSCs), as a kind of pluripotent stem cells, have attracted much attention in orthopedic diseases, geriatric diseases, metabolic diseases, and sports functions due to their osteogenic potential, chondrogenic differentiation ability, and adipocyte differentiation. Anti-inflammation, anti-fibrosis, angiogenesis promotion, neurogenesis, immune regulation, and secreted growth factors, proteases, hormones, cytokines, and chemokines of MSCs have been widely studied in liver and kidney diseases, cardiovascular and cerebrovascular diseases. In recent years, many studies have shown that the extracellular vesicles of MSCs have similar functions to MSCs transplantation in all the above aspects. Here we review the research progress of MSCs and their exocrine vesicles in recent years.
The Chromosome-Level Genome of Hestina assimilis (Lepidoptera: Nymphalidae) Reveals the Evolution of Saprophagy-Related Genes in Brush-Footed Butterflies
Authors: Zhao Lu , Li Xiao-Dong , Jiang Tao , Wang Hang , Dan Zhicuo , Xu Sheng-Quan , Guan De-Long
Published: January 2023

Most butterflies feed on nectar, while some saprophagous butterflies forage on various non-nectar foods. To date, little is known about the genomic and molecular shifts associated with the evolution of the saprophagous feeding strategy. Here, we assembled the high-quality chromosome-level genome of Hestina assimilis to explore its saprophagous molecular and genetic mechanisms. This chromosome-level genome of H. assimilis is 412.82 Mb, with a scaffold N50 of 15.70 Mb. In total, 98.11% of contigs were anchored to 30 chromosomes. Compared with H. assimilis and other Nymphalidae butterflies, the genes of metabolism and detoxification experienced expansions. We annotated 80 cytochrome P450 (CYP) genes in the H. assimilis genome, among which genes belonging to the CYP4 subfamily were significantly expanded (p < 0.01). These P450 genes were unevenly distributed and mainly concentrated on chromosomes 6–9. We identified 33 olfactory receptor (OR), 20 odorant-binding protein (OBP), and six gustatory receptor (GR) genes in the H. assimilis genome, which were fewer than in the nectarivorous Danaus plexippus. A decreased number of OBP, OR, and GR genes implied that H. assimilis should resort less to olfaction and gustation than their nectarivorous counterparts, which need highly specialized olfactory and gustatory functions. Moreover, we found one site under positive selection occurred in residue 996 (phenylalanine) of GR genes exclusive to H. assimilis, which is conservative in most lineages. Our study provides support for the adaptive evolution of feeding habits in butterflies.
Triacylglycerol Composition and Chemical-Physical Properties of Cocoa Butter and Its Derivatives: NMR, DSC, X-ray, Rheological Investigation
Authors: Colella Maria Francesca , Marino Nadia , Oliviero Rossi Cesare , Seta Lucia , Caputo Paolino , De Luca Giuseppina
Published: January 2023

In recent years, the food industry has become increasingly involved in researching vegetable fats and oils with appropriate mechanical properties (ease of transport, processing, and storage) and a specific lipidic composition to ensure healthy products for consumers. The chemical–physical behavior of these matrices depends on their composition in terms of single fatty acids (FA). However, as we demonstrate in this work, these properties, as well as the absorption, digestion and uptake in humans of specific FAs, are also largely determined by their regiosomerism within the TriAcylGlycerols (TAG) moieties (sn-1,2,3 positions). The goal of this work is to study for the first time vegetable fats obtained directly from a sample of natural cocoa butter (CB) through a process that manipulates the distribution of FAs but not their nature. Even if the initial percentage of each FA in the mixture remains the same, CB derivatives seem to show improved chemical–physical features. In order to understand which factors account for their physical and chemical characteristics, and to check whether or not the obtained new matrices could be considered as valid alternatives to other vegetable fats (e.g., palm oil (PO)), we carried out an experimental investigation at both the macroscopic and molecular level including: (i) Differential Scanning Calorimetry (DSC) analyses to examine thermal features; (ii) rheological testing to explore mechanical properties; (iii) powder X-ray diffraction (PXRD) to evaluate the solid-state phases of the obtained fats; and (iv) 1H and 13C Nuclear Magnetic Resonance (NMR, 1D and 2D) spectroscopy to rapidly analyze fatty acid composition including regioisomeric distribution on the glycerol backbone. These last results open up the possibility of using NMR spectroscopy as an alternative to the chromatographic techniques routinely employed for the investigation of similar matrices.
Myelin Basic Protein Fragmentation by Engineered Human Proteasomes with Different Catalytic Phenotypes Revealed Direct Peptide Ligands of MS-Associated and Protective HLA Class I Molecules
Authors: Saratov George A. , Vladimirov Vasiliy I. , Novoselov Alexey L. , Ziganshin Rustam H. , Chen Guo , Baymukhametov Timur N. , Konevega Andrey L. , Belogurov Alexey A. , Kudriaeva Anna A.
Published: January 2023

