bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Erythropoiesis by a Phytoestrogen Diarylheptanoid from Curcuma comosa
Authors: Bhukhai Kanit , Fouquet Guillemette , Rittavee Yutthana , Tanhuad Nopmullee , Lakmuang Chaiyaporn , Borwornpinyo Suparerk , Anurathapan Usanarat , Suksamrarn Apichart , Piyachaturawat Pawinee , Chairoungdua Arthit , Hermine Olivier , Hongeng Suradej
Published: June 2022

Erythropoietin (Epo) is widely used for the treatment of anemia; however, non-hematopoietic effects and cancer risk limit its clinical applications. Therefore, alternative molecules to improve erythropoiesis in anemia patients are urgently needed. Here, we investigated the potential effects of a phytoestrogen diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, (ASPP 049) isolated from Curcuma comosa on promoting erythropoiesis. Treatment with C. comosa extract improved anemia symptoms demonstrated by increasing red blood cell numbers, hematocrit, and hemoglobin content in anemic mice. In addition, ASPP 049, the major compound isolated from C. comosa, enhanced the suboptimal Epo dosages to improve erythroid cell differentiation from hematopoietic stem cells, which was inhibited by the estrogen receptor (ER) antagonist, ICI 182,780. Moreover, the ASPP 049-activated Epo-Epo receptor (EpoR) complex subsequently induced phosphorylation of EpoR-mediated erythropoiesis pathways: STAT5, MAPK/ERK, and PI3K/AKT in Epo-sensitive UT-7 cells. Taken together, these results suggest that C. comosa extract and ASPP 049 increased erythropoiesis through ER- and EpoR-mediated signaling cascades. Our findings provide insight into the specific interaction between a phytoestrogen diarylheptanoid and Epo-EpoR in a hematopoietic system for the potential treatment of anemia.
Ldlr-Deficient Mice with an Atherosclerosis-Resistant Background Develop Severe Hyperglycemia and Type 2 Diabetes on a Western-Type Diet
Authors: Shi Weibin , Li Jing , Bao Kelly , Chen Mei-Hua , Liu Zhenqi
Published: June 2022

Apoe-/- and Ldlr-/- mice are two animal models extensively used for atherosclerosis research. We previously reported that Apoe-/- mice on certain genetic backgrounds, including C3H/HeJ (C3H), develop type 2 diabetes when fed a Western diet. We sought to characterize diabetes-related traits in C3H-Ldlr-/- mice through comparing with C3H-Apoe-/- mice. On a chow diet, Ldlr-/- mice had lower plasma total and non-HDL cholesterol levels but higher HDL levels than Apoe-/- mice. Fasting plasma glucose was much lower in Ldlr-/- than Apoe-/- mice (male: 122.5 ± 5.9 vs. 229.4 ± 17.5 mg/dL; female: 144.1 ± 12.4 vs. 232.7 ± 6.4 mg/dL). When fed a Western diet, Ldlr-/- and Apoe-/- mice developed severe hypercholesterolemia and also hyperglycemia with fasting plasma glucose levels exceeding 250 mg/dL. Both knockouts had similar non-HDL cholesterol and triglyceride levels, and their fasting glucose levels were also similar. Male Ldlr-/- mice exhibited greater glucose tolerance and insulin sensitivity compared to their Apoe-/- counterpart. Female mice showed similar glucose tolerance and insulin sensitivity though Ldlr-/- mice had higher non-fasting glucose levels. Male Ldlr-/- and Apoe-/- mice developed moderate obesity on the Western diet, but female mice did not. These results indicate that the Western diet and ensuing hyperlipidemia lead to the development of type 2 diabetes, irrespective of underlying genetic causes.
Antibacterial and Anti-Inflammatory Effects of Apolipoprotein E
Authors: Puthia Manoj , Marzinek Jan K. , Petruk Ganna , Ertürk Bergdahl Gizem , Bond Peter J. , Petrlova Jitka
Published: June 2022

Apolipoprotein E (APOE) is a lipid-transport protein that functions as a key mediator of lipid transport and cholesterol metabolism. Recent studies have shown that peptides derived from human APOE display anti-inflammatory and antimicrobial effects. Here, we applied in vitro assays and fluorescent microscopy to investigate the anti-bacterial effects of full-length APOE. The interaction of APOE with endotoxins from Escherichia coli was explored using surface plasmon resonance, binding assays, transmission electron microscopy and all-atom molecular dynamics (MD) simulations. We also studied the immunomodulatory activity of APOE using in vitro cell assays and an in vivo mouse model in combination with advanced imaging techniques. We observed that APOE exhibits anti-bacterial activity against several Gram-negative bacterial strains of Pseudomonas aeruginosa and Escherichia coli. In addition, we showed that APOE exhibits a significant binding affinity for lipopolysaccharide (LPS) and lipid A as well as heparin. MD simulations identified the low-density lipoprotein receptor (LDLR) binding region in helix 4 of APOE as a primary binding site for these molecules via electrostatic interactions. Together, our data suggest that APOE may have an important role in controlling inflammation during Gram-negative bacterial infection.
Prevalence of Hearing Impairment by Age: 2nd to 10th Decades of Life
Authors: Wasano Koichiro , Nakagawa Takashi , Ogawa Kaoru
Published: June 2022