Proteasomes exist in mammalian cells in multiple combinatorial variants due to the diverse regulatory particles and exchange of catalytic subunits. Here, using biotin carboxyl carrier domain of transcarboxylase from Propionibacterium shermanii fused with different proteasome subunits of catalytic and regulatory particles, we report comprehensive characterization of highly homogenous one-step purified human constitutive and immune 20S and 26S/30S proteasomes. Hydrolysis of a multiple sclerosis (MS) autoantigen, myelin basic protein (MBP), by engineered human proteasomes with different catalytic phenotypes, revealed that peptides which may be directly loaded on the HLA class I molecules are produced mainly by immunoproteasomes. We detected at least five MBP immunodominant core regions, namely, LPRHRDTGIL, SLPQKSHGR, QDENPVVHFF, KGRGLSLSRF and GYGGRASDY. All peptides, except QDENPVVHFF, which originates from the encephalitogenic MBP part, were associated with HLA I alleles considered to increase MS risk. Prediction of the affinity of HLA class I to this peptide demonstrated that MS-protective HLA-A*44 and -B*35 molecules are high-affinity binders, whereas MS-associated HLA-A*23, -A*24, -A*26 and -B*51 molecules tend to have moderate to low affinity. The HLA-A*44 molecules may bind QDENPVVHFF and its deamidated form in several registers with unprecedently high affinity, probably linking its distinct protective phenotype with thymic depletion of the repertoire of autoreactive cytotoxic T cells or induction of CD8+ regulatory T cells, specific to the encephalitogenic MBP peptide.
Are YouTube Videos a Useful and Reliable Source of Information for Patients with Temporomandibular Joint Disorders?
Authors: Vaira Luigi Angelo , Sergnese Silvia , Salzano Giovanni , Maglitto Fabio , Arena Antonio , Carraturo Emanuele , Abbate Vincenzo , Committeri Umberto , Vellone Valentino , Biglio Andrea , Lechien Jérome R. , De Riu Giacomo
Published: January 2023

Counseling is considered a first-line conservative therapy with respect to temporomandibular joint disorders (TMJD). Nowadays, 50 to 80% of patients acquire health information from the internet before turning to professionals. The purpose of this study has been to investigate the quality of information about TMJD that patients can obtain from YouTube. A YouTube.com search was conducted using the terms “temporomandibular joint disorder”; “limited movement of the mandible”; and “mandibular joint pain”. The videos identified were assessed independently by two panels of three professional and lay reviewers with HONcode, modified DISCERN (MD) and the global quality scale (GQS). A total of 106 videos were included. The professional reviewers reported a mean HONcode score of 4.148 ± 1.314 and a mean MD score of 2.519 ± 1.267, testifying to a modest general quality of the videos. The mean GQS score was 2.987 ± 1.012 for the professional and 3.469 ± 0.891 for the lay reviewers (p < 0.001). The correlations between the ratings were significant between the reviewers within the same group but not between the two groups. The presence of animations significantly influenced the GQS score expressed by the lay reviewers (p = 0.011) but not that of the professionals (p = 0.640). The quality of the information on TMJD on YouTube is generally of poor quality. Healthcare systems and professionals should be prepared to correct misinformation and build trusting relationships with patients which are based on quality counseling. Similarly, academic institutions should produce quality content that leads patients with TMJD toward a correct diagnostic-therapeutic process.
Diagnostic Efficiency of Pan-Immune-Inflammation Value to Predict Prostate Cancer in Patients with Prostate-Specific Antigen between 4 and 20 ng/mL
Authors: Zhu Meikai , Zhou Yongheng , Liu Zhifeng , Jiang Zhiwen , Qi Wenqiang , Chen Shouzhen , Wang Wenfu , Shi Benkang , Zhu Yaofeng
Published: January 2023

Introduction: To evaluate the predictive value of the pan-immune-inflammation value (PIV) and other systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), for prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) in patients with a prostate-specific antigen (PSA) value between 4 and 20 ng/mL. Patients and Methods: The clinical data of 319 eligible patients who underwent prostate biopsies in our hospital from August 2019 to June 2022 were retrospectively analyzed. CSPCa was defined as a “Gleason grade group of ≥2”. A univariable logistic regression analysis and multivariable logistic regression analysis were conducted to analyze the association between the PIV, SII, MLR, and PCa/CSPCa. For the inflammatory indicators included in the multivariable logistic regression analysis, we constructed models by combining the separate inflammatory indicator and other significant predictors and compared the area under the curve (AUC). A nomogram based on the PIV for PCa was developed. Results: We included 148 PCa patients (including 127 CSPCa patients) and 171 non-PCa patients in total. The patients with PCa were older, had higher MLR, SII, PIV, and total PSA (TPSA) values, consumed more alcohol, and had lower free/total PSA (f/T) values than the other patients. Compared with the non-CSPCa group, the CSPCa group had higher BMI, MLR, PIV, TPSA values, consumed more alcohol, and had lower f/T values. The univariable regression analysis showed that drinking history, higher MLR, PIV, and TPSA values, and lower f/T values were independent predictors of PCa and CSPCa. The AUC of the PIV in the multivariable logistic regression model was higher than those of the MLR and SII. In addition, the diagnostic value of the PIV + PSA for PCa was better than the PSA value. However, the diagnostic value for CSPCa was not significantly different from that of using PSA alone, while the AUC of the PIV + PSA was higher than the individual indicator of the PSA value. Conclusions: Our study suggests that for the patients who were diagnosed with PSA values between 4 and 20 ng/mL, the PIV and MLR are potential indicators for predicting PCa and CSPCa. In addition, our study indicates that the new inflammatory index PIV has clinical value in the diagnosis of PCa and CSPCa.
Would Surgeons Like to Be Submitted to Anal Fistulotomy? An International Web-Based Survey
Authors: Ratto Carlo , Marra Angelo Alessandro , Parello Angelo , De Simone Veronica , Campennì Paola , Litta Francesco
Published: January 2023

Traditional fistulotomy is the most performed surgical procedure in anal fistula surgery. We conducted an international online survey to explore colorectal surgeons’ opinions and preferences on fistulotomy. Considering the healing and continence impairment rates reported in the literature, surgeons were invited to answer as a hypothetic patient susceptible to being submitted to fistulotomy for low and high anal fistula. A total of 767 surgeons completed the survey from 72 countries. The majority of respondents were consultants, having treated more than 20 anal fistulas in the last year. Most of them declared that anal fistula would be able to negatively affect quality of life and would be worried/anxious about it. Taking into account all aspects, 87.5% and 37.8% of respondents would agree to be treated with a fistulotomy in case of a low and high fistula, respectively, with an acceptance rate that varied worldwide. At multivariate analysis, factors correlated to the acceptance of anal fistulotomy were male gender (p = 0.003), practice of less than 20 fistula operations during last year (p = 0.020), and low fistula (p < 0.001). Surgeons recognized the extreme complexity of this approach. This study highlighted the necessity of an accurate patients’ selection and the adoption of alternative strategy to reduce the risk of anal continence impairment.
Clinical Decision Making for Intraoperative Auditory Brainstem Response Testing in Children following Tympanostomy Tube Placement
Authors: Dietrich Maria , Schade Heike , Nadal Jennifer , Keiner Sabine , Schade Götz
Published: January 2023