Background: Accurate data on the prevalence of hearing impairment and severity across age and gender are paramount to formulate hearing health policies. Here, we sought to analyze audiometric data from a large group of age-diverse people in Japan, which has not been previously described in detail. Methods: We analyzed retrospective hearing threshold data of 23,860 participants (10–99 years; left-right hearing threshold difference <15 dB; air-bone gap ≤10 dB) at 500, 1000, 2000, and 4000 Hz, and then classified them for hearing impairment severity according to the WHO Classification. Findings: There was a significant gender difference in median hearing thresholds, starting in 20-year-olds up to early 80-year-olds. Twenty-five percent of men in their late 50s had some level of HI, ~50% in their late 60s, and ~75% in their late 70s. For women, 25% had some level of HI in their early 60s, ~50% in their early 70s, and ~75% in their late 70s. For participants in their early 80s, 50% of either gender had moderate or more severe HI. Interpretation: Our results, derived from a large number of participants, provide basic information about the prevalence of hearing loss by age decade. Since people can expect to live longer than those in previous generations, our detailed data can inform national social systems responsible for hearing screening in making decisions about hearing-aid qualification, which may reduce barriers to older people’s independence, productivity, and quality of life.
Urinary MicroRNA Sensing Using Electrochemical Biosensor to Evaluate Colorectal Cancer Progression
Authors: Pang Sow-Neng , Lin Yu-Lun , Chiou Yueh-Er , Leung Wai-Hung , Weng Wen-Hui
Published: June 2022

Research in cancer diagnostics has recently established its footing and significance in the biosensor sphere, emphasizing the idea of a unique probe design used as a sensor and actuator, to identify the presence of protein, DNA, RNA, or miRNA. The fluorescein isothiocyanate (FITC) probe and biotinylated probe are designed for a two-pronged approach to the detection of the urinary miR-21 and miR-141, both of which have demonstrated significance in the development and progression of colorectal cancer, a leading cause of mortality and morbidity. The remainder of the apparatus is composed of a modified screen-printed carbon electrode (SPCE), to which the probes adhere, that transduces signals via the redox reaction between H2O2 and HRP, measured with chronoamperometry and cyclic voltammetry. The precise nature of our ultra-non-invasive biosensor makes for a highly sensitive and practical cancer detector, concluded by the significance when establishing disease presence (miR-21 p-value = 0.0176, miR-141 p-value = 0.0032), disease follow-up (miR-21 p-value = 0.00154, miR141 p-value < 0.0005), and even disease severity. This article hopes to emphasize the potential of an additional clinical tool for the management of colorectal cancer.
Gene Expression-Based Functional Differences between the Bladder Body and Trigonal Urothelium in Adolescent Female Patients with Micturition Dysfunction
Authors: Zeber-Lubecka Natalia , Kulecka Maria , Załęska-Oracka Katarzyna , Dąbrowska Michalina , Bałabas Aneta , Hennig Ewa E. , Szymanek-Szwed Magdalena , Mikula Michał , Jurkiewicz Beata , Ostrowski Jerzy
Published: June 2022

The aim of this study is to determine the molecular differences between the urothelial transcriptomes of the bladder body and trigone. The transcriptomes of the bladder body and trigonal epithelia were analyzed by massive sequencing of total epithelial RNA. The profiles of urothelial and urinal microbiomes were assessed by amplicon sequencing of bacterial 16S rRNA genes in 17 adolescent females with pain and micturition dysfunction and control female subjects. The RNA sequencing identified 10,261 differentially expressed genes (DEGs) in the urothelia of the bladder body and trigone, with the top 1000 DEGs at these locations annotated to 36 and 77 of the Reactome-related pathways in the bladder body and trigone, respectively. These pathways represented 11 categories enriched in the bladder body urothelium, including extracellular matrix organization, the neuronal system, and 15 categories enriched in the trigonal epithelium, including RHO GTPase effectors, cornified envelope formation, and neutrophil degranulation. Five bacterial taxa in urine differed significantly in patients and healthy adolescent controls. The evaluation of their transcriptomes indicated that the bladder body and trigonal urothelia were functionally different tissues. The molecular differences between the body and trigonal urothelia responsible for clinical symptoms in adolescents with bladder pain syndrome/interstitial cystitis remain unclear.
Phthalate Exposure and Oxidative/Nitrosative Stress in Childhood Asthma: A Nested Case-Control Study with Propensity Score Matching
Authors: Chang Jung-Wei , Chen Hsin-Chang , Hu Heng-Zhao , Chang Wan-Ting , Huang Po-Chin , Wang I-Jen
Published: June 2022

Whether low-dose phthalate exposure triggers asthma among children, and its underlying mechanisms, remain debatable. Here, we evaluated the individual and mixed effects of low-dose phthalate exposure on children with asthma and five (oxidative/nitrosative stress/lipid peroxidation) mechanistic biomarkers—8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-isoprostaglandin F2α (8-isoPF2α), and malondialdehyde (MDA)—using a propensity score-matched case-control study (case vs. control = 41 vs. 111). The median monobenzyl phthalate (MBzP) concentrations in the case group were significantly higher than those in the control group (3.94 vs. 2.52 ng/mL, p = 0.02), indicating that dust could be an important source. After adjustment for confounders, the associations of high monomethyl phthalate (MMP) (75th percentile) with 8-NO2Gua (adjusted odds ratio (aOR): 2.66, 95% confidence interval (CI): 1.03–6.92) and 8-isoPF2α (aOR: 4.04, 95% CI: 1.51–10.8) and the associations of mono-iso-butyl phthalate (MiBP) with 8-isoPF2α (aOR: 2.96, 95% CI: 1.13–7.79) were observed. Weighted quantile sum regression revealed that MBzP contributed more than half of the association (56.8%), followed by MiBP (26.6%) and mono-iso-nonyl phthalate (MiNP) (8.77%). Our findings supported the adjuvant effect of phthalates in enhancing the immune system response.
Clinical Application for Tissue Engineering Focused on Materials
Authors: Kitsuka Takahiro , Hama Rikako , Ulziibayar Anudari , Matsuzaki Yuichi , Kelly John , Shinoka Toshiharu
Published: June 2022

Cardiovascular-related medical conditions remain a significant cause of death worldwide despite the advent of tissue engineering research more than half a century ago. Although autologous tissue is still the preferred treatment, donor tissue is limited, and there remains a need for tissue-engineered vascular grafts (TEVGs). The production of extensive vascular tissue (>1 cm3) in vitro meets the clinical needs of tissue grafts and biological research applications. The use of TEVGs in human patients remains limited due to issues related to thrombogenesis and stenosis. In addition to the advancement of simple manufacturing methods, the shift of attention to the combination of synthetic polymers and bio-derived materials and cell sources has enabled synergistic combinations of vascular tissue development. This review details the selection of biomaterials, cell sources and relevant clinical trials related to large diameter vascular grafts. Finally, we will discuss the remaining challenges in the tissue engineering field resulting from complex requirements by covering both basic and clinical research from the perspective of material design.
SMART-LAMP: A Smartphone-Operated Handheld Device for Real-Time Colorimetric Point-of-Care Diagnosis of Infectious Diseases via Loop-Mediated Isothermal Amplification
Authors: García-Bernalt Diego Juan , Fernández-Soto Pedro , Márquez-Sánchez Sergio , Santos Santos Daniel , Febrer-Sendra Begoña , Crego-Vicente Beatriz , Muñoz-Bellido Juan Luis , Belhassen-García Moncef , Corchado Rodríguez Juan M. , Muro Antonio
Published: June 2022

Nucleic acid amplification diagnostics offer outstanding features of sensitivity and specificity. However, they still lack speed and robustness, require extensive infrastructure, and are neither affordable nor user-friendly. Thus, they have not been extensively applied in point-of-care diagnostics, particularly in low-resource settings. In this work, we have combined the loop-mediated isothermal amplification (LAMP) technology with a handheld portable device (SMART-LAMP) developed to perform real-time isothermal nucleic acid amplification reactions, based on simple colorimetric measurements, all of which are Bluetooth-controlled by a dedicated smartphone app. We have validated its diagnostic utility regarding different infectious diseases, including Schistosomiasis, Strongyloidiasis, and COVID-19, and analyzed clinical samples from suspected COVID-19 patients. Finally, we have proved that the combination of long-term stabilized LAMP master mixes, stored and transported at room temperature with our developed SMART-LAMP device, provides an improvement towards true point-of-care diagnosis of infectious diseases in settings with limited infrastructure. Our proposal could be easily adapted to the diagnosis of other infectious diseases.
Scientific Landscape of Embodied Experience in the Virtual Environment: A Bibliometric Analysis
Authors: Lee Sanghee , Park Eun Joo
Published: June 2022

The realm of architecture has been influenced by the expansion in virtual environments (VEs), along with Industry 4.0 technologies transforming human–VE interactions. Despite increasing scholarly interest in embodied experience-integrated VE, there have been few comprehensive literature reviews undertaken on VEs from a holistic experience perspective. Therefore, this article reviews the literature on the embodied experiential dimension of VEs that has become necessary to adapt theories and methodologies in a way that enhances the user experience in a VE. This study employs a bibliometric analysis to review research performance and undertake a science mapping of the literature. The 969 pieces of data retrieved from Web of Science were subjected to a performance analysis, and VOSviewer was used to visualize the intellectual structure and research themes. The results of this study emphasize the strength and growing interest in VEs from the embodied experience perspective. Another significant finding is that VE experience studies are mostly based on embodied technologies. In this paper, the results of analyses are discussed in terms of productivity, collaboration, and research themes for future. This study contributes to the literature by providing a significant theoretical reference for the potential of the embodied experience in VE research, which will mostly attract the interest of architectural design researchers.
Position Paper Introducing a Sustainable, Universal Approach to Retrofitting Residential Buildings
Authors: Fedorczak-Cisak Małgorzata , Bomberg Mark , Yarbrough David W. , Lingo Lowell E. , Romanska-Zapala Anna
Published: June 2022

Protests during the 2021 Climate Conference in Glasgow exemplified our dilemma. The establishment perpetuates old thinking, while young people demand a new approach to mitigate the impact of climate change. The authors agree with the young people, and as a solution we propose to replace the current fragmentary approach with a new holistic one. The passive house approach that was conceptualized by the University of Illinois and built in Canada in 1977 showed us that energy consumption can be reduced about half of that used in the traditional design. Seventeen years later, a European passive house was built in Darmstadt. In 2008, a demonstration house in Syracuse, NY, showed that integrated passive measures produced energy use by about half of the NY state code for 2004. At the same time, some advanced houses in the USA showed total energy use of about 70 kWh/(m2∙y). In 2008, at the first Building Enclosure Science and Technology Conference, two equally important objectives for 2030 were proposed by the Lawrence Berkeley National Laboratory: (1) a 90% reduction of energy use in new buildings and (2) 50% for the retrofitting of existing buildings, i.e., to the level achieved in the 1980s. The first objective has recently been achieved in small buildings while the large residential buildings remain on the level obtained in the 2000s. Yet, the retrofitting of existing buildings (the second objective) has been a dismal failure. This paper acknowledges progress in hydronic heating and cooling involving electric heat pumps and hybrid solar panels, building automatics used for operation of HVAC, and modification of air distribution systems that comes from experience with the SARS-CoV-2 pandemic. Furthermore, it highlights that to accelerate energy efficiency and carbon emission reductions, there must be broad public-private educational programs with demonstrations of a new generation of retrofitting. Economically and ecologically retrofitted buildings will create a new approach to real estate investment.
Perioperative Carcinoid Crisis: A Systematic Review and Meta-Analysis
Authors: Xu Aileen , Suz Pilar , Reljic Tea , Are Abhirup C. , Kumar Ambuj , Powers Benjamin , Strosberg Jonathan , Denbo Jason W. , Fleming Jason B. , Anaya Daniel A.
Published: June 2022