Intraoperative auditory brainstem response (ioABR) testing following tympanostomy tube (TT) placement may be biased due to temporary threshold shifts (TTS). The purpose of the study was to assess the evidence for TTS in children who have undergone ioABR using prolonged latencies of wave I (males > 1.95 ms, females > 1.88 ms) as a marker of a persisting air–bone gap. Eighty-three children underwent ioABR following surgical procedures at University Hospital Bonn, Germany. The primary outcome measure was the latency of wave I at 80-dB SPL. The total sample consisted of 66 males (79.5%) and 17 females (20.5%) with a mean (SD) age of 46.4 (26.6) months. Of 163 operated ears (83 children), 72 (44.2%) had no middle ear fluid, 19 (11.6%) serous fluid, and 72 (44.2%) mucoid fluid. The risk of having a prolonged latency of wave I at 80-dB SPL was OR 4.61 (95% CI 2.01–10.59; p < 0.001) in those with mucoid fluid as compared to those without mucoid fluid. Intraoperative ABR results should account for sex differences and be interpreted with caution and be verified. Ultimately, parents should be engaged in a preoperative discussion to decide if an ioABR should be postponed if mucoid fluid was found.
Identification of a Novel Frameshift Variant of ARR3 Related to X-Linked Female-Limited Early-Onset High Myopia and Study on the Effect of X Chromosome Inactivation on the Myopia Severity
Authors: Xiao Xuan , Yang Jingmin , Li Ying , Yang Hongxia , Zhu Yijian , Li Lianbing , Zhou Qinlinglan , Lu Daru , Chen Ting , Tian Yafei
Published: January 2023

X-linked myopia 26 (Myopia 26, MIM #301010), which is caused by the variants of ARR3 (MIM *301770), is characterized by female-limited early-onset high myopia (eo-HM). Clinical characteristics include a tigroid appearance in the fundus and a temporal crescent of the optic nerve head. At present, the limited literature on eo-HM caused by ARR3 mutations shows that its inheritance mode is complex, which brings certain difficulties to pre-pregnancy genetic counseling, pre-implantation genetic diagnosis, and prenatal diagnosis. Here, we investigated the genetic underpinning of a Chinese family with eo-HM. Whole exome sequencing of the proband revealed a novel frameshift mutation in ARR3 (NM_004312, exon10, c.666delC, p. Asn222LysfsTer22). Although the mode of inheritance of the eo-HM family fits the X-linked pattern of ARR3, the phenotypes of three patients deviate from the typical early-onset high myopia. Through X-chromosome inactivation experiments, the patient’s different phenotypes can be precisely explained. In addition, this study not only enhanced the correlation between ARR3 and early-onset high myopia but also provided explanations for different phenotypes, which may inspire follow-up studies. Our results enrich the knowledge of the variant spectrum in ARR3 and provide critical information for preimplantation and prenatal genetic testing, diagnosis, and counseling.
Magnetic Nanomaterials Mediate Electromagnetic Stimulations of Nerves for Applications in Stem Cell and Cancer Treatments
Authors: Wang Lei , Duan Yefan , Lu Shujie , Sun Jianfei
Published: January 2023

Although some progress has been made in the treatment of cancer, challenges remain. In recent years, advancements in nanotechnology and stem cell therapy have provided new approaches for use in regenerative medicine and cancer treatment. Among them, magnetic nanomaterials have attracted widespread attention in the field of regenerative medicine and cancer; this is because they have high levels of safety and low levels of invasibility, promote stem cell differentiation, and affect biological nerve signals. In contrast to pure magnetic stimulation, magnetic nanomaterials can act as amplifiers of an applied electromagnetic field in vivo, and by generating different effects (thermal, electrical, magnetic, mechanical, etc.), the corresponding ion channels are activated, thus enabling the modulation of neuronal activity with higher levels of precision and local modulation. In this review, first, we focused on the relationship between biological nerve signals and stem cell differentiation, and tumor development. In addition, the effects of magnetic nanomaterials on biological neural signals and the tumor environment were discussed. Finally, we introduced the application of magnetic-nanomaterial-mediated electromagnetic stimulation in regenerative medicine and its potential in the field of cancer therapy.
Multisystem Inflammatory Syndrome in Adults (MIS-A) Reported in Patient with Hematological Malignancy: A Case Report
Authors: Kalicińska Elżbieta , Jabłonowska Paula , Wróbel Tomasz
Published: January 2023