Background: Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication. Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting its use. We sought to evaluate existing evidence characterizing CC and evaluating the efficacy of prophylactic octreotide. Methods: A systematic review was performed on studies including patients having surgery for well-differentiated NET and/or NET liver metastasis (2000–2021), and reporting data on the incidence, risk factors, or prognosis of CC, and/or use of prophylactic octreotide. Meta-analysis was performed using random-effects models. Results: Eight studies met inclusion criteria (n = 943 operations). The pooled incidence of CC was 19% (95% CI [0.06–0.36]). Liver metastasis (odds ratio 2.85 [1.49–5.47]) and gender (male 0.58 [0.34–0.99]) were the only significant risk factors. The occurrence of CC was associated with increased risk of major postoperative complications (2.12 [1.03–4.35]). The use of prophylactic octreotide was not associated with decreased risk of CC (0.73 [0.32–1.66]). Notably, there was no standard prophylactic octreotide strategy used. Conclusions: Intraoperative carcinoid crisis is a common complication occurring in up to 20% of patients with midgut NET and/or liver metastasis undergoing surgery. Prophylactic octreotide may not provide an efficient way to prevent this complication. Future studies should focus on prospective evaluation of well-defined prophylactic protocols using a standardized definition for CC.
Central Nervous System Progression in Primary Vitreoretinal Lymphoma with Bilateral and Unilateral Involvement: A Systematic Review and Meta-Analysis
Authors: van Rooij Josephus L. M. , Tokarska Klaudia A. , ten Dam-van Loon Ninette H. , Wessels Peter H. , Seute Tatjana , Minnema Monique C. , Snijders Tom J.
Published: June 2022

Background: Primary vitreoretinal lymphoma (PVRL) is either unilateral or bilateral at initial presentation. Progression to a central nervous system (CNS) lymphoma is regularly observed and these patients seem to have an inferior survival. Knowledge of the predictive value of laterality for CNS progression may facilitate risk stratification and the development of more effective treatment strategies, and eventually, improve outcomes. The objective of this analysis is to estimate the risk of CNS progression for patients with bilateral versus unilateral involvement of PVRL. Methods: Systematic literature search for studies on CNS progression in PVRL with bilateral and unilateral involvement according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We assessed the risk of bias and the methodological quality of studies using the Quality in Prognosis Studies (QUIPS) tool. Risk ratios of CNS progression in PVRL with bilateral and unilateral involvement were calculated and combined via a meta-analysis. Results: Twenty-five small-sized (total n = 371 cases) studies were included. The majority of the studies were at medium to high risk of bias. Results suggest no significant difference in CNS progression between bilateral and unilateral PVRL, with a pooled relative risk ratio of 1.12 (95% confidence interval 0.89–1.41). Conclusions: CNS progression is common in PVRL. From the limited available evidence, there is no significant difference in CNS progression between bilateral and unilateral PVRL.
Oncogenic Signalling of PEAK2 Pseudokinase in Colon Cancer
Authors: Lecointre Céline , Fourgous Elise , Montarras Ingrid , Kerneur Clément , Simon Valérie , Boublik Yvan , Bonenfant Débora , Robert Bruno , Martineau Pierre , Roche Serge
Published: June 2022

The PEAK family pseudokinases are essential components of tyrosine kinase (TK) pathways that regulate cell growth and adhesion; however, their role in human cancer remains unclear. Here, we report an oncogenic activity of the pseudokinase PEAK2 in colorectal cancer (CRC). Notably, high PRAG1 expression, which encodes PEAK2, was associated with a bad prognosis in CRC patients. Functionally, PEAK2 depletion reduced CRC cell growth and invasion in vitro, while its overexpression increased these transforming effects. PEAK2 depletion also reduced CRC development in nude mice. Mechanistically, PEAK2 expression induced cellular protein tyrosine phosphorylation, despite its catalytic inactivity. Phosphoproteomic analysis identified regulators of cell adhesion and F-actin dynamics as PEAK2 targets. Additionally, PEAK2 was identified as a novel ABL TK activator. In line with this, PEAK2 expression localized at focal adhesions of CRC cells and induced ABL-dependent formation of actin-rich plasma membrane protrusions filopodia that function to drive cell invasion. Interestingly, all these PEAK2 transforming activities were regulated by its main phosphorylation site, Tyr413, which implicates the SRC oncogene. Thus, our results uncover a protumoural function of PEAK2 in CRC and suggest that its deregulation affects adhesive properties of CRC cells to enable cancer progression.
mpMRI-US Fusion-Guided Targeted Cryotherapy in Patients with Primary Localized Prostate Cancer: A Prospective Analysis of Oncological and Functional Outcomes
Authors: Fernández-Pascual Esaú , Manfredi Celeste , Martín Cristina , Martínez-Ballesteros Claudio , Balmori Carlos , Lledó-García Enrique , Quintana Luis Miguel , Curvo Raphael , Carballido-Rodríguez Joaquín , Bianco Fernando J. , Martínez-Salamanca Juan Ignacio
Published: June 2022

Targeted therapy (TT) for prostate cancer (PCa) aims to ablate the malignant lesion with an adequate margin of safety in order to obtain similar oncological outcomes, but with less toxicity than radical treatments. The main aim of this study was to evaluate the recurrence rate (RR) in patients with primary localized PCa undergoing mpMRI/US fusion targeted cryotherapy (FTC). A secondary objective was to evaluate prostate-specific antigen (PSA) as a predictor of recurrences. We designed a prospective single-center single-cohort study. Patients with primary localized PCa, mono or multifocal lesions, PSA ≤ 15 ng/mL, and a Gleason score (GS) ≤ 4 + 3 undergoing FTC were enrolled. RR was chosen as the primary outcome. Recurrence was defined as the presence of clinically significant prostate cancer in the treated areas. PSA values measured at different times were tested as predictors of recurrence. Continuous variables were assessed with the Bayesian t-test and categorical assessments with the chix-squared test. Univariate and logistic regression assessment were used for predictions. A total of 75 cases were included in the study. Ten subjects developed a recurrence (RR: 15.2%), while fifty-six (84.8%) patients showed a recurrence-free status. A %PSA drop of 31.5% during the first 12 months after treatment predicted a recurrence with a sensitivity of 53.8% and a specificity of 79.2%. A PSA drop of 55.3% 12 months after treatment predicted a recurrence with a sensitivity of 91.7% and a specificity of 51.9%. FTC for primary localized PCa seems to be associated with a low but not negligible percentage of recurrences. Serum PSA levels may have a role indicating RR.
Underlying Facets of Cancer Metastasis
Authors: Tyagi Abhishek
Published: June 2022

Even though metastasis, a hallmark of cancer, is responsible for up to 90% of cancer-related mortality, it is still the least understood aspect of cancer pathogenesis [...]
Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond
Authors: Pozzo Federico , Bittolo Tamara , Tissino Erika , Zucchetto Antonella , Bomben Riccardo , Polcik Laura , Dannewitz Prosseda Svenja , Hartmann Tanja Nicole , Gattei Valter
Published: June 2022

The Notch signaling pathway plays a fundamental role for the terminal differentiation of multiple cell types, including B and T lymphocytes. The Notch receptors are transmembrane proteins that, upon ligand engagement, undergo multiple processing steps that ultimately release their intracytoplasmic portion. The activated protein ultimately operates as a nuclear transcriptional co-factor, whose stability is finely regulated. The Notch pathway has gained growing attention in chronic lymphocytic leukemia (CLL) because of the high rate of somatic mutations of the NOTCH1 gene. In CLL, NOTCH1 mutations represent a validated prognostic marker and a potential predictive marker for anti-CD20-based therapies, as pathological alterations of the Notch pathway can provide significant growth and survival advantage to neoplastic clone. However, beside NOTCH1 mutation, other events have been demonstrated to perturb the Notch pathway, namely somatic mutations of upstream, or even apparently unrelated, proteins such as FBXW7, MED12, SPEN, SF3B1, as well as physiological signals from other pathways such as the B-cell receptor. Here we review these mechanisms of activation of the NOTCH1 pathway in the context of CLL; the resulting picture highlights how multiple different mechanisms, that might occur under specific genomic, phenotypic and microenvironmental contexts, ultimately result in the same search for proliferative and survival advantages (through activation of MYC), as well as immune escape and therapy evasion (from anti-CD20 biological therapies). Understanding the preferential strategies through which CLL cells hijack NOTCH1 signaling may present important clues for designing targeted treatment strategies for the management of CLL.
Solvent Effect in Catalytic Lignin Hydrogenolysis
Authors: Panke Dennis , Bechthold German , Müller Thomas E.
Published: June 2022

The solvent effect in the catalytic depolymerization of the three-dimensional network of lignin is discussed based on recent reports in this field. Also, the results of an experimental study on the depolymerization of kraft lignin are presented. The cleavage of ether bonds within the lignin network was promoted using ruthenium and platinum on activated carbon (Ru/C and Pt/C), two common hydrogenolysis catalysts. Methanol was identified as a suitable solvent. Noteworthy, under the chosen reaction conditions, the catalysts showed significant resilience to the sulfur present in kraft lignin. The conversion of kraft lignin to lignin oil was strongly affected by the reaction conditions. Although the Ru/C catalyst provided the highest yield at supercritical conditions, a maximum yield was obtained for the Pt/C catalyst at near-critical conditions. The formation of guaiacol, 4-alkylguaiacols, isoeugenol, and 4-ethyl-2,6-dimethoxyphenol is attributed to the solubility of oligomeric lignin fragments in the solvent and the relative propensity of specific groups to adsorb on the catalyst surface.
Circular RNA as a Novel Biomarker and Therapeutic Target for HCC
Authors: Meng Hongwu , Niu Ruowen , Huang Cheng , Li Jun
Published: June 2022

Circular RNA (circRNA) is a kind of endogenous non-coding RNA (ncRNA), which is produced by the reverse splicing of precursor mRNA (pre mRNA). It is widely expressed in a variety of biological cells. Due to the special formation mode, circRNA does not have a 5′ terminal cap and 3′ poly (A) tail structure. Compared with linear RNA, circRNA is more stable to exonuclease and ribonuclease. In addition, circRNA is structurally conserved, has a stable sequence and is tissue-specific. With the development of high-throughput sequencing and bioinformatics technology, more and more circRNAs have been found. CircRNA plays an important pathophysiological role in the occurrence and development of alcoholic liver injury (ALI), hepatic fibrosis (HF), hepatocellular carcinoma (HCC), and other liver diseases. Our group has been committed to the research of liver disease diagnosis and treatment targets. We review the function and mechanism of circRNA in ALI, HF and HCC, expecting to provide new ideas for the diagnosis, treatment, and prognosis of liver diseases.
Population Scale Analysis of Centromeric Satellite DNA Reveals Highly Dynamic Evolutionary Patterns and Genomic Organization in Long-Tailed and Rhesus Macaques
Authors: Singchat Worapong , Ahmad Syed Farhan , Jaisamut Kitipong , Panthum Thitipong , Ariyaraphong Nattakan , Kraichak Ekaphan , Muangmai Narongrit , Duengkae Prateep , Payungporn Sunchai , Malaivijitnond Suchinda , Srikulnath Kornsorn
Published: June 2022