Background: The coronavirus disease 2019 (COVID-19) has persisted for over 2 years worldwide and has long-term effects on the health and quality of life of convalescents. Multisystem inflammatory syndrome, primary observed in children is currently increasingly recognized in adults. Immunopathology might play a crucial role in the pathogenesis of multisystem inflammatory syndrome in adults (MIS-A); therefore, the occurrence of MIS-A in non-immunocompetent patients is a significant challenge in diagnosis and treatment. Case presentation: We described a 65-year-old patient with Waldenström’s macroglobulinemia (WM) who suffered from MIS-A after COVID-19 and was successfully treated with high doses of immunoglobulins and steroids. Conclusion: Our study presents for the first time a case of MIS-A in a hematological patient with a broad spectrum of symptoms reflecting multiorgan damage and suggests the long-term consequences of MIS-A as persistent immune dysregulation involving T-cell response.
Mesenchymal Stem Cell-Derived Exosomes Enhance 3D-Printed Scaffold Functions and Promote Alveolar Bone Defect Repair by Enhancing Angiogenesis
Authors: Sun Xiaodi , Mao Yupu , Liu Beibei , Gu Ke , Liu Han , Du Wei , Li Ruixin , Zhang Jian
Published: January 2023

The reconstruction of severe alveolar bone defects remains a complex and challenging field for clinicians. Three-dimensional-printed scaffolds can adapt precisely to the complicated shape of the bone defects, which is an alternative solution to bone tissue engineering. Our previous study constructed an innovative low-temperature 3D-printed silk fibroin/collagen I/nano-hydroxyapatite (SF/COL-I/nHA) composite scaffold with a stable structure and remarkable biocompatibility. However, the clinical translation of most scaffolds is limited by insufficient angiogenesis and osteogenesis. In this study, we investigated the effects of human umbilical cord mesenchymal-stem-cell-derived exosomes (hUCMSC-Exos) on bone regeneration, especially from the perspective of inducing angiogenesis. HUCMSC-Exos were isolated and characterized. In vitro, the effect of hUCMSC-Exos on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) was examined. Moreover, the loading and release of hUCMSC-Exos on 3D-printed SF/COL-I/nHA scaffolds were evaluated. In vivo, hUCMSC-Exos and 3D-printed SF/COL-I/nHA scaffolds were implanted into alveolar bone defects, and bone regeneration and angiogenesis were investigated by micro-CT, HE staining, Masson staining, and immunohistochemical analysis. The results showed that hUCMSC-Exos stimulated HUVEC proliferation, migration, and tube formation in vitro, and the effect increased with increasing exosome concentrations. In vivo, the combination of hUCMSC-Exos and 3D-printed SF/COL-I/nHA scaffolds promoted alveolar bone defect repair by enhancing angiogenesis and osteogenesis. We constructed an elaborate cell-free bone-tissue-engineering system by combining hUCMSC-Exos with 3D-printed SF/COL-I/nHA scaffolds, potentially providing new ideas for treating alveolar bone defects.
Agro-Ecological Impact of Irrigation and Nutrient Management on Spinach (Spinacia oleracea L.) Grown in Semi-Arid Conditions
Authors: Delgado-Iniesta María José , Girona-Ruíz Aldara , Sánchez-Navarro Antonio
Published: January 2023