Centromeric satellite DNA (cen-satDNA) consists of highly divergent repeat monomers, each approximately 171 base pairs in length. Here, we investigated the genetic diversity in the centromeric region of two primate species: long-tailed (Macaca fascicularis) and rhesus (Macaca mulatta) macaques. Fluorescence in situ hybridization and bioinformatic analysis showed the chromosome-specific organization and dynamic nature of cen-satDNAsequences, and their substantial diversity, with distinct subfamilies across macaque populations, suggesting increased turnovers. Comparative genomics identified high level polymorphisms spanning a 120 bp deletion region and a remarkable interspecific variability in cen-satDNA size and structure. Population structure analysis detected admixture patterns within populations, indicating their high divergence and rapid evolution. However, differences in cen-satDNA profiles appear to not be involved in hybrid incompatibility between the two species. Our study provides a genomic landscape of centromeric repeats in wild macaques and opens new avenues for exploring their impact on the adaptive evolution and speciation of primates.
Promising Novel Barium Carbonate One-Dimensional Nanostructures and Their Gas Sensing Application: Preparation and Characterization
Authors: Shaalan Nagih M.
Published: June 2022

Recently, barium carbonate-based nanomaterials have been used for sensor and catalysis applications. The sensing performance can be improved with a suitable one-dimensional nanostructure. In this regard, novel nanosized BaCO3 materials were fabricated by a one-pot designed thermal evaporation system. Ten milligrams of Ba as raw material were used to deposit BaCO3 nanostructures at a pressure of 0.85 torr and a temperature of 850 °C in a partial oxygen atmosphere of the ambient. This simple method for fabricating novel BaCO3 nanostructures is presented here. X-ray diffraction was indexed on the orthorhombic polycrystalline structure of the prepared BaCO3. The nanostructures deposited here could be described as Datura-like structures linked with nanowires of 20–50 nm in diameter and 5 µm in length. The BaCO3 nanostructure prepared by the current method exhibited a semiconductor-like behavior with an activation energy of 0.68 eV. This behavior was ascribed to the nature of the morphology, which may possess large defective points. Thus, this nanostructure was subjected to gas sensing measurements, showing high activity toward NO2 gas. The proposed sensor also underwent deep investigation toward NO2 at various gas concentrations and working. The response and recovery time constants were recorded in the ranges of 6–20 s and 30–150 s, respectively. The sensor showed its reversibility toward NO2 when the sensor signal was repeated at various cycles of various concentrations. The sensor was exposed to different levels of humidity, showing high performance toward NO2 gas at 250 °C. The sensor exhibited fast response and recovery toward NO2 gas.
Metal Oxide Semiconductor Sensors for Triethylamine Detection: Sensing Performance and Improvements
Authors: Zhang Hua , Guo Yinghao , Meng Fanli
Published: June 2022

Triethylamine (TEA) is an organic compound that is commonly used in industries, but its volatile, inflammable, corrosive, and toxic nature leads to explosions and tissue damage. A sensitive, accurate, and in situ monitoring of TEA is of great significance to production safety and human health. Metal oxide semiconductors (MOSs) are widely used as gas sensors for volatile organic compounds due to their high bandgap and unique microstructure. This review aims to provide insights into the further development of MOSs by generalizing existing MOSs for TEA detection and measures to improve their sensing performance. This review starts by proposing the basic gas-sensing characteristics of the sensor and two typical TEA sensing mechanisms. Then, recent developments to improve the sensing performance of TEA sensors are summarized from different aspects, such as the optimization of material morphology, the incorporation of other materials (metal elements, conducting polymers, etc.), the development of new materials (graphene, TMDs, etc.), the application of advanced fabrication devices, and the introduction of external stimulation. Finally, this review concludes with prospects for using the aforementioned methods in the fabrication of high-performance TEA gas sensors, as well as highlighting the significance and research challenges in this emerging field.
Diagnostic Performance of Height-Estimated Baseline Creatinine in Diagnosing Acute Kidney Injury in Children with Type 1 Diabetes Mellitus Onset
Authors: Guarino Stefano , Rivetti Giulio , Di Sessa Anna , De Lucia Maeva , Palma Pier Luigi , Miraglia del Giudice Emanuele , Polito Cesare , Marzuillo Pierluigi
Published: June 2022

At type 1 diabetes mellitus (T1DM) onset, acute kidney injury (AKI) is very common. To diagnose AKI, the availability of a baseline serum creatinine (bSCr) is pivotal. However, in most hospitalized children the bSCr is unknown. We aimed to test whether the bSCr estimated on the basis of height (ebSCr) could be a reliable surrogate for AKI diagnosis compared with the measured bSCr (mbSCr). As the mbSCr, we considered the creatinine measured 14 days after T1DM onset while ebSCr (mg/dL) = (k × height [cm])/120 mL/min/1.73 m2, where k = 0.55 for children and adolescent girls and k = 0.7 for adolescent boys. AKI was defined as serum creatinine values >1.5 times the baseline creatinine. Kappa statistics and the percentage of agreement in AKI classification by ebSCr–AKI versus mbSCr–AKI definition methods were calculated. Bland–Altman plots were used to show the agreement between the creatinine ratio (highest/baseline creatinine; HC/BC) calculated with mbSCr and ebSCr. The number of 163 patients with T1DM onset were included. On the basis of mbSCr, 66/163 (40.5%) presented AKI while, on the basis of ebSCr, 50/163 (30.7%) accomplished AKI definition. ebSCr showed good correlation with mbSCr using both the Spearman test (rho = 0.67; p < 0.001) and regression analysis (r = 0.68; p < 0.001). Moreover, at the Bland–Altman plots, the bias of the highest/baseline creatinine ratio calculated on the basis of the mbSCr compared to ebSCr was minimal (bias = −0.08 mg/dL; 95% limits of agreement = −0.23/0.39). AKI determined using ebSCr showed 90% agreement with AKI determined using mbSCr (kappa = 0.66; p < 0.001). Finally, we compared the area under a receiver–operating characteristic curve (AUROC) of HC/BC ratio calculated on the basis of ebSCr with AUROC of the gold standard HC/BC ratio calculated on the basis of mbSCr. As expected, the gold standard had an AUROC = 1.00 with a 95% confidence interval (CI) between 0.98 and 1.00, p < 0.001. The HC/BC ratio calculated on the basis of ebSCr also had significant AUROC (AUROC = 0.94; 95% CI: 0.90–0.97; p < 0.001). The comparison of the two ROC curves showed a p < 0.001. In conclusion, when mbSCr is unknown in patients with T1DM onset, the ebSCr calculated on the basis of height could be an alternative to orientate clinicians toward AKI diagnosis.
Caregiver Perspectives on Patient Participation in Biological Pediatric Cancer Research
Authors: Kendel Nicole E. , Belsky Jennifer A. , Stanek Joseph R. , Streby Keri A. , Shah Nilay
Published: June 2022

Adolescent cancer patients and their caregivers have demonstrated willingness to participate in invasive biological sampling, either for their own potential benefit or for research purposes. However, many malignancies occur primarily in prepubescent patients and there are no similar studies in this population. Our study objective was to assess the willingness of caregivers to consent to research studies involving invasive biological sampling in children ≤ 13 years of age. Participants completed a survey assessing their willingness to allow various procedures both with and without clinical benefit to their children. Most respondents were willing to allow additional blood draws regardless of potential benefit to their children (95.6% were willing when there would be benefits and 95.6% were willing when there would not). Although the overall willingness was lower with other hypothetical procedures, the majority of respondents were still willing to allow additional biopsies for research purposes. Caregivers of young children with cancer will allow their children to undergo additional invasive procedures for research purposes. This willingness decreased with more invasive procedures without potential direct benefit, but interest remained in more than half of participants. Caregivers for young patients with cancer should be approached for participation in future biological/correlative studies.
Dental Caries, Oral Health Behavior, and Living Conditions in 6–8-Year-Old Romanian School Children
Authors: Dumitrescu Ramona , Sava-Rosianu Ruxandra , Jumanca Daniela , Balean Octavia , Damian Lia-Raluca , Campus Guglielmo Giuseppe , Maricutoiu Laurentiu , Alexa Vlad Tiberiu , Sfeatcu Ruxandra , Daguci Constantin , Postolache Mariana , Galuscan Atena
Published: June 2022

Dental caries still have a high prevalence in Romania. The aim of this paper is to determine the prevalence of caries in children (aged 6 to 8 years) correlated with individual-level predictors and socio-economic variables. A stratified, randomized nationally representative sample was established, taking into consideration the total number of preschool children and based on administrative units and residence. Self-assessment was performed by means of the Oral Health Questionnaire for Children (WHO). Examinations were conducted by 10 standardized examiners, with International Caries Detection and Assessment System (ICDAS) caries codes higher than 3 considered as dentinal caries, missing teeth as MT, and restorations as FT. DMFT and SiC indexes were calculated accordingly. The dataset for each outcome variable was analyzed by the Hurdle approach analyzed. The gender distribution was similar (47.22% male and 52.78% female), with 42.65% residing in rural areas. The mean DMFT value for the sample was 4.89 and SiC index 9.83. A negative association could be seen between DMFT and the father’s level of education (β = −0.33, SE = 0.07, p < 0.01) as well as the mother’s education (β = −0.25, SE = 0.07, p < 0.01). In conclusion, caries prevalence is very high in Romania as compared to the World Health Organization (WHO) recommendation for this age group in correlation with socio-economic factors and oral health behavior.
VEGF Pathway Gene Expression Profile of Proliferating versus Involuting Infantile Hemangiomas: Preliminary Evidence and Review of the Literature
Authors: Heredea Rodica Elena , Melnic Eugen , Cirligeriu Laura Elena , Berzava Patricia Lorena , Stănciulescu Maria Corina , Popoiu Călin Marius , Cimpean Anca Maria
Published: June 2022