The environment is affected by most anthropogenic activities; among them, agriculture is one activity with more negative effects, especially when management is inadequate, causing soil degradation or contamination. This paper presents the results of an agronomic field trial on a spinach (Spinacia oleracea L.) crop. The objective of which was to monitor soil and crop properties under two doses of irrigation and organic fertilization. The results showed that the use of excessive doses of irrigation and fertilization increased the electrical conductivity (ECext) from 5.5 to 8.5 dS m−1 and the concentration of ions in the soil solution which, for the most soluble ions (NO3−, Cl−, Na+), leached towards the deep horizons, reaching 2194.8 mg L−1 in the case of NO3−. However, their use did not increase spinach production and is thus a waste of resources that increases the risk of soil salinization. Nutrient inputs to the soil were much higher than extractions (between 12% for N and 99% for Fe), partly because of agronomic management and especially because of the return of crop residues, which increased the organic carbon stock by about 2500 kg ha−1 (4–6%), enhancing its function as a CO2 sink. These surpluses form part of complex organic structures or are immobilized as carbonates or alkaline phosphates. Preservation of the agrosystem studied requires limiting the use of low-quality irrigation water and adjusting fertilization.
Endoscopic Vacuum Therapy (EVT) versus Self-Expandable Metal Stent (SEMS) for Anastomotic Leaks after Upper Gastrointestinal Surgery: Systematic Review and Meta-Analysis
Authors: Mandarino Francesco Vito , Barchi Alberto , D’Amico Ferdinando , Fanti Lorella , Azzolini Francesco , Viale Edi , Esposito Dario , Rosati Riccardo , Fiorino Gionata , Bemelman Willem Adrianus , Elmore Ugo , Barbieri Lavinia , Puccetti Francesco , Testoni Sabrina Gloria Giulia , Danese Silvio
Published: January 2023

Background: Endoscopic treatment of post-esophagectomy/gastrectomy anastomotic dehiscence includes Self-Expandable Metal Stents (SEMS), which have represented the “gold standard” for many years, and Endoscopic Vacuum Therapy (EVT), which was recently introduced, showing promising results. The aim of the study was to compare outcomes of SEMS and EVT in the treatment of post-esophagectomy/gastrectomy anastomotic leaks, focusing on oncologic surgery. Methods: A systematic search was performed on Pubmed and Embase, identifying studies comparing EVT versus SEMS for the treatment of leaks after upper gastro-intestinal surgery for malignant or benign pathologies. The primary outcome was the rate of successful leak closure. A meta-analysis was conducted, performing an a priori-defined subgroup analysis for the oncologic surgery group. Results: Eight retrospective studies with 357 patients were eligible. Overall, the EVT group showed a higher success rate (odd ratio [OR] 2.58, 95% CI 1.43–4.66), a lower number of devices (pooled mean difference [pmd] 4.90, 95% CI 3.08–6.71), shorter treatment duration (pmd −9.18, 95% CI −17.05–−1.32), lower short-term complication (OR 0.35, 95% CI 0.18–0.71) and mortality rates (OR 0.47, 95% CI 0.24–0.92) compared to stenting. In the oncologic surgery subgroup analysis, no differences in the success rate were found (OR 1.59, 95% CI 0.74–3.40, I2 = 0%). Conclusions: Overall, EVT has been revealed to be more effective and less burdened by complications compared to stenting. In the oncologic surgery subgroup analysis, efficacy rates were similar between the two groups. Further prospective data need to define a unique management algorithm for anastomotic leaks.
Biosensors Based on Phenol Oxidases (Laccase, Tyrosinase, and Their Mixture) for Estimating the Total Phenolic Index in Food-Related Samples
Authors: Tarasov Aleksey , Stozhko Natalia , Bukharinova Maria , Khamzina Ekaterina
Published: January 2023

Plant phenolic compounds demonstrate bioactive properties in vitro and/or in vivo, which creates demand for their precise determination in life sciences and industry. Measuring the concentration of individual phenolic compounds is a complex task, since approximately 9000 plant phenolic substances have been identified so far. The determination of the total phenolic content (TPC) is less laborious and is used for the qualimetric evaluation of complex multicomponent samples in routine analyses. Biosensors based on phenol oxidases (POs) have been proposed as alternative analytical devices for detecting phenolic compounds; however, their effectiveness in the analysis of food and vegetal matrices has not been addressed in detail. This review describes catalytic properties of laccase and tyrosinase and reports on the enzymatic and bienzymatic sensors based on laccase and tyrosinase for estimating the total phenolic index (TPI) in food-related samples (FRSs). The review presents the classification of biosensors, POs immobilization, the functions of nanomaterials, the biosensing catalytic cycle, interference, validation, and some other aspects related to TPI assessment. Nanomaterials are involved in the processes of immobilization, electron transfer, signal formation, and amplification, and they improve the performance of PO-based biosensors. Possible strategies for reducing interference in PO-based biosensors are discussed, namely the removal of ascorbic acid and the use of highly purified enzymes.
Fabrication, Structural and Biological Characterization of Zinc-Containing Bioactive Glasses and Their Use in Membranes for Guided Bone Regeneration
Authors: Gavinho Sílvia R. , Pádua Ana Sofia , Sá-Nogueira Isabel , Silva Jorge C. , Borges João P. , Costa Luis C. , Graça Manuel Pedro F.
Published: January 2023

Polymeric membranes are widely used in guided bone regeneration (GBR), particularly in dentistry. In addition, bioactive glasses can be added to the polymers in order to develop a matrix that is osteoconductive and osteoinductive, increasing cell adhesion and proliferation. The bioactive glasses allow the insertion into its network of therapeutic ions in order to add specific biological properties. The addition of zinc into bioactive glasses can promote antibacterial activity and induce the differentiation and proliferation of the bone cells. In this study, bioactive glasses containing zinc (0.25, 0.5, 1 and 2 mol%) were developed and structurally and biologically characterized. The biological results show that the Zn-containing bioactive glasses do not present significant antibacterial activity, but the addition of zinc at the highest concentration does not compromise the bioactivity and promotes the viability of Saos-2 cells. The cell culture assays in the membranes (PCL, PCL:BG and PCL:BGZn2) showed that zinc addition promotes cell viability and an increase in alkaline phosphatase (ALP) production.
A p–n Junction by Coupling Amine-Enriched Brookite–TiO2 Nanorods with CuxS Nanoparticles for Improved Photocatalytic CO2 Reduction
Authors: Chen Zhangjing , Zhu Xueteng , Xiong Jinyan , Wen Zhipan , Cheng Gang
Published: January 2023

Photocatalytic CO2 reduction is a promising technology for reaching the aim of “carbon peaking and carbon neutrality”, and it is crucial to design efficient photocatalysts with a rational surface and interface tailoring. Considering that amine modification on the surface of the photocatalyst could offer a favorable impact on the adsorption and activation of CO2, in this work, amine-modified brookite TiO2 nanorods (NH2-B-TiO2) coupled with CuxS (NH2-B-TiO2-CuxS) were effectively fabricated via a facile refluxing method. The formation of a p–n junction at the interface between the NH2-B-TiO2 and the CuxS could facilitate the separation and transfer of photogenerated carriers. Consequently, under light irradiation for 4 h, when the CuxS content is 16%, the maximum performance for conversion of CO2 to CH4 reaches at a rate of 3.34 μmol g−1 h−1 in the NH2-B-TiO2-CuxS composite, which is approximately 4 times greater than that of pure NH2-B-TiO2. It is hoped that this work could deliver an approach to construct an amine-enriched p–n junction for efficient CO2 photoreduction.
Hydration Characteristics and Early Strength Evolution of Classified Fine Tailings Cemented Backfill
Authors: Kou Yunpeng , Deng Yuchao , Tan Yuye , Han Chongchong , Song Weidong
Published: January 2023

To explore the hydration characteristics and early strength evolution of classified fine tailings cemented backfill (CFTCB), a nuclear magnetic resonance (NMR) analysis and a volume resistivity test were performed on classified fine tailings filling slurry (CFTFS). The early hydration products of CFTCB were studied by scanning electron microscopy (SEM) and X-ray diffraction (XRD) phase analysis. Uniaxial compressive strength (UCS) test was carried out, and the microscopic characteristics and strength rules of the hydration reaction of CFTCB were analyzed. Based on the experiment, we found the law of water content change and porosity evolution. The early hydration reaction can be divided into the dissolution, setting, and hardening stages. The volume resistivity test results show that the volume resistance of filling slurry increases slowly at first then decreases, and finally increases rapidly. The variation trend of volume resistivity is related to the degree of hydration reaction. When combined with the hydration characteristics of backfill materials, the hydration reaction rate determines the growth rate of early strength of backfill, and the formation of hydration products is the reason for the early strength increase in backfill. The research conclusion has an important theoretical guiding value and engineering significance in mine filling production organization and filling ratio parameter optimization.