Background. Infantile hemangiomas may have unexpected behavior. Initial regression (spontaneously or drug-induced) may be followed by unexplained recurrences. At this moment, there are no well-established criteria to predict infantile hemangioma reccurrences. Methods. We compared the VEGF pathway gene expression profile for one case of involuting infantile hemangioma versus one case of recurrent proliferative infantile hemangioma using TaqMan Array. Results. We found ten genes upregulated for both involuting and recurrent proliferative hemangiomas: ACTB, KRAS, MAP2K1, HRAS, NOS3, BAD, HSPB1, HPRT1, GUSB, and CASP9. Thirteen genes were downregulated for both involuting and proliferative hemangiomas: FIGF, ACTG1, GRB2, MAPKAPK2, ACTG2, MAP2K2, MAPK3, HSP90AA1, MAP2K6, NRAS, ACTA1, KDR, and MAPK1. Three genes showed divergent expression between proliferating and involuting hemangiomas. Proliferating hemangioma had MAPK14 and AKT1 gene upregulation and ACTA2 downregulation. Involuting infantile hemangioma was characterized by ACTA2 upregulation and AKT1 and MAPK14 downregulation. Conclusions. Three genes, AKT1, p38/MAPK14, and ACTA2, were found to have divergent expression in proliferating and involuting infantile hemangiomas. Excepting AKT1, which was mentioned in the last ISSVA classification (strictly related to Proteus Syndrome), none of the other genes were reported. An accurate gene expression profile mapping of infantile hemangiomas together with a gene expression-based hemangioma classification is stringently needed.
A Comparison between Three Different Techniques Considering Quality Skills, Fatigue and Hand Pain during a Prolonged Infant Resuscitation: A Cross-Over Study with Lifeguards
Authors: Barcala-Furelos Roberto , Barcala-Furelos Martín , Cano-Noguera Francisco , Otero-Agra Martín , Alonso-Calvete Alejandra , Martínez-Isasi Santiago , Aranda-García Silvia , López-García Sergio , Rodríguez-Núñez Antonio
Published: June 2022

The aim of the study was to compare the quality of CPR (Q-CPR), as well as the perceived fatigue and hand pain in a prolonged infant cardiopulmonary resuscitation (CPR) performed by lifeguards using three different techniques. A randomized crossover simulation study was used to compare three infant CPR techniques: the two-finger technique (TF); the two-thumb encircling technique (TTE) and the two-thumb-fist technique (TTF). 58 professional lifeguards performed three tests in pairs during a 20-min period of CPR. The rescuers performed compressions and ventilations in 15:2 cycles and changed their roles every 2 min. The variables of analysis were CPR quality components, rate of perceived exertion (RPE) and hand pain with numeric rating scale (NRS). All three techniques showed high Q-CPR results (TF: 86 ± 9%/TTE: 88 ± 9%/TTF: 86 ± 16%), and the TTE showed higher values than the TF (p = 0.03). In the RPE analysis, fatigue was not excessive with any of the three techniques (values 20 min between 3.2 for TF, 2.4 in TTE and 2.5 in TTF on a 10-point scale). TF reached a higher value in RPE than TTF in all the intervals analyzed (p < 0.05). In relation to NRS, TF showed significantly higher values than TTE and TTF (NRS minute 20 = TF 4.7 vs. TTE 2.5 & TTF 2.2; p < 0.001). In conclusion, all techniques have been shown to be effective in high-quality infant CPR in a prolonged resuscitation carried out by lifeguards. However, the two-finger technique is less efficient in relation to fatigue and hand pain compared with two-thumb technique (TF vs. TTF, p = 0.01).
Fabrication of Efficient Gold−Nickel-Supported Titania Nanotube Electrocatalysts for Sodium Borohydride−Hydrogen Peroxide Fuel Cells
Authors: Balčiūnaitė Aldona , Zabielaitė Aušrinė , Sukackienė Zita , Kepenienė Virginija , Šimkūnaitė Dijana , Selskis Algirdas , Tamašauskaitė-Tamašiūnaitė Loreta , Norkus Eugenijus
Published: June 2022

Here we report the optimization of the fabrication conditions for AuNi bimetallic catalysts supported on self-ordered titania nanotube arrays (AuNi-TiO2ntb). A series of efficient AuNi-TiO2ntb catalysts with small amounts of Au in the range of 1.74 to 15.7 μgAu·cm−2 have been fabricated by anodization, electroless Ni plating, and galvanic displacement techniques. The electrocatalytic activity of the catalysts has been evaluated for BH4− ion oxidation in an alkaline medium using cyclic voltammetry and chronoamperometry. The performance of a NaBH4-H2O2 fuel cell with Ni-TiO2ntb and AuNi-TiO2ntb anode catalysts has been investigated at different temperatures. It was found that the electrocatalytic activity of AuNi-TiO2ntbs catalysts was improved remarkably when the Ni layer of 100 and 400 nm was used for the deposition of Au crystallites. The Ni-TiO2ntb catalyst generates the maximum power density values of ca. 85–121 mW·cm−2 at a temperature of 25–55 °C, whereas the AuNi-TiO2ntb catalysts that have the Au loading of 3.07 and 15.7 μgAu·cm−2 achieve the power density values of ca. 104–147 and 119–170 mW·cm−2, respectively, at a temperature of 25–55 °C.
RETRACTED: Zhu et al. The Effect of Vacuum Annealing Temperature on the Properties of AlCrTiSiN Coating Prepared by Arc Ion Plating. Coatings 2022, 12, 316
Authors: Zhu Qiang , Liu Yanmei , Cong Wanqi , Chang Dongmei , Fan Qixiang , Cao Fengting , Wang Tie-Gang
Published: June 2022

The author and journal retract the article (The Effect of Vacuum Annealing Temperature on the Properties of AlCrTiSiN Coating Prepared by Arc Ion Plating) [...]
Synthesis and Characterization of Functional Magnetic Nanomaterials
Authors: Gandhi Ashish Chhaganlal
Published: June 2022

Nanoscale materials have grabbed the attention of researchers from a fundamental and application point of view for over a century [...